Composite C-reactive protein–triglyceride–glucose–adiposity indices and incident cardiovascular disease in the CHARLS cohort: a prospective cohort study

BACKGROUND & AIMS: Cardiovascular disease (CVD) is influenced by metabolic dysfunction, chronic inflammation, and adiposity. The C-reactive protein-triglyceride-glucose index (CTI) integrates inflammatory and metabolic information, but the associations of CTI-derived adiposity indices with incident CVD remain insufficiently characterized. We aimed to examine the associations of several CTI-derived adiposity indices with incident CVD and compare their relative performance in a nationwide cohort of middle-aged and older adults. METHODS: We analyzed data from 6,161 participants aged ≥ 45 years without baseline CVD from the China Health and Retirement Longitudinal Study (CHARLS). Four CTI-derived adiposity indices were evaluated: CTI-WHtR, CTI-BMI, CTI-BRI, and CTI-WWI. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD. Dose-response relationships were assessed using restricted cubic splines (RCS). Kaplan-Meier, discrimination and reclassification, cumulative exposure, trajectory, subgroup, component-outcome, mediation, and sensitivity analyses were also performed. RESULTS: During a median follow-up of 9 years, 1,503 participants (24.39%) developed CVD. Higher levels of CTI-derived adiposity indices were associated with increased CVD risk. In fully adjusted models, participants in the highest quartile had higher CVD risk than those in the lowest quartile for CTI-WHtR (HR = 1.57, 95% CI 1.24-2.00), CTI-BMI (HR = 1.55, 95% CI 1.23-1.97), CTI-BRI (HR = 1.40, 95% CI 1.11-1.78), and CTI-WWI (HR = 1.37, 95% CI 1.08-1.74), with significant trends across quartiles. RCS analyses showed predominantly linear dose-response relationships. Discrimination was modest, with AUCs ranging from 0.558 for CTI-WWI to 0.573 for CTI-WHtR, compared with 0.522 for CTI. All CTI-derived indices improved continuous net reclassification improvement and integrated discrimination improvement beyond the conventional risk factor model. Higher cumulative exposure and higher trajectory clusters of CTI-derived indices were also associated with increased CVD risk. Mediation analyses suggested interrelationships between metabolic-inflammatory dysregulation and adiposity in relation to CVD. CONCLUSIONS: CTI-derived adiposity indices were associated with incident CVD in middle-aged and older adults, with CTI-WHtR showing the most consistent overall performance among the evaluated indices. These findings support the epidemiological relevance of integrating metabolic-inflammatory burden with adiposity-related phenotypes in cardiovascular risk assessment.