Mortality and Cardiovascular End Points In Relation to the Aortic Pulse Wave Components: An Individual-Participant Meta-Analysis

Abstract

Background: Wave separation analysis enables individualized evaluation of the aortic pulse wave components. Previous studies focused on the pressure height with overall positive but differing results. In the present analysis, we assessed the associations of the pressure of forward and backward (P_for and P_ref) pulse waves with prospective cardiovascular end points, with extended analysis for time to pressure peak (T_for and T_ref).

Methods: Participants in 3 IDCARS (International Database of Central Arterial Properties for Risk Stratification) cohorts (Argentina, Belgium, and Finland) aged ≥20 years with valid pulse wave analysis and follow-up data were included. Pulse wave analysis was done using the SphygmoCor device, and pulse wave separation was done using the triangular method. The primary end points consisted of cardiovascular mortality and nonfatal cardiovascular and cerebrovascular events. Multivariable-adjusted Cox regression was used to calculate hazard ratios.

Results: A total of 2206 participants (mean age, 57.0 years; 55.0% women) were analyzed. Mean±SDs for P_for, P_ref, T_for, and T_for/T_ref were 31.0±9.1 mm Hg, 20.8±8.4 mm Hg, 130.8±35.5, and 0.51±0.11, respectively. Over a median follow-up of 4.4 years, 146 (6.6%) participants experienced a primary end point. Every 1 SD increment in P_for, T_for, and T_for/T_ref was associated with 27% (95% CI, 1.07-1.49), 25% (95% CI, 1.07-1.45), and 32% (95% CI, 1.12-1.56) higher risk, respectively. Adding T_for and T_for/T_ref to existing risk models improved model prediction (∆Uno's C, 0.020; P<0.01).

Conclusions: Pulse wave components were predictive of composite cardiovascular end points, with T_for/T_ref showing significant improvement in risk prediction. Pending further confirmation, the ratio of time to forward and backward pressure peak may be useful to evaluate increased afterload and signify increased cardiovascular risk.

Keywords: cardiovascular diseases; heart disease risk factors; prospective studies; pulse wave analysis; risk factors.

Figure 1.

Cumulative incidence of the composite cardiovascular end point by thirds of aortic pulse wave components. Shown are the amplitude and time to pressure peak of the forward (P_for and T_for; A and D) and reflected (P_ref and T_ref; B and E) aortic pulse wave components, the reflection magnitude (RM; C), and the ratio of forward and backward pressure peak time (T_for/T_ref; F). Tabulated data are the number of participants at risk at 2.5-year intervals. P values were derived from Log-rank test. CVD indicates cardiovascular disease.

Figure 2.

Heat plots for the composition of aortic pulse wave components and the 5-year risk of the primary composite end point. Forward and backward pulse wave components (A and C) are mutually included in the multivariable adjusted models (B and D) with covariables of sex, age, body mass index, mean arterial pressure, heart rate, total cholesterol, current smoking, antihypertensive treatment, history of diabetes, and previous cardiovascular disease (CVD) with backward elimination and adjusted for cohort.

Figure 3.

Subgroup analysis of selected aortic pulse wave components for primary end point. Hazard ratios in subgroups adjusted for cohort, sex, age, body mass index, mean arterial pressure, heart rate, total cholesterol, current smoking, antihypertensive treatment, history of diabetes, and previous cardiovascular disease. CVD indicates cardiovascular disease; eGFR, glomerular filtration rate estimated from serum creatinine; HR, hazard ratio; HT, hypertension; ISH, isolated systolic hypertension; P_for, aortic forward wave pressure; PP, pulse pressure; T_for, forward pressure peak time; and T_ref, backward pressure peak time.