Association of vascular aging and insulin resistance with cardiovascular outcomes in China: PURE cohort study

Background: Although vascular aging and insulin resistance (IR) are recognized contributors to cardiovascular disease (CVD) pathophysiology, their independent and joint associations with CVD outcomes have not been fully clarified in large population-based cohorts. Evidence regarding their complementary rather than mediating roles remains limited. Methods: We used data from the Prospective Urban Rural Epidemiology (PURE) China study, a large prospective cohort comprising 47 931 individuals from 12 provinces across China. Vascular aging was assessed using estimated pulse wave velocity and categorized into supernormal (SVA), healthy (HVA), and early vascular aging (EVA) based on cohort percentiles. IR was evaluated using the triglyceride–glucose (TyG) index. The primary outcome was major CVD events (myocardial infarction, stroke, and heart failure). Cox frailty models with center-level random effects were used to estimate adjusted hazard ratios (aHRs). Results: A total of 40 513 participants with complete information were included in the current study. Over a median follow-up of 11.9 years (interquartile ranges 9.5–12.5), 3615 major CVD events, 829 CVD deaths, and 2344 all-cause deaths occurred. Compared with HVA, EVA was associated with substantially higher risks of major CVD events aHR = 2.17, 95% confidence interval (CI): 1.99–2.35, CVD mortality (aHR = 4.07, 95% CI: 3.47–4.76), and all-cause mortality (aHR = 2.93, 95% CI: 2.65–3.23), while SVA showed consistently lower risks. Furthermore, higher TyG index levels were independently associated with major CVD event risk in a dose-response manner. Exploratory analyses revealed no significant mediation by the TyG index or interaction between vascular aging and TyG levels. Joint analysis revealed that individuals with both EVA and high TyG had the greatest major CVD risk (aHR = 2.20, 95% CI: 1.75–2.77). Conclusions: EVA and IR were independently associated with higher CVD risk, highlighting the need for integrated vascular-metabolic risk assessment in clinical practice, although further validation is warranted.