Sustained blood pressure control and coronary heart disease, stroke, heart failure, and mortality: An observational analysis of ALLHAT.
ABSTRACT: Achieving blood pressure (BP) control is associated with lower cardiovascular disease (CVD) risk, but less is known about CVD risk associated with sustained BP control over time. This observational analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was restricted to participants with four to seven visits with systolic BP (SBP) measurements during a 22-month period (n = 24 309). The authors categorized participants as having sustained BP control (SBP < 140 mm Hg) at 100%, 75% to <100%, 50% to <75%, and <50% of visits during this period. Outcomes included fatal coronary heart disease (CHD)/nonfatal myocardial infarction (MI), stroke, heart failure (HF), a composite CVD outcome (fatal CHD/nonfatal MI, stroke, or HF), and mortality. Hazard ratios (HRs) for the association of category of sustained BP control for each outcome were obtained using proportional hazards models. SBP control was present among 20.0% of participants at 100%, 16.4% at 75% to less than 100%, 27.0% at 50% to less than 75%, and 36.6% at less than 50% of visits. Compared to those with SBP control at 100% visits, adjusted HR (95% CI) among those with SBP control at <50% of visits was 1.16 (0.93-1.44) for fatal CHD/nonfatal MI, 1.71 (1.26-2.32) for stroke, 1.63 (1.30-2.06) for HF, 1.39 (1.20-1.62) for the composite CVD outcome, and 1.14 (0.99-1.30) for mortality. Sustained SBP control may be beneficial for preventing stroke, HF, and CVD outcomes in adults taking antihypertensive medication.
Project description:Variability of blood pressure (BP) across outpatient visits is frequently dismissed as random fluctuation around a patient's underlying BP.To examine the association of visit-to-visit variability (VVV) of systolic BP (SBP) and diastolic BP with cardiovascular disease (CVD) and mortality outcomes.Prospective cohort study.Post hoc analysis of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).25 814 ALLHAT participants.The VVV of SBP was defined as the SD across SBP measurements obtained at 7 visits conducted from 6 to 28 months after ALLHAT enrollment. Participants without CVD events during the first 28 months of follow-up were followed from the 28-month visit through the end of active ALLHAT follow-up. Outcomes included fatal coronary heart disease (CHD) or nonfatal myocardial infarction, all-cause mortality, stroke, and heart failure.During follow-up, 1194 fatal CHD or nonfatal MI events, 1948 deaths, 606 strokes, and 921 heart failure events occurred. After multivariable adjustment, including for mean SBP, the hazard ratio comparing participants in the highest versus lowest quintile of SD of SBP (?14.4 mm Hg vs. <6.5 mm Hg) was 1.30 (95% CI, 1.06 to 1.59) for fatal CHD or nonfatal MI, 1.58 (CI, 1.32 to 1.90) for all-cause mortality, 1.46 (CI, 1.06 to 2.01) for stroke, and 1.25 (CI, 0.97 to 1.61) for heart failure. Higher VVV of diastolic BP was also associated with CVD events and mortality.Long-term outcomes were not available.Higher VVV of SBP is associated with an increased risk for CVD and mortality. Future studies should examine whether reducing VVV of BP lowers this risk.National Institutes of Health.
Project description:Background High levels of physical activity have been associated with longer life expectancy free of cardiovascular disease (CVD), but specific types of CVD and sedentary behavior have not been examined. We examined associations of leisure-time moderate-to-vigorous physical activity (LTPA) and television viewing with life expectancy free of 3 types of CVD. Methods and Results We included 13 534 participants from the ARIC (Atherosclerosis Risk in Communities) cohort. We used multistate survival models to estimate associations of LTPA in the past year (no LTPA, less than the median, equal to or greater than the median) and television viewing (often or very often, sometimes, seldom or rarely) with life expectancy at age 50 free of nonfatal coronary heart disease (CHD), stroke, and heart failure (HF). Over 27 years of follow-up, 4519 participants developed one of the 3 nonfatal CVDs and 5475 deaths occurred. Compared with participants who engaged in no LTPA, participants who engaged in LTPA equal to or greater than the median had longer life expectancy free of nonfatal CHD (men: 1.5 years [95% CI, 1.0-2.0]; women: 1.6 years [95% CI, 1.1-2.2]), stroke (men: 1.8 years [95% CI, 1.2-2.3]; women: 1.8 years [95% CI, 1.3-2.3]), and HF (men: 1.6 years [95% CI, 1.1-2.1]; women: 1.7 years [95% CI, 1.2-2.2]). Compared with viewing more television, watching less television was associated with longer life expectancy free of CHD, stroke, and HF (?0.8 year). Conclusions Higher levels of LTPA and less television viewing were associated with longer life expectancy free of CHD, stroke, and HF. Engaging in LTPA and watching less television may increase the number of years lived free of CHD, stroke, and HF.
Project description:BACKGROUND:Blood pressure (BP) and cholesterol are major modifiable risk factors for cardiovascular disease (CVD), but effects of exposures during young adulthood on later life CVD risk have not been well quantified. OBJECTIVE:The authors sought to evaluate the independent associations between young adult exposures to risk factors and later life CVD risk, accounting for later life exposures. METHODS:The authors pooled data from 6 U.S. cohorts with observations spanning the life course from young adulthood to later life, and imputed risk factor trajectories for low-density lipoprotein (LDL) and high-density lipoprotein cholesterols, systolic and diastolic BP starting from age 18 years for every participant. Time-weighted average exposures to each risk factor during young (age 18 to 39 years) and later adulthood (age ?40 years) were calculated and linked to subsequent risks of coronary heart disease (CHD), heart failure (HF), or stroke. RESULTS:A total of 36,030 participants were included. During a median follow-up of 17 years, there were 4,570 CHD, 5,119 HF, and 2,862 stroke events. When young and later adult risk factors were considered jointly in the model, young adult LDL ?100 mg/dl (compared with <100 mg/dl) was associated with a 64% increased risk for CHD, independent of later adult exposures. Similarly, young adult SBP ?130 mm Hg (compared with <120 mm Hg) was associated with a 37% increased risk for HF, and young adult DBP ?80 mm Hg (compared with <80 mm Hg) was associated with a 21% increased risk. CONCLUSIONS:Cumulative young adult exposures to elevated systolic BP, diastolic BP and LDL were associated with increased CVD risks in later life, independent of later adult exposures.
Project description:BACKGROUND:Data from before the 2000s indicate that the majority of incident cardiovascular disease (CVD) events occur among US adults with systolic and diastolic blood pressure (SBP/DBP) ?140/90 mm?Hg. Over the past several decades, BP has declined and hypertension control has improved. METHODS:We estimated the percentage of incident CVD events that occur at SBP/DBP <140/90 mm?Hg in a pooled analysis of 3 contemporary US cohorts: the REGARDS study (Reasons for Geographic and Racial Differences in Stroke), the MESA (Multi-Ethnic Study of Atherosclerosis), and the JHS (Jackson Heart Study) (n=31?856; REGARDS=21?208; MESA=6779; JHS=3869). Baseline study visits were conducted in 2003 to 2007 for REGARDS, 2000 to 2002 for MESA, and 2000 to 2004 for JHS. BP was measured by trained staff using standardized methods. Antihypertensive medication use was self-reported. The primary outcome was incident CVD, defined by the first occurrence of fatal or nonfatal stroke, nonfatal myocardial infarction, fatal coronary heart disease, or heart failure. Events were adjudicated in each study. RESULTS:Over a mean follow-up of 7.7 years, 2584 participants had incident CVD events. Overall, 63.0% (95% confidence interval [CI], 54.9-71.1) of events occurred in participants with SBP/DBP <140/90 mm?Hg; 58.4% (95% CI, 47.7-69.2) and 68.1% (95% CI, 60.1-76.0) among those taking and not taking antihypertensive medication, respectively. The majority of events occurred in participants with SBP/DBP <140/90 mm?Hg among those <65 years of age (66.7%; 95% CI, 60.5-73.0) and ?65 years of age (60.3%; 95% CI, 51.0-69.5), women (61.4%; 95% CI, 49.9-72.9) and men (63.8%; 95% CI, 58.4-69.1), and for whites (68.7%; 95% CI, 66.1-71.3), blacks (59.0%; 95% CI, 49.5-68.6), Hispanics (52.7%; 95% CI, 45.1-60.4), and Chinese-Americans (58.5%; 95% CI, 45.2-71.8). Among participants taking antihypertensive medication with SBP/DBP <140/90 mm?Hg, 76.6% (95% CI, 75.8-77.5) were eligible for statin treatment, but only 33.2% (95% CI, 32.1-34.3) were taking one, and 19.5% (95% CI, 18.5-20.5) met the SPRINT (Systolic Blood Pressure Intervention Trial) eligibility criteria and may benefit from a SBP target goal of 120 mm?Hg. CONCLUSIONS:Although higher BP levels are associated with increased CVD risk, in the modern era, the majority of incident CVD events occur in US adults with SBP/DBP <140/90 mm?Hg. While absolute risk and cost-effectiveness should be considered, additional CVD risk-reduction measures for adults with SBP/DBP <140/90 mm?Hg at high risk for CVD may be warranted.
Project description:Given that observational associations may be inaccurate, we used offspring blood pressure (BP) to provide alternative estimates of the associations between own BP and mortality. Observational associations between BP and mortality, estimated as hazard ratios (HRs) from Cox regression, were compared to HRs obtained using offspring BP as an instrumental variable (IV) for own BP (N?=?32,227 mother-offspring and 27,535 father-offspring pairs). Observationally, there were positive associations between own BP and mortality from all-causes, cardiovascular disease (CVD), coronary heart disease (CHD), stroke and diabetes. Point estimates of the associations between BP and mortality from all-causes, CVD and CHD were amplified in magnitude when using offspring BP as an IV. For example, the HR for all-cause mortality per standard deviation (SD) increase in own systolic BP (SBP) obtained in conventional observational analyses increased from 1.10 (95% CI: 1.09-1.12; P?<?0.0001) to 1.31 (95% CI: 1.19-1.43; P?<?0.0001). Additionally, SBP was positively associated with diabetes and cancer mortality (HRs: 2.00; 95% CI: 1.12-3.35; P?=?0.02 and 1.20; 95% CI: 1.02-1.42; P?=?0.03, respectively), and diastolic BP (DBP) with stroke mortality (HR: 1.30; 95% CI: 1.02-1.66; P?=?0.03). Results support positive associations between BP and mortality from all-causes, CVD, and CHD, SBP on cancer mortality, and DBP on stroke mortality.
Project description:Importance:Little is known regarding the association between level of blood pressure (BP) in young adulthood and cardiovascular disease (CVD) events by middle age. Objective:To assess whether young adults who developed hypertension, defined by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) BP guideline, before age 40 years have higher risk for CVD events compared with those who maintained normal BP. Design, Setting, and Participants:Analyses were conducted in the prospective cohort Coronary Artery Risk Development in Young Adults (CARDIA) study, started in March 1985. CARDIA enrolled 5115 African American and white participants aged 18 to 30 years from 4 US field centers (Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California). Outcomes were available through August 2015. Exposures:Using the highest BP measured from the first examination to the examination closest to, but not after, age 40 years, each participant was categorized as having normal BP (untreated systolic BP [SBP] <120 mm Hg and diastolic BP [DBP] <80 mm Hg; n?=?2574); elevated BP (untreated SBP 120-129 mm Hg and DBP <80 mm Hg; n?=?445); stage 1 hypertension (untreated SBP 130-139 mm Hg or DBP 80-89 mm Hg; n?=?1194); or stage 2 hypertension (SBP ?140 mm Hg, DBP ?90 mm Hg, or taking antihypertensive medication; n?=?638). Main Outcomes and Measures:CVD events: fatal and nonfatal coronary heart disease (CHD), heart failure, stroke, transient ischemic attack, or intervention for peripheral artery disease (PAD). Results:The final cohort included 4851 adults (mean age when follow-up for outcomes began, 35.7 years [SD, 3.6]; 2657 women [55%]; 2441 African American [50%]; 206 taking antihypertensive medication [4%]). Over a median follow-up of 18.8 years, 228 incident CVD events occurred (CHD, 109; stroke, 63; heart failure, 48; PAD, 8). CVD incidence rates for normal BP, elevated BP, stage 1 hypertension, and stage 2 hypertension were 1.37 (95% CI, 1.07-1.75), 2.74 (95% CI, 1.78-4.20), 3.15 (95% CI, 2.47-4.02), and 8.04 (95% CI, 6.45-10.03) per 1000 person-years, respectively. After multivariable adjustment, hazard ratios for CVD events for elevated BP, stage 1 hypertension, and stage 2 hypertension vs normal BP were 1.67 (95% CI, 1.01-2.77), 1.75 (95% CI, 1.22-2.53), and 3.49 (95% CI, 2.42-5.05), respectively. Conclusions and Relevance:Among young adults, those with elevated blood pressure, stage 1 hypertension, and stage 2 hypertension before age 40 years, as defined by the blood pressure classification in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, had significantly higher risk for subsequent cardiovascular disease events compared with those with normal blood pressure before age 40 years. The ACC/AHA blood pressure classification system may help identify young adults at higher risk for cardiovascular disease events.
Project description:Common blood pressure (BP) trajectories are not well established in elderly persons, and their association with clinical outcomes is uncertain.We used hierarchical cluster analysis to identify discrete BP trajectories among 4,067 participants in the Cardiovascular Health Study using repeated BP measures from years 0 to 7. We then evaluated associations of each BP trajectory cluster with all-cause mortality, incident cardiovascular disease (CVD, defined as stroke or myocardial infarction) (N = 2,837), and incident congestive heart failure (HF) (N = 3,633) using Cox proportional hazard models.Median age was 77 years at year 7. Over a median 9.3 years of follow-up, there were 2,475 deaths, 659 CVD events, and 1,049 HF events. The cluster analysis identified 3 distinct trajectory groups. Participants in cluster 1 (N = 1,838) had increases in both systolic (SBP) and diastolic (DBP) BPs, whereas persons in cluster 2 (N = 1,109) had little change in SBP but declines in DBP. Persons in cluster 3 (N = 1,120) experienced declines in both SBP and DBP. After multivariable adjustment, clusters 2 and 3 were associated with increased mortality risk relative to cluster 1 (hazard ratio = 1.21, 95% confidence interval: 1.06-1.37 and hazard ratio = 1.20, 95% confidence interval: 1.05-1.36, respectively). Compared to cluster 1, cluster 3 had higher rates of incident CVD but associations were not statistically significant in demographic-adjusted models (hazard ratio = 1.16, 95% confidence interval: 0.96-1.39). Findings were similar when stratified by use of antihypertensive therapy.Among community-dwelling elders, distinct BP trajectories were identified by integrating both SBP and DBP. These clusters were found to have differential associations with outcomes.
Project description:OBJECTIVE:The prognostic value of long-term glycemic variability is incompletely understood. We evaluated the influence of visit-to-visit variability (VVV) of fasting blood glucose (FBG) on incident cardiovascular disease (CVD) and mortality. RESEARCH DESIGN AND METHODS:We conducted a prospective cohort analysis including 4,982 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) who attended the baseline, 24-month, and 48-month visits. VVV of FBG was defined as the SD or variability independent of the mean (VIM) across FBG measurements obtained at the three visits. Participants free of CVD during the first 48 months of the study were followed for incident CVD (coronary heart disease [CHD], stroke, and heart failure [HF]) and all-cause mortality. RESULTS:Over a median follow-up of 5 years, there were 305 CVD events (189 CHD, 45 stroke, and 81 HF) and 154 deaths. The adjusted hazard ratio (HR) comparing participants in the highest versus lowest quartile of SD of FBG (?26.4 vs. <5.5 mg/dL) was 1.43 (95% CI 0.93-2.19) for CVD and 2.22 (95% CI 1.22-4.04) for all-cause mortality. HR for VIM was 1.17 (95% CI 0.84-1.62) for CVD and 1.89 (95% CI 1.21-2.93) for all-cause mortality. Among individuals without diabetes, the highest quartile of SD of FBG (HR 2.67 [95% CI 0.14-6.25]) or VIM (HR 2.50 [95% CI 1.40-4.46]) conferred a higher risk of death. CONCLUSIONS:Greater VVV of FBG is associated with increased mortality risk. Our data highlight the importance of achieving normal and consistent glycemic levels for improving clinical outcomes.
Project description:BACKGROUND:Cardiovascular disease (CVD) and its most common manifestations--including coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF)--are major causes of morbidity and mortality. In many industrialized countries, cardiovascular disease (CVD) claims more lives each year than any other disease. Heart disease and stroke are the first and third leading causes of death in the United States. Prior investigations have reported several single gene variants associated with CHD, stroke, HF, and AF. We report a community-based genome-wide association study of major CVD outcomes. METHODS:In 1345 Framingham Heart Study participants from the largest 310 pedigrees (54% women, mean age 33 years at entry), we analyzed associations of 70,987 qualifying SNPs (Affymetrix 100K GeneChip) to four major CVD outcomes: major atherosclerotic CVD (n = 142; myocardial infarction, stroke, CHD death), major CHD (n = 118; myocardial infarction, CHD death), AF (n = 151), and HF (n = 73). Participants free of the condition at entry were included in proportional hazards models. We analyzed model-based deviance residuals using generalized estimating equations to test associations between SNP genotypes and traits in additive genetic models restricted to autosomal SNPs with minor allele frequency > or =0.10, genotype call rate > or =0.80, and Hardy-Weinberg equilibrium p-value > or = 0.001. RESULTS:Six associations yielded p < 10(-5). The lowest p-values for each CVD trait were as follows: major CVD, rs499818, p = 6.6 x 10(-6); major CHD, rs2549513, p = 9.7 x 10(-6); AF, rs958546, p = 4.8 x 10(-6); HF: rs740363, p = 8.8 x 10(-6). Of note, we found associations of a 13 Kb region on chromosome 9p21 with major CVD (p 1.7-1.9 x 10(-5)) and major CHD (p 2.5-3.5 x 10(-4)) that confirm associations with CHD in two recently reported genome-wide association studies. Also, rs10501920 in CNTN5 was associated with AF (p = 9.4 x 10(-6)) and HF (p = 1.2 x 10(-4)). Complete results for these phenotypes can be found at the dbgap website http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 webcite. CONCLUSION:No association attained genome-wide significance, but several intriguing findings emerged. Notably, we replicated associations of chromosome 9p21 with major CVD. Additional studies are needed to validate these results. Finding genetic variants associated with CVD may point to novel disease pathways and identify potential targeted preventive therapies.
Project description:Although orthostatic hypotension (OH) is often considered a contraindication to blood pressure (BP) treatment, evidence is lacking. We examined the effect of BP goal or initial medication choice on OH in AASK (African American Study of Kidney Disease and Hypertension), a 2×3 factorial trial. Blacks with chronic kidney disease attributed to hypertension were randomly assigned 1 of 2 BP goals: intensive (mean arterial pressure, ?92 mm?Hg) or standard (mean arterial pressure, 102-107 mm?Hg) and 1 of 3 initial medications (ramipril, metoprolol, and amlodipine). Postural changes in systolic BP, diastolic BP, or heart rate (HR) were determined after 2 minutes and 45 seconds of standing. OH was assessed each visit and defined using the consensus definition (drop in systolic BP ?20 mm?Hg or diastolic BP ?10 mm?Hg). Median follow-up was 4 years. Outcomes were congestive heart failure, stroke, nonfatal cardiovascular disease (CVD), fatal CVD, any CVD (composite of preceding events), and all-cause mortality. There were 1094 participants (mean age, 54.5±10.7 years; 38.8% female; OH was assessed at 52?864 visits). Mean seated systolic BP, diastolic BP, and HR were 150.3±23.9 mm?Hg, 95.5±14.2 mm?Hg, and 72.0±12.6 bpm, respectively. A more intensive BP goal did not alter the distributions of standing BP and was not associated with OH, but metoprolol was associated with systolic OH compared with ramipril (odds ratio, 1.68; 95% CI, 1.15-2.46) and amlodipine (odds ratio, 1.94; 95% CI, 1.09-3.44). Although consensus OH was associated with stroke (HR, 5.01; 95% CI, 1.80-13.92), nonfatal CVD (HR, 2.28; 95% CI, 1.21-4.30), and any CVD event (HR, 2.12; 95% CI, 1.12-3.98), neither BP goal or medication altered this risk. Concerns about causing OH or its CVD consequences should not deter a lower BP goal among adults with chronic kidney disease attributed to hypertension.