Ambulatory blood pressure monitoring in 9357 subjects from 11 populations highlights missed opportunities for cardiovascular prevention in women

Abstract

To analyze sex-specific relative and absolute risks associated with blood pressure (BP), we performed conventional and 24-hour ambulatory BP measurements in 9357 subjects (mean age, 52.8 years; 47% women) recruited from 11 populations. We computed standardized multivariable-adjusted hazard ratios for associations between outcome and systolic BP. During a course of 11.2 years (median), 1245 participants died, 472 of cardiovascular causes. The number of fatal combined with nonfatal events was 1080, 525, and 458 for cardiovascular and cardiac events and for stroke, respectively. In women and men alike, systolic BP predicted outcome, irrespective of the type of BP measurement. Women compared with men were at lower risk (hazard ratios for death and all cardiovascular events=0.66 and 0.62, respectively; P<0.001). However, the relation of all cardiovascular events with 24-hour BP (P=0.020) and the relations of total mortality (P=0.023) and all cardiovascular (P=0.0013), cerebrovascular (P=0.045), and cardiac (P=0.034) events with nighttime BP were steeper in women than in men. Consequently, per a 1-SD decrease, the proportion of potentially preventable events was higher in women than in men for all cardiovascular events (35.9% vs 24.2%) in relation to 24-hour systolic BP (1-SD, 13.4 mm Hg) and for all-cause mortality (23.1% vs 12.3%) and cardiovascular (35.1% vs 19.4%), cerebrovascular (38.3% vs 25.9%), and cardiac (31.0% vs 16.0%) events in relation to systolic nighttime BP (1-SD, 14.1 mm Hg). In conclusion, although absolute risks associated with systolic BP were lower in women than men, our results reveal a vast and largely unused potential for cardiovascular prevention by BP-lowering treatment in women.

Figure 1.

Incidence of total mortality (A, C) and all cardiovascular events (B, D) in relation to the 24-hour systolic BP in 4397 women (A, B) and 4960 men (C, D). Incidence rates were standardized for cohort and age by the direct method. Mortality rates are plotted separately for total, noncardiovascular (non-CV), and cardiovascular (CV) mortality. Cardiovascular events refer to the composite of all fatal plus nonfatal cardiovascular events. The number of end points contributing to the rates is presented.

Figure 2.

Kaplan-Meier survival function estimates for total mortality (A) and the composite of all fatal plus nonfatal cardiovascular events (B) in 4397 women and 4960 men. Follow-up time spans the 5th to 95th percentile interval. Numbers refer to women and men at risk at the beginning of each 4-year interval. Vertical lines represent the SE of the survival function estimates. HR refers to the hazard ratio, which expresses the risk of women compared with men, with adjustment applied for cohort, age, body mass index, smoking and drinking, serum total cholesterol, history of cardiovascular disease, presence of diabetes mellitus, and antihypertensive drug treatment at baseline.

Figure 3.

Absolute 10-year risk of death (A), a composite cardiovascular (CV) end point (B), a fatal or nonfatal stroke (C), or a fatal or nonfatal cardiac event (D) in relation to the 24-hour systolic BP. The continuous risk functions cover the 5th to 95th percentile interval of the 24-hour systolic BP and were fitted by Cox regression with adjustment for cohort, age, body mass index, smoking and drinking, serum total cholesterol, history of cardiovascular disease, presence of diabetes mellitus, and antihypertensive drug treatment at baseline. Circles (women) and squares (men) represent the multivariable-adjusted HRs in quintiles of the distribution of the 24-hour systolic BP and have a size proportional to the inverse of the variance of the HR. The number of events in each quintile is given next to each circle or square; n_e is the total number of events by disease category and sex. The probability values for interaction were derived from multivariable-adjusted Cox models as given in Tables 2 and 3.

Figure 4.

Changes in the incidence of mortality and cardiovascular (CV) events that would be associated with a 1-SD decrease in the 24-hour systolic BP (A) or in the nighttime BP (B) in women (circles) and men (squares). Estimates were derived from the multivariable-adjusted Cox models presented in Tables 2 and 3 and the observed number of each end point. Probability values indicate significant sex differences.