Insulin Resistance–related Indices and Incident Cardiovascular Disease in Individuals with PREVENT-estimated 10-Year ASCVD Risk < 5%

The PREVENT equations have been recommended by recent AHA guidelines for estimating 10-year ASCVD risk to inform lipid-lowering strategies in primary prevention. Among individuals with low-to-borderline 10-year ASCVD risk according to the PREVENT equations, treatment decisions should be further refined by considering risk-enhancing factors. Although insulin resistance (IR) is closely associated with ASCVD, it remains unclear whether IR-related indices capture residual risk in this low-to-borderline risk population and whether commonly used indices differ in their associations with incident ASCVD or incremental predictive performance. This prospective cohort study included 2,664 participants from CHARLS with low-to-borderline risk. Six IR-related indices were assessed, including the TyG, its derived measures, and estimated glucose disposal rate (eGDR). The primary outcome was incident ASCVD. Associations with incident ASCVD were examined using Cox proportional hazards models. Kaplan–Meier analyses and restricted cubic spline (RCS) models were used to evaluate cumulative incidence patterns and dose-response relationships. Standalone discrimination was assessed using receiver operating characteristic curves (ROC), and incremental performance beyond the base PREVENT model was evaluated using changes in AUC, calibration, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Calibration was assessed using bootstrap-corrected calibration curves with 500 resamples. Over the observation period, 324 participants developed ASCVD. In Model 3, TyG-BMI, TyG-WHtR, and TyG-CVAI were positively related to ASCVD occurrence, whereas eGDR was linked to lower risk. In ROC analyses, TyG-CVAI, eGDR, TyG-BMI, and TyG-WHtR yielded higher AUCs than TyG and CTI. TyG-CVAI had the highest AUC (0.578, 95