The combined effect of aortic stiffness and pressure wave reflections on mortality in the very old with cardiovascular disease: the PROTEGER Study

Abstract

Aortic stiffness (pulse wave velocity, PWV) and pressure wave reflections (augmentation index, AI) are two interrelated markers of mortality. Their potential synergistic effect on mortality has never been studied. We sought to investigate the association as well as the combined effect of PWV and AI on mortality in a cohort (PROTEGER Study) of very old (>70 years, mean age ( ± s.d.): 85.4 ± 7.4 years). Aortic PWV and pressure wave AI were assessed by pulse wave analysis; carotid structure and cardiac function were analyzed by ultrasound. The analysis was performed in 259 patients who had all the data available. Neither PWV nor AI was, in separate, predictors of mortality (log-rank test: P=0.278 and P=0.433, respectively, Kaplan-Meier analysis). No linear association was found between PWV and AI (P=0.278). To investigate the possible synergistic effect of PWV and AI on mortality, the population was analyzed according to the tertiles of PWV and AI. Subjects with combined high PWV (third tertile) and moderate-to-high AI (second and third tertiles) had lower survival compared with the rest of the population (Kaplan-Meier survival curve, log-rank test: P=0.030). Cox regression analysis showed that this effect was independent from age, gender, blood pressure, cardiac/carotid parameters and other confounders, except creatinine and insulin resistance. The present study provides further insight on the pathophysiological association between large artery stiffness and pressure wave reflections, suggesting that when both are elevated they may increase the mortality in the elderly.