Predictive power of 24-h ambulatory pulse pressure and its components for mortality and cardiovascular outcomes in 11 848 participants recruited from 13 populations

Abstract

Background: The role of pulse pressure (PP) 'widening' at older and younger age as a cardiovascular risk factor is still controversial. Mean PP, as determined from repeated blood pressure (BP) readings, can be expressed as a sum of two components: 'elastic PP' (elPP) and 'stiffening PP' (stPP) associated, respectively, with stiffness at the diastole and its relative change during the systole. We investigated the association of 24-h ambulatory PP, elPP, and stPP ('PP variables') with mortality and composite cardiovascular events in different age classes.

Method: Longitudinal population-based cohort study of adults with baseline observations that included 24-h ambulatory BP. Age classes were age 40 or less, 40-50, 50-60, 60-70, and over 70 years. Co-primary endpoints were total mortality and composite cardiovascular events. The relative risk expressed by hazard ratio per 1SD increase for each of the PP variables was calculated from multivariable-adjusted Cox regression models.

Results: The 11 848 participants from 13 cohorts (age 53 ± 16 years, 50% men) were followed for up for 13.7 ± 6.7 years. A total of 2946 participants died (18.1 per 1000 person-years) and 2093 experienced a fatal or nonfatal cardiovascular event (12.9 per 1000 person-years). Mean PP, elPP, and stPP were, respectively, 49.7, 43.5, and 6.2 mmHg, and elPP and stPP were uncorrelated ( r = -0.07). At age 50-60 years, all PP variables displayed association with risk for almost all outcomes. From age over 60 years to age over 70 years, hazard ratios of of PP and elPP were similar and decreased gradually but differently for pulse rate lower than or higher than 70 bpm, whereas stPP lacked predictive power in most cases. For age 40 years or less, elPP showed protective power for coronary events, whereas stPP and PP predicted stroke events. Adjusted and unadjusted hazard ratio variations were similar over the entire age range.

Conclusion: This study provides a new basis for associating PP components with outcome and arterial properties in different age groups and at different pulse rates for both old and young age. The similarity between adjusted and unadjusted hazard ratios supports the clinical usefulness of PP components but further studies are needed to assess the prognostic significance of the PP components, especially at the young age.

FIGURE 1

The concept of pulse pressure components [22]. (a) Illustration of the distending arterial pressure (P) and volume (V) that stands also for cross-sectional lumen area, or lumen diameter. (b) and (c) show, respectively, a linear P–V and nonlinear P–V relationship. At each selected pressure (empty circle), stiffness is defined as the ratio between small incremental changes in P and V, so-called ‘tangent slope’, which is the tangent of the angle between the tangent to the curve, at that point, and the x-axis. Thus, in (b), stiffness is simply the slope of the line, characterizing a simple elastic tube having constant elasticity (‘elastic behavior’), whereas in (c), stiffness increases for higher pressure (or volume), characterizing the ‘stiffening behavior’ displayed by real arteries (see Introduction). (d) The variation of the distending arterial pressure from its diastolic level to systolic level (DBP to SBP, respectively) during the early systole, which is the pulse pressure (PP); the corresponding volume change (‘pulse volume’ ΔV), and the stiffness change from its ‘diastolic’ to ‘systolic’ level. This diagram enables to view, in general, the P–V relationship during the early systole, as a superposition of a linear relationship (‘elastic’) having the slope of the diastolic stiffness and a nonlinear relationship (the original P–V relationship minus the elastic relationship). This procedure splits a given PP into the illustrated ‘elastic component’ (elPP, equals to ΔV · [diastolic stiffness]), and a ‘stiffening component’ (stPP equals to PP-elPP) expressing the extra pressure required to overcome the increased resistance of the arterial wall because of the increased stiffness using the given formulas for quantitative determination of elPP and stPP (Supplemental Methods, http://links.lww.com/HJH/C43). PP, pulse pressure.

FIGURE 2

Variation of pulse pressure variables with age stratified by sex. Data points represent means of each pulse pressure (PP) variable for age grouped in 5-year intervals, fully adjusted in (a) and adjusted to cohorts only in (b), determined using two-way ANOVA taking grouped age and sex as the independent variables. The covariables in (a) were cohorts, BMI, smoking and drinking, serum cholesterol, antihypertensive drug intake, history of cardiovascular disease and diabetes mellitus, and mean 24-h DBP and heart rate. The covariables for (b) were merely cohorts. Values of grouped age were ‘25’, ‘30’, …, and ‘80’, standing for, respectively, age 27.5 or less, 27.5 less than age, 32.5 or less, …, and age more than 77.5 years. The black and blue lines correspond, respectively, to males (‘M’) and females (‘F’). The ‘ = ’ and ‘ + ’ symbols reminds that PP is the sum of elPP and stPP. elPP, elastic pulse pressure; stPP, stiffening PP.