Statins and Fibrates for Diabetic Retinopathy: Protocol for a Systematic Review Hypertension and Its Treatment in Postmenopausal Women: Baseline Data from the Women’s Health Initiative Resting blood pressure reductions following isometric handgrip exercise training and the impact of age and sex: protocol for a systematic review Legacy Effect of Delayed Blood Pressure-Lowering Pharmacotherapy in Middle-Aged Individuals Stratified by Absolute Cardiovascular Disease Risk: Protocol for a Systematic Review The 2001 Canadian recommendations for the management of hypertension: Part two--Therapy. Cardiorespiratory Fitness in Childhood and Adolescence Affects Future Cardiovascular Risk Factors: A Systematic Review of Longitudinal Studies The Australian Therapeutic Trial in Mild Hypertension. Aspirin for primary prevention: yes or no? Effectiveness of blood pressure-lowering drug treatment by levels of absolute risk: post hoc analysis of the Australian National Blood Pressure Study Chocolate and Prevention of Cardiovascular Disease: A Systematic Review The effectiveness of group medical visits on diabetes mellitus type 2 (dm2) specific outcomes in adults: a systematic review 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 Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia) Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies Canadian Cardiovascular Society position statement--recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease. Twenty-four hour ambulatory blood pressure in the International Nifedipine GITS Study Intervention as a Goal in Hypertension Treatment (INSIGHT) EFFICACY OF ANTIHYPERTENSIVE DRUG TREATMENT ACCORDING TO AGE, SEX, BLOOD PRESSURE, AND PREVIOUS CARDIOVASCULAR DISEASE IN PATIENTS OVER THE AGE OF 60 Addressing Dichotomous Data for Participants Excluded from Trial Analysis: A Guide for Systematic Reviewers Morbidity, mortality, and antihypertensive treatment effects by extent of atherosclerosis in older adults with isolated systolic hypertension. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial Evaluation of computer based clinical decision support system and risk chart for management of hypertension in primary care: randomised controlled trial The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2 - therapy. Comorbidity Affects the Relationship Between Glycemic Control and Cardiovascular Outcomes in Diabetes Relationship of Antihypertensive Treatment Regimens and Change in Blood Pressure to Risk for Heart Failure in Hypertensive Patients Randomly Assigned to Doxazosin or Chlorthalidone: Further Analyses from the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial Do sugar-sweetened beverages cause adverse health outcomes in children? A systematic review protocol Arterial stiffness parameters: how do they differ? Comparison of the Effects of Antihypertensive Agents on Central Blood Pressure and Arterial Stiffness in Isolated Systolic Hypertension
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 Little is known about the patterns of treatment and adequacy of blood pressure control in older women . The Women ’s Health Initiative , a 40-center national study of risk factors and prevention of heart disease , breast and colorectal cancer , and osteoporosis in postmenopausal women , provides a unique opportunity to examine these issues in the largest , multiethnic , best-characterized such cohort . Baseline data from the initial 98 705 women , aged 50 to 79 years , enrolled were analyzed to relate prevalence , treatment , and control of hypertension to demographic , clinical , and risk-factor covariates , and logistic regression analyses were performed to estimate odds ratios after adjusting for multiple potential confounders . Overall , 37.8 % of the women had hypertension , which is defined as systolic blood pressure ≥140 mm Hg and /or diastolic blood pressure ≥90 mm Hg or being on medication for high blood pressure ; 64.3 % were treated with drugs , and blood pressure was controlled in only 36.1 % of the hypertensive women , with lower rates of control in the oldest group . After adjustment for multiple covariates , current hormone users had higher prevalence than did nonusers ( odds ratio 1.25 ) . Hypertensive women had more comorbid conditions than did nonhypertensive women , and women with comorbidities were more likely to be treated pharmacologically . Diuretics were used by 44.3 % of hypertensives either as monotherapy or in combination with other drug classes . As monotherapy ,  calcium channel blockers were used in 16 % , angiotensin-converting enzyme inhibitors in 14 % , & bgr;-blockers in 9 % , and diuretics in 14 % of the hypertensive women . Diuretics as monotherapy were associated with better blood pressure control than any of the other drug classes as monotherapy . In conclusion , hypertension in older women is not being treated aggressively enough because a large proportion , especially those most at risk for stroke and heart disease by virtue of age , does not have sufficient blood pressure control Background The risk of developing cardiovascular disease is directly correlated to one ’s resting blood pressure ( BP ) , age , and biological sex . Resting BP can be reduced using h and grip exercise training , but the impact of age and sex on the effectiveness of training is not well documented . Methods / design A systematic search of the literature will be conducted for all experimental studies ( including r and omized controlled trials and prospect i ve experiments ) that report the influence of isometric h and grip exercise training on resting systolic blood pressure . The data bases Medline , Embase , Cochrane Review s , Cumulative Index to Nursing and Allied Health Literature ( CINAHL ) , SPORTD iscus , Web of Science , Allied and Complementary Medicine ( AMED ) , PubMed , and Scopus will be search ed until 1 December 2015 . Screening of potential articles , data abstract ion , and quality appraisal will be completed in duplicate independently . When necessary , corresponding authors will be contacted in order to facilitate the separation of pooled data into age and sex categories . Method ological quality will be determined using the Quality Assessment Framework developed by the Cochrane Collaboration and the Newcastle-Ottawa Quality Assessment Scale as appropriate . Any discrepancies will be resolved by a third author . Findings will be presented in accordance with the preferred reporting items for systematic review s and meta- analysis ( PRISMA ) guidelines . Discussion This systematic review will determine the overall effectiveness  of h and grip exercise training in improving resting blood pressure . A novel , focused assessment will contrast  effectiveness of h and grip training  based on the age ( younger 18–54 years , older > 55 years ) and the sex ( men , women ) of study participants . This information is essential to consoli date before moving forward with the development and implementation of h and grip exercise training programmes which are design ed to best meet the needs of particular cohorts . Systematic review registration PROSPERO 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 OBJECTIVE To provide up date d , evidence -based recommendations for the therapy of hypertension in adults . OPTIONS For patients with hypertension , a number of antihypertensive agents may control blood pressure . R and omized trials evaluating first-line therapy with thiazides , beta-adrenergic antagonists , angiotensin-converting enzyme inhibitors , calcium channel blockers , alpha-blockers , central ly acting agents or angiotensin II receptor antagonists were review ed . OUTCOMES The health outcomes that were considered were changes in blood pressure , cardiovascular morbidity , and cardiovascular and /or all-cause mortality rates . Economic outcomes were not considered due to insufficient evidence . EVIDENCE MEDLINE was search ed for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension . Reference lists were scanned , experts were polled , and the personal files of the subgroup members and authors were used to identify other published studies . All relevant articles were review ed and appraised , using prespecified levels of evidence , by content experts and method ological experts . VALUES A high value was placed on the avoidance of cardiovascular morbidity and mortality . BENEFITS , HARMS AND COSTS Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension . In certain setting s , and for specific classes of drugs , blood-pressure lowering has been associated with reduced cardiovascular morbidity and /or mortality . RECOMMENDATIONS The present document contains detailed recommendations pertaining to treatment thresholds , target blood pressures , and choice of agents in various setting s in patients with hypertension . The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus , the amalgamation of the previous sections on treatment of hypertension in the young and old into one section , increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke . Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk , the presence and /or absence of target organ damage , and comorbidities . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group . Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation . Only those recommendations achieving high levels of consensus are reported here . These guidelines will continue to be up date d annually Background Although cardiorespiratory fitness ( CRF ) in childhood and adolescence may be linked to future cardiovascular health , there is currently limited evidence for a longitudinal association . Objectives To provide a systematic review on the prospect i ve association between CRF in childhood and adolescence and cardiovascular disease ( CVD ) risk factors at least 2 years later . Methods Using a systematic search of Medline , Embase , and SPORTD iscus , relevant articles were identified by the following criteria : generally healthy children and adolescents between 3 and 18 years of age with CRF assessed at baseline , and a follow-up period of ≥ 2 years . The outcome measures were CVD risk factors . We appraised quality of the included articles with STROBE and QUIPS checklists . Results After screening 7524 titles and abstract s , we included 38 articles , assessing 44,169 children and adolescents followed up for a median of 6 years . Eleven articles were of high quality . There was considerable heterogeneity in methodology , measurement of CRF , and outcomes , which hampered meta- analysis . In approximately half of the included articles higher CRF in childhood and adolescence was associated with lower body mass index ( BMI ) , waist circumference , body fatness and lower prevalence of metabolic syndrome in later life . No associations between CRF in childhood and adolescence and future waist-to-hip ratio , blood pressure , lipid profile , and glucose homeostasis were observed . Conclusion Although about half of the included articles reported inverse associations between CRF in childhood and adolescence and future BMI , body fatness , and metabolic syndrome , evidence for other CVD risk factors was unconvincing . Many articles did not account for important confounding factors such as adiposity . Recommendations for future research include st and ardizing the measurement of CRF , i.e. by reporting VO2max , using st and ardized outcome assessment s , and performing individual patient data meta-analyses In the Australian Therapeutic Trial in Mild Hypertension treated patients had significantly lower cardiovascular mortality and a significantly lower incidence of cerebrovascular complications than patients given placebos .  There was , however , no difference in the incidence of nonfatal myocardial infa rct ion or other new manifestations of ischaemic heart disease . Although the evidence of benefit from treatment was clear-cut , the number of cardiovascular complications in the control group was small . This was due to several factors . Patients admitted to the trial had no preceding evidence of cardiovascular complications  , the blood pressure fell spontaneously to below 95 mm Hg in almost half the control group , and patients whose blood pressures rose to levels above 110 mm Hg were given treatment , but remained in the placebo group for analysis . In both treated and placebo groups , trial end-points occurred more frequently in persons whose average diastolic blood pressure during the study remained raised . Ischaemic heart disease and many cases of stroke are due to atherosclerotic arterial disease . This appears not to be favourably influenced by antihypertensive drug therapy 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 Objectives In many current guidelines , blood pressure (BP)-lowering drug treatment for primary prevention of cardiovascular disease ( CVD ) is based on absolute risk . However , in clinical practice , therapeutic decisions are often based on BP levels alone . We sought to investigate which approach was superior by conducting a post hoc analysis of the Australian National Blood Pressure ( ANBP ) cohort , a seminal study establishing the efficacy of BP lowering in ‘ mild hypertensive ’ persons . Design A post hoc subgroup analysis of the ANBP trial results by baseline absolute risk tertile . Setting and participants 3244 participants aged 35–69 years in a community-based r and omised placebo controlled trial of blood pressure-lowering medication . Interventions Chlorothiazide500 mg versus placebo . Primary outcome measures All-cause mortality and non-fatal events ( non-fatal CVD , congestive cardiac failure , renal failure , hypertensive retinopathy or encephalopathy ) . Results Treatment effects were assessed by HR , absolute risk reduction and number needed to treat . Participants had an average 5-year CVD risk in the intermediate range ( 10.5±6.5 ) with moderately elevated BP ( mean 159/103 mmHg ) and were middle aged ( 52±8 years ) . In a subgroup analysis , the relative effects ( HR ) and absolute effects ( absolute risk reduction and number needed to treat ) did not statistically differ across the three risk groups except for the absolute benefit in all-cause mortality ( p for heterogeneity=0.04 ) . With respect to absolute benefit , drug treatment significantly reduced the number of events in the high-risk group regarding any event with a number needed to treat of 18 ( 10 to 64 ) , death from any cause with 45 ( 25 to 196 ) and major CVD events with 23 ( 12 to 193 ) . Conclusion Our analysis confirms that the benefit of treatment was substantial only in the high-risk tertile , reaffirming the rationale of treating elevated blood pressure in the setting of all risk factors rather than in isolation Background Consumption of chocolate has been often hypothesized to reduce the risk of cardiovascular disease ( CVD ) due to chocolate 's high levels of stearic acid and antioxidant flavonoids . However , debate still lingers regarding the true long term beneficial cardiovascular effects of chocolate overall . Methods We review ed English- language MEDLINE publications from 1966 through January 2005 for experimental , observational , and clinical studies of relations between cocoa , cacao , chocolate , stearic acid , flavonoids ( including flavonols , flavanols , catechins , epicatechins , and procynadins ) and the risk of cardiovascular disease ( coronary heart disease ( CHD ) , stroke ) . A total of 136 publications were selected based on relevance , and quality of design and methods . An up date d meta- analysis of flavonoid intake and CHD mortality was also conducted . Results The body of short-term r and omized feeding trials suggests cocoa and chocolate may exert beneficial effects on cardiovascular risk via effects on lowering blood pressure , anti-inflammation , anti-platelet function , higher HDL , decreased LDL oxidation . Additionally , a large body of trials of stearic acid suggests it is indeed cholesterol-neutral . However , epidemiologic studies of serum and dietary stearic acid are inconclusive due to many method ologic limitations . Meanwhile , the large body of prospect i ve studies of flavonoids suggests the flavonoid content of chocolate may reduce risk of cardiovascular mortality . Our up date d meta- analysis indicates that intake of flavonoids may lower risk of CHD mortality , RR = 0.81 ( 95 % CI : 0.71–0.92 ) comparing highest and lowest tertiles . Conclusion Multiple lines of evidence from laboratory experiments and r and omized trials suggest stearic acid may be neutral , while flavonoids are likely protective against CHD mortality . The highest priority now is to conduct larger r and omized trials to definitively investigate the impact of chocolate consumption on long-term cardiovascular outcomes Background The prevalence of diabetes mellitus is ubiquitous . Complications and costs of diabetes are rising and are depleting limited re sources . It is imperative for healthcare professionals and patients alike to confront this chronic condition by exploring new interventions . An innovative health care delivery model has emerged in the last 25 years in the form of the group medical visit . Group medical visits can range from of six to twenty patients scheduled together with time allotted for individual care as well as in the group setting . Objectives The review objective was to conduct a systematic review and meta‐ analysis to synthesize the best available evidence related to effectiveness of group medical visits on HbA1c , blood pressure and cholesterol measurements /levels for adult patients with type II diabetes in outpatient setting s. Search strategy A three‐step literature search for studies in English language from 1990 to 2010 was conducted utilising ( a ) a primary search of Medline , CINAHL , PsycINFO and Cochrane Central Register of Controlled Trials , ( b ) a secondary search of non‐indexed data bases , and ( c ) a search of the grey literature . In addition , a manual review of the reference lists of all identified reports and articles was performed to identify additional studies . Inclusion criteria All r and omised and quasi‐experimental studies of adult patients ( > 18 ) with type II diabetes mellitus seen in outpatient health setting s were considered if they met one or more of the following diagnostic outcome measurements : haemoglobin A1c , systolic and diastolic blood pressure , and low density lipoprotein cholesterol . Critical appraisal , data collection and analysis Each of the eligible articles was review ed by two independent review ers . Disagreements between the review ers were resolved through discussion , or with a third review er . Studies that met the inclusion criteria were assessed for method ological quality using the JBI st and ardized critical appraisal tools . Data extraction was undertaken using the st and ardised data extraction tool from JBI‐MAStARI . Main results The search strategy identified 2,040 articles in the published and unpublished literature . Of these , 11 r and omised controlled trials and 4 quasi‐experimental trials met the inclusion criteria and represented 2240 patients included in the final review . There are clear benefits of group medical visits for patients ' HbA1c levels which are consistent in the post‐intervention and change from baseline effect sizes . The most significant effect observed is with the change from baseline results . Some evidence suggests post‐intervention and change from baseline systolic blood pressure improvement at the nine to twelve month interval and change from baseline improvement at the 4 year timeframe . There is no evidence that group visits improve LDL cholesterol values of the group visit participants . Conclusions Group medical visits should be considered by clinicians as an effective non‐pharmacologic intervention that can have a positive impact on biologic markers such as haemoglobin A1c and systolic blood pressure . Implication s for practice The evidence suggests that the most powerful model of Group medical visits ( GMV ) is when a clinician prescriber is present during or immediately after GMV sessions for medication reconciliation or individual patient needs . Implication s for research Future research should include this GMV intervention in r and omised controlled trials across different health systems and socio‐economic and ethnic groups 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 [ BACKGROUND In diabetic nephropathy , angiotensin-converting-enzyme ( ACE ) inhibitors have a greater effect than other antihypertensive drugs on proteinuria and the progressive decline in glomerular filtration rate ( GFR ) . Whether this difference applies to progression of nondiabetic proteinuric nephropathies is not clear . The Ramipril Efficacy in Nephropathy study of chronic nondiabetic nephropathies aim ed to address whether glomerular protein traffic influences renal-disease progression , and whether an ACE inhibitor was superior to conventional treatment , with the same blood-pressure control , in reducing proteinuria , limiting GFR decline , and preventing endstage renal disease . METHODS In this prospect i ve double-blind trial , 352 patients were classified according to baseline proteinuria ( stratum 1 : 1 - 3 g/24 h ; stratum 2 : > or = 3 g/24 h ) , and r and omly assigned ramipril or placebo plus conventional antihypertensive therapy targeted at achieving diastolic blood pressure under 90 mm Hg . The primary endpoint was the rate of GFR decline . Analysis was by intention to treat . FINDINGS At the second planned interim analysis , the difference in decline in GFR between the ramipril and placebo groups in stratum 2 was highly significant ( p = 0.001 ) . The Independent Adjudicating Panel therefore decided to open the r and omisation code and do the final analysis in this stratum ( stratum 1 continued in the trial ) . Data ( at least three GFR measurements including baseline ) were available for 56 ramipril-assigned patients and 61 placebo-assigned patients . The decline in GFR per month was significantly lower in the ramipril group than the placebo group ( 0.53 [ 0.08 ] vs 0.88 [ 0.13 ] mL/min , p = 0.03 ) . Among the ramipril-assigned patients , percentage reduction in proteinuria was inversely correlated with decline in GFR ( p = 0.035 ) and predicted the reduction in risk of doubling of baseline creatinine or endstage renal failure ( 18 ramipril vs 40 placebo , p = 0.04 ) . The risk of progression was still significantly reduced after adjustment for changes in systolic ( p = 0.04 ) and diastolic ( p = 0.04 ) blood pressure , but not after adjustment for changes in proteinuria . Blood-pressure control and the overall number of cardiovascular events were similar in the two treatment groups . INTERPRETATION In chronic nephropathies with proteinuria of 3 g or more per 24 h , ramipril safely reduces proteinuria and the rate of GFR decline to an extent that seems to exceed the reduction expected for the degree of blood-pressure lowering BACKGROUND cardiovascular risk factors are associated with  dementia and cognitive decline  . We investigated the effects of renin-angiotensin system blockade on cognitive function in patients aged 55 years and older with established atherosclerotic cardiovascular disease or diabetes with end-organ damage in two clinical trials . METHODS in the main study , ONTARGET , a double-blind , double-dummy , r and omised controlled trial , the effects on cardiovascular outcomes of st and ard doses of an angiotensin-converting enzyme ( ACE ) inhibitor ( ramipril ) , an angiotensin-receptor blocker ( telmisartan ) , and a combination of the drugs were evaluated in 25 620 participants . In the parallel TRANSCEND trial , the effects of telmisartan were compared with those of placebo in 5926 participants intolerant to ACE inhibitors . Secondary outcomes included cognitive impairment ( defined by investigator-reported diagnosis of dementia or significant cognitive dysfunction , or a score of ≤ 23 on the Mini-Mental State Examination [ MMSE ] ) and cognitive decline ( a decrease of ≤ 3 points on the MMSE from baseline during follow-up ) . Analyses were by intention to treat . We pooled data from these studies to identify baseline predictors of cognitive impairment and its frequency according to mean systolic blood pressure during follow-up . These studies were registered with Clinical Trials.gov , number NCT00153101 . FINDINGS During a median duration of 56 months ( IQR 51 - 64 ) of follow-up in ONTARGET , cognitive impairment occurred in 652 ( 8 % ) of 7865 patients allocated ramipril , 584 ( 7 % ) of 7797 allocated telmisartan , and 618 ( 8 % ) of 7807 allocated combination treatment ( combination vs ramipril , odds ratio [ OR ] 0·95 , 95 % CI 0·85 - 1·07 , p= 0·39 ; telmisartan vs ramipril , OR 0·90 , 0·80 - 1·01 , p = 0·06 ) . Corresponding figures for cognitive decline were 1314 ( 17 % ) , 1279 ( 17 % ) , and 1240 ( 17 % ) in each of the groups , respectively ( telmisartan vs ramipril , OR 0·97 , 0·89 - 1·06 , p= 0·53 ; combination vs ramipril , OR 0·95 , 0·88 - 1·04 , p=0·28 ) . In TRANSCEND , cognitive impairment occurred in 239 ( 9 % ) of 2694 participants allocated telmisartan compared with 245 ( 9 % ) of 2689 allocated placebo ( OR 0·97 , 0·81 - 1·17 , p= 0·76 ) . The corresponding figures for cognitive decline were 454 ( 17 % ) and 412 ( 16 % ; OR 1·10 , 0·95 - 1·27 , p= 0·22 ) . INTERPRETATION In patients with cardiovascular disease or diabetes , different approaches to blocking of the renin-angiotensin system had no clear effects on cognitive outcomes . Although patients with the lowest systolic blood pressure had the greatest preservation of cognitive function , meta-regression analyses did not show any benefits of blood-pressure lowering on cognition over several years of treatment Since the last publication of the recommendations for the management and treatment of dyslipidemia , new clinical trial data have emerged that support a more vigorous approach to lipid lowering in specific patient groups . The decision was made to up date the lipid guidelines in collaboration with the Canadian Cardiovascular Society . A systematic electronic search of medical literature for original research consisting of blinded , r and omized controlled trials was performed . Meta-analyses of studies of the efficacy and safety of lipid-lowering therapies , and of the predictive value of established and emerging risk factors were also review ed . All recommendations are evidence -based , and have been review ed in detail by primary and secondary review panels . Major changes include a lower low-density lipoprotein cholesterol ( LDL-C ) treatment target ( lower than 2.0 mmol/L ) for high-risk patients , a slightly higher intervention point for the initiation of drug therapy in most low-risk individuals ( LDL-C of 5.0 mmol/L or a total cholesterol to high-density lipoprotein cholesterol ratio of 6.0 ) and recommendations regarding additional investigations of potential use in the further evaluation of coronary artery disease risk in subjects in the moderate-risk category Objectives The International Nifedipine GITS Study Intervention as a Goal in Hypertension Treatment ( INSIGHT ) showed , by means of office blood pressure measurements , that long-term treatment with nifedipine GITS is as effective as diuretics in preventing cardiovascular and cerebrovascular complications . However , since office blood pressure measurements reflect to a limited extent blood pressure outside the office , a side-arm INSIGHT study in which patients underwent both office measurement and 24 h ambulatory blood pressure monitoring was also performed . Design and methods The study had a r and omized , double-blind , parallel group design . After 4 weeks of placebo , mild-to-moderate essential hypertensive patients were r and omized to nifedipine GITS 30 mg or amiloride 2.5 + hydrochlorothiazide  5 mg for 3.1 years . Dose titration was performed by dose doubling and addition of atenolol 25–50 mg or enalapril 5–10 mg , or other drugs when needed . Analysis was carried out by intention-to-treat and included computation of 24 h , day and night ambulatory blood pressure and heart rate values . Additional analyses included computation of the trough-to-peak ratio and the smoothness index ( the ratio between the average of the 24-hourly blood pressure reductions after treatment and its st and ard deviation ) . Results A total of 151 patients were recruited and 149 were valid for analysis : 78 patients had 24 h ambulatory recordings both at baseline and during treatment and 134 during treatment . Office , 24 h and day and night blood pressures were all significantly and similarly reduced by both treatments . Office and ambulatory heart rate was left unchanged by diuretics , while it was slightly reduced by nifedipine . Median trough-to-peak ratios were always > 0.5 and superimposable between the two treatment groups . Similarly , smoothness indices of systolic and diastolic blood pressures were comparably high for nifedipine and diuretics , thus demonstrating a similar well-balanced antihypertensive response to both drugs . No significant differences were observed between the two treatment groups in the number of cardiovascular events ( 17 in the nifedipine-based and 26 in the diuretics-based treatment group ) . Conclusions In the INSIGHT study , the long-term antihypertensive effect on 24 h blood pressure and the cardiovascular protection of nifedipine was similar to that of diuretics Results of the European Working Party on High Blood Pressure in the Elderly ( EWPHE ) trial have been analysed in relation to age , sex , blood pressure , and previous cardiovascular disease . Cardiovascular mortality and the cardiovascular study -terminating events were significantly and independently related to treatment , age , cardiovascular complications at r and omisation , and systolic but not diastolic blood pressure . The benefits of treatment observed in the trial seemed to be independent of entry blood pressure and the presence or absence of cardiovascular complications at entry . There was some evidence that treatment effect decreases with advancing age . Little or no benefit from treatment could be demonstrated in patients over the age of 80 years , the great majority of whom were women Introduction Systematic review er authors intending to include all r and omized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data . Objective The objective of this paper is to provide systematic review er authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of r and omized trials . Methods This guide is based on a review of the Cochrane h and book and published method ological research . The guide deals with participants excluded from the analysis who were considered ‘ non-adherent to the protocol ’ but for whom data are available , and participants with missing data . Results Systematic review er authors should include data from ‘ non-adherent ’ participants excluded from the primary study authors ' analysis but for whom data are available . For missing , unavailable participant data , authors may conduct a complete case analysis ( excluding those with missing data ) as the primary analysis . Alternatively , they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data . When the primary analysis suggests important benefit , sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis . The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta- analysis . The proposed guide does not take into account the uncertainty associated with assumed events . Conclusions This guide proposes methods for h and ling participants excluded from analyses of r and omized trials . These methods can help in establishing the extent to which risk of bias impacts meta- analysis results BACKGROUND AND PURPOSE The Systolic Hypertension in the Elderly Program ( SHEP ) demonstrated a significant reduction in stroke and coronary event rates among participants r and omly assigned to active blood pressure treatment . Selected participants were evaluated for peripheral atherosclerosis and followed up for cardiovascular events beyond the end of the SHEP trial . Antihypertensive treatment effects were evaluated based on the presence or absence of clinical or sub clinical atherosclerosis . METHODS As an ancillary study to SHEP , 190 participants at the Pittsburgh center were evaluated for peripheral atherosclerosis , defined as either an internal carotid stenosis ( by duplex scan ) or lower extremity arterial disease ( identified by ankle blood pressure ) . Participants were subsequently followed up for cardiovascular events . RESULTS Estimates of 4-year mortality rates were 4.8 % for participants with no atherosclerosis , 16.7 % for those with sub clinical atherosclerosis , and 23 % among those with clinical evidence of atherosclerosis ( P < .001 ) . Fatal plus nonfatal cardiovascular event rates were 10.9 % , 29.8 % , and 58.3 % for the three groups , respectively ( P < .001 ) . Differences remained significant after adjustment for age , sex , treatment assignment , smoking , and high-density lipoprotein cholesterol . Individuals assigned to placebo at the beginning of SHEP had higher cardiovascular event rates than individuals assigned to active treatment ( P = .011 ) , with the most striking difference 3 or more years after the end of the SHEP trial . When this analysis was stratified by the presence or absence of detectable atherosclerosis , the absolute treatment effect was largest among those with evidence of disease . CONCLUSIONS Individuals with systolic hypertension and evidence of peripheral atherosclerosis are at high risk for cardiovascular events . Targeting this group for antihypertensive therapy would result in the prevention of a large number of cardiovascular events Background The prognostic benefits of blood pressure lowering treatment in elderly hypertensive patients were established more than a decade ago , but are less clear in those with mildly to moderately elevated blood pressure . Objective To assess whether c and esartan-based antihypertensive treatment in elderly patients with mildly to moderately elevated blood pressure confers a reduction in cardiovascular events , cognitive decline and dementia . Design Prospect i ve , double-blind , r and omized , parallel-group study conducted in 1997–2002 . Setting and participants The study was of 4964 patients aged 70–89 years , with systolic blood pressure 160–179 mmHg , and /or diastolic blood pressure 90–99 mmHg , and a Mini Mental State Examination ( MMSE ) test score ⩾ 24 . A total of 527 centres in 15 countries participated in the study . Intervention Patients were assigned r and omly to receive the angiotensin receptor blocker c and esartan or placebo , with open-label active antihypertensive therapy added as needed . As a consequence , active antihypertensive therapy was extensively used in the control group ( 84 % of patients ) . Mean follow-up was 3.7 years . Main outcome measures The primary outcome measure was major cardiovascular events , a composite of cardiovascular death , non-fatal stroke and non-fatal myocardial infa rct ion . Secondary outcome measures included cardiovascular death , non-fatal and fatal stroke and myocardial infa rct ion , cognitive function measured by the MMSE and dementia . Results Blood pressure fell by 21.7/10.8 mmHg in the c and esartan group and by 18.5/9.2 mmHg in the control group . A first major cardiovascular event occurred in 242 c and esartan patients and in 268 control patients ; risk reduction with c and esartan was 10.9 % [ 95 % confidence interval ( CI ) , −6.0 to 25.1 , P = 0.19 ] . C and esartan-based treatment reduced non-fatal stroke by 27.8 % ( 95 % CI , 1.3 to 47.2 , P = 0.04 ) , and all stroke by 23.6 % ( 95 % CI , −0.7 to 42.1 , P = 0.056 ) . There were no significant differences in myocardial infa rct ion and cardiovascular mortality . Mean MMSE score fell from 28.5 to 28.0 in the c and esartan group and from 28.5 to 27.9 in the control group ( P = 0.20 ) . The proportions of patients who had a significant cognitive decline or developed dementia were not different in the two treatment groups . Conclusions In elderly hypertensive patients , a slightly more effective blood pressure reduction during c and esartan-based therapy , compared with control therapy , was associated with a modest , statistically non-significant , reduction in major cardiovascular events and with a marked reduction in non-fatal stroke . Cognitive function was well maintained in both treatment groups in the presence of substantial blood pressure reductions . Both treatment regimens were generally well tolerated Abstract Objectives : To investigate the effect of a computer based clinical decision support system and a risk chart on absolute cardiovascular risk , blood pressure , and prescribing of cardiovascular drugs in hypertensive patients . Design : Cluster r and omised controlled trial . Setting : 27 general practice s in Avon . Participants : 614 patients aged between 60 and 79 years with high blood pressure . Interventions : Patients were r and omised to computer based clinical decision support system plus cardiovascular risk chart ; cardiovascular risk chart alone ; or usual care . Main outcome measures : Percentage of patients in each group with a five year cardiovascular risk≥10 % , systolic blood pressure , diastolic blood pressure , prescribing of cardiovascular drugs . Results : Patients in the computer based clinical decision support system and chart only groups were no more likely to have cardiovascular risk reduced to below 10 % than patients receiving usual care . Patients in the computer based clinical decision support group were more likely to have a cardiovascular risk≥10 % than chart only patients , odds ratio 2.3 ( 95 % confidence interval 1.1 to 4.8 ) . The chart only group had significantly lower systolic blood pressure compared with the usual care group ( difference in means−4.6 mm Hg ( 95 % confidence interval−8.4 to−0.8 ) . Reduction of diastolic blood pressure did not differ between the three groups . The chart only group were twice as likely to be prescribed two classes of cardiovascular drugs and over three times as likely to be prescribed three or more classes of drugs compared with the other groups . Conclusions : The computer based clinical decision support system did not confer any benefit in absolute risk reduction or blood pressure control and requires further development and evaluation before use in clinical care can be recommended . Use of chart guidelines are associated with a potentially important reduction in systolic blood pressure OBJECTIVE To provide up date d , evidence -based recommendations for the prevention and management of hypertension in adults . OPTIONS AND OUTCOMES For lifestyle and pharmacological interventions , evidence was review ed from r and omized controlled trials and systematic review s of trials . Changes in cardiovascular morbidity and mortality were the primary outcomes of interest . However , for lifestyle interventions , blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field . For treatment of patients with kidney disease , the progression of kidney dysfunction was also accepted as a clinical ly relevant primary outcome . EVIDENCE A Cochrane collaboration librarian conducted an independent MEDLINE search from 2005 to August 2006 to up date the 2006 Canadian Hypertension Education Program recommendations . In addition , reference lists were scanned and experts were contacted to identify additional published studies . All relevant articles were review ed and appraised independently by both content and method ological experts using prespecified levels of evidence . RECOMMENDATIONS Dietary lifestyle modifications for prevention of hypertension , in addition to a well-balanced diet , include a dietary sodium intake of less than 100 mmol/day . In hypertensive patients , the dietary sodium intake should be limited to 65 mmol/day to 100 mmol/day . Other lifestyle modifications for both normotensive and hypertensive patients include : performing 30 min to 60 min of aerobic exercise four to seven days per week ; maintaining a healthy body weight ( body mass index of 18.5 kg/m2 to 24.9 kg/m2 ) and waist circumference ( less than 102 cm in men and less than 88 cm in women ) ; limiting alcohol consumption to no more than 14 units per week in men or nine units per week in women ; following a diet reduced in saturated fat and cholesterol , and one that emphasizes fruits , vegetables and low-fat dairy products , dietary and soluble fibre , whole grains and protein from plant sources ; and considering stress management in selected individuals with hypertension . For the pharmacological management of hypertension , treatment thresholds and targets should take into account each individual 's global atherosclerotic risk , target organ damage and any comorbid conditions : blood pressure should be lowered to lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease . Most patients require more than one agent to achieve these blood pressure targets . In adults without compelling indications for other agents , initial therapy should include thiazide diuretics ; other agents appropriate for first-line therapy for diastolic and /or systolic hypertension include angiotensin-converting enzyme ( ACE ) inhibitors ( except in black patients ) , long-acting calcium channel blockers ( CCBs ) , angiotensin receptor blockers ( ARBs ) or beta-blockers ( in those younger than 60 years of age ) . First-line therapy for isolated systolic hypertension includes long-acting dihydropyridine CCBs or ARBs . Certain comorbid conditions provide compelling indications for first-line use of other agents : in patients with angina , recent myocardial infa rct ion , or heart failure , beta-blockers and ACE inhibitors are recommended as first-line therapy ; in patients with cerebrovascular disease , an ACE inhibitor plus diuretic combination is preferred ; in patients with nondiabetic chronic kidney disease , ACE inhibitors are recommended ; and in patients with diabetes mellitus , ACE inhibitors or ARBs ( or , in patients without albuminuria , thiazides or dihydropyridine CCBs ) are appropriate first-line therapies . All hypertensive patients with dyslipidemia should be treated using the thresholds , targets and agents outlined in the Canadian Cardiovascular Society position statement ( recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease ) . Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy . Once blood pressure is controlled , acetylsalicylic acid therapy should be considered . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence -Based Recommendations Task Force . All recommendations reported here achieved at least 95 % consensus . These guidelines will continue to be up date d annually Context The effectiveness of glycemic control in reducing cardiovascular events among patients with type 2 diabetes is uncertain . Recent analyses of trial data suggest that the benefit of tight control may differ according to a person 's age and comorbid conditions . Contribution This observational study of 2613 patients with type 2 diabetes in 205 practice s in Italy found that tight control was associated with lower risk for cardiovascular events over 5 years in patients with low to moderate , but not high , comorbidity . Caution Observational data can not prove a causal association between glycemic control and outcomes . Implication The relationship of glycemic control and cardiovascular outcomes differs by patients ' level of comorbidity . The Editors Major professional organizations recommend that attaining a hemoglobin A1c ( HbA1c ) value less than 7.0 % may be less appropriate for patients with limited life expectancy , advanced complications , and extensive comorbidity ( 13 ) . Evidence suggests that the benefit of intensive glucose-lowering therapy is not uniform across all patients with type 2 diabetes . Three large r and omized , controlled trials that used HbA1c targets of 6.5 % or lower ( 46 ) each found no association between intensive therapy and an overall reduction in risk for macrovascular complications . However , when data from these and other trials were considered in 2 recent meta-analyses ( 7 , 8) , the investigators observed statistically significant relationships between tight glycemic control and reduced cardiovascular events . Post hoc analyses of data from these clinical trials suggest that benefit from aggressive glycemic control may be confined to younger diabetic patients ( 4 ) and patients without previous heart disease ( 4 , 5 ) . Data from the 10-year posttrial follow-up ( 9 ) to the UKPDS ( United Kingdom Prospect i ve Diabetes Study ) ( 10 ) also showed a reduction in cardiovascular events from intensive glucose-lowering therapy initiated in a young and healthy sample of patients with recently diagnosed type 2 diabetes . Recent decision analyses based on UKPDS risk models suggest that , independent of age , high levels of comorbidity may diminish the benefits of achieving tight control ( 11 ) , owing to the complex interplay of multiple conditions , their treatments , and their burden on patient re sources ( 12 ) . Among the comorbid conditions prevalent among diabetic patients , cardiovascular diseases are the most important contributors to mortality and subsequent cardiovascular events . However , additional conditions , such as chronic lung disease , may also bring functional impairment , treatment burden , and risk for adverse events and may diminish a patient 's likelihood to benefit from tight control ( 13 , 14 ) . In a 5-year observational study of a community-based sample of older patients with type 2 diabetes , we tested whether attaining glycemic control targets of HbA1c levels of 6.5 % or less or 7.0 % or less at baseline provided differential benefits for patients with higher versus lower levels of comorbidity . We further compared the unique contribution of comorbid conditions with that of other risk factors ( such as age or duration of diabetes ) to the differential benefit from glycemic control on future cardiovascular events . Methods Our study , described in detail elsewhere ( 1517 ) , was a 5-year longitudinal observational study ( 1999 to 2004 ) that examined the association of the quality of diabetes care with the incidence of cardiovascular events and mortality . Patients were followed for a median of 4.96 years ( interquartile range , 3.35 to 5.00 years ) . Patients We identified medical practice s in all regions of Italy and selected them according to their willingness to participate in the project . Participating practice s included 101 of approximately 605 eligible diabetes outpatient clinics and 103 of approximately 1000 eligible community-based general practitioners enrolled in a nationwide network of practitioners interested in facilitating research . We considered all patients with type 2 diabetes mellitus ( fasting venous plasma glucose concentration 7.8 mmol/L [ 140 mg/dL ] on 2 separate occasions or treated with antidiabetic drugs ) to be eligible for the project , regardless of age , diabetes duration , or treatment . At the diabetes outpatient clinics , patients were r and omly sample d from clinic rosters and stratified by patient age ( < 65 or 65 years ) . We asked each diabetes outpatient clinic to recruit at least 30 patients . Community-based general practitioners consecutively enrolled only patients for whom they were primarily responsible for diabetes care , up to a maximum of 10 patients . Clinical Measures The main outcome of the study was incident cardiovascular events , defined as any of the following outcomes : angina , myocardial infa rct ion , stroke , transient ischemic attack , coronary revascularization procedures , lower limb complications ( claudication , ulcer , gangrene , amputation , or aorticfemoral revascularization procedures ) , or cardiovascular mortality . Participating physicians certified the occurrence of any cardiovascular event over the 5-year study period , on the basis of study -wide criteria . In addition , participating physicians reported the death of any study patient from any cause ; this information was used to compute total mortality rates . Participating physicians abstract ed demographic and clinical data , including age , body mass index , duration of diabetes , HbA1c level , lipid levels , and blood pressure ( collected and entered into models as continuous variables ) , as well as sex , smoking status and the presence of diabetes complications ( collected and entered into models as categorical variables ) from clinical records and reported these data to the coordinating center at Mario Negri Sud . Because normal ranges for HbA1c varied in the different centers , the percentage change with respect to the upper normal value ( actual value vs. upper limit of normal ) was estimated and multiplied by 6.0 ( 16 ) . Total cholesterol was used as a measure of lipid control because low-density lipoprotein levels were not routinely measured in many of the study patients . We used the last blood pressure value in the clinical record before the data collection point . Data were collected at baseline and at 6-month intervals for 5 years . Measure of Comorbidity We requested that all recruited patients complete the Total Illness Burden Index ( TIBI ) question naire ( 1820 ) . The TIBI , which was specifically developed for office practice population s , uses patient reports to assess the presence and severity of 8 dimensions of comorbid conditions , problems , and diseases ( atherosclerotic heart disease , lung disease , congestive heart failure , arthritis , genitourinary disease , vision loss , gastrointestinal conditions , and foot disease ) by using items similar to those in the traditional review of systems . We scored these responses to assess the severity of the 8 dimensions and then aggregated the scores by using an algorithm that weighted each dimension according to its predicted effect on functional outcomes . We also performed analyses that used a version of the TIBI score that excluded previous cardiovascular events to examine the effects of the noncardiac components of the TIBI on future events . We refer to this version as the noncardiovascular TIBI score . The TIBI can be completed and scored in office practice s for use by physicians at the time of treatment and has been vali date d as a predictor of 3.5-year mortality ( 20 ) and health-related quality of life ( 18 , 19 ) . Statistical Analysis We conducted univariate analyses to describe patient characteristics and reported means and SDs for continuous variables and frequencies and percentages for categorical variables . We calculated the probabilities of incident cardiovascular events by using the KaplanMeier method and carried out comparisons by using the log-rank test . We divided patients into 2 prespecified subgroups at a threshold TIBI score of 12 , which has been demonstrated to discriminate between persons at greater and lesser risk for death ( 20 ) . We defined patients with TIBI scores less than 12 as the low-to-moderate comorbidity subgroup and patients with scores of 12 or greater as the high comorbidity subgroup . To account for the hierarchical nature of the data ( patients clustered within center ) , and to control for possible confounding or clustering by center of variables , we used multivariate Cox proportional hazards regression models , stratified by center , to investigate whether a dichotomized TIBI score was an independent predictor of clinical outcomes . In all analyses , we expressed outcome risk in terms of hazard ratios ( HRs ) with 95 % CIs in models adjusted for age ( as a continuous variable ) and sex ( as a categorical variable ) . To demonstrate that the threshold TIBI score of 12 differentiated patients ' risk both for cardiovascular events and for total mortality in the current sample , we computed hazard ratios for relative risk for each outcome between participants with TIBI scores of 12 or greater and patients with scores less than 12 . To demonstrate that any association observed between comorbidity and outcome risk was not an artifact of the selected TIBI score cut-point , we computed hazard ratios for both cardiovascular event risk and mortality risk by using the TIBI score as a continuous , independent variable . We replicated the analysis by using the noncardiovascular TIBI score to examine its association with future cardiovascular events and mortality . To determine whether the benefit of attaining recommended targets for glycemic control was greater for patients with low-to-moderate or high levels of comorbidity , we tested whether baseline HbA1c levels of 6.5 % or less or 7.0 % or less were associated with lower incidence of cardiovascular events in each comorbidity subgroup . To examine whether any observed association between attaining glycemic control targets and reduced cardiovascular event risk was sensitive Context Previously published results of this r and omized , double-blind trial showed that hypertensive patients treated with doxazosin rather than chlorthalidone more often developed heart failure . Did differences in blood pressure control or treatment with other drugs explain these findings ? Contribution This analysis shows that the slightly worse blood pressure control achieved with doxazosin did not explain higher risks for heart failure . Risks with doxazosin versus chlorthalidone were highest among patients who received monotherapy ( relative risk , 3.10 ) and lowest among patients who received stepped care with additional drugs ( relative risk , 1.42 ) . Implication s Increased risks for heart failure with doxazosin versus chlorthalidone are attenuated but not eliminated when additional antihypertensive drugs are used . The Editors The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial ( ALLHAT ) , a r and omized , double-blind , multicenter clinical trial including 42 418 participants at 623 clinical sites , is design ed to determine whether treatment begun with a calcium-channel blocker ( amlodipine ) , an angiotensin-converting enzyme inhibitor ( lisinopril ) , or an -adrenergic blocker ( doxazosin ) compared to treatment with a diuretic ( chlorthalidone ) reduces the incidence of fatal coronary heart disease or nonfatal myocardial infa rct ion in high-risk patients with hypertension ( 1 ) . Secondary end points are all-cause mortality , stroke , and other cardiovascular events . A lipid-lowering trial in a subset of 10 356 participants is design ed to determine whether decreasing cholesterol levels with a hydroxymethyl glutamyl coenzyme A reductase inhibitor ( pravastatin ) compared with usual care reduces all-cause mortality in older , moderately hypercholesterolemic patients . In January 2000 , the doxazosin arm of the trial was discontinued ( 2 ) because major cardiovascular disease ( relative risk , 1.25 [ 95 % CI , 1.17 to 1.33 ] ; P < 0.001 ) , especially heart failure ( relative risk , 2.04 [ 95 % CI , 1.79 to 2.32 ] ; P < 0.001 ) , was significantly increased compared with the chlorthalidone arm . Equally important , a low probability existed that doxazosin would show benefit over chlorthalidone for the primary end point by the scheduled study end , given the lack of difference ( relative risk , 1.02 [ 95 % CI , 0.90 to 1.17 ] ; P > 0.2 ] at that time . These intention-to-treat analyses compared patients assigned to chlorthalidone with patients assigned to doxazosin . In this article , we analyze how treatment changes may have affected the comparison of doxazosin with chlorthalidone in terms of heart failure . Our major objectives are to ascertain to what extent the relative risk with doxazosin versus chlorthalidone depends on 1 ) whether the assigned drugs were used as monotherapy or in combination with other agents and 2 ) the difference in decreases in systolic and diastolic blood pressure . Methods Study Design The rationale and design of ALLHAT are described in detail elsewhere ( 1 ) . In brief , eligible participants were men and women 55 years of age or older who had systolic or diastolic hypertension ( 140/90 mm Hg or hypertension controlled with medication ) plus at least one additional risk factor for coronary heart disease events . The risk factors included previous ( > 6 months ) myocardial infa rct ion or stroke , left ventricular hypertrophy on electrocardiography or echocardiography , history of type 2 diabetes , current cigarette smoking , and a low high-density lipoprotein cholesterol level . Persons with a history of hospitalized or treated symptomatic heart failure or a known ejection fraction less than 0.35 were excluded . Unless the drug regimen required tapering for safety , participants who had been taking antihypertensive medications continued to do so until the day of r and omization , at which point they stopped taking all previous medications . On the day after r and omization , treatment with the study drug was initiated . Enrollment occurred from February 1994 through January 1998 . The original reported number of 42 448 participants and 625 sites changed because 30 patients with poor documentation of informed consent were excluded ( 2 ) . Participants were assigned by a computer-generated r and omization schedule in a ratio of 1.7:1 to receive chlorthalidone or doxazosin . R and omization was stratified by center and blocked over time to maintain the ratio . All participants gave written informed consent , and all centers obtained institutional review board approval . Ascertainment of Outcomes At each clinic visit , occurrence of study end points was assessed by the clinical investigator . A hospital discharge summary was required for each hospitalized study outcome , and a death certificate was required for each death . ALLHAT defined symptomatic heart failure as clear-cut signs or symptoms of left or right ventricular dysfunction that can not be attributed to other causes . A patient had to have at least one symptom ( paroxysmal nocturnal dyspnea , dyspnea at rest , New York Heart Association class III dyspnea or other symptoms [ on less than ordinary exertion ] , or orthopnea ) and one sign ( rales , ankle edema , tachycardia , cardiomegaly or characteristic pulmonary pattern on chest radiography , S3 gallop , or jugular venous distention ) ( 3 ) . Symptoms and signs were determined by the clinic investigator through patient history , chart review , or consultation with the treating physician , but such data were not collected central ly . A one-time sample of 24 hospitalized or fatal heart failure events was review ed in a blinded manner by the ALLHAT Endpoints Subcommittee ; 20 of 24 ( 83 % ) were deemed to have complete data for a definitive diagnosis . Of the 20 cases , the agreement rate between the subcommittee and the clinic investigators was 90 % ( 18 of 20 ) and similar in both treatment groups . Details on the validity of diagnosis of heart failure will be provided in a future report . Measurement and Treatment of Blood Pressure The ALLHAT protocol specified a stepped-care treatment program for hypertension . Trained observers using st and ardized techniques measured blood pressures during the trial ( 1 , 2 ) . All blood pressures were calculated as the average of two measurements obtained with a 30-second interval between them . The blood pressure goal in all four study arms was less than 140/90 mm Hg . This level was to be achieved with the lowest possible dose of blinded first-line drug , with addition of second- and third-line open-label therapy as needed after reaching the maximal dose of first-line drug . Chlorthalidone and doxazosin were to be taken once daily in the morning . By design , doses were selected to achieve equivalent blood pressure control in the treatment groups . The first , second , and third dosage levels were 12.5 mg/d , 12.5 mg/d ( sham titration ) , and 25 mg/d , respectively , for chlorthalidone and 2 mg/d , 4 mg/d , and 8 mg/d for doxazosin . Double-blinded 1-mg and 12.5-mg doses of doxazosin and chlorthalidone , respectively , were used for the first week to minimize the frequency of postural hypotension associated with doxazosin . The identity of drugs was masked at each dosage level , but dosage level was not . After r and omization , patients were seen for dose titration as needed at 1 and 3 months per the protocol , but they could return more often until target blood pressure was reached . Subsequently , required visits occurred at 3-month intervals during the first year and at 4-month intervals thereafter . Open-label second-step drugs were added as needed and tolerated . These agents were reserpine ( 0.05 to 0.2 mg/d ) , clonidine ( 0.1 to 0.3 mg twice daily ) , and atenolol ( 25 to 100 mg/d ) . The choice of second-step drug was at the discretion of the treating clinician-investigator . The third-step agent was hydralazine ( 25 to 100 mg twice daily ) . Details of these therapies are provided elsewhere ( 1 ) . Investigators could choose to prescribe open-label antihypertensive drugs other than those provided by the study . However , use of the drug classes under study thiazide diuretics , calcium antagonists , angiotensin-converting enzyme inhibitors , and -adrenergic blockerswas strongly discouraged to avoid dilution of treatment comparisons . When clinical conditions other than uncontrolled hypertension ( for example , angina or heart failure ) were present , drugs from any study class could be used . If a step 1 drug was specifically required for blood pressure control while blinded drug treatment was continued , the step 1 drug could be added as open-label therapy but the dose could not exceed one half the maximum recommended by the Fifth Joint National Committee ( 4 ) . In most such cases , unblinding the patient or the investigator to treatment assignment was not necessary . ( Overall , < 1 % of drug identities were provided to either participant or investigator . ) Any of nine possible open-label drug typesdiuretic , calcium-channel blocker , angiotensin-converting enzyme inhibitor , -adrenergic blocker , atenolol , reserpine , clonidine , hydralazine , and other antihypertensive drug ( which could include nonatenolol -blockers , although drug name was not logged)could be recorded at each visit . Because diuretics , angiotensin-converting enzyme inhibitors , and -blockers are beneficial in preventing or treating heart failure , we call these antihypertensive heart failure drugs . Data on  antihypertensive drug use before study enrollment were collected , but not by drug class . Statistical Analysis Data were analyzed for use of additional drugs according to participants ' r and omized treatment assignments and regardless of continuation of blinded study treatment . The outcomes all heart failure ( treated outside hospital , hospitalized , or fatal ) and hospitalized or fatal heart failure were examined by treatment group for the entire cohort . The time to event for the previously published as-r and omized analyses was the interval from r and omization to first diagnosis of heart failure for patients who had an outcome , or from r and omization to Background Cardiovascular disease and type 2 diabetes are examples of chronic diseases that impose significant morbidity and mortality in the general population worldwide . Most chronic diseases are associated with underlying preventable risk factors , such as elevated blood pressure , high blood glucose or glucose intolerance , high lipid levels , physical inactivity , excessive sedentary behaviours , and overweight/obesity . The occurrence of intermediate outcomes during childhood increases the risk of disease in adulthood . Sugar-sweetened beverages are known to be significant sources of additional caloric intake , and given recent attention to their contribution in the development of chronic diseases , a systematic review is warranted . We will assess whether the consumption of sugar-sweetened beverages in children is associated with adverse health outcomes and what the potential moderating factors are . Methods / Design Of interest are studies addressing sugar-sweetened beverage consumption , taking a broad perspective . Both direct consumption studies as well as those evaluating interventions that influence consumption ( e.g. school policy , educational ) will be relevant . Non-specific or multi-faceted behavioural , educational , or policy interventions may also be included subject to the level of evidence that exists for the other interventions /exposures . Comparisons of interest and endpoints of interest are pre-specified . We will include r and omized controlled trials , controlled clinical trials , interrupted time series studies , controlled before-after studies , prospect i ve and retrospective comparative cohort studies , case – control studies , and nested case – control design s. The MEDLINE ® , Embase , The Cochrane Library , CINAHL , ERIC , and PsycINFO ® data bases and grey literature sources will be search ed . The processes for selecting studies , abstract ing data , and resolving conflicts are described . We will assess risk of bias using design -specific tools . To determine sets of confounding variables that should be adjusted for , we have developed causal directed acyclic graphs and will use those to inform our risk of bias assessment s. Meta- analysis will be conducted where appropriate ; parameters for exploring statistical heterogeneity and effect modifiers are pre-specified . The Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach will be used to determine the quality of evidence for outcomes . Systematic review registration PROSPERO CRD42014009641 BACKGROUND Carotid-femoral pulse wave velocity ( PWV ) , as a parameter of aortic stiffness , is an established marker of cardiovascular risk . There has been increasing use of arterial stiffness parameters combining aortic and muscular stiffness or a parameter derived from PWV - the stiffness index beta ( BETA = ln(systolic/diastolic pressure ) × 2 blood viscosity/pulse pressure × PWV(2 ) ) . The aim of this study was to compare different arterial stiffness parameters in a general population r and om sample . METHODS AND RESULTS In 809 individuals from the Czech post-MONICA study ( aged 54 ± 13.5 years , 47 % men ) , we compared the association of  carotid-femoral PWV ( cfPWV ) , carotid-ankle PWV ( caPWV ) , and BETA  with cardiovascular risk factors , parameters of sub clinical organ damage , and presence of manifest cardiovascular disease . Both cfPWV and caPWV were similarly associated with blood pressure and glucose level , while cfPWV was more strongly associated with age , cholesterol level and glomerular filtration rate whereas caPWV with Sokolow-Lyon index . BETA derived from cfPWV and caPWV was less dependent on blood pressure , while it showed a closer association with coronary heart disease presence , as compared to cfPWV and caPWV . CONCLUSIONS Addition of lower extremity to aortic stiffness has an effect on the association with cardiovascular risk factors while having no effect on the association with manifest cardiovascular disease . Beta transformation of PWV decreases its dependence on blood pressure and may increase its power in cardiovascular risk prediction Isolated systolic hypertension is an important risk factor for cardiovascular disease and results primarily from elastic artery stiffening . Although various drug therapies are used to lower peripheral blood pressure ( BP ) in patients with isolated systolic hypertension , the effects of the 4 major classes of antihypertensive agents on central BP , pulse pressure ( PP ) amplification , and arterial stiffness in this condition are not clear . Fifty-nine patients over the age of 60 years with untreated isolated systolic hypertension ( systolic BP ≥140 mm Hg and diastolic BP ≤90 mm Hg ) were r and omly assigned to receive 1 of the following 4 antihypertensive agents : perindopril , atenolol , lercanidipine , or bendrofluazide  . BP was measured using a mercury sphygmomanometer , and augmentation index and carotid-femoral ( aortic ) pulse wave velocity were measured at baseline , after 2 weeks of placebo therapy , and at the end of 10 weeks of active therapy . Peripheral systolic BP and peripheral PP were reduced similarly after treatment with all 4 classes of drug . However , central PP was only reduced significantly by perindopril , lercanidipine , and bendrofluazide , whereas atenolol had no effect . Lercanidipine reduced the augmentation index , whereas atenolol increased it . Aortic pulse wave velocity was not changed by any of the drugs . In summary , despite similar reductions in peripheral systolic and PPs with the 4 classes of drug , changes in central pressure and augmentation index varied . Because central PP and increased wave reflections are considered important risk factors in patients with isolated systolic hypertension , the choice of therapy may be influenced by these findings in the future
There was no clear evidence that proportional risk reductions in major cardiovascular disease differed by baseline disease history , except for diabetes and chronic kidney disease , for which smaller , but significant , risk reductions were detected .
β blockers were inferior to other drugs for the prevention of major cardiovascular disease events , stroke , and renal failure .
Calcium channel blockers were superior to other drugs for the prevention of stroke .
For the prevention of heart failure , calcium channel blockers were inferior and diuretics were superior to other drug classes .
INTERPRETATION Blood pressure lowering significantly reduces vascular risk across various baseline blood pressure levels and comorbidities .
BACKGROUND The benefits of blood pressure lowering treatment for prevention of cardiovascular disease are well established .
However , the extent to which these effects differ by baseline blood pressure , presence of comorbidities , or drug class is less clear .
We therefore performed a systematic review and meta- analysis to clarify these differences .