Within-subject blood pressure level--not variability--predicts fatal and nonfatal outcomes in a general population.
ABSTRACT: To assess the prognostic significance of blood pressure (BP) variability, we followed health outcomes in a family-based random population sample representative of the general population (n=2944; mean age: 44.9 years; 50.7% women). At baseline, BP was measured 5 times consecutively at each of 2 home visits 2 to 4 weeks apart. We assessed within-subject overall (10 readings), within- and between-visit systolic BP variability from variability independent of the mean, the difference between maximum and minimum BP, and average real variability. Over a median follow-up of 12 years, 401 deaths occurred and 311 participants experienced a fatal or nonfatal cardiovascular event. Overall systolic BP variability averaged (SD) 5.45 (2.82) units, 15.87 (8.36) mmHg, and 4.08 (2.05) mmHg for variability independent of the mean, difference between maximum and minimum BP, and average real variability, respectively. Female sex, older age, higher-mean systolic BP, lower body mass index, a history of peripheral arterial disease, and use of ?-blockers were the main correlates of systolic BP variability. In multivariable-adjusted analyses, overall and within- and between-visit BP variability did not predict total or cardiovascular mortality or the composite of any fatal plus nonfatal cardiovascular end point. For instance, the hazard ratios for all cardiovascular events combined in relation to overall variability independent of the mean, difference between maximum and minimum BP, and average real variability were 1.05 (0.96-1.15), 1.06 (0.96-1.16), and 1.08 (0.98-1.19), respectively. By contrast, mean systolic BP was a significant predictor of all end points under study, independent of BP variability. In conclusion, in an unbiased population sample, BP variability did not contribute to risk stratification over and beyond mean systolic BP.
Project description:Average real variability (ARV) is a recently proposed index for short-term blood pressure (BP) variability. We aimed to determine the minimum number of BP readings required to compute ARV without loss of prognostic information.ARV was calculated from a discovery dataset that included 24-hour ambulatory BP measurements for 1,254 residents (mean age = 56.6 years; 43.5% women) of Copenhagen, Denmark. Concordance between ARV from full (?80 BP readings) and randomly reduced 24-hour BP recordings was examined, as was prognostic accuracy. A test dataset that included 5,353 subjects (mean age = 54.0 years; 45.6% women) with at least 48 BP measurements from 11 randomly recruited population cohorts was used to validate the results.In the discovery dataset, a minimum of 48 BP readings allowed an accurate assessment of the association between cardiovascular risk and ARV. In the test dataset, over 10.2 years (median), 806 participants died (335 cardiovascular deaths, 206 cardiac deaths) and 696 experienced a major fatal or nonfatal cardiovascular event. Standardized multivariable-adjusted hazard ratios (HRs) were computed for associations between outcome and BP variability. Higher diastolic ARV in 24-hour ambulatory BP recordings predicted (P < 0.01) total (HR = 1.12), cardiovascular (HR = 1.19), and cardiac (HR = 1.19) mortality and fatal combined with nonfatal cerebrovascular events (HR = 1.16). Higher systolic ARV in 24-hour ambulatory BP recordings predicted (P < 0.01) total (HR = 1.12), cardiovascular (HR = 1.17), and cardiac (HR = 1.24) mortality.Forty-eight BP readings over 24 hours were observed to be adequate to compute ARV without meaningful loss of prognostic information.
Project description:Increased visit-to-visit variability of BP is associated with cardiovascular disease risk. We examined the association of visit-to-visit variability of BP with renal outcomes among 21,245 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.We measured mean BP and visit-to-visit variability of BP, defined as SD, across five to seven visits occurring 6-28 months after participants were randomized to chlorthalidone, amlodipine, or lisinopril. The composite outcome included incident ESRD after assessment of SD of systolic BP or ?50% decline in eGFR between 24 months and 48 or 72 months after randomization. We repeated the analyses using average real variability and peak value of systolic BP and for visit-to-visit variability of diastolic BP.Over a mean follow-up of 3.5 years, 297 outcomes occurred. After multivariable adjustment, including baseline eGFR and mean systolic BP, the hazard ratios for the composite end point were 1.29 (95% confidence interval [95% CI], 0.75 to 2.22), 1.76 (95% CI, 1.06 to 2.91), 1.46 (95% CI, 0.88 to 2.45), and 2.05 (95% CI, 1.25 to 3.36) for the second through fifth (SD of systolic BP =6.63-8.82, 8.83-11.14, 11.15-14.56, and >14.56 mmHg, respectively) versus the first (SD of systolic BP <6.63 mmHg) quintile of SD of systolic BP, respectively (P trend =0.004). The association was similar when ESRD and a 50% decline in eGFR were analyzed separately, for other measures of visit-to-visit variability of systolic BP, and for visit-to-visit variability of diastolic BP.Higher visit-to-visit variability of BP is associated with higher risk of renal outcomes independent of mean BP.
Project description:Low adherence to antihypertensive medication has been hypothesized to increase visit-to-visit variability (VVV) of blood pressure (BP). We assessed the association between antihypertensive medication adherence and VVV of BP in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). VVV of BP was calculated using SD independent of mean, SD, and average real variability across study visits conducted 6 to 28 months after randomization. Participants who reported taking <80% of their antihypertensive medication at ?1 study visits were categorized as nonadherent. Participants were followed up for cardiovascular events and mortality after the assessment of adherence and VVV of BP. SD independent of mean of BP was higher for nonadherent (n=2912) versus adherent (n=16?878) participants; 11.4±4.9 versus 10.5±4.5 for systolic BP; 6.8±2.8 versus 6.2±2.6 for diastolic BP (each P<0.001). SD independent of mean of BP remained higher among nonadherent than among adherent participants after multivariable adjustment (0.8 [95% confidence interval, 0.7-1.0] higher for systolic BP and 0.4 [95% confidence interval, 0.3-0.5] higher for diastolic BP]. SD and average real variability of systolic BP and diastolic BP were also higher among nonadherent than among adherent participants. Adjustment for nonadherence did not explain the association of VVV of BP with higher fatal coronary heart disease or nonfatal myocardial infarction, stroke, heart failure, or mortality risk. In conclusion, improving medication adherence may lower VVV of BP. However, VVV of BP is associated with cardiovascular outcomes independent of medication adherence.
Project description:Orthostatic hypotension (OH) is associated with hypertension and diabetes mellitus. However, in populations with both hypertension and diabetes mellitus, its prevalence, the effect of intensive versus standard systolic blood pressure (BP) targets on incident OH, and its prognostic significance are unclear. In 4266 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) BP trial, seated BP was measured 3×, followed by readings every minute for 3 minutes after standing. Orthostatic BP change, calculated as the minimum standing minus the mean seated systolic BP and diastolic BP, was assessed at baseline, 12 months, and 48 months. The relationship between OH and clinical outcomes (total and cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalization or death and the primary composite outcome of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) was assessed using proportional hazards analysis. Consensus OH, defined by orthostatic decline in systolic BP ?20 mm?Hg or diastolic BP ?10 mm?Hg, occurred at ?1 time point in 20% of participants. Neither age nor systolic BP treatment target (intensive, <120 mm?Hg versus standard, <140 mm?Hg) was related to OH incidence. Over a median follow-up of 46.9 months, OH was associated with increased risk of total death (hazard ratio, 1.61; 95% confidence interval, 1.11-2.36) and heart failure death/hospitalization (hazard ratio, 1.85, 95% confidence interval, 1.17-2.93), but not with the primary outcome or other prespecified outcomes. In patients with type 2 diabetes mellitus and hypertension, OH was common, not associated with intensive versus standard BP treatment goals, and predicted increased mortality and heart failure events.
Project description:Blood pressure variability based on office measurement predicts outcome in selected patients. We explored whether novel indices of blood pressure variability derived from the self-measured home blood pressure predicted outcome in a general population. We monitored mortality and stroke in 2421 Ohasama residents (Iwate Prefecture, Japan). At enrollment (1988-1995), participants (mean age, 58.6 years; 60.9% women; 27.1% treated) measured their blood pressure at home, using an oscillometric device. In multivariable-adjusted Cox models, we assessed the independent predictive value of the within-subject mean systolic blood pressure (SBP) and corresponding variability as estimated by variability independent of the mean, difference between maximum and minimum blood pressure, and average real variability. Over 12.0 years (median), 412 participants died, 139 of cardiovascular causes, and 223 had a stroke. In models including morning SBP, variability independent of the mean and average real variability (median, 26 readings) predicted total and cardiovascular mortality in all of the participants (P?0.044); variability independent of the mean predicted cardiovascular mortality in treated (P=0.014) but not in untreated (P=0.23) participants; and morning maximum and minimum blood pressure did not predict any end point (P?0.085). In models already including evening SBP, only variability independent of the mean predicted cardiovascular mortality in all and in untreated participants (P?0.046). The R(2) statistics, a measure for the incremental risk explained by adding blood pressure variability to models already including SBP and covariables, ranged from <0.01% to 0.88%. In a general population, new indices of blood pressure variability derived from home blood pressure did not incrementally predict outcome over and beyond mean SBP.
Project description:Meta-analyses have shown that supervised isometric handgrip training reduces blood pressure in hypertensives. However, the mechanism(s) underlying these effects in medicated hypertensive patients, as well as the effects from home-based exercise training, is uncertain. The purpose of this study was to compare the effects of supervised and home-based isometric handgrip training on cardiovascular parameters in medicated hypertensives. In this randomized controlled trial, 72 hypertensive individuals (38-79 years old, 70% female) were randomly assigned to three groups: home-based, supervised isometric handgrip training or control groups. Home-based and supervised isometric handgrip training was completed thrice weekly (4 × 2 min at 30% of maximal voluntary contraction, with 1-min rest between bouts, alternating the hands). Before and after 12 weeks brachial, central and ambulatory blood pressures (BP), arterial stiffness, heart rate variability, vascular function, oxidative stress and inflammation markers were obtained. No significant (p > 0.05) effect was observed for ambulatory BP, arterial stiffness, heart rate variability, vascular function and oxidative stress and inflammatory markers in all three groups. Brachial BP decreased in the supervised group (Systolic: 132 ± 4 vs. 120 ± 3 mmHg; Diastolic: 71 ± 2 vs. 66 ± 2 mmHg, p < 0.05), whereas no significant differences were observed in the home-based (Systolic: 130 ± 4 vs. 126 ± 3 mmHg; diastolic: 73 ± 3 vs. 71 ± 3 mmHg) and control groups (p > 0.05). Supervised handgrip exercise also reduced central BP systolic (120 ± 5 vs. 109 ± 5 mmHg), diastolic (73 ± 2 vs. 67 ± 2 mmHg); and mean BP (93 ± 3 vs. 84 ± 3 mmHg), whereas no significant effects were found in the home-based (Systolic: 119 ± 4 vs. 115 ± 3 mmHg; Diastolic: 74 ± 3 vs. 71 ± 3 mmHg) and control groups (p > 0.05). In conclusion, supervised, but not home-based, isometric training lowered brachial and central BP in hypertensives.
Project description:An exaggerated blood pressure (BP) response to exercise has been linked to cardiovascular disease, but little is known about the impact of age and sex on this response. Therefore, this study examined the hemodynamic and skeletal muscle metabolic response to dynamic plantar flexion exercise, at 40% of maximum plantar flexion work rate, in 40 physical activity-matched young (23 ± 1 yr, n = 20) and old (73 ± 2 yr, n = 20), equally distributed, male and female subjects. Central hemodynamics and BP (finometer), popliteal artery blood flow (Doppler ultrasound), and skeletal muscle metabolism (31P-magnetic resonance spectroscopy) were measured during 5 min of plantar flexion exercise. Popliteal artery blood flow and high-energy phosphate responses to exercise were not affected by age or sex, whereas aging, independent of sex, attenuated stroke volume and cardiac output responses. Systolic BP and mean arterial pressure responses were exaggerated in old women (?42 ± 4 and ?28 ± 3 mmHg, respectively), with all other groups exhibiting similar increases in systolic BP (old men: ?27 ± 8 mmHg, young men: ?27 ± 3 mmHg, and young women: ?22 ± 3 mmHg) and mean arterial pressure (old men: ?15 ± 4 mmHg, young men: ?19 ± 2 mmHg, and young women: ?17 ± 2 mmHg). Interestingly, the exercise-induced change in systemic vascular resistance in old women (?0.8 ± 1.0 mmHg·l-1·min-1) was augmented compared with young women and young and old men (?-2.8 ± 0.5, ?-1.6 ± 0.6, and ?-3.18 ± 1.4 mmHg·l-1·min-1, respectively, P < 0.05). Thus, in combination, advancing age and female sex results in an exaggerated BP response to exercise, likely the result of a failure to reduce systemic vascular resistance. NEW & NOTEWORTHY An exaggerated blood pressure response to exercise has been linked to cardiovascular disease; however, little is known about how age and sex impact this response in healthy individuals. During dynamic exercise, older women exhibited an exaggerated blood pressure response driven by an inability to lower systemic vascular resistance.
Project description:AIMS:Sulodexide is a highly purified mixture of glycosaminoglycans that has been studied for its anti-albuminuric potential. Considering the effects of glycosaminoglycans on endothelial function and sodium homeostasis, we hypothesized that sulodexide may lower blood pressure (BP). In this meta-analysis, we therefore investigated the antihypertensive effects of sulodexide treatment. METHODS:We selected randomized controlled trials that investigated sulodexide treatment of at least 4 weeks and measured BP at baseline and after treatment. Two reviewers independently extracted data on study design, risk of bias, population characteristics and outcome measures. In addition, we contacted authors and pharmaceutical companies to provide missing data. RESULTS:Eight studies, totalling 3019 subjects (mean follow-up 4.4 months) were included. Mean age was 61 years and mean baseline BP was 135/75 mmHg. Compared with control treatment, sulodexide resulted in a significant systolic (2.2 mmHg [95% CI 0.3, 4.1], P = 0.02) and diastolic BP reduction (1.7 mmHg [95% CI 0.6, 2.9], P = 0.004). Hypertensive patients displayed the largest systolic BP and diastolic BP reductions (10.2/5.4 mmHg, P < 0.001). Higher baseline systolic and diastolic BP were significantly associated with larger systolic (r(2)=0.83, P < 0.001) and diastolic BP (r(2)=0.41, P = 0.02) reductions after sulodexide treatment. In addition, systolic (r(2)=0.41, P = 0.03) and diastolic BP reductions (r(2)=0.60, P = 0.005) were significantly associated with albuminuria reduction. CONCLUSION:Our data suggest that sulodexide treatment results in a significant BP reduction, especially in hypertensive subjects. This indicates that endothelial glycosaminoglycans might be an independent therapy target in cardiovascular disease. Future studies should further address the BP lowering potential of sulodexide.
Project description:Increasing BP during maintenance hemodialysis or intradialytic hypertension is associated with increased morbidity and mortality. In hemodialysis patients, ambulatory BP measurements predict adverse cardiovascular outcomes better than in-center measurements. We hypothesized that patients with intradialytic hypertension have higher interdialytic ambulatory systolic BP than those without intradialytic hypertension.We performed a case-control study in adult hemodialysis patients. Cases consisted of subjects with intradialytic-hypertension (systolic BP increase ?10 mmHg from pre- to posthemodialysis in at least four of six treatments), and controls were subjects with ?10 mmHg decreases from pre- to posthemodialysis in at least four of six treatments. The primary outcome was mean interdialytic 44-hour systolic ambulatory BP.Fifty subjects with a mean age of 54.5 years were enrolled (25 per group) among whom 80% were men, 86% diabetic, 62% Hispanic, and 38% African American. The mean prehemodialysis systolic BP for the intradialytic-hypertension and control groups were 144.0 and 155.5 mmHg, respectively. Mean posthemodialysis systolic BP was 159.0 and 128.1 mmHg, for the intradialytic-hypertension and control groups, respectively. The mean systolic ambulatory BP was 155.4 and 142.4 mmHg for the intradialytic-hypertension and control groups, respectively (P = 0.005). Both daytime and nocturnal systolic BP were higher among those with intradialytic hypertension as compared with controls. There was no difference in interdialytic weight gain between groups.Time-integrated BP burden as measured by 44-hour ambulatory BP is higher in hemodialysis patients with intradialytic hypertension than those without intradialytic hypertension.
Project description:BACKGROUND: Morning hypertension is a risk factor for cardiovascular and cerebrovascular events, and consequently diagnosis and control of morning hypertension are considered very important. We previously reported the results of the Azelnidipine Treatment for Hypertension Open-label Monitoring in the Early morning (At-HOME) Study, which indicated that azelnidipine effectively controlled morning hypertension. OBJECTIVES: The objective of this At-HOME subgroup analysis was to evaluate the sustained blood pressure (BP)-lowering effect of azelnidipine, using mean morning and evening systolic BP [ME average] and morning systolic BP minus evening systolic BP (ME difference). METHODS: We analyzed the self-measured home BP data (measured in the morning and at bedtime) from this 16-week prospective observational study to clarify the effect of morning dosing of azelnidipine (mean [± standard deviation] maximum dose 14.3 ± 3.6 mg/day). A subgroup of patients from the At-HOME Study who had an evening home BP measurement within 28 days prior to the baseline date were used for efficacy analysis (n = 2,546; mean age, 65.1 years; female, 53.6 %). RESULTS: Home systolic BP/diastolic BP levels in the morning and evening were significantly lowered (p < 0.0001) by -19.4 ± 17.1/-10.3 ± 10.6 and -16.9 ± 17.0/-9.4 ± 10.6 mmHg, respectively. Home pulse rates in the morning and evening were also significantly lowered (p < 0.0001) by -3.5 ± 7.8 and -3.5 ± 7.3 beats/min, respectively. At baseline, patients whose ME average was ?135 mmHg and whose ME difference was ?15 mmHg (defined as morning-predominant hypertension) accounted for 20.4 % of the study population. However, at the end of the study, the number of such patients was significantly reduced to 7.9 % (p < 0.0001). Patients whose ME average was ?135 mmHg and whose ME difference was <15 mmHg (defined as sustained hypertension) accounted for 71.1 % of the study population at baseline. This was reduced significantly to 42.8 % at the end of the study (p < 0.0001). ME average decreased significantly from 153.8 ± 15.5 mmHg to 135.6 ± 11.9 mmHg, and ME difference also decreased significantly from 6.7 ± 13.1 mmHg to 4.7 ± 10.8 mmHg (both p < 0.0001). CONCLUSION: These results suggest that azelnidipine improved morning hypertension with its sustained BP-lowering effect.