Comparative analysis of 16 baseline obesity and lipid-related indices for cardiovascular disease risk prediction in adults with cardiovascular-kidney-metabolic syndrome stages 0–3: a nationwide prospective cohort study

OBJECTIVE: In the context of the newly defined cardiovascular-kidney-metabolic (CKM) syndrome, this study aimed to systematically compare the predictive value of 16 different obesity- and lipid-related indices for new-onset cardiovascular disease (CVD) in a population with CKM stages 0-3. METHODS: This prospective cohort study utilized data from the China Health and Retirement Longitudinal Study (CHARLS). A total of 5,782 participants aged 45 and older, free of CVD at baseline and classified within CKM stages 0-3, were included. We evaluated 16 indices, including traditional markers (e.g., BMI, WHtR) and novel composite markers (e.g., TyG-WC, CVAI, CTI). The primary outcome was incident CVD over a 6-year follow-up. Cox proportional hazards models were used to assess associations. Predictive performance was compared using the C-index, Akaike Information Criterion (AIC), Integrated Discrimination Improvement (IDI), and Decision Curve Analysis (DCA). RESULTS: During the 6-year follow-up, 1,134 incident CVD events occurred. In the fully adjusted Cox model, the triglyceride-glucose waist circumference index (TyG-WC) demonstrated the strongest association with CVD risk, with each 1-standard deviation increase corresponding to a 15% higher risk (HR = 1.15, 95% CI: 1.08-1.22, P < 0.001). A prediction model incorporating TyG-WC showed the best performance, with a higher C-index (0.6434), a significant improvement in discrimination (IDI = 0.0035, P < 0.001), and the greatest net benefit in Decision Curve Analysis. The findings remained robust in both landmark and sensitivity analyses. CONCLUSION: This study, based on nationally representative CHARLS cohort data, systematically compared the CVD risk prediction ability of 16 obesity and lipid-related indices in adults with CKM stages 0-3. The study found that the TyG-WC index demonstrated the strongest CVD risk prediction ability. These indices provide effective assessment tools for CVD risk stratification in CKM stages 0-3 populations through different pathophysiological mechanisms.