Numerous studies addressed the predictive value of the nighttime blood pressure (BP) as captured by ambulatory monitoring. However, arbitrary cutoff limits in dichotomized analyses of continuous ...variables, data dredging across selected subgroups, extrapolation of cross-sectional studies to prospective outcomes, and lack of comprehensive adjustments for confounders make interpretation of the literature difficult. We reviewed prospective studies with total mortality or a composite cardiovascular end point as an outcome in relation to the level and the circadian profile of systolic BP. We analyzed studies in hypertensive patients (n = 23 856) separately from those in individuals randomly recruited from populations (n = 9641). We pooled summary statistics and individual subject data, respectively. In both patients and populations, in analyses in which nighttime BP was additionally adjusted for daytime BP and vice versa, nighttime BP was a stronger predictor than daytime BP. With adjustment for the 24-hour BP, both the night-to-day BP ratio and dipping status remained significant predictors of outcome but added little prognostic value over and beyond the 24-hour BP level. In the absence of conclusive evidence proving that nondipping is a reversible risk factor, the option whether or not to restore the diurnal blood pressure profile to a normal pattern should be left to the clinical judgment of doctors and should be individualized for each patient. Current guidelines on the interpretation of ambulatory BP recording need to be updated.
Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear. It has been suggested that antihypertensive therapy may reduce the risk of stroke, ...despite possibly increasing the risk of death.
We randomly assigned 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting-enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke.
The active-treatment group (1933 patients) and the placebo group (1912 patients) were well matched (mean age, 83.6 years; mean blood pressure while sitting, 173.0/90.8 mm Hg); 11.8% had a history of cardiovascular disease. Median follow-up was 1.8 years. At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. In an intention-to-treat analysis, active treatment was associated with a 30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval CI, -1 to 51; P=0.06), a 39% reduction in the rate of death from stroke (95% CI, 1 to 62; P=0.05), a 21% reduction in the rate of death from any cause (95% CI, 4 to 35; P=0.02), a 23% reduction in the rate of death from cardiovascular causes (95% CI, -1 to 40; P=0.06), and a 64% reduction in the rate of heart failure (95% CI, 42 to 78; P<0.001). Fewer serious adverse events were reported in the active-treatment group (358, vs. 448 in the placebo group; P=0.001).
The results provide evidence that antihypertensive treatment with indapamide (sustained release), with or without perindopril, in persons 80 years of age or older is beneficial. (ClinicalTrials.gov number, NCT00122811 ClinicalTrials.gov.).
Hypertension guidelines recommend blood pressure self-measurement at home (HBP), but no previous trial has assessed cardiovascular outcomes in hypertensive patients treated according to HBP. The ...multicenter Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP; 2001-2010) trial involved 3518 patients (50% women; mean age 59.6 years) with an untreated systolic/diastolic HBP of 135-179/85-119 mm Hg. In a 2 × 3 design, patients were randomized to usual control (125-134/80-84 mm Hg (UC)) vs. tight control (<125/<80 mm Hg (TC)) of HBP and to initiation of drug treatment with angiotensin converting enzyme inhibitors, angiotensin receptor blockers or calcium channel blockers. During follow-up, a computer algorithm automatically generated treatment recommendations based on HBP. At the last follow-up (median 5.3 years), TC patients used more antihypertensive drugs than UC patients (1.82 vs. 1.74 defined daily doses, P=0.045) and had a greater HBP reduction (21.3/13.1 mm Hg vs. 22.7/13.9 mm Hg, P=0.018/0.020), but they less frequently achieved the lower HBP targets (37.4 vs. 63.5%, P<0.0001). The primary end point, cardiovascular death plus stroke and myocardial infarction, occurred in 25 UC and 26 TC patients (hazard ratio, 1.02; 95% confidence interval, 0.59-1.77; P=0.94). Rates were similar (P≥0.13) in the three drug groups. In all patients combined, the risk of the primary end point independently increased by 41% (6-89%; P=0.019) and 47% (15-87%; P=0.0020) for a 1-s.d. increase in baseline (12.5 mm Hg) and follow-up (13.2 mm Hg) systolic HBP. The 5-year risk was minimal (≤1%) if on-treatment systolic HBP was 131.6 mm Hg or less. HOMED-BP proved the feasibility of adjusting antihypertensive drug treatment based on HBP and suggests that a systolic HBP level of 130 mm Hg should be an achievable and safe target.
We assessed, in a double-blind, placebo-controlled trial, whether lowering blood pressure (BP) prevents the recurrence of stroke in Chinese patients with cerebrovascular disease. Patients were ...randomized into two groups: 2825 patients received a placebo and 2840 patients received 2.5 mg of indapamide daily. The primary and secondary outcomes were the recurrence of fatal or nonfatal stroke and major fatal and nonfatal cardiovascular events, respectively. The average systolic/diastolic BP at randomization was 153.8/92.8 mm Hg. At median follow-up (2 years), BP was, on an average, 6.8/3.3 mm Hg lower in patients on active treatment. In total, 143 patients on indapamide and 219 patients on placebo had recurrent strokes (hazard ratio for indapamide, 0.69; 95% confidence interval (CI): 0.54-0.89; P<0.001). In addition, 199 patients on indapamide and 258 patients on placebo had a cardiovascular event (hazard ratio, 0.75; 95% CI: 0.89-0.62; P=0.002). We performed a systematic review of literature that included our new results. Across 10 trials, the odds ratio for the prevention of stroke recurrence by BP lowering was 0.78 (95% CI: 0.68-0.90; P=0.0007). The pooled odds ratio was 0.63 (95% CI: 0.54-0.73; P<0.0001) for trials involving diuretics as a component of therapy and 0.93 (95% CI: 0.87-1.01; P=0.086) for trials in which treatment included renin system inhibitors (P<0.0001 for heterogeneity). The weighted correlation between the odds for stroke recurrence and the reduction in systolic BP was -0.57 (P=0.067). In conclusion, BP lowering by indapamide treatment reduced the recurrence of stroke and the incidence of cardiovascular events in Chinese patients with cerebrovascular disease. Whether prevention of stroke recurrence depends on drug class, degree of BP lowering or both requires further investigation.
Summary Background Few studies have formally compared the predictive value of the blood pressure at night over and beyond the daytime value. We investigated the prognostic significance of the ...ambulatory blood pressure during night and day and of the night-to-day blood pressure ratio. Methods We did 24-h blood pressure monitoring in 7458 people (mean age 56·8 years SD 13·9) enrolled in prospective population studies in Denmark, Belgium, Japan, Sweden, Uruguay, and China. We calculated multivariate-adjusted hazard ratios for daytime and night-time blood pressure and the systolic night-to-day ratio, while adjusting for cohort and cardiovascular risk factors. Findings Median follow-up was 9·6 years (5th to 95th percentile 2·5–13·7). Adjusted for daytime blood pressure, night-time blood pressure predicted total (n=983; p<0·0001), cardiovascular (n=387; p<0·01), and non-cardiovascular (n=560; p<0·001) mortality. Conversely, adjusted for night-time blood pressure, daytime blood pressure predicted only non-cardiovascular mortality (p<0·05), with lower blood pressure levels being associated with increased risk. Both daytime and night-time blood pressure consistently predicted all cardiovascular events (n=943; p<0·05) and stroke (n=420; p<0·01). Adjusted for night-time blood pressure, daytime blood pressure lost prognostic significance only for cardiac events (n=525; p≥0·07). Adjusted for the 24-h blood pressure, night-to-day ratio predicted mortality, but not fatal combined with non-fatal events. Antihypertensive drug treatment removed the significant association between cardiovascular events and the daytime blood pressure. Participants with systolic night-to-day ratio value of 1 or more were older, at higher risk of death, and died at an older age than those whose night-to-day ratio was normal (≥0·80 to <0·90). Interpretation In contrast to commonly held views, daytime blood pressure adjusted for night-time blood pressure predicts fatal combined with non-fatal cardiovascular events, except in treated patients, in whom antihypertensive drugs might reduce blood pressure during the day, but not at night. The increased mortality in patients with higher night-time than daytime blood pressure probably indicates reverse causality. Our findings support recording the ambulatory blood pressure during the whole day.
We assessed the feasibility of ambulatory pulse wave analysis by comparing this approach with an established tonometric technique. We investigated 35 volunteers (45.6 years; 51.0% women) exclusively ...at rest (R study) and 83 volunteers (49.9 years; 61.4% women) at rest and during daytime (1000-2000 h) ambulatory monitoring (R+A study). We recorded central systolic (cSP), diastolic (cDP) and pulse (cPP) pressures, augmentation index (cAI) and pulse wave velocity (PWV) by brachial oscillometry (Mobil-O-Graph 24h PWA Monitor) and radial tonometry (SphygmoCor). We applied the Bland and Altman's statistics. In the R study, tonometric and oscillometric estimates of cSP (105.6 vs. 106.9 mm Hg), cDP (74.6 vs. 74.7 mm Hg), cPP (31.0 vs. 32.1 mm Hg), cAI (21.1 vs. 20.6%) and PWV (7.3 vs. 7.0 m s(-1)) were similar (P0.11). In the R+A study, tonometric vs. oscillometric assessment yielded similar values for cSP (115.4 vs. 113.9 mm Hg; P=0.19) and cAI (26.5 vs. 25.3%; P=0.54), but lower cDP (77.8 vs. 81.9 mm Hg; P<0.0001), so that cPP was higher (37.6 vs. 32.1 mm Hg; P<0.0001). PWV (7.9 vs. 7.4 m s(-1)) was higher (P=0.0002) on tonometric assessment. The differences between tonometric and oscillometric estimates increased (P0.004) with cSP (r=0.37), cAI (r=0.39) and PWV (r=0.39), but not (P0.17) with cDP (r=0.15) or cPP (r=0.13). Irrespective of measurement conditions, brachial oscillometry compared with an established tonometric method provided similar estimates for cSP and systolic augmentation, but slightly underestimated PWV. Pending further validation, ambulatory assessment of central hemodynamic variables is feasible.
Few population studies addressed the prognostic significance of aortic pulse wave velocity (APWV) above and beyond other cardiovascular risk factors.
We studied a sex- and age-stratified random ...sample of 1678 Danes aged 40 to 70 years. We used Cox regression to investigate the prognostic value of APWV, office pulse pressure (PP), and 24-hour ambulatory PP while adjusting for mean arterial pressure (MAP) and other covariates. Over a median follow-up of 9.4 years, the incidence of fatal and nonfatal cardiovascular end points, cardiovascular mortality, and fatal and nonfatal coronary heart disease amounted to 154, 62, and 101 cases, respectively. We adjusted for sex, age, body mass index, MAP measured in the office (conventional PP and APWV) or by ambulatory monitoring (24-hour PP), smoking, and alcohol intake. With these adjustments, APWV maintained its prognostic significance in relation to each end point (P<0.05), whereas office and 24-hour PP lost their predictive value (P>0.19), except for office PP in relation to coronary heart disease (P=0.02). For each 1-SD increment in APWV (3.4 m/s), the risk of an event increased by 16% to 20%. In sensitivity analyses, APWV still predicted all cardiovascular events after standardization to a heart rate of 60 beats per minute, after adjustment for 24-hour MAP instead of office MAP, and/or after additional adjustment for the ratio of total to HDL serum cholesterol and diabetes mellitus at baseline.
In a general Danish population, APWV predicted a composite of cardiovascular outcomes above and beyond traditional cardiovascular risk factors, including 24-hour MAP.
Accumulation of mitochondrial DNA (mtDNA) mutations leads to alterations of mitochondrial biogenesis and function that might produce a decrease in mtDNA content within cells. This implies that mtDNA ...content might be a potential biomarker associated with oxidative stress and inflammation. However, data on correlates of mtDNA content in a general population are sparse. Our goal in the present study was to describe in a randomly recruited population sample the distribution and determinants of peripheral blood mtDNA content. From 2009 to 2013, we examined 689 persons (50.4% women; mean age = 54.4 years) randomly selected from a Flemish population (Flemish Study on Environment, Genes, and Health Outcomes). Relative mtDNA copy number as compared with nuclear DNA was measured by quantitative real-time polymerase chain reaction in peripheral blood. There was a curvilinear relationship between relative mtDNA copy number and age. mtDNA content slightly increased until the fifth decade of life and declined in older subjects (Page (2) = 0.0002). mtDNA content was significantly higher in women (P = 0.007) and increased with platelet count (P < 0.0001), whereas it was inversely associated with white blood cell count (P < 0.0001). We also observed lower mtDNA content in women using estroprogestogens (P = 0.044). This study demonstrated in a general population that peripheral blood mtDNA content is significantly associated with sex and age. Blood mtDNA content is also influenced by platelet and white blood cell counts and estroprogestogen intake. Further studies are required to clarify the impact of chronic inflammation and hormone therapy on mitochondrial function.
Our aim was to assess the prognostic significance of nighttime and daytime ambulatory blood pressure and their ratio for mortality and cause-specific cardiovascular events in hypertensive patients ...without major cardiovascular disease at baseline. We performed a meta-analysis on individual data of 3468 patients from 4 prospective studies performed in Europe. Age of the subjects averaged 61+/-13 years, 45% were men, 13.7% smoked, 8.4% had diabetes, and 61% were under antihypertensive treatment at the time of ambulatory blood pressure monitoring. Office, daytime, and nighttime blood pressure averaged 159+/-20/91+/-12, 143+/-17/87+/-12, and 130+/-18/75+/-12 mm Hg. Total follow-up amounted to 23 164 patient-years. We used multivariable Cox regression analysis to assess the hazard ratios associated with 1 standard deviation higher blood pressure. Daytime and nighttime systolic blood pressure predicted all-cause and cardiovascular mortality, coronary heart disease, and stroke, independently from office blood pressure and confounding variables. When these blood pressures were entered simultaneously into the models, nighttime blood pressure predicted all outcomes, whereas daytime blood pressure did not add prognostic precision to nighttime pressure. Appropriate interaction terms indicated that the results were similar in men and women, in younger and older patients, and in treated and untreated patients The systolic night-day blood pressure ratio predicted all outcomes, which only persisted for all-cause mortality after adjustment for 24-hour blood pressure. In conclusion, nighttime blood pressure is in general a better predictor of outcome than daytime pressure in hypertensive patients, and the night-day blood pressure ratio predicts mortality, even after adjustment for 24-hour blood pressure.
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