Differential association between vascular and chronological age with cardiovascular outcomes

Abstract Background/Introduction Increased pulse wave velocity (PWV), is a reliable marker of early vascular aging (EVA). However, the identification of individuals whose arteries are abnormally healthy in comparison to their age and cardiovascular (CV) risk profile might be of interest, to discover novel pathways of cardioprotection and provide preventive strategies for successful vascular aging. Purpose 1) to provide a novel calculation for vascular age and examine his determinants; 2) to test the hypothesis that individuals with the largest difference between chronological and vascular age (C-V age) show a lower rate of CV events than their counterparts, and may thus be defined as the supernormal vascular aging group (SUPERNOVA). Methods Vascular age was defined as predicted age based on classical CV risk factors and PWV. The best fitting model for vascular age was investigated in the multicenter, European, cross-sectional Reference Values for Arterial stiffness Collaboration Database (n=11406). Continuous variables were modelled as smoothing splines. Thereafter, the risk of fatal and non-fatal CV events associated with C-V age was examined in the longitudinal cohort of the Malmo Diet and Cancer Study (n=2663) using Cox proprotional hazard regression models. C-V age was examined as a continuous variable (natural splines) and as a 3 levels categorical variables based on the best grouping of the deciles of C-V age and corresponding to the EVA (<3.0 years), normal vascular aging (3.0 to 8.8 years) and SUPERNOVA (>8.8 years) respectively. Results In the Reference Values Cohort (age range 17–85 years, 52.4% men, 38.1% hypertensives, 3.9% diabetics, average PWV 7.8 m/s), the most significant predictor of vascular age (full model r2 0.598) was PWV. In the Malmo Diet and Cancer Study Cohort (age 61–89 years, 63.6% men, 64.0% hypertensives, 12.9% diabetics, PWV 11.5 m/s), during follow-up (6.6 years on average), 286 individuals developed a first cardiovascular event. In the Cox survival analysis, C-V age was significantly and inversely associated with CV events. Compare to normal vascular aging, participants with SUPERNOVA had lower risk for CV events [HR 0.51 (0.34–0.76)] whereas those with EVA had a higher risk [HR 2.71 (1.80–4.09)]. Instead, there was no significant association with all-cause mortality. Conclusions The use of PWV and CV risk factors may be useful to define early and supernormal vascular aging in particular, and to assess its clinical relevance towards the risk of cardiovascular disease and death.