Insulin Resistance Indices and Genetic Predisposition in Relation to the Risk of Incident and Recurrent Coronary Artery Disease

BACKGROUND: Insulin resistance contributes to the pathogenesis of coronary artery disease (CAD), yet its association with recurrent CAD and the potential role of genetic susceptibility remain unclear. METHODS: We analyzed data from the UK Biobank. Four triglyceride-glucose (TyG)-based indices were calculated to assess insulin resistance, including TyG, TyG-body mass index, TyG-waist circumference, and TyG-waist-to-height ratio. The polygenic risk score for CAD was categorized into tertiles, representing low, medium, and high genetic risk. Cox proportional hazards models were used to evaluate the associations of TyG-based indices and polygenic risk score with the risk of incident and recurrent CAD. RESULTS: During follow-up, 27 378 of 408 759 (6.7%) participants without baseline CAD developed incident CAD, and 7620 of 12 895 (59.1%) participants with preexisting CAD experienced recurrent CAD. When comparing the highest versus lowest quartile (Q4 versus Q1), the hazard ratios (HRs) and 95% CIs for incident CAD were 1.57 (1.51-1.63) for TyG, 1.79 (1.72-1.86) for TyG-body mass index, 1.95 (1.86-2.04) for TyG-waist circumference, and 1.96 (1.88-2.05) for TyG-waist-to-height ratio. The corresponding HRs for recurrent CAD were 1.18 (95% CI, 1.10-1.26), 1.20 (95% CI, 1.12-1.28), 1.23 (95% CI, 1.15-1.32), and 1.26 (95% CI, 1.17-1.34), respectively. We observed significant interactions between TyG-based indices and genetic risk for incident CAD, with stronger associations among participants with medium/high polygenic risk score. However, no significant interactions were detected for recurrent CAD. CONCLUSIONS: Elevated TyG-based indices were associated with a higher risk of incident and recurrent CAD. Interactions between TyG-based indices and polygenic risk score were observed for incident but not recurrent CAD.