TyG Index and Frailty as Composite Biomarkers of Cardiometabolic Risk and Mortality Across CKM Stages 0–3

Background: Cardiovascular disease and mortality are common outcomes of cardiovascular–kidney–metabolic (CKM) syndrome. The integrated role of metabolic dysfunction and frailty, quantified by the triglyceride–glucose–frailty index (TyG-FI), remains insufficiently explored. This study examined the association between TyG-FI and incident composite outcomes among participants with CKM stages 0–3. Methods: Data were obtained from two large cohort studies conducted in China and the United States. The analysis focused on participants classified as CKM stages 0–3. Cox proportional hazards models were used to estimate the relationship between TyG-FI and incident composite outcomes. Nonlinear associations were explored using spline functions. Additional analyses were performed across different subgroups and under varied assumptions. Model performance over time was also assessed. Results: Significant differences in outcome incidence were observed across TyG-FI levels. Higher quartiles showed a gradual increase in risk and displayed a dose–response pattern, with inflection points at 1.01 and 2.29. Associations were consistent across subgroups, and TyG-FI demonstrated moderate discrimination (AUCs 0.714 and 0.744). Conclusions: In the CHARLS and HRS cohorts, higher TyG-FI scores were independently associated with an increased risk of incident composite outcomes among participants with CKM stages 0–3, with a nonlinear relationship observed. Its discriminatory power was moderate, suggesting that TyG-FI may serve as a supplementary indicator for risk stratification in the early to mid-stages, although its clinical predictive value requires further validation.