Statins for Primary Prevention: The Debate Is Intense, but the Data Are Weak. The Role of Statins in the Management of Nonalcoholic Fatty Liver Disease. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Rationale and Design of the Standard Versus Intensive Statin Therapy for Hypercholesterolemic Patients with Diabetic Retinopathy (EMPATHY) Study: a Randomized Controlled Trial. Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT) Evaluation of a toolkit to improve cardiovascular disease screening and treatment for people with type 2 diabetes: protocol for a cluster-randomized pragmatic trial Impact of adherence to statins on chronic heart failure in primary prevention. Impact of better adherence to statin agents in the primary prevention of coronary artery disease A tailored lifestyle intervention to reduce the cardiovascular disease risk of individuals with Familial Hypercholesterolemia (FH): design of the PRO-FIT randomised controlled trial The International Polycap Study-3 (TIPS-3): Design, baseline characteristics and challenges in conduct Interaction between Mediterranean diet and statins on mortality risk in patients with cardiovascular disease: Findings from the Moli-sani Study. The ACC/AHA 2013 guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: the good the bad and the uncertain: a comparison with ESC/EAS guidelines for the management of dyslipidaemias 2011. Aspirin for primary prevention: yes or no? Global Risk Assessment to Guide Blood Pressure Management in Cardiovascular Disease Prevention A pragmatic randomized trial of a polypill-based strategy to improve use of indicated preventive treatments in people at high cardiovascular disease risk Evaluating the impact of population and high-risk strategies for the primary prevention of cardiovascular disease. Cardiac risk factors and the use of cardioprotective medications in patients with chronic renal insufficiency. Cost-Effectiveness and Population Impact of Statins for Primary Prevention in Adults Aged 75 Years or Older in the United States Saxagliptin Efficacy and Safety in Patients With Type 2 Diabetes Mellitus and Cardiovascular Disease History or Cardiovascular Risk Factors: Results of a Pooled Analysis of Phase 3 Clinical Trials Atorvastatin in Factorial with Omega-3 EE90 Risk Reduction in Diabetes (AFORRD): a randomised controlled trial Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial. Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease Risk in Adults: Synopsis of the 2013 American College of Cardiology/American Heart Association Cholesterol Guideline Lipoprotein(a) as a cardiovascular risk factor: current status An assessment of cholesterol goal attainment in patients with chronic kidney disease. Comparision of the risk of cardiovascular events and death in patients treated with degarelix compared with LHRH agonists. Glycated hemoglobin measurement and prediction of cardiovascular disease. Blood Pressure and Risk of Secondary Cardiovascular Events in Women: The Women’s Antioxidant Cardiovascular Study (WACS) An integrated general practice and pharmacy-based intervention to promote the use of appropriate preventive medications among individuals at high cardiovascular disease risk: protocol for a cluster randomized controlled trial Two-year statin therapy does not alter the progression of intima-media thickness in patients with type 2 diabetes without manifest cardiovascular disease. Statins and Fibrates for Diabetic Retinopathy: Protocol for a Systematic Review Association of Cardiovascular Risk With Inhaled Long-Acting Bronchodilators in Patients With Chronic Obstructive Pulmonary Disease: A Nested Case-Control Study Legacy Effect of Delayed Blood Pressure-Lowering Pharmacotherapy in Middle-Aged Individuals Stratified by Absolute Cardiovascular Disease Risk: Protocol for a Systematic Review Cardiovascular Outcomes in High-Risk Hypertensive Patients Stratified by Baseline Glomerular Filtration Rate Visit-to-Visit Variability of Blood Pressure and Coronary Heart Disease, Stroke, Heart Failure, and Mortality Circulating N‐Linked Glycoprotein Side‐Chain Biomarker, Rosuvastatin Therapy, and Incident Cardiovascular Disease: An Analysis From the JUPITER Trial A score for the prediction of cardiovascular events in the hypertensive aged. Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Comparison of three different methods of assessing cardiovascular disease risk in New Zealanders with Type 2 diabetes mellitus. Effect of lovastatin on primary prevention of cardiovascular events in mild CKD and kidney function loss: a post hoc analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study. Using mobile technology to support lower-salt food choices for people with cardiovascular disease: protocol for the SaltSwitch randomized controlled trial Saxagliptin Efficacy and Safety in Patients with Type 2 Diabetes Mellitus Stratified by Cardiovascular Disease History and Cardiovascular Risk Factors: Analysis of 3 Clinical Trials Rheumatoid arthritis is associated with a high prevalence of hypothyroidism that amplifies its cardiovascular risk Performance of the QRISK cardiovascular risk prediction algorithm in an independent UK sample of patients from general practice: a validation study Vitamin supplement use in a low-risk population of US male physicians and subsequent cardiovascular mortality. Long-term cardiovascular outcomes in patients with atrial fibrillation and atherothrombosis in the REACH Registry. A clustered randomized trial of the effects of feedback using academic detailing compared to postal bulletin on prescribing of preventative cardiovascular therapy. Improving diabetes care: multi-component cardiovascular disease risk reduction strategies for people with diabetes in South Asia--the CARRS multi-center translation trial. A cardiovascular disease policy model that predicts life expectancy taking into account socioeconomic deprivation Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial Cardiovascular disease risk reduction in rural China: a clustered randomized controlled trial in Zhejiang Chronic Ingestion of Flavan-3-ols and Isoflavones Improves Insulin Sensitivity and Lipoprotein Status and Attenuates Estimated 10-Year CVD Risk in Medicated Postmenopausal Women With Type 2 Diabetes C-reactive protein, fibrinogen, and cardiovascular disease prediction. IMProving Adherence using Combination Therapy (IMPACT): design and protocol of a randomised controlled trial in primary care. Genetic variation at the LDL receptor and HMG-CoA reductase gene loci, lipid levels, statin response, and cardiovascular disease incidence in PROSPER. 2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. The Effect of How Outcomes Are Framed on Decisions about Whether to Take Antihypertensive Medication: A Randomized Trial Circulating Interleukin-10 and Risk of Cardiovascular Events: A Prospective Study in the Elderly at Risk Association of Statin Therapy with Outcomes of Acute Coronary Syndromes: The GRACE Study No significant improvement of cardiovascular disease risk indicators by a lifestyle intervention in people with Familial Hypercholesterolemia compared to usual care: results of a randomised controlled trial Use of a Multidrug Pill In Reducing cardiovascular Events (UMPIRE): rationale and design of a randomised controlled trial of a cardiovascular preventive polypill-based strategy in India and Europe One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease. Impact of socioeconomic deprivation on screening for cardiovascular disease risk in a primary prevention population: a cross-sectional study The effect of Mediterranean diet on the risk of the development of acute coronary syndromes in hypercholesterolemic people: a case–control study (CARDIO2000) Estimating the benefits of modifying risk factors of cardiovascular disease: a comparison of primary vs secondary prevention. The 719Arg Variant of KIF6 and Cardiovascular Outcomes in Statin-Treated, Stable Coronary Patients of the Treating to New Targets and Incremental Decrease in End Points Through Aggressive Lipid-Lowering Prospective Studies Effect of intensive lipid-lowering therapy on cardiovascular outcome in patients with and those without inflammatory joint disease. Some problems with Cochrane reviews of diet and chronic disease Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the diabetes prevention program. Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: results of the Primary Prevention Project (PPP) trial. Effect of low doses of n-3 fatty acids on cardiovascular diseases in 4,837 post-myocardial infarction patients: design and baseline characteristics of the Alpha Omega Trial. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial Glycemic Control in Diabetes: A Tale of Three Studies Changes in CVD risk factors in the activity counseling trial Laboratory-based and office-based risk scores and charts to predict 10-year risk of cardiovascular disease in 182 countries: a pooled analysis of prospective cohorts and health surveys. Knowledge, Attitudes and Cardiovascular Risk Factors in Danish Adults Rationale and design of the Kanyini guidelines adherence with the polypill (Kanyini-GAP) study: a randomised controlled trial of a polypill-based strategy amongst Indigenous and non Indigenous people at high cardiovascular risk Impact of a nurse-led intervention to improve screening for cardiovascular risk factors in people with severe mental illnesses. Phase-two cluster randomised feasibility trial of community mental health teams Information and Risk Modification Trial (INFORM): design of a randomised controlled trial of communicating different types of information about coronary heart disease risk, alongside lifestyle advice, to achieve change in health-related behaviour The Effectiveness of Pharmacist Interventions on Cardiovascular Risk: The Multicenter Randomized Controlled RxEACH Trial. Reducing salt intake for prevention of cardiovascular diseases in high-risk patients by advanced health education intervention (RESIP-CVD study), Northern Thailand: study protocol for a cluster randomized trial C-Reactive Protein and Prediction of Coronary Heart Disease and Global Vascular Events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) Childhood risk factors predict cardiovascular disease, impaired fasting glucose plus type 2 diabetes mellitus, and high blood pressure 26 years later at a mean age of 38 years: the Princeton-lipid research clinics follow-up study. Does training of general practitioners for intensive treatment of people with screen-detected diabetes have a spillover effect on mortality and cardiovascular morbidity in ‘at risk’ individuals with normoglycaemia? Results from the ADDITION-Denmark cluster-randomised controlled trial Arriba: effects of an educational intervention on prescribing behaviour in prevention of CVD in general practice Is intake of breakfast cereals related to total and cause-specific mortality in men? Cardiovascular risk factors in women with and without rheumatoid arthritis. Ten-year legacy effects of baseline blood pressure ‘treatment naivety’ in the Second Australian National Blood Pressure study Depression and cardiovascular sequelae in postmenopausal women. The Women's Health Initiative (WHI). Evidence Supporting a Systolic Blood Pressure Goal of Less Than 150 mm Hg in Patients Aged 60 Years or Older: The Minority View The systematic coronary risk evaluation (SCORE) for the prevention of cardiovascular diseases. Does evidence exist for its effectiveness? A systematic review Results of a five-year community-based programme for cardiovascular disease prevention: The ATS-Sardegna Campaign A population-based lifestyle intervention to promote healthy weight and physical activity in people with cardiac disease: The PANACHE (Physical Activity, Nutrition And Cardiac HEalth) study protocol Electronic Health Record-Based Patient Identification and Individualized Mailed Outreach for Primary Cardiovascular Disease Prevention: A Cluster Randomized Trial A simple risk score using routine data for predicting cardiovascular disease in primary care. Effects of a global risk educational tool on primary coronary prevention: the Atherosclerosis Assessment Via Total Risk (AVIATOR) study Cardiovascular disease, risk factors and heart rate variability in the elderly general population: Design and objectives of the CARdiovascular disease, Living and Ageing in Halle (CARLA) Study Gonadal steroids, gonadotropins and DHEAS in young adults with familial hypercholesterolemia who had initiated statin therapy in childhood. Alteration of vascular function is an important factor in the correlation between visit-to-visit blood pressure variability and cardiovascular disease The effects of Hartcoach, a life style intervention provided by telephone on the reduction of coronary risk factors: a randomised trial Effect of 24 weeks of statin therapy on systemic and vascular inflammation in HIV-infected subjects receiving antiretroviral therapy. Predictive factors of stroke in patients undergoing coronary bypass grafting: statins are protective. A Polypill for primary prevention of cardiovascular disease: A feasibility study of the World Health Organization Which Patients Does the SPRINT Study Not Apply To and What Are the Appropriate Blood Pressure Goals in These Populations? Association of serum uric acid with cardiovascular disease in rheumatoid arthritis. A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women's Antioxidant Cardiovascular Study. The effect of statin therapy on endothelial function in type 2 diabetes without manifest cardiovascular disease. The MRC/BHF Heart Protection Study: preliminary results. Seven-year changes in alcohol consumption and subsequent risk of cardiovascular disease in men. Endogenous Sex Hormones and Cardiovascular Disease Incidence in Men Fruit and vegetable intake and risk of cardiovascular disease: the Women's Health Study. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Prevalence of Dyslipidemia and Lipid Goal Attainment in Statin-Treated Subjects From 3 Data Sources: A Retrospective Analysis Psychological distress as a risk factor for cardiovascular events: pathophysiological and behavioral mechanisms. Overweight and obesity and weight change in middle aged men: impact on cardiovascular disease and diabetes Effectiveness of Dader Method for pharmaceutical care on control of blood pressure and total cholesterol in outpatients with cardiovascular disease or cardiovascular risk: EMDADER-CV randomized controlled trial. Preventing the next event in the elderly: the PROSPER perspective. National Study of Physician Awareness and Adherence to Cardiovascular Disease Prevention Guidelines Aspirin, Statins, or Both Drugs for the Primary Prevention of Coronary Heart Disease Events in Men: A CostUtility Analysis [Effect of lifestyle interventions on reduction of cardiovascular disease events and its mortality in pre-diabetic patients:long-term follow-up of Da Qing Diabetes Prevention Study]. A prospective study of dietary fiber intake and risk of cardiovascular disease among women. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. Effectiveness-based guidelines for the prevention of cardiovascular disease in women--2011 update: a guideline from the American Heart Association. Plasma lycopene, other carotenoids, and retinol and the risk of cardiovascular disease in men. Sex Disparities in Control and Treatment of Modifiable Cardiovascular Disease Risk Factors Among Patients With Diabetes Rationale and design for the blood pressure intervention of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Beneficial impact of Xuezhikang on cardiovascular events and mortality in elderly hypertensive patients with previous myocardial infarction from the China Coronary Secondary Prevention Study (CCSPS). Update on the Vitamin D and OmegA-3 trial (VITAL) Efforts to improve subsequent treatment of cardiovascular risk factors in older patients with diabetes hospitalized for a cardiac event. Low intake of fruits, berries and vegetables is associated with excess mortality in men: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. Continuation of statin treatment and all-cause mortality: a population-based cohort study. Effect of screening for type 2 diabetes on risk of cardiovascular disease and mortality: a controlled trial among 139,075 individuals diagnosed with diabetes in Denmark between 2001 and 2009 Effect of Collaborative Care for Depression on Risk of Cardiovascular Events: Data From the IMPACT Randomized Controlled Trial Evaluating the use of mobile phone technology to enhance cardiovascular disease screening by community health workers Independent association of HbA(1c) and incident cardiovascular disease in people without diabetes. Physicians' perception, knowledge and awareness of cardiovascular risk factors and adherence to prevention guidelines: the PERCRO-DOC survey. Impaired Fasting Glucose and Cardiovascular Outcomes in Postmenopausal Women with Coronary Artery Disease Effects of Ramipril and Rosiglitazone on Cardiovascular and Renal Outcomes in People With Impaired Glucose Tolerance or Impaired Fasting Glucose Medication effectiveness may not be the major reason for accepting cardiovascular preventive medication: A population-based survey
This issue of JAMA contains the latest US Preventive Services Task Force ( USPSTF ) recommendation statement on statins for prevention of cardiovascular disease in adults,1 along with the accompanying evidence report and systematic review 2 on which the recommendations are based . The evidence report summarized data from 19 trials including a total of 71 344 patients and concluded that statin therapy was associated with reduced risk of all-cause and cardiovascular mortality and cardiovascular disease ( CVD ) events . Thus , the task force recommended “ initiating use of lowto moderate-dose statins in adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors and a calculated 10-year CVD event risk of 10 % or greater ( B recommendation ) ” or “ 7.5 % to 10 % ( C recommendation ) .”1 Although the task force did their usual careful job of review ing the evidence , the evidence for treating asymptomatic persons with statins does not appear to merit a grade B or even a grade C recommendation . The task force evidence report estimated an absolute benefit for use of statins of 0.40 % for all-cause mortality and 0.43 % for cardiovascular mortality and indicated that the absolute benefit was greater for patients at greater baseline risk.2 Notably , the evidence report did not exclude studies that included patients taking statins for secondary prevention , who have a higher baseline risk of cardiac events and death and thus are more likely to benefit from therapy that inflates the benefit attributed to a primary prevention population . The task force did perform a sensitivity analysis that excluded 3 trials with persons for whom there were prior “ hard ” cardiovascular events and obtained similar results of benefits ( eTable 5 in the article by Chou et al2 ) . This sensitivity analysis did not exclude WOSCOPS , which included patients receiving statins for secondary prevention—5 % had angina and 3 % had intermittent claudication,3 accounting for 15 % of the total weight in the meta- analysis . In contrast , a meta- analysis of 11 studies and 65 229 patients receiving statins for primary prevention , in which patients receiving statins for secondary prevention were excluded , found no benefit of statins for reducing all-cause mortality.4 The confidence intervals of these 2 analyses overlap , and the difference between these findings likely reflects differences in studies included . The USPSTF and authors of the evidence report did not have access to the primary data ( clinical study reports and anonymized patient-level data ) from the statin clinical trials . Rather , they had to rely on peer- review ed published reports as the basis for these recommendations . Exacerbating the potential bias , all of the trials included in the task force evidence report2 were industry-sponsored except 1 trial,5 and that trial contributed 0.2 % of the weight to the mortality calculation . Industry-sponsored studies have been shown to report greater benefit and lesser adverse effects than noncommercially sponsored trials of the same drugs.6 Whether this is true for statins and primary prevention of CVD is unknown . Among the 19 r and omized clinical trials of statins vs placebo or no statin included in the evidence report for the task force recommendations , only 15 reported all-cause mortality , 10 reported cardiovascular mortality , 12 reported fatal and nonfatal myocardial infa rct ion  , and 13 reported fatal and nonfatal stroke.2,7  Reliance on selective reporting of the most important outcomes , which are likely included in the clinical trial data , makes reporting bias possible . Furthermore , after allcause mortality , the comparative incidence of serious adverse events between treatment and control groups is arguably the second most important measure of the effect of active therapy in r and omized clinical trials . Underst and ing the evidence base in evaluating harms of statin therapy is also critically important . Although the benefits of any preventive therapy accrue according to risk of disease ( greater benefit in higher-risk patients ) , the harms of therapy usually distribute equally over all risk levels . Thus , persons at low risk have little chance of benefit but equal chance of harms and thus are more likely to have a net harm . The evidence base for harms of statins , despite the introduction of these drugs more than 20 years ago , is incomplete . Many of the trials did not ask about commonly reported statin effects , such as muscle pains and weakness , and only recorded myopathy , for which an increase in creatine kinase levels was required . Because most muscle problems do not involve an increase in creatine kinase levels , this leads to a significant underestimate of muscle problems . Other studies have estimated that closer to 20 % of statin users have muscle problems.8 Additionally , the actual trial data are largely held by the Cholesterol Treatment Trialists ’ Collaboration on behalf of the industry sponsor and have not been made available to other research ers , despite multiple requests over many years.9 Although reported rates of adverse events in clinical trials are low , this does not reflect the experience of clinicians who see patients who are taking statins . For instance , the experience of an NPR reporter with a calculated 2.9 % risk of heart disease over 10 years using the recommended American College of Cardiology/American Heart Association ( ACC/AHA ) risk calculator,10 but still prescribed a statin , and experiencing adverse effects from the medication , is typical of what many Related articles at jama.com BACKGROUND Non-alcoholic fatty liver disease ( NAFLD ) and its advanced form non-alcoholic steatohepatitis ( NASH ) are the most common causes of elevated liver enzymes in the general population . NASH , and to a lesser extent NAFLD have been associated with increased liver-related , cardiovascular disease ( CVD ) , and allcause mortality . No effective treatment is widely acceptable . OBJECTIVE The purpose of this review is to summarize available data on the impact of statins on NAFLD and NASH . METHOD A comprehensive review of the literature was performed to identify studies assessing the effect of statin use in NAFLD/NASH . RESULTS Recent reports have shown that the use of statins in patients with elevated plasma aminotransferases may be beneficial . Post hoc data from three large prospect i ve r and omized clinical trials ( n>11 , 000 ) suggest that specific statins ( mainly atorvastatin ) ameliorate NAFLD/NASH and reduce CVD events twice as much as in those with normal liver function . Several biopsy studies have found that rosuvastatin use is related with significant histological ameliorating effects in the setting of NASH . Statin treatment may also protect from hepatocellular carcinoma ( HCC ) related to NAFLD/NASH . CONCLUSION Since NAFLD/NASH patients have high CVD risk , they will probably require a statin . Thus , why not select a specific statins ( atorvastatin or rosuvastatin , both generic now ) that offer a substantial liver- and CVDrelated adverse event reduction ? The administration of statins in these patients is as safe as in the general population Most patients with type 2 diabetes mellitus develop cardiovascular disease ( CVD ) , with substantial loss of life expectancy . Nonfatal CVD contributes greatly to excess healthcare costs and decreased quality of life in patients with diabetes . The current epidemic of obesity has raised expectations that CVD associated with type 2 diabetes will become an even greater public health challenge . Despite the importance of this health problem , there is a lack of definitive data on the effects of the intensive control of glycemia and other CVD risk factors on CVD event rates in patients with type 2 diabetes . The Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial is a r and omized , multicenter , double 2 x 2 factorial design study involving 10,251 middle-aged and older participants with type 2 diabetes who are at high risk for CVD events because of existing CVD or additional risk factors . ACCORD is testing the effects of 3 medical treatment strategies to reduce CVD morbidity and mortality . All participants are in the glycemia trial , which is testing the hypothesis that a therapeutic strategy that targets a glycosylated hemoglobin ( HbA1c ) level of < 6.0 % will reduce the rate of CVD events more than a strategy that targets an HbA1c level of 7.0%-7.9 % . The lipid trial includes 5,518 of the participants , who receive either fenofibrate or placebo in a double-masked fashion to test the hypothesis of whether , in the context of good glycemic control , a therapeutic strategy that uses a fibrate to increase high-density lipoprotein cholesterol and lower triglyceride levels together with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ( statin ) to lower low-density lipoprotein cholesterol will reduce the rate of CVD events compared with a strategy that uses a statin plus a placebo . The blood pressure trial includes the remaining 4,733 participants and tests the hypothesis that a therapeutic strategy that targets a systolic blood pressure of < 120 mm Hg in the context of good glycemic control will reduce the rate of CVD events compared with a strategy that targets a systolic blood pressure of < 140 mm Hg . The primary outcome measure for all 3 research questions is the first occurrence of a major CVD event , specifically nonfatal myocardial infa rct ion , nonfatal stroke , or cardiovascular death . Upon the expected completion of participant follow-up in 2009 , the ACCORD trial should document for the first time the benefits and risks of intensive glucose control , intensive blood pressure control , and the combination of fibrate and statin drugs in managing blood lipids in high-risk patients with type 2 diabetes AIM Hyperlipidemia and diabetic retinopathy increase the risk of cardiovascular disease ( CVD ) . The st and ard versus intEnsive statin therapy for hypercholesteroleMic Patients with diAbetic retinopaTHY ( EMPATHY ) study examines whether intensive lipid-lowering therapy is superior to st and ard therapy in reducing the incidence of cardiovascular events in patients with hyperlipidemia and diabetic retinopathy , but without a history of coronary artery disease . METHODS Patients who had elevated low-density lipoprotein cholesterol ( LDL-C ) and diabetic retinopathy without a history of coronary artery disease were eligible for the study . Patients were r and omly assigned in a 1:1 ratio to receive intensive or st and ard therapy . Patients are being treated with monotherapy with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor ( statin ) for a maximum of 5.5 years to achieve the following LDL-C target : ＜70 mg/dL for the intensive therapy group or ≥100 and ＜120 mg/dL for the st and ard therapy group . The primary endpoint is a composite of incidence of CVD and death from CVD . RESULTS Between May 2010 and October 2013 , 5,995 patients were assessed for eligibility , and 5,144 were assigned to the study treatment ( 2,571 and 2,573 in the intensive and st and ard therapy groups , respectively ) , and baseline data were analyzed from 5,107 ( 2,550 in the intensive therapy group and 2,557 in the st and ard therapy group ) . CONCLUSIONS This is the first study assessing the benefits of intensive statin therapy in patients with hypercholesterolemia and diabetic retinopathy in a primary prevention setting . Furthermore , this study evaluates the appropriateness of the treat-to-target approach because all patients are treated to achieve specific LDL-C targets by titrating statin therapy . CLINICAL TRIAL REGISTRATION NUMBER UMIN000003486 Background The prognosis for young people diagnosed with diabetes during childhood remains poor and this is mainly related to the long-term risk of developing vascular complications . Microalbuminuria identifies subjects at risk for diabetic nephropathy ( DN ) and cardiovascular disease ( CVD ) . It is often detected in adolescence but is rarely treated before the age of 18 years , as at the end of puberty albumin excretion may decline and in some subjects will return into the normal range . However , evidence indicates that subjects with both transient and persistent microalbuminuria have experienced renal damage during puberty and thus reno-protection to prevent long-term complications is warranted . In adults with diabetes and microalbuminuria , the use of angiotensin converting enzyme inhibitors ( ACEI ) and Statins is increasing , and in order to determine whether these agents are of value in the adolescent population a large r and omized controlled clinical trial is needed . Methods / Design The Adolescent type 1 Diabetes cardio-renal Intervention Trial ( AdDIT ) is a multi-center , r and omized , double-blind , placebo-controlled trial of ACEI and Statin therapy in adolescents with type 1 diabetes . 500 high-risk adolescents , defined on the basis of their albumin excretion , are r and omized to receive either ACEI ( Quinapril ) or Statins ( Atorvastatin ) or combination therapy or placebo for 3 - 4 years . There will also be a parallel open observational study , based on the follow-up of 400 low-risk non-r and omized adolescents . The major endpoint of the study is the change in albumin excretion ; secondary endpoints include markers of CVD , renal function , retinopathy , quality of life combined with assessment of compliance and potential health economic benefits . Discussion AdDIT will provide important data on the potential renal and cardiovascular protective effects of ACEI and Statins in high-risk adolescents . Long-term follow-up of the r and omized subjects will provide direct evidence of disease outcomes , in addition to the data on early surrogate measures of DN and CVD . Follow-up of non-r and omized low-risk subjects will determine the potential impact of intervention on DN and CVD . AdDIT will help to determine whether , in addition to encouraging young people to achieve good glycaemic control , pharmacological cardio-renal protection should also be implemented . EudraCT Number 2007 - 001039 - 72 Trial Registration Number IS RCT Background The gap between the level of care recommended by evidence -based clinical practice guidelines and the actual care delivered to patients in practice has been well established . The Canadian Diabetes Association ( CDA ) created an implementation strategy to improve the implementation of its 2008 guidelines . This study will evaluate the impact of the strategy to improve cardiovascular disease ( CVD ) screening , prevention and treatment for people with diabetes . Design A pragmatic cluster-r and omized trial will be conducted to evaluate the CDA 's CVD Toolkit .  All family physicians in Ontario , Canada were r and omly allocated to receive the Toolkit , which includes several printed educational material s targeting CVD screening , prevention and treatment , either in spring 2009 ( intervention arm ) or in spring 2010 ( control arm ) . R and omization occurred at the level of the practice . Forty family physicians from each arm will be recruited to participate , and the medical records for 20 of their diabetic patients at high risk for CVD will be retrospectively review ed . Outcome measures will be assessed for each patient between July 2009 and March 2010 . The primary outcome will be that the patient is receiving a statin .  Secondary outcomes will include 1 ) the receipt of an angiotensin converting enzyme inhibitor or angiotensin receptor blocker , 2 ) various intermediate measures ( A1c , blood pressure , LDL-cholesterol , total-/HDL-cholesterol ratio , body mass index and waist circumference ) , and 3 ) clinical inertia ( the failure to change therapy in response to an abnormal A1c , blood pressure or cholesterol reading ) . The analysis will be carried out using multilevel hierarchical logistic regression models to account for the clustered nature of the data . The group assignment will be a physician-level variable . In addition , a process evaluation study with six focus groups of family physicians will assess the acceptability of the CDA 's Toolkit and will explore factors contributing to any change or lack of change in behaviour , from the perspectives of family physicians . Discussion Printed educational material s for physicians have been shown to exert small-to-moderate changes in patient care . The CDA 's CVD Toolkit is an example of a practice guideline implementation strategy that can be disseminated to a wide audience relatively inexpensively , and so demonstrating its effectiveness at improving diabetes care could have important consequences for guideline developers , policy makers and clinicians . Trial Registration The trial is registered with http://www . clinical trials.gov , ID # AIMS Statins are effective in the prevention of an atherosclerotic event , e.g. coronary artery disease and cerebrovascular disease . Patients at high risk of cardiovascular disease ( CVD ) , such as chronic heart failure ( CHF ) , might benefit from the effects of statin therapy . However , one question that has not yet been answered and that may clarify the role of statins in CHF is whether statins prevent the development of CHF in patients with a low risk of CVD . Our aim was to evaluate the impact of adherence to statins on the incidence of CHF . METHODS A cohort of 111,481 patients was reconstructed using the Régie de l'Assurance Maladie du Québec data bases . Patients were eligible if they were between 45 and 85 years old , without CVD , and newly treated with statins between 1999 and 2004 . A nested case-control design was used to study CHF . Every case of CHF was matched for age and duration of follow-up in up to 15 r and omly selected controls . The adherence level was measured by calculating the medication possession ratio . Rate ratios ( RR ) of CHF were estimated by conditional logistic regression adjusting for several covariables . RESULTS The mean patient age was 63 years , 49 % had hypertension , 21 % had diabetes and 41 % were male . A high level of adherence to statins was associated with a reduction of CHF ( RR 0.81 ; 0.71 , 0.91 ) . The risks associated with CHF were the development of CVD during follow-up , being a social-aid recipient , and suffering from hypertension , diabetes mellitus , or having a higher chronic disease score . CONCLUSION Our study indicates that better adherence to statins is associated with a reduced risk of CHF Background Statins reduce cardiovascular morbidity and mortality after continuous treatment . Studies have shown that less than 50 % of patients take 80 % or more of prescribed doses 1 year after starting therapy . Objective To evaluate the impact of statin adherence on the incidence of coronary artery disease ( CAD ) . Methods A cohort of 115,290 patients was reconstructed using the Régie de l’assurance maladie du Québec data bases . Patients aged 45 to 85 years , without indication of cardiovascular disease ( CVD ) , and newly treated with statins between 1999 and 2004 were eligible . A nested case-control design was used to study CAD . Every case was matched for age and duration of follow-up with r and omly selected controls . The adherence level was measured by calculating the medication possession ratio . Rate ratios ( RR ) of CAD were determined through conditional logistic regression adjusted for several covariates . Results The mean patient age was 63 years , 54 % had hypertension , 26 % had diabetes , and 41 % were males . The proportion of patients with high adherence level to statins  ( ≥ 80 % ) was 74 % during the first year and 53 % after 1 year of follow-up . High adherence was associated with a risk reduction of 18 % [ RR : 0.82 ( 95 % CI : 0.77 - 0.87 ) ] compared to an adherence level of < 20 % . Developing a CVD during follow-up , being male , having been diagnosed with hypertension or diabetes , or having a high chronic disease score increased the risk of CAD . Conclusion Our study suggests that better adherence to statin agents is associated with a significant risk reduction of CAD . Adherence to statin agents needs to be improved so that patients can benefit from the full protective effects of statin therapies Background Because of a high cardiovascular disease ( CVD ) risk in people with Familial Hypercholesterolemia ( FH ) , early prevention of cardiovascular disease is important for health gain and cost reduction . This project focuses on the development and evaluation of an innovative intervention aim ing to reduce CVD risk by promoting a healthy lifestyle among people with FH . Methods This project is design ed as a r and omised controlled trial in which individuals with FH will be assigned r and omly to a control or intervention group . In the intervention group ( n = 200 ) , participants will receive a personalized intervention which is a combination of web-based tailored lifestyle advice and personal counselling by a lifestyle coach .  The control group ( n = 200 ) will receive care as usual . Primary outcomes are biological indicators of CVD risk : systolic blood pressure , glucose , BMI , waist circumference and lipids ( triglycerides , total , LDL and HDL cholesterol ) . Secondary outcomes are : healthy lifestyle behaviour ( with regard to smoking , physical activity , dietary pattern and compliance to statin therapy ) and psychological correlates and determinants of healthy lifestyle behaviour ( knowledge , attitude , risk perception , social influence , self-efficacy , cues to action , intention and autonomy ) . Measurement will take place at baseline , and at 3 and 12 months after r and omisation . Additionally , a throughout process-evaluation will be conducted to assess and monitor intervention implementation during the trial . Discussion Results of the PRO-FIT project will provide information about the effects and implementation of a healthy lifestyle intervention for individuals with FH . Our experiences with this intervention will be indicative about the suitability , feasibility and benefits of this approach for future interventions in other high-risk groups , such as Familial Combined Hypercholesterolemia ( FCH ) and diabetes . Trial registration Background It is hypothesized that in individuals without clinical cardiovascular disease ( CVD ) , but at increased CVD risk , a 50 % to 60 % reduction in CVD risk could be achieved using fixed dose combination ( FDC ) therapy ( usually comprised of multiple blood‐pressure agents and a statin [ with or without aspirin ] ) in a single “ polypill ” . However , the impact of a polypill in preventing clinical CV events has not been evaluated in a large r and omized controlled trial . Methods TIPS‐3 is a 2x2x2 factorial r and omized controlled trial that will examine the effect of a FDC polypill on major CV outcomes in a primary prevention population . This study aims to determine whether the Polycap ( comprised of atenolol , ramipril , hydrochlorothiazide , and a statin )  reduces CV events in persons without a history of CVD , but who are at least at intermediate CVD risk . Additional interventions in the factorial design of the study will compare the effect of ( 1 ) aspirin versus placebo on CV events ( and cancer ) , ( 2 ) vitamin D versus placebo on the risk of fractures , and ( 3 ) the combined effect of aspirin and the Polycap on CV events . Results The study has r and omized 5713 participants across 9 countries . Mean age of the study population is 63.9 years , and 53 % are female . Mean INTERHEART risk score is 16.8 , which is consistent with a study population at intermediate CVD risk . Conclusion Results of the TIP‐3 study will be key to determining the appropriateness of FDC therapy as a strategy in the global prevention of CVD BACKGROUND Statins are prescribed for patients with cardiovascular disease ( CVD ) , along with the recommendation of adopting healthy diets . We evaluated the independent and the combined effect of statins and Mediterranean diet ( MD ) towards mortality risk in patients with previous CVD by using real-life data from a population -based prospect i ve cohort . METHODS Longitudinal analysis on 1180 subjects ( mean age 67.7 ± 10 ) with prior CVD at enrollment in the Moli-sani Study and followed up for 7.9 y ( median ) .  Adherence to MD was appraised by a Mediterranean diet score .  Hazard ratios ( HR ) with 95 % confidence intervals ( 95 % CI ) were calculated by multivariable Cox regression and competing risk models . RESULTS Multivariable risk estimates associated with a 2-point increase in MD score were 0.84 ( 95 % CI 0.70 - 1.00 ) , 0.77 ( 0.61 - 0.97 ) and 0.70 ( 0.52 - 0.93 ) for overall , cardiovascular and coronary artery disease (CAD)/cerebrovascular deaths , respectively  . Statins were not associated with death risk . Subjects combining statins and average-high adherence to MD had much lower than expected risk of cardiovascular and CAD/cerebrovascular mortality ( p for interaction = 0.045 and 0.0015 , respectively ) as compared to those neither using statins nor having average-high MD . The combination of average-high MD and statins was associated in a likely synergistic way with reduced low- grade inflammation , but not with blood cholesterol . CONCLUSIONS MD lowered the risk of all-cause , cardiovascular and CAD/cerebrovascular mortality CVD patients , net of statins . In the same population , statins  reduced CVD death risk only in combination with MD . Low- grade inflammation , rather than lipids , is likely to be on the pathway of the interaction between MD and statins towards mortality risk Atherosclerotic cardiovascular disease is the most important public health problem of our time in both Europe and the rest of the world , accounting for the greatest expenditure in most healthcare budgets . Achieving consistency of clinical care , incorporating new evidence and their synthesis into practical recommendations for clinicians is the task of various guideline committees throughout the world . Any change in a set of guidelines therefore can have far reaching consequences , particularly if they appear to be at variance with the existing guidelines . The present article discusses the recent American College of Cardiology (ACC)/American Heart Association ( AHA ) guidelines 2013 on the control of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults . When compared with the ESC/EAS guidelines on lipid modification in 2011 , the ACC/AHA guidelines of 2013 differ markedly . Specifically , ( i ) the scope is limited to r and omized trials only , which excludes a significant body of data and promotes essentially a statin centric approach only ; ( ii ) the abolition of low-density lipoprotein cholesterol ( LDL-C ) targets in favour of specific statin regimens that produce a 30 - 50 % reduction in LDL-C we believe will confuse many physicians and miss the opportunity for medication adherence and patient engagement in self-management ; ( iii ) the absence of target LDL-C levels in very high-risk patients with high absolute risk or residual risk factors will discourage clinicians to consider the addition of lipid modification treatments and individualize patient care ; ( iv ) a reduction in the threshold for treatment in primary prevention will result in a greater number of patients being prescribed statin therapy , which is potentially good in young patients with high life time risk , but will result in a very large number of older patients offered therapy ; and ( v ) the mixed pool risk calculator used to asses CVD risk in the guidelines for primary prevention has not been fully evaluated . This article discusses the potential implication s of adopting the ACC/AHA guidelines on patient care in Europe and beyond and concludes with the opinion that the ESC/EAS guidelines from 2011 seem to be the most wide ranging , pragmatic and appropriate choice for European countries AIM To assess benefit versus harm of aspirin for cardiovascular disease ( CVD ) primary prevention by age group , gender and risk category and to interpret these results in light of current New Zeal and CVD risk assessment and management guidelines . METHODS Rates of benefit ( avoided vascular events ) and harm ( additional major extracranial bleeds ) for each gender and age group were calculated from data from the six r and omised controlled trials included in the Anti-Thrombotic Trialists ' ( ATT ) Collaboration meta- analysis . These rates were applied to CVD risk categories to calculate the net benefit or net harm likely to occur from the use of aspirin in primary prevention of CVD as monotherapy and when added to lipid and blood pressure-loweringtherapies . RESULTS Benefits of aspirin monotherapy outweigh the harms for both men and women aged up to 80 years with calculated five-year CVD risk > 15 % in primary prevention . Harm may outweigh benefit for primary prevention for those over 80 years . For men 70 - 79 years the benefit of aspirin in primary prevention is marginal when added to lipid and blood pressure-lowering therapies . DISCUSSION The recent ATT Collaboration meta- analysis has raised doubts about the relative safety of aspirin in primary prevention of CVD . However , modelling by risk category and age group suggests that current guidelines are justified in recommending aspirin for primary prevention of CVD in those with five-year CVD risk > or = 15 % up to the age of 80 years . For men 70 - 79 , consider lipid and blood pressure-lowering therapies first then reassess whether aspirin adds additional net benefit Elevated blood pressure ( BP ) is a causal risk factor for cardiovascular disease ( CVD ) . Epidemiological analyses have established the grade d and continuous association between higher BP and CVD . Moreover , r and omized clinical trials among individuals with hypertension have demonstrated , in aggregate , a reduction in CVD events by 20 % , coronary heart disease ( CHD ) by 17 % , stroke by 27 % , and heart failure by 28 % for every 10 mm Hg systolic BP ( SBP ) lowering with medical therapy.1 Therefore , prevention , detection , treatment , and control of elevated BP , and its clinical correlate hypertension , is an important public health priority and a primary target for CVD prevention . Although national health surveys have demonstrated improvements in hypertension awareness and treatment , strategic opportunities to improve the efficiency and efficacy of applying BP-lowering therapy in patients most likely to benefit remain.2 Global CVD risk assessment , using multivariable prediction models that estimate absolute CVD risk from routinely measured clinical variables , has been promulgated in several CVD prevention guidelines for cholesterol management to target the most intensive preventive therapies to those at highest absolute CVD risk.3–5 Hypertension guidelines , however , have instead relied solely on isolated BP thresholds and BP goals to guide treatment initiation and intensity . In this review , we provide a rationale for incorporating global CVD risk assessment in BP treatment decision-making and propose a framework to guide its implementation in future CVD prevention guidelines . Epidemiological analyses have firmly established that CVD is a multifactorial condition and that modest increases of several CVD risk factors can often lead to greater overall risk than a severe elevation of a Background Most individuals at high cardiovascular disease ( CVD ) risk worldwide do not receive any or optimal preventive drugs . We aim ed to determine whether fixed dose combinations of generic drugs ( ‘ polypills ’ ) would promote use of such medications . Methods We conducted a r and omized , open-label trial involving 623 participants from Australian general practice s. Participants had established CVD or an estimated five-year CVD risk of ≥15 % , with indications for antiplatelet , statin and ≥2 blood pressure lowering drugs ( ‘ combination treatment ’ ) . Participants r and omized to the ‘ polypill-based strategy ’  received a polypill containing aspirin 75 mg , simvastatin 40 mg , lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg . Participants r and omized to ‘ usual care ’ continued with separate medications and doses as prescribed by their doctor . Primary outcomes were self-reported combination treatment use , systolic blood pressure and total cholesterol . Results After a median of 18 months , the polypill-based strategy was associated with greater use of combination treatment ( 70 % vs. 47 % ; relative risk 1.49 , ( 95 % confidence interval ( CI ) 1.30 to 1.72 ) p < 0.0001 ; number needed to treat = 4.4 ( 3.3 to 6.6 ) ) without differences in systolic blood pressure ( −1.5 mmHg ( 95 % CI −4.0 to 1.0 ) p = 0.24 ) or total cholesterol ( 0.08 mmol/l ( 95 % CI −0.06 to 0.22 ) p = 0.26 ) . At study end , 17 % and 67 % of participants in polypill and usual care groups , respectively , were taking  atorvastatin  or rosuvastatin . Conclusion Provision of a polypill improved self-reported use of indicated preventive treatments . The lack of differences in blood pressure and cholesterol may reflect limited study power , although for cholesterol , improved statin use in the polypill group counter-balanced use of more potent statins with usual care AIMS To estimate the potential effectiveness of different " high-risk " and " population " approaches to the primary prevention of  cardiovascular disease ( CVD ) in middle-aged British men , after correction for regression dilution bias . METHODS AND RESULTS We used a combination of cohort and r and omised controlled trial evidence to estimate the effectiveness of high-risk strategies , based on the identification of high-risk factors or high absolute risk , and strategies based on population -wide reductions in cholesterol and blood pressure . High-risk strategies were potentially effective but would need to be used widely to have a substantial effect on CVD in the population . Aggressive pharmacological treatment ( using statins , beta-blockers , ACE-inhibitors and aspirin ) in individuals with a 10-year Framingham event risk of > or=30 % ( 6 % of population ) would have reduced major CVD by at most 11 % . This figure increased to 34 % at a > or=20 % treatment threshold ( 26 % of population ) . In contrast , modest downwards shifts in the population distributions of serum total cholesterol and systolic blood pressure led to marked expected reductions in major CVD . Taking regression dilution bias into account , 10 % reductions in long-term mean blood cholesterol and blood pressure could have reduced major CVD by 45 % . CONCLUSIONS If high-risk strategies are to have a major impact on CVD in the population , they need to be more widely used than previously envisaged . Population -wide reduction of major risk factors is needed if CVD is to be substantially reduced Cardiovascular disease ( CVD ) is a major cause of morbidity and mortality among patients with chronic renal insufficiency ( CRI ) .  beta-Adrenergic blockers , acetylsalicylic acid ( ASA ) , angiotensin-converting enzyme ( ACE ) inhibitors , and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) all reduce CVD mortality , but little is known about the extent to which these medications are used in patients with CRI . This study , a prospect i ve cross-sectional study of consecutive patients seen by nephrologists in four Canadian centers for follow-up of progressive CRI in 1999 , was performed to investigate the prevalence of coronary risk factors and use of cardioprotective medications among patients with CRI . Patients had creatinine clearances of 75 mL/min or less but were not on dialysis therapy . Three hundred four consecutive patients meeting the inclusion criteria were enrolled . Mean age was 60.8 + /- 15.7 years , mean creatinine clearance was 30.3 + /- 18 mL/min , and the case mix of kidney diseases was similar to that in the Canadian Organ Replacement Registry data . One hundred seventeen of 304 patients ( 38.5 % ) had a history of previous CVD , and the prevalence of CVD was greater in patients with more severe CRI . Two hundred forty-three patients ( 79.9 % ) had a history of hypertension , 132 patients ( 43.4 % ) had hyperlipidemia , 114 patients ( 37.5 % ) had diabetes mellitus , and 71 patients ( 27.3 % ) were smokers . Thirty-five percent of the patients with CVD had blood pressures greater than 140/90 mm Hg ; 103 patients ( 33.9 % ) were administered beta-blockers ; 196 patients ( 64.5 % ) , ACE inhibitors or angiotensin-receptor blockers ; 83 patients ( 27.3 % ) , ASA ; and 56 patients ( 18.4 % ) , statins . Patients with diabetes were not more likely than those without diabetes to be prescribed cardioprotective medications . CVD is common in the predialysis population , and its prevalence increases with more severe kidney failure . Despite this , the use of cardioprotective medications  is relatively low , and many patients had suboptimal blood pressure control . Given the high burden of disease in these patients , beta-blockers and ACE inhibitors should be used to control hypertension and /or for cardioprotection , and the increased use of ASA and statins should be considered Editors ' Notes Context Clinical guidelines provide conflicting recommendations about whether to prescribe statins in persons aged 75 years or older for primary prevention of unwanted cardiovascular outcomes . Contribution This study used information from clinical trials to model the tradeoffs between benefits and harms and found that using  statins  in all persons aged 75 to 94 years would prevent new myocardial infa rct ions and deaths from coronary heart disease at an acceptable cost . Caution Small increases in the frequency or severity of harms would negate the benefits . Implication Additional research is warranted to better underst and the tradeoffs between benefits and harms in this age group . Statins are commonly used in adults aged 75 years or older ( 1 ) . Despite their widespread use , evidence for their effectiveness for primary prevention in elderly adults is unclear , and guidelines for their use in this population are inconsistent . The recently published American College of Cardiology/American Heart Association ( ACC/AHA ) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults gave limited recommendations for statin use for primary prevention in adults aged 75 years or older ( 2 ) , noting that few data were available to indicate an atherosclerotic cardiovascular disease event reduction benefit in primary prevention among individuals > 75 years of age who do not have clinical year atherosclerotic cardiovascular disease , and suggesting that comorbid conditions , safety , and priorities of care are recommended for joint provider and patient decision making . The American Medical Directors Association , a professional group of long-term care providers , recommended that statins not be routinely prescribed in adults aged 70 years or older as part of the American Board of Internal Medicine Choosing Wisely campaign ( 3 ) . This recommendation was based on the lack of an association between high cholesterol levels and outcomes in older adults as well as the potential for an increased risk for statin-related adverse events , including cognitive impairment , falls , neuropathy , and muscle damage ( 3 ) . The variation in these treatment recommendations reflects uncertainty about the balance between the benefits and risks of statin use in older adults compared with younger adults as well as the more limited evidence base in this population . Adults aged 75 years or older have been underrepresented in trials of statins for primary prevention , so the effectiveness of statins is less clear in this population . Results from observational studies suggest that the associations between low-density lipoprotein ( LDL ) cholesterol levels and outcomes are attenuated in older adults ( 47 ) . Although the baseline risk for cardiovascular disease is increased in older adults , their life expectancy is shorter and their risks for competing mortality are greater . Finally , there has been concern about geriatric-specific adverse effects , especially functional limitation due to muscle pain , weakness , and mild cognitive impairment ( 816 ) . In the presence of uncertainty about the riskbenefit tradeoff , computer simulations can provide estimates of the potential benefits of various treatment strategies as well as the costs and potential risk for harms . We evaluated the population benefit and cost-effectiveness of statins in persons aged 75 years or older without a history of cardiovascular disease in the United States . This investigation was conducted using the Cardiovascular Disease Policy Model ( CVDPM ) , a Markov model of the U.S. population ( 17 ) . We simulated the impact of statins for primary prevention based on treatment of the high-risk groups identified by the ACC/AHA guidelines , the associated costs , and potential harms that could offset the potential cardiovascular benefits in the U.S. population of adults aged 75 to 94 years over the next 10 years . Methods The Model The CVDPM is an established state-transition ( Markov ) model of the incidence , prevalence , mortality , and cost of CHD and stroke in U.S. residents aged 35 to 94 years ( 17 ) . The present study was limited to adults aged 75 to 94 years . The model comprises 3 components . First , the demographic-epidemiologic submodel estimates the incidence of coronary heart disease ( CHD ) ( cardiac arrest , myocardial infa rct ion [ MI ] , angina , or CHD death ) , ischemic stroke , and death from other causes on the basis of age , sex , systolic blood pressure , smoking , high-density lipoprotein and LDL cholesterol levels , diabetes , body mass index , and statin use . Second , the bridge submodel characterizes the initial CHD or stroke event and related events in the subsequent 30 days . Third , the disease-history submodel predicts the number of subsequent CHD and stroke events , revascularization procedures , and deaths among patients with cardiovascular disease , stratified according to age , sex , and history of cardiovascular disease events . In addition , persons may exit the model at any stage through a non-CHD , nonstroke mortality function , allowing for competing risk . Modifiable components of the model include population distributions , risk factor levels , risk factor coefficients , event rates , case-fatality rates , costs , and disability adjustments ( 17 ) . Costs for stroke requiring hospitalization , CHD , and acute stroke rehabilitation were estimated using California hospital data ( 18 ) and were deflated using costcharge ratios and the ratio of the U.S. national average costs to the California average ( 19 , 20 ) . Age- and sex-specific background health care costs were estimated using national data ( 21 ) . All model costs were inflated to 2014 costs by using the medical component of the Consumer Price Index ( 22 ) . All disability weights associated with the CHD and stroke event states were based on the Global Burden of Disease Study ( 23 , 24 ) . Additional details are provided in the Appendix . Simulation Inputs We modeled the effect of statins on LDL cholesterol level based on PROSPER ( Prospect i ve Study of Pravastatin in the Elderly at Risk of Vascular Disease ) , a r and omized , placebo-controlled trial of 5804 men and women aged 70 to 82 years ( 25 ) . In that trial , the mean reduction in LDL cholesterol level was 34 % for participants with an average initial level of 147 mg/dL , consistent with the estimated effect of a moderate-dose statin in the 2013 ACC/AHA guideline ( 2 ) . We included 3 estimates for the effectiveness of a decrease in LDL cholesterol level on events . The primary estimates were derived by extrapolating the age-stratified effect sizes of a 1.0-mmol/L reduction in LDL cholesterol level from the Cholesterol Treatment Trialists ' meta- analysis ( 26 ) . We fit a regression line to the 3 age strata reported in that analysis ( 60 years , > 60 to 70 years , and > 70 years ) to estimate the effect sizes at ages 80 and 90 years . In a sensitivity analysis , we used a high estimate based on the age-pooled estimate of effect of a 1.0-mmol/L reduction in LDL cholesterol level on major coronary events in the meta- analysis . We used a low estimate based on the effect size from PROSPER for primary prevention ( 25 ) . Statin costs were derived from the National Average Drug Acquisition Cost ( NADAC ) data base ( 27 ) . Our primary cost estimate ( $ 5.59 for a 30-day supply ) was the average of the NADAC costs for the 4 moderate-dose statins that are available in generic form : atorvastatin , 10 mg ; simvastatin , 20 mg ; pravastatin , 40 mg ; and lovastatin , 40 mg . This cost estimate was $ 5.00 when indexed to 2010 dollars based on the medical component of the Consumer Price Index ( 22 ) . In addition , we used a low cost estimate of $ 4 per month , based on the price of generic statins from multiple discount retailers ( such as Walmart , Target , and Walgreens ) . For a high cost estimate , we used $ 30 for a 30-day supply ; the low and high cost estimates have been used similarly in other contemporary cost-effectiveness analyses ( 28 , 29 ) . Adults aged 65 years or older use a median of 4 medications ; therefore , we estimated the cost of an additional 0.25 physician visit per year for statin use , assuming that medication management could be covered in 1 visit ( 30 , 31 ) . We estimated 1 lipid panel per year for monitoring ( 32 ) . Event rates for myopathy and hemorrhagic stroke were estimated as 0.001 per statin-year of use , based on the ACC/AHA guideline statement ( 2 ) . Although many major and minor adverse effects have been reported to be associated with statin use , we focused on 2 that are important to geriatric population s and that have generated concern in the scientific literature : functional limitation due to muscle pain and weakness , and mild cognitive impairment ( 816 ) . Both are prevalent in older adults and can have a substantial effect on quality of life and the ability to live independently . A recent review of late-life activity limitations in the United States reported data on participants in 5 nationally representative surveys . The prevalence of limitations in activities of daily living was 27 % in adults aged 75 to 84 years and 45 % in those aged 85 years or older ( 33 ) . The population -weighted average of these estimates is 32 % for adults aged 75 to 94 years . Widely varying prevalence estimates for mild cognitive impairment have been reported due to the differential measures of this condition and the differences between population s. A recent review reported prevalence of mild cognitive impairment of 19 % to 28 % in studies of older U.S. adults ; we used the average of the 4 U.S. studies , which was 25 % ( 34 ) . Disability-adjusted life-years for the corresponding states were calculated as 1 minus the disability weights reported in the Global Burden of Disease Study ( 24 ) . Because the statin-associated relative risk for these adverse effects is uncertain , we assumed no elevated risk for these adverse effects in our base-case scenario . The goal of this investigation was not to evaluate the strength of the literature regarding the presence of these adverse Abstract Objective : This post hoc analysis sought to assess the efficacy , safety , and tolerability of saxagliptin in patients with type 2 diabetes mellitus and cardiovascular ( CV ) risk factors or disease ( CVD ) . Methods : Data from 5 r and omized controlled trials were pooled to compare saxagliptin 5 mg with placebo : 2 studies of saxagliptin as monotherapy in drug-naïve patients and 1 each of saxagliptin as add-on therapy to metformin , glyburide , or a thiazolidinedione . Analysis was performed according to the following baseline/trial entry criteria : 1 ) history /no history of CVD ; 2 ) ≥ 2 versus 0 to 1 CV risk factors ; 3 ) statin use versus no statin use ; and 4 ) hypertension versus no hypertension . Change from baseline glycated hemoglobin ( HbA1c ) , fasting plasma glucose , and postpr and ial glucose levels ; and the proportion of patients achieving an HbA1c level < 7 % were analyzed ( week 24 ) . Safety was assessed by adverse events , hypoglycemia , and body weight . Results : In total , 882 patients received saxagliptin 5 mg and 799 received placebo . Differences in adjusted mean change from baseline HbA1c ( 95 % CI ) were greater with saxagliptin compared with placebo in patients with a history of CVD ( −0.64 % [ −0.90 to −0.38 ] ) and no history of CVD ( −0.68 % [ −0.78 to −0.58 ] ) ; with ≥ 2 CV risk factors ( −0.73 % [ −0.85 to −0.60 ] ) and 0 to 1 CV risk factor ( −0.62 % [ −0.75 to −0.48 ] ) ; with statin use ( −0.70 % [ −0.89 to −0.52 ] ) and no statin use ( −0.66 % [ −0.77 to −0.56 ] ) ; and with hypertension ( −0.69 % [ −0.82 to −0.57 ] ) and no hypertension ( −0.66 % [ −0.80 to −0.52 ] ) . Saxagliptin was well tolerated , with similar adverse event rates and types compared with placebo . There was a < 1 % rate of confirmed hypoglycemia in all groups except in patients with CV history who received placebo ( 2.1 % ) . Conclusion : Saxagliptin improved glycemic measures , result ed in low rates of confirmed hypoglycemia , and was well tolerated in patients with or without CVD and CV risk factors Abstract Aims /hypothesisThe aim of the study was to examine the impact of statin or omega-3-acid ethyl esters 90 ( omega-3 EE90 ; omega-3-acid ethyl esters 90 refers to a mixture of ethyl esters of n-3 fatty acids ) on estimated cardiovascular disease ( CVD ) risk in community-based people with type 2 diabetes but without known CVD and not taking lipid-lowering therapy . Methods A central computer r and omised 800 patients in 59 UK general practice s to atorvastatin ( n = 401 , 20 mg/day ) or placebo ( n = 399 ) and omega-3 EE90 ( n = 397 , 2 g/day ) or placebo  ( n = 403 ) in a concealed factorial manner . Participants with LDL-cholesterol < 2.6 mmol/l , triacylglycerol < 1.5 mmol/l and estimated 10-year CVD risk < 20 % were compared at 4 months . Results Mean ( SD ) age was 63.5 ( 11.7 ) years , HbA1c 6.9 ( 1.1 ) % and known diabetes duration ( median [ interquartile range ] ) was 4 ( 2–8 ) years . Fifty-seven per cent were men , 90 % white and 74 % had an estimated 10-year CVD risk ≥20 % . Of 732 patients with 4-month data , more allocated atorvastatin ( n = 371 ) compared with placebo ( n = 361 ) achieved LDL-cholesterol < 2.6 mmol/l ( 91 % vs 24 % , p < 0.001 ) and had estimated 10-year CVD risks < 20 % ( 38 % vs 26 % , p < 0.001 ) . No differences were seen between those allocated omega-3 EE90 ( n = 371 ) compared with placebo ( n = 361 ) for participants achieving triacylglycerol < 1.5 mmol/l ( 65 % vs 60 % , p = 0.18 ) or estimated 10-year CVD risks < 20 % ( 34 % vs 30 % , p = 0.18 ) . There were no side effects of note . Conclusions /interpretationMany community-based diabetic patients without known CVD remain at high CVD risk despite statin treatment and require additional risk-reduction strategies . The impact of omega-3 EE90 on CVD risk will remain uncertain until clinical endpoint trial results are available . Trial registration : IS RCT no. 76737502 Funding : The study was funded by Pfizer IMPORTANCE Most patients with cardiovascular disease ( CVD ) do not take recommended medications long-term . The use of fixed-dose combinations ( FDCs ) improves adherence in several clinical areas . Previous trials of cardiovascular FDCs have assessed short-term effects compared with placebo or no treatment . OBJECTIVE To assess whether FDC delivery of aspirin , statin , and 2 blood pressure-lowering agents vs usual care improves long-term adherence to indicated therapy and 2 major CVD risk factors , systolic blood pressure ( SBP ) and low-density lipoprotein cholesterol ( LDL-C ) . DESIGN , SETTING , AND PARTICIPANTS The UMPIRE trial , a r and omized , open-label , blinded-end-point trial among 2004 participants with established CVD or at risk of CVD enrolled July 2010-July 2011 in India and Europe . The trial follow-up concluded in July 2012 . INTERVENTIONS Participants were r and omly assigned ( 1:1 ) to an FDC-based strategy  ( n=1002 ) containing either ( 1 ) 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril , and 50 mg atenolol or ( 2 ) 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril , and 12.5 mg hydrochlorothiazide or to usual care ( n=1002 ) . MAIN OUTCOMES AND MEASURES Adherence to medication ( defined as self-reported use of antiplatelet , statin , and ≥2 BP-lowering medications ) and changes in SBP and LDL-C from baseline . RESULTS At baseline , mean BP was 137/78 mm Hg , LDL-C was 91.5 mg/dL , and 1233 ( 61.5 % ) of 2004 participants reported use of antiplatelet , statin , and 2 or more BP-lowering medications . Median follow-up was 15 months ( interquartile range , 12 - 18 months ) . The FDC group had improved adherence vs usual care ( 86 % vs 65 % ; relative risk [ RR ] of being adherent , 1.33 ; 95 % CI , 1.26 - 1.41 ; P < .001 ) with concurrent reductions in SBP ( -2.6 mm Hg ; 95 % CI , -4.0 to -1.1 mm Hg ; P < .001 ) and LDL-C ( -4.2 mg/dL ; 95 % CI , -6.6 to -1.9 mg/dL ; P < .001 ) at the end of the study . Although there was consistency of effects across predefined subgroups , evidence existed of larger benefits in patients with lower adherence at baseline . In this subgroup of 727 participants ( 36 % ) , adherence at the end of study was 77 % vs 23 % ( RR , 3.35 ; 95 % CI , 2.74 - 4.09 ; P < .001 for interaction ) , SBP was reduced by 4.9 mm Hg ( 95 % CI 7.3 - 2.6 mm Hg ; P = .01 for interaction ) , and LDL-C was reduced by 6.7 mg/dL ( 95 % CI , 10.5 - 2.8 mg/dL ; P = .11 for interaction ) . There were no significant differences in serious adverse events or cardiovascular events ( 50 [ 5 % ] in the FDC group and 35 [ 3.5 % ] in the usual care group ; RR , 1.45 ; 95 % CI , 0.94 - 2.24 ; P=.09 ) between the groups . CONCLUSIONS AND RELEVANCE Among patients with or at high risk of CVD , use of an FDC strategy for blood pressure , cholesterol , and platelet control vs usual care result ed in significantly improved medication adherence at 15 months and statistically significant but small improvements in SBP and LDL-C. TRIAL REGISTRATION clinical trials.gov Identifier : NCT01057537 Atherosclerotic cardiovascular disease ( ASCVD ) is the leading cause of death , decreased quality of life , and medical costs in the United States . Nearly 1 in 3 Americans die of heart disease and stroke ( 1 ) . Most ASCVD is preventable through a healthy lifestyle and effective treatment of cholesterol and blood pressure . The 2013 Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults from the American College of Cardiology and American Heart Association ( ACC/AHA ) provides an evidence -based approach to reducing ASCVD risk ( 2 ) . Guideline Development Process In 2008 , the National Heart , Lung , and Blood Institute ( NHLBI ) convened the Adult Treatment Panel ( ATP ) IV to up date the 2001 ATP-III cholesterol guidelines using a rigorous systematic process to identify and review r and omized , controlled trials ( RCTs ) with cardiovascular outcomes and meta-analyses of these RCTs . The panel comprised experts and clinicians from the fields of cardiology , epidemiology , primary care , and endocrinology ( 2 ) and received support from the Lifestyle Management and Risk Assessment Work Groups ( 3 , 4 ) . Systematic evidence review s conducted according to principles recommended by the Institute of Medicine ( 5 ) were performed to answer 3 questions relevant to clinical care . Two questions focused on the evidence supporting low-density lipoprotein cholesterol ( LDL-C ) and nonhigh-density lipoprotein cholesterol ( HDL-C ) levels as targets of treatment . One question examined the reduction in ASCVD events and adverse effects for each cholesterol-lowering drug class . The panel synthesized the evidence from these 3 review s as well as from Lifestyle Management and Risk Assessment Work Groups review s ( 3 , 4 ) that addressed 5 additional critical questions . Systematic electronic search es of relevant data bases of the peer- review ed English- language literature published from 1 January 1995 through 1 December 2009 for each critical question were conducted by an NHLBI-selected independent contractor and focused on RCTs and systematic review s and meta-analyses of RCTs assessed as fair to good quality . In addition , RCTs with ASCVD outcomes that included coronary heart disease , stroke , and cardiovascular deaths published after that date were eligible for consideration through July 2013 . Evidence tables were constructed , and the strength of evidence was rated according to the NHLBI ( Table 1 of the Supplement ) . Recommendations were grade d according to criteria from the NHLBI ( Table 2 of the Supplement ) and ACC/AHA ( Table 3 of the Supplement ) . Because of the inherent differences in grading systems and the clinical questions driving the recommendations , alignment between the NHLBI and ACC/AHA formats was imperfect . A complete description of the methods used and results of the evidence review are provided in the guideline ( 2 ) and the NHLBI evidence report ( www.nhlbi.nih.gov/ guidelines /cholesterol/ser/index.htm ) . Supplement . NHLBI and ACC/AHA Criteria for Rating Strength of Evidence To help clinicians estimate ASCVD risk , the risk assessment working group developed the Pooled Cohort Equations using data from 5 NHLBI-sponsored longitudinal , population -based cohorts of African American and non-Hispanic white men and women to estimate risk for a first myocardial infa rct ion , coronary heart disease death , or fatal or nonfatal stroke on the basis of age , sex , race , smoking status , total cholesterol level , HDL-C level , systolic blood pressure , antihypertensive therapy , and diabetes ( 4 , 6 ) . These equations significantly advance ASCVD risk estimation by providing sex- and race-specific estimates and including stroke as an outcome . The earlier Framingham equations calculated only coronary heart disease risk for non-Hispanic whites . The draft recommendations were review ed by 23 experts and representatives of federal agencies identified by the NHLBI . In September 2013 , the recommendations developed by the panel were transitioned to the ACC/AHA and had additional review by 4 experts nominated by the ACC Foundation and the AHA . The governing bodies of the ACC and AHA approved the guideline , which also received endorsement from the American Association of Cardiovascular and Pulmonary Rehabilitation , American Pharmacists Association , American Society for Preventive Cardiology , Association of Black Cardiologists , Preventive Cardiovascular Nurses Association , and WomenHeart : The National Coalition for Women with Heart Disease . Recommendations The guideline focuses on treatment of blood cholesterol to reduce ASCVD risk in adults . Major recommendations are summarized here and in Table 1 . The guideline report provides a complete listing of recommendations and supporting evidence behind each recommendation ( 2 ) . Table 1 . Major Recommendations for the Treatment of Blood Cholesterol to Reduce ASCVD Risk in Adults * 1 . Encourage Adherence to a Healthy Lifestyle A healthy lifestyle is the foundation for cardiovascular health . The panel endorsed the 2013 ACC/AHA Lifestyle Management Guideline ( 3 ) for a diet that is low in saturated fat , trans fat , and sodium ; emphasizes vegetables , fruits , whole grains , low-fat dairy products , poultry , fish , legumes , nontropical vegetable oils , and nuts ; and limits sweets , sugar-sweetened beverages , and red meats and engage in regular aerobic physical activity . Adults also should maintain a healthy body weight , avoid smoking , and control hypertension and diabetes when present . 2 . Statin Therapy Is Recommended for Adults in Groups Demonstrated to Benefit Strong RCT evidence shows that reduction in ASCVD events from statin therapy exceeds adverse events for 4 patient groups : those with clinical ASCVD ( acute coronary syndromes , myocardial infa rct ion , stable angina , coronary or other arterial revascularization , stroke , transient ischemic attack , or peripheral arterial disease of atherosclerotic origin ) when  statins are used for secondary prevention , and those with LDL-C levels 190 mg/dL ; those aged 40 to 75 years with diabetes and LDL-C levels 70 to 189 mg/dL ; and those aged 40 to 75 years without diabetes and with a 10-year ASCVD risk 7.5 % when statins are used for primary prevention . Moderate evidence supports consideration of statin therapy for primary prevention in individuals with a 10-year ASCVD risk of 5 % to < 7.5 % . Routine initiation of statin therapy is not recommended in adults with New York Heart Association heart failure class II to IV or those receiving maintenance hemodialysis . R and omized , controlled trials in these groups showed no reduction in ASCVD . 3 . Statins have an Acceptable Margin of Safety When Used in Properly Selected Individuals and Appropriately Monitored Strong RCT evidence supports safety of statins when they are used as directed in conjunction with regular follow-up assessment s in properly selected patients . Adjustment of statin intensity is recommended in individuals older than 75 years with a history of statin intolerance or other characteristics ( 2 ) or those receiving drug therapy that may increase statin adverse events . Routine monitoring of hepatic aminotransferase level or creatine kinase level is not recommended unless clinical ly indicated by symptoms suggesting hepatotoxicity or myopathy . Given the potential for decreasing ASCVD events and death , the relationship of muscle and other symptoms to statin treatment must be confirmed . Therefore , eliciting a history of muscle symptoms before statin initiation and carefully monitoring symptoms during statin discontinuation and rechallenge is recommended . Severe myopathy , rhabdomyolysis , and possibly hemorrhagic stroke are rare complications of statin therapy . Although statin therapy modestly increases the risk for type 2 diabetes , ASCVD risk reduction outweighs the excess risk for diabetes for high-intensity statins in secondary prevention or for 10-year ASCVD risk 7.5 % . Similarly , ASCVD risk reduction outweighs the excess risk for diabetes for moderate-intensity statin therapy in adults with a 10-year ASCVD risk 5 % . 4 . Engage in a ClinicianPatient Discussion Before Initiating Statin Therapy , Especially for Primary Prevention in Patients With Lower ASCVD Risk Decisions to initiate statin therapy in primary prevention should be based on clinical judgment and preferences of informed patients . In adults without clinical ASCVD or diabetes whose LDL-C level is < 190 mg/dL , calculating the estimated 10-year ASCVD risk should be the start of the clinicianpatient discussion and should not automatically lead to statin initiation . As the absolute risk for ASCVD events decreases , so does the net benefit of the intervention . Therefore , discussion of the potential for ASCVD event reduction , adverse effects , drugdrug interactions , and patient preferences is especially important for lower-risk primary prevention . The discussion provides the opportunity to encourage healthy lifestyle habits and control other risk factors . Additional factors may be considered when a risk-based decision is uncertain , including LDL-C levels 160 mg/dL , family history of premature ASCVD , elevated  lifetime ASCVD risk  , high-sensitivity C-reactive protein level 2.0 mg/L ,  coronary artery calcification score  > 300 Agatston units , and anklebrachial index < 0.9 . After age 75 years , comorbid conditions , anticipated longevity , safety considerations , and patient preferences should play a large role in decision making . 5 . Use the Newly Developed Pooled Cohort Equations for Estimating 10-Year ASCVD Risk The Pooled Cohort Equations are currently the best available method for estimating 10-year ASCVD risk to guide statin initiation ( 4 , 6 ) . Application of the inclusion and exclusion criteria from RCTs is cumbersome and results in underidentifying high-risk and overidentifying low-risk individuals for statin treatment . The Pooled Cohort Equations were developed using recent data from 5 NHLBI-sponsored , longitudinal , population -based cohorts of African American and white men and women ( ARIC [ Aims The aims of the study were , first , to critically evaluate lipoprotein(a ) [ Lp(a ) ] as a cardiovascular risk factor and , second , to advise on screening for elevated plasma Lp(a ) , on desirable levels , and on therapeutic strategies . Methods and results The robust and specific association between elevated Lp(a ) levels and increased cardiovascular disease (CVD)/coronary heart disease ( CHD ) risk , together with recent genetic findings , indicates that elevated Lp(a ) , like elevated LDL-cholesterol , is causally related to premature CVD/CHD . The association is continuous without a threshold or dependence on LDL- or non-HDL-cholesterol levels . Mechanistically , elevated Lp(a ) levels may either induce a prothrombotic/anti-fibrinolytic effect as apolipoprotein(a ) resembles both plasminogen and plasmin but has no fibrinolytic activity , or may accelerate atherosclerosis because , like LDL , the Lp(a ) particle is cholesterol-rich , or both . We advise that Lp(a ) be measured once , using an isoform-insensitive assay , in subjects at intermediate or high CVD/CHD risk with premature CVD , familial hypercholesterolaemia , a family history of premature CVD and /or elevated Lp(a ) , recurrent CVD despite statin treatment , ≥3 % 10-year risk of fatal CVD according to European guidelines , and /or ≥10 % 10-year risk of fatal + non-fatal CHD according to US guidelines . As a secondary priority after LDL-cholesterol reduction , we recommend a desirable level for Lp(a ) < 80th percentile ( less than ∼50 mg/dL ) . Treatment should primarily be niacin 1–3 g/day , as a meta- analysis of r and omized , controlled intervention trials demonstrates reduced CVD  by niacin treatment . In extreme cases , LDL-apheresis is efficacious in removing Lp(a ) . Conclusion We recommend screening for elevated Lp(a ) in those at intermediate or high CVD/CHD risk , a desirable level < 50 mg/dL as a function of global cardiovascular risk , and use of niacin for Lp(a ) and CVD/CHD risk reduction BACKGROUND Patients with chronic kidney disease ( CKD ) are at significant risk for cardiovascular disease ( CVD ) . The National Kidney Foundation developed clinical practice guidelines ( Kidney Disease Outcomes Quality Initiative ) for targeting low-density lipoprotein cholesterol ( LDL-C ) goals . OBJECTIVE This study evaluated the extent to which these guidelines were adhered to among patients with CKD and to examine factors associated with the attainment of LDL-C goals . METHODS In this cross-sectional study we evaluated patients with a glomerular filtration rate of 15 to 59 mL/min per 1.73 m² . Patients with previous CVD , who were receiving dialysis , or were post kidney transplant were excluded . Administrative data bases were used to determine the percentage of patients with a fasting lipid profile performed within the previous year , the percentage who attained a LDL-C goal less than 100 mg/dL , and to determine lipid-lowering medications prescribed . Logistic regression analysis was used to identify factors associated with LDL-C goal attainment . RESULTS Of the 4541 patients evaluated , 3157 ( 69.5 % ) had a fasting lipid profile performed within the previous year . Overall , 60.8 % attained a LDL-C less than 100 mg/dL. Among patients at goal , 72.2 % were taking lipid-lowering therapy compared with 37.9 % of those not at goal ( P < .01 ) . Characteristics independently associated with LDL-C goal attainment were increasing age , male gender , increasing chronic disease score , history of diabetes , and statin use . CONCLUSION Although most patients were screened and attained LDL-C goal , there was room for improvement . Statin use was independently associated with LDL-C goal attainment . Future prospect i ve studies should focus on evaluating clinical outcomes of lipid-lowering interventions within the CKD population 42 Background : LHRH agonists are used to treat patients ( pts ) with advanced prostate cancer and have been associated with an increased risk of cardiovascular ( CV ) events and related deaths .  Degarelix is a GnRH antagonist that appears to mitigate this risk . METHODS Results were pooled from 2328 pts participating in 6 prospect i ve r and omised trials . Most pts ( n=1,686 ) received 1 year of GnRH antagonist or LHRH agonist treatment ; the remainder ( n=642 ) had 3 - 7 months ' treatment . Data were classified based on the MedDRA system and analysed using Kaplan Meier plots and a Cox proportional hazard model . Event analysis was based on death from any cause or CV event defined as arterial embolic/thrombotic ; haemorrhagic or ischemic cerebrovascular ; myocardial infa rct ion or other ischemic heart disease .  High risk pts were defined as men with a baseline CV disease ( CVD ) history . RESULTS Treatment groups ( GnRH antagonist , n=1,491 [ degarelix ] ; LHRH agonist , n=837 [ goserelin , n=458 ; leuprolide , n=379 ] ) were balanced for baseline characteristics and CVD history ( 31 % vs. 29 % ) . Characteristics associated with CVD ( e.g. statin medication , elevated blood pressure , diabetes , cholesterol > 6.2 mmol/L ) were similar between groups . The risk of a CV event or death was significantly lower in pts receiving degarelix during the first year of treatment ( see Table ) . In pts with baseline CVD the findings remained significant . In pts with no baseline CVD , there was no difference in subsequent CVD events or death in either group . In analysis by time to CV event only in all pts and pts with baseline CVD ( see Table ) , men receiving GnRH antagonist had a significantly lower risk of CV events . CONCLUSIONS In all pts treated with a GnRH antagonist ( degarelix ) risk of a CV event or death was significantly lower than in pts receiving an LHRH agonist over a treatment period of up to 1 year . In pts with baseline CVD , risk reduction remained significant at ~50 % . [ Table : see text ] IMPORTANCE The value of measuring levels of glycated hemoglobin ( HbA1c ) for the prediction of first cardiovascular events is uncertain . OBJECTIVE To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease ( CVD ) risk . DESIGN , SETTING , AND PARTICIPANTS Analysis of individual-participant data available from 73 prospect i ve studies involving 294,998 participants without a known history of diabetes mellitus or CVD at the baseline assessment . MAIN OUTCOMES AND MEASURES Measures of risk discrimination for CVD outcomes ( eg , C-index ) and reclassification ( eg , net reclassification improvement ) of participants across predicted 10-year risk categories of low ( < 5 % ) , intermediate ( 5 % to < 7.5 % ) , and high ( ≥ 7.5 % ) risk . RESULTS During a median follow-up of 9.9 ( interquartile range , 7.6 - 13.2 ) years , 20,840 incident fatal and nonfatal CVD outcomes ( 13,237 coronary heart disease and 7603 stroke outcomes ) were recorded . In analyses adjusted for several conventional cardiovascular risk factors , there was an approximately J-shaped association between HbA1c values and CVD risk . The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate , but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein . The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 ( 95 % CI , 0.7350 to 0.7517 ) . The addition of information on HbA1c was associated with a C-index change of 0.0018 ( 0.0003 to 0.0033 ) and a net reclassification improvement of 0.42 ( -0.63 to 1.48 ) for the categories of predicted 10-year CVD risk . The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting , r and om , or postload plasma glucose levels . CONCLUSIONS AND RELEVANCE In a study of individuals without known CVD or diabetes , additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk Background —In apparently healthy people , the relation between blood pressure and risk of subsequent cardiovascular disease ( CVD ) is linear . In persons with CVD , the relation is uncertain . Methods and Results —We conducted a prospect i ve study of 5218 older women with CVD who reported their blood pressure at baseline in the Women ’s Antioxidant Cardiovascular Study ( WACS ) , an ongoing double-blind , placebo-controlled secondary prevention trial of the benefits and risks of antioxidant vitamins , folic acid , vitamin B6 , and vitamin B12 among women with CVD or ≥3 coronary risk factors . A total of 661 confirmed CVD events ( nonfatal myocardial infa rct ion , nonfatal stroke , coronary artery bypass graft procedure , percutaneous coronary angioplasty , or CVD death ) occurred during a median follow-up of 6.5 years . After controlling for age , r and omized treatment assignment , antihypertensive medication use , and coronary risk factors , we found that systolic blood pressure ( SBP ) was a strong predictor of CVD events and that the relation between SBP and CVD risk was positive , continuous , and linear ( P for linear trend=0.001 ) . For each 10-mm Hg increment in SBP , there was a 9 % ( 95 % CI 4 % to 15 % ) increase in risk of secondary CVD events . Diastolic blood pressure , mean arterial pressure , and pulse pressure were weaker predictors of CVD risk in this cohort , and joint consideration of SBP and diastolic blood pressure found that only SBP significantly predicted risk . Use of antihypertensive medication did not modify the relationship of SBP with CVD events . Conclusions —In this population of women with CVD , we observed a strong , continuous , and linear association between SBP and risk of secondary CVD events . SBP was the blood pressure measure most strongly related to CVD risk Background Cardiovascular diseases ( CVD ) are responsible for significant morbidity , premature mortality , and economic burden . Despite established evidence that supports the use of preventive medications among patients at high CVD risk , treatment gaps remain . Building on prior evidence and a theoretical framework , a complex intervention has been design ed to address these gaps among high-risk , under-treated patients in the Australian primary care setting . This intervention comprises a general practice quality improvement tool incorporating clinical decision support and audit/feedback capabilities ; availability of a range of CVD polypills ( fixed-dose combinations of two blood pressure lowering agents , a statin ± aspirin ) for prescription when appropriate ; and access to a pharmacy-based program to support long-term medication adherence and lifestyle modification . Methods Following a systematic development process , the intervention will be evaluated in a pragmatic cluster r and omized controlled trial including 70 general practice s for a median period of 18 months . The 35 general practice s in the intervention group  will work with a nominated partner pharmacy , whereas those in the control group will provide usual care without access to the intervention tools . The primary outcome is the proportion of patients at high CVD risk who were inadequately treated at baseline who achieve target blood pressure ( BP ) and low-density lipoprotein cholesterol ( LDL-C ) levels at the study end . The outcomes will be analyzed using data from electronic medical records , utilizing a vali date d extraction tool . Detailed process and economic evaluations will also be performed . Discussion The study intends to establish evidence about an intervention that combines technological innovation with team collaboration between patients , pharmacists , and general practitioners ( GPs ) for CVD prevention . Trial registration Australian New Zeal and Clinical Trials Registry OBJECTIVE Cardiovascular disease ( CVD ) is the most important cause of mortality in patients with type 2 diabetes . We aim ed to determine the effect of statin therapy versus placebo on the progression of carotid intima-media thickness ( IMT ) in type 2 diabetic patients without manifest CVD . RESEARCH DESIGN AND METHODS A r and omized , placebo-controlled , double-blind clinical trial was performed in 250 patients with type 2 diabetes . Patients were given either 0.4 mg cerivastatin or placebo daily . In August 2001 , when cerivastatin was withdrawn from the market , 0.4 mg cerivastatin was replaced by 20 mg simvastatin without deblinding the study . The primary end point was the change of mean common carotid IMT , as measured by B-mode ultrasound , over 2 years . RESULTS Common carotid IMT at baseline was 0.780 mm in the placebo group and 0.763 mm in the statin group and did not change significantly after 2 years . There was no significant difference in IMT change in any carotid segment between the groups . LDL cholesterol was reduced by 25 % in the statin group and increased by 8 % in the placebo group ( P < 0.001 ) . Cardiovascular events occurred in 12 patients in the placebo group and two patients in the statin group ( P=0.006 ) . CONCLUSIONS There was no effect of 2 years ' statin therapy on carotid IMT in type 2 diabetic subjects . The natural history of IMT in our patients was milder than anticipated . In contrast , we observed a significantly lower cardiovascular event rate on statin therapy . Prognostic tools other than IMT should be explored in this patient group Background Diabetic retinopathy ( DR ) is a common microvascular complication of diabetes mellitus , and more than 75 % of patients who have had diabetes for more than 20 years will have some degree of DR . This disease is highly destructive to self-esteem and puts a high burden on public health and pension systems due to the effects that it has on people of working age . The current mainstay of treatment is laser photocoagulation , which causes impairment of vision and discomfort to patients . Thus , finding a systemic drug that could act on all microcirculation and prevent direct manipulation of the eyes would be highly desirable . Objective To assess the efficacy and safety of the drugs in the statin and /or fibrate groups for the prevention and treatment of DR . Methods In this systematic review , we will select r and omized controlled trials of fibrates or statins used for the treatment or prevention of DR . Our search strategy will include free text terms and controlled vocabulary ( eg , MeSH , Emtree ) for , “ diabetic retinopathy ” , “ statins ” , “ fibrates ” , “ hypolipidemic agents ” , and for drugs from both groups . Data bases that will be used include Medical Literature Analysis and Retrieval System/ PubMed , Embase , Cochrane Central Register of Controlled Trials , Latin American and Caribbean Center on Health Sciences Information , Clinical trials.gov , World Health Organization International Clinical Trials Registry Platform , and OpenGrey , and we will not have language or date limits . Two review authors will independently select eligible studies and assess the risk of bias using the Cochrane Collaboration ’s tool . We will report structured summaries of the included studies and , if possible , conduct meta-analyses . Results This is a protocol for a systematic review , therefore results are not available . We registered a short version of this protocol before progressing in the review and we are currently in the process of selecting the studies for inclusion . Conclusions Intensive glucose control and lowering blood pressure and lipids are mechanisms that protect macrocirculation in diabetic patients . Both macrovascular and microvascular events in diabetic patients appear to have a common pathway , starting with endothelial injury . Thus , prevention and treatment of microvascular events may benefit from the same interventions . In the review for which we have written this protocol , we will assess whether the use of lipid-lowering oral drugs of the statin and /or fibrate groups may prevent and /or retard progression of DR , with the added benefit of preserving visual acuity . Trial Registration PROSPERO Importance The associations between cardiovascular disease ( CVD ) and inhaled long-acting & bgr;2-agonists ( LABAs ) or long-acting antimuscarinic antagonists ( LAMAs ) in chronic obstructive pulmonary disease ( COPD ) are greatly debated . Pivotal and relevant r and omized clinical trials included prior LABA or LAMA users and excluded patients with baseline CVD ; therefore , cardiovascular events arising from first-time LABA or LAMA use , if any , could not be observed . There is an urgent need to examine whether new use of and duration since initiating LABAs and LAMAs could act as important determinants of cardiovascular events . Objective To investigate risk of CVD associated with LABAs and LAMAs , focusing on the initiation and duration of LABA and LAMA therapies . Design , Setting , and Participants This nested case-control study included 284 220 LABA-LAMA – naïve patients with COPD at least 40 years old ( mean age , 71.4 years ; 68.9 % men ) , retrieved from the Taiwan National Health Insurance Research Data base for health care cl aims from 2007 to 2011 . Exposure LABA or LAMA use was measured in the year preceding the event or index date , stratified by duration since initiation of LABA or LAMA treatment , new and prevalent users , concomitant COPD medications , and individual agents . Main Outcomes and Measures Cases with inpatient or emergency care visits for coronary artery disease , heart failure , ischemic stroke , or arrhythmia were identified and individually matched to 4 r and omly selected controls . Conditional logistic regressions were performed to estimate odds ratios of CVD from LABA and LAMA treatment . Results During a mean follow-up of 2.0 years , 37 719 patients with CVD ( mean age , 75.6 years ; 71.6 % men ) and 146 139 matched controls ( mean age , 75.2 years ; 70.1 % men ) were identified .  New LABA and LAMA use in COPD was associated with a 1.50-fold ( 95 % CI , 1.35 - 1.67 ; P < .001 ) and a 1.52-fold ( 95 % CI , 1.28 - 1.80 ; P < .001 ) increased cardiovascular risk within 30 days of initiation , respectively , whereas the risk was absent , or even reduced with prevalent use . Individual LABA agents , LAMA dosage forms , and concomitant COPD regimens did not differ in the CVD risks . The risk persisted in an alternative case-crossover study and remained across subgroups without CVD history or prior exacerbations . Conclusions and Relevance New initiation of LABAs or LAMAs in patients with COPD is associated with an approximate 1.5-fold increased severe cardiovascular risk , irrespective of prior CVD status and history of exacerbations Background Many national and international guidelines recommend that the initiation of blood pressure (BP)-lowering drug treatment for the primary prevention of cardiovascular disease ( CVD ) should no longer be based on BP level alone , but on absolute cardiovascular risk . While BP-lowering drug treatment is beneficial in high-risk individuals at any level of elevated BP , clinicians are concerned about legacy effects on patients with low-to-moderate risk and mildly elevated BP who remain “ untreated ” . Objective We aim to investigate the legacy effect of delayed BP-lowering pharmacotherapy in middle-aged individuals ( 45 - 65 years ) with mildly elevated BP ( systolic BP 140 - 159 mmHg and /or diastolic BP 90 - 99 mmHg ) stratified by absolute risk for primary prevention of CVD , but particularly in the low-risk ( < 10 % five-year absolute risk ) group . Methods R and omized trials of BP-lowering therapy versus placebo or pretreated subjects in active comparator studies with posttrial follow-up will be identified using a 2-step process . First , r and omized trials of BP-lowering therapy will be identified by ( 1 ) retrieving the references of trials included in published systematic review s of BP-lowering therapy , ( 2 ) retrieving studies published by the Blood Pressure Lowering Treatment Trialists ’ Collaboration ( BPLTTC ) , and ( 3 ) checking studies referenced in the 1993 World Health Organization/International Society of Hypertension meeting memor and um on BP management . Posttrial follow-up studies will then be identified by forward citation search ing the r and omized trials identified in step 1 through Web of Science . The search will include r and omized controlled trials with at least 1-year in-trial period and a posttrial follow-up phase . Age is the major determinant of absolute cardiovascular risk , so the participants in our review will be restricted to middle-aged adults who are more likely to have a lower cardiovascular risk profile . The primary outcome will be all-cause mortality . Secondary outcomes will include cardiovascular mortality , fatal stroke , fatal myocardial infa rct ion , and death due to heart failure . Results The search es for existing systematic review s and BPLTTC studies were piloted and modified . The study is expected to be completed before June 2018 . Conclusions The findings of this study will contribute to the body of knowledge concerning the beneficial , neutral , or harmful effects of delayed BP-lowering drug treatment on the primary prevention of CVD in patients with mildly elevated BP and low-to-moderate CVD risk . Trial Registration PROSPERO International Prospect i ve Register of Systematic Review s : CRD42017058414 ; https://www.crd.york.ac.uk/ PROSPERO /display_record.asp?ID = CRD42017058414 ( Archived by WebCite ® at http://www.webcitation.org/6t6sa8O2Q Context Long-term outcomes of patients with a reduced glomerular filtration rate ( GFR ) who are treated for hypertension are not well-known . Contribution This analysis of a large multicenter trial found that coronary heart disease ( CHD ) was much more common than end-stage renal disease ( 15 % vs. 6 % ) in hypertensive patients with moderate to severe reductions in GFR who were followed for 6 years . Lower baseline GFR was associated with higher risk for CHD independent of other risk factors . Neither amlodipine nor lisinopril is superior to chlorthalidone in preventing CHD , stroke , or combined CVD , and chlorthalidone is superior to both for preventing heart failure , independent of level of renal function . Caution s These are post hoc subgroup findings , and proteinuria was not measured . The Editors It is estimated that more than 10 million Americans have chronic kidney disease ( 1 , 2 ) . The prevalence of chronic kidney disease is particularly high in older adults ; it is estimated to be greater than 25 % in persons older than 70 years of age . Patients with chronic kidney disease are at very high risk for cardiovascular disease ( CVD ) ( 3 - 8 ) . However , the long-term outcomes of older patients who have a mild or moderate reduction in glomerular filtration rate ( GFR )  , particularly with regard to CVD , are not well-known . Because of the large population of older adults with chronic kidney disease , it is important , from a public health and a clinical st and point , to quantify and underst and the comparative risks for CVD and renal disease in these patients . Management of hypertension is an important aspect of management in patients with chronic kidney disease ; in patients with proteinuria , drugs that inhibit the reninangiotensin axis have been shown to be superior to conventional antihypertensive drug therapy for preservation of renal function ( 1 , 9 , 10 ) . However , it is uncertain whether the choice of antihypertensive drug therapy affects risk for CVD in patients with chronic kidney disease ( 11 , 12 ) . The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) is a large clinical trial design ed to compare the efficacy of treatment with different first-line antihypertensive agents on CVD outcomes in high-risk patients with hypertension who are older than 55 years of age ( 13 - 15 ) . The objectives of this report from the ALLHAT data are to 1 ) compare rates of cardiovascular events with rates of development of end-stage renal disease ( ESRD ) in high-risk older adults with hypertension who have reduced GFR ; 2 ) determine whether reduced GFR is independently associated with an increased risk for CVD after adjusting for traditional cardiovascular risk factors ; and 3 ) report the efficacy of first-step treatment with a calcium-channel blocker ( amlodipine ) or an angiotensin-converting enzyme ( ACE ) inhibitor ( lisinopril ) , each compared with a diuretic ( chlorthalidone ) , in modifying CVD outcomes in high-risk patients with hypertension who are stratified by baseline GFR . Methods The rationale and design of ALLHAT have been presented in detail elsewhere ( 13 ) . The study received institutional review board approval , and participants provided written informed consent . Participants were men and women 55 years of age or older who had hypertension with at least 1 additional risk factor for coronary heart disease ( CHD ) . The risk factors included previous ( > 6 months ) myocardial infa rct ion ( MI ) or stroke , left ventricular hypertrophy demonstrated by electrocardiography or echocardiography , history of type 2 diabetes , current cigarette smoking , high-density lipoprotein cholesterol level of less than 0.91 mmol/L ( < 35 mg/dL ) , and documentation of other atherosclerotic CVD . Exclusion criteria included a history of symptomatic heart failure and /or a known left ventricular ejection fraction of less than 0.35 and a serum creatinine level greater than 176.8 mol/L ( > 2 mg/dL ) as reported by the investigator . Participants ( n= 33 357 ) were recruited at 623 centers in the United States , Canada , Puerto Rico , and the U.S. Virgin Isl and s between February 1994 and January 1998 ( Appendix Figure 1 ) . Appendix Figure 1 . R and omization and follow-up of participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) by treatment group . Block r and omization was stratified by center . Participants were r and omly assigned in a double-blind manner and in a 1.7:1:1 ratio to chlorthalidone , amlodipine , or lisinopril . A fourth arm of the study using the -blocker doxazosin was stopped early and is not considered in this report ( 16 ) . The goal blood pressure in each r and omly assigned group was less than 140/90 mm Hg , to be achieved by titrating the assigned study drug ( step 1 ) and by adding study -supplied , open-label agents ( atenolol , clonidine , or reserpine [ step 2 ] or hydralazine [ step 3 ] ) when necessary , at the physician 's discretion ( 16 , 17 ) . Nonpharmacologic lifestyle approaches to treatment of hypertension were recommended according to national guidelines . Other drugs , including low doses of open-label step 1 drug classes , were permitted if clinical ly indicated . Follow-up visits were at 1 month ; 3 , 6 , 9 , and 12 months ; and every 4 months thereafter . Levels of serum creatinine were measured in a single central laboratory using VITROS ( Ortho Clinical Diagnostics , Rochester , New York ) , which had a coefficient of variation of approximately 2 % . Creatinine measurements were calibrated to the Modification of Diet in Renal Disease ( MDRD ) laboratory , and no additional correction was found to be necessary ( 18 ) . A total of 1460 participants ( 4.4 % ) were missing creatinine values , and thus estimated GFR , at baseline . The simplified MDRD Study equation was used to estimate GFR ( mL/min per 1.73 m2 ) according to the following formula : 186.3 ( serum creatinine in mg/dL 1.154 ) ( age in years 0.203 ) 1.212 ( if black ) 0.742 ( if female ) ( 19 ) . Patients were classified into 3 baseline categories of GFR consistent with recommendations in the National Kidney Foundation Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines on Chronic Kidney Disease : normal or increased ( 90 mL/min per 1.73 m2 ) , mild reduction ( 60 to 89 mL/min per 1.73 m2 ) , and moderate or severe reduction ( < 60 mL/min per 1.73 m2 ) ( 1 ) . Because a serum creatinine level of greater than 176.8 mol/L ( > 2 mg/dL ) was an exclusion criterion , the percentage of patients with severe chronic kidney disease ( estimated GFR 29 mL/min per 1.73 m2 ) at baseline was very small ( 0.6 % ) . Therefore , as in another study ( 6 ) , these participants were considered along with those with moderate chronic kidney disease ( GFR 30 to 59 mL/min per 1.73 m2 ) . Patients were also classified as diabetic or not diabetic by baseline history of diabetes . The primary outcome was fatal CHD or nonfatal MI . Combined CVD was defined as a composite of the primary outcome , coronary revascularization , hospitalized angina , stroke , other treated angina , heart failure ( fatal , hospitalized , or treated nonhospitalized ) , and peripheral arterial disease . Coronary revascularization included coronary artery bypass grafting , percutaneous angioplasty , insertion of stents , and atherectomy . Peripheral vascular disease included intermittent claudication or arterial disease of the lower extremities leading to procedures , such as revascularizations , angioplasty of peripheral arteries , or amputation . End-stage renal disease included death from kidney disease , kidney transplantation , and start of long-term kidney dialysis . Study outcomes were defined in the ALLHAT Manual of Operations ( available from the authors on request ) , were assessed by site investigators at follow-up visits , and were reported to the Clinical Trials Center . Medical review ers from the Clinical Trials Center review ed all events for concordance with study criteria . More detailed information was collected on a r and om ( 10 % ) subset of CHD and stroke events and was review ed by the Endpoints Subcommittee to vali date the procedure of using physician diagnoses . Statistical Analyses Data were analyzed according to the participants ' r and omly assigned treatments regardless of their subsequent medications ( intention-to-treat analysis ) . Baseline characteristics were compared across treatments and the 3 GFR groups by using the Z-test for continuous covariates and contingency table analyses for categorical data . Cox proportional hazards models were used to obtain hazard ratios and 95 % CIs for time to CHD , combined CVD , and stroke to assess the effects of treatment within each of the 3 GFR strata . Because baseline characteristics are similar across treatment groups , no adjustment was deemed necessary . Additional models were used to assess the impact of baseline GFR ( using deciles ) on CHD and combined CVD . Baseline characteristics are not expected to be similar across the various GFR groups defined by deciles ; therefore , adjustments are necessary . Cox test assumptions were examined using loglog plots and tests of treatment by time ( time-dependent ) interaction terms . Because the assumptions were violated in the case of heart failure , logistic models were used to estimate odds ratios for this end point . The consistency of treatment effects across subgroups was examined in the Cox and logistic models by calculating the differences in the log likelihood for models with and without the interaction terms . Treatment effects by GFR subgroup were also analyzed for participants with a history of diabetes by using the aforementioned methods . A P value less than 0.05 indicated statistical significance for the results . Role of the Funding Sources This study was supported by contract NO1-HC-35130 from the National Heart , Lung , and Blood Institute ( NHLBI ) ; the NHLBI was involved in the collection , analysis , and interpretation of the data and the decision to su bmi t the manuscript for publication but was not involved in the direct operations of the study centers . Study medications were supplied by Context It is not clear whether variability in a patient 's outpatient blood pressure ( BP ) measurements has prognostic importance . Contribution Patients with greater visit-to-visit variability in BP readings had an increased risk for cardiovascular events and mortality , which was independent of their overall degree of BP control . Implication Further studies are warranted to assess whether reducing visit-to-visit BP variations will alter the risk for adverse cardiovascular outcomes . The prognostic value of blood pressure ( BP ) is mainly based on measurements obtained in a clinical setting , typically from a few visits ( 1 ) . Until recently , variability of BP across outpatient visits was dismissed as r and om fluctuation around a patient 's true underlying BP ( 2 , 3 ) . Although some studies have reported associations between higher visit-to-visit variability ( VVV ) of systolic BP ( SBP ) and an increased risk for stroke and coronary heart disease ( CHD ) , other analyses have failed to show such associations ( 410 ) . The method applied in estimating VVV of BP varied widely across previous studies . In addition , studies have used as few as 3 visits and as many as 56 visits to estimate the VVV of BP , and the time between visits has ranged from 2 days to as long as 4 years ( 5 , 11 , 12 ) . These factors not only influence VVV of BP but could also affect the strength of its association with cardiovascular disease ( CVD ) outcomes ( 4 , 13 ) . To address the inconsistent findings from previous studies , we did a secondary data analysis of ALLHAT ( Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ) to examine whether VVV of BP is associated with CVD and mortality events . ALLHAT provides the opportunity to evaluate the association between VVV of BP and major clinical outcomes in a large and diverse population with hypertension in which visits were conducted at set time intervals , BP was measured by following a st and ardized protocol , and outcomes were evaluated over several years of follow-up . Methods Study Design We did a cohort study as a secondary analysis using data from ALLHAT . Figure 1 shows the timeline for assessment of VVV of BP and outcome events within ALLHAT . The primary exposure of interest , VVV of SBP , was ascertained at the 7 study visits conducted between 6 and 28 months after r and omization . We studied 4 outcomes : fatal CHD or nonfatal myocardial infa rct ion ( MI ) , all-cause mortality , stroke , and heart failure . Participants were followed from their 28-month visit until the occurrence of an outcome event or the end of active ALLHAT follow-up ( October 2001 to March 2002 ) . Participants who had an event before their 28-month visit were excluded from all analyses . Figure 1 . Study design evaluating the association between VVV of BP and cardiovascular outcomes and all-cause mortality in ALLHAT . ALLHAT = Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ; BP = blood pressure ; DBP = diastolic blood pressure ; SBP = systolic blood pressure ; VVV = visit-to-visit variability . * Participants were followed for a mean of 2.7 to 2.9 y ( maximum , 5.7 y ) depending on the outcome after assessment of VVV of BP . ALLHAT was a multicenter , double-blind , r and omized clinical trial sponsored by the National Heart , Lung , and Blood Institute of the National Institutes of Health . A complete description of the rationale and design of ALLHAT has been previously published ( 14 ) . In brief , ALLHAT was design ed to determine whether treatment initiated with a calcium-channel blocker ( amlodipine ) , angiotensin-converting enzyme inhibitor ( lisinopril ) , or -blocker (doxazosin)each compared with treatment initiated with a diuretic (chlorthalidone)would lower major cardiovascular outcomes . The primary end point was incidence of fatal CHD or nonfatal MI .  A total of 42418 hypertensive adults aged 55 years or older with 1 or more additional risk factor for CVD were enrolled at 623 clinical sites across the United States , Canada , Puerto Rico , and the U.S. Virgin Isl and s between February 1994 and January 1998 . The doxazosin treatment group was discontinued in 2000 because of the small chance of finding a benefit on CHD outcomes and an increased risk for CVD than in the chlorthalidone group ( 15 ) . The main results comparing participants r and omly assigned to chlorthalidone , amlodipine , or lisinopril were published in December 2002 ( 16 ) . The trial was approved by local institutional review boards , and all participants provided written informed consent . Our current analysis was approved by the Institutional Review Board at the University of Alabama at Birmingham . Study Visits , BP Measurements , and Calculation of VVV of BP To calculate intraindividual VVV of SBP and diastolic BP ( DBP ) , we used data from 7 follow-up visits that occurred 6 , 9 , 12 , 16 , 20 , 24 , and 28 months after r and omization . We chose to begin the assessment period at the 6-month follow-up visit to avoid confounding by the initial reduction in BP that occurred between r and omization and this visit ( SBP , 6 to 10 mm Hg ; DBP , approximately 5 mm Hg ) due to early medication titration . To increase the precision of estimates , we calculated VVV of BP for participants with BP measurements at 5 , 6 , or 7 visits conducted between month 6 and 28 after r and omization . The VVV of BP was imputed for participants who attended fewer than 5 visits between months 6 and 28 . To maximize follow-up time , we did not extend the assessment past the 28-month follow-up visit . At each follow-up visit ,  BP was measured twice by a trained observer by means of a st and ardized technique ( 17 ) . Using the average BP at each visit , we defined VVV of BP by the intraindividual SD across visits . Average real variability ( ARV ) and SD independent of the mean ( SDIM ) were calculated as alternative metrics for VVV of BP ( Appendix Figure ) ( 18 ) . The VVV of DBP was also calculated in secondary analyses . Appendix Figure . Formulas used to calculate VVV of BP metrics . ARV = average real variability ; BP = blood pressure ; SDIM = SD independent of the mean ; VVV = visit-to-visit variability . Outcome Ascertainment We studied 4 outcomes , including fatal CHD or nonfatal MI , all-cause mortality , stroke , and heart failure . The event ascertainment process is detailed elsewhere ( 14 , 16 ) . Participants were followed from the end of the assessment period to the date of each outcome , their date of death , or the end of active ALLHAT follow-up ( 1 October 2001 through 31 March 2002 ) . Covariate Information Covariates used for adjustment were selected a priori on the basis of their potential role as confounders . Baseline ( before r and omization ) variables included age , sex , race/ethnicity , education , current cigarette smoking status , body mass index , use of aspirin , high-density lipoprotein cholesterol level less than 0.91 mmol/L ( < 35 mg/dL ) ( at 2 occasions in the 5 years before ALLHAT enrollment ) ,  total cholesterol level , estimated glomerular filtration rate ( eGFR ) , diabetes , history of MI or stroke , documentation of other atherosclerotic CVD , history of revascularization , atrial fibrillation by electrocardiography , left ventricular hypertrophy ( LVH ) , the presence of ST depression and T-wave inversion , and use of antihypertensive medication  before ALLHAT r and omization . The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation ( 19 ) . Data collected at visits conducted 6 to 28 months after r and omization were used to calculate mean SBP and DBP ; pulse pressure ; the use of antihypertensive medications beyond the r and omization drug ; changes in antihypertensive medication regimen ( adding , stopping , or changing antihypertensive medications ) ; use of statins ; and low adherence , which is defined as a report of a participant receiving less than 80 % of the r and omization drug at any visit between months 6 and 28 . Participants who reported taking 80 % or more of their r and omization drug at every visit between months 6 and 28 were considered to have high adherence . Statistical Analysis Because of limited follow-up available after the assessment period for participants r and omly assigned to receive doxazosin , we restricted our analyses to the 33357 ALLHAT participants r and omly assigned to receive chlorthalidone , amlodipine , or lisinopril .  We excluded 7543 participants who had CVD events or died before the 28-month visit . We imputed VVV of BP for participants with fewer than 5 visits and BP measurements between months 6 and 28 of follow-up . In addition , missing data for covariates were imputed ( Appendix Table 1 ) . Imputation was performed with 10 data sets using chained equations . Appendix Table 1 . Percentage of Missing Data for Participants Included in the Current Analyses Characteristics of participants included in the current analyses were calculated after participants were stratified into a quintile of SD of SBP . The KaplanMeier method was used to calculate the cumulative incidence of each outcome by quintile of SD of SBP . Cox proportional hazards regression was used to calculate multivariable-adjusted hazard ratios ( HRs ) for each outcome associated with a quintile of SD of SBP , with the lowest quintile serving as the reference . Four nested models were constructed . Model 1 included adjustment for age , race/ethnicity , sex , region of residence , and antihypertensive r and omization assignment . Model 2 includes the variables in model 1 and additional adjustment for education , smoking status , body mass index , use of aspirin , low high-density lipoprotein cholesterol level , total cholesterol level , eGFR , diabetes , history of MI or stroke , history of other atherosclerotic CVD , history of coronary revascularization , atrial fibrillation by electrocardiography , major ST depression or T-wave inversion , LVH , use of antihypertensive medications before ALLHAT r and omization , and  statin use during the assessment period ( months 6 through 28 of follow-up ) . Model 3 includes the variables in model 2 and additional adjustment for mean pulse pressure , Background GlycA , a novel protein glycan biomarker of N‐acetyl side chains of acute‐phase proteins , was recently associated with incident cardiovascular disease ( CVD ) in healthy women . Whether GlycA predicts CVD events in the setting of statin therapy in men and women without CVD but with evidence of chronic inflammation is unknown . Methods and Results In the Justfication for the Use of Statins in Prevention : an Intervention Trial Evaluating Rosuvastatin ( JUPITER ) trial ( NCT00239681 ) , participants with low‐density lipoprotein cholesterol < 130 mg/dL and high‐sensitivity C‐reactive protein ( hsCRP ) ≥2 mg/L were r and omized to rosuvastatin 20 mg/day or placebo . GlycA was quantified by nuclear magnetic resonance spectroscopy in 12 527 before r and omization and 10 039 participants at 1 year . A total of 310 first primary CVD events occurred during maximum follow‐up of 5.0 years ( median , 1.9 ) . GlycA changed minimally after 1 year on study treatment : 6.8 % and 4.7 % decrease in the rosuvastatin and placebo groups , respectively . Overall , baseline GlycA levels were associated with increased risk of CVD : multivariable‐adjusted hazard ratio ( HR ) per SD increment , 1.20 ( 95 % CI , 1.08–1.34 ; P=0.0006 ) . After additionally adjusting for hsCRP , this was slightly attenuated ( HR , 1.18 ; 95 % CI , 1.04–1.35 ; P=0.01 ) . On‐treatment GlycA levels were also associated with CVD ; corresponding multivariable‐adjusted HRs per SD before and after additionally adjusting for hsCRP : 1.27 ( 95 % CI , 1.13–1.42 ; P<0.0001 ) and 1.24 ( 95 % CI , 1.07–1.44 ; P=0.004 ) , respectively . Tests for heterogeneity by treatment arm were not significant ( P for interaction , > 0.20 ) . Conclusion In the JUPITER trial , increased levels of GlycA were associated with an increased risk of CVD events independent of traditional risk factors and hsCRP . Clinical Trials Registration URL : http://www . clinical trials.gov . Unique identifier : NCT00239681 BACKGROUND With few exceptions , tools used to estimate cardiovascular disease ( CVD ) risk in those without prior events are based mainly on data from middle-aged subjects . Given the ever increasing number of older people , many with hypertension , a risk score relevant to this group is warranted . Our aim was to develop a cardiovascular risk equation suitable for risk prediction in elderly , hypertensive population s. METHODS We utilized  cardiovascular end point data from 4.1 years median follow-up in 5,426 hypertensive subjects without previous CVD from the Second Australian National Blood Pressure Study ( ANBP2 ) . Our risk model , based on Cox regression , was developed using 75 % of subjects without evident CVD ( n = 4,072 ) , r and omly selected and stratified by age and gender , and internally vali date d using the remaining 25 % . The model was also externally vali date d against the Dubbo Study data set . RESULTS The final model included sex , age , physical activity in the 2 weeks prior to entry into study , family history , use of anticoagulants , central ly acting antihypertensive agents or diabetes medication , and an interaction term for sex and diabetes medication . The C-statistic was 0.65 ( 0.62 - 0.67 ) for our predictive model on the model development data set and 0.62 ( 0.57 - 0.67 ) on the internal validation data set . The Dubbo Data C-statistic for CVD was 0.68 ( 95 % CI 0.65 - 0.71 ) . CONCLUSIONS All models performed similarly . Because of greater ease of implementation , we recommend that existing algorithms be extended into older age groups The American Heart Association/American Stroke Association ( AHA/ASA ) Writing Committee for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack ( TIA ) has review ed the results of recent trials that were published after our previous recommendations were issued.1 Our intention in the present statement is to provide a brief review of the new data , to up date specific recommendations , and to provide the reasons for any modifications . The 2 areas in which major new clinical trials have been published are ( 1 ) the use of specific antiplatelet agents for stroke prevention in patients with a history of noncardioembolic ischemic stroke or TIA and ( 2 ) the use of statins in the prevention of recurrent stroke . Recently published trials have added to the evidence of the benefit of the use of specific antiplatelet agents for stroke prevention in patients with a history of noncardioembolic ischemic stroke or TIA . The secondary prevention guidelines 1 have been up date d to reflect this new evidence . # # # Addition of Clopidogrel to Aspirin for Prevention of Vascular Events The Clopidogrel and Aspirin Versus Aspirin Alone for the Prevention of Atherothrombotic Events ( CHARISMA ) trial2 was a double-blinded study that r and omized 15 603 subjects with cardiovascular disease or multiple risk factors for cardiovascular disease to either clopidogrel 75 mg plus low-dose aspirin ( 75 to 162 mg ) or placebo plus aspirin ( 75 to 162 mg ) . Roughly 35 % of subjects ( n=4320 ) qualified on the basis of the presence of cerebrovascular disease within 5 years of enrollment ; approximately a third experienced TIA . The median follow-up was 28 months . No significant differences were seen in the rates of nonfatal ischemic stroke between the 2 groups ( 1.7 % versus 2.1 % , P = 0.07 ) . The placebo plus aspirin group showed a higher rate of nonfatal stroke than did the clopidogrel group ( 1.9 % versus 2.4 % , P = 0.03 ) . The 2 groups experienced no differences in the rate of intracerebral hemorrhage AIM To compare three methods of assessing 5-year absolute risk of cardiovascular disease ( CVD ) in adults with type 2 diabetes ; the Framingham CVD equation , the UK Prospect i ve Diabetes Study ( UKPDS ) coronary heart disease plus stroke equations and the New Zeal and Guidelines Group (NZGG)-modified Framingham CVD equation . METHODS Participants were 423 people with newly ( n=118 ) or previously diagnosed ( n=305 ) Type 2 diabetes mellitus aged 35 to 74 years with no past history of cardiovascular disease or nephropathy from an interviewed study population of 4049 adults .  Absolute 5-year CVD risks were calculated in 5-year age b and s by gender ; Maori , Pacific , and European ethnicity ; and newly and previously diagnosed diabetes . RESULTS The mean 5-year CVD risk score was 2.9 % ( 95%CI : 2.40 - 3.42 ; p<0.0001 ) lower for the UKPDS risk engine compared to the original Framingham equation in absolute terms , and 7.6 % ( 95%CI : 7.05 - 8.08 ; p<0.0001 ) lower than the NZGG-modified Framingham equation . In general , 5-year CVD risks were highest using the NZGG-modified equation , intermediate using the original Framingham equation and lowest using the combined UKPDS coronary heart disease plus stroke equations , in all age groups by gender , ethnicity , and time of diagnosis of Type 2 diabetes . However , the 5-year CVD risks are themselves potentially low as they include treated blood pressure and lipid values . Compared to the UKPDS 15 % level of risk , the NZ Guidelines modified 15 % level of risk results in people with diabetes being recommended for CVD drug management 10 to 17 years earlier . CONCLUSIONS In general , among people with Type 2 diabetes , the Framingham equations showed higher 5-year CVD risk estimates compared to combined UKPDS coronary heart disease plus stroke equations and the NZGG-modified Framingham equation showed the highest 5-year CVD risks . In practice , people with type 2 diabetes will be managed earlier and more intensively based on their risk estimated by the current NZGG guidelines than if the UKPDS or original Framingham equations were used BACKGROUND Chronic kidney disease ( CKD ) is associated with an increased risk of incident cardiovascular disease ( CVD ) ; however , the role of statins for the primary prevention of acute cardiovascular events in patients with CKD and the effect of statins on kidney function loss in persons without prevalent CVD have not been studied . STUDY DESIGN Post hoc analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study . SETTING & PARTICIPANTS Multicenter , r and omized , double-blind , placebo-controlled trial of 5,608 men and 997 women without CVD r and omly assigned to treatment with lovastatin or placebo .  INTERVENTION Placebo or lovastatin , 20 mg/d . OUTCOMES & MEASUREMENTS First major acute cardiovascular event in participants with mild CKD and kidney function loss in persons with or without CKD .  Estimated glomerular filtration rate was calculated using the 4-variable Modification of Diet in Renal Disease Study equation . RESULTS At baseline ,  mean estimated glomerular filtration rate in participants with CKD ( n = 304 ) was 53.0 + /- 6.0 mL/min/1.73 m(2 ) . After an average follow-up of 5.3 + /- 0.8 years , the incidence of a fatal and nonfatal CVD event was lower in participants with CKD receiving lovastatin than in those receiving placebo ( adjusted relative risk [ RR ] , 0.31 ; 95 % CI , 0.13 - 0.72 ; P = 0.01 ) . Tests for interaction suggested that the benefit of lovastatin was independent of the presence of CKD . Lovastatin did not reduce the annualized mean decrease in estimated glomerular filtration rate ( -1.3 + /- 0.07 vs -1.4 + /- 0.07 mL/min/1.73 m(2)/y , respectively ; P = 0.1 ) or the frequency of a > or = 25 % decrease in kidney function ( adjusted RR , 1.10 ; 95 % CI , 0.96 - 1.28 ; P = 0.2 ) or incident CKD ( adjusted RR , 1.04 ; 95 % CI , 0.86 - 1.27 ; P = 0.6 ) . LIMITATIONS Unable to determine the cause and duration of kidney disease , and information regarding proteinuria was not available . CONCLUSIONS Lovastatin is effective for the primary prevention of CVD in patients with CKD , but is not effective in decreasing kidney function loss in persons with no CVD Background Cardiovascular disease ( CVD ) is the leading cause of early death worldwide , responsible for an estimated 29 % of all global deaths . Reducing salt intake lowers blood pressure and risk of secondary cardiac events . However , identifying low salt foods can be challenging . SaltSwitch is a simple smartphone application ( app ) that enables shoppers to scan the barcode of packaged foods and receive an immediate , interpretive , traffic light nutrition label on the screen , along with suggestions for healthier lower-salt alternatives . A growing body of evidence suggests mobile technologies can support healthy behaviour change . However , robust evidence for the impact of smartphone interventions is lacking . This manuscript outlines the rationale and methods for a r and omized controlled trial design ed to determine the effectiveness of SaltSwitch in supporting people with CVD to make lower-salt food choices . Design / Methods A 6-week , two-arm , parallel , r and omized controlled trial is being undertaken in New Zeal and ( 2 weeks baseline and 4 weeks intervention ) . Three hundred adults aged 40 years and older with CVD and their main household shoppers are recruited from research lists , cardiac rehabilitation clinics , and communities in Auckl and . Participants are r and omized to receive either the SaltSwitch smartphone app or no intervention ( control ) . R and omisation is stratified by ethnicity and age . The primary outcome is the salt content of household food purchases . Secondary outcomes are the saturated fat and energy content of household food purchases , household food expenditure , use and acceptability of the SaltSwitch app by shoppers , and urinary sodium and blood pressure of participants with CVD . Ambulatory blood pressure and potential longer-term impact ( 12 weeks ) of SaltSwitch will be assessed in sub- studies ( n ~ 40 and n ~ 20 , respectively ) . Household purchases of salt and other nutrients will be assessed using till receipt data electronically linked with br and ed food composition data . Discussion The results of the SaltSwitch trial will determine the effectiveness , use and acceptability of a smartphone application to support lower salt food choices and secondary prevention of CVD.Trial registration ACTRN12614000206628 . Registered 30 March 2014 Abstract Objective : To test the effectiveness and safety of saxagliptin 5 mg/d in patients with type 2 diabetes mellitus ( T2DM ) with and without history of cardiovascular disease ( CVD ) or cardiovascular ( CV ) risk factors . Methods : The authors conducted a post hoc analysis of data from 3 r and omized studies that compared saxagliptin versus placebo as initial combination therapy with metformin for 24 weeks ( N = 648 ) and versus placebo as an add-on to insulin with and without metformin for 24 weeks ( N = 455 ) , and assessed noninferiority to glipizide as an add-on to metformin for 52 weeks ( N = 858 ) . Efficacy outcomes were the adjusted mean change from baseline in glycated hemoglobin ( HbA1c ) level , fasting plasma glucose concentration , and body weight and the proportion of patients achieving an HbA1c level < 7 % . Pairwise comparisons were performed in subgroups with 1 ) history/no history of CVD , 2 ) ≥ 2 versus 0 to 1 CV risk factors , 3 ) hypertension/no hypertension , and 4 ) statin use/no statin use . Adverse events ( AE ) and hypoglycemia were monitored . Results : In the initial combination therapy study , reductions in HbA1c level from baseline were greater with saxagliptin versus placebo in all subgroups ( difference [ saxagliptin - placebo ] , −0.38 % to −0.67 % ) . In the add-on to insulin ± metformin study , differences in adjusted mean change in HbA1c level versus placebo ranged from −0.23 % to −0.58 % across subgroups . In the noninferiority to glipizide study , adjusted mean changes in HbA1c level were comparable between saxagliptin and glipizide , across subgroups ( difference , 0.08%–0.21 % ) . No evidence suggested clinical ly relevant treatment-by-subgroup interactions in pairwise comparison . Incidences of ≥ 1 AE were comparable across subgroups . Incidences of confirmed hypoglycemia with saxagliptin were 0 in both metformin add-on studies and 1.2 % to 7.8 % with saxagliptin + insulin ± metformin . Conclusion : In patients with T2DM , saxagliptin 5 mg/d was similarly effective in improving glycemic control , with an AE profile similar to that of placebo , irrespective of CVD history , number of CV risk factors , hypertension , or statin use . Trial registration : www . Clinical Trials.gov identifiers : NCT00327015 , NCT00575588 , Objective : Rheumatoid arthritis ( RA ) patients have an increased risk of developing cardiovascular diseases ( CVD ) . Other autoimmune diseases such as hypothyroidism are also associated with an enhanced risk for CVD . Our objective was to determine first , the prevalence of hypothyroid disorders in RA patients , and second , the risk of CVD in RA patients with hypothyroid abnormalities . Methods : Subjects were RA patients who participated in an ongoing prospect i ve cohort study of cardiovascular mortality and morbidity ( n = 358 ) in which hypothyroid abnormalities were assessed .  CVD was defined as a verified medical history of coronary , cerebral or peripheral arterial disease . Results : Clinical hypothyroidism was observed in 16 of 236 female RA patients ( 6.8 % ) , which is significantly higher than in the general population of The Netherl and s. Sub clinical hypothyroidism was detected in 6 out of 236 RA women ( 2.5 % ) . In female RA patients , CVD was present in 6 out of 16 ( 37.5 % ) of all hypothyroid women . The odds ratio for CVD comparing female hypothyroid RA patients with female euthyroid RA patients was 4.1 ( 95 % CI 1.2–14.3 ) after adjustment for sex , age , diabetes , smoking ( ever ) , hypertension and statin use . Conclusions : Clinical hypothyroidism was observed three times more often in female RA patients than females in the general population . In female RA patients , clinical hypothyroidism was associated with a fourfold higher risk of CVD in comparison with euthyroid female RA patients independently of the traditional risk factors Aim : To assess the performance of the QRISK score for predicting cardiovascular disease ( CVD )  in an independent UK sample from general practice and compare with the Framingham score . Design : Prospect i ve open cohort study Setting : UK general practice s contributing to the THIN and Q RESEARCH data bases . Cohort : The THIN validation cohort consisted of 1.07 million patients , aged 35–74 years registered at 288 THIN practice s between 1 January 1995 and 1 April 2006 . The Q RESEARCH validation cohort consisted of 0.61 million patients from 160 practice s ( one-third of the full data base ) with data until 1 January 2007 . Patients receiving statins , those with diabetes or CVD at baseline were excluded . End point : First diagnosis of CVD ( myocardial infa rct ion , coronary heart disease ( CHD ) , stroke and transient ischaemic attack ) recorded on the clinical computer system during the study period . Exposures : Age , sex , smoking status , systolic blood pressure , total/high-density lipoprotein cholesterol ratio , body mass index , family history of premature CHD , deprivation and antihypertensive medication . Results : Characteristics of both cohorts were similar , except that THIN patients were from slightly more affluent areas and had lower recording of family history of CHD . QRISK performed better than Framingham for every discrimination and calibration statistic in both cohorts . Framingham overpredicted risk by 23 % in the THIN cohort , while QRISK underpredicted risk by 12 % . Conclusion : This analysis demonstrated that QRISK is better calibrated to the UK population than Framingham and has better discrimination . The results suggest that QRISK is likely to provide more appropriate risk estimates than Framingham to help identify patients at high risk of CVD in the UK BACKGROUND Although basic research suggests that vitamins may have an important role in the prevention of cardiovascular diseases ( CVD ) , the data from cohort studies and clinical trials are inconclusive . METHODS This prospect i ve cohort study was conducted among 83 639 male physicians residing in the United States who had no history of CVD or cancer . At baseline , data on use of vitamin E , ascorbic acid ( vitamin C ) , and multivitamin supplements were provided by a self-administered question naire . Mortality from CVD and coronary heart disease ( CHD ) was assessed by death certificate review . RESULTS Use of supplements was reported by 29 % of the participants . During a mean follow-up of 5.5 years , 1037 CVD deaths occurred , including 608 CHD deaths . After adjustment for several cardiovascular risk factors , supplement use was not significantly associated with total CVD or CHD mortality . For vitamin E use , the relative risks ( RRs ) were 0.92 ( 95 % confidence interval [ CI ] , 0.70 - 1.21 ) for total CVD mortality and 0.88 ( 95 % CI , 0.61 - 1.27 ) for CHD mortality ; for use of vitamin C , the RRs were 0.88 ( 95 % CI , 0.70 - 1.12 ) for total CVD mortality and 0.86 ( 95 % CI , 0.63 - 1.18 ) for CHD mortality ; and for use of multivitamin supplements , the RRs were 1.07 ( 95 % CI , 0.91 - 1.25 ) for total CVD mortality and 1.02 ( 95 % CI , 0.83 - 1.25 ) for CHD mortality . CONCLUSIONS In this large cohort of apparently healthy US male physicians , self-selected supplementation with vitamin E , vitamin C , or multivitamins was not associated with a significant decrease in total CVD or CHD mortality . Data from ongoing large r and omized trials will be necessary to definitely establish small potential benefits of vitamin supplements on subsequent cardiovascular risk BACKGROUND Patients with atrial fibrillation ( AF )  are at increased risk of thromboembolic events . The long-term prognostic implication s of AF in patients with atherothrombosis are unknown . METHODS We compared 4-year CV outcomes in patients with and without a history of AF recorded at their baseline visit in the REACH Registry , an international , prospect i ve cohort of patients with established atherosclerotic arterial disease ( CAD , CVD , PAD ) or at least 3 risk factors ( RFO ) . RESULTS AF status and 4 year follow-up data were available on 44,518 patients . The prevalence of AF at baseline was 10.3 % ( n=4582 ) . Overall , patients with AF had approximately a 2-fold increase in the composite of CV death , MI , or stroke compared with patients without AF after adjustment for age , gender , prior ischemic event , vascular disease , congestive heart failure , diabetes , smoking , body mass index , region , aspirin and statin use ( 18.9 % vs. 9.4 % , p<0.0001 ) . This increased risk was observed both in patients with established atherothrombosis ( CAD : 15.5 % vs. 8.0 % , p=0.0001 ; CVD : 23.6 % vs. 13.6 % , p<0.0001 ; PAD : 24.3 % vs. 13.5 % , p=0.089 ) and those with multiple risk factors ( RFO : 12.1 % vs. 5.9 % , p=0.017 ) . Only 52 % of patients with a history of AF at baseline were receiving anticoagulation at 4 years . CONCLUSIONS Patients with a history of both AF and atherothrombosis have particularly high long-term CV risk . Despite this increased risk , almost half of all patients with AF do not receive guideline recommended anticoagulation , highlighting an important public health priority BACKGROUND Interventions to promote prescribing of preventive therapies in patients with cardiovascular disease ( CVD ) or diabetes have reported variable success . OBJECTIVE ( i ) To evaluate the effect of prescribing feedback on GP practice using academic detailing compared to postal bulletin on prescribing of CVD preventive therapies in patients with CVD or diabetes at 3 and 6 months post intervention and ( ii ) to evaluate the intervention from a GP 's perspective . METHODS Volunteer GP practice s ( n = 98 ) were r and omized to receive individualized prescribing feedback via academic detailing ( postal bulletin plus outreach visit ) ( n = 48 ) or postal bulletin ( n = 50 ) . The proportion of  CVD or diabetic patients on  statins and antiplatelet agents/warfarin  pre- and post-intervention was calculated for each GP practice . Multivariate regression with a r and om effects model was used to compare differences between the groups adjusting for GP clustering and confounding factors . beta-Coefficients and 95 % confidence intervals ( CIs ) are presented . RESULTS There was a 3 % increase in statin prescribing in CVD patients at 6 months post-intervention for both r and omized groups , but there was no statistical difference between the groups ( beta = 0.004 ; 95 % CI = -0.01 to 0.02 ) .  Statin and antiplatelet/warfarin prescribing also increased in the diabetic population ; there was no significant differences between the groups . GPs participating in the project expressed a high level of satisfaction with both interventions . CONCLUSION Prescribing of preventive therapies increased in both r and omized groups over the study period . But academic detailing did not have an additional effect on changing prescribing over the postal bulletin alone AIMS Cardiovascular disease ( CVD ) is the leading cause of morbidity and mortality in people with diabetes in South Asia . The CARRS Translation Trial tests the effectiveness , cost-effectiveness , and sustainability of a clinic-based multi-component CVD risk reduction intervention among people with diabetes in India and Pakistan . METHODS We r and omly assigned 1146 adults with diabetes recruited from 10 urban clinic sites , to receive usual care by physicians or to receive an integrated multi-component CVD risk reduction intervention . The intervention involves electronic health record management , decision-support prompts to the healthcare team , and the support of a care coordinator to actively facilitate patient and provider adherence to evidence -based guidelines . The primary outcome is a composite of multiple CVD risk factor control ( blood glucose and either blood pressure or cholesterol , or all three ) . Other outcomes include control of the individual CVD risk factors , process and patient-centered measures , cost-effectiveness , and acceptability/feasibility . CONCLUSION The CARRS Translation Trial tests a low-cost diabetes care delivery model in urban South Asia to achieve comprehensive cardio-metabolic disease case-management of high-risk patients ( clinical trials.gov number : NCT01212328 ) Objectives A policy model is a model that can evaluate the effectiveness and cost-effectiveness of interventions and inform policy decisions . In this study , we introduce a cardiovascular disease ( CVD ) policy model which can be used to model remaining life expectancy including a measure of socioeconomic deprivation as an independent risk factor for CVD . Design A state transition model was developed using the Scottish Heart Health Extended Cohort ( SHHEC ) linked to Scottish morbidity and death records . Individuals start in a CVD-free state and can transit to three CVD event states plus a non-CVD death state . Individuals who have a non-fatal first event are then followed up until death . Taking a competing risk approach , the cause-specific hazards of a first event are modelled using parametric survival analysis . Survival following a first non-fatal event is also modelled parametrically . We assessed discrimination , validation and calibration of our model . Results Our model achieved a good level of discrimination in each component ( c-statistics for men (women)—non-fatal coronary heart disease ( CHD ) : 0.70 ( 0.74 ) , non-fatal cerebrovascular disease ( CBVD ) : 0.73 ( 0.76 ) , fatal CVD : 0.77 ( 0.80 ) , fatal non-CVD : 0.74 ( 0.72 ) , survival after non-fatal CHD : 0.68 ( 0.67 ) and survival after non-fatal CBVD : 0.65 ( 0.66 ) ) . In general , our model predictions were comparable with observed event rates for a Scottish r and omised statin trial population which has an overlapping follow-up period with SHHEC . After applying a calibration factor , our predictions of life expectancy closely match those published in recent national life tables . Conclusions Our model can be used to estimate the impact of primary prevention interventions on life expectancy and can assess the impact of interventions on inequalities Aims A r and omized , double-blind , placebo-controlled study was conducted to investigate the safety and efficacy of mipomersen , an apolipoprotein B-100 ( apoB ) synthesis inhibitor , in patients who are statin intolerant and at high risk for cardiovascular disease ( CVD ) . Methods and results Thirty-three subjects , not receiving statin therapy because of statin intolerance , received a weekly subcutaneous dose of 200 mg mipomersen or placebo ( 2:1 r and omization ) for 26 weeks . The primary endpoint was per cent change in LDL cholesterol ( LDL-c ) from the baseline to Week 28 . The other efficacy endpoints were per cent change in apoB and lipoprotein a [ Lp(a ) ] . Safety was determined using the incidence of treatment-emergent adverse events ( AEs ) and clinical laboratory evaluations . After 26 weeks of mipomersen  administration , LDL-c was reduced by 47 ± 18 % ( P < 0.001 vs. placebo ) . apoB and Lp(a ) were also significantly reduced by 46 and 27 % , respectively ( P < 0.001 vs. placebo ) . Four mipomersen ( 19 % ) and two placebo subjects ( 17 % ) discontinued dosing prematurely due to AEs . Persistent liver transaminase increases ≥3 × the upper limit of normal were observed in seven ( 33 % ) subjects assigned to mipomersen . In selected subjects , liver fat content was assessed , during and after treatment , using magnetic resonance spectroscopy . Liver fat content in these patients ranged from 0.8 to 47.3 % . Liver needle biopsy was performed in two of these subjects , confirming hepatic steatosis with minimal inflammation or fibrosis . Conclusion The present data suggest that mipomersen is a potential therapeutic option in statin-intolerant patients at high risk for CVD . The long-term follow-up of liver safety is required . Clinical Trial Registration : Clinical Trials.gov identifier : Background Cardiovascular disease ( CVD ) is a major cause of death in China . Despite government efforts , the majority of hypertensive and diabetic patients in China do not receive proper treatment . Reducing CVD events requires long-term care that is proactive , patient-centred , community-based , and sustainable . We have design ed a package of interventions for patients at high risk of CVD to be implemented by family doctors based in township hospitals ( providers of primary care ) in rural Zhejiang , China . This trial aims to determine whether the systematic CVD risk reduction package results in reduced CVD events among patients at risk of CVD compared with usual care , and whether the package is cost-effective and suitable for routine implementation and scale-up . Methods / Design This is a prospect i ve , open-label , cluster r and omized controlled trial ( RCT ) with blinded data analysis . The trial will r and omize 67 township hospitals with 31,708 participants in three counties in Zhejiang Province . Participants will be identified from existing health records and will comprise adults aged 50 to 74 years , with a calculated 10-year CVD risk of 20 % or higher , or diabetes . In the intervention arm , participants will receive a package of interventions including : 1 ) healthy lifestyle counseling ( smoking cessation , and salt , oil , and alcohol reduction ) ; 2 ) prescription of a combination of drugs ( antihypertensives , aspirin , and statin ) ; and 3 ) adherence support for drug compliance and healthy lifestyle change . In the control arm , participants will receive usual care for hypertension and diabetes management at individual clinicians ’ discretion . The primary outcome is the incidence of severe CVD events over 24 months of follow-up . All CVD events will be defined according to the World Health Organization ( WHO ) monitoring of trends and determinants in cardiovascular disease ( MONICA ) definitions , diagnosed at the county hospital or higher level , and reported by the Zhejiang surveillance system . Secondary outcomes include : mean systolic and diastolic blood pressure , blood glucose , serum total cholesterol ( TC ) , and adherence to appointments , and drugs and lifestyle changes . Discussion This trial focuses on risk reduction of CVD rather than specific diseases . It is not design ed to compare therapeutic and healthy lifestyle interventions , but rather their combined effects in primary care setting s. Through the trial , we intend to underst and the effectiveness of the comprehensive CVD reduction package in routine practice . We also intend to underst and the barriers and facilitators to implementing the package , and thus to advise on policy and practice change . Trial registration Current Controlled Trials : IS RCT OBJECTIVE To assess the effect of dietary flavonoids on cardiovascular disease ( CVD ) risk in postmenopausal women with type 2 diabetes on established statin and hypoglycemic therapy . RESEARCH DESIGN AND METHODS Despite being medicated , patients with type 2 diabetes have elevated CVD risk , particularly postmenopausal women . Although dietary flavonoids have been shown to reduce CVD risk factors in healthy participants , no long-term trials have examined the additional benefits of flavonoids to CVD risk in medicated postmenopausal women with type 2 diabetes . We conducted a parallel- design , placebo-controlled trial with type 2 diabetic patients r and omized to consume 27 g/day ( split dose ) flavonoid-enriched chocolate ( containing 850 mg flavan-3-ols [ 90 mg epicatechin ] and 100 mg isoflavones [ aglycone equivalents)]/day ) or matched placebo for 1 year . RESULTS Ninety-three patients completed the trial , and adherence was high ( flavonoid 91.3 % ; placebo 91.6 % ) . Compared with the placebo group , the combined flavonoid intervention result ed in a significant reduction in estimated peripheral insulin resistance ( homeostasis model assessment of insulin resistance [ HOMA-IR ] −0.3 ± 0.2 ; P = 0.004 ) and improvement in insulin sensitivity ( quantitative insulin sensitivity index [ QUICKI ] 0.003 ± 0.00 ; P = 0.04 ) as a result of a significant decrease in insulin levels ( −0.8 ± 0.5 mU/L ; P = 0.02 ) . Significant reductions in total cholesterol : HDL-cholesterol ( HDL-C ) ratio ( −0.2 ± 0.1 ; P = 0.01 ) and LDL-cholesterol ( LDL-C ) ( −0.1 ± 0.1 mmol/L ; P = 0.04 ) were also observed . Estimated 10-year total coronary heart disease risk ( derived from UK Prospect i ve Diabetes Study algorithm ) was attenuated after flavonoid intervention ( flavonoid + 0.1 ± 0.3 vs. placebo 1.1 ± 0.3 ; P = 0.02 ) . No effect on blood pressure , HbA1c , or glucose was observed . CONCLUSIONS One-year intervention with flavan-3-ols and isoflavones improved biomarkers of CVD risk , highlighting the additional benefit of flavonoids to st and ard drug therapy in managing CVD risk in postmenopausal type 2 diabetic patients BACKGROUND There is debate about the value of assessing levels of C-reactive protein ( CRP ) and other biomarkers of inflammation for the prediction of first cardiovascular events . METHODS We analyzed data from 52 prospect i ve studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk . We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implication s of initiation of statin therapy after the assessment of CRP or fibrinogen . RESULTS The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age , sex , smoking status , blood pressure , history of diabetes , and total cholesterol level increased the C-index , a measure of risk discrimination , by 0.0050 . The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027 , respectively ( P<0.001 ) , and yielded a net reclassification improvement of 1.52 % and 0.83 % , respectively , for the predicted 10-year risk categories of " low " ( < 10 % ) , " intermediate " ( 10 % to < 20 % ) , and " high " ( ≥20 % ) ( P<0.02 for both comparisons ) . We estimated that among 100,000 adults 40 years of age or older , 15,025 persons would initially be classified as being at intermediate risk for a cardiovascular event if conventional risk factors alone were used to calculate risk . Assuming that statin therapy would be initiated in accordance with Adult Treatment Panel III guidelines ( i.e. , for persons with a predicted risk of ≥20 % and for those with certain other risk factors , such as diabetes , irrespective of their 10-year predicted risk ) , additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years . CONCLUSIONS In a study of people without known cardiovascular disease , we estimated that under current treatment guidelines , assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened . ( Funded by the British Heart Foundation and others . ) BACKGROUND Cardiovascular disease ( CVD ) is the leading cause of death , and principal reason for the large difference in life expectancy between indigenous Māori and the non-indigenous population in New Zeal and . CVD guidelines recommend that people who are at high risk or who have had previous CVD should be offered aspirin , blood pressure lowering and lipid lowering therapies . However , prescribing and adherence rates are low and CVD events remain high . AIM To assess whether a medication strategy using a fixed dose combination pill ( ' polypill ' ) could improve prescribing and adherence to recommended medications , lower blood pressure and improve lipids compared with current care over 12 months . METHODS IMProving Adherence using Combination Therapy ( IMPACT ) is an open-label r and omised controlled trial comparing a once-daily polypill containing four preventive medications with usual care .  Six hundred participants who have had previous CVD events or are at high risk of CVD will be enrolled , including 300 Māori . Participants are identified , enrolled and prescribed either the polypill or current medications at their usual primary health care practice , with medications ( including the polypill ) dispensed through local community pharmacies . The polypill contains 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril and either 12.5 mg hydrochlorothiazide or 50 mg atenolol . Primary outcomes are adherence to guidelines -recommended medications and changes in systolic blood pressure and low density lipoprotein at 12 months . Secondary outcomes include other lipids , medication dispensing , barriers to adherence , CVD and other serious adverse events , quality of life and prescriber acceptability . The trial is registered with the Australian New Zeal and Clinical Trial Registry ( ACTRN12606000067572 ) Our purpose was to evaluate associations of single nucleotide polymorphisms ( SNPs ) at the low density lipoprotein ( LDL ) receptor ( LDLR C44857 T , minor allele frequency ( MAF ) 0.26 , and A44964 G , MAF 0.25 , both in the untranslated region ) and HMG-CoA reductase ( HMGCR i18 T > G , MAF 0.019 ) gene loci with baseline lipid values , statin-induced LDL-cholesterol ( C ) lowering response , and incident coronary heart disease ( CHD ) and cardiovascular disease ( CVD ) on trial . Our population consisted of 5804 elderly men and women with vascular disease or one or more vascular disease risk factors , who were r and omly allocated to pravastatin or placebo .  Other risk factors and apolipoprotein ( apo ) E phenotype were controlled for in the analysis . Despite a prior report , no relationships with the HMGCR SNP were noted . For the LDLR SNPs C44857 T and A44964 G we noted significant associations of the rare alleles with baseline LDL-C and triglyceride levels , a modest association of the C44857 T with LDL-C lowering to pravastatin in men , and significant associations with incident CHD and CVD of both SNPs , especially in men on pravastatin . Our data indicate that genetic variation at the LDLR locus can affect baseline lipids , response to pravastatin , and CVD risk in subjects placed on statin treatment In 2016 , the American College of Cardiology published the first expert consensus decision pathway ( ECDP ) on the role of non-statin therapies for low-density lipoprotein (LDL)-cholesterol lowering in the management of atherosclerotic cardiovascular disease ( ASCVD ) risk . Since the publication of that document , additional evidence and perspectives have emerged from r and omized clinical trials and other sources , particularly considering the longer-term efficacy and safety of proprotein convertase subtilisin/kexin 9 ( PCSK9 ) inhibitors in secondary prevention of ASCVD . Most notably , the FOURIER ( Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk ) trial and SPIRE-1 and -2 ( Studies of PCSK9 Inhibition and the Reduction of Vascular Events ) , assessing evolocumab and bococizumab , respectively , have published final results of cardiovascular outcomes trials in patients with clinical ASCVD and in a smaller number of high-risk primary prevention patients . In addition , further evidence on the types of patients most likely to benefit from the use of ezetimibe in addition to statin therapy after acute coronary syndrome has been published . Based on results from these important analyses , the ECDP writing committee judged that it would be desirable to provide a focused up date to help guide clinicians more clearly on decision making regarding the use of ezetimibe and PCSK9 inhibitors in patients with clinical ASCVD with or without comorbidities . In the following summary table , changes from the 2016 ECDP to the 2017 ECDP Focused Up date are highlighted , and a brief rationale is provided . The content of the full document has been changed accordingly , with more extensive and detailed guidance regarding decision making provided both in the text and in the up date d algorithms . Revised recommendations are provided for patients with clinical ASCVD with or without comorbidities  on statin therapy for secondary prevention . The ECDP writing committee judged that these new data did not warrant changes to the decision pathways and algorithms regarding the use of ezetimibe or PCSK9 inhibitors in primary prevention patients with LDL-C < 190 mg/dL with or without diabetes mellitus or patients without ASCVD and LDL-C ≥190 mg/dL not due to secondary causes . Based on feedback and further deliberation , the ECDP writing committee down- grade d recommendations regarding bile acid sequestrant use , recommending bile acid sequestrants only as optional secondary agents for consideration in patients intolerant to ezetimibe . For clarification , the writing committee has also included new information on diagnostic categories of heterozygous and homozygous familial hypercholesterolemia , based on clinical criteria with and without genetic testing . Other changes to the original document were kept to a minimum to provide consistent guidance to clinicians , unless there was a compelling reason or new evidence , in which case justification is provided Background We conducted an Internet-based r and omized trial comparing three valence framing presentations of the benefits of antihypertensive medication in preventing cardiovascular disease ( CVD ) for people with newly diagnosed hypertension to determine which framing presentation result ed in choices most consistent with participants ' values . Methods and Findings In this second in a series of televised trials in cooperation with the Norwegian Broadcasting Company , adult volunteers rated the relative importance of the consequences of taking antihypertensive medication using visual analogue scales ( VAS ) . Participants viewed information ( or no information ) to which they were r and omized and decided whether or not to take medication . We compared positive framing over 10 years ( the number escaping CVD per 1000 ) ; negative framing over 10 years ( the number that will have CVD ) and negative framing per year over 10 years of the effects of antihypertensive medication on the 10-year risk for CVD for a 40 year-old man with newly diagnosed hypertension without other risk factors . Finally , all participants were shown all presentations and detailed patient information about hypertension and were asked to decide again . We calculated a relative importance score ( RIS ) by subtracting the VAS-scores for the undesirable consequences of antihypertensive medication from the VAS-score for the benefit of CVD risk reduction . We used logistic regression to determine the association between participants ' RIS and their choice . 1,528 participants completed the study . The statistically significant differences between the groups in the likelihood of choosing to take antihypertensive medication in relation to different values ( RIS ) increased as the RIS increased . Positively framed information lead to decisions most consistent with those made by everyone for the second , more fully informed decision . There was a statistically significant decrease in deciding to take antihypertensives on the second decision , both within groups and overall . Conclusions For decisions about taking antihypertensive medication for people with a relatively low baseline risk of CVD ( 70 per 1000 over 10 years ) , both positive and negative framing result ed in significantly more people deciding to take medication compared to what participants decided after being shown all three of the presentations . Trial Registration International St and ard R and omised Controlled Trial Number Register IS RCT N Objective —The goal of this study was to examine the association of the antiinflammatory interleukin-10 ( IL-10 ) with risk of cardiovascular disease ( CVD ) . Methods and Results —In the PROSPER ( PROspect i ve Study of Pravastatin in the Elderly at Risk ) cohort , we related baseline concentrations of circulating IL-10 to risk of CVD events in a nested case (n=819)-control ( n=1618 ) study of 3.2 years of follow-up . Circulating IL-10 showed few strong associations with classical risk factors but was positively correlated with IL-6 and C-reactive protein . IL-10 was positively associated with risk of CVD events ( odds ratio [ OR ] 1.17 , 95 % CI 1.05 to 1.31 per unit increase in log IL-10 ) after adjusting for classical risk factors and C-reactive protein . Furthermore , IL-10 was associated more strongly with CVD risk among those with no previous history of CVD ( OR 1.42 , 95 % CI 1.18 to 1.70 ) , compared with those with previous CVD ( OR 1.04 , 95 % CI 0.90 to 1.19 ; P=0.018 ) . Overall , IL-10 showed a modest ability to add discrimination to classical risk factors ( C-statistic + 0.005 , P=0.002 ) . Conclusion —Baseline circulating levels of the antiinflammatory IL-10 are positively associated with risk of CVD among the elderly without prior CVD events , although the association is less evident in those with a history of CVD . Additional epidemiological and mechanistic studies investigating the role of IL-10 in CVD are warranted Context While the benefits of statins in the primary and secondary prevention of coronary artery disease are clear , the value of statin therapy in acute coronary syndromes is uncertain . Contribution Analyzing data from a large , international observational study of acute coronary syndromes , these investigators identified associations between statin use before and during acute coronary events and favorable outcomes . Caution s While these data suggest a potential benefit of statins during acute coronary events , trials are necessary to determine the most appropriate use of statins in the treatment of acute coronary events . The Editors Data from r and omized clinical trials support the efficacy of lipid-lowering medications , particularly statins , in the primary and secondary prevention of coronary artery disease ( 1 - 3 ) . The benefits of statins , however , were not readily apparent until after several months of therapy , suggesting that the drugs ' lipid-lowering capabilities were largely responsible . In vitro work has suggested that statins may have an abundance of pleiotropic effects ( 4 ) . These include modulation of inflammation , inhibition of platelet function and thrombosis , and enhancement of endothelial cell function . The demonstrated ability of statins to immediately affect basic pathophysiologic mechanisms has result ed in increased interest in their potential role in the setting of acute coronary syndromes . The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering ( MIRACL ) trial found that early treatment with high-dose atorvastatin modestly reduced event rates of recurrent ischemia in statin-naive patients presenting with an acute coronary syndrome ( 5 ) . These observations , while intriguing , did not conclusively establish the role of statins in patients with acute coronary syndromes . In the MIRACL trial , the failure of statins to significantly affect more concrete trial end points ( for example , death or recurrent myocardial infa rct ion [ MI ] ) was disappointing . Whether this reflected a true lack of physiologic impact of early statin treatment or merely indicated that the study was underpowered to detect differences in these end points remains unclear . In a sub study using data from the Platelet Receptor Inhibition for Ischemic Syndrome Management ( PRISM ) trial in patients with acute coronary syndromes , patients already taking statins  had better short-term outcomes ( decreased risk for death or nonfatal MI ) than those not previously receiving statin therapy , unless statin therapy was discontinued in the hospital ( 6 ) . Initiation of statin therapy after the onset of an acute coronary syndrome appeared to be less effective than treatment with statins before symptom onset . Using data from the Global Registry of Acute Coronary Events ( GRACE ) project , a large , multinational , observational study of patients with acute coronary syndromes , we examined the association between previous statin therapy  , presentation characteristics of acute coronary syndromes , and hospital outcomes . We also examined the effect of early in-hospital statin therapy ( or withdrawal of statins ) on important hospital outcomes , including death or the development of recurrent MI or stroke . Methods Full details of the GRACE rationale and methods have been published elsewhere and are outlined below ( 7 - 9 ) . Site Selection The GRACE project is design ed to reflect an unbiased population of patients with acute coronary syndromes , regardless of geographic region . Currently , 94 hospitals located in 14 countries ( Argentina , Australia , Austria , Belgium , Brazil , Canada , France , Germany , Italy , New Zeal and , Pol and , Spain , the United Kingdom , and the United States ) are participating in this observational study . Patients entered in the registry must be at least 18 years of age and alive at the time of hospital presentation ; be admitted with an acute coronary syndrome as a presumptive diagnosis ( that is , have symptoms consistent with acute ischemia ) ; and have at least 1 of the following : electrocardiographic changes consistent with an acute coronary syndrome , serial increases in serum biochemical markers of cardiac necrosis , or documentation of coronary artery disease ( 7 - 9 ) . The qualifying acute coronary syndrome must not be precipitated by a significant noncardiovascular comorbid condition ( for example , trauma or surgery ) . To ensure the enrollment of an unbiased sample , the first 10 to 20 consecutive patients ( depending on each site 's patient volume ) are recruited from each site on a monthly basis . Where required , study investigators received approval from their local hospital ethics or institutional review board . Data Collection At each site , a trained coordinator collected data using a st and ardized case-report form . Data on demographic characteristics , medical history , presenting symptoms , duration of prehospital delay , biochemical and electrocardiographic findings , treatment practice s , and hospital outcome were collected . St and ardized definitions of all patient-related variables and clinical diagnoses were used . All cases were assigned to 1 of the following categories : ST-segment elevation MI , nonST-segment elevation MI , unstable angina , and other cardiac or noncardiac diagnoses that have been previously described ( 7 - 9 ) . St and ardized definitions were also used for selected hospital complications and outcomes . Patient Sample For the current study , patients who were subsequently found to have noncardiac or other cardiac ( nonacute coronary syndrome ) primary diagnoses and those who transferred into or out of GRACE registry hospitals were excluded from further consideration . Treatments defined as previous use were those taken by the patient on a long-term basis at home and within 7 days of the presenting event , based on the review of information contained in medical records and abstract ed by trained study physicians and nurses . Treatments received in the hospital ( within the first 24 hours or thereafter ) were categorized as within hospital . Agents prescribed for use after discharge from participating hospitals were categorized as at discharge . Patient treatment categories were defined according to the following groupings : no previous treatment with statins and no treatment with statins during hospitalization , no previous therapy with statins but statin therapy  instituted during hospitalization , previous therapy with statins and statin therapy continued during hospitalization , and previous  therapy with statins but statin therapy not continued during the index hospitalization . Statistical Analysis We used the chi-square tests for discrete variables to analyze differences in demographic and clinical characteristics , treatment practice s , clinical presentation ( ST-segment elevation vs. nonST-segment elevation , large infa rct [ creatine phosphokinase level > 2 times the upper limit of normal ] vs. small infa rct ) , subsequent diagnosis ( ST-segment elevation MI , nonST-segment elevation MI , unstable angina ) , and hospital complications ( death , congestive heart failure or pulmonary edema , cardiogenic shock , stroke , ventricular tachycardia or ventricular fibrillation , and cardiac arrest ) in relation to statin use . The Wilcoxon rank-sum test was used to analyze differences between respective comparison groups for continuous variables . While controlling for potentially confounding variables , we performed multivariate regression analyses to examine the association between previous statin therapy and hospital presentation ( ST-segment elevation vs. no ST-segment elevation , creatine phosphokinase level 2 times normal vs. creatine phosphokinase level < 2 times the upper limit of normal ) , as well as any association between previous or in-hospital statin therapy and hospital outcomes ( death , recurrent MI or MI after 24 hours , and stroke ) or a composite end point of all 3 outcomes . C and i date variables for inclusion in the regression models evaluating previous statin use and hospital presentation included patient age , sex , smoking status , diabetes , history of vascular disease ( previous MI , stroke , positive angiogram , peripheral vascular disease , percutaneous coronary intervention , or coronary artery bypass graft surgery ) , hypertension , hyperlipidemia , and previous therapies ( aspirin , angiotensin-converting enzyme [ ACE ] inhibitors , -blockers , and other lipid-lowering agents ) . C and i date variables for regression models evaluating previous or in-hospital statin use and hospital outcomes included all of the previously listed characteristics plus characteristics present at the time of hospital admission ( heart rate , systolic blood pressure , Killip class , ST-segment elevation or left bundle-branch block pattern , and positive cardiac enzymes ) and receipt of in-hospital therapies ( aspirin and other antiplatelet agents , -blockers , unfractionated heparin , low-molecular-weight heparin , glycoprotein IIb/IIIa inhibitors , cardiac catheterization , percutaneous coronary intervention , or coronary artery bypass graft surgery ) . C and i date variables possibly associated with the outcomes of interest ( P < 0.25 after univariate analysis ) were included in the multivariate models . Variables for which the P value exceeded 0.05 were eliminated in a stepwise fashion so that only those that had a statistically significant association with the outcome of interest were included in the final regression models . Because of their clinical relevance and potential importance , age , sex , and history of hyperlipidemia were retained in the final multivariable models for clinical outcomes regardless of statistical significance . Final models were evaluated for goodness of fit by the HosmerLemeshow test . Because between-hospital variation in use of statin treatment could be considerable and potentially affect our study results , we adjusted for hospital r and om effects on the observed outcomes . We used a generalized estimating equation modeling technique , assuming patients were repeated measures within each hospital . Variable Background People with Familial Hypercholesterolemia ( FH ) may benefit from lifestyle changes supporting their primary treatment of dyslipidaemia . This project evaluated the efficacy of an individualised tailored lifestyle intervention on lipids ( low density lipoprotein cholesterol ( LDL-C ) , high density lipoprotein cholesterol ( HDL-C ) , total cholesterol ( TC ) and triglycerides ) , systolic blood pressure , glucose , body mass index ( BMI ) and waist circumference in people with FH . Methods Adults with FH ( n = 340 ) , recruited from a Dutch cascade screening program , were r and omly assigned to either a control group or an intervention group . The personalised intervention consisted of web-based tailored lifestyle advice and personal counselling . The control group received care as usual .  Lipids , systolic blood pressure , glucose , BMI , and waist circumference were measured at baseline and after 12 months . Regression analyses were conducted to examine differences between both groups . Results After 12 months , no significant between-group differences of cardiovascular disease ( CVD ) risk indicators were observed . LDL-C levels had decreased in both the intervention and control group . This difference between intervention and control group was not statistically significant . Conclusions This project suggests that an individually tailored lifestyle intervention did not have an additional effect in improving CVD risk indicators among people with FH . The cumulative effect of many small improvements in all indicators on long term CVD risk remains to be assessed in future studies .Trial registration NTR1899 at The use of preventive medications in people at high risk of cardiovascular disease is conceptually straightforward , yet in practice the adoption of such measures is disappointingly low , plus there is wide international variation in preventive therapies . Several barriers might explain this shortfall and variation , but the simplicity and economy of a polypill-based strategy might overcome some barriers . The ‘ Use of a Multidrug Pill In Reducing cardiovascular Events ’ ( UMPIRE ) trial assesses whether a polypill strategy ( by combining aspirin , a statin and two blood pressure lowering agents ) would improve adherence to guideline -indicated therapies and would lower both blood pressure and cholesterol , in people with established cardiovascular disease . UMPIRE , running in India and three European countries ( Engl and , Irel and and the Netherl and s ) , is an open , r and omised , controlled trial design ed to include 1000 participants in India and 1000 in Europe , with a followup of 12–24 months . Participants were r and omised to one of two versions of the polypill or relegated to usual care . The primary study outcomes were the self-reported use of aspirin , a statin and at least two blood pressure lowering agents ; as well as changes in blood pressure and cholesterol . Secondary outcomes included : any cardiovascular events , reasons for stopping medications , serious adverse events and perceived changes in quality of life . Interpretation of the study data will be enhanced by health , economic and process-related evaluations . UMPIRE is registered with the European Clinical Trials data base , as EudraCT : 2009 - 016278 - 34 and the Clinical Trials Registry , India as CTRI/2010/091/000250 . The trial was part of the ‘ Single Pill Against Cardiovascular Events ( SPACE ) ’ collaboration , which encompasses the ‘ IMProving Adherence using Combination Therapy ( IMPACT ) ’ and ‘ Kanyini Guidelines Adherence with the Polypill ( Kanyini-GAP ) ’ trials The search for complementary treatments in primary prevention of cardiovascular disease ( CVD ) is a high-priority challenge . Grape and wine polyphenol resveratrol confers CV benefits , in part by exerting anti-inflammatory effects . However , the evidence in human long-term clinical trials has yet to be established . We aim ed to investigate the effects of a dietary resveratrol-rich grape supplement on the inflammatory and fibrinolytic status of subjects at high risk of CVD and treated according to current guidelines for primary prevention of CVD . Seventy-five patients undergoing primary prevention of CVD participated in this triple-blinded , r and omized , parallel , dose-response , placebo-controlled , 1-year follow-up trial . Patients , allocated in 3 groups , consumed placebo ( maltodextrin ) , a resveratrol-rich grape supplement ( resveratrol 8 mg ) , or a conventional grape supplement lacking resveratrol , for the first 6 months and a double dose for the next 6 months . In contrast to placebo and conventional grape supplement , the resveratrol-rich grape supplement  significantly decreased high-sensitivity C-reactive protein ( -26 % , p = 0.03 ) , tumor necrosis factor-α ( -19.8 % , p = 0.01 ) , plasminogen activator inhibitor type 1 ( -16.8 % , p = 0.03 ) , and interleukin-6/interleukin-10 ratio ( -24 % , p = 0.04 ) and increased anti-inflammatory interleukin-10 ( 19.8 % , p = 0.00 ) . Adiponectin ( 6.5 % , p = 0.07 ) and soluble intercellular adhesion molecule-1 ( -5.7 % , p = 0.06 ) tended to increase and decrease , respectively . No adverse effects were observed in any patient . In conclusion , 1-year consumption of a resveratrol-rich grape supplement  improved the inflammatory and fibrinolytic status in patients who were on statins for primary prevention of CVD and at high CVD risk ( i.e. , with diabetes or hypercholesterolemia plus ≥1 other CV risk factor ) . Our results show for the first time that a dietary intervention with grape resveratrol could complement the gold st and ard therapy in the primary prevention of CVD Objectives Investigate the association between socioeconomic deprivation and completeness of cardiovascular disease ( CVD ) risk factor recording in primary care , uptake of screening in people with incomplete risk factor recording and with actual CVD risk within the screened subgroup . Design Cross-sectional study . Setting Nine UK general practice s. Participants 7987 people aged 50–74 years with no CVD diagnosis . Methods CVD risk was estimated using the Framingham equation from data extracted from primary care electronic health records . Where there was insufficient information to calculate risk , patients were invited to attend a screening assessment . Analysis Proportion of patients for whom clinical data were sufficiently complete to enable CVD risk to be calculated ; proportion of patients invited to screening who attended ; proportion of patients who attended screening whose 10-year risk of a cardiovascular event was high ( > 20 % ) . For each outcome , a set of logistic regression models were run . Crude and adjusted ORs were estimated for person-level deprivation , age , gender and smoking status . We included practice -level deprivation as a continuous variable and practice as a r and om effect to account for clustering . Results People who had lower  Indices of Multiple Deprivation ( IMD ) scores ( less deprived ) had significantly worse routine CVD risk factor recording ( adjusted OR 0.97 ( 0.95 to 1.00 ) per IMD decile ; p=0.042 ) . Screening attendance was poorer in those with more deprivation ( adjusted OR 0.89 ( 0.86 to 0.91 ) per IMD decile ; p<0.001 ) . Among those who attended screening , the most deprived were more likely to have CVD risk > 20 % ( OR 1.09 ( 1.03 to 1.15 ) per IMD decile ; p=0.004 ) . Conclusions Our data suggest that those who had the most to gain from screening were least likely to attend , potentially exacerbating existing health inequalities . Future research should focus on tailoring the delivery of CVD screening to ensure engagement of socioeconomically deprived groups Background Hypercholesterolemia has been identified as a major risk factor for the development of coronary artery disease . The aim of this study was to assess the effect of a Mediterranean diet on the development of non-fatal acute coronary syndromes ( ACS ) in hypercholesterolemic people , with or without statin treatment . Methods During 2000–2001 , 848 r and omly selected patients with a first event of coronary heart disease and 1078 cardiovascular disease-free people , matched to the patients by sex , age and region , were studied . Treatment of hypercholesterolemia with statin and the adoption of a Mediterranean diet were recorded . Results Hypercholesterolemia was present in 534 ( 63 % ) out of 848 coronary patients and 399 ( 37 % ) out of 1078 control participants . One hundred and seventy-one ( 32 % ) of the hypercholesterolemic patients and 168 ( 42 % ) of the hypercholesterolemic control participants were treated with statins and also followed a Mediterranean diet . The analysis showed that the combination of a Mediterranean diet and  statin medical therapy is associated with an additional reduction of the coronary risk ( odds ratio = 0.57 , P < 0.01 ) , independently from cholesterol levels and the other cardiovascular factors . Conclusion The adoption of a Mediterranean diet by hypercholesterolemic people seems to reinforce the benefits from statin treatment on lipid levels and reduces the risk of developing ACS . However , it is hard to cl aim that our findings suggest causal evidence , and in order to explain the potential common mechanism between diet and statin treatment much remains to be learned OBJECTIVES To compare the potential years of life saved ( YOLS ) associated with risk factor modification in the primary and secondary prevention of cardiovascular disease ( CVD ) . METHODS The CVD life expectancy model estimates the risk of death due to coronary disease , stroke , and other causes based on the levels of independent risk factors ( such as age , blood pressure , and blood lipid levels ) found in the cohort of the Lipid Research Clinics . The model was vali date d by comparing its predictions with the observed fatal outcomes of 9 r and omized clinical trials . We then estimated the YOLS associated with treating hyperlipidemia or hypertension among hypothetical patient groups with and without CVD at baseline . We defined high-risk patients as those with 3 risk factors ( hyperlipidemia , cigarette smoking , and hypertension ) and low-risk patients as those with isolated hypertension or hyperlipidemia . RESULTS The fatal events predicted by the model were consistent with the clinical trial results . Among men and women with hyperlipidemia without CVD , the forecasted benefits of lipid therapy  were substantially greater among high-risk groups vs low-risk groups ( 4.74 - 0.78 YOLS vs 2.50 - 0.25 YOLS , respectively ) . Among those with CVD , the forecasted benefits of treatment were similar for both high-risk and low-risk groups ( 4.65 - 0.65 YOLS vs 3.84 - 0.58 YOLS , respectively ) . The results for  hypertension  therapy also demonstrated greater benefits for high-risk vs low-risk patients undergoing primary prevention therapy ( 1.34 - 0.29 YOLS vs 0.85 - 0.13 YOLS , respectively ) , and the forecasted benefits in secondary prevention were similar ( 1.26 - 0.23 YOLS vs 1.00 - 0.23 YOLS , respectively ) . CONCLUSIONS The clinical approach to risk factor modification in primary prevention should be different from that in secondary prevention . The forecasted benefits of therapy among patients without CVD are greatest in the presence of other risk factors . Among those with CVD , the benefits of therapy are equivalent , thereby obviating the need to target high-risk patients Background — Carriers of the KIF6 719Arg variant may be at increased risk for CVD and may benefit more from statin therapy , in terms of CVD risk reduction , than noncarriers . Our objective was to investigate whether carriers of the KIF6 719Arg genetic variant ( rs20455 ) are at increased cardiovascular risk and obtain more benefit from high-dose statin therapy than do noncarriers . Methods and Results — We used an adjusted Cox proportional hazard model to assess the hazard ratio ( HR ) for the reduction of major cardiovascular events by 80 mg/d atorvastatin over 10 mg/d atorvastatin in 4599 patients of the Treating to New Targets ( TNT ) study and by 80 mg/d atorvastatin over 20–40 mg/d simvastatin in 6541 patients of the Incremental Decrease in End Points Through Aggressive Lipid-Lowering ( IDEAL ) study . A total of 381 and 648 patients had a cardiovascular event during follow-up in TNT and IDEAL , respectively . Heterozygotes and homozygotes for the minor allele were not at increased risk compared with noncarriers . In TNT , for noncarriers of the 719Arg allele , the HR for high- versus low-dose  atorvastatin was 0.81 ( 95 % confidence interval , 0.59–1.11 ) . In carriers of 1 or 2 minor alleles , the HR was 0.85 ( 0.66–1.11 ) and carriers of 2 copies of the minor allele obtained a significant risk reduction ( HR : 0.44 , 95 % confidence interval , 0.23–0.84 ) . In IDEAL , the respective HRs were 0.85 ( 0.67–1.10 ) , 0.88 ( 0.62–1.07 ) and 0.91 ( 0.58–1.43 ) . The interaction term for carrier status by treatment was also nonsignificant ( P=0.810 in TNT and P=0.909 in IDEAL ) . Conclusions — In these 2 large , r and omized clinical trials , carriers of the KIF6 719Arg allele were not at increased cardiovascular risk and did not obtain consistent cardiovascular benefit from high-dose statin therapy compared with noncarriers . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00327691 OBJECTIVE To examine the effect of intensive lipid-lowering therapy on a composite cardiovascular outcome ( cardiovascular disease [ CVD ] ) , consisting of mortality and morbidity end points , in patients with inflammatory joint disease ( rheumatoid arthritis [ RA ] , ankylosing spondylitis [ AS ] , or psoriatic arthritis [ PsA ] ) by post hoc analysis of 2 prospect i ve trials of statins with a secondary end point of CVD outcome ( the Treating to New Targets [ TNT ] and Incremental Decrease in End Points Through Aggressive Lipid Lowering [ IDEAL ] studies ) . METHODS Of the 18,889 patients participating in the 2 trials , 199 had RA , 46 had AS , and 35 had PsA.  Lipid-lowering therapy consisted of an intensive regimen of atorvastatin 80 mg or a conventional/low-dose regimen of atorvastatin 10 mg or simvastatin 20 - 40 mg . The median duration of followup was nearly 5 years . Changes in lipid levels were examined by analyses of covariance . The effect on CVD was examined by Cox regression analyses , and heterogeneity tests were performed . RESULTS Patients with RA and those with AS had lower baseline cholesterol levels than patients without inflammatory joint disease ( least squares mean ± SEM 180.7 ± 2.3 mg/dl and 176.5 ± 4.7 mg/dl , respectively , versus 185.6 ± 0.2 mg/dl ; P = 0.03 and P = 0.05 , respectively ) . Statin treatment led to a comparable decrease in lipid levels and a 20 % reduction in overall risk of CVD in both patients with and those without inflammatory joint disease . CONCLUSION Our findings indicate that patients with and those without inflammatory joint disease experience comparable lipid-lowering effects and CVD risk reduction after intensive treatment with statins The sum of evidence -based nutrition has to be more than a Cochrane-type meta- analysis of r and omised controlled trials ( RCTs ) . Most of the evidence base in nutrition is observational , especially cohort studies . RCTs of diet change through to disease outcome are uncommon and the change has usually been addition or removal of only a single food component . Trials with whole diets through to disease outcome are rare and dietary changes made by individuals are unlikely to be an exact copy of the prescription . It is hard to even imagine a trial in which half ( r and omised ) of a large group of middle-aged people agree to avoid vegetables for 5 y and be followed up to see who will develop cancer . Most of the USA 's health cl aims , permitted by the Food and Drug Administration , are not supported by RCTs . But where controlled trials of nutritional change and disease outcome have been achieved , they must be review ed very carefully . Two Cochrane review s on diet and cardiovascular disease ( CVD ) , published in the widely read British Medical Journal ( BMJ ) , were criticised after their publication and the conclusions have not been subsequently adopted by expert committees . The first of these review s was ‘ Dietary fat and prevention of CVD : a systematic review ’ . The second was ‘ Systematic review of long term effects of advice to reduce dietary salt in adults ’ . A critique of these two Cochrane review s is presented here as a contribution to our discussion of the potential of Cochrane methodology to the reliability of knowledge about diet and disease OBJECTIVE The Diabetes Prevention Program demonstrated the ability to delay or prevent type 2 diabetes in participants with impaired glucose tolerance ( IGT ) . Participants with IGT are at high risk for cardiovascular disease ( CVD ) , with a marked increase in the number and severity of CVD risk factors . We prospect ively assessed the impact of our interventions on hypertension , dyslipidemia , and CVD events . RESEARCH DESIGN AND METHODS The study group consisted of 3,234 individuals with IGT r and omly assigned to receive intensive lifestyle intervention , metformin , or placebo . Annual assessment of blood pressure , lipids , electrocardiogram , and CVD events was undertaken . RESULTS Hypertension was present in 30 % of participants at study entry and then increased in the placebo and metformin groups , although it significantly decreased with intensive lifestyle intervention . Triglyceride levels fell in all treatment groups , but fell significantly more with intensive lifestyle intervention . Total cholesterol and LDL cholesterol levels were similar among treatment groups . Intensive lifestyle intervention significantly increased the HDL cholesterol level and reduced the cumulative incidence of the proatherogenic LDL phenotype B. At 3 years of follow-up , the use for pharmacologic therapy to achieve established goals in the intensive lifestyle group was 27 - 28 % less for hypertension and 25 % less for hyperlipidemia compared with placebo and metformin groups . Over an average of 3 years , 89 CVD events from 64 participants were positively adjudicated study wide , with no differences among treatment groups . CONCLUSIONS Lifestyle intervention improves CVD risk factor status compared with placebo and metformin therapy . Although no differences in CVD events were noted after 3 years , achieved risk factor modifications suggest that longer intervention may reduce CVD event rates OBJECTIVE We investigated in general practice the efficacy of antiplatelets and antioxidants in primary prevention of cardiovascular events in people with type 2 diabetes . RESEARCH DESIGN AND METHODS The Primary Prevention Project ( PPP ) is a r and omized , open trial with a two-by-two factorial design aim ed to investigate low-dose aspirin ( 100 mg/day ) and vitamin E ( 300 mg/day ) in the prevention of cardiovascular events in patients with one or more cardiovascular risk factors . The primary end point was a composite end point of cardiovascular death , stroke , or myocardial infa rct ion . A total of 1,031 people with diabetes in the PPP , aged > /=50 years , without a previous cardiovascular event were enrolled by 316 general practitioners and 14 diabetes outpatient clinics . RESULTS The PPP trial was prematurely stopped ( after a median of 3.7 years ) by the independent data safety and monitoring board because of a consistent benefit of aspirin compared with the control group in a population of 4,495 patients with one or more major cardiovascular risk factors . In diabetic patients , aspirin treatment was associated with a nonsignificant reduction in the main end point ( relative risk [ RR ] = 0.90 , 95 % CI 0.50 - 1.62 ) and in total cardiovascular events ( 0.89 , 0.62 - 1.26 ) and with a nonsignificant increase in cardiovascular deaths ( 1.23 , 0.69 - 2.19 ) . In nondiabetic subjects , RRs for the main end point , total cardiovascular events , and cardiovascular deaths were 0.59 ( 0.37 - 0.94 ) , 0.69 ( 0.53 - 0.90 ) , and 0.32 ( 0.14 - 0.72 ) , respectively . No significant reduction in any of the end points considered could be found with vitamin E in either diabetic or nondiabetic subjects . CONCLUSIONS Our data suggest a lower effect of primary prevention of cardiovascular disease ( CVD ) with low-dose aspirin in diabetic patients as opposed to subjects with other cardiovascular risk factors . If confirmed , these findings might indicate that the antiplatelet effects of aspirin in diabetic patients are overwhelmed by aspirin-insensitive mechanisms of platelet activation and thrombus formation , thus making the balance between benefits and harms of aspirin treatment unfavorable . Further large-scale trials investigating the role of aspirin in the primary prevention of CVD in diabetic patients are urgently needed BACKGROUND Weekly fish consumption has been related to a lower risk of fatal coronary heart disease ( CHD ) and incident stroke in population s with a low fish intake . This relation has mainly been attributed to n-3 fatty acids in fish , that is , eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) . It is at present unclear whether alpha-linolenic acid ( ALA ) , a n-3 fatty acid from vegetable origin , could also be protective against cardiovascular diseases ( CVDs ) . There is a need for food-based trials to establish the efficacy of low doses of n-3 fatty acids in CVD prevention . OBJECTIVES The aim of the study was to evaluate the effect of an additional daily intake of 400 mg of EPA + DHA and 2 g of ALA on CVD morbidity and mortality in free-living subjects with a history of myocardial infa rct ion . DESIGN The multicenter Alpha Omega Trial is a r and omized , double-blind , placebo-controlled trial with a 2 x 2 factorial design . Between May 2002 and December 2006 , we enrolled a total of 4,837 men and women aged 60 through 80 who experienced a myocardial infa rct ion within 10 years before entering the study . Subjects were r and omized to 1 of 4 margarine spreads that were enriched with EPA + DHA and /or ALA , or placebo . Compliance was monitored via tub counts and assessment of n-3 fatty acids in plasma . Subjects were observed for 40 months for the occurrence of fatal and nonfatal CVD . RESULTS The cohort was on average 69 years old at the start of the study and comprised 22 % women . Subjects had their ( last ) myocardial infa rct ion approximately 4 years before enrollment . Mean body mass index was 27.7 kg/m(2 ) , and 17 % smoked . Average serum total and high-density lipoprotein cholesterol were 4.7 and 1.3 mmol/L , respectively , and 85 % used statins . Mean blood pressure was 142/80 mm Hg , and most subjects were on antihypertensive medication ( 88 % ) . Diabetes mellitus was reported by 17 % of the subjects , and 7 % reported a history of stroke . The overall mortality rate during the trial period was 23 per 1,000 person-years , with approximately 40 % due to CVD . CURRENT STATUS Follow-up of the patients was completed in November 2009 , and findings will be reported in the second part of 2010 BACKGROUND Type 2 diabetes is associated with a substantially increased risk of cardiovascular disease , but the role of lipid-lowering therapy with statins for the primary prevention of cardiovascular disease in diabetes is inadequately defined . We aim ed to assess the effectiveness of atorvastatin 10 mg daily for primary prevention of major cardiovascular events in patients with type 2 diabetes without high concentrations of LDL-cholesterol . METHODS 2838 patients aged 40 - 75 years in 132 centres in the UK and Irel and were r and omised to placebo  ( n=1410 ) or atorvastatin 10 mg daily ( n=1428 ) . Study entrants had no documented previous history of cardiovascular disease , an LDL-cholesterol concentration of 4.14 mmol/L or lower , a fasting triglyceride amount of 6.78 mmol/L or less , and at least one of the following : retinopathy , albuminuria , current smoking , or hypertension . The primary endpoint was time to first occurrence of the following : acute coronary heart disease events , coronary revascularisation , or stroke . Analysis was by intention to treat . FINDINGS The trial was terminated 2 years earlier than expected because the prespecified early stopping rule for efficacy had been met . Median duration of follow-up was 3.9 years ( IQR 3.0 - 4.7 ) . 127 patients allocated placebo ( 2.46 per 100 person-years at risk ) and 83 allocated atorvastatin ( 1.54 per 100 person-years at risk ) had at least one major cardiovascular event ( rate reduction 37 % [ 95 % CI -52 to -17 ] , p=0.001 ) . Treatment would be expected to prevent at least 37 major vascular events per 1000 such people treated for 4 years . Assessed separately , acute coronary heart disease events were reduced by 36 % ( -55 to -9 ) , coronary revascularisations by 31 % ( -59 to 16 ) , and rate of stroke by 48 % ( -69 to -11 ) . Atorvastatin reduced the death rate by 27 % ( -48 to 1 , p=0.059 ) . No excess of adverse events was noted in the atorvastatin group . INTERPRETATION Atorvastatin 10 mg daily is safe and efficacious in reducing the risk of first cardiovascular disease events , including stroke , in patients with type 2 diabetes without high LDL-cholesterol . No justification is available for having a particular threshold level of LDL-cholesterol as the sole arbiter of which patients with type 2 diabetes should receive statins . The debate about whether all people with this disorder warrant statin treatment should now focus on whether any patients are at sufficiently low risk for this treatment to be withheld Much of the controversy at the American Diabetes Association Scientific Sessions , held 6–10 June 2008 in San Francisco , California , pertained to questions raised about the benefits of intensive glycemic control by three large clinical studies : the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial , the Action in Diabetes and Vascular Disease ( ADVANCE ) trial , and the Veterans ’ Administration Diabetes Trial ( VADT ) . All three presented somewhat negative study results . David Goff ( Winston-Salem , NC ) discussed the ACCORD study design . The goal of ACCORD was to determine whether cardiovascular disease ( CVD ) event rates could be reduced by intensively treating three important risk factors ( hyperglycemia , dyslipidemia , and high blood pressure ) in a double 2 × 2 factorial design . For glycemia , the question of A1C < 6 vs. 7–7.9 % was addressed . Goff review ed previous studies that led to the decision to aim for the low A1C target . In the UK Prospect i ve Diabetes Study ( UKPDS ) , insulin and sulfonylurea treatment achieved a mean A1C level of 7 % , with 7.9 % in a control group . The 16 % CVD reduction just missed statistical significance . Metformin treatment in this study achieved a mean A1C level of 7.4 % with 8 % in a control group , associated with a significant 39 % CVD reduction . ( Goff did not mention that , compared with sulfonylureas alone , the other UKPDS metformin sub study showed that metformin with a sulfonylurea was associated with 96 , 60 , and 9 % increases in diabetes-related and all-cause mortality and in myocardial infa rct ion [ 1 ] . ) A nonsignificant CVD risk reduction of ∼50 % was seen in the Kumamoto study , while there was also a nonsignificant CVD risk increase of ∼50 % in the Veterans ’ Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes ( VACSDM ) ; both studies showed A1C 7.1 % in the treatment group and 9.3–9.4 % in the control group . Analysis of a number of observational studies Primary care facilities may be a natural setting for delivering interventions that focus on behaviors that improve cardiovascular disease ( CVD ) risk factors . The purpose of this study was to examine the 24-month effects of the Activity Counseling Trial ( ACT ) on CVD risk factors , to examine whether changes in CVD risk factors differed according to baseline risk factor status , and to examine whether changes in fitness were associated with changes in CVD risk factors . ACT was a 24-month multicenter r and omized controlled trial to increase physical activity .  Participants were 874 inactive men and women aged 35–74 years . Participants were r and omly assigned to one of three arms that varied by level of counseling , intensity , and re source requirements . Because there were no significant differences in change over time between arms on any of the CVD risk factors examined , all arms were combined , and the effects of time , independent of arm , were examined separately for men and women . Time × Baseline risk factor status interactions examined whether changes in CVD risk factors differed according to baseline risk factor status . Significant improvements in total cholesterol , high-density lipoprotein cholesterol ( HDL-C ) and low-density lipoprotein cholesterol , the ratio of total cholesterol to HDL-C , and triglycerides were seen in both men and women who had high ( or low for HDL-C ) baseline levels of risk factors , whereas significant improvements in diastolic blood pressure were seen only in those men with high baseline levels . There were no improvements in any risk factors among participants with normal baseline levels . Changes in fitness were associated with changes in a number of CVD risk factors . However , most relationships disappeared after controlling for changes in body weight . Improvements in lipids from the ACT interventions could reduce the risk of coronary heart disease in people with already high levels of lipids by 16%–26 % in men and 11%–16 % in women . Interventions that can be implemented in health care setting s nationwide and result in meaningful population -wide changes in CVD risk factors are needed . The ACT physical activity interventions produced substantial improvements among men and women with elevated CVD risk factors BACKGROUND Worldwide implementation of risk-based cardiovascular disease ( CVD ) prevention requires risk prediction tools that are contemporarily recalibrated for the target country and can be used where laboratory measurements are unavailable . We present two cardiovascular risk scores , with and without laboratory-based measurements , and the corresponding risk charts for 182 countries to predict 10-year risk of fatal and non-fatal CVD in adults aged 40 - 74 years . METHODS Based on our previous laboratory-based prediction model ( Globorisk ) , we used data from eight prospect i ve studies to estimate coefficients of the risk equations using proportional hazard regressions . The laboratory-based risk score included age , sex , smoking , blood pressure , diabetes , and total cholesterol ; in the non-laboratory ( office-based ) risk score , we replaced diabetes and total cholesterol with BMI . We recalibrated risk scores for each sex and age group in each country using country-specific mean risk factor levels and CVD rates . We used recalibrated risk scores and data from national surveys ( using data from adults aged 40 - 64 years ) to estimate the proportion of the population at different levels of CVD risk  for ten countries from different world regions as examples of the information the risk scores provide ; we applied a risk threshold for high risk of at least 10 % for high-income countries ( HICs ) and at least 20 % for low-income and middle-income countries ( LMICs ) on the basis of national and international guidelines for CVD prevention . We estimated the proportion of men and women who were similarly categorised as high risk or low risk by the two risk scores . FINDINGS Predicted risks for the same risk factor profile were generally lower in HICs than in LMICs , with the highest risks in countries in central and southeast Asia and eastern Europe , including China and Russia . In HICs , the proportion of people aged 40 - 64 years at high risk of CVD ranged from 1 % for South Korean women to 42 % for Czech men ( using a ≥10 % risk threshold ) , and in low-income countries ranged from 2 % in Ug and a ( men and women ) to 13 % in Iranian men ( using a ≥20 % risk threshold ) . More than 80 % of adults were similarly classified as low or high risk by the laboratory-based and office-based risk scores . However , the office-based model substantially underestimated the risk among patients with diabetes . INTERPRETATION Our risk charts provide risk assessment tools that are recalibrated for each country and make the estimation of CVD risk possible without using laboratory-based measurements . FUNDING National Institutes of Health A community cardiovascular disease ( CVD ) prevention programme was undertaken in 1989 in a Danish County ( Vejle ) . A r and om sample of 5192 adults were asked to complete a mailed question naire on  knowledge , attitudes , and behaviour  in relation to CVD risk factors . The response rate was 56 % . The question naire produced baseline data for programme planning and measuring the success of on-going interventions . Smoking , overweight , and unhealthy food habits were the most prevalent CVD risk factors . A CVD risk score was calculated from the data on smoking , food habits , exercise , stress , overweight , self-reported presence of hypertension , diabetes , and gender . A high score was commoner in men , in the least educated , in groups who judged their own risk as high , and in groups with negative health beliefs . The level of knowledge about CVD risk factors was high in general . Low knowledge was commonest in the youngest age group , in the least educated , in unskilled workers , and in groups with negative health beliefs . As social position and personality factors seem to play an important role in actions people may take in prevention of CVD , they should be considered in the planning of the health promotion activities in Vejle Background The Kanyini Guidelines Adherence with the Polypill ( Kanyini-GAP ) Study aims to examine whether a polypill-based strategy ( using a single capsule containing aspirin , a statin and two blood pressure-lowering agents ) amongst Indigenous and non-Indigenous people at high risk of experiencing a cardiovascular event will improve adherence to guideline -indicated therapies , and lower blood pressure and cholesterol levels . Methods / Design The study is an open , r and omised , controlled , multi-centre trial involving 1000 participants at high risk of cardiovascular events recruited from mainstream general practice s and Aboriginal Medical Services , followed for an average of 18 months . The participants will be r and omised to one of two  versions  of  the polypill  , the version chosen by the treating health professional according to clinical features of the patient , or to usual care . The primary study outcomes will be changes , from baseline measures , in serum cholesterol and systolic blood pressure and self-reported current use of aspirin , a statin and at least two blood pressure lowering agents . Secondary study outcomes include cardiovascular events , renal outcomes , self-reported barriers to indicated therapy , prescription of indicated therapy , occurrence of serious adverse events and changes in quality -of-life . The trial will be supplemented by formal economic and process evaluations . Discussion The Kanyini-GAP trial will provide new evidence as to whether or not a polypill-based strategy improves adherence to effective cardiovascular medications amongst individuals in whom these treatments are indicated . Trial Registration This trial is registered with the Australian New Zeal and Clinical Trial Registry ACTRN126080005833347 Background People with severe mental illnesses ( SMI ) are at increased risk of cardiovascular disease ( CVD ) . Clinical guidelines recommend regular screening for CVD risk factors . We evaluated a nurse led intervention to improve screening rates across the primary - secondary care interface . Methods Six community mental health teams ( CMHTs ) were r and omised to receive either the nurse led intervention plus education pack ( n = 3 ) or education pack only ( n = 3 ) . Intervention ( 6 months ) : The nurse promoted CVD screening in primary care and then in CMHTs . Patients who remained unscreened were offered screening by the nurse . After the intervention participants with SMI were recruited from each CMHT to collect outcome data . Main outcome : Numbers screened during the six months , confirmed in General Practice notes . Results All six CMHTs approached agreed to r and omisation . 121 people with SMI participated in outcome interviews during two waves of recruitment ( intervention arm n = 59 , control arm n = 62 ) . Participants from both arms of the trial had similar demographic profiles and rates of previous CVD screening in the previous year , with less than 20 % having been screened for each risk factor . After the trial , CVD screening had increased in both arms but participants from the intervention arm were significantly more likely to have received screening for blood pressure ( 96 % vs 68 % ; adjusted Odds Ratio ( OR ) 13.6 ; 95 % CI : 3.5 - 38.4 ) , cholesterol ( 66.7 % vs 26.9 % , OR 6.1 ; 3.2 - 11.5 ) , glucose ( 66.7 % vs 36.5 % OR 4.4 ; 2.7 - 7.1 ) , BMI ( 92.5 % vs 65.2 % OR 6.5 ; 2.1 - 19.6 ) , and smoking status ( 88.2 % vs 57.8 % OR 5.5 ; 3.2 - 9.5 ) and have a 10 year CVD risk score calculated ( 38.2 % vs 10.9 % ) OR 5.2 1.8 - 15.3 ) . Within the intervention arm approximately half the screening was performed in general practice and half by the trial nurse . Conclusions The nurse-led intervention was superior , result ing in an absolute increase of approximately 30 % more people with SMI receiving screening for each CVD risk factor . The feasibility of the trial was confirmed in terms of CMHT recruitment and the intervention , but the response rate for outcome collection was disappointing ; possibly a result of the cluster design . The trial was not large or long enough to detect changes in risk factors . Trial Registration International St and ard R and omised Controlled Trial Registration Number ( IS RCT RN ) 58625025 Background Cardiovascular disease ( CVD ) remains the leading cause of death globally . Primary prevention of CVD requires cost-effective strategies to identify individuals at high risk in order to help target preventive interventions . An integral part of this approach is the use of CVD risk scores . Limitations in previous studies have prevented reliable inference about the potential advantages and the potential harms of using CVD risk scores as part of preventive strategies . We aim to evaluate short-term effects of providing different types of information about coronary heart disease ( CHD ) risk , alongside lifestyle advice , on health-related behaviours . Methods / Design In a parallel-group , open r and omised trial , we are allocating 932 male and female blood donors with no previous history of CVD aged 40–84 years in Engl and to either no intervention ( control group ) or to one of three active intervention groups : i ) lifestyle advice only ; ii ) lifestyle advice plus information on estimated 10-year CHD risk based on phenotypic characteristics ; and iii ) lifestyle advice plus information on estimated 10-year CHD risk based on phenotypic and genetic characteristics . The primary outcome is change in objective ly measured physical activity . Secondary outcomes include : objective ly measured dietary behaviours ; cardiovascular risk factors ; current medication and healthcare usage ; perceived risk ; cognitive evaluation of provision of CHD risk scores ; and psychological outcomes . The follow-up assessment takes place 12 weeks after r and omisation . The experiences , attitudes and concerns of a subset of participants will be also studied using individual interviews and focus groups . Discussion The INFORM study has been design ed to provide robust findings about the short-term effects of providing different types of information on estimated 10-year CHD risk and lifestyle advice on health-related behaviours . Trial registration Current Controlled Trials IS RCT N17721237 . Registered 12 January 2015 BACKGROUND Despite the cardiovascular disease ( CVD ) risk associated with hypertension , diabetes , dyslipidemia , and smoking , these risk factors remain poorly identified and controlled . OBJECTIVES The study sought to evaluate the effectiveness of a community pharmacy-based case finding and intervention on cardiovascular risk . METHODS The RxEACH ( Alberta Vascular Risk Reduction Community Pharmacy Project ) study was a r and omized trial conducted in 56 community pharmacies . Participants were recruited by their pharmacist , who enrolled adults at high risk for CVD . Patients were r and omized to usual care ( usual pharmacist care with no specific intervention ) or intervention , comprising a Medication Therapy Management review from their pharmacist and CVD risk assessment and education . Pharmacists prescribed medications and ordered laboratory tests as per their scope of practice to achieve treatment targets . Subjects received monthly follow-up visits for 3 months . The primary outcome was difference in change in estimated CVD risk between groups at 3 months . CVD risk was estimated using the greater of the Framingham , International , or United Kingdom Prospect i ve Diabetes Study risk scores . RESULTS We enrolled 723 patients ( mean 62 years of age ; 58 % male , and 27 % smokers ) . After adjusting for baseline values and center effect , there was a 21 % difference in change in risk for CVD events ( p < 0.001 ) between the intervention and usual care groups . The intervention group had greater improvements in low-density lipoprotein cholesterol ( -0.2 mmol/l ; p < 0.001 ) , systolic blood pressure ( -9.37 mm Hg ; p < 0.001 ) , glycosylated hemoglobin ( -0.92 % ; p < 0.001 ) , and smoking cessation ( 20.2 % ; p = 0.002 ) . CONCLUSIONS The RxEACH study was the first large r and omized trial of CVD risk reduction by community pharmacists , demonstrating a significant reduction in risk for CVD events . Engagement of community pharmacists with an exp and ed scope of practice could have significant public health implication s. ( The Alberta Vascular Risk Reduction Community Pharmacy Project : RxEACH [ RxEACH ] ; NCT01979471 ) Background Decreasing salt consumption can prevent cardiovascular diseases ( CVD ) . Practically , it is difficult to promote people ’s awareness of daily salt intake and to change their eating habits in terms of reducing salt intake for better cardiovascular health . Health education programs visualizing daily dietary salt content and intake may promote lifestyle changes in patients at high risk of cardiovascular diseases . Methods / Design This is a cluster r and omized trial . A total of 800 high-CVD-risk patients attending diabetes and hypertension clinics at health centers in Muang District , Chiang Rai province , Thail and , will be studied with informed consent . A health center recruiting 100 participants is a cluster , the unit of r and omization . Eight clusters will be r and omized into intervention and control arms and followed up for 1 year . Within the intervention clusters the following will be undertaken : ( 1 )  salt content in the daily diet will be measured and shown to study participants ; ( 2 )  24-hour salt intake will be estimated in overnight-collected urine and the results shown to the participants ; ( 3 ) a dietician will assist small group health education classes in cooking meals with less salt . The primary outcome is blood pressure change at the 1-year follow-up . Secondary outcomes at the 1-year follow-up are estimated 24-hoursalt intake , incidence of CVD events and CVD death . The intention-to-treat analysis will be followed . Blood pressure and estimated 24-hour salt intake will be compared between intervention and control groups at the cluster and individual level at the 1-year follow-up . Clinical CVD events and deaths will be analyzed by time-event analysis . Retinal blood vessel calibers of CVD-risk patients will be assessed cross-sectionally . Behavioral change to reduce salt intake and the influencing factors will be determined by structured equation model ( SEM ) . Multilevel regression analyses will be applied . Finally , the cost effectiveness of the intervention will be analyzed . Discussion This study is unique as it will recruit the individuals most vulnerable to CVD morbidity and mortality by applying the general Framingham CVD risk scoring system . Dietary salt reduction will be applied as a prioritized , community level intervention for the prevention of CVD in a developing country . Trial registration IS RCT Background — The role of C-reactive protein ( CRP ) in predicting vascular events and response to statin therapy remains uncertain . Additional large prospect i ve studies are required . Methods and Results — Baseline CRP was related to risk over 3.2 years for primary a combined end point ( definite or suspected death from coronary heart disease , nonfatal myocardial infa rct ion , and fatal or nonfatal stroke ; n=865 events ) and secondary ( coronary heart disease events or stroke alone ) and tertiary ( stroke plus transient ischemic attack ) end points in the Prospect i ve Study of Pravastatin in the Elderly at Risk ( n=5804 men and women ; age , 70 to 82 years ) .  CRP levels were higher in subjects who had a subsequent primary end-point event compared with those who did not ( geometric mean ; 3.64 mg/L [ SD , 3.08 mg/L ] versus 3.01 mg/L [ SD , 3.05 mg/L ] ; P<0.0001 ) . CRP correlated positively with body mass index and smoking status and negatively with high-density lipoprotein cholesterol . The unadjusted hazard ratio for the primary end point was 1.48 ( 95 % CI , 1.26 to 1.74 ) in a comparison of top and bottom thirds for CRP , falling to 1.36 ( 95 % CI , 1.15 to 1.61 ) with adjustment for established predictors and body mass index . Similar results were obtained for other end points or when results were examined separately by history of vascular disease . However , baseline CRP added minimally to risk prediction beyond conventional predictors and did not relate to the magnitude of pravastatin benefit . Conclusions — Elevated CRP minimally enhances cardiovascular disease prediction beyond established vascular risk factors and does not predict response to statin therapy in elderly subjects at risk . These data suggest that CRP has limited clinical value in cardiovascular disease risk stratification or predicting response to statin therapy in elderly people The objective was to assess whether pediatric risk factors predict cardiovascular disease ( CVD ) , impaired fasting glucose ( IFG ) + type 2 diabetes mellitus ( T2DM ) , and high blood pressure ( HBP ) in young adulthood . We performed a prospect i ve follow-up of 909 public-parochial suburban schoolchildren first studied at ages 6 to 18 years and 26 years later at a mean age of 38 years .  Pediatric triglycerides ( TGs ) , blood pressure , low-density lipoprotein cholesterol , body mass index , and glucose above and high-density lipoprotein cholesterol below established pediatric cutoffs , along with race , cigarette smoking , family history of CVD , T2DM , and HBP , were assessed as determinants of young adult CVD , a composite variable including IFG + T2DM and HBP . By stepwise logistic regression , adult CVD ( 19 yes , 862 no ) was associated with pediatric high TG ( odds ratio [ OR ] , 5.85 ; 95 % confidence interval [ CI ] , 2.3 - 14.7 ) . High TG in pediatric prob and s with young adult CVD was familial and was associated with early CVD in their high-TG parents . Adult IFG + T2DM ( 114 yes , 535 no ) was associated with parental T2DM ( OR , 2.2 ; 95 % CI , 1.38 - 3.6 ) , high childhood glucose ( OR , 4.43 ; 95 % CI , 2 - 9.7 ) , and childhood cigarette smoking ( OR , 1.64 ; 95 % CI , 1.03 - 2.61 ) . Adult HBP ( 133 yes , 475 no ) was associated with pediatric high body mass index ( OR , 2.7 ; 95 % CI , 1.7 - 4.3 ) and HBP ( OR , 2.5 ; 95 % CI , 1.5 - 4.3 ) . Pediatric risk factors are significantly , independently related to young adult CVD , IFG + T2DM , and HBP . Identification of pediatric risk factors for CVD  , IFG + T2DM , and HBP facilitates initiation of primary prevention programs to reduce development of adult CVD , IFG + T2DM , and HBP Aims /hypothesisWithin a trial of intensive treatment of people with screen-detected diabetes , we aim ed to assess a potential spillover effect of the trial intervention on incident cardiovascular disease ( CVD ) and all-cause mortality among people who screened positive on a diabetes risk question naire but who were normoglycaemic . Methods In the Anglo – Danish – Dutch Study of Intensive Treatment In People with Screen-Detected Diabetes in Primary Care (ADDITION)-Denmark trial , 175 general practice s were cluster-r and omised into : ( 1 ) screening plus routine care of individuals with screen-detected diabetes ( control group ) ;  or (  2 ) screening plus training and support in intensive multifactorial treatment of individuals with screen-detected diabetes ( intervention  group  ) . We identified all individuals who screened positive on a diabetes risk question naire in ADDITION-Denmark but were normoglycaemic following biochemical testing for use in this secondary analysis . After a median 8.9 years follow-up , we used data from national registers to compare rates of first CVD events and all-cause mortality in individuals in the routine care group with those in the intensive treatment group . Results In total , 21,513 individuals screened positive for high risk of diabetes but were normoglycaemic on biochemical testing in ADDITION-Denmark practice s between 2001 and 2006 ( 10,289 in the routine care group and 11,224 in the intensive treatment group ) . During 9 years of follow-up , there were 3784 first CVD events and 1748 deaths . The incidence of CVD was lower among the intensive treatment group compared with the routine care group ( HR 0.92 [ 95 % CI 0.85 , 0.99 ] ) . This association was stronger among individuals at highest CVD risk ( heart SCORE ≥ 10 ; HR 0.85 [ 95 % CI 0.75 , 0.96 ] ) . There was no difference in mortality between the two treatment groups ( HR 1.02 [ 95 % CI 0.92 , 1.14 ] ) . Conclusions /interpretationTraining of general practitioners to provide target-driven intensive management of blood glucose levels and other cardiovascular risk factors showed some evidence of a spillover effect on the risk of CVD over a 9 year period among individuals at high risk of diabetes . The effect was particularly pronounced among those at highest risk of CVD . There was no effect on mortality . Trial registration : Clinical Trials.gov Background : Evidence on the effectiveness of educational interventions on prescribing behaviour modification in prevention of cardiovascular disease is still insufficient . We evaluated the effects of a brief educational intervention on prescription of hydroxymethylglutaryl-CoA reductase inhibitors ( statins ) , inhibitors of platelet aggregation ( IPA ) , and antihypertensive agents ( AH ) . Design : Cluster r and omised controlled trial with continuous medical education ( CME ) groups of general practitioners ( GPs ) . Methods : Prescription of statins , IPA , and AH were verified prior to study start ( BL ) , immediately after index consultation ( IC ) , and at follow-up after 6 months ( FU ) . Prescription in patients at high risk ( > 15 % risk of a cardiovascular event in 10 years , based on the Framingham equation ) and no prescription in low-risk patients ( ≤ 15 % ) were considered appropriate . Results : An intervention effect on prescribing could only be found for IPA . Generally , changes in prescription over time were all directed towards higher prescription rates and persisted to FU , independent of risk status and group allocation . Conclusions : The active implementation of a brief evidence -based educational intervention on global risk in CVD did not lead directly to risk-adjusted changes in prescription . Investigations on an extended time scale would capture whether decision support of this kind would improve prescribing risk-adjusted sustainably BACKGROUND Prospect i ve studies suggested that substituting whole-grain products for refined-grain products lowers the risks of type 2 diabetes and cardiovascular disease ( CVD ) in women . Although breakfast cereals are a major source of whole and refined grains , little is known about their direct association with the risk of premature mortality . OBJECTIVE We prospect ively evaluated the association between whole- and refined-grain breakfast cereal intakes and total and CVD-specific mortality in a cohort of US men . DESIGN We examined 86,190 US male physicians aged 40 - 84 y in 1982 who were free of known CVD and cancer at baseline . RESULTS During 5.5 y , we documented 3114 deaths from all causes , including 1381 due to  CVD  ( 488 myocardial infa rct ions and 146 strokes ) . Whole-grain breakfast cereal intake was inversely associated with total and CVD-specific mortality , independent of age ; body mass index ; smoking ; alcohol intake ; physical activity ; history of diabetes , hypertension , or high cholesterol ; and use of multivitamins . Compared with men who rarely or never consumed whole-grain cereal , men in the highest category of whole-grain cereal intake ( > or = 1 serving/d ) had multivariate-estimated relative risks of total and CVD-specific mortality of 0.83 ( 95 % CI : 0.73 , 0.94 ; P for trend < 0.001 ) and 0.80 ( 0.66 , 0.97 ; P for trend < 0.001 ) , respectively . In contrast , total and refined-grain breakfast cereal intakes were not significantly associated with total and CVD-specific mortality . These findings persisted in analyses stratified by history of type 2 diabetes , hypertension , and high cholesterol . CONCLUSIONS Both total mortality and CVD-specific mortality were inversely associated with whole-grain but not refined-grain breakfast cereal intake . These prospect i ve data highlight the importance of distinguishing whole-grain from refined-grain cereals in the prevention of chronic diseases OBJECTIVE The risk of cardiovascular disease ( CVD ) is increased in patients with rheumatoid arthritis ( RA ) . The objective of this study was to examine the distribution of known CVD risk factors and biomarkers of CVD in women with and without RA . METHODS This study included two components : an examination of clinical CVD risk factors among women participating in the Nurses ' Health Study , a prospect i ve longitudinal cohort , and an analysis of CVD biomarkers among a subgroup of women from this cohort who provided a blood specimen in 1989 ( biospecimen cohort ) . Data regarding clinical risk factors for CVD were collected in 1990 by mailed question naire . The diagnosis of RA was confirmed through a structured medical record abstract ion . We compared clinical risk factors for CVD and biomarkers of CVD between women with and without RA , adjusting for age , body mass index ( BMI ) , smoking status , and menopause status . RESULTS Women with RA ( n = 287 ) were significantly more likely than women without RA ( n = 87,019 ) to report no alcohol use ( 48.2 % versus 39.4 % ) and past cigarette smoking ( 47.8 % versus 38.0 % ) . No significant differences between these groups were observed for current smoker status , BMI , regular aspirin use , diabetes , hypertension , physical activity , and family history of early myocardial infa rct ion . In the biospecimen cohort ( 69 RA cases and 491 controls ) , the levels of several inflammatory biomarkers linked to CVD were significantly elevated in women with RA , including CRP , fibrinogen , sICAM-1 , sTNFRI , sTNFRII , and osteoprotegerin . Levels of total cholesterol , low-density lipoprotein , triglycerides , apolipoprotein B , and Lp(a ) were similar between groups . Levels of homocysteine were similar , but vitamin B(12 ) was significantly higher among women with RA than among the controls . CONCLUSION In women participating in the Nurses ' Health Study , most traditional CVD risk factors were similar between those who had RA and those who did not . However , as expected , biomarkers of inflammation associated with CVD were generally elevated in women with RA Objectives : Current blood pressure ( BP ) management guidelines recommend that treatment thresholds for BP be based on absolute cardiovascular disease ( CVD ) risk rather than on elevated BP levels alone . Clinicians are concerned that delayed pharmacotherapy in individuals with high BP , but low CVD risk , may increase long-term CVD events . To investigate this , we examined differences in CVD events within the Second Australian National BP study ( ANBP2 ) for those previously on pharmacotherapy and those who were not , as well as fatal events in the 6-year post-trial period . Methods : Population consisted of ANBP2 participants without a prior CVD event . Adjusted Cox-regression hazard models were used to assess the effects of prior BP pharmacotherapy use on cardiovascular endpoints within ANBP2 . An extended 6-year follow-up analysis for cardiovascular and all-cause mortality was also conducted . Results : We found a higher in-trial CVD and all-cause mortality rate and incidence of new-onset diabetes for those on previous treatment versus those who were treatment-naive . We investigated whether this was an effect of the in-trial protocol , but this did not explain the observed differences . No difference in CVD or all-cause mortality at 10 years was observed between ‘ treatment-naive ’ and ‘ previous treatment ’ groups . Conclusion : We found no long-term adverse mortality associated with treatment naivety of elevated BP in an elderly hypertensive cohort , but this finding is likely to be confounded as seen by the lower in-trial mortality in the ‘ treatment-naive ’ group . Legacy effects need to be explored in r and omized trials of middle-aged population s where the clinical concern lies BACKGROUND Sub clinical depression , often clinical ly unrecognized , may pose increased risk of cardiovascular disease . Few studies have prospect ively investigated cardiovascular events related to depression in older women . We describe prevalence , cardiovascular correlates , and relationship to subsequent cardiovascular events of depressive symptoms among generally healthy postmenopausal women . METHODS The Women 's Health Initiative Observational Study followed up 93 676 women for an average of 4.1 years .  Depression was measured at baseline with a short form of the Center for Epidemiological Studies Depression Scale .  Risks of cardiovascular disease ( CVD ) events were estimated from Cox proportional hazards models adjusting for multiple demographic , clinical , and risk factor covariates . RESULTS Current depressive symptoms above the screening cutoff point were reported by 15.8 % of women . Depression was significantly related to CVD risk and comorbidity ( odds ratios ranging from 1.12 for hypertension to 1.60 for history of stroke or angina ) . Among women with no history of CVD , depression was an independent predictor of CVD death ( relative risk , 1.50 ) and all-cause mortality ( relative risk , 1.32 ) after adjustment for age , race , education , income , diabetes , hypertension , smoking , high cholesterol level requiring medication , body mass index , and physical activity . Taking antidepressant medications did not alter the depression-associated risks associated . CONCLUSIONS A large proportion of older women report levels of depressive symptoms that are significantly related to increased risk of CVD death and all-cause mortality , even after controlling for established CVD risk factors . Whether early recognition and treatment of sub clinical depression will lower CVD risk remains to be determined in clinical trials The 2014 Evidence -Based Guideline for the Management of  High Blood Pressure In Adults : Report From the Panel Members Appointed to the Eighth Joint National Committee ( JNC 8) recommends several major changes from the JNC 7 report ( 1 , 2 ) . The 2014 guideline is based on a systematic review of r and omized , controlled trials ( RCTs ) by a multidisciplinary panel using a process informed by Institute of Medicine recommendations for guideline development ( 3 ) . Although there was almost unanimous agreement on nearly all recommendations , a minority of the panel ( the authors of this commentary ) disagreed with the recommendation to increase the target systolic blood pressure ( SBP ) from 140 to 150 mm Hg in persons aged 60 years or older without diabetes mellitus ( DM ) or chronic kidney disease ( CKD ) . This target guides both the initiation of therapy and treatment goals . Although this issue has major clinical and public health implication s , the guideline only briefly summarized the concerns underlying the minority opinion to maintain the target of less than 140 mm Hg . The Institute of Medicine recommendation for guideline development encourages guidelines to provide a description and explanation of any differences of opinion regarding the recommendation ( 3 ) . This summarizes the evidence and rationale underlying the minority opinion to maintain the SBP target of 140 mm Hg or lower in persons aged 60 years or older until there is greater certainty of the risks and benefits of a higher target . First , increasing the target will probably reduce the intensity of antihypertensive treatment in a large population at high risk for cardiovascular disease ( CVD ) ( Table 1 ) . The higher SBP goal would apply to some of the groups at highest cardiovascular risk , such as African Americans , hypertensive patients with multiple CVD risk factors other than DM or CKD , and those with clinical CVD . Second , the evidence supporting increasing the SBP target from 140 to 150 mm Hg in persons aged 60 years or older was insufficient and inconsistent with the evidence supporting the panel 's recommendations for an SBP target of less than 140 mm Hg in persons younger than 60 years and those aged 60 years or older with DM or CKD . Third , the higher SBP goal in individuals aged 60 years or older may reverse the decades-long decline in CVD , especially stroke mortality ( 4 ) . In the absence of definitive evidence defining the optimum SBP target , observational studies and RCT data that the panel did not systematic ally review more strongly support the SBP goal of less than 140 mm Hg , especially in high-risk individuals . Other recent guideline groups review ing similar evidence have recommended a goal of less than 140 mm Hg , particularly in persons aged 80 years or younger ( 59 ) . Table 1 . U.S. Cardiovascular Disease Death Rates for Persons Younger and Older Than 65 y Persons Aged 60 Years or Older With Hypertension and SBP Controlled to 140 mm Hg or Lower More than half of the 72 million persons with hypertension in the United States are aged 60 years or older ( 10 , 11 ) . Among these individuals , the 2014 guideline recommends the SBP goal of 140 mm Hg or lower only for those with DM and those younger than 70 years with CKD ( 2 ) . Although the prevalence of hypertension in this age group ( 65 % to 67 % ) did not change between 1999 and 2010 , the percentage with adequate blood pressure control increased from 27.4 % ( 19992000 ) to 50.5 % ( 20112012 ) , with 82.2 % now receiving antihypertensive medications ( 10 , 12 ) . Data from NHANES ( National Health and Nutrition Examination Survey ) from 2001 to 2008 show that among treated and untreated hypertensive adults aged 60 years or older , median SBPs were 136 mm Hg and 152 mm Hg , respectively ( 13 ) , and SBPs have been decreasing in this age group over the past 5 decades ( Figure ) ( 4 ) . Thus , a target of less than 150 mm Hg would likely increase blood pressures in the treated hypertensive population and would suggest that nearly half of the untreated hypertensive patients in this age range should remain untreated . The large population at high risk for CVD , with most currently at an SBP of 140 mm Hg or lower , creates concern that a higher SBP target will adversely affect public health . Figure . Smoothed weighted frequency distribution , median , and 90th percentile of systolic blood pressure for persons aged 60 to 74 y : United States , 19592010 . Reproduced from Lackl and and colleagues ( 4 ) . NHANES = National Health and Nutrition Examination Survey ; NHES = National Health Examination Survey . High Risk in Persons With the Higher Goal Age substantially increases risk for cardiovascular events ( Table 1 ) , so differences in cardiovascular risk do not justify different targets for patients older and younger than 60 years . The risk range for white and African American men aged 60 years is 9 % to 30 % , depending on risk factor profile . For men of both ethnicities who are aged 70 years or older and have SBP controlled to 140 mm Hg , even without clinical CVD or DM , the 10-year risk exceeds 20 % ( 14 ) . Thus , on the basis of absolute risk , using an age threshold of 60 years to define eligibility for less aggressive treatment lacks consistency . Persons aged 60 to 79 years are at higher risk than those who are younger , even if the younger persons have DM . Insufficient Evidence for Differential Hypertension Treatment Benefit for Patients Older and Younger Than 60 Years The 2014 guideline panel failed to identify evidence of differential benefits or harms of treatment using an SBP goal of 140 mm Hg with an age threshold of 60 years . There is little RCT evidence of risk or benefit in treating persons younger than 60 years to this target , except in those with diastolic hypertension . The guideline indicates that no qualifying evidence was found comparing an SBP less than 140 mm Hg to any other SBP goal for persons younger than 60 years ( 2 ) . However , in persons aged 60 years or older , the SHEP ( Systolic Hypertension in the Elderly Program ) trial showed benefit of treating hypertension to an SBP goal between 140 and 145 mm Hg ( Table 2 ) ( 15 ) . HYVET ( Hypertension in the Very Elderly Trial ) found a benefit of an SBP target of less than 150 mm Hg on health outcomes , including mortality in persons aged 80 years or older ( 16 ) . Patients in the HYVET treatment group achieved an SBP of 144 mm Hg at 2 years compared with 159 mm Hg in the control group , and blood pressures continued to decrease in both groups until the end of the trial . Therefore , HYVET and the SHEP trial provide evidence that reducing SBP to around 140 mm Hg has substantial benefit without major harm in older persons . Thus , the best evidence available for an SBP target around 140 mm Hg , which meets the guideline RCT criteria , is in persons older than 60 years . The lack of benefit seen in 2 Japanese trials in older individuals ( JATOS [ Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients ] [ 17 ] and the VALISH [ Valsartan in Elderly Isolated Systolic Hypertension ] trial [ 18 ] ) was cited by some to rationalize the higher SBP target , but these trials were underpowered ( Table 2 ) . The SHEP trial and HYVET together reported 365 strokes and more than 285 coronary heart disease events , whereas JATOS and the VALISH trial only had a combined total of 125 strokes and 67 coronary heart disease events . In addition , the much larger FEVER ( Felodipine Event Reduction ) trial ( 19 ) did not meet criteria for inclusion in the panel 's deliberation ( Table 2 ) . This trial , which was conducted in a Chinese population ( age range , 50 to 79 years ; mean age , 62 years ) , reported a significant 27 % reduction in its primary outcome , as well as significant reductions in all CVD , total mortality , coronary heart disease , and heart failure in patients treated to an SBP of 137 mm Hg with a thiazide diureticcalcium-channel blocker combination versus 143 mm Hg with a thiazide diuretic plus placebo ( 19 ) . Table 2 . Trials Comparing Different Systolic Blood Pressure Thresholds In addition , generalizability of the Japanese trials to other population s of patients older than 60 years , such as African Americans , is uncertain . African Americans are at highest risk for all complications of hypertension and are historically undertreated . Thus , we believe that recommending less aggressive targets in this or other high-risk population s requires stronger justification than the guideline cites . Three recent guidelines from other countries have concluded that the appropriate cut point for an age-related differential SBP goal is 80 years or older ( 57 ) . We agree that this higher treatment target in frail hypertensive patients aged 80 years or older better reflects existing evidence . Safety and Adverse Event Risk in Hypertensive Patients Aged 60 Years or Older Despite the limited number of end points in JATOS and the VALISH trial , their size and duration provide evidence of safety of the SBP target of less than 140 mm Hg . The VALISH investigators concluded that this target was safe in relatively healthy patients aged 70 years or older with isolated systolic hypertension ( 18 ) . In JATOS , adverse events requiring treatment discontinuation were reported in only 36 patients , with no differences in discontinuation rate between groups ( 17 ) . This evidence and the favorable results at slightly higher blood pressures in the SHEP trial and HYVET provide reassurance of the safety of an SBP goal of less than 140 mm Hg in older , nonfrail persons . Other Trial Evidence of Benefit of Treatment at an SBP of 140 mm Hg or Lower Results of the SPS3 ( Secondary Prevention of Small Subcortical Strokes ) trial indicated that an SBP target of less than 130 mm Hg versus 144 mm Hg in 3020 patients ( mean age , 63 years ) reduced subsequent strokes by 19 % ( P= 0.08 ) and hemorrhagic strokes by nearly 50 % ( P < 0.01 ) ( 20 ) . Of note , the FEVER trial reported a 44 % ( P < 0.001 ) reduction in all strokes in a subgroup analysis of patients older than 65 years ( 17 ) . Finally , 2 meta-analyses Objectives : The SCORE model predicts the ten-year risk of cardiovascular mortality but it is still unknown whether applying the SCORE in clinical practice subsequently improves cardiovascular disease ( CVD ) outcomes . The objective of this study is to assess the effect of total cardiovascular risk estimation using the SCORE in preventing serious cardiovascular events in European adults without prior CVD . Methods and results : Data sources : eight bibliographical data bases ( 2003 – August 2015 ) , other internet sources and reference lists of articles were checked . This was supplemented by contact with the board members of the European Society of Cardiology ( ESC ) and the authors of the SCORE model . Study eligibility criteria : all prospect i ve studies in any language investigating the effect of using the SCORE on the clinical outcome ( CVD death , major events and adverse outcomes ) in an adult population were examined . Two review ers assessed the studies independently ( titles , abstract s , full texts ) . After removal of duplicates , 5,256 records were screened and 14 full text papers considered . No eligible studies were identified . An extensive literature search revealed no r and omized control trial or other prospect i ve study comparing significant clinical outcomes between groups that used the SCORE and those who did not . Conclusions : The effect of using the SCORE ( with or without subsequent intervention ) on CVD death , all-cause mortality , major CVD events like myocardial infa rct ion and stroke , as well as adverse outcomes , is still unknown . A cluster r and omised controlled trial is warranted to evaluate the use of the SCORE on important outcomes The objective of this study was to evaluate the effects of the ATS-Sardegna Campaign on lifestyle and cardiovascular disease ( CVD ) risk factors in the Sardinian population . The Campaign was a community-based public health action programme funded by the Sardinian Government with a view to prevent CVD and promote healthy behaviour . It was also part of the Targeted Project FAT.MA . of the Italian National Research Council ( CNR ) , with the main purpose of evaluating the effects of this public health initiative after a five- year intervention . The evaluation was effected with three parallel procedures : individual interviews with 1486 r and omly chosen people ; assessment of eating patterns through a food-frequency question  naire ; measurement of the mean levels of the major CVD risk factors in 1729 r and omly chosen subjects ( 1044 in the calendar year 1992 , and 685 in 1995 , two and five years , respectively , after the beginning of the Campaign ) . Overall , we recorded a favourable trend in eating habits in both sexes ; a significant decrease in LDL-cholesterol in males , and in systolic and diastolic blood pressure in both sexes ; a non- significant decrease in prevalence of smokers among males and increase among females . The ATS-Sardegna Campaign was the first CVD prevention programme in Italy to have attained reduction in the risk profile of an entire region at the lowest ever borne cost Background Maintaining a healthy weight and undertaking regular physical activity are important for the secondary prevention of cardiovascular disease ( CVD ) . However , many people with CVD are overweight and insufficiently active . In addition , in Australia only 20 - 30 % of people requiring cardiac rehabilitation ( CR ) for CVD actually attend . To improve outcomes of and access to CR the efficacy , effectiveness and cost-effectiveness of alternative approaches to CR need to be established . This research will determine the efficacy of a telephone-delivered lifestyle intervention , promoting healthy weight and physical activity , in people with CVD in urban and rural setting s. The control group will also act as a replication study of a previously proven physical activity intervention , to establish whether those findings can be repeated in different urban and rural locations . The cost-effectiveness and acceptability of the intervention to CR staff and participants will also be determined . Methods / Design This study is a r and omised controlled trial . People referred for CR at two urban and two rural Australian hospitals will be invited to participate . The intervention ( healthy weight ) group will participate in four telephone delivered behavioural coaching and goal setting sessions over eight weeks . The coaching sessions will be on weight , nutrition and physical activity and will be supported by written material s , a pedometer and two follow-up booster telephone calls . The control ( physical activity ) group will participate in a six week intervention previously shown to increase physical activity , consisting of two telephone delivered behavioural coaching and goal setting sessions on physical activity , supported by written material s , a pedometer and two booster phone calls . Data will be collected at baseline , eight weeks and eight months for the intervention group ( baseline , six weeks and six months for the control group ) . The primary outcome is weight change . Secondary outcomes include physical activity , sedentary time and nutrition habits . Costs will be compared with outcomes to determine the relative cost-effectiveness of the healthy weight and physical activity interventions . Discussion This study addresses a significant gap in public health practice by providing evidence for the efficacy and cost-effectiveness of a low cost , low contact , high reach intervention promoting healthy weight and physical activity among people with CVD in rural and urban areas in Australia . The replication arm of the study , undertaken by the control group , will demonstrate whether the findings of the previously proven physical activity intervention can be generalised to new setting s. This population -based approach could potentially improve access to and outcomes of secondary prevention programs , particularly for rural or disadvantaged communities . Trial Registration ABSTRACT BACKGROUND Many individuals at higher risk for cardiovascular disease ( CVD ) do not receive recommended treatments . Prior interventions using personalized risk information to promote prevention did not test clinic-wide effectiveness . OBJECTIVE AND DESIGN To perform a 9-month cluster-r and omized trial , comparing a strategy of electronic health record-based identification of patients with increased CVD risk and individualized mailed outreach to usual care . PARTICIPANTS Patients of participating physicians with a Framingham Risk Score of at least 5 % , low-density lipoprotein (LDL)-cholesterol level above guideline threshold for drug treatment , and not prescribed a lipid-lowering medication were included in the intention-to-treat analysis .INTERVENTION Patients of physicians r and omized to the intervention group were mailed individualized CVD risk messages that described benefits of using a statin ( and controlling hypertension or quitting smoking when relevant).MAIN MEASURES The primary outcome was occurrence of a LDL-cholesterol level , repeated in routine practice , that was at least 30 mg/dl lower than prior . A secondary outcome was lipid-lowering drug prescribing . Clinical trials.gov identifier : NCT01286311.KEY RESULTS Fourteen physicians with 218 patients were r and omized to intervention , and 15 physicians with 217 patients to control . The mean patient age was 60.7 years and 77 % were male . There was no difference in the primary outcome ( 11.0 % vs. 11.1 % , OR 0.99 , 95 % CI 0.56–1.74 , P = 0.96 ) , but intervention group patients were twice as likely to receive a prescription for lipid-lowering medication ( 11.9 % , vs. 6.0 % , OR 2.13 , 95 % CI 1.05–4.32 , p = 0.038 ) . In post hoc analysis with extended follow-up to 18 months , the primary outcome occurred more often in the intervention group ( 22.5 % vs. 16.1 % , OR 1.59 , 95 % CI 1.05–2.41 , P = 0.029 ) . CONCLUSIONS In this effectiveness trial , individualized mailed CVD risk messages increased the frequency of new lipid-lowering drug prescriptions , but we observed no difference in proportions lowering LDL-cholesterol after 9 months . With longer follow-up , the intervention ’s effect on LDL-cholesterol levels was apparent BACKGROUND Population -based screening for cardiovascular disease ( CVD ) risk , incorporating blood tests , is proposed in several countries . AIM The aim of this study was to evaluate whether a simple approach to identifying individuals at high risk of CVD using routine data might be effective . DESIGN OF STUDY Prospect i ve cohort study ( EPIC-Norfolk ) . SETTING Norfolk area , UK . METHOD A total of 21 867 men and women aged 40 - 74 years , who were free from CVD and diabetes at baseline , participated in the study . The discrimination ( the area under the receiver operating characteristic curve [ aROC ] ) , calibration , sensitivity/specificity , and positive/negative predictive value were evaluated for different risk thresholds of the Framingham risk equations and the Cambridge diabetes risk score ( as an example of a simple risk score using routine data from electronic general practice records ) . RESULTS During 203 664 person-years of follow-up , 2213 participants developed a first CVD event ( 10.9 per 1000 person-years ) . The Cambridge diabetes risk score predicted CVD events reasonably well ( aROC 0.72 ; 95 % confidence interval [ CI ] = 0.71 to 0.73 ) , while the Framingham risk score had the best predictive ability ( aROC 0.77 ; 95 % CI = 0.76 to 0.78 ) . The Framingham risk score overestimated risk of developing CVD in this representative British population by 60 % . CONCLUSION A risk score incorporating routinely available data from GP records performed reasonably well at predicting CVD events . This suggests that it might be more efficient to use routine data as the first stage in a stepwise population screening programme to identify people at high risk of developing CVD before more time- and re source -consuming tests are used ABSTRACT Objective : The use of Framingham equations to determine 10-year absolute coronary risk ( “ global risk ” ) represents an accepted strategy to target coronary prevention measures and enhance clinical outcomes . The aim of this study was to determine the effects of providing global risk scores to physicians on the prescription of lipid-lowering therapy for patients at increased coronary risk . Research design and methods : This prospect i ve , r and omized controlled trial enrolled 368 primary -care patients without a history of coronary heart disease and not on therapy with a hydroxymethylglutaryl coenzyme A reductase inhibitor ( i.e. statin ) .  The study was conducted in the general medical clinics of an academic US teaching hospital . In the intervention group ( n = 186 ) patients ’ charts were review ed , 10‐year absolute coronary risk computed , and this information conveyed via a simple educational tool appended to charts . In the control group ( n = 182 ) , charts were accompanied by a form with general information on coronary prevention goals and strategies . Main outcome measure : The primary endpoint was the proportion of high-risk patients receiving a new statin prescription . Secondary and tertiary endpoints included ( 1 ) the proportion of moderate-risk patients receiving a statin prescription ; and ( 2 ) the proportion of patients in the whole cohort who had other coronary prevention measures recommended . Results : There was no significant difference in statin prescription to high-risk individuals in the intervention group ( 40.0 % ) compared with the control group ( 37.9 % ; p = 0.86 ) . Moderate-risk individuals who were not eligible for treatment according to the National Cholesterol Education Program Adult Treatment Panel II guidelines were more likely to receive a statin prescription in the intervention group versus the control group ( 28.8 % vs. 12.5 % . p = 0.036 ) Conclusions : Although a simple global risk educational tool did not improve the targeting of statin therapy to patients at high absolute coronary risk , it may be of benefit in targeting moderate-risk individuals who do not have markedly elevated low-density lipoprotein cholesterol ( LDL‐C ) levels . Future research should evaluate the effects of physicians performing their own Framingham risk calculations on statin prescribing and on cholesterol goal attainment Background The increasing burden of cardiovascular diseases ( CVD ) in the ageing population of industrialized nations requires an intensive search for means of reducing this epidemic . In order to improve prevention , detection , therapy and prognosis of cardiovascular diseases on the population level in Eastern Germany , it is necessary to examine reasons for the East-West gradient of CVD morbidity and mortality , potential causal mechanisms and prognostic factors in the elderly . Psychosocial and nutritional factors have previously been discussed as possible causes for the unexplained part of the East-West gradient . A reduced heart rate variability appears to be associated with cardiovascular disease as well as with psychosocial and other cardiovascular risk factors and decreases with age . Nevertheless , there is a lack of population -based data to examine the role of heart rate variability and its interaction with psychosocial and nutritional factors regarding the effect on cardiovascular disease in the ageing population . There also is a paucity of epidemiological data describing the health situation in Eastern Germany . Therefore , we conduct a population -based study to examine the distribution of CVD , heart rate variability and CVD risk factors and their associations in an elderly East German population . This paper describes the design and objectives of the CARLA Study . Methods / design For this study , a r and om sample of 45–80 year-old inhabitants of the city of Halle ( Saale ) in Eastern Germany was drawn from the population registry . By the end of the baseline examination ( 2002–2005 ) , 1750 study participants will have been examined . A multi-step recruitment strategy aims at achieving a 70 % response rate . Detailed information is collected on own and family medical history , socioeconomic , psychosocial , behavioural and biomedical factors . Medical examinations include  anthropometric measures , blood pressure of arm and ankle , a 10-second and a 20-minute electrocardiogram , a general physical examination , an echocardiogram , and laboratory analyses of venous blood sample s.  On 200 participants , a 24-hour electrocardiogram  is recorded . A detailed system of quality control ensures high data quality . A follow-up examination is planned . Discussion This study will help to eluci date pathways to CVD involving autonomic dysfunction and lifestyle factors which might be responsible for the CVD epidemic in some population OBJECTIVE Statins are currently the preferred pharmacological therapy in children with familial hypercholesterolemia ( FH ) with the aim to prevent premature cardiovascular disease ( CVD ) . However , concerns have been raised that lowering cholesterol levels with statins could interfere with hormone production . In this study hormone concentrations were assessed in young adult FH subjects before and 10 years after the initiation of statins , and compared with their unaffected siblings . METHODS All 214 FH children ( 8 - 18 years ) who were previously r and omized into a placebo-controlled trial evaluating the 2-year efficacy and safety of pravastatin , and their 95 unaffected siblings , were eligible . Women using oral contraceptives were excluded . Fasted blood sample s were taken to measure lipids and testosterone ( males ) , estradiol ( females ) , luteinizing hormone ( LH ) , follicle-stimulating hormone ( FSH ) and dehydroepi and osterone ( DHEAS ) . RESULTS After ten years , gonadal steroid and gonadotropin concentrations were within the reference interval and did not differ between FH subjects ( n = 88 ) and unaffected siblings ( n = 62 ) . Mean DHEAS concentrations ( ±st and ard deviation ) in the FH subjects and female siblings were normally distributed within the reference interval , whereas male siblings had a higher mean DHEAS concentration than their FH brothers ( 12.9 [ ± 4.9 ] vs. 8.4 [ ± 3.0 ] μmol/L , respectively , p < 0.0001 ) . CONCLUSION After ten years of statin  treatment , testosterone , estradiol , LH and FSH concentrations in young adult FH patients are within the reference interval and comparable to their unaffected siblings . These results strengthen current guidelines that statins in FH subjects could be safely used from childhood onwards to prevent premature CVD Objective : To assess how visit-to-visit variability of SBP correlates with systemic atherosclerotic change and various prognoses . Background : Visit-to-visit SBP variability correlates with cardiovascular events . However , the mechanisms underlying the impact of visit-to-visit SBP variability on prognoses are poorly understood . Methods and results : A total of 485 patients with essential hypertension from the Non-Invasive Atherosclerotic Evaluation in Hypertension ( NOAH ) study cohort were included . We analyzed the correlation between visit-to-visit SBP variability and multiple clinical parameters . Next , we prospect ively examined the correlation of SBP variability and frequency of cardiovascular disease ( CVD ) and total mortality . Patients with higher SBP variability exhibited significantly higher rates of statin use , as well as higher pulse wave velocity ( PWV ) , left-ventricular mass index ( LVMI ) , plaque score , and resistive index of the common carotid artery ; these patients also exhibited lower estimated glomerular filtration rate . Kaplan – Meier analysis demonstrated that patients with higher SBP variability have a significantly higher incidence of CVD and mortality rate . The hazard ratio of SBP variability for incidence of CVD was greatly diminished after adjustment for intima – media thickness , plaque score , and resistive index , and was slightly diminished after adjustment for PWV and LVMI . Visit-to-visit SBP variability remained an independent risk factor for mortality after adjustment . Conclusion : Visit-to-visit SBP variability correlates significantly with systemic atherosclerotic change , incidence of CVD , and mortality rate . Altered arterial functions , such as macrovascular atherosclerosis and vascular resistance , are responsible for the correlations between visit-to-visit SBP variability and incidence of CVD Background Cardiovascular disease ( CVD ) is the leading cause of death worldwide . Secondary prevention is essential , but participation rates for cardiac rehabilitation are low . Furthermore , current programmes do not accomplish that patients with CVD change their lifestyle in a way that their individual risk factors for recurrent events decrease , therefore more effective interventions are needed . In this study , the effectiveness of the Hartcoach-programme , a telephonic secondary prevention program focussing on self management , is studied . Methods / design A multicenter , r and omised parallel-group study is being conducted . Participants are 400 patients with acute myocardial infa rct ion ( STEMI , NSTEMI , ) and patients with chronic or unstable angina pectoris ( IAP ) . Patients are recruited through the participating hospitals and r and omly assigned to the experimental group ( Hartcoach-programme plus usual care ) or the control group ( usual care).The Hartcoach-programme consists of a period of six months during which the coach contacts the patient every four to six weeks by telephone . Coaches train patients to take responsibility for the achievement and maintenance of the defined target levels for their particular individual modifiable risk factors . Target levels and treatment goals are agreed by the nurse and patient together . Data collection is blinded and occurs at baseline and after 26 weeks ( post-intervention ) . Primary outcome is change in cardiovascular risk factors ( cholesterol , body mass index , waist circumference , blood pressure , physical activity and diet ) . Secondary outcomes include chances in glucose , HbA1c , medication adherence , self-management and quality of life . Discussion This study evaluates the effects of the Hartcoach-programme on the reduction of individual risk factors of patients with CVDs . Patients who are not invited to follow a hospital based rehabilitation programme or patients who are unable to adhere to such a programme , may be reached by this home based Hartcoach-programme . If positive results are found , the implementation of the Hartcoach-programme will be extended , having implication s for the management of many people with CVD.Trial registration BACKGROUND Human immunodeficiency virus (HIV)-infected individuals are at increased risk of cardiovascular disease ( CVD ) due in part to inflammation . Statins decrease inflammation in the general population , but their effect during HIV infection is largely unknown . METHODS This is an ongoing r and omized , double-blinded , placebo-controlled trial to evaluate the effect of statin therapy on inflammatory markers during HIV infection . Subjects received rosuvastatin 10 mg daily or placebo for 24 weeks . Subjects were receiving stable ( > 12 weeks ) antiretroviral therapy and had a low-density lipoprotein ( LDL ) cholesterol level of ≤130 mg/dL and evidence of heightened immune activation or inflammation . This was a prespecified interim analysis . RESULTS A total of 147 subjects were enrolled ( 78 % were male , 70 % were black , and the median age was 47 years ) . By 24 weeks , LDL cholesterol levels had decreased in the statin group , compared with an increase in the placebo group ( -28 % vs + 3.8 % ; P < .01 ) . A 10 % reduction in the lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) level was seen in the statin group , compared with a 2 % reduction in the placebo group ( P < .01 ) . In multivariable regression , receipt of statin treatment and having a nadir CD4(+ ) T-cell count of ≤100 cell/µL were the only statistically significant predictors of a decrease in Lp-PLA2 level . Markers of systemic inflammation did not change significantly between groups . CONCLUSIONS Twenty-four weeks of rosuvastatin therapy significantly decreased the level of Lp-PLA2 , a vascular-specific , inflammatory enzyme that predicts cardiovascular events in the general population . Statins may hold promise as a means of attenuating CVD risk in HIV-infected individuals by decreasing Lp-PLA2 levels BACKGROUND Despite major improvement in surgical techniques and intensive care management , stroke remains one of the most devastating complications of coronary artery bypass grafting ( CABG ) . We aim ed to determine factors predicting the occurrence of stroke during CABG . A special interest was focused on preoperative therapies . METHODS We prospect ively enrolled 810 consecutive c and i date s for CABG alone in a specific data base , including all pre- and perioperative data ( history , clinical , therapeutic , cardiac catheterization , surgical and intensive care data ) .  Univariate tests and then multiple logistic regression analysis were used to determine independent predictive factors . RESULTS During the first postoperative month , stroke occurred in 11 cases and transient ischemic attack ( TIA ) in 4 additive cases ( cumulative rate : 1.85 % ) . After the multivariate analysis , the following factors remained significant ( p<0.05 ) in the predictive model , with corresponding odds ratios between brackets : redo cardiac surgery ( 7.45 ) , unstable cardiac status ( 4.74 ) , past history of cerebrovascular disease ( 4.14 ) , past history of peripheral arterial disease ( 3.55 ) , whereas the presence of preoperative statins was protective ( 0.24 , 95 % IC : 0.07 - 0.78 ) . The addition of perioperative data ( aortic calcification , postoperative arrhythmia , on/off-pump surgery ) did not change the final predictive model . CONCLUSION To our knowledge , this is the first real-world observational report highlighting the interest of statins for the prevention of stroke in the very special situation of CABG . Even though according to r and omized trials coronary patients have a benefit from these drugs , a special level of interest should be directed towards those presenting the above-mentioned risk factors Background The feasibility of conducting a large-scale Polypill clinical trial in developing countries remains unclear . More information is needed regarding the efficacy in reducing the risk factors of cardiovascular disease ( CVD ) , side effects , improvement in adherence and physician/patient " acceptability " of the Polypill . Methods We conducted an open-label , parallel-group , r and omized clinical trial involving three sites in Sri Lanka that enrolled a total of 216 patients without established CVD . The trial compared a Polypill ( 75 mg aspirin , 20 mg simvastatin , 10 mg lisinopril and 12.5 mg hydrochlorothiazide ) to St and ard Practice . After r and omization , patients were followed monthly for three months . Pre-specified primary outcomes included reduction in systolic blood pressure , total cholesterol and estimated 10-year CVD risk . We also evaluated the recruitment process and acceptability of the Polypill by both physicians and patients . Results Patients were recruited in a six-month period as planned . Two hundred three patients ( 94.0 % ) completed the treatment program and returned for their three-month follow-up visits . No safety concerns were reported . These findings suggest a high rate of patient acceptability , a finding that is bolstered by the majority of patients completing the trial ( 90 % ) indicating that they would take the Polypill " for life " if proven to be effective in reducing CVD risk . Approximately 86 % of the physicians surveyed agreed with and supported use of the Polypill for primary prevention and 93 % for secondary prevention of CVD . Both the Polypill and St and ard Practice result ed in marked reductions in systolic blood pressure , total cholesterol and 10-year risk of CVD . However , the differences between the treatment groups were not statistically significant . Conclusions We successfully completed a Polypill feasibility trial in Sri Lanka . We were able to document high acceptability of the Polypill to patients and physicians . We were unable to estimate the risk factor reductions on the Polypill because the control group received similar treatment with individual drugs . The Polypill was however simpler and achieved comparable risk factor reductions , highlighting its potential usefulness in the prevention of CVD.Trial registration number Clinical trials.gov : The Systolic Blood Pressure Intervention Trial ( SPRINT ) is a large National Institutes of Health– sponsored multicenter r and omized controlled trial that enrolled 9361 patients with a systolic blood pressure ( SBP ) of at least 130 mm Hg . The primary goal of SPRINT was to test whether reducing SBP to a lower goal ( < 120 mm Hg ) than currently recommended ( < 140 mm Hg ) would reduce the occurrence of cardiovascular disease ( CVD ) and chronic kidney disease ( CKD ) events . Enrolled patients were 50 years or older with an SBP ≥130 mm Hg and at least one of the following : a history of CVD , stage 3 CKD ( estimated glomerular filtration rate 20–59 mL/min/1.73 m ) , an intermediate to high risk for CVD other than stroke , or age 75 years or older . A patient was defined as having CVD if they had a prior myocardial infa rct ion , percutaneous coronary intervention , coronary artery bypass grafting , carotid endarterectomy or carotid stenting , peripheral arterial disease with revascularization , acute coronary syndrome , abdominal aortic aneurysm ≥5 cm with or without repair , a coronary calcium score > 400 , or left ventricular hypertrophy . Patients were defined as at intermediate or high risk for CVD based on the following : Framingham Risk Score for 10-year CVD risk of 15 % based on laboratory work performed for lipids within the past 12 months . The primary outcome was a composite of cardiovascular events . The SPRINT study was terminated early after 3.26 years on advisory of the data safety monitoring board . The results of the SPRINT study showed a 25 % reduction in the primary combined cardiovascular outcome and a 27 % reduction in mortality in the group r and omized to SBP < 120 mm Hg . This obviously has important implication s for blood pressure ( BP ) guidelines in this population . The baseline mean systolic and diastolic BPs were 139.7 mm Hg and 78.1 mm Hg , respectively . At 1 year , the mean SBP was 121.4 mm Hg in the intensive treatment group and 136.2 mm Hg in the st and ard treatment group . The SPRINT study included 28 % of patients with CKD , 28 % of patients were older than 75 years , 36 % were women , and 20 % had prior CVD . The sample was diverse and included 29.9 % black , 10.5 % Hispanic , and 57.7 % white patients .  Importantly , SPRINT excluded many patients with hypertension . Who were these population s ? The following groups of patients with hypertension were excluded : those with a history of prior stroke , diabetes , polycystic kidney disease , any secondary cause for hypertension , glomerular filtration rate ( GFR ) < 20 cc/ min , > 1 g of proteinuria per 24 hours , glomerulonephritis treated with immunosuppressive therapy , symptomatic heart failure within the past 6 months or left ventricular ejection fraction < 35 % , expected survival less than 3 years , cancer diagnosed within the past 2 years , organ transplant , cardiovascular event , procedure or hospitalization for unstable angina within the past 3 months , and all patients younger than 50 years . Why were these patients excluded ? Patients with diabetes were excluded as it was felt that this population had already been studied in the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) BP trial , which did not show a cardiovascular advantage of lower SBP ( < 120 mm Hg ) vs st and ard BP ( < 140 mm Hg ) although there was a decreased risk of stroke .  Patients with polycystic kidney disease have also been studied separately in the HALT Progression of Polycystic Kidney Disease study , which recently showed that rigorous BP control was associated with a slower increase in total kidney volume , no overall change in the estimated GFR , a greater decline in the left ventricular mass index , and greater reduction in urinary albumin excretion .  Patients with excessive proteinuria > 1 g per 24 hours were also excluded , but , based on data from the Modification of Diet in Renal Disease ( MDRD ) , the Blood Pressure Control for Renoprotection in Patients With Nondiabetic Chronic Renal Disease ( REIN ) , and the African American Study of Kidney Disease and Hypertension ( AASK ) studies , lower BP goals ( < 130/80 mm Hg ) have been suggested and recommended by some guidelines in this patient population . Renal transplant recipients were excluded in this population . There are no r and omized controlled trials examining optimal levels of BP and this is a population that needs to be studied . BP threshold for treatment of kidney transplant recipients remains at 130/80 mm Hg , regardless of proteinuria . The Secondary Prevention of Small Subcortical Strokes ( SPS3 ) trial , which compared an SBP treatment target of < 130 mm Hg with a target of 130 mm Hg to 149 mm Hg in participants with a recent lacunar stroke , showed a nonsignificant reduction in recurrent stroke in the group r and omized to the lower target . There are no specific studies that have evaluated BP targets in patients without other comorbidities who are Address for correspondence : Debbie L. Cohen , MD , Renal , Electrolyte and Hypertension Division , Perelman School of Medicine at the University of Pennsylvania , 1 Founders Building , 3400 Spruce Street , Philadelphia , PA 19104 E-mail : OBJECTIVES Elevated serum uric acid ( SUA ) levels have been associated with cardiovascular disease ( CVD ) in the general population . Rheumatoid arthritis ( RA ) is not thought to associate with high SUA but is characterized by increased CVD morbidity and mortality . We aim ed to explore a potential association of SUA with CVD in RA patients and to evaluate whether such an association is present when the traditional CVD risk factors are taken into account . METHODS . 400 consecutive RA patients were recruited in this cross-sectional study and had all traditional CVD risk factors and SUA assessed . The association of SUA levels with other variables was assessed using bivariate correlations . Subsequent binary logistic models with appropriate adjustments were used to test the independence of the association between SUA and CVD . RESULTS SUA levels were significantly higher in RA patients with CVD ( RA + CVD ) compared with RA patients without CVD ( RA - CVD ) ( 5.68 + /- 1.81 mg dl(-1 ) vs 5.06 + /- 1.41 mg dl(-1 ) , P = 0.001 ) . After adjusting for CVD risk factors , physical function ( health assessment question naire , HAQ ) and use of diuretics and /or statins the association between SUA and CVD in RA patients remained significant [ Odds ratio ( OR ) = 1.36 , 95 % confidence interval ( CI ) 1.04 - 1.79 , P = 0.025 ] . Compared with subjects with SUA levels in the lowest quintile ( < 3.86 mg dl(-1 ) ) , those within the highest quintile ( > /=6.38 mg dl(-1 ) ) had a 6-fold increase in the odds of having CVD ( adjusted OR 6.46 , 95 % CI 1.66 - 25.05 , P = 0.007 ) . CONCLUSIONS This cross-sectional study suggests that SUA may be independently associated with CVD in RA patients . This needs to be confirmed in prospect i ve studies BACKGROUND R and omized trials have largely failed to support an effect of antioxidant vitamins on the risk of cardiovascular disease ( CVD ) . Few trials have examined interactions among antioxidants , and , to our knowledge , no previous trial has examined the individual effect of ascorbic acid ( vitamin C ) on CVD . METHODS The Women 's Antioxidant Cardiovascular Study tested the effects of ascorbic acid ( 500 mg/d ) , vitamin E ( 600 IU every other day ) , and beta carotene ( 50 mg every other day ) on the combined outcome of myocardial infa rct ion , stroke , coronary revascularization , or CVD death among 8171 female health professionals at increased risk in a 2 x 2 x 2 factorial design . Participants were 40 years or older with a history of CVD or 3 or more CVD risk factors and were followed up for a mean duration of 9.4 years , from 1995 - 1996 to 2005 . RESULTS A total of 1450 women experienced 1 or more CVD outcomes . There was no overall effect of ascorbic acid ( relative risk [ RR ] , 1.02 ; 95 % CI , 0.92 - 1.13 [ P = .71 ] ) , vitamin E ( RR , 0.94 ; 95 % CI , 0.85 - 1.04 [ P = .23 ] ) , or beta carotene ( RR , 1.02 ; 95 % CI , 0.92 - 1.13 [ P = .71 ] ) on the primary combined end point or on the individual secondary outcomes of myocardial infa rct ion , stroke , coronary revascularization , or CVD death . A marginally significant reduction in the primary outcome with active vitamin E was observed among the prespecified subgroup of women with prior CVD ( RR , 0.89 ; 95 % CI , 0.79 - 1.00 [ P = .04 ] ; P value for interaction , .07 ) . There were no significant interactions between agents for the primary end point , but those r and omized to both active ascorbic acid and vitamin E experienced fewer strokes ( P value for interaction , .03 ) . CONCLUSION There were no overall effects of ascorbic acid , vitamin E , or beta carotene on cardiovascular events among women at high risk for CVD OBJECTIVE Cardiovascular disease ( CVD ) is the most important cause of mortality in patients with type 2 diabetes and is preceded by endothelial dysfunction . Flow-mediated dilation ( FMD ) is a noninvasive technique for measuring endothelial dysfunction . We aim ed to determine the effect of long-term statin therapy versus placebo on FMD in patients with type 2 diabetes without manifest CVD . RESEARCH DESIGN AND METHODS A r and omized , placebo-controlled , double-blind trial was performed with 250 type 2 diabetic patients . Patients were given 0.4 mg cerivastatin or placebo daily . In August 2001 , when cerivastatin was withdrawn from the market , the 0.4 mg cerivastatin was replaced by 20 mg simvastatin , without deblinding the study . The primary end point was the change in FMD , measured by B-mode ultrasound , after 2 years . RESULTS Determinants of baseline FMD were diabetes duration , common carotid intima-media thickness , and brachial artery diameter . FMD at baseline was 1.51 % in the placebo group and 1.66 % in the statin group and did not change significantly after 2 years . CONCLUSIONS The 2-year statin therapy had no effect on FMD in type 2 diabetes . Statin-induced improvement of cardiovascular risk in patients with type 2 diabetes may be mediated through mechanisms other than increased nitric oxide availability The Heart Protection Study ( HPS ) , with over 20,500 subjects , is the largest trial of statin therapy ever conducted . It provides important and definitive new information on women , the elderly , diabetics , and people with low baseline cholesterol pre-treatment and those with prior occlusive non-coronary vascular disease . It is a prospect i ve double blind r and omised controlled trial with a 2 x 2 factorial design investigating prolonged use ( > 5 years ) of simvastatin 40 mg and a cocktail of antioxidant vitamins ( 650 mg vitamin E , 250 mg vitamin C and 20 mg beta-carotene ) . The HPS specifically included patients with high risk for coronary heart disease ( CHD ) but characteristics that excluded them from participation in previous statin trials .  Simvastatin 40 mg treatment showed benefit across all patient groups regardless of age , gender or baseline cholesterol value and proved safe and well tolerated . Results show a 12 % reduction in total mortality , a 17 % reduction in vascular mortality , a 24 % reduction in CHD events , a 27 % reduction in all strokes and a 16 % reduction in non-coronary revascularisations . Among high-risk patients in this western population ( with a minimum total cholesterol [ TC ] > or = 3.5 mmol/l at entry ) there appears to be no threshold cholesterol value below which statin therapy is not associated with benefit ; even among those with pre-treatment cholesterol levels below current national recommended targets . Over the 5.5 year study period patients and their doctors were encouraged to add an active non- study statin to the study regimen if they wished to do so . Thus the trial eventually had only two-thirds complying with the original intention-to-treat design . Nevertheless , results were highly significant for the study statin -- simvastatin 40 mg once daily . Preliminary results of the HPS are negative for the antioxidant vitamin cocktail but provide reassurance that vitamins do no harm BACKGROUND Few studies have examined whether changes in alcohol consumption influence future cardiovascular risk . OBJECTIVE To examine whether 7-year changes in alcohol consumption are associated with the subsequent risk of cardiovascular disease ( CVD ) . METHODS We prospect ively followed up 18,455 men aged 40 to 84 years from the Physicians ' Health Study with no history of CVD or cancer .  Alcohol consumption  was reported on the baseline and the 7-year question naires ; follow-up for this analysis began after the 7-year question naire ( median follow-up , 5.8 years ) . There were 1091 CVD cases , including myocardial infa rct ion , angina pectoris , revascularization , stroke , and CVD-related death .  RESULTS Among men initially consuming 1 drink per week or less ( n=7360 ) , those with moderate increases ( > 1 to < 6 drinks per week ) in alcohol consumption had a borderline significant ( P=.05 ) 29 % reduced risk of CVD compared with men with no changes ( -1 to 1 drink per week ) . Among men initially consuming greater than 1 to 6 drinks per week ( n=6612 ) , those with moderate increases had a nonsignificant ( P=.32 ) 15 % decrease in CVD risk compared with men with no changes . Finally , among men initially consuming 1 drink per day or more ( n=4483 ) , those who increased intake had a 63 % increased risk of CVD compared with men with no changes . CONCLUSIONS These prospect i ve data suggest that , among men with initially low alcohol consumption ( < /=1 drink per week ) , a subsequent moderate increase in alcohol consumption may lower their CVD risk . The possible reduction in CVD risk from increasing alcohol intake did not extend to men initially consuming greater than 1 drink per week . Given the potential risks and benefits associated with alcohol consumption , physician counseling of patients must be individualized in the context of the primary prevention of CVD Context Studies of the role of endogenous sex hormones in  cardiovascular disease ( CVD ) in men have been inconclusive . Contribution A total of 2084 men from 2 Framingham Heart Study cohorts had levels of  total serum estrogen , testosterone , and dehydroepi and rosterone sulfate ( DHEA-S )  measured in 1981 to 1985 for the original cohort and in 1987 to 1991 for the offspring cohort . Testosterone and DHEA-S levels were not associated with CVD risk . Estrogen levels were inversely related : Risk for CVD in the highest quartile was 0.68 ( 95 % CI , 0.50 to 0.92 ) times that in the lowest level . Caution s Investigators studied only white men and did not study free unbound hormone levels . Implication s Endogenous estrogen may be vasculoprotective in men , which is in contrast to the effects of exogenous estrogen . The Editors Male sex is an independent risk factor for cardiovascular disease ( CVD ) ( 1 ) . Scientists have postulated that the 5- to 10-year lag period in CVD incidence in women ( compared with men ) may be related to differences in endogenous sex hormones ( 27 ) . Indeed , substantial evidence suggests that sex hormones ( testosterone , estrogen , and dehydroepi and rosterone sulfate [ DHEA-S ] ) influence traditional and newer CVD risk factors ( 27 ) . Interest in the role of sex hormones in the pathogenesis of CVD has been rekindled by the observation that men with genetic defects of estrogen synthesis ( 8) or action ( 9 ) develop premature atherosclerosis . In addition , genetic variation in estrogen receptor- has been associated with prevalent CVD ( 10 , 11 ) , and and rogen and estrogen receptor expression in coronary arteries has been reported to influence coronary atherosclerosis in men ( 12 ) . In contrast to the aforementioned data , prospect i ve studies relating circulating sex hormone levels to incident CVD in men have been inconclusive . For example , low serum testosterone levels have been associated with greater progression of sub clinical atherosclerosis in 2 previous investigations ( 13 , 14 ) , but other studies have reported no association of testosterone levels with CVD events ( 1521 ) . On a parallel note , low DHEA-S levels have been linked to greater CVD risk in some studies ( 18 , 2224 ) but not in other studies ( 13 , 20 , 2529 ) . Investigations relating serum estradiol levels to CVD risk in men have generally found no statistically significant association ( 1520 ) . Some previous investigations were limited by modest sample sizes ( 14 , 17 , 18 , 22 , 25 , 26 ) ; an insufficient number of CVD events ( 1518 , 22 , 23 , 26 ) ; and , in some instances , a retrospective study design ( 1721 , 25 , 26 ) . In addition , some reports ( 15 , 22 , 24 ) focused on CVD death ( they did not evaluate nonfatal CVD events ) . Thus , a large prospect i ve community-based study relating sex hormones to CVD risk with adequate power to detect modest potential associations is needed . Accordingly , we evaluated the associations of serum levels of sex hormones that were measured at a routine baseline examination with CVD incidence in a prospect ively assembled cohort of participants . Methods Study Sample The Framingham Heart Study , a prospect i ve study of the risk factors for the development of heart disease and stroke , began in 1948 with the recruitment of 5209 men and women between 30 and 60 years of age who resided in Framingham , Massachusetts ( 30 ) . The Framingham Offspring Study began in 1971 with the recruitment of 5124 participants who were the children of the original cohort and the spouses of the children ( 31 ) . Participants in the original cohort are examined every 2 years , while offspring cohort members are assessed every 4 years . At each Framingham Heart Study examination , attendees undergo a physical examination and laboratory assessment of risk factors ( 31 ) . We evaluated 2789 men who attended the 17th biennial examination ( 19811983 ) of the original cohort or the fourth quadrennial examination ( 19871991 ) of the offspring cohort . We measured serum total testosterone and estradiol levels at these examinations , and we measured DHEA-S levels at the 18th examination ( 19831985 ) for the original cohort and at the fourth examination for the offspring cohort . We excluded 705 men because of prevalent CVD ( n= 541 ) and nonavailable testosterone data ( n= 164 ) . After exclusions , 2084 men ( 74.7 % ; 525 original cohort participants ) without previous CVD were eligible . Data on serum estradiol levels and serum DHEA-S levels were available in 2047 men and 1928 participants , respectively . All participants gave written informed consent , and the institutional review board at the Boston Medical Center approved the study protocol . Biochemical Assessment of Sex Hormones As described previously ( 32 ) , we measured total testosterone , total estradiol , and DHEA-S levels from serum sample s by using radioimmunoassays ( Diagnostic Products Corp. , Los Angeles , California ) for total testosterone ( interassay coefficient of variation , 11 % ) , total estradiol ( interassay coefficient of variation , 4 % ) , and DHEA-S ( interassay coefficient of variation , 11 % ) . We also measured serum luteinizing hormone levels at the baseline examinations ( interassay coefficient of variation , 6 % ) . Cardiovascular Outcomes All participants were under continuous surveillance for the occurrence of  CVD events and death . Participants are evaluated periodically at the Framingham Heart Study and through health history up date s between examinations ( obtained via telephone interviews ) . Three experienced investigators obtained and review ed hospitalization and physician office visit records . We defined incident CVD as coronary heart disease ( recognized or unrecognized myocardial infa rct ion , angina pectoris , coronary insufficiency , or coronary heart disease death ) , cerebrovascular disease ( stroke or transient ischemic attack ) , congestive heart failure ( by Framingham criteria ) , or peripheral vascular disease ( intermittent claudication ) . Criteria for the diagnoses of cardiovascular events have been described elsewhere ( 33 ) . We considered that an unrecognized myocardial infa rct ion occurred if we found electrocardiographic evidence of clinical ly significant loss of R waves or appearance of pathologic Q waves on serial tracings in the absence of a clinical ly recognized event ( 33 ) . We defined the follow-up period a priori as 10 years from the baseline examination ( up to 1995 for the original cohort and 2002 for the offspring cohort ) to permit equal duration s of follow-up of original and offspring cohort participants and because sex hormone levels change considerably with age ( 34 ) . The analyses that combined the original and offspring cohorts had greater statistical power and allowed us to evaluate participants over a wider age range . Statistical Analyses Serum testosterone levels were normally distributed . Serum estradiol and DHEA-S levels were skewed and were log-transformed . We examined the associations between baseline sex hormone levels and CVD incidence during follow-up ( separate analyses for each hormone ) . We chose incident CVD as the outcome because the effects of sex hormones are not limited to a given vascular territory and this maximized our statistical power and limited multiple statistical testing ( as opposed to analysis for each CVD component ) . We stratified all analyses by the cohort ( offspring cohort vs. original cohort ) . We verified that the assumption of proportionality of hazards was satisfied for each hormone . We calculated age- and multivariable-adjusted 10-year incidence rates for CVD for each hormone quartile ( 35 ) . We prespecified 2 types of models : Primary analyses evaluated the sex hormones as continuous variables to maximize statistical power ( model A ) , and additional analyses compared CVD risk in hormone quartiles 2 to 4 with that in quartile 1 ( referent ) ( model B ) . These models facilitated assessment of potential nonlinear relations . For each hormone , we used proportional hazards regression ( 36 ) that adjusted for 1 ) age alone and 2 ) age , smoking , systolic and diastolic blood pressure , antihypertensive medication use , ratio of total and high-density lipoprotein ( HDL ) cholesterol , diabetes mellitus , and body mass index ( BMI ) . We evaluated models adjusted for age alone because some risk factors may fall along the causal pathway from estradiol to CVD . Adjustment for BMI was performed because adiposity is a strong correlate of sex hormone levels ( 37 ) and of sex hormonebinding globulin ( 38 ) . Sex hormonebinding globulin strongly influences measurements of total circulating sex hormone levels and the amount of bound hormone versus free hormone . We also evaluated models without BMI as a covariate to assess whether adjustment for BMI attenuated relations of sex hormones with CVD and models that were adjusted additionally for the use of aspirin or lipid-lowering medications , alcohol consumption , and education level . We incorporated statistical interaction terms to evaluate effect modification by age , BMI , smoking status , systolic blood pressure , and total cholesterolHDL cholesterol ratio . To gain additional insights into potential nonlinearity of associations between hormone levels and CVD risk , we examined generalized additive Cox models using penalized splines ( 39 , 40 ) for hormones that were statistically significantly related to CVD risk . Because potential relationships of sex hormones to CVD risk may be mediated by the development of risk factors during follow-up , we prespecified examination of time-dependent Cox models ( updating established CVD risk factors [ covariates in the multivariable-adjusted proportional hazards regression ] every 4 years at follow-up examinations ) for analyses of any sex hormone that was statistically significantly related to CVD events in the initial analyses . Additional Analyses We performed secondary analyses relating CVD risk to the estradioltestosterone ratio ( 37 , 41 ) . In addition , we investigated whether hypogonadism was related to CVD risk . We defined hypogonadism empirically as a serum testosterone level less than 10.4 nmol/L ( BACKGROUND Prospect i ve data relating fruit and vegetable intake to cardiovascular disease ( CVD ) risk are sparse , particularly for women . OBJECTIVE In a large , prospect i ve cohort of women , we examined the hypothesis that higher fruit and vegetable intake reduces CVD risk . DESIGN In 1993 we assessed fruit and vegetable intake among 39876 female health professionals with no previous history of CVD or cancer by use of a detailed food-frequency question naire . We subsequently followed these women for an average of 5 y for incidence of nonfatal myocardial infa rct ion ( MI ) , stroke , percutaneous transluminal coronary angioplasty , coronary artery bypass graft , or death due to CVD . RESULTS During 195647 person-years of follow-up , we documented 418 incident cases of CVD including 126 MIs . After adjustment for age , r and omized treatment status , and smoking , we observed a significant inverse association between fruit and vegetable intake and CVD risk . For increasing quintiles of total fruit and vegetable intake ( median servings/d : 2 . 6 , 4.1 , 5.5 , 7.1 , and 10.2 ) , the corresponding relative risks ( RRs ) were 1.0 ( reference ) , 0.78 , 0.72 , 0.68 , and 0.68 ( 95 % CI comparing the 2 extreme quintiles : 0.51 , 0.92 ; P : for trend = 0.01 ) . An inverse , though not statistically significant , trend remained after additional adjustment for other known CVD risk factors , with RRs of 1.0 , 0.75 , 0.83 , 0.80 , and 0.85 ( 95 % CI for extreme quintiles : 0.61 , 1.17 ) . After excluding participants with a self-reported history of diabetes , hypertension , or high cholesterol at baseline , the multivariate-adjusted RR was 0.45 when extreme quintiles were compared ( 95 % CI : 0.22 , 0.91 ; P : for trend = 0.09 ) . Higher fruit and vegetable intake was also associated with a lower risk of MI , with an adjusted RR of 0.62 for extreme quintiles ( 95 % CI : 0.37 , 1.04 ; P : for trend = 0.07 ) . CONCLUSION These data suggest that higher intake of fruit and vegetables  may be protective against CVD and support current dietary guidelines to increase fruit and vegetable intake In 1998 , the American Heart Association convened Prevention Conference V to examine strategies for the identification of high-risk patients who need primary prevention . Among the strategies discussed was the measurement of markers of inflammation.1  The Conference concluded that “ many of these markers ( including inflammatory markers ) are not yet considered applicable for routine risk assessment because of : ( 1 ) lack of measurement st and ardization , ( 2 ) lack of consistency in epidemiological findings from prospect i ve studies with endpoints , and ( 3 ) lack of evidence that the novel marker adds to risk prediction over and above that already achievable through the use of established risk factors . ” The National Cholesterol Education Program Adult Treatment Panel III Guidelines identified these markers as emerging risk factors,1a which could be used as an optional risk factor measurement to adjust estimates of absolute risk obtained using st and ard risk factors . Since these publications , a large number of peer- review ed scientific reports have been published relating inflammatory markers to cardiovascular disease ( CVD ) . Several commercial assays for inflammatory markers have become available . As a consequence of the exp and ing research base and availability of assays , the number of inflammatory marker tests ordered by clinicians for CVD risk prediction has grown rapidly . Despite this , there has been no consensus from professional societies or governmental agencies as to how these assays of markers of inflammation should be used in clinical practice . On March 14 and 15 , 2002 , a workshop titled “ CDC/AHA Workshop on Inflammatory Markers and Cardiovascular Disease : Applications to Clinical and Public Health Practice ” was convened in Atlanta , Ga , to address these issues . The goals of this workshop were to determine which of the currently available tests should be used ; what results should be used to define high risk ; which patients should be tested ; and the indications for which the tests would be most useful . These Background Evidence -based r and omized clinical trials have shown significant benefit of statin treatment with regard to cardiovascular disease . In anticipation of the National Cholesterol Education Program Adult Treatment Panel IV guidelines , we wanted to assess the current state of lipid goal attainment in the high-risk secondary prevention population in the United States . The objectives of the study were to estimate the proportion of high-risk patients treated with statin monotherapy  who achieved Adult Treatment Panel III – recommended low-density lipoprotein cholesterol ( LDL-C ) goals ( < 100 mg/dL ; optional < 70 mg/dL ) as well as non – high-density lipoprotein cholesterol goals ( < 130 mg/dL ; optional < 100 mg/dL ) . Methods and Results This is a cross-sectional , retrospective study of 3 data sources : electronic medical records ( 2003–September 2010 ) , administrative cl aims data ( 2003–2010 ) , and National Health and Nutrition Examination Survey data ( 2007–2008 ) . High-risk patients ( ≥18 years of age ) were defined as those with a history of coronary heart disease or coronary heart disease risk equivalent who had the latest complete lipid panel measurement and had been treated with statin monotherapy for > 90 days at the time of the lipid panel . Cardiovascular disease , coronary heart disease , and coronary heart disease risk equivalents were defined on the basis of availability , specific to each data source . Across the 3 data sources , 20 % to 26 % of high-risk patients treated with statin monotherapy for > 90 days had LDL-C < 70 mg/dL , and 67 % to 77 % had LDL-C < 100 mg/dL. The percentages of those attaining both LDL-C goals and non – high-density lipoprotein cholesterol goals were quantitatively smaller ( 13.5 % to 19.0 % and 46 % to 70 % ) . Conclusions Across the 3 data sources , there was consistency in the proportion of high-risk patients treated with statin monotherapy who were at LDL-C goal . A significant number of these statin-treated patients had additional dyslipidemias OBJECTIVES This study sought to estimate the extent to which behavioral and pathophysiological risk factors account for the association between  psychological distress  and incident cardiovascular events . BACKGROUND The intermediate processes through which psychological distress increases the risk of cardiovascular disease ( CVD ) are incompletely understood . An underst and ing of these processes is important for treating psychological distress in an attempt to reduce CVD risk . METHODS In a prospect i ve study of 6,576 healthy men and women ( ages 50.9 + /- 13.1 years ) , we measured psychological distress ( using the 12-item version of the General Health Question naire > or=4 ) and behavioral ( smoking , alcohol , physical activity ) and pathophysiological ( C-reactive protein , fibrinogen , total and high-density lipoprotein cholesterol , obesity , hypertension ) risk factors at baseline . The main outcome was CVD events ( hospitalization for nonfatal myocardial infa rct ion , coronary artery bypass , angioplasty , stroke , heart failure , and CVD-related mortality ) . RESULTS Cigarette smoking , physical activity , alcohol intake , C-reactive protein , and hypertension were independently associated with psychological distress . There were 223 incident CVD events ( 63 fatal ) over an average follow-up of 7.2 years . The risk of CVD increased in relation to presence of psychological distress in age- and sex-adjusted models ( hazard ratio : 1.54 , 95 % confidence interval : 1.09 to 2.18 , p = 0.013 ) . In models that were adjusted for potential mediators , behavioral factors explained the largest proportion of variance ( approximately 65 % ) , whereas pathophysiological factors accounted for a modest amount ( C-reactive protein approximately 5.5 % , hypertension , approximately 13 % ) . CONCLUSIONS The association between psychological distress and CVD risk is largely explained by behavioral processes . Therefore , treatment of psychological distress that aims to reduce CVD risk should primarily focus on health behavior change Context : The benefit of weight reduction for cardiovascular disease ( CVD ) outcomes remains uncertain . Objective : To examine the effects of baseline body mass index on major CVD outcomes and diabetes over a 20 year follow up , and of weight change in the first five years over the subsequent 15 years . Design and setting : A prospect i ve study of British men followed up for 20 years . Participants : Men aged 40–59 years with no diagnosis of CVD or diabetes ( n = 7176 ) of whom 6798 provided full information on weight change five years later . Outcome measures : Major CVD events ( fatal and non-fatal myocardial infa rct ion and stroke , angina , “ other ” CVD deaths ) and diabetes . Results : During the 20 year follow up there were 1989 major CVD events and 449 incident cases of diabetes in the 7176 men . Risk of major CVD and diabetes increased significantly with increasing overweight and obesity . During the 15 year follow up , weight gain was associated with increased risk of CVD and diabetes . Weight loss was associated with lower risk of diabetes than the stable group irrespective of initial weight . No significant cardiovascular benefit was seen for weight loss in any men , except possibly in considerably overweight ( BMI 27.5–29.9 kg/m2 ) younger middle aged men ( RR = 0.42 ; 95 % CI 0.22 to 0.81 ) . Conclusion : Long term risk of CVD and diabetes increased significantly with increasing overweight and obesity . Weight loss was associated with significant reduction in risk of diabetes but not CVD , except possibly in considerably overweight younger men . Duration and severity of obesity seem to limit the cardiovascular benefits of weight reduction in older men BACKGROUND Although some studies have demonstrated that pharmacist intervention can improve drug therapy among patients with cardiovascular disease ( CVD ) , more evidence derived from r and omized controlled trials ( RCTs ) is needed , including assessment of the effect of community pharmacist interventions in patients with CVD . OBJECTIVE To assess the effectiveness of the Dader Method for pharmaceutical care on achieving therapeutic goals for blood pressure ( BP ) , total cholesterol ( TC ) , and both BP and TC ( BP/TC ) in patients with CVD and /or high or intermediate cardiovascular ( CV ) risk attending community pharmacies in Spain . METHODS Patients aged 25 to 74 years attending community pharmacies with a prescription for at least 1 drug indicated for CVD or CV risk factors were r and omized to 2 groups : an intervention group that received pharmaceutical care , which was provided by specially trained pharmacists working in collaboration with physicians , and a control group that received usual care ( routine dispensing counseling ) and verbal and written counseling regarding CVD prevention .  Patients were recruited from December 2005 to September 2006 , and both groups were followed for 8 months . Study outcomes were assessed at baseline and at 16 and 32 weeks after r and omization . The primary outcome measures were the proportions of patients achieving BP , TC , and BP/TC therapeutic goals ( BP lower than 140/90 mm Hg for patients with uncomplicated hypertension and lower than 130/80 mm Hg for patients with diabetes , chronic kidney disease , or history of myocardial infa rct ion or stroke ; TC lower than 200 mg per dL for patients without CVD and lower than 175 mg per dL for patients with CVD ) . Secondary outcomes were mean BP and TC values . BP was assessed manually by the pharmacist after a 10-minute rest in the supine position . This measurement was performed twice for every participant , and the average of the 2 measurements was calculated . TC was measured by the pharmacist during the study visit using the enzymatic dry method . Statistical analyses were performed using 2-tailed McNemar tests , Pearson chi-square tests , and Student 's t-tests ; P < 0.05 was considered statistically significant . RESULTS 714 patients were included in the study ( 356 intervention , 358 control ) , and the mean [ SD ] age was 62.8 [ 8.1 ] years . The 2 groups were similar at baseline in clinical and demographic characteristics , including the proportion of patients at therapeutic goals for BP , TC , and BP/TC . After 8 months of follow-up , there were statistically significant differences in favor of pharmaceutical care in the proportions of patients who achieved therapeutic goals for BP ( 52.5 % vs. 43.0 % , P=0.017 ) , TC ( 56.5 % vs. 44.1 % , P=0.001 ) , and BP/TC ( 37.1 % vs. 21.8 % , P < 0.001 ) . CONCLUSION Compared with usual care plus written education , pharmaceutical care focused on patient evaluation and follow-up in collaboration with physicians improved the achievement of BP , TC , and BP/TC treatment goals in patients with CVD and /or high or intermediate CV risk attending community pharmacies in Spain Statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals but their efficacy and safety in elderly people has not been confirmed . Several clinical trials including the Cholesterol and Recurrent Events ( CARE ) and Long-term Intervention with Pravastatin in Ischemic Disease ( LIPID ) , have sub-analysed their results for the ' elderly ' cohort , but the Prospect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) trial is the first trial to specifically evaluate the benefits of statin therapy on vascular risk in elderly men and women . The results have shown that pravastatin , given for 3 years , reduced the risk of coronary heart disease in elderly individuals . Within this same time frame , there was no significant benefit on the risk reduction of stroke but there was a trend to reduce the risk of transient ischemic attacks . It was discovered that those patients with the lowest baseline high-density lipoprotein cholesterol gained the most benefit from the intervention . Drug interactions between pravastatin and the concomitant medications seen in this elderly cohort , was not a significant clinical issue . Therefore , PROSPER extends to elderly individuals the treatment strategy currently used in middle-aged people Background —Few data have evaluated physician adherence to cardiovascular disease ( CVD ) prevention guidelines according to physician specialty or patient characteristics , particularly gender . Methods and Results —An online study of 500 r and omly selected physicians ( 300 primary care physicians , 100 obstetricians/gynecologists , and 100 cardiologists ) used a st and ardized question naire to assess awareness of , adoption of , and barriers to national CVD prevention guidelines by specialty . An experimental case study design tested physician accuracy and determinants of CVD risk level assignment and application of guidelines among high- , intermediate- , or low-risk patients . Intermediate-risk women , as assessed by the Framingham risk score , were significantly more likely to be assigned to a lower-risk category by primary care physicians than men with identical risk profiles ( P<0.0001 ) , and trends were similar for obstetricians/gynecologists and cardiologists . Assignment of risk level significantly predicted recommendations for lifestyle  and preventive pharmacotherapy . After adjustment for risk assignment , the impact of patient gender on preventive care was not significant except for less aspirin ( P<0.01 ) and more weight management recommended ( P<0.04 ) for intermediate-risk women . Physicians did not rate themselves as very effective in their ability to help patients prevent CVD . Fewer than 1 in 5 physicians knew that more women than men die each year from CVD . Conclusions —Perception of risk was the primary factor associated with CVD preventive recommendations . Gender disparities in recommendations for preventive therapy were explained largely by the lower perceived risk despite similar calculated risk for women versus men . Educational interventions for physicians are needed to improve the quality of CVD preventive care and lower morbidity and mortality from CVD for men and women Context National guidelines recommend aspirin or statin drugs individually to reduce first coronary heart disease ( CHD )  events , but there are no guidelines about taking both . Contribution The authors used a Markov model to estimate the cost-effectiveness of aspirin , statins , both drugs , or neither in men . In patients with a 10-year risk for CHD of 7.5 % , aspirin alone reduced costs and lengthened life compared with no treatment . Adding a statin cost $ 56200 per additional quality -adjusted life-year at a 7.5 % risk but only $ 42500 at a 10 % risk . Caution s The authors ' analysis was limited to men . Implication s Therapy with aspirin alone is effective and cost-effective in men with an average level of risk for CHD . The addition of a statin is more cost-effective as risk increases . The Editors Aspirin and statin drugs have been shown to be effective for preventing first coronary heart disease ( CHD ) events ( 1 - 3 ) . Systematic review s and meta-analyses suggest that the relative risk reductions with both forms of therapy are similar in magnitude and seem to be independent and relatively constant across the range of underlying risk for CHD ( 2 - 5 ) . The absolute benefit from these treatments seems to be proportional to the patient 's underlying risk for CHD . National treatment guidelines recommend aspirin and statin drugs individually for the primary prevention of cardiovascular events in men who are at increased risk ( 4 , 6 , 7 ) . However , no U.S. guidelines have addressed how these drugs should be used together , and we are unaware of any previous analyses that have reported the cost-effectiveness of these drugs when used in combination for CHD prevention . To help inform clinical and policy decisions about primary CHD prevention , we performed a costutility analysis that examined the use of aspirin therapy , statin therapy , or combination therapy with both drugs in men with various underlying levels of risk for CHD . Methods To examine the cost and utility associated with aspirin and with statin use , we used Microsoft Excel 2002 for Windows ( Microsoft Corp. , Redmond , Washington ) to develop a Markov state-transition model . The model was design ed to simulate cohorts of initially healthy middle-aged men with no history of cardiovascular events and with various levels of 10-year risk for CHD ( Figure 1 ) . Figure 1 . General structure of the Markov model . Base-Case Scenario In our base-case scenario , we compared the effectiveness of 10 years of aspirin therapy , statin therapy , combination therapy with both drugs , and no therapy in 45-year-old men with a 10-year risk for CHD of 7.5 % . After 10 years , both groups adopted the treatment used in the intervention group . Although the differences in therapy were maintained for only 10 years , we examined the effects of these therapies over a lifetime . Model Assumptions All persons were initially healthy and progressed through the model in annual cycles . In each cycle , an individual remained healthy , had an initial cardiovascular event ( angina , myocardial infa rct ion , or stroke ) , experienced adverse effects from therapy ( gastrointestinal bleeding from aspirin or myopathy from statins ) , or died . We assumed that those who had cardiovascular events or adverse events stayed in the subacute state for the remainder of that cycle and then entered a postevent state . Adherence to treatment was assumed to be 100 % in the absence of adverse effects , although the treatment efficacy data were based on the actual rates of adherence in the clinical trials . Persons who had adverse effects from therapy stopped taking the offending medication ; their procession through the model was similar to that of healthy patients after the initial cycle . All costs and outcomes were discounted at 3 % in accordance with current consensus recommendations ( 8) . Model Parameters Model parameters , including base-case values , ranges , and references , are shown in Table 1 ( 1 - 3 , 9 - 29 ) . Table 1 . Base-Case Estimates and Ranges Used in Sensitivity Analyses Noncardiovascular Mortality Age-dependent noncardiovascular mortality rates were estimated from the National Vital Statistics life tables ( 31 ) . Rates were adjusted as the cohort aged over the time horizon of the analysis . Cardiovascular Event Rates Baseline risks for initial cardiovascular events ( myocardial infa rct ion , stroke , angina , and death from CHD ) were drawn from Framingham risk equations by using hypothetical scenarios of nonsmoking , nonhypertensive , nondiabetic men at different levels of risk for CHD ( Appendix Table ) ( 32 ) . Assuming an exponential distribution , we translated these 10-year risks into annual event-related transition probabilities . These probabilities were allowed to change over time to reflect increasing risk for CHD over the time horizon of the analysis . Appendix Table . Sample Baseline Characteristics of 45-Year-Old Men by Risk Level Because we were interested in primary prevention , we did not simulate or examine the details of a patient 's course after a primary , nonfatal event . Instead , we assigned them an increased risk for death , increased costs , and decreased utilities by using data from the literature regarding the average experience of patients after an initial event . The increased relative risk for death after an initial event ( Table 1 ) was drawn from population -based studies in the United Kingdom ( 12 , 16 ) and applied to the general mortality rates from the U.S. life tables to generate the estimated postevent mortality rates . We modified these event rates by assuming that all patients received optimal secondary prevention . Adverse Effects The excess risks for gastrointestinal bleeding with aspirin use and for myopathy with statin use were drawn from systematic review s of r and omized trials and a recent secondary data analysis ( 2 , 26 , 27 ) . Risks for gastrointestinal bleeding and myopathy in untreated patients were assumed to be zero so that only treatment-induced adverse events were counted . Because better data were not available , we estimated the risks for death from aspirin-related gastrointestinal bleeding and statin-induced myopathy and varied them in sensitivity analysis . Patients who had nonfatal adverse effects were not given therapy with alternate agents for primary prevention of CHD . Modeling Stroke Because many r and omized trials of aspirin prophylaxis did not distinguish by stroke type , we had difficulty estimating the precise effect of aspirin on ischemic and hemorrhagic strokes ( 30 ) . To account for this limitation , we used 2 approaches to model the effect of aspirin on stroke . In the base-case analysis , we followed the approach that was used in a recent meta- analysis ( 9 ) by including hemorrhagic stroke and ischemic stroke together in 1 estimate of the effect of aspirin on total stroke ( relative risk for stroke with aspirin , 1.06 ) . In an alternate scenario , we modeled hemorrhagic stroke and ischemic stroke as separate health states . We assumed that aspirin was associated with an excess annual risk of 20 hemorrhagic strokes per 100000 users on the basis of published meta-analyses and that one third of these hemorrhagic strokes would be fatal ( 19 , 30 , 33 ) . We conservatively assumed that aspirin had no effect on ischemic stroke ( 30 ) . The costs and utilities of ischemic stroke and hemorrhagic stroke were also considered separately . Treatment Efficacy We used summary relative risk estimates from existing meta-analyses or relative risks from individual trials to estimate the efficacy of aspirin and statin therapy , either alone or in combination , for preventing CHD events ( 3 , 24 , 29 ) . Where data were limited , we made conservative assumptions . The efficacy of the combined use of aspirin and statins was assumed to be independent on the basis of data from secondary prevention trials ( 5 ) . We did not model the effect of aspirin or statins on initial use of revascularization procedures in the absence of a cardiovascular event . All patients who survived an initial cardiovascular event were assumed to have received secondary preventive therapy with aspirin and a statin or with an alternate agent if  they could not tolerate  aspirin  or  statins . The effect of treatments on all-cause mortality was estimated from meta-analyses of secondary prevention trials ( 18 - 20 ) . Costs We conducted our analysis from the perspective of a third-party payer . State costs ( Table 1 ) , which were derived from data from the published literature and several recent national data bases , are expressed in 2003 dollars . To estimate the costs during the year in which an event occurred , we estimated acute care costs by drawing on data regarding hospital charges from the Healthcare Utilization Project data base and by converting these values to costs . To convert hospital charges to costs , we used the 1999 cost-to-charge ratio value of 0.4501 , which was derived from the Medicare Provider Analysis and Review of short-stay hospitals ( 28 ) . We then used the Medical Consumer Price Index to generate an inflation factor of 1.195 , which was applied to the 1999 cost figure to convert 1999 dollars to 2003 dollars ( 17 ) . In addition to the acute care costs , we assumed that each patient who survived an acute event would also incur one half of the estimated ongoing annual costs of care for the first year . Costs for subsequent years were based on ongoing costs of care that were drawn from the medical literature ( 22 - 25 ) . Drug costs were obtained from the 2003 Red Book average wholesale prices ( 21 ) . For our base-case analysis , we set the annual  statin cost to $ 730 by averaging the Red Book prices of simvastatin ( $ 922 for 10 mg/d ) and lovastatin ( $ 503 for 10 mg/d ) . The base-case cost of aspirin was based on an annual cost of $ 16 for Bayer aspirin ( Bayer Healthcare LLC , Morristown , New Jersey ) . The annual cost of generic aspirin  was estimated at approximately $ 6 ( 21 ) . We varied the costs of each drug over wide ranges in sensitivity analysis . To check our cost estimates , we compared our derived values with other cost estimates OBJECTIVE To investigate if a six-year intensive lifestyle intervention in people with pre-diabetes lead to reduction of cardiovascular events and cardiovascular disease ( CVD ) mortality in subsequent 23 years . METHODS Five hundreds and nineteen subjects with normal glucose tolerance ( NGT ) and 577 subjects with impaired glucose tolerance ( IGT ) in Da Qing city were recruited in the study in 1986 . The IGT subjects r and omly assigned to either the no-intervention group or one of three lifestyle intervention groups ( diet , exercise , or diet plus exercise ) to receive a 6-year lifestyle intervention . In 2009 , the participants were followed up to assess the primary outcomes of cardiovascular events and CVD mortality by a question naire and medical records . RESULTS Subjects in IGT no-intervention group had the highest incidences of cardiovascular events ( 44.44 % ) and CVD mortality ( 20.00 % ) , while those in NGT group had the lowest incidences of cardiovascular events ( 29.59 % ) and CVD mortality ( 7.52 % ) after 23-year follow-up . The incidences of cardiovascular events and CVD mortality in IGT intervention subjects were 37.84 % and 12.53 % , respectively . The multivariable analyses showed that , after controlling of age , gender , BMI smoking , blood pressure and cardiovascular event at baseline , the CVD mortality and incidence of cardiovascular events in IGT no-intervention group was 1.89 ( HR = 1.89 , 95%CI 1.11 - 3.22 , P = 0.02 ) and 1.38 ( HR = 1.38 , 95%CI 1.01 - 1.90 , P = 0.04 ) times of those in NGT group . However , the CVD mortality and incidence of cardiovascular events were not different in the IGT intervention group compared with those in the NGT group ( HR = 1.39 , 95%CI 0.89 - 2.18 , P = 0.15 and HR = 1.25 , 95%CI 0.98 - 1.59 , P = 0.07 , respectively ) . CONCLUSIONS Subjects with IGT were at high risk for cardiovascular events and mortality . A six-year lifestyle intervention in this population can reduce both the incidence of cardiovascular event and CVD mortality OBJECTIVES This study was design ed to examine the hypothesis that higher intake of dietary fiber is inversely related to the  risk of cardiovascular disease ( CVD ) and myocardial infa rct ion ( MI ) in a large prospect i ve cohort of women . BACKGROUND Although dietary fiber has been suggested to reduce the risk of coronary disease , few prospect i ve studies have examined the association between the types and amounts of dietary fiber and CVD risk , particularly among women . METHODS In 1993 , we used a semi-quantitative food frequency question naire to assess dietary fiber intake among 39,876 female health professionals with no previous history of CVD or cancer . Women were subsequently followed for an average of six years for incidence of nonfatal MI , stroke , percutaneous transluminal coronary angioplasty , coronary artery bypass graft or death due to CVD confirmed by medical records or death certificates . RESULTS During 230,006 person-years of follow-up , 570 incident cases of CVD were documented , including 177 MIs . After adjustment for age and r and omized treatment status , a significant inverse association was observed between dietary fiber intake and CVD risk . Comparing the highest quintile of fiber intake ( median : 26.3 g/day ) with the lowest quintile ( median : 12.5 g/day ) , the relative risks ( RR ) were 0.65 ( 95 % confidence interval [ CI ] : 0.51 , 0.84 ) for total CVD and 0.46 ( 95 % CI : 0.30 , 0.72 ) for MI . Additional adjustment for CVD risk factors reduced the RRs to 0.79 ( 95 % CI : 0.58 , 1.09 ) for total CVD and 0.68 ( 95 % CI : 0.36 , 1.22 ) for MI . The inverse trends across categories generally remained , although they were no longer statistically significant . Inverse relations were observed between both soluble and insoluble fiber and risk of CVD and MI , and among those who had never smoked and those with body mass index < 25 . CONCLUSIONS A higher intake of  dietary fiber was associated with a lower risk of CVD and MI , although the association was not statistically significant after further adjusting for multiple confounding factors . Nevertheless , these prospect i ve data generally support current dietary recommendations to increase the consumption of fiber-rich whole grains and fruits and vegetables as a primary preventive measure against CVD CONTEXT Recent r and omized trials among patients with preexisting cardiovascular disease ( CVD ) have failed to support benefits of B-vitamin supplementation on cardiovascular risk . Observational data suggest benefits may be greater among women , yet women have been underrepresented in published r and omized trials . OBJECTIVE To test whether a combination of folic acid , vitamin B6 , and vitamin B12 lowers risk of CVD among high-risk women with and without CVD . DESIGN , SETTING , AND PARTICIPANTS Within an ongoing r and omized trial of antioxidant vitamins , 5442 women who were US health professionals aged 42 years or older , with either a history of CVD or 3 or more coronary risk factors , were enrolled in a r and omized , double-blind , placebo-controlled trial to receive a combination pill containing folic acid , vitamin B6 , and vitamin B12 or a matching placebo , and were treated for 7.3 years from April 1998 through July 2005 . INTERVENTION Daily intake of a combination pill of 2.5 mg of folic acid , 50 mg of vitamin B6 , and 1 mg of vitamin B12 . MAIN OUTCOME MEASURES A composite outcome of myocardial infa rct ion , stroke , coronary revascularization , or CVD mortality . RESULTS Compared with placebo , a total of 796 women experienced a confirmed CVD event ( 406 in the active group and 390 in the placebo group ) . Patients receiving active vitamin treatment had similar risk for the composite CVD primary end point ( 226.9/10,000 person-years vs 219.2/10,000 person-years for the active vs placebo group ; relative risk [ RR ] , 1.03 ; 95 % confidence interval [ CI ] , 0.90 - 1.19 ; P = .65 ) , as well as for the secondary outcomes including myocardial infa rct ion ( 34.5/10,000 person-years vs 39.5/10,000 person-years ; RR , 0.87 ; 95 % CI , 0.63 - 1.22 ; P = .42 ) , stroke ( 41.9/10,000 person-years vs 36.8/10,000 person-years ; RR , 1.14 ; 95 % CI , 0.82 - 1.57 ; P = .44 ) , and CVD mortality ( 50.3/10,000 person-years vs 49.6/10,000 person-years ; RR , 1.01 ; 95 % CI , 0.76 - 1.35 ; P = .93 ) . In a blood sub study , geometric mean plasma homocysteine level was decreased by 18.5 % ( 95 % CI , 12.5%-24.1 % ; P < .001 ) in the active group ( n = 150 ) over that observed in the placebo group ( n = 150 ) , for a difference of 2.27 micromol/L ( 95 % CI , 1.54 - 2.96 micromol/L ) . CONCLUSION After 7.3 years of treatment and follow-up , a combination pill of folic acid , vitamin B6 , and vitamin B12 did not reduce a combined end point of total cardiovascular events among high-risk women , despite significant homocysteine lowering . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000541 Substantial progress has been made in the awareness , treatment , and prevention of  cardiovascular disease ( CVD ) in women since the first women-specific clinical recommendations for the prevention of CVD were published by the American Heart Association ( AHA ) in 1999.1 The myth that heart disease is a “ man 's disease ” has been debunked ; the rate of public awareness of CVD as the leading cause of death among US women has increased from 30 % in 1997 to 54 % in 2009.2 The age-adjusted death rate result ing from  coronary heart disease ( CHD ) in females , which accounts for about half of all CVD deaths in women , was 95.7 per 100 000 females in 2007 , a third of what it was in 1980.3,4 Approximately 50 % of this decline in CHD deaths has been attributed to reducing major risk factors and the other half to treatment of CHD including secondary preventive therapies.4 Major r and omized controlled clinical trials such as the Women 's Health Initiative have changed the practice of CVD prevention in women over the past decade.5 The investment in combating this major public health issue for women has been significant , as have the scientific and medical achievements . Despite the gains that have been made , considerable challenges remain . In 2007 , CVD still caused ≈1 death per minute among women in the United States.6 These represent 421 918 deaths , more women 's lives than were cl aim ed by cancer , chronic lower respiratory disease , Alzheimer disease , and accidents combined.6 Reversing a trend of the past 4 decades , CHD death rates in US women 35 to 54 years of age now actually appear to be increasing , likely because of the effects of the obesity epidemic.4 CVD rates in the United States are significantly higher for black females compared with their white counterparts ( 286.1/100 000 versus BACKGROUND Emerging evidence suggests a possible role of lycopene in the primary prevention of cardiovascular disease ( CVD ) . OBJECTIVE We examined whether plasma lycopene concentrations in the Physicians ' Health Study were associated with CVD in a prospect i ve , nested , case-control design . DESIGN Baseline blood sample s were collected starting in 1996 . During a mean follow-up of 2.1 y , we identified 499 cases of CVD ( confirmed myocardial infa rct ion , stroke , CVD death , or revascularization procedures ) and an equal number of men free of CVD and matched for age ( x : 69.7 y ) , follow-up time , and smoking status . We collected self-reported coronary disease risk factors and measured plasma carotenoids , retinol , lipids , and C-reactive protein . RESULTS In matched analyses with additional adjustment for plasma total cholesterol and r and omized treatment , the relative risks ( RRs ) of CVD for men in the lowest to highest quartiles of plasma lycopene were 1.00 ( reference ) , 0.92 , 1.04 , and 0.95 ( P for linear trend = 0.93 ) . With multivariate adjustment , the RRs of total CVD were 1.00 ( reference ) , 1.08 , 0.94 , and 1.03 ( P for linear trend = 0.98 ) . For important vascular events ( 241 cases ) , excluding revascularization procedures , the multivariate RRs remained nonsignificant ( P for linear trend = 0.50 ) . Adding plasma carotenoids , lipids , or C-reactive protein to multivariate models had a minimal effect on the RRs of total CVD for plasma lycopene . Compared with lycopene , higher concentrations of plasma lutein/zeaxanthin and retinol suggested a moderate increase in CVD risk , whereas no association was found for beta-cryptoxanthin , alpha-carotene , and beta-carotene . CONCLUSIONS Higher plasma lycopene concentrations were not associated with the risk of CVD in this study of older men . Further evaluation in diverse population s is necessary OBJECTIVE —Cardiovascular disease ( CVD ) mortality has decreased in men but not in women with diabetes . We investigated whether sex differences in control and treatment of CVD risk factors might underlie this disparity . RESEARCH DESIGN AND METHODS —We performed cross-sectional analyses from a cohort of patients with diabetes sample d from 10 U.S. managed care health plans . Study end points included not being in control for CVD risk factors ( ≥140 mmHg for systolic blood pressure [ SBP ] , ≥3.35 mmol/l for LDL cholesterol , and ≥8.0 % for A1C ) and the intensity of medication management ( number of medication classes ) for patients not in control . Logistic regression models with r and om intercepts were used to adjust probabilities of control and management for demographics , clinical characteristics , and clustering within health plans . RESULTS —There were 1,315 women and 1,575 men with a history of CVD and 3,415 women and 2,516 men without a history of CVD . Among patients with CVD , adjusted estimated probabilities for not being in control and risk differences varied significantly between men and women for SBP ( men 41.2 % , women 46.6 % ; risk difference −5.4 % [ 95 % CI −9.5 to −1.3 ] ) and LDL cholesterol ( men 22.4 % , women 28.3 % ; risk difference −5.9 % [ −9.9 to −1.8 ] ) . There were no significant sex differences in intensity of medication management for patients not in control . In patients without CVD there were no significant differences in control or intensity of medication management . CONCLUSIONS —In diabetic patients with CVD , poorer control of SBP and LDL cholesterol for women may contribute to the sex disparity in CVD mortality trends The Action to Control Cardiovascular Disease in Diabetes ( ACCORD ) blood pressure trial is an unmasked , open-label , r and omized trial with a sample size of 4,733 participants . This report describes the rationale , design , and methods of the blood pressure interventions in ACCORD . Participants eligible for the blood pressure trial are r and omized to 1 of 2 groups with different treatment goals : systolic blood pressure < 120 mm Hg for the more intensive goal and systolic blood pressure < 140 mm Hg for the less intensive goal .  The primary outcome measure for the trial is the first occurrence of a major cardiovascular disease ( CVD ) event , specifically nonfatal myocardial infa rct ion or stroke , or cardiovascular death during a follow-up period ranging from 4 - 8 years . The ACCORD blood pressure trial should provide the first definitive clinical trial data on the possible benefit of treating to a more aggressive systolic blood pressure goal in reducing CVD events in patients with diabetes mellitus Coronary heart disease , hypertension , and dyslipidemia are highly prevalent and commonly coexist in people who are middle-aged and older . Previous data suggested that lowering cholesterol concentrations in individuals at high risk of cardiovascular disease improved clinical outcomes . Xuezhikang , a partial extract of red yeast rice containing statin , has a marked impact on lipids . The purpose of this study , therefore , was to evaluate the impact of Xuezhikang on reducing cardiovascular events and mortality in elderly Chinese hypertensive patients with a history of myocardial infa rct ion ( MI ) enrolled in the Chinese Coronary Secondary Prevention Study . In this r and omized trial , 1530 elderly hypertensive patients ( > or = 65-years-old ) with previous MI were assigned either to placebo ( n = 758 ) or to Xuezhikang ( n = 772 ) daily for an average of 4.5 years . The primary endpoint was recurrent coronary events ; the secondary endpoint was all-cause mortality and other clinical events , including adverse effects . There were 68 cases of coronary events ( 8.8 % ) detected in the Xuezhikang group and 108 cases ( 14.3 % ) in the placebo group ( 38.2 % risk reduction by Xuezhikang therapy ) . Death from coronary heart disease ( CHD ) totaled 49 cases in the Xuezhikang group ( 6.4 % ) and 68 cases in the placebo group ( 9.0 % ) , indicating that Xuezhikang significantly decreased the risk of CHD death by 29.2 % . Our study demonstrated that Xuezhikang therapy could effectively and safely reduce cardiovascular events and all-cause death in Chinese elderly hypertensive patients with previous MI . This finding may have an important implication for the treatment of elderly hypertensive patients with CHD Despite continued appreciation of the potential role of vitamin D and omega-3 fatty acids in the prevention of cancer and cardiovascular disease ( CVD ) , there remain no completed large-scale , r and omized trials of these agents for the primary prevention of cancer or CVD in a population that has not been selected on the basis of elevated risk . The VITamin D and OmegA-3 TriaL ( VITAL ) is a 2 × 2 factorial r and omized , double-blind , placebo-controlled trial of the benefits and risks of vitamin D ( vitamin D3 [ cholecalciferol ] , 2000 IU/d ) and marine omega-3 fatty acids ( Omacor ( ® ) fish oil , a 1 g/d ) in the primary prevention of cancer and CVD among 25,875 men and women , aged ≥50 and ≥55 years , respectively . R and omization began in November 2011 and was completed in March 2014 . This report will describe the rationale for the trial and currently available r and omized trial data , summarize related ongoing large-scale trials , and provide a brief overview of study design , and an up date on r and omization milestones , racial/ethnic diversity , biorepository activities , in-depth phenotyping of a subcohort , and ancillary studies OBJECTIVE To improve the treatment of risk factors of cardiovascular disease ( CVD ) for older patients with diabetes after a cardiac event by using a low-literacy reminder card describing these risk factors in community setting s. STUDY DESIGN A multicenter , r and omized , interventional study . METHODS Patients aged 55 years or older with diabetes hospitalized with an acute myocardial infa rct ion , congestive heart failure exacerbation , or unstable angina were eligible to enter the study . Control and experimental patients were recruited from 4 sites and were enrolled in the study before discharge from the hospital . Experimental subjects received education and a reminder card describing risk factors of CVD . They were instructed to discuss the risk factors described on the reminder card with their primary care physician on their first appointment after discharge . Control subjects did not receive any intervention but were given consent to be able to review their charts . RESULTS One hundred sixty patients completed the study , 82 in the control group and 78 in the experimental group . At the end of the study there was no difference in blood pressure control , lipid levels , and glycosylated hemoglobin levels between the control and experimental patients . Aspirin use and ACE inhibitor use were found to be significantly higher in the control group ( P = .001 and .03 , respectively ) . CONCLUSIONS Reminder cards given to patients to discuss with their primary care providers in community setting s did not improve process measures of CVD risk in patients with documented CVD and diabetes . Other approaches will be needed to improve the treatment of risk factors in these high-risk patients Diets rich in fruits and vegetables have been of interest because of their potential health benefits against chronic diseases such as cardiovascular disease ( CVD ) and cancer . The aim of this work was to assess the association of the dietary intake of a food group that includes fruits , berries and vegetables with all-cause , CVD-related and non-CVD-related mortality .  The subjects were Finnish men aged 42 - 60 y examined in 1984 - 1989 in the prospect i ve Kuopio Ischaemic Heart Disease Risk Factor ( KIHD ) Study .  Dietary intakes were assessed by 4-d food intake record during the baseline phase of the KIHD Study . The risk of all-cause and non-CVD-related deaths was studied in 2641 men and the risk of CVD-related death in 1950 men who had no history of CVD at baseline . During a mean follow-up time of 12.8 y , cardiovascular as well as noncardiovascular and all-cause mortality were lower among men with the highest consumption of fruits , berries and vegetables . After adjustment for the major CVD risk factors , the relative risk for men in the highest fifth of fruit , berry and vegetable intake for all-cause death , CVD-related and non-CVD-related death was 0.66 [ 95 % confidence interval ( CI ) 0.50 - 0.88 ] , 0.59 ( 0.33 - 1.06 ) , and 0.68 ( 0.46 - 1.00 ) , respectively , compared with men in the lowest fifth . These data show that a high fruit , berry and vegetable intake is associated with reduced risk of mortality in middle-aged Finnish men . Consequently , the findings of this work indicate that diets that are rich in plant-derived foods can promote longevity BACKGROUND The beneficial effects of statins on cardiovascular mortality in secondary prevention have been established in several long-term , placebo-controlled trials . However , the value of statin therapy in reduction of overall mortality in patients without coronary heart disease ( CHD ) is question able . This study evaluated the effect of statin therapy in subjects with no indication of cardiovascular disease ( primary prevention ) and patients with known CHD ( secondary prevention ) . METHODS This retrospective cohort study included 229 918 adult enrollees in a health maintenance organization in Israel who initiated statin treatment from 1998 through 2006 ( mean age , 57.6 years ; 50.8 % female ) .  Proportion of days covered ( PDC ) with  statins  was measured by the number of dispensed  statin prescriptions during the interval between the date of the first statin prescription and the end of follow-up . RESULTS During a mean of 4.0 and 5.0 years of follow-up , there were 4259 and 8906 deaths among the primary prevention and secondary prevention cohorts , respectively . In both cohorts , continuity of treatment with statins ( PDC , > or = 90 % ) conferred at least a 45 % reduction in risk of death compared with patients with a PDC of less than 10 % . A stronger risk reduction was calculated among patients with high baseline low-density lipoprotein cholesterol level and patients initially treated with high-efficacy statins . CONCLUSIONS Better continuity of statin treatment provided an ongoing reduction in mortality among patients with and without a known history of CHD . The observed benefits from statins were greater than expected from r and omized clinical trials Aims /hypothesisThere is continuing debate about the net benefits of population screening for type 2 diabetes . We compared the risk of cardiovascular disease ( CVD ) and mortality among incident cases of type 2 diabetes in a  screened group with those in an unscreened group . Methods In this register-based non-r and omised controlled trial , eligible individuals were all men and women aged 40–69 years without known diabetes , registered with a general practice in Denmark ( n = 1,912,392 ) . Between 2001 and 2006 , 153,107 individuals registered with 181 practice s participating in the Anglo – Danish – Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)-Denmark study were sent a diabetes-risk-score question naire . Individuals at moderate-to-high risk were invited to visit their family doctor for assessment of diabetes status and cardiovascular risk ( screening group ) . The 1,759,285 individuals registered with all other practice s in Denmark constituted the retrospectively constructed no-screening ( control ) group . In this post hoc analysis , we identified individuals from the  screening and no-screening groups who were diagnosed with diabetes between 2001 and 2009 ( n = 139,075 ) , and compared risk of CVD and mortality in these groups between 2001 and 2012 . Results In the screening group , 27,177/153,107 ( 18 % ) individuals attended for screening , of whom 1533 were diagnosed with diabetes . Between 2001 and 2009 , 13,992 people were newly diagnosed with diabetes in the screening group ( including those diagnosed by screening ) and 125,083 in the no-screening group . Between 2001 and 2012 , the risks of CVD and mortality were lower among individuals with diabetes in the screening group compared with individuals with diabetes in the no-screening ( control ) group ( CVD HR 0.84 , 95 % CI 0.80 , 0.89 ; mortality HR 0.79 , 95 % CI 0.74 , 0.84 ) . Conclusions /interpretationA single round of diabetes screening and cardiovascular risk assessment in middle-aged Danish adults in general practice was associated with a significant reduction in risk of all-cause mortality and CVD events in those diagnosed with diabetes Objective Although depression is a risk and prognostic factor for cardiovascular disease ( CVD ) , depression trials involving cardiac patients have not observed the anticipated cardiovascular benefits . To test our hypothesis that depression treatment delivered before clinical CVD onset reduces risk of CVD events , we conducted an 8-year follow-up study of the Indiana sites of the Improving Mood-Promoting Access to Collaborative Treatment ( IMPACT ) r and omized controlled trial . Methods Participants were 235 primary care patients 60 years or older with major depression or dysthymia who were r and omized to a 12-month collaborative care program involving antidepressants and psychotherapy ( 85 without and 35 with baseline CVD ) or usual care ( 83 without and 32 with baseline CVD ) . Hard CVD events ( fatal/nonfatal ) were identified using electronic medical record and Medicare/Medicaid data . Results A total of 119 patients ( 51 % ) had a hard CVD event . As hypothesized , the treatment × baseline CVD interaction was significant ( p = .021 ) . IMPACT patients without baseline CVD had a 48 % lower risk of an event than did usual care patients ( 28 % versus 47 % , hazard ratio = 0.52 , 95 % confidence interval = 0.31–0.86 ) . The number needed to treat to prevent one event for 5 years was 6.1 . The likelihood of an event did not differ between IMPACT and usual care patients with baseline CVD ( 86 % versus 81 % , hazard ratio = 1.19 , 95 % confidence interval , 0.70–2.03 ) . Conclusions Collaborative depression care delivered before CVD onset halved the excess risk of hard CVD events among older , depressed patients . Our findings raise the possibility that the IMPACT intervention could be used as a CVD primary prevention strategy . Trial Registration : clinical trials.gov Identifier : NCT01561105 BACKGROUND Primary prevention of cardiovascular disease (CVD),by identifying individuals at risk is a well-established , but costly strategy when based on measurements that depend on laboratory analyses . A non-laboratory , paper-based CVD risk assessment chart tool has previously been developed to make screening more affordable in developing countries . Task shifting to community health workers ( CHWs ) is being investigated to further scale CVD risk screening . This study aim ed to develop a mobile phone CVD risk assessment application and to evaluate its impact on CHW training and the duration of screening for CVD in the community by CHWs . METHODS A feature phone application was developed using the open source online platform , CommCare ( © ) . CHWs ( n=24 ) were trained to use both paper-based and mobile phone CVD risk assessment tools . They were r and omly allocated to using one of the risk tools to screen 10 - 20 community members and then crossed over to screen the same number , using the alternate risk tool . The impact on CHW training time , screening time and margin of error in calculating risk scores was recorded . A focus group discussion evaluated experiences of CHWs using the two tools . RESULTS The training time was 12.3h for the paper-based chart tool and 3h for the mobile phone application . 537 people were screened . The mean screening time was 36 min ( SD=12.6 ) using the paper-base chart tool and 21 min ( SD=8.71 ) using the mobile phone application , p=<0.0001 . Incorrect calculations ( 4.3 % of average systolic BP measurements , 10.4 % of BMI and 3.8 % of CVD risk score ) were found when using the paper-based chart tool while all the mobile phone calculations were correct . Qualitative findings from the focus group discussion corresponded with the findings of the pilot study . CONCLUSION The reduction in CHW training time , CVD risk screening time , lack of errors in calculation of a CVD risk score and end user satisfaction when using a mobile phone application , has implication s in terms of adoption and sustainability of this primary prevention strategy to identify people with high CVD risk who can be referred for appropriate diagnoses and treatment Recent studies have reported no association between elevated glycated hemoglobin ( HbA(1c ) ) and incident cardiovascular disease ( CVD ) among women without diabetes . This study describes associations between HbA(1c ) and new onset  CVD  in a representative adult population cohort . Assessment of participants in The North West Adelaide Health Study ( NWAHS ) , a population study of r and omly selected adults ( age > or = 18 years , n = 4,060 ) , included measurement of height , weight , blood pressure , fasting lipids , glucose , and HbA(1c ) . A self-completed question naire assessed doctor-diagnosed diabetes , CVD and stroke , smoking status , and demographics . The cohort was followed for an average 3.5 years . Of the 2,913 adults free of diabetes at baseline and follow-up , 94 ( 3.5 % ) reported new onset coronary heart disease ( CHD ) and /or stroke . Compared with those with an HbA(1c ) < or = 5.0 % , risk of new onset CVD was increased in those with HbA(1c ) 5.4 - 5.6 % ( odds ratio ( OR ) 2.5 , 95 % confidence interval ( CI ) 1.4 , 4.6 ) , and > or = 5.7 % ( OR 1.9 , 95 % CI 1.1 , 3.4 ) , after adjustment for other risk factors . The association was stronger in women than men ( P = 0.03 ) , and attenuated to only a small degree by addition of impaired fasting glucose ( IFG ) , hypertension , hypercholesterolemia , BMI , waist circumference , or smoking to the model . Elevated HbA(1c ) is related to new onset CVD over a relatively short follow-up period in both men and women without diabetes and who do not develop diabetes , after adjustment for other major risk factors . Unlike previous studies , this relationship was not substantially attenuated by other traditional risk factors BACKGROUND Cardiovascular diseases ( CVD ) are the major cause of premature death in the world . This study was design ed to examine the physicians ' knowledge and perception of CVD risk factors and perceived implementation of CVD prevention guidelines as well as barriers to their implementation . METHODS A question naire survey by face-to-face interviews was performed among 1382 r and omly selected physicians ( general practitioners/family medicine specialists , internists and cardiologists ) from different regions of Croatia . RESULTS Most physicians believe that guidelines are useful but only 56.9 % are really using some guidelines . 40.2 % favour Joint European guidelines . More primary care physicians use their own personal experience in prevention while internists and cardiologists tend more to use the guidelines . 80.6 % believe that they treat their patients with dyslipidemia well but only 53.3 % knew the LDL-cholesterol goal value for high-risk patients and only 56.2 % knew which HDL-cholesterol level is the marker of increased risk . Hypertension was perceived as the most important risk factor , particularly by primary care physicians , while cardiologists tend to favour diabetes . Although most physicians considered the lack of financial re sources as the main barrier in CVD prevention , at the same time most of them believe that it could primarily be improved by better patient education . CONCLUSIONS Although most physicians support the guidelines use , only half of them use them and in average their knowledge of guidelines is not satisfactory . This is , together with the lack of time and finances and perceived lack of patients ' awareness , probably one of the main causes why they do not manage risk factors better Context Impaired fasting glucose levels increase the risk for cardiovascular events , but the effect on recurrent cardiovascular events among people with known coronary heart disease ( CHD ) is unknown . Contribution This study followed 2763 postmenopausal women with known CHD for 6.8 years and found no association between fasting glucose levels of 5.6 to 6.9 mmol/L ( 100 to 125 mg/dL ) ( the 2003 definition of impaired fasting glucose ) and new cardiovascular events . Women with fasting glucose levels of 6.1 to 6.9 mmol/L ( 110 to 125 mg/dL ) ( the 1997 definition of impaired fasting glucose ) were at increased risk for new CHD events but not for congestive heart failure hospitalization , stroke , or transient ischemic attack . Implication s Impaired fasting glucose is not a powerful risk factor for cardiovascular disease events among women who have already had a CHD event . The Editors An estimated 18 million U.S. adults have diabetes ( 1 ) , and another 44 million have impaired fasting glucose , defined as a fasting glucose level between 5.6 mmol/L ( 100 mg/dL ) and 6.9 mmol/L ( 125 mg/dL ) ( 2 ) . Diabetes is associated with increased risk for cardiovascular disease ( CVD ) in both men and women in most racial or ethnic groups and in almost every population studied ( 3 , 4 ) . Current national guidelines recommend that diabetes be considered a coronary heart disease ( CHD ) equivalent ( 5 ) . Individuals with impaired fasting glucose have increased risk for future diabetes , and impaired fasting glucose is associated with other cardiovascular risk factors ( 6 , 7 ) . Moreover , individuals with impaired fasting glucose may also have increased risk for CVD ( 8 - 11 ) . If impaired fasting glucose is associated with increased risk for CHD , then initiation of preventive interventions could be considered for this group of patients . This issue is complicated by the fact that the definition of impaired fasting glucose has recently changed . In 2003 , the American Diabetes Association Expert Committee recommended that the glucose level for impaired fasting glucose be lowered from 6.1 mmol/L ( 110 mg/dL ) to 5.6 mmol/L ( 100 mg/dL ) ( 12 ) . This decision was prompted partly by population -based studies showing that a cut-point of 5.6 mmol/L would increase the sensitivity of predicting future diabetes . No studies to date have examined the association between impaired fasting glucose according to this exp and ed definition and risk for future cardiovascular events . We examined data from 2763 postmenopausal women enrolled in the Heart and Estrogen/progestin Replacement Study ( HERS ) who were followed for an average of 6.8 years . We aim ed to determine whether women with known coronary artery disease and impaired fasting glucose at baseline had an increased risk for a new CHD event , cerebrovascular event , hospitalization for congestive heart failure ( CHF ) , or any cardiovascular event and to compare the magnitude of this increase with that observed in women with diabetes . We also evaluated the effect of lowering the cut-point for defining impaired fasting glucose on the association with cardiovascular outcomes . Methods Study Setting , Patients , and Design The design , methods , baseline characteristics ( 13 ) , and main findings of the trial ( 14 ) and the cohort follow-up ( 15 ) have been published . Briefly , HERS was a r and omized , blinded , controlled trial that evaluated daily hormone therapy for preventing coronary events in postmenopausal women with established CHD . Participants were r and omly assigned to 0.625 mg of conjugated estrogens daily plus 2.5 mg of medroxyprogesterone acetate or placebo and were followed for a mean of 4.1 years . The trial enrolled 2763 women at 20 clinical centers in the United States between January 1993 and September 1994 . The combined primary outcome of nonfatal myocardial infa rct ion ( MI ) and CHD death did not significantly differ between women assigned to hormone therapy and those assigned to placebo ( 14 ) . After completion of the trial , women enrolled in HERS were invited to enroll in a prospect i ve cohort study for an additional 2.7 years . Of the 2510 women alive at the end of HERS , 2321 ( 92.4 % ) enrolled in HERS II . Contact information was available for more than 99 % of the women in HERS II at the end of that trial ( 15 ) . After 6.8 years of follow-up , hormone therapy did not reduce the risk for cardiovascular events in women with established CHD ( 15 ) . For this analysis , we classified women as having diabetes if they reported a physician diagnosis of diabetes , were taking diabetes medication , or had a  fasting serum glucose level  of 7.0 mmol/L or more ( 126 mg/dL ) . We up date d the diabetes category with incident cases of diabetes if the participant self-reported new diabetes or a complication directly related to diabetes , initiated therapy with a hypoglycemic medication at any point during follow-up , or had a fasting glucose level of 7.0 mmol/L or more ( 126 mg/dL ) at the first annual visit or trial closeout visit . We classified impaired fasting glucose by using either the 1997 definition ( fasting glucose level , 6.1 to 6.9 mmol/L [ 110 to 125 mg/dL ] ) or the 2003 definition ( fasting glucose level , 5.6 to 6.9 mmol/L [ 100 to 125 mg/dL ] ) at baseline and up date d it at the first annual visit and the trial closeout visit . Data Collection At baseline , participants completed a question naire that asked about their age , race or ethnicity , education , chronic medical illnesses , and previous percutaneous transluminal coronary angioplasty or coronary artery bypass grafting . We also assessed history of MI , percutaneous transluminal coronary angioplasty , or coronary artery bypass grafting by review ing medical records at the end of the study period . At baseline , participants reported smoking habits ( current , former , or never ) , alcohol consumption ( drinks per week ) , regular exercise or walking activity , and overall general health . At baseline and at each annual visit , we performed a cardiac examination and assessed the following physical examination variables : body weight , height , waist and hip circumference , and systolic and diastolic blood pressure . We calculated body mass index  ( BMI ) and performed st and ard 12-lead electrocardiography at baseline and at each annual visit . At the baseline , first annual , and end-of-trial visits , participants had fasting blood tests for measurement of total cholesterol , high-density lipoprotein ( HDL ) cholesterol , triglyceride , and lipoprotein(a ) levels  by the Lipoprotein Analytical Laboratory at Johns Hopkins Hospital , Baltimore , Maryl and .  Fasting serum glucose levels  were measured at these 3 clinical visits by SmithKline Beecham Clinical Laboratory , Van Nuys , California , using the hexokinase enzymatic method . Outcome Ascertainment The primary outcome of HERS was any new CHD event , defined as a fatal or nonfatal MI , sudden CHD death , or other CHD death . We based the diagnosis of nonfatal MI on an algorithm that included ischemic symptoms , electrocardiogram abnormalities , and elevated cardiac enzyme levels ( 13 ) . Independent physicians adjudicated CHD death if the participant had a fatal documented MI , sudden death within 1 hour of symptom onset , unobserved out-of-hospital death without another known cause , or death due to CHF or coronary revascularization procedure . The secondary cardiovascular outcomes we examined included stroke and transient ischemic attack ( TIA ) , hospitalizations for CHF , and any CVD event ( an aggregate of all cardiovascular outcomes examined in our analysis ) . Statistical Analysis We assessed the effects of glucose status on various study end points by using multivariable Cox proportional hazards models . We adjusted our models for potential confounders that we determined a priori : age , race or ethnicity , education , current smoking , physical activity , alcoholic drinks per week , BMI , self-reported health ( poor/fair vs. good/very good/excellent ) , previous percutaneous transluminal coronary angioplasty , previous  coronary artery bypass grafting  , signs of CHF on physical examination , more than 1 previous MI , statin use , diuretic use , angiotensin-converting enzyme inhibitor use , and hormone therapy assignment . We also stratified our models by clinical center . We up date d information on glucose status , current smoking , exercise , alcoholic drinks per week , BMI , overall health status , statin use , diuretic use , and angiotensin-converting enzyme inhibitor use by using time-dependent covariates , and we modeled the effect of hormone therapy assignment by year . In supplementary analyses , we further adjusted for variables that may be in the causal pathway between hyperglycemia and cardiovascular outcomes , such as waist circumference , HDL cholesterol level , triglyceride level , systolic blood pressure , and lipoprotein(a ) level , all as time-dependent covariates . We qualitatively compared the difference in cardiovascular outcomes for the impaired fasting glucose group by using the 1997 definition ( fasting glucose level , 6.1 to 6.9 mmol/L [ 110 to 125 mg/dL ] [ 16 ] ) and the 2003 definition ( fasting glucose level , 5.6 to 6.9 mmol/L [ 100 to 125 mg/dL ] [ 12 ] ) . We also evaluated the effect of a baseline fasting glucose level of 5.6 to 6.0 mmol/L ( 100 to 109 mg/dL ) on each cardiovascular outcome , adjusting for the potential confounders listed . We also obtained an approximate test of the equivalence of the 1997 and 2003 definitions of impaired fasting glucose by comparing the Cox model coefficients for the subgroups with fasting glucose levels of 5.6 to 6.0 mmol/L ( 100 to 109 mg/dL ) and 6.1 to 6.9 mmol/L ( 110 to 125 mg/dL ) . In model checking , we examined potential interactions of impaired fasting glucose and diabetes with age , race or ethnicity , and hormone therapy use , as well as interactions of diabetes and oral hypoglycemic medication or insulin use , by using product terms . We assessed the proportional hazards assumption by fitting models that allowed for variation in the relative hazards for diabetes and impaired fasting glucose either smoothly , by using OBJECTIVE —Impaired glucose tolerance ( IGT ) and /or impaired fasting glucose ( IFG ) are risk factors for diabetes , cardiovascular disease ( CVD ) , and kidney disease . We determined the effects of ramipril and rosiglitazone on combined and individual CVD and renal outcomes in people with IGT and /or IFG in the Diabetes REduction Assessment With ramipril and rosiglitazone Medication ( DREAM ) trial . RESEARCH DESIGN AND METHODS —A total of 5,269 people aged ≥30 years , with IGT and /or IFG without known CVD or renal insufficiency , were r and omized to 15 mg/day ramipril versus placebo and 8 mg/day rosiglitazone versus placebo . A composite cardiorenal outcome and its CVD and renal components were assessed during the 3-year follow-up . RESULTS —Compared with placebo , neither ramipril ( 15.7 % [ 412 of 2,623 ] vs. 16.0 % [ 424 of 2,646 ] ; hazard ratio [ HR ] 0.98 [ 95 % CI 0.84–1.13 ] ; P = 0.75 ) nor rosiglitazone ( 15.0 % [ 394 of 2,635 ] vs. 16.8 % [ 442 of 2,634 ] ; 0.87 [ 0.75–1.01 ] ; P = 0.07 ) reduced the risk of the cardiorenal composite outcome . Ramipril had no impact on the CVD and renal components .  Rosiglitazone  increased heart failure ( 0.53 vs. 0.08 % ; HR 7.04 [ 95 % CI 1.60–31.0 ] ; P = 0.01 ) but reduced the risk of the renal component ( 0.80 [ 0.68–0.93 ] ; P = 0.005 ) ; prevention of diabetes was independently associated with prevention of the renal component ( P < 0.001 ) . CONCLUSIONS —Ramipril did not alter the cardiorenal outcome or its components . Rosiglitazone , which reduced diabetes , also reduced the development of renal disease but not the cardiorenal outcome and increased the risk of heart failure Background Shared decision-making and patients ’ choice of interventions are areas of increasing importance , not least seen in the light of the fact that chronic conditions are increasing , interventions considered important for public health , and still non-acceptance of especially risk-reducing treatments of cardiovascular diseases ( CVD ) is prevalent . A better underst and ing of patients ’ medication-taking behavior is needed and may be reached by study ing the reasons why people accept or decline medication recommendations . The aim of this paper was to identify factors that may influence people ’s decisions and reasoning for accepting or declining a cardiovascular preventive medication offer . Methods From a r and om sample of 4,000 people aged 40–59 years in a Danish population , 1,169 participants were asked to imagine being at increased risk of cardiovascular disease and being offered a preventive medication . After receiving ‘ complete ’ information about effectiveness of the medication they were asked whether they would accept medication . Finally , they were asked about reasons for the decision . Results A total of 725 ( 67 % ) of 1,082 participants accepted the medication offer . Even quite large effects of medication ( up to 8 percentage points absolute risk reduction ) had a smaller impact on acceptance to medication than personal experience with cardiovascular disease . Furthermore , increasing age of the participant and living with a partner were significantly associated with acceptance . Some 45 % of the respondents accepting justified their choice as being for health reasons , and they were more likely to be women , live alone , have higher income and higher education levels . Among those who did not accept the medication offer , 56 % indicated that they would rather prefer to change lifestyle . Conclusions Medication effectiveness seems to have a moderate influence on people ’s decisions to accept preventive medication , while factors such as personal experience with cardiovascular disease may have an equally strong or stronger influence , indicating that practitioners could do well to carefully identify the reasons for their patients ’ treatment decisions
Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects .
There was no evidence of any serious harm caused by statin prescription .
Evidence available to date showed that primary prevention with statins is likely to be cost-effective and may improve patient quality of life .
Recent findings from the Cholesterol Treatment Trialists study using individual patient data meta- analysis indicate that these benefits are similar in people at lower ( < 1 % per year ) risk of a major cardiovascular event .
AUTHORS ' CONCLUSIONS Reductions in all-cause mortality , major vascular events and revascularisations were found with no excess of adverse events among people without evidence of CVD treated with statins
BACKGROUND Reducing high blood cholesterol , a risk factor for cardiovascular disease ( CVD ) events in people with and without a past history of CVD is an important goal of pharmacotherapy .
Statins are the first-choice agents .
Previous review s of the effects of statins have highlighted their benefits in people with CVD .
The case for primary prevention was uncertain when the last version of this review was published ( 2011 ) and in light of new data an up date of this review is required .
OBJECTIVES To assess the effects , both harms and benefits , of statins in people with no history of CVD .