Arterial stiffness mediates insulin resistance-related risk of atherosclerotic cardiovascular disease: a real-life, prospective cohort study

Abstract Background The precise pathways connecting insulin resistance (IR) to atherosclerotic cardiovascular disease (ASCVD) remain undefined. The present study aimed to examine the mediating role of arterial stiffness in the association between IR and ASCVD, providing epidemiology insights into the potential mechanisms driving IR to incident ASCVD. Methods A total of 59,777 participants from the Kailuan Study Arterial Stiffness Subcohort who were free of ASCVD at baseline were enrolled in the present study. Arterial stiffness was assessed using baPWV and IR was assessed by triglyceride glucose index (TyG) or metabolic score for insulin resistance (METS-IR). Mediation analysis was adopted to explore the mediating effects of baPWV on the associations between IR and ASCVD and its subtypes. Results Over a median follow-up of 5.97 years, a total of 2073 cases of ASCVD were identified, with 478 cases of coronary heart disease (CHD) and 1636 cases of ischemic stroke. Mediation analyses revealed that 11.1% of the total association (HR 1.23; 95% CI 1.17 to 1.30) between the TyG index and ASCVD was mediated through baPWV. Specifically, 6.58% and 14.0% of the total associations of the TyG index with CHD and ischemic stroke, respectively, were mediated through baPWV. Similar patterns were observed for METS-IR. These results remained consistent when assessed through causal mediation analysis, time-lagged mediation analysis, and various sensitivity analyses. Conclusions The association between IR indices and ASCVD was found to be partly mediated by baPWV, indicating a pathway connecting IR to ASCVD outcomes and the potential for interventions targeting arterial stiffness for ASCVD prevention.