Associations of C-reactive protein-triglyceride-glucose index and cholesterol-high-density lipoprotein-glucose index with heart disease risk in individuals with cardiovascular-kidney-metabolic syndrome stages 0–3: a cohort study from CHARLS

Abstract Background Although the C-reactive protein-triglyceride-glucose index (CTI) and cholesterol-high-density lipoprotein-glucose index (CHG) have both been implicated in adverse cardiovascular outcomes, their comparative predictive performance for incident heart disease among individuals with cardiovascular-kidney-metabolic (CKM) syndrome stages 0–3 remains to be elucidated. Methods We analyzed 6,740 participants with CKM syndrome stages 0–3 from the China Health and Retirement Longitudinal Study (CHARLS) database. Stratified Cox regression models were constructed to examine the associations of CTI and CHG with incident heart disease. Restricted cubic spline (RCS) analysis was applied to explore potential nonlinear relationships. Kaplan-Meier curves were plotted to compare heart disease-free survival across groups, and time-dependent receiver operating characteristic (ROC) analyses were performed to evaluate the discriminatory performance of CTI and CHG. Causal mediation analysis was conducted to assess the mediating role of systolic blood pressure (SBP). Subgroup and sensitivity analyses were undertaken to verify the robustness of our findings. Results Over a 9-year follow-up period, 1,229 participants (18.2%) developed heart disease. In fully adjusted models, compared with the lowest quartile, participants in the highest quartile of CTI exhibited a 35% elevated risk of heart disease (HR = 1.35, 95% CI: 1.14–1.60), while those in the highest quartile of CHG showed a 19% elevated risk (HR = 1.19, 95% CI: 1.01–1.41). Both indices demonstrated positive linear associations with heart disease risk, with cumulative incidence increasing progressively across ascending quartiles. CTI exhibited slightly superior discriminatory performance compared to CHG at the 2- and 4-year follow-up time points. SBP mediated 16.4% of the association between CTI and heart disease, and 18.0% of the association between CHG and heart disease. Subgroup and sensitivity analyses consistently supported the robustness of these findings. Conclusions Both CTI and CHG are independently associated with incident heart disease in individuals with CKM syndrome stages 0–3. CTI demonstrates modestly superior predictive performance, particularly during early follow-up, suggesting that incorporating inflammatory biomarkers may enhance heart disease risk stratification beyond metabolic indicators alone.