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.
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
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 .