Relative and Absolute Risk to Guide the Management of Pulse Pressure, an Age-Related Cardiovascular Risk Factor

Abstract

Background: Pulse pressure (PP) reflects the age-related stiffening of the central arteries, but no study addressed the management of the PP-related risk over the human lifespan.

Methods: In 4,663 young (18-49 years) and 7,185 older adults (≥50 years), brachial PP was recorded over 24 hours. Total mortality and all major cardiovascular events (MACEs) combined were coprimary endpoints. Cardiovascular death, coronary events, and stroke were secondary endpoints.

Results: In young adults (median follow-up, 14.1 years; mean PP, 45.1 mm Hg), greater PP was not associated with absolute risk; the endpoint rates were ≤2.01 per 1,000 person-years. The adjusted hazard ratios expressed per 10-mm Hg PP increments were less than unity (P ≤ 0.027) for MACE (0.67; 95% confidence interval [CI], 0.47-0.96) and cardiovascular death (0.33; 95% CI, 0.11-0.75). In older adults (median follow-up, 13.1 years; mean PP, 52.7 mm Hg), the endpoint rates, expressing absolute risk, ranged from 22.5 to 45.4 per 1,000 person-years and the adjusted hazard ratios, reflecting relative risk, from 1.09 to 1.54 (P < 0.0001). The PP-related relative risks of death, MACE, and stroke decreased >3-fold from age 55 to 75 years, whereas absolute risk rose by a factor 3.

Conclusions: From 50 years onwards, the PP-related relative risk decreases, whereas absolute risk increases. From a lifecourse perspective, young adulthood provides a window of opportunity to manage risk factors and prevent target organ damage as forerunner of premature death and MACE. In older adults, treatment should address absolute risk, thereby extending life in years and quality.

Keywords: arterial stiffness; blood pressure; cardiovascular disease; hypertension; mortality; population science; pulse pressure.

Graphical Abstract

Figure 1.

Cumulative incidence of the primary endpoints by pulse pressure quartiles in older adults. The incidence of total mortality (a, b) and the composite cardiovascular endpoint (c, b) was first adjusted for cohort and sex (a, c) and next additionally for age (b, d). Considering age significantly attenuated the gradient from the low to the high pulse pressure quartile (P < 0.0001). Tabulated data are the number of participants at risk and those experiencing an endpoint at 2-year intervals.

Figure 2.

Heatmaps relating the 5-year risks of the primary endpoints to age and pulse pressure in older adults. Age was plotted along the horizontal axis and pulse pressure (PP) along the vertical axis. Numbers in the panel a grid represent the percentage of participants within each age × PP cross-classification category. Numbers in the other grids represent the 5-year risk of total mortality (b) and the composite cardiovascular endpoint (c) associated with age and PP. Estimates were generated by Cox proportional hazard regression with age and PP analyzed as continuous variables and adjusted for cohort, sex, body mass index, 24-hour mean arterial pressure, 24-hour heart rate, total cholesterol, smoking and drinking status, antihypertensive treatment at baseline, and history of cardiovascular disease and diabetes. Pint indicates the significance of the interaction term between age and PP. Models accounted for competing risks according to the Fine and Gray approach.