Effect of age on blood pressure parameters and risk of cardiovascular death in men. World Salt Awareness Week. Global Risk Assessment to Guide Blood Pressure Management in Cardiovascular Disease Prevention Role of Time-of-Day of Hypertension Treatment on the J-Shaped Relationship Between Blood Pressure and Cardiovascular Risk Relation between insulin and aortic stiffness: a population-based study Legacy Effect of Delayed Blood Pressure-Lowering Pharmacotherapy in Middle-Aged Individuals Stratified by Absolute Cardiovascular Disease Risk: Protocol for a Systematic Review Ten-year legacy effects of baseline blood pressure ‘treatment naivety’ in the Second Australian National Blood Pressure study Effectiveness of blood pressure-lowering drug treatment by levels of absolute risk: post hoc analysis of the Australian National Blood Pressure Study 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. Pulse Pressure Compared With Other Blood Pressure Indexes in the Prediction of 25-Year Cardiovascular and All-Cause Mortality Rates: The Chicago Heart Association Detection Project in Industry Study Reducing cardiovascular disease risk in medically underserved urban and rural communities. Which Patients Does the SPRINT Study Not Apply To and What Are the Appropriate Blood Pressure Goals in These Populations? Outcomes of Combined Cardiovascular Risk Factor Management Strategies in Type 2 Diabetes: The ACCORD Randomized Trial Visit-to-Visit Variability of Blood Pressure and Coronary Heart Disease, Stroke, Heart Failure, and Mortality Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion. Congestive heart failure in renal transplant recipients: risk factors, outcomes, and relationship with ischemic heart disease. Aliskiren alone or with other antihypertensives in the elderly with borderline and stage 1 hypertension: the APOLLO trial. Action Schools! BC: a school-based physical activity intervention designed to decrease cardiovascular disease risk factors in children. Combined influence of cardiorespiratory fitness and body mass index on cardiovascular disease risk factors among 8-18 year old youth: The Aerobics Center Longitudinal Study. Cardiovascular disease risk factors and blood pressure response during exercise in healthy children and adolescents: the European Youth Heart Study. Administration-Time-Dependent Effects of Hypertension Treatment on Ambulatory Blood Pressure in Patients With Chronic Kidney Disease INFLUENCE OF CIRCADIAN TIME OF HYPERTENSION TREATMENT ON CARDIOVASCULAR RISK: RESULTS OF THE MAPEC STUDY Smoking and the risk of incident hypertension in middle-aged and older men. Chocolate consumption in relation to blood pressure and risk of cardiovascular disease in German adults. Blood pressure is associated with occult cardiovascular disease in prospectively studied Hodgkin lymphoma survivors after chest radiation Differences in cardiovascular disease risk when antihypertensive medication adherence is assessed by pharmacy fill versus self-report: the Cohort Study of Medication Adherence among Older Adults (CoSMO) e-Care for heart wellness: a feasibility trial to decrease blood pressure and cardiovascular risk. Physical activity, cardiovascular health, quality of life and blood pressure control in hypertensive subjects: randomized clinical trial Rationale and design of the Optimal Macro-Nutrient Intake Heart Trial to Prevent Heart Disease (OMNI-Heart) How effective are current dietary guidelines for cardiovascular disease prevention in healthy middle-aged and older men and women? A randomized 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. Increased targeting of cardiovascular risk factors in patients with chronic kidney disease does not improve atheroma burden or cardiovascular function. The effects of 12-week psyllium fibre supplementation or healthy diet on blood pressure and arterial stiffness in overweight and obese individuals. Examination of lower targets for low-density lipoprotein cholesterol and blood pressure in diabetes--the Stop Atherosclerosis in Native Diabetics Study (SANDS). Effects of individual risk factors on the incidence of cardiovascular events in the treated hypertensive patients of the Hypertension Optimal Treatment Study. HOT Study Group. Long-term follow-up of cardiovascular risk factors after exercise training in obese children. A controlled study of the effects of the Transcendental Meditation program on cardiovascular reactivity and ambulatory blood pressure. Obstructive sleep apnea and diurnal nondipping hemodynamic indices in patients at increased cardiovascular risk Simultaneous treatment to attain blood pressure and lipid goals and reduced CV risk burden using amlodipine/atorvastatin single-pill therapy in treated hypertensive participants in a randomized controlled trial Comparative effectiveness of aerobic, resistance, and combined training on cardiovascular disease risk factors: A randomized controlled trial Effects of a psychosocial skills training workshop on psychophysiological and psychosocial risk in patients undergoing coronary artery bypass grafting. Impact of elevated blood pressure on mortality from all causes, cardiovascular diseases, heart disease and stroke among Japanese: 14 year follow-up of randomly selected population from Japanese — Nippon data 80 Antihypertensive and antioxidant effects of dietary black sesame meal in pre-hypertensive humans Fish oil in combination with high or low intakes of linoleic acid lowers plasma triacylglycerols but does not affect other cardiovascular risk markers in healthy men. Outcomes of Stage 3–5 Chronic Kidney Disease before End-Stage Renal Disease at a Single Center in Taiwan Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease. Overall findings and differences by age for 316,099 white men. Multiple Risk Factor Intervention Trial Research Group. Effects of dietary saturated, monounsaturated, and n-3 fatty acids on blood pressure in healthy subjects. Hypertensive eye ground changes. Prevalence, relation to blood pressure and prognostic importance. The study of men born in 1913. The effect of farmed trout on cardiovascular risk markers in healthy men. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research Group. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial--clinical implications. The effect of a worksite based walking programme on cardiovascular risk in previously sedentary civil servants [NCT00284479] Added Predictive Value of Night-Time Blood Pressure Variability for Cardiovascular Events and Mortality: The Ambulatory Blood Pressure–International Study Prognostic importance of clinic and home blood pressure recordings in patients with chronic kidney disease. Effect of lifestyle modifications on blood pressure by race, sex, hypertension status, and age Dose Response to Exercise in Women aged 45-75 yr (DREW): design and rationale. Impact of achieved blood pressure on cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial. Cardiovascular disease risk factors, depression symptoms and antidepressant medicine use in the Look AHEAD (Action for Health in Diabetes) clinical trial of weight loss in diabetes Increased visit-to-visit blood pressure variability is associated with worse cardiovascular outcomes in low ejection fraction heart failure patients: Insights from the HEAAL study.
BACKGROUND Elevated blood pressure ( BP ) is a risk factor for cardiovascular disease ( CVD ) , but it remains unclear which component-alone or in combination-is the best predictor . We sought to determine which BP parameters are important predictors of CVD death across a wide age range . METHODS We used a prospect i ve cohort study design with 53,163 men followed for cause-specific death during a median of 5.7 years in the Physicians ' Health Study enrollment cohort . Baseline age , systolic BP and diastolic BP were collected . We calculated relative risks ( RRs ) and their 95 % confidence intervals using Cox proportional hazard models adjusting for major risk factors for CVD , and then stratified by age ( 39 to 49 , 50 to 59 , 60 to 69 , and 70 to 84 years ) . RESULTS There were 459 CVD deaths during follow-up . For each 10 mm Hg increase in systolic BP , the multivariable RRs by ascending age group were 1.46 , 1.43 , 1.24 , and 1.13 . The multivariable RRs for each 10 mm Hg increase in diastolic BP were 1.25 , 1.20 , 1.28 , and 1.07 . Compared with systolic BP , pulse pressure and mean arterial pressure were not consistent predictors across age ranges , and combining systolic BP with another parameter did not improve the model compared with using systolic BP alone in any age group ( all P > .05 ) . CONCLUSIONS In this large cohort of healthy men with no history of hypertension , systolic BP was the most consistent and significant predictor of CVD death across all ages . Diastolic BP was not as strongly associated with risk . Our results support the continuing emphasis on using systolic BP in predicting cardiovascular risk Cardiovascular disease ( CVD ) , including stroke , heart attack and heart failure , is the leading cause of death and disability worldwide . Raised blood pressure ( BP ) is a major cause of CVD , responsible for 62 % of stroke and 49 % of coronary heart disease cases . There is much evidence for a causal relationship between salt intake and BP . The current salt intake in many countries around the world is between 9 g ⁄d and 12 g ⁄d ( ie , 3.6–4.8 g of sodium ) . R and omized trials have demonstrated that a modest reduction in salt intake lowers BP in individuals with raised BP and also in those with ‘ ‘ normal ’ ’ BP . Furthermore , there is a dose-response relationship . Within the range of 12 g ⁄d to 3 g ⁄d , the lower the salt intake , the lower the BP . Because raised BP throughout its range is a major cause of CVD , salt reduction would reduce cardiovascular risk . It was estimated that a reduction of 6 g ⁄d in salt intake would reduce stroke by 24 % and coronary heart disease by 18 % . This would prevent approximately 35,000 stroke and coronary heart disease deaths a year in the United Kingdom and approximately 2.5 million deaths worldwide . Both prospect i ve studies and outcome trials have demonstrated that a lower salt intake is related to a reduced risk of CVD .  Salt reduction is one of the most cost-effective interventions to reduce CVD in both developed and developing countries . For example , the UK salt reduction campaign , which result ed in a fall in salt intake by approximately 10 % ( ie , from 9.5 g ⁄d in 2003 to 8.6 g ⁄d by May 2008 ) , cost just £ 15 million and led to approximately 6000 fewer CVD deaths per year , saving the UK economy approximately £ 1.5 billion per annum according to the recent report by the UK government ’s health advisory agency , the National Institute for Health and Clinical Excellence . In most developed countries , approximately 80 % of salt consumed is added to foods at the stage of manufacturing , and the consumers have no say over how much salt is added . Therefore , to achieve a reduction in population salt intake , it is imperative that the food industry make a gradual and sustained reduction in the amount of salt that is added to all foods . This approach has been successful in the United Kingdom and is now being exp and ed worldwide . World Salt Awareness Week was introduced by the salt reduction action group World Action on Salt and Health ( WASH ) in 2008 . The event serves as a platform for international experts in the fields of hypertension and nephrology to raise the profile of the importance of salt reduction to both the public and health professionals worldwide 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 Several previous studies found that too great a reduction of clinic blood pressure ( BP ) by treatment increased cardiovascular disease ( CVD ) risk , whereas moderate reduction decreased it . Thus , it has been suggested that the relationship between BP and CVD events is J-shaped , with CVD risk decreasing as BP is lowered , and then rising as BP is further decreased . Correlation between BP level and CVD risk , however , is stronger for ambulatory BP monitoring ( ABPM ) than clinical BP measurements . We previously established that the hypertension treatment-time regimen , upon awakening versus at bedtime , exerts differential effect on BP control during the day and nighttime , which translates into a differential degree of CVD risk prevention . We , therefore , investigated the role of hypertension treatment-time scheme on the nature of the relationship between achieved clinic and ambulatory BP and CVD risk in the MAPEC ( Monitorización Ambulatoria para Predicción de Eventos Cardiovasculares , i.e. , Ambulatory Blood Pressure Monitoring for Prediction of Cardiovascular Events ) study , a prospect i ve , open-label , blinded-endpoint trial on 2156 hypertensive patients ( 1044 men/1112 women ) , 55.6 ± 13.6 ( mean ± SD ) yrs of age , r and omized to ingest all prescribed once-a-day hypertension medications upon awakening or the entire daily dose of ≥1 of them at bedtime  . Ambulatory BP was measured for 48-h at baseline and annually thereafter , and more frequently ( quarterly ) when adjustment of treatment was necessary . After a median follow-up of 5.6 yrs , a J-shaped relationship was detected between total CVD events and clinic as well as awake BP mean , but only for the group of patients ingesting all medications upon awakening . The relationship was different in the group of patients who ingested ≥1 medications at bedtime ; the risk of CVD events progressively diminished in a linear , rather than J-shaped , manner with treatment-induced decrease in awake BP mean . The adjusted hazard ratio of CVD events was significantly lower with the progressive reduction in the asleep BP mean , independent of the hypertension treatment-time regimen . There was no single major event , i.e. , CVD death , myocardial infa rct ion , or stroke , in patients who achieved an asleep systolic BP mean < 103 mm Hg . Our findings indicate that bedtime hypertension treatment is not associated with a J-shaped relationship between achieved BP and CVD risk . The decreased CVD risk associated with the progressive reduction in asleep BP , more feasible by bedtime than morning hypertension treatment , has clinical implication s , in particular , the need to consider the proper timing of hypertension medications , in conjunction with ABPM for proper assessment of BP control , as an improved and potentially safer means of reducing CVD risk of hypertensive patients . ( Author correspondence : rhermida@uvigo.es Recent studies have suggested that a high pulse wave velocity ( PWV ) , a measure of aortic stiffness , may be a stronger risk factor for cardiovascular disease ( CVD ) than a high blood pressure ( BP ) . The relation between insulin , believed to play an important role in the development and clinical course of high BP , and PWV is not yet clear . Therefore , we decided to examine the relationship between insulin and PWV in a large population -based study . The study population consisted of a r and om sample of 1213 women and 1207 men ( age range , 41–72 years ) without a history of myocardial infa rct ion or stroke .  Fasting insulin was determined together with conventional risk factors for CVD . PWV was recorded transcutaneously by a mechanical electrical principle with one transducer positioned over the left common carotid artery , and another over the left femoral artery . In univariate analysis , insulin was highly significantly related to PWV ( st and ardized regression coefficient : 0.0669±0.0051 ; P<0.001 ) . In multivariate analysis , controlling for all well-established predictors of PWV , such as age , systolic BP or mean BP and pulse pressure , sex , and heart rate , as well as controlling for conventional risk factors for CVD and use of BP-lowering drugs , the level of insulin remained a significant predictor of PWV ( st and ardized regression coefficient : 0.0122±0.0048 ; P=0.012 ) . In conclusion , the present study found that a higher insulin level  was related to a higher PWV . This indicates that hyperinsulinaemia may affect BP and risk of CVD by increasing aortic stiffness 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 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 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 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 We compared the relations of 4 blood pressure ( BP ) indexes ( pulse pressure [ PP ] , systolic BP [ SBP ] , diastolic BP [ DBP ] , and mean arterial pressure [ MAP ] ) with 25-year mortality rates for coronary heart disease ( CHD ) , cardiovascular disease ( CVD ) , and all causes in younger , middle-aged , and older men and women by using data from a long-term prospect i ve epidemiological study of employed persons who were screened between 1967 and 1973 . A single supine BP measurement was obtained at baseline . Vital status was determined through 1995 . We report on 5 groups ( total , 28 360 participants ) consisting of men age 18 to 39 , 40 to 59 , and 60 to 74 years and of women age 40 to 59 and 60 to 74 years who were not receiving antihypertensive treatment , had no history of CHD , and did not have diabetes . Cox proportional hazards analyses were used to determine multivariate-adjusted hazard ratios with a 1-SD higher value for each BP index ; Wald & khgr;2 tests were used to compare the strength of relations . Relations of PP were less strong than were those of SBP for all end points in all age/gender groups . SBP or MAP showed the strongest relations to all end points in all age/gender groups ( hazard ratio , 1.17 to 1.36 ) . The relations of SBP to death were stronger than were those of DBP , except for middle-aged men and for CVD in women . DBP showed significant positive associations with death , after control for SBP , in middle-aged participants . In conclusion , these data indicate that the long-term risk of high BP should be assessed mainly on the basis of SBP or of SBP and DBP together , not on the basis of PP , in apparently healthy adults OBJECTIVES The aim of this study is to evaluate methods for lowering cardiovascular disease ( CVD ) risk in asymptomatic urban and rural underserved subjects . BACKGROUND Medically underserved population s are at increased CVD risk , and systems to lower CVD risk are needed . Nurse management ( NM ) and telemedicine ( T ) systems may provide low-cost solutions for this care . METHODS We r and omized 465 subjects without overt CVD , with Framingham CVD risk > 10 % to NM with 4 visits over 1 year , or NM plus T to facilitate weight , blood pressure ( BP ) , and physical activity reporting . The study goal was to reduce CVD risk by 5 % . RESULTS Three hundred eighty-eight subjects completed the study . Cardiovascular disease risk fell by ≥ 5 % in 32 % of the NM group and 26 % of the T group ( P , nonsignificant ) . In hyperlipidemic subjects , total cholesterol decreased ( NM -21.9 ± 39.4 , T -22.7 ± 41.3 mg/dL ) significantly . In subjects with grade II hypertension ( systolic BP ≥ 160 mm Hg , 24 % of subjects ) , both NM and T groups had a similar BP response ( average study BP : NM 147.4 ± 17.5 , T 145.3 . ± 18.4 , P is nonsignificant ) , and for those with grade I hypertension ( 37 % of subjects ) , T had a lower average study BP compared to NM ( NM 140.4 ± 16.9 , T 134.6 ± 15.0 , P = .058 ) . In subjects at high risk ( Framingham score ≥ 20 % ) , risk fell 6.0 % ± 9.9 % ; in subjects at intermediate risk ( Framingham score ≥ 10 , < 20 ) , risk fell 1.3 % ± 4.5 % ( P < .001 compared to high-risk subjects ) . Medication adherence was similar in both high- and intermediate-risk subjects . CONCLUSIONS In 2 underserved population s , CVD risk  was reduced by a nurse intervention ; T did not add to the risk improvement . Reductions in BP and blood lipids occurred in both high- and intermediate-risk subjects with greatest reductions noted in the high-risk subjects . Frequent communication using a nurse intervention contributes to improved CVD risk in asymptomatic , underserved subjects with increased CVD risk . Telemedicine did not change the effectiveness of the nurse intervention 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 : OBJECTIVE To compare effects of combinations of st and ard and intensive treatment of glycemia and either blood pressure ( BP ) or lipids in the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial . RESEARCH DESIGN AND METHODS ACCORD enrolled 10,251 type 2 diabetes patients aged 40–79 years at high risk for cardiovascular disease ( CVD ) events . Participants were r and omly assigned to hemoglobin A1c goals of < 6.0 % ( < 42 mmol/mol ; intensive glycemia ) or 7.0–7.9 % ( 53–63 mmol/mol ; st and ard glycemia ) and then r and omized a second time to either 1 ) systolic BP goals of < 120 mmHg ( intensive BP ) or < 140 mmHg ( st and ard BP ) or 2 ) simvastatin plus fenofibrate ( intensive lipid ) or simvastatin plus placebo ( st and ard lipid ) . Proportional hazards models were used to assess combinations of treatment assignments on the composite primary ( deaths due to CVD , nonfatal myocardial infa rct ion [ MI ] , and nonfatal stroke ) and secondary outcomes . RESULTS In the BP trial , risk of the primary outcome was lower in the groups intensively treated for glycemia ( hazard ratio [ HR ] 0.67 ; 95 % CI 0.50–0.91 ) , BP ( HR 0.74 ; 95 % CI 0.55–1.00 ) , or both ( HR 0.71 ; 95 % CI 0.52–0.96 ) compared with combined st and ard BP and glycemia treatment . For secondary outcomes , MI was significantly reduced by intensive glycemia treatment and stroke by intensive BP treatment ; most other HRs were neutral or favored intensive treatment groups . In the lipid trial , the general pattern of results showed no evidence of benefit of intensive regimens ( whether single or combined ) compared with combined st and ard lipid and glycemia treatment . The mortality HR was 1.33 ( 95 % CI 1.02–1.74 ) in the st and ard lipid/intensive glycemia group compared with the st and ard lipid/st and ard glycemia group . CONCLUSIONS In the ACCORD BP trial , compared with combined st and ard treatment , intensive BP or intensive glycemia treatment alone improved major CVD outcomes , without additional benefit from combining the two . In the ACCORD lipid trial , neither intensive lipid nor glycemia treatment produced an overall benefit , but intensive glycemia treatment increased mortality 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 , CONTEXT Extrapolations from observational studies and short-term intervention trials suggest that population -wide moderation of salt intake might reduce cardiovascular events . OBJECTIVE To assess whether 24-hour urinary sodium excretion predicts blood pressure ( BP ) and health outcomes . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve population study , involving 3681 participants without cardiovascular disease ( CVD ) who are members of families that were r and omly enrolled in the Flemish Study on Genes , Environment , and Health Outcomes ( 1985 - 2004 ) or in the European Project on Genes in Hypertension ( 1999 - 2001 ) . Of 3681 participants without CVD , 2096 were normotensive at baseline and 1499 had BP and sodium excretion measured at baseline and last follow-up ( 2005 - 2008 ) . MAIN OUTCOME MEASURES Incidence of mortality and morbidity and association between changes in BP and sodium excretion . Multivariable-adjusted hazard ratios ( HRs ) express the risk in tertiles of sodium excretion relative to average risk in the whole study population . RESULTS Among 3681 participants followed up for a median 7.9 years , CVD deaths decreased across increasing tertiles of 24-hour sodium excretion , from 50 deaths in the low ( mean , 107 mmol ) , 24 in the medium ( mean , 168 mmol ) , and 10 in the high excretion group ( mean , 260 mmol ; P < .001 ) , result ing in respective death rates of 4.1 % ( 95 % confidence interval [ CI ] , 3.5%-4.7 % ) , 1.9 % ( 95 % CI , 1.5%-2.3 % ) , and 0.8 % ( 95 % CI , 0.5%-1.1 % ) . In multivariable-adjusted analyses , this inverse association retained significance ( P = .02 ) : the HR in the low tertile was 1.56 ( 95 % CI , 1.02 - 2.36 ; P = .04 ) . Baseline sodium excretion predicted neither total mortality ( P = .10 ) nor fatal combined with nonfatal CVD events ( P = .55 ) . Among 2096 participants followed up for 6.5 years , the risk of hypertension did not increase across increasing tertiles ( P = .93 ) . Incident hypertension was 187 ( 27.0 % ; HR , 1.00 ; 95 % CI , 0.87 - 1.16 ) in the low , 190 ( 26.6 % ; HR , 1.02 ; 95 % CI , 0.89 - 1.16 ) in the medium , and 175 ( 25.4 % ; HR , 0.98 ; 95 % CI , 0.86 - 1.12 ) in the high sodium excretion group . In 1499 participants followed up for 6.1 years , systolic blood pressure increased by 0.37 mm Hg per year ( P < .001 ) , whereas sodium excretion did not change ( -0.45 mmol per year , P = .15 ) . However , in multivariable-adjusted analyses , a 100-mmol increase in sodium excretion was associated with 1.71 mm Hg increase in systolic blood pressure ( P.<001 ) but no change in diastolic BP . CONCLUSIONS In this population -based cohort , systolic blood pressure , but not diastolic pressure , changes over time aligned with change in sodium excretion , but this association did not translate into a higher risk of hypertension or CVD complications . Lower sodium excretion was associated with higher CVD mortality Cardiovascular disease ( CVD ) is the major cause of death in renal transplant recipients ( RTR ) . Several cohort studies have examined CVD in RTR , but none have addressed the development of congestive heart failure ( CHF ) . CHF would hypothetically be a frequent and prognostically important event in RTR . A retrolective cohort study was , therefore , conducted in two Canadian centers to describe the incidence , risk factors for , and interrelationships between de novo CHF , de novo ischemic heart disease ( IHD ) , and mortality in 638 consecutive adult RTR who were free of cardiac disease at 1 yr posttransplant . Detailed clinic and hospital records were available for 99 % of patients . Median follow-up was 7 yr ( range , 1 to 28 yr ) . De novo CHF occurred as frequently as de novo IHD ( 1.26 versus 1.22 events/100 patient-years , respectively ) and appeared to carry a similar prognosis ( relative risk for death , 1.78 [ confidence interval , 1.21 to 2.61 ] for CHF versus 1.50 [ 1.05 to 2.13 ] for IHD ) . The incidence of CHF was considerably higher than that in the Framingham cohort , whereas the incidence of IHD was not , suggesting that renal transplantation might correspond more to a state of " accelerated heart failure " than to " accelerated atherosclerosis . " Age , diabetes , gender , BP , and anemia were identified as independent risk factors for de novo CHF , whereas age , diabetes , gender , BP , and rejection were independent risk factors for de novo IHD . Optimal strategies for treatment of BP and anemia in RTR will need to be determined in r and omized controlled trials AIMS We studied the unclear question whether blood pressure ( BP ) lowering reduces cardiovascular disease ( CVD ) in elderly individuals with systolic BP < 160 mm Hg . METHODS AND RESULTS We initiated a r and omized placebo-controlled stratified 2 × 2 factorial clinical trial evaluating the effects of BP lowering in 11 000 elderly individuals with systolic blood pressure ( SBP ) between 130 and 159 mm Hg , for 5 years . Following 5-week active run-in , participants were r and omized to aliskiren ( 300 mg ) or placebo , and to an additional antihypertensive [ hydrochlorothiazide ( 25 mg ) or amlodipine ( 5 mg ) ] , or their respective placeboes . Study was terminated by sponsor after 1759 subjects ( age 72.1 ± 5.2 years , 88 % receiving at least one antihypertensive ) were r and omized and followed for 0.6 year . Study drugs were well tolerated with few serious adverse events during run-in and after r and omization , with no significant differences between treatment groups . By design , three levels of BP reductions were achieved , adjusted mean BP reductions of 3.5/1.7 mm Hg ( P < 0.001 ) by aliskiren , 6.8/3.3 mm Hg ( P < 0.001 ) by hydrochlorothiazide or amlodipine , and 10.3/5.0 mm Hg ( P < 0.001 ) by double therapy compared with placebo . Twenty-five major CVD events occurred . Non-significant trends towards fewer CVD events with greater BP reductions are evident : hazard ratios ( HR ) 0.82 [ 95 % confidence interval ( CI ) : 0.37 - 1.81 ] for 3.5 mm Hg SBP reduction ; HR 0.45 ( 95 % CI : 0.19 - 1.04 ) for 6.8 mm Hg ; and HR 0.25 ( 0.05 - 1.18 ) for 10.3 mm Hg reduction for primary composite of CV death , MI , stroke , or significant heart failure . CONCLUSIONS Sizeable reductions in BP , with potential for substantial CVD reduction , can be safely achieved using combinations of BP drugs in the elderly with normal high and Stage 1 hypertension . CLINICAL TRIAL REGISTRATION NCT01259297 OBJECTIVE Our primary objective was to determine whether a novel ' active school ' model -- Action Schools ! BC -- improved the cardiovascular disease ( CVD ) risk profile in elementary-school children . Our secondary objective was to determine the percentage of children with elevated CVD risk factors . METHODS We undertook a cluster-r and omized controlled school-based trial with 8 elementary schools across 1 school year , in British Columbia , Canada , beginning in 2003 . Boys and girls ( n=268 , age 9 - 11 years ) were r and omly assigned ( by school ) to usual practice ( UP , 2 schools ) or intervention ( INT , 6 schools ) groups . We assessed change between groups in cardiovascular fitness ( 20-m Shuttle Run ) , blood pressure ( BP ) , and body mass index ( BMI , wt/ht(2 ) ) . We evaluated total cholesterol ( TC ) , total : high-density cholesterol ( TC : HDL-C ) , low-density lipoprotein , apolipoprotein B , C-reactive protein and fibrinogen on a subset of volunteers ( n=77 ) . RESULTS INT children had a 20 % greater increase in fitness and a 5.7 % smaller increase in BP compared with children attending UP schools ( P<0.05 ) . Forty five percent of children had at least one elevated risk factor ( fitness , BP or BMI ) at baseline . There were no significant differences between groups for change in BMI or in any of the blood variables . CONCLUSION Action Schools ! BC was an effective school-based physical activity model for improving the CVD risk profile of elementary-school children . Our multi-component intervention exposed children to fitness enhancing physical activity . It may be important for education stakeholders to adequately re source the delivery of the active school models if cardiovascular health benefits are to be achieved on a population basis OBJECTIVE The purpose of this study was to examine differences in cardiovascular disease ( CVD ) risk factors across four cross-tabulated groups of cardiorespiratory fitness and body mass index in 8- to 18-year-old children and adolescents . METHODS The sample included 296 boys and 188 girls ( mean age=15.7 years ) participating in the Aerobics Center Longitudinal Study . Participants were cross tabulated into four groups using a median split of age-adjusted treadmill time to exhaustion ( TM ) and body mass index ( BMI ) . Group differences in CVD risk factors ( blood pressure [ BP ] , fasting total cholesterol [ TC ] , low density lipoprotein-cholesterol [ LDL-C ] , high density lipoprotein-cholesterol [ HDL-C ] , TC : HDL-C , triglycerides [ TG ] , glucose , and a metabolic syndrome score ) were examined by ANCOVA , controlling for age . RESULTS In males , significant differences across groups were observed for systolic BP , mean arterial pressure ( MAP ) , TC , LDL-C , TC : HDL-C and the metabolic syndrome score ( p<0.05 ) . In females , only TG was significantly different across groups ( p<0.05 ) . A trend for significance was also observed for DBP and TG in males ( p=0.09 to 0.11 ) and diastolic BP , MAP , HDL-C , and the metabolic syndrome score in females ( p=0.14 to 0.16 ) . In general , males and females in the low BMI group , either fit or unfit , had lower BP and blood lipid values than those in the high BMI group . In both sexes , the high BMI /low fit group had the highest ( most adverse ) metabolic syndrome score . CONCLUSION This study utilized a unique approach to examine the possible interaction of fitness and fatness on CVD risk factors in children and adolescents . The results provide some evidence for the consideration of both variables when interpreting CVD risk factors in young people Raised blood pressure ( BP ) response during exercise independently predicts future hypertension . Subjects with higher BP in childhood also have elevated BP later in life . Therefore , the factors related to the regulation of exercise BP in children needs to be well understood . We hypothesized that physiological cardiovascular disease ( CVD ) risk factors would influence BP response during exercise in children and adolescents . This is a cross-sectional study of 439 Danish third- grade children and 364 ninth- grade adolescents .  Systolic blood pressure ( SBP ) was measured with sphygmomanometer during a maximal aerobic fitness test . Examined CVD risk factors were high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol , triglyceride , homeostasis model of assessment of insulin resistance ( HOMA-IR ) score , body mass index ( BMI ) , waist circumference , and aerobic fitness . A r and om effect model was used to test the hypotheses . In boys  , HOMA-IR score and BMI were positively related to SBP response during exercise ( β = 1.03 , P = 0.001 , and β = 0.58 , P = 0.017 , respectively ) . The effects sizes of HOMA-IR score and BMI and the significance levels only changed slightly ( β = 0.91 , P = 0.004 , and β = 0.43 , P = 0.08 , respectively ) when the two variables were added in the same model . A significant positive association was observed between aerobic fitness and SBP response in girls ( β = 3.13 and P = 0.002 ) . HOMA-IR score and BMI were found to be positively related to the SBP response in male children and youth . At least partly , adiposity and insulin sensitivity seem to influence exercise SBP through different mechanisms . The positive relationship observed between aerobic fitness and SBP response in girls remains unexplainable for us , although post hoc analyses revealed that it was the case in the ninth grade rs only Many published prospect i ve trials have reported clinical ly meaningful morning-evening , treatment-time differences in the blood pressure (BP)-lowering efficacy , duration of action , and safety of most classes of hypertension medications . Most important , it was recently documented that routine ingestion of the full daily dose of ≥1 hypertension medications at bedtime , compared with ingestion of all of them upon awakening , significantly reduces cardiovascular disease ( CVD ) events . Nocturnal hypertension and non-dipping ( < 10 % decline in the asleep relative to the awake BP mean ) , as determined by ambulatory BP monitoring ( ABPM ) , are frequent in chronic kidney disease ( CKD ) and both are associated with increased CVD risk . Here , we investigated the influence of hypertension treatment time on the circadian BP pattern and degree of BP control of hypertensive patients with CKD evaluated by 48-h ABPM . This cross-sectional study evaluated 2659 such patients ( 1585 men/1074 women ) , 64.9 ± 13.2 ( mean ± SD ) yrs of age , enrolled in the Hygia Project , involving primary care centers of northwest Spain and design ed to evaluate prospect ively CVD risk by ABPM ; 1446 were ingesting all BP-lowering medications upon awakening , whereas 1213 patients were ingesting ≥1 medications at bedtime . Among the latter , 359 patients were ingesting all medications at bedtime , whereas 854 were ingesting the full daily dose of some medications upon awakening and the others at bedtime . Those ingesting all medications upon awakening had significantly higher total cholesterol and low-density lipoprotein ( LDL ) cholesterol than those ingesting ≥1 medications at bedtime . Moreover , patients ingesting all medications at bedtime had the lowest fasting glucose , serum creatinine , and uric acid . Ingestion of ≥1 medications at bedtime was significantly associated with lower asleep systolic ( SBP ) and diastolic ( DBP ) BP means than treatment with all medications upon awakening . The sleep-time relative SBP decline was significantly attenuated in patients ingesting all medications upon awakening ( p < .001 ) . Thus , the prevalence of non-dipping was significantly higher when all hypertension medications were ingested upon awakening ( 68.3 % ) than when ≥1 of them was ingested at bedtime ( 54.2 % ; p < .001 between groups ) , and even further attenuated ( 47.9 % ) when all of them were ingested at bedtime ( p < .001 ) . Additionally , the prevalence of a riser BP pattern , associated with highest CVD risk , was much greater ( 21.5 % ) among patients ingesting all medications upon awakening , compared with those ingesting some ( 15.7 % ) or all medications at bedtime ( 10.6 % ; p < .001 between groups ) , independent of CKD severity ( disease stage ) . The latter group also showed a significantly higher prevalence of properly controlled ambulatory BP ( p < .001 ) that was achieved by a significantly lower number of hypertension medications ( p < .001 ) compared with patients treated upon awakening . Our findings demonstrate significantly lower asleep SBP and DBP means and attenuated prevalence of a blunted nighttime BP decline , i.e. , lower prevalence of markers of CVD risk , in patients with CKD ingesting hypertension medications at bedtime than in those ingesting all of them upon awakening . These collective findings indicate that bedtime hypertension treatment , in conjunction with proper patient evaluation by ABPM to corroborate the diagnosis of hypertension and avoid treatment-induced nocturnal hypotension , should be the preferred therapeutic scheme for CKD . ( Author correspondence : rhermida@uvigo.es Clinical studies have documented morning-evening , administration-time differences of several different classes of hypertension medications in blood pressure (BP)-lowering efficacy , duration of action , safety profile , and /or effects on the circadian BP pattern . In spite of these published findings , most hypertensive subjects , including those under combination therapy  , are instructed by their physicians and pharmacists to ingest all of their BP-lowering medications in the morning . The potential differential reduction of cardiovascular ( CVD ) morbidity and mortality risk by a bedtime versus upon-awakening treatment schedule has never been evaluated prospect ively . The prospect i ve MAPEC study was specifically design ed to test the hypothesis that bedtime chronotherapy with ≥1 hypertension medications exerts better BP control and CVD risk reduction than conventional therapy , i.e. , all medications ingested in the morning . A total of 2156 hypertensive subjects , 1044 men/1112 women , 55.6 ± 13.6 ( mean ± SD ) yrs of age , were r and omized to ingest all their prescribed hypertension medications upon awakening or ≥1 of them at bedtime . At baseline , BP was measured at 20-min intervals from 07:00 to 23:00 h and at 30-min intervals at night for 48 h. Physical activity was simultaneously monitored every min by wrist actigraphy to accurately determine the beginning and end of daytime activity and nocturnal sleep . Identical assessment was scheduled annually and more frequently ( quarterly ) if treatment adjustment was required . Despite lack of differences in ambulatory BP between groups at baseline , subjects ingesting medication at bedtime showed at their last available evaluation significantly lower mean sleep-time BP , higher sleep-time relative BP decline , reduced prevalence of non-dipping ( 34 % versus 62 % ; p < .001 ) , and higher prevalence of controlled ambulatory BP ( 62 % versus 53 % ; p < .001 ) . After a median follow-up of 5.6 yrs , subjects ingesting ≥1 BP-lowering medications at bedtime exhibited a significantly lower relative risk of total CVD events than those ingesting all medications upon awakening ( 0.39 [ 0.29–0.51 ] ; number of events 187 versus 68 ; p < .001 ) . The difference between the treatment-time groups in the relative risk of major events ( including CVD death , myocardial infa rct ion , ischemic stroke , and hemorrhagic stroke ) was also highly statistically significant ( 0.33 [ 0.19–0.55 ] ; number of events : 55 versus 18 ; p < .001 ) . The progressive decrease in asleep BP and increase in sleep-time relative BP decline towards a more normal dipping pattern , two novel therapeutic targets requiring proper patient evaluation by ambulatory BP , were best achieved with bedtime therapy , and they were the most significant predictors of event-free survival . Bedtime chronotherapy with ≥1 BP-lowering medications , compared to conventional upon-waking treatment with all medications , more effectively improved BP control , better decreased the prevalence of non-dipping , and , most importantly , significantly reduced CVD morbidity and mortality . ( Author correspondence : rhermida@uvigo.es BACKGROUND Cigarette smoking is a known risk factor for cardiovascular disease ( CVD ) , but its relationship to the development of hypertension is unclear . Previous epidemiological studies have shown inconsistent results , having demonstrated inverse and positive associations between cigarette smoking and the development of hypertension . METHODS We analyzed 13,529 male participants from the Physicians ' Health Study free of baseline hypertension and CVD who provided information about smoking status . Smoking status was categorized as never , past , or current < 20 cigarettes/day , or current > or = 20 cigarettes/day .  Incident hypertension was defined as either the initiation of antihypertensive treatment , self-reported systolic blood pressure ( BP ) > or = 140 mm Hg , or diastolic BP > or = 90 mm Hg . RESULTS Over a median follow-up of 14.5 years , 4,904 men developed hypertension .  We modeled the risk of developing hypertension by baseline smoking status adjusting for known risk factors for hypertension or CVD . In a fully adjusted Cox proportional hazards model , we found that compared with never smokers , past smokers and current smokers had corresponding relative risks ( RRs ) of 1.08 and 1.15 of developing hypertension . The risk for smokers did not appear to differ based on number of cigarettes smoked daily . Further , the RR of hypertension was higher for men with normal vs. prehypertensive levels of systolic ( SBP ) or diastolic BP ( DBP ) . CONCLUSIONS This prospect i ve cohort data suggests that cigarette smoking may be a modest but important risk factor for the development of hypertension AIMS To investigate the association of chocolate consumption with measured blood pressure ( BP ) and the incidence of cardiovascular disease ( CVD ) . METHODS AND RESULTS Dietary intake , including chocolate , and BP were assessed at baseline ( 1994 - 98 ) in 19 357 participants ( aged 35 - 65 years ) free of myocardial infa rct ion ( MI ) and stroke and not using antihypertensive medication of the Potsdam arm of the European Prospect i ve Investigation into Cancer and Nutrition . Incident cases of MI ( n = 166 ) and stroke ( n = 136 ) were identified after a mean follow-up of approximately 8 years . Mean systolic BP was 1.0 mmHg [ 95 % confidence interval ( CI ) -1.6 to -0.4 mmHg ] and mean diastolic BP 0.9 mmHg ( 95 % CI -1.3 to -0.5 mmHg ) lower in the top quartile compared with the bottom quartile of chocolate consumption . The relative risk of the combined outcome of MI and stroke for top vs. bottom quartiles was 0.61 ( 95 % CI 0.44 - 0.87 ; P linear trend = 0.014 ) . Baseline BP explained 12 % of this lower risk ( 95 % CI 3 - 36 % ) . The inverse association was stronger for stroke than for MI . CONCLUSION Chocolate consumption appears to lower CVD risk , in part through reducing BP . The inverse association may be stronger for stroke than for MI . Further research is needed , in particular r and omized trials Abstract The objectives of this study were to prospect ively screen a cohort of asymptomatic long-term survivors of Hodgkin lymphoma ( HL ) treated with chest irradiation  for occult cardiovascular disease ( CVD ) , and correlate screen-detected disease with prospect ively measured cardiovascular risk factors ( CRFs ) . A total of 182 HL survivors treated with chest irradiation ( median follow-up time 14.8 years ) were enrolled and underwent prospect i ve CRF measurement and resting and stress echocardiography to assess coronary artery disease (CAD)/valve disease and left ventricular systolic dysfunction ( LVSD ) . Forty-seven ( 26 % ) patients had occult CAD/valve disease and /or LVSD . LVSD was not correlated with CRFs . Controlling for treatment factors , hypertension ( odds ratio [ OR ] = 3.0 ) and elevated high-sensitivity C-reactive protein ( hs-CRP ) ( OR = 2.7 ) increased the likelihood of occult CAD/valve disease . Risk of CAD/valve disease rose exponentially with increasing blood pressure ( BP ) values , even in the normal range . Our findings suggest that BP screening may be useful in determining those survivors at greatest risk for occult CVD Background : Pharmacy refill adherence assesses the medication-filling behaviors , whereas self-report adherence assesses the medication-taking behaviors . We contrasted the association of pharmacy refill and self-reported antihypertensive medication adherence with blood pressure ( BP ) control and cardiovascular disease ( CVD ) incidence . Methods and results : Adults ( n = 2075 ) from the prospect i ve Cohort Study of Medication Adherence among Older Adults recruited between August 2006 and September 2007 were included .  Antihypertensive medication adherence was determined using a pharmacy refill  measure , medication possession ratio ( MPR ; low , medium , and high MPR : < 0.5 , 0.5 to < 0.8 , and ≥0.8 , respectively ) and a self-reported measure , eight-item Morisky Medication Adherence Scale ( MMAS-8 ; low , medium , and high MMAS-8 : < 6 , 6 to < 8 , and 8 , respectively ) . Incident CVD events ( stroke , myocardial infa rct ion , congestive heart failure , or CVD death ) through February 2011 were identified and adjudicated . The prevalence of low , medium , and high adherence was 4.5 , 23.7 , and 71.8 % for MPR and 14.0 , 34.3 , and 51.8 % for MMAS-8 , respectively . During a median of 3.8 years ’ follow-up , 240 ( 11.5 % ) people had a CVD event . Low MPR and low MMAS-8 were associated with uncontrolled BP at baseline and during follow up . After multivariable adjustment and compared to those with high MPR , the hazard ratios for CVD associated with medium and low MPR were 1.17 [ 95 % confidence interval ( CI ) 0.87–1.56 ) ] and 1.87 ( 95 % CI : 1.06–3.30 ) , respectively . Compared to those with high MMAS-8 , the hazard ratios ( 95 % CI ) for MMAS-8 for medium and low MMAS-8 were 1.04 ( 0.79–1.38 ) and 0.89 ( 0.58–1.35 ) , respectively . Conclusion : While both adherence measures were associated with BP control  , pharmacy refill but not self-report antihypertensive medication adherence was associated with incident CVD . The differences in these associations may be because of the distinctions in what each adherence measure assesses BACKGROUND Pharmacist- or nurse-led team care decreases  patient blood pressure ( BP ) and cardiovascular disease ( CVD ) risk . PURPOSE To evaluate whether a Web-based dietitian-led ( WD ) team care intervention was feasible and result ed in decreased BP , CVD risk , and weight compared to usual care ( UC ) . METHODS Electronic health record ( EHR ) data identified patients aged 30 - 69 years with BMI > 26 , elevated BP , and 10%-25 % 10-year Framingham CVD risk who were registered patient website users . Patients with uncontrolled BP at screening were r and omized to UC or WD , which included a home BP monitor , scale , and dietitian team care . WD participants had a single in-person dietitian visit to obtain baseline information and create a plan to reduce CVD risk . Planned follow-up occurred via secure messaging to report BP , weight , and fruit and vegetable intake and receive ongoing feedback . If needed , dietitians encouraged patients and their physicians to intensify antihypertensive and lipid-lowering medications . Primary outcomes were change in systolic BP and weight loss ≥4 kg at 6 months . Feasibility outcomes included intervention utilization and satisfaction . RESULTS Between 2010 and 2011 , a total of 90 of 101 participants completed 6-month follow-ups . The WD group had higher rates of secure messaging utilization and patient satisfaction . The WD group lost significantly more weight than the UC group ( adjusted net difference=-3.2 kg , 95 % CI=-5.0 , -1.5 , p<0.001 ) and was more likely to lose ≥4 kg ( adjusted relative risk [RRadj]=2.96 , 95 % CI=1.16 , 7.53 ) . BP control and CVD risk reduction were greater in WD than UC , but differences were not statistically significant . CONCLUSIONS WD intervention was feasible and result ed in decreased weight , BP , and CVD risk . A larger trial is justified . TRIAL REGISTRATION NUMBER Trial Registration Number : NCT01077388 Background Physical activity ( PA ) promotes cardiovascular health and health related quality of life ( HRQoL ) , although the effect of that on blood pressure ( BP ) control has rarely been studied in hypertensive subjects . Our aim was to evaluate the effectiveness of a PA intervention programme on cardiovascular disease ( CVD ) risk , HRQoL and BP control  in hypertensive subjects . Methods A r and omized clinical trial , with a PA intervention programme of 9 months duration , comprising a walking group of 120 min/week , supervised , and with socio-cultural activities .  Participants were 207 hypertensive subjects ( 68.2 years , 76.8 % women ) .  PA ( IPAQ-s ) , diet , CVD risk , BP , BMI , smoking , and HRQoL ( SF-36 ) were assessed at baseline and at the end of the intervention . Changes in CVD risk and in HRQoL during the intervention was calculated ( end-baseline score ) . Multivariate models were applied . Results In multivariate models , the PA intervention programme , with no modification of the diet , decreased CVD risk ( − 1.19 points ) and the systolic BP ( − 8.68 mmHg ) , and increased some areas of HRQoL ( 4.45 to 14.62 points ) . An increase in the percentage of subjects with controlled BP was observed by the PA programme itself ( OR 5.395 to 5.785 according to multivariate models ) , and by the changes during the intervention in the decrease in CVD risk ( OR 0.609 ) and in the increase in the HRQoL in physical component summary ( OR 1.041 ) , role physical ( OR 1.010 ) , and bodily pain ( OR 1.014 ) , independently of controlled BP at baseline . Conclusions This PA intervention programme  improved cardiovascular health and HRQoL , and favoured BP control in primary care users with hypertension . Trial registration Clinical trials.gov ID NCT02767739 ; Trial registered on May 5th , 2016 . Retrospectively registered Background The DASH ( Dietary Approaches to Stop Hypertension ) diet is a carbohydrate-rich , reduced-fat diet that lowers blood pressure ( BP ) and LDL-cholesterol . Whether partial replacement of some carbohydrate ( C ) with either protein ( P ) or unsaturated fat ( U ) can further improve these and other cardiovascular ( CVD ) risk factors is unknown . Methods OmniHeart is a r and omized , three-period , crossover feeding study design ed to compare the effects on BP and blood lipids of a carbohydrate-rich diet ( CARB , similar to the DASH diet ) with a diet rich in protein ( PROT , predominantly from nonmeat sources ) and a diet rich in unsaturated fat ( UNSAT , predominantly monounsaturated ) . Throughout feeding ( run in and the three intervention periods ) , participants are provided with all of their meals that meet the nutrient profile of their assigned diet . Calorie intake is adjusted to maintain weight . The target sample size is 160 ( 50 % African-American ) . Participants are adults , aged 30 or older , with prehypertension or Stage 1 hypertension ( systolic BP 120–159 or diastolic BP 80–99 mmHg ) . The primary outcome variables are systolic BP and LDL-cholesterol . Secondary outcomes are diastolic BP , HDL-cholesterol , and triglycerides . Other outcome variables are total cholesterol , apolipoproteins VLDL-apoB , VLDL-apoCIII , apolipoprotein B , non-HDL cholesterol , and lipoprotein(a ) , and insulin resistance , as measured by Homeostasis Model Assessment ( HOMA ) . Conclusions OMNI-Heart should advance our fundamental knowledge of the effects of diet on both traditional and emerging risk factors , and , in the process , guide policy makers , health care providers and the general public on the relative benefits of carbohydrate , protein , and unsaturated fat as a means to reduce CVD risk BACKGROUND Controversy surrounds the effectiveness of dietary guidelines for cardiovascular disease ( CVD ) prevention in healthy middle-aged and older men and women . OBJECTIVE The objective was to compare effects on vascular and lipid CVD risk factors of following the United Kingdom dietary guidelines with a traditional British diet ( control ) . DESIGN With the use of a parallel- design ed r and omized controlled trial in 165 healthy nonsmoking men and women ( aged 40 - 70 y ) , we measured ambulatory blood pressure ( BP ) on 5 occasions , vascular function , and CVD risk factors at baseline and during 12 wk after r and om assignment to treatment . The primary outcomes were differences between treatments in daytime ambulatory systolic BP , flow-mediated dilation , and total cholesterol/HDL cholesterol . Secondary outcomes were differences between treatment in carotid-to-femoral pulse wave velocity , high-sensitivity C-reactive protein , and a measure of insulin sensitivity ( Revised Quantitative Insulin Sensitivity Check Index ) . RESULTS Data were available on 162 participants , and adherence to the dietary advice was confirmed from dietary records and biomarkers of compliance . In the dietary guidelines group ( n = 80 ) compared with control ( n = 82 ) , daytime systolic BP was 4.2 mm Hg ( 95 % CI : 1.7 , 6.6 mm Hg ; P < 0.001 ) lower , the treatment effect on flow-mediated dilation [ -0.62 % ( 95 % CI : -1.48 % , 0.24 % ) ] was not significant , the total cholesterol : HDL cholesterol ratio was 0.13 ( 95 % CI : 0 , 0.26 ; P = 0.044 ) lower , pulse wave velocity was 0.29 m/s ( 95 % CI : 0.07 , 0.52 m/s ; P = 0.011 ) lower , high-sensitivity C-reactive protein was 36 % ( 95 % CI : 7 % , 48 % ; P = 0.017 ) lower , the treatment effect on the Revised Quantitative Insulin Sensitivity Check Index [ 2 % ( 95 % CI : -2 % , 5 % ) ] was not significant , and body weight was 1.9 kg ( 95 % CI : 1.3 , 2.5 kg ; P < 0.001 ) lower . Causal mediated effects analysis based on urinary sodium excretion indicated that sodium reduction explained 2.4 mm Hg ( 95 % CI : 1.0 , 3.9 mm Hg ) of the fall in blood pressure . CONCLUSION Selecting a diet consistent with current dietary guidelines lowers BP and lipids , which would be expected to reduce the risk of CVD by one-third in healthy middle-aged and older men and women . This study is registered at www.is rct n.com as 92382106 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 BACKGROUND Although multiple risk factor intervention ( MRFI ) is recommended to reduce the increased morbidity and mortality of cardiovascular disease ( CVD ) in chronic kidney disease ( CKD ) , its efficacy is unknown . We studied the efficacy of a MRFI program in CKD . METHODS This r and omized controlled study of 200 patients with stage 4 or 5 CKD compared a physician-supervised , nurse-driven MRFI clinic ( focused on dyslipidemia , hyperhomocysteinemia , blood pressure [ BP ] , anemia , and hyperphosphatemia ) with conventional care in CKD .  One hundred eleven subjects completed 2 years of follow-up ( median follow-up 674 days [ interquartile range { IQR } 348 - 719 days ] ) . Outcome measures were atheroma burden ( carotid intimamedia thickness [ IMT ] ) and endothelial function ( brachial artery reactivity [ BAR ] ) . RESULTS The MRFI group showed significant improvements , compared with usual care , in serum low-density lipoprotein cholesterol ( -30.9 mg/dL vs -12.7 mg/dL , P = .001 ) , homocysteine ( -6.95 vs -0.67 micromol/L , P < .001 ) , systolic BP ( -6.9 vs -0.2 mm Hg , P = .049 ) , and diastolic BP ( -4.8 vs -1.0 mm of Hg , P = .043 ) . No significant changes were seen in serum phosphate or hemoglobin level . Despite observed improvements in risk factors , no differences from baseline were demonstrated for IMT ( -0.00 vs -0.01 mm , P = .533 ) or BAR ( 0.09 % vs 0.22 % , P = .834 ) . Forty-two patients reached a composite end point of CVD death , acute coronary syndrome , revascularization , nonfatal stroke , and amputation and this was similar between groups ( 23 vs 19 events , P = .475 ) . CONCLUSIONS A MRFI program was not associated with improvement in vascular structure or function in stage 4 or 5 patients with CKD Endothelial dysfunction and increased arterial stiffness occur early in the pathogenesis of the metabolic syndrome and they are both powerful independent predictors of cardiovascular risk . A high-fibre diet has been correlated with lower BMI and a lower incidence of hyperlipidaemia , CVD , hypertension and diabetes . The present r and omised , parallel- design study compared the effects of fibre intake from a healthy diet v. fibre supplement diets on blood pressure ( BP ) and vascular function over 12 weeks . Overweight and obese adults were r and omised to one of three groups : control ( with placebo ) , fibre supplement ( FIB ) or healthy eating group with placebo ( HLT ) . Systolic blood pressure ( SBP ) was lower in the FIB group compared with the control group at week 6 , but not at week 12 . However , SBP was lower in the HLT group compared with control group at week 12 . At week 6 , the FIB group presented lower diastolic blood pressure and augmentation index compared with the control group , but this result did not persist to the end of the study . The present study did not show any improvements in BP or vascular function in overweight and obese individuals with psyllium fibre supplementation over 12 weeks of intervention . However , a healthy diet provided the greatest improvements in BP in overweight and obese subjects . Further research with hypertensive individuals is necessary to eluci date whether increased fibre consumption in the form of psyllium supplementation may provide a safe and acceptable means to reduce BP , vascular function and the risk of developing CVD Diabetes incidence is increasing rapidly in the United States . Diabetes increases the risk for cardiovascular disease , the major cause of death in diabetic individuals . The conventional cardiovascular risk factors of hyperlipidemia and hypertension worsen diabetic vascular disease . Treatment targets for low-density lipoprotein cholesterol ( LDL-C ) and blood pressure in diabetic individuals are being debated . The S AND S is a r and omized , open-label , 3-year trial to examine the effects of aggressive LDL-C ( goal < 70 mg/dL ) and blood pressure ( BP ) ( goal < 115/75 mm Hg ) reduction versus the st and ard goals of < 100 mg/dL for LDL-C and < 130/85 mm Hg for BP .  Five hundred forty-nine American-Indian men and women > 40 years old with type 2 diabetes were r and omized to 1 of 2 groups . Lipids and BP are managed using Food and Drug Administration-approved medications in an algorithmic approach . The presence and progression of atherosclerosis are evaluated by carotid ultrasonography ; echocardiography assesses cardiac function . The primary end point is the composite outcome of change in carotid artery intimal medial thickness and fatal/nonfatal cardiovascular events . These outcomes are combined by using a ranked analysis for carotid thickness and assigning a " worst rank " for a cardiovascular event . Secondary end points include carotid plaque score , left ventricular geometry and function , serum C-reactive protein , and safety measures . Unique aspects of the study design and analysis plan involve the use of a composite outcome and changes during the trial of LDL-C treatment goals for participants with baseline or incident cardiovascular disease in the conventional group because of changes in the st and ard of care . Study results will further underst and ing of the effects of aggressive risk factor reduction on atherosclerosis burden and cardiac function in diabetic individuals in US population s and will help determine optimal LDL-C and BP treatment goals for diabetic patients BACKGROUND The Hypertension Optimal Treatment ( HOT ) Study has provided information about cardiovascular events in 18790 hypertensives , subjected to pronounced blood pressure ( BP ) lowering for a mean of 3.8 years . The HOT study data have subsequently been analysed after stratification of the patients according to global cardiovascular risk , and it has been found that , despite intensive blood pressure lowering in all risk strata , morbid event rates increased with increasing risk stratum . OBJECTIVES Previously analysed global risk strata were based on combinations of risk factors . The analyses presented here were intended to provide information on the relative role that the presence of each individual factor may have in increasing cardiovascular risk , despite good BP control . METHODS Risk ratios ( RR ) for patients with and those without a risk factor were calculated with 95 % confidence intervals ( CI ) using a Cox proportional hazard model , and adjusted for all variables except the one under examination . RESULTS For all risk factors considered and for all types of event , RR were always greater than 1 , indicating a greater risk in the presence , compared with that in the absence of each factor . The male gender was a statistically significant risk for cardiovascular ( CV ) events , CV and total mortality and particularly for myocardial infa rct ion ( MI ) ; age > or = 65 years for CV events , stroke , CV and particularly total mortality ; smoking for all events analysed , but particularly for total mortality ( twice higher in smokers than in non-smokers ) ; high serum cholesterol ( > 6.8 mmol/l ) for CV events , MI and CV mortality ; high serum creatinine ( > 155 micromol/l ) for CV events , stroke , CV and total mortality ; diabetes for CV events , stroke , total mortality and particularly CV mortality ; and ischaemic heart disease for all events analysed . Adjusted RR were often close to or greater than 2 . CONCLUSIONS Each of the risk factors considered was found to be an important cause of residual risk , despite good BP control . These findings emphasize the importance of addressing other correctable risk factors , e.g. smoking , hypercholesterolaemia and diabetes , as well as rigorous control of blood pressure , and of initiating antihypertensive therapy before cardiovascular and renal damage becomes manifest OBJECTIVE We previously demonstrated beneficial effects of physical activity on cardiovascular disease ( CVD ) risk factors , body mass index ( BMI ) and fat mass in  pre-pubescent obese children . The aim of this study was to determine whether these changes were maintained 2 years later . METHODS Two years after the R and omised Controlled Trial , we performed a follow-up study with 20 of 38 subjects ( 11.4 ± 1.8 years ) . Outcomes included blood pressure ( BP ) by ambulatory monitoring ; arterial function and structure using high-resolution ultrasound , BMI , body composition by dual-energy x-ray absorptiometry ( DXA ) , physical activity using accelerometer , and biological markers . RESULTS During the 2-year follow-up period , mean 24-hour diastolic BP z-score significantly decreased ( 1.4 ± 1.2 vs. 0.3 ± 1.4 , p = 0.04 ) , while systolic BP z-score was slightly reduced ( 2.4 ± 1.5 vs. 1.4 ± 1.7 , p = 0.067 ) . Blood pressure changes were greater in children who diminished their BMI z-score compared with the ones who did not . Systolic hypertension rates dropped from 50 to 28 % and diastolic hypertension from 42 to 6 % . In addition , arterial intima-media thickness ( 0.51 ± 0.03 vs. 0.51 ± 0.06 , p = 0.79 ) , BMI z-score ( 2.9 ± 0.8 vs. 2.9 ± 1.1 kg.cm(-2 ) , p = 0.27 ) , body fat ( 41.9 ± 6.9 vs. 42.8 ± 6.7 % ; p = 0.39 ) and physical activity count ( 703 ± 209 vs. 574 ± 244 cpm , p = 0.30 ) were stable . CONCLUSION To our knowledge , this is the first study reporting that beneficial effects on adiposity and CVD risk factors of a physical activity centred intervention are sustained 2 years after the cessation of training in obese children . Subjects stabilized BMI z-score and maintained physical activity with further improvement of BP and stabilization of arterial wall remodelling . We conclude that it is important to encourage physical activity in this population . Effects of Aerobic Exercise Training on Arterial Function and Insulin Resistance Syndrome in Obese Children : A R and omised Controlled Trial : NCT00801645 Cardiovascular responses to stress reactivity has been proposed as a risk factor for hypertension . In this study , we evaluated the effects of stress reduction on both laboratory cardiovascular reactivity and ambulatory blood pressure in real life on 39 normotensive male subjects who were pretested for ambulatory blood pressure and cardiovascular reactivity to stress using a battery of laboratory stressors . Thereafter , subjects were r and omly assigned to practice either the Transcendental Meditation ( TM ) technique or a cognitive-based stress education control ( SEC ) for four months . After 4 months , there was no change in cardiovascular response to stressors between the TM and control groups . However , the subjects regularly practicing TM demonstrated a significant reduction of 9 mm Hg ( p < .04 ) in average ambulatory DBP compared to controls . Since ambulatory BP monitoring has been shown to be a better predictor of cardiovascular complications of hypertension than clinic BP , this finding may have important implication s for primary prevention of CVD in normotensive subjects Rationale : We hypothesized increasing obstructive sleep apnea ( OSA ) severity would be associated with nondipping blood pressure ( BP ) in increased cardiovascular disease ( CVD ) risk . Methods : Baseline data from 298 cardiology patients recruited for a multicenter r and omized controlled trial were examined . Dipping was defined as a sleep-related BP or heart rate ( HR ) reduction of at least 10 % . Logistic regression models were fit , adjusting for age , sex , race , BMI , CVD risk factors , CVD , and study site . Results : There was a statistically significant 4 % increase in the odds of nondipping SBP per 1-unit increase in both apnea hypopnea index ( AHI ) and oxygen desaturation index ( ODI ) . There was no significant relationship between AHI and nondipping mean arterial pressure ( MAP ) ; however , a 3 % increase in the odds of nondipping MAP per 1-unit increase in ODI was observed [ odds ratio ( OR ) = 1.03 ; 95 % confidence interval ( CI ) 1.00–1.05 ] . At severe OSA levels , a 10 and 4 % increase in odds of nondipping DBP per 1-unit increase in AHI and ODI were observed , respectively . A 6 % [ OR = 1.06 ; 95 % CI ( 1.01–1.10 ) ] increase in nondipping HR odds was observed with each increase in ODI until the upper quartile of ODI . Conclusion : In patients at cardiovascular risk and moderate-to-severe OSA , increasing AHI and /or ODI were associated with increased odds of nondipping SBP and nondipping MAP . More severe levels of AHI and ODI also were associated with nondipping DBP . These results support progressive BP burden associated with increased OSA severity even in patients managed by cardiology specialty care TOGETHER investigated whether targeting multiple cardiovascular ( CV ) risk factors using single-pill amlodipine/atorvastatin ( AML/ATO ) and therapeutic lifestyle changes ( TLC ) results in greater blood pressure (BP)/lipid control and additional reduction in estimated cardiovascular disease ( CVD ) risk compared with blood pressure intervention only using amlodipine ( AML ) + TLC . TOGETHER was a 6-week , r and omized , double-blind , double-dummy trial using hypertensive participants with additional CV risk factors without CVD/diabetes . Participants were r and omized to either AML/ATO ( 5 to 10/20 mg ) + TLC or AML ( 5 to 10 mg ) + TLC . The primary end point was the difference in proportion of participants attaining both BP ( < 140/90 mm Hg ) and low-density lipoprotein cholesterol ( LDL-C ) ( < 100 mg/dL ) goals at week 6 . At week 6 , 67.8 % of participants receiving AML/ATO + TLC attained the combined BP/LDL-C goal versus 9.6 % with AML + TLC ( RD [ A – B ] : 58.2 ; 95 % CI [ 48.1 to 68.4 ] P < 0.001 ; OR : 19.0 ; 95 % CI 9.1 to 39.6 ; P < 0.001 ) . Significant reductions from baseline in LDL-C , total cholesterol and triglycerides and estimated 10-year Framingham risk were also observed . Treatment with AML/ATO was well tolerated . In conclusion , a multifactorial CV management approach is more effective in achieving combined BP/LDL-C targets as well as CV risk reduction compared with BP intervention only in this patient population Although exercise has well-documented health benefits on cardiovascular disease ( CVD ) , the benefit of combination exercise on CVD risk factors in individuals with elevated risk has not been fully eluci date d. We compared the effects of aerobic , resistance , and a combination of both aerobic and resistance training on CVD risk factors including peripheral and central BP , cardiorespiratory fitness ( CRF ) , muscular strength , body composition , blood glucose and lipids .  Sixty-nine adults ( 58±7 years ) with an elevated blood pressure or hypertension , overweight/obesity , and sedentary lifestyle were r and omized to one of the three 8-week exercise programs or a non-exercise control group . Participants in all three exercise groups had an equal total exercise time , 3 days/week ( aerobic : 60 minutes/session vs. resistance : 60 minutes/session vs. combination : aerobic 30 minutes/session plus resistance 30 minutes/session ) . Combined training provided significant reductions in peripheral ( -4 mmHg ) and central diastolic BP ( -4 mmHg ) , increase in CRF ( 4.9 ml/kg/min ) , increase in upper ( 4 kg ) and lower ( 11 kg ) body strength , and increase in lean body mass ( 0.8 kg ) ( p < 0.05 ) . Aerobic training only increased CRF ( 7.7 ml/kg/min ) , and reduced body weight ( -1.0 kg ) and fat mass ( -0.9 kg ) ( p < 0.05 ) . Resistance training only increased lower body strength ( 13 kg ) and reduced waist circumference ( -1.7 cm ) ( p < 0.05 ) . However , neither aerobic or resistance training alone showed significant reductions in BP ( p>0.05 ) . Furthermore , a composite score of CVD risk factors indicated a greater reduction with combination training compared to the control group . In conclusion , among individuals at an increased risk for CVD , as little as 8-weeks of combined training may provide more comprehensive CVD benefits compared to time-matched aerobic or resistance training alone Substantial evidence links high levels of hostility , stress , depression , and social isolation with increased risk of cardiovascular disease ( CVD ) , along with poorer prognosis after myocardial infa rct ion ( MI ) . Further , these variables have been shown to cluster in particular individuals , producing even greater risk . One of the mechanisms thought to link psychosocial factors with CVD is cardiovascular reactivity ( CVR ) . Exaggerated CVR to stress has been shown to be associated with accelerated atherosclerosis , increased CVD risk , and stroke incidence . Interventions for reducing psychosocial coronary risk factors and promoting recovery from coronary heart disease ( CHD ) have included both educational programs aim ed at lifestyle and behavior change and cognitivebehavioral interventions targeted at changing specific psychosocial risk factors such as hostility . A recent meta- analysis found that stress management and educational programs for CHD patients significantly reduced blood pressure ( BP ) , cholesterol , body weight , and emotional distress and lowered the recurrence of MI and mortality by 29 % and 34 % , respectively . However , not all of the trials evaluating these interventions have been r and omized , and some have had small sample sizes . In addition , a number of these interventions have been targeted at patients identified as being at high psychosocial risk , which raises questions about the extent to which the effectiveness of such programs is limited to high-risk patients as compared with the patient The objectives of the study were to clarify the relationship between blood pressure and mortality from stroke , heart disease , cardiovascular diseases and all causes of death among representative population of Japanese and to estimate category-specific excess mortality from stroke due to blood pressure ( BP ) level . The study design comprised a retrospective cohort study using the 1980 National Survey on Cardiovascular Diseases and identification of underlying causes of death using national vital statistics data . In 1994 , a 14-year follow-up cohort study was conducted among participants of the National Survey on Cardiovascular Diseases in 1980 , r and omly selected from the Japanese population . With a collaboration of 300 public health centres , which had conducted the original survey in 1980 , 91.4 % of the participants of the original survey could be followed up . Total observed person-years were 53 948 for men and 70 932 for women . During follow-up , 1327 deaths were observed . BP levels were significantly related to mortality from strokes , cardiovascular diseases and all causes of death for both sexes ( P<0.001 ) . Heart disease mortality was significantly related to BP levels among men ( P<0.05 ) while not among women . Estimated excess mortality was 130 % for men and 42 % for women and chiefly observed among moderate hypertensives ( 48 % for men and 16 % for women ) . In conclusion , high blood pressure was a risk factor for mortality from all causes as well as those from cardiovascular diseases , stroke and heart disease among Japanese . Since the major part of excess mortality was due to mild hypertension , a population strategy to reduce blood pressure should be encouraged Background It has been known that hypertension is an independent risk factor for cardiovascular disease ( CVD ) . CVD is the major cause of morbidity and mortality in developed and developing countries . Elevation of blood pressure ( BP ) increases the adverse effect for cardiovascular outcomes . Prevention of increased BP plays a crucial role in a reduction of those outcomes , leading to a decrease in mortality . Therefore , the purpose of this study was to investigate the effects of dietary black sesame meal on BP and oxidative stress in individuals with prehypertension . Methods Twenty-two women and eight men ( aged 49.8 ± 6.6 years ) with prehypertension were r and omly divided into two groups , 15 subjects per group . They ingested 2.52 g black sesame meal capsules or placebo capsules each day for 4 weeks . Blood sample s were obtained after overnight fasting for measurement of plasma lipid , malondialdehyde ( MDA ) and vitamin E levels . Anthropometry , body composition and BP were measured before and after 4-week administration of black sesame meal or a placebo . Results The results showed that 4-week administration of black sesame meal significantly decreased systolic BP ( 129.3 ± 6.8 vs. 121.0 ± 9.0 mmHg , P < 0.05 ) and MDA level ( 1.8 ± 0.6 vs. 1.2 ± 0.6 μmol/L , P < 0.05 ) , and increased vitamin E level ( 29.4 ± 6.0 vs. 38.2 ± 7.8 μmol/L , P < 0.01 ) . In the black sesame meal group , the change in SBP tended to be positively related to the change in MDA ( R = 0.50 , P = 0.05 ) , while the change in DBP was negatively related to the change in vitamin E ( R = -0.55 , P < 0.05 ) . There were no correlations between changes in BP and oxidative stress in the control group . Conclusions These results suggest the possible antihypertensive effects of black sesame meal on improving antioxidant status and decreasing oxidant stress . These data may imply a beneficial effect of black sesame meal on prevention of CVD Both ( n-3 ) long-chain PUFA ( LCPUFA ) and linoleic acid [ LA , 18:2(n-6 ) ] improve cardiovascular disease ( CVD ) risk factors , but a high-LA intake may weaken the effect of ( n-3 ) LCPUFA . In a controlled , double-blind , 2 x 2-factorial 8-wk intervention , we investigated whether fish oil combined with a high- or low-LA intake affects overall CVD risk profile .  Healthy men ( n = 64 ) were r and omized to 5 mL/d fish oil capsules ( FO ) [ mean intake 3.1 g/d ( n-3 ) LCPUFA ] or olive oil capsules ( control ) and to oils and spreads with either a high ( S/B ) or a low ( R/K ) LA content , result ing in a 7.3 g/d higher LA intake in the S/B groups than in the R/K groups . Diet , ( n-3 ) LCPUFA in peripheral blood mononuclear cells , blood pressure ( BP ) , heart rate ( HR ) , and plasma CVD risk markers were measured before and after the intervention . FO lowered fasting plasma triacylglycerol ( TAG ) ( P < 0.001 ) by 51 % and 19 % in the FO+R/K-group and FO+S/B-group , respectively , which was also reflected in postpr and ial TAG measured after the intervention ( P < 0.01 ) . Although a fat x FO interaction was found for monocyte chemoattractant protein-1 , neither the FO nor fat intervention affected fasting plasma cholesterol , glucose , insulin , fibrinogen , C-reactive protein , interleukin-6 , vascular cell adhesion molecule-1 , P-selectin , oxidized LDL , cluster of differentiation antigen 40 lig and ( CD40L ) , adiponectin , or fasting or postpr and ial BP or HR after adjustment for body weight changes . In conclusion , neither fish oil supplementation nor the LA intake had immediate pronounced effects on the overall CVD risk profile  in healthy men , but fish oil lowered plasma TAG in healthy subjects with initially low concentrations Background : Taiwan has the highest incidence of end-stage renal disease ( ESRD ) in the world , but little is known about the outcomes of patients with chronic kidney disease ( CKD ) before ESRD in Taiwan . This study investigated the rate of renal progression and predictors for ESRD and death in a prospect i ve cohort of patients under usual nephrologic care at a single center . Methods : A total of 433 patients at CKD stage 3–5 short of dialysis were recruited from nephrology clinics .  Patients were monitored for up to 36 months or until ESRD , death or loss to follow-up  . Glomerular filtration rates ( GFR ) were calculated by the Modification of Diet in Renal Disease abbreviated formula . Results : At baseline , mean age was 65.6 years , 61.7 % were male , 33.3 % were diabetic and 29.1 % had cardiovascular diseases ( CVD ) . At the end of follow-up , 123 patients ( 28.4 % ) had advanced to ESRD and 41 ( 9.5 % ) had died . Mean annual declines in GFR were 2.24 , 4.22 , and 3.23 ml/min/1.73 m2 for stages 3 , 4 , and 5 , respectively . By Cox regression model , patients with CVD , lower BMI and higher systolic BP were more likely to develop ESRD .  Older patients with CVD and lower systolic BP were more likely to die . Conclusion : In this CKD cohort , patients were more likely to develop ESRD than cardiovascular death . The rate of GFR decline and predictors of ESRD were comparable to those reported in Western countries . Thus , the high incidence of ESRD in Taiwan may be attributed , at least in part , to lower cardiovascular mortality To assess the combined influence of blood pressure ( BP ) , serum cholesterol level , and cigarette smoking on death from coronary heart disease ( CHD ) and to describe how these associations vary with age , data on those factors and on mortality for 316,099 men screened for the Multiple Risk Factor Intervention Trial ( MRFIT ) were examined . Vital status of participants has been determined after an average follow-up of 12 years ; 6327 deaths from CHD have been identified . Strong grade d relationships between serum cholesterol levels above 4.65 mmol/L ( 180 mg/dL ) , systolic BP above 110 mm Hg , and diastolic BP above 70 mm Hg and mortality due to CHD were evident . Smokers with serum cholesterol and systolic BP levels in the highest quintiles had CHD death rates that were approximately 20 times greater than nonsmoking men with systolic BP and cholesterol levels in the lowest quintile . Systolic and diastolic BP , serum cholesterol level , and cigarettes per day were significant predictors of death due to CHD in all age groups . Systolic BP was a stronger predictor than diastolic BP . These results , together with the findings of clinical trials , offer strong support for intensified preventive efforts in all age groups BACKGROUND The quantity and quality of fats consumed in the diet influence the risk of cardiovascular disease ( CVD ) . Although the effect of diet on plasma lipids and lipoproteins is well documented , less information exists on the role of fats on blood pressure ( BP ) . OBJECTIVE The objective was to evaluate the effects of different types of dietary fat on BP in healthy subjects . DESIGN Healthy subjects ( n = 162 ) were r and omly assigned for 3 mo to follow 1 of 2 isoenergetic diets : 1 rich in monounsaturated fatty acids ( MUFA diet ) and the other rich in saturated fatty acids ( SFA diet ) . Each group was further r and omly assigned to receive supplementation with fish oil ( 3.6 g n-3 fatty acids/d ) or placebo . RESULTS Systolic BP ( SBP ) and diastolic BP ( DBP ) decreased with the MUFA diet [ -2.2 % ( P = 0.009 ) and -3.8 % ( P = 0.0001 ) , respectively ] but did not change with the SFA diet [ -1.0 % ( P = 0.2084 ) and -1.1 % ( P = 0.2116 ) ] . The MUFA diet caused a significantly lower DBP than did the SFA diet ( P = 0.0475 ) . Interestingly , the favorable effects of MUFA on DBP disappeared at a total fat intake above the median ( > 37 % of energy ) . The addition of n-3 fatty acids influenced neither SBP nor DBP . CONCLUSIONS Changing the proportions of dietary fat by decreasing SFAs and increasing MUFAs decreased diastolic BP . Interestingly , the beneficial effect on BP induced by fat quality was negated by the consumption of a high total fat intake . The addition of n-3 fatty acids to the diet had no significant effect on BP ABSTRACT . As part of a prospect i ve population study of cardiovascular disease , ophthalmoscopic examination was performed in 855 r and omly selected 50-year-old men in 1963 . The examination was repeated four years later , in 1967 . On both occasions haemorrhages , exu date s and papillary aedema were rarely seen . Attenuating arterioles , focal narrowing , crossing phenomena and broadened light reflex were all related to BP but attenuating arterioles and /or focal narrowing discriminated BP best . Isolated broadened reflex and /or crossing phenomena were not related to BP . The change in BP over four and ten years was the same in those who had and those who did not have hypertensive eye ground changes at the initial examination , indicating that eye ground changes do not precede hypertension . Mortality data and the morbidity in myocardial infa rct ion and stroke were followed up until 1975 . The importance of the separate eye ground variables for these mortality and morbidity end-points was analyzed , taking into account the importance of BP , serum cholesterol and smoking . Focal narrowings were of importance for mortality , regardless of its cause , for stroke and for death from malignancy . Crossing phenomena were of importance for mortality , regardless of cause , for fatal coronary heert disease , for stroke and for deaths other than cardiovascular and cancer deaths . The eye ground variables are thus of differing importance for different end-points . Grouping them as in Keith and Wagener 's or other classification systems , means a loss of information and should be avoided Increased intake of marine long-chain n-3 PUFA ( n-3 LCPUFA ) may decrease the risk of CVD and reduce mortality by lowering serum TAG and blood pressure ( BP ) . Furthermore , n-3 LCPUFA may affect novel CVD risk markers related to inflammation and vascular function . The objective of the present study was to examine the effect of farmed trout on novel and traditional CVD risk markers in healthy men , and to evaluate whether this was affected by the aquacultural feed regime . We performed a parallel , 8-week intervention study in which sixty-eight healthy male volunteers were r and omised to consume either a daily meal with 150 g farmed trout raised on either marine or vegetable-based feed , or a reference meal containing 150 g chicken . Twenty-four hour BP , pulse wave velocity , augmentation index , fatty acid composition of erythrocyte ( RBC ) , and concentrations of TAG , HDL-cholesterol , LDL-cholesterol , glucose , insulin , C-reactive protein ( CRP ) and other markers of inflammation were measured at weeks 0 and 8 . RBC content of total n-3 LCPUFA , both EPA and DHA , was significantly higher among men consuming trout raised on marine feed compared with men consuming the  vegetable-fed trout or chicken . The three intervention groups did not differ significantly with respect to any of the other outcome variables , although there were trends towards associations between the changes in RBC n-3 LCPUFA and those in BP and CRP . In the present study , we conclude that we could not confirm the fish oil-induced reduction in CVD risk markers after daily consumption of trout with high or low n-3 LCPUFA content . However , trout raised on vegetable-based feed had less pronounced impact on RBC n-3 LCPUFA status OBJECTIVE To assess the effect of low-dose , diuretic-based antihypertensive treatment on major cardiovascular disease ( CVD ) event rates in older , non-insulin-treated diabetic patients with isolated systolic hypertension ( ISH ) , compared with nondiabetic patients . DESIGN Double-blind , r and omized , placebo-controlled trial : the Systolic Hypertension in the Elderly Program ( SHEP ) . SETTING Multiple clinical and support centers in the United States . PARTICIPANTS A total of 4736 men and women aged 60 years and older at baseline with ISH ( systolic blood pressure [ BP ] , > or = 160 mm Hg ; diastolic BP , < 90 mm Hg ) at baseline , 583 non-insulin-dependent diabetic patients and 4149 nondiabetic patients ( 4 additional patients not so classifiable were r and omized but not included in these analyses ) . Diabetes mellitus defined as physician diagnosis , taking oral hypoglycemic drugs , fasting glucose level of 7.8 mmol/L or more ( > or = 140 mg/dL ) , or any combination of these characteristics . INTERVENTION The active treatment group received a low dose of chlorthalidone ( 12.5 - 25.0 mg/d ) with a step-up to atenolol ( 25.0 - 50.0 mg/d ) or reserpine ( 0.05 - 0.10 mg/d ) if needed . The placebo group received placebo and any active antihypertensive drugs prescribed by patient 's private physician for persistently high BP . MAIN OUTCOME MEASURES The 5-year rates of major CVD events , nonfatal plus fatal stroke , nonfatal myocardial infa rct ion ( MI ) and fatal coronary heart disease ( CHD ) , major CHD events , and all-cause mortality . RESULTS The SHEP antihypertensive drug regimen lowered BP of both diabetic and nondiabetic patients , with few adverse effects . For both diabetic and nondiabetic patients , all outcome rates were lower for participants r and omized to the active treatment group than for those r and omized to the placebo group . Thus , 5-year major CVD rate was lower by 34 % for active treatment compared with placebo , both for diabetic patients ( 95 % confidence interval [ CI ] , 6%-54 % ) and nondiabetic patients ( 95 % CI , 21%-45 % ) . Absolute risk reduction with active treatment compared with placebo was twice as great for diabetic vs nondiabetic patients ( 101/1000 vs 51/1000 r and omized participants at the 5-year follow-up ) , reflecting the higher risk of diabetic patients . CONCLUSION Low-dose diuretic-based ( chlorthalidone ) treatment is effective in preventing major CVD events , cerebral and cardiac , in both non-insulin-treated diabetic and nondiabetic older patients with ISH Patients with type 2 diabetes are at high risk for several serious health problems , including premature death , cardiovascular disease (CVD),2 blindness , and kidney failure . Moreover , there is a strong positive association between the degree of glycemia , measured as plasma glucose or glycated hemoglobin ( Hb A1c ) , and the above outcomes . Hence , it has been hypothesized that the mortality and morbidity of type 2 diabetes can be reduced with intensive control of glycemia . The Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial tested this hypothesis by determining whether a therapeutic strategy that targeted a typical Hb A1c value of < 6.0 % , compared with a strategy that targeted an Hb A1c value of 7.0%–7.9 % , would reduce CVD ( 1 ) . The primary outcome was a composite of CVD death , nonfatal myocardial infa rct ion , and nonfatal stroke . Secondary outcomes included all-cause mortality , development and progression of microvascular disease , frequency of severe hypoglycemia , and progression of retinopathy . The trial also tested the effects of intensive blood pressure ( BP ) control and the addition of a fibrate in selected patients . The study r and omized 10 251 participants with well-established type 2 diabetes . Entry criteria included a history of a cardiovascular event or at least 2 risk factors for CVD , and a normal serum creatinine concentration . The trial was not design ed to test the efficacy of any particular medication or combination of medications . What differed between the 2 arms was the glycemic target and consequently the frequency of use of glycemia medications and , to a lesser extent , the dosage . All participants made frequent clinic visits , during which lifestyle education and hypoglycemia prevention were emphasized . Within 8 months after enrollment , the median Hb A1c values in the intensive and st and ard glycemia arms reached 6.4 % and 7.5 % , respectively , and remained stable with a difference between the medians of 1.1 % Background A significant proportion of Europeans do not meet the recommendations for 30 mins of physical activity 5 times per week . Whether lower frequency , moderate intensity exercise alters cardiovascular disease ( CVD ) risk has received little attention . This study examined the effects of 45 minutes self-paced walking , 2 d · wk-1 on aerobic fitness , blood pressure ( BP ) , body composition , lipids and C-Reactive Protein ( CRP ) in previously sedentary civil servants . Methods 37 subjects ( 24 women ) aged 41.5 ± 9.3 years were r and omly assigned to either two 45 minute walks per week ( walking group ) or no training ( control group ) . Aerobic fitness , body composition , blood pressure ( BP ) , CRP and lipoprotein variables were measured at baseline and following 8 weeks . Steps counts were measured at baseline and during weeks 4 and 8 of the intervention . Results Compared to the control group , the walking group showed a significant reduction in systolic BP and maintained body fat levels ( P < 0.05 ) . There were no changes other risk factors . Subjects took significantly more steps on the days when prescribed walking was performed ( 9303 ± 2665 ) compared to rest days ( 5803 ± 2749 ; P < 0.001 ) . Conclusion These findings suggest that walking twice per week for 45 minutes at ~ 62 % HRmax , improves activity levels , reduces systolic BP and prevents an increase in body fat in previously sedentary adults .  This walking prescription , however , failed to induce significant improvements in other markers of cardiovascular disease risk following eight weeks of training The association of ambulatory blood pressure ( BP ) variability with mortality and cardiovascular events is controversial . To investigate whether BP variability predicts cardiovascular events and mortality in hypertension , we analyzed 7112 untreated hypertensive participants ( 3996 men ) aged 52±15 years enrolled in 6 prospect i ve studies . Median follow-up was 5.5 years . SD of night-time BP was positively associated with age , body mass index , smoking , diabetes mellitus , and average night-time BP ( all P<0.001 ) . In a multivariable Cox model , night-time  BP variability was an independent predictor of all-cause mortality ( systolic , P<0.001/diastolic , P<0.0001 ) , cardiovascular mortality ( P=0.008/<0.0001 ) , and cardiovascular events ( P<0.001/<0.0001 ) . In contrast , daytime BP variability was not an independent predictor of outcomes in any model . In fully adjusted models , a night-time systolic BP SD of ≥12.2 mm Hg was associated with a 41 % greater risk of cardiovascular events , a 55 % greater risk of cardiovascular death , and a 59 % increased risk of all-cause mortality compared with an SD of < 12.2 mm Hg . The corresponding values for a diastolic BP SD of ≥7.9 mm Hg were 48 % , 132 % , and 77 % . The addition of night-time BP variability to fully adjusted models had a significant impact on risk reclassification and integrated discrimination for all outcomes ( relative integrated discrimination improvement for systolic BP variability : 9 % cardiovascular events , 14.5 % all-cause death , 8.5 % cardiovascular death , and for diastolic BP variability : 10 % cardiovascular events , 19.1 % all-cause death , 23 % cardiovascular death , all P<0.01 ) . Thus , addition of BP variability to models of long-term outcomes improved the ability to stratify appropriately patients with hypertension among risk categories defined by st and ard clinical and laboratory variables Blood  pressure ( BP ) measured only in the clinic substantially misclassifies hypertension in patients with chronic kidney disease ( CKD ) . The role of out-of-clinic recordings of BP in predicting  end-stage renal disease ( ESRD )  and death in patients with CKD is unknown . A prospect i ve cohort study was conducted in 217 Veterans with CKD .  BP was measured at home and in the clinic by ' routine ' and st and ardized methods .  Patients were followed over a median of 3.5 years to assess the end points of total mortality , ESRD or the composite outcome of ESRD or death . Home BP  was 147.0+/-21.4/78.3+/-11.6 mmHg and  clinic BPs  were 155.2+/-25.6/84.7+/-14.2 mmHg by st and ardized method and 144.5+/-24.2/75.4+/-14.7 mmHg by the ' routine ' method . The composite renal end point occurred in 75 patients ( 34.5 % ) , death in 52 patients ( 24.0 % ) , and ESRD in 36/178 patients ( 20.2 % ) . One st and ard deviation ( s.d . ) increase in systolic BP increased the risk of renal end point by 1.27 ( 95 % confidence interval ( CI ) 1.01 - 1.60 ) for routine clinic measurement , by 1.69 ( 95 % CI 1.32 - 2.17 ) for st and ardized clinic measurement and by 1.84 ( 95 % CI 1.46 - 2.32 ) for home BP recording . One s.d . increase in home systolic BP increased the risk of ESRD by 1.74 ( 95 % CI 1.04 - 2.93 ) when adjusted for st and ardized clinic systolic BP , proteinuria , estimated glomerular filtration rate , and other risk factors . In patients with CKD , BPs obtained at home are a stronger predictor of ESRD or death compared to BPs obtained in the clinic . Systolic home BP is an independent predictor for ESRD Recommendations for control of high blood pressure ( BP ) emphasize lifestyle modification , including weight loss , reduced sodium intake , increased physical activity , and limited alcohol consumption . The Dietary Approaches to Stop Hypertension ( DASH ) dietary pattern also lowers BP . The PREMIER r and omized trial tested multicomponent lifestyle interventions on BP in demographic and clinical subgroups . Participants with above-optimal BP through stage 1 hypertension were r and omized to an Advice Only group or one of two behavioural interventions that implement established recommendations ( Est ) or established recommendations plus DASH diet ( Est plus DASH ) . The primary outcome was change in systolic BP at 6 months . The study population was 810 individuals with an average age of 50 years , 62 % women , 34 % African American ( AA ) , 95 % overweight/obese , and 38 % hypertensive . Participants in all the three groups made lifestyle changes . Mean net reductions in systolic ( S ) BP in the Est intervention were 1.2 mmHg in AA women , 6.0 in AA men , 4.5 in non-AA women , and 4.2 in non-AA men . The mean effects of the  Est Plus DASH intervention were 2.1 , 4.6 , 4.2 , and 5.7 mmHg in the four race – sex subgroups , respectively . BP changes were consistently greater in hypertensives than in nonhypertensives , although interaction tests were nonsignificant . The Est intervention caused statistically significant BP reductions in individuals over and under age 50 . The Est Plus DASH intervention lowered BP in both age groups , and significantly more so in older individuals . In conclusion , diverse groups of people can adopt multiple lifestyle changes that can lead to improved BP control and reduced CVD risk INTRODUCTION AND PURPOSE Physical inactivity in postmenopausal women contributes to a rise in atherogenic risk factors associated with the metabolic syndrome . Although regular physical activity positively contributes to health , inactivity progressively increases with age . The Dose Response to Exercise in Women aged 45 - 75 yr ( DREW ) study is design ed to investigate the effect of different amounts of exercise training on cardiorespiratory fitness and risk factors for cardiovascular disease ( CVD ) in postmenopausal women at moderately increased risk of CVD . METHODS DREW will recruit 450 sedentary , healthy , postmenopausal women with a body mass index of 25 - 40 kg.m-2 , resting systolic blood pressure ( BP ) of 120 - 159 mm Hg , and a resting diastolic BP of < or = 99 mm Hg . Laboratory and self-report measures completed at baseline and 6 months include maximal oxygen consumption ( .VO2max ) , resting BP , anthropometry , dietary habits , physical activity history , medication use , menstrual history , personal and family medical history , and fasting HDL cholesterol , LDL cholesterol , triglycerides , and glucose . Eligible participants are r and omly assigned to a nonexercise group or one of three exercise groups . Participants exercise 3 to 4x wk-1 at a heart rate equivalent to 50 % of .VO2max expending 4 , 8 , or 12 kcal.kg-1.wk-1 , depending on group assignment . This study will allow quantification of possible dose-response relations ( 50 % , 100 % , and 150 % of the consensus physical activity recommendation ) between exercise training and study outcomes . CONCLUSION DREW can make important contributions to our underst and ing of the effects of physical activity in postmenopausal women and help refine public health and clinical recommendations for this group Elevated arterial pressure enhances the risk for cardiovascular ( CV ) events in patients with diabetic nephropathy . The optimal BP and the component of the elevated BP that affect the risk have not been defined . A post hoc analysis was performed to assess the impact of achieved systolic , diastolic , and pulse pressures on CV outcomes in 1590 adults who had overt diabetic nephropathy and were enrolled in the Irbesartan Diabetic Nephropathy Trial ( IDNT ) and had a baseline serum creatinine above the normal range , up to 266 micromol/L ( 3.0 mg/dL ) , 24-h urine protein > 900 mg/d , and at least 6 mo of follow-up . Patients were r and omized to irbesartan , amlodipine , or placebo , with other antihypertensive agents to a BP goal of < or = 135/85 mmHg . Progressively lower achieved systolic BP ( SBP ) to 120 mmHg predicted a decrease in CV mortality and congestive heart failure ( CHF ) but not myocardial infa rct ions ( MI ) . A SBP below this threshold was associated with increased risk for CV deaths and CHF events . Achieved diastolic BP < 85 mmHg was associated with a trend to increase in all-cause mortality , significant increase in MI , but decreased risk for strokes . Increased pulse pressure predicted increased all-cause mortality , CV mortality , MI , and CHF . It is concluded that achieved SBP approaching 120 mmHg and diastolic BP of 85 mmHg are associated with the best protection against CV events in these patients . BP < or = 120/85 may be associated with an increase in CV events Aims /hypothesisTo determine the associations of baseline depression symptoms and use of antidepressant medicines ( ADMs ) with baseline cardiovascular disease ( CVD ) risk factors in Look AHEAD ( Action for Health in Diabetes ) trial participants . Methods Look AHEAD participants ( n = 5,145 ; age 58.7 ± 6.8 years ; BMI 35.8 ± 5.8 kg/m2 ) were assessed for CVD risk factors ( elevated HbA1c or insulin use , elevated BP or antihypertensive use , elevated lipid levels or lipid-lowering medication , current smoking , BMI ≥30 kg/m2 , lower peak exercise capacity assessed as metabolic equivalents [ METs ] , and ankle – brachial index < 0.9 or > 1.3 ) . Participants also completed the Beck Depression Inventory ( BDI ) and reported their use of ADMs . Results Of the participants , 14.7 % had BDI scores ≥11 , consistent with mild-moderate depression , and 16.5 % took ADMs ; 4.4 % had both depression markers ( i.e. elevated symptom scores and took ADMs ) . In logistic regression analyses of CVD risk ( elevated risk factor or use of medication to control the risk factor ) , controlled for demographic factors , continuous BDI  scores and ADM use were each independently associated with elevated BP ( or medication ) , current smoking , BMI ≥30 kg/m2 and lower MET values . ADM use was also associated with elevated serum lipids or use of lipid-lowering medication . Conclusions /interpretationAmong Look AHEAD participants , depression symptoms or ADM use on entry to the study were each independently associated with a wide range of CVD risk factors . Future research should assess the temporal dynamics of the relationships  of depression symptoms and ADM use with CVD risk factors . Trial registration Clinical trials.gov NCT00017953 Funding This study is funded by the National Institutes of Health with additional support from the Centers for Disease Control and Prevention BACKGROUND Recent data have highlighted shortcomings of the usual blood pressure ( BP ) hypothesis in several population s , and emphasized the importance of visit-to-visit variability of BP in predicting cardiovascular events . Herein , we aim ed at assessing the association between visit-to-visit BP variability and outcomes in chronic heart failure ( CHF ) patients enrolled in the Heart failure Endpoint evaluation of Angiotensin II Antagonist Losartan ( HEAAL ) . METHODS AND RESULTS The HEAAL study r and omized 3834 patients with HF and reduced ejection fraction administered 150 mg or 50 mg losartan daily in a double blind , r and omized , controlled trial . The patients were followed up for up to 6.8 years after r and omization , and BP was measured at 3 time points in the first year and at semi-annual visits in the years thereafter . Three measures of visit-to-visit BP variability were computed for each subject : the st and ard deviation , the coefficient of variation and the average absolute visit-to-visit variation . Cox proportional hazard models were used to investigate the relationship between variations in systolic blood pressure , baseline covariates and the time to death or heart failure hospitalization ( i.e. primary outcome ) . In multivariate analyses stratified on baseline BP , the patients with higher visit-to visit BP variability exhibited poorer outcomes ( average absolute difference in SBP in mmHg : hazard ratio : 1.023 [ 95 % CI ( 1.013 , 1.034 ) , P<0.0001 ] ) , independent from high dose losartan ( still beneficial ) . CONCLUSIONS For the first time , visit-to-visit BP variability was found elevated in CHF patients with reduced ejection fraction , and associated with poorer cardiovascular outcomes . Such assessment s should be prioritized for testing prevention strategies in CHF . CLINICAL TRIAL REGISTRATION This study is registered with the Clinical Trials.gov , number NCT00090259
In primary prevention , the association of BP-lowering treatment with major cardiovascular events was dependent on baseline systolic BP ( SBP ) .
Conclusions and Relevance Primary preventive BP lowering is associated with reduced risk for death and CVD if baseline SBP is 140 mm Hg or higher .
At lower BP levels , treatment is not associated with any benefit in primary prevention but might offer additional protection in patients with CHD
Importance High blood pressure ( BP ) is the most important risk factor for death and cardiovascular disease ( CVD ) worldwide .
The optimal cutoff for treatment of high BP is debated .
Objective To assess the association between BP lowering treatment and death and CVD at different BP levels .