Association of Fatal and Nonfatal Cardiovascular Outcomes With 24-Hour Mean Arterial Pressure

Abstract

Major adverse cardiovascular events are closely associated with 24-hour blood pressure (BP). We determined outcome-driven thresholds for 24-hour mean arterial pressure (MAP), a BP index estimated by oscillometric devices. We assessed the association of major adverse cardiovascular events with 24-hour MAP, systolic BP (SBP), and diastolic BP (DBP) in a population-based cohort (n=11 596). Statistics included multivariable Cox regression and the generalized R² statistic to test model fit. Baseline office and 24-hour MAP averaged 97.4 and 90.4 mm Hg. Over 13.6 years (median), 2034 major adverse cardiovascular events occurred. Twenty-four-hour MAP levels of <90 (normotension, n=6183), 90 to <92 (elevated MAP, n=909), 92 to <96 (stage-1 hypertension, n=1544), and ≥96 (stage-2 hypertension, n=2960) mm Hg yielded equivalent 10-year major adverse cardiovascular events risks as office MAP categorized using 2017 American thresholds for office SBP and DBP. Compared with 24-hour MAP normotension, hazard ratios were 0.96 (95% CI, 0.80-1.16), 1.32 (1.15-1.51), and 1.77 (1.59-1.97), for elevated and stage-1 and stage-2 hypertensive MAP. On top of 24-hour MAP, higher 24-hour SBP increased, whereas higher 24-hour DBP attenuated risk (P<0.001). Considering the 24-hour measurements, R² statistics were similar for SBP (1.34) and MAP (1.28), lower for DBP than for MAP (0.47), and reduced to null, if the base model included SBP and DBP; if the ambulatory BP indexes were dichotomized according to the 2017 American guideline and the proposed 92 mm Hg for MAP, the R² values were 0.71, 0.89, 0.32, and 0.10, respectively. In conclusion, the clinical application of 24-hour MAP thresholds in conjunction with SBP and DBP refines risk estimates.

Keywords: cardiovascular disease; hypertension; mean arterial pressure; mortality; oscillometry.

Figure 1.

Multivariable-adjusted hazard ratios (HRs; 95% CI) for the primary end point in relation to 24-h blood pressure (BP). A, The analysis was stratified by the median (90 mm Hg) of mean arterial pressure (MAP). HRs were computed comparing participants with MAP ≤80, ≤82, ≤84, ≤86, or ≤88 with those with MAP >90 mm Hg and comparing participants with MAP ≥92, ≥94, ≥96, ≥98, ≥100, or ≥102 with those with MAP <90 mm Hg. Hazard ratios were adjusted for cohort (random effect), sex, and baseline characteristics including age, body mass index, smoking and drinking, serum cholesterol, antihypertensive drug intake, history of cardiovascular disease, and diabetes. Vertical bars denote 95% CIs. This plot confirmed the increase in risk when MAP was ≥92 mm Hg. B and C, The 11 596 participants were subdivided according the American College of Cardiology/American Heart Association thresholds for 24-h systolic BP (SBP) and diastolic BP (DBP) and the calculated 24-h MAP thresholds (Table 2). The multivariable-adjusted HRs, given with 95% CI, represent the risk of a primary end point with normotension for SBP and MAP (B) or normotension for diastolic and MAP (C) as reference. E/AR indicates number of participants with a primary end point/number of participants at risk; and NT/HT, normotension/hypertension, and E/AR number of participants with a primary endpoint/number of participants at risk.

Figure 2.

Heat maps depicting the 10-y risk of a primary end point in relation to 24-h mean arterial, systolic and diastolic BP in 11 596 participants. Numbers in the (A) and (B) grids represent the percentage of participants within each BP cross-classification category; numbers in (C) and (D) represent the 10-y risks. Heat maps were derived by Cox proportional hazards regression with systolic BP (C) or diastolic BP (D) plotted along the vertical axis and mean arterial pressure (MAP) along the horizontal axis. Estimates of the 10-y risk were standardized to the average of the distributions in the whole study population (mean or ratio) of all covariables. Higher MAP consistently conferred greater risk (P<0.001) with an additional contribution of systolic BP (P<0.001 [C]), whereas higher diastolic BP attenuated the risk (P<0.001 [D]).