Comparison of CTI and its modified indices in predicting cardiovascular disease risk across different glycemic statuses: a nationwide prospective cohort study

BACKGROUND: The C-reactive protein-triglyceride glucose index (CTI) has emerged as a promising composite biomarker for cardiovascular disease (CVD) risk. However, whether incorporating obesity-related metrics such as waist circumference (WC), body mass index (BMI), or waist-to-height ratio (WHtR) into CTI to form modified indices such as CTI-WC, CTI-BMI, and CTI-WHtR improves predictive performance remains uncertain. The performance of these modified indices requires validation in large-scale prospective cohorts stratified by glycemic status. METHODS: This study used data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2020, involving 7,579 participants aged ≥ 45 years. Multivariate Cox regression and restricted cubic splines (RCSs) analyses were used to assess the associations of the CTI and its modified indices with CVD risk. To compare the predictive performance, time-dependent Harrell's C-indices, integrated discrimination improvement and net reclassification index were utilized. Weighted quantile sum (WQS) regression was used to evaluate component contributions. RESULTS: During a mean follow-up of 8.28 years, 1,871 (24.69%) participants experienced their first CVD event. The CTI and its modified indices were effective in predicting CVD incidence in the general population. RCS analysis revealed positive linear dose-response relationships between these indices and CVD risk in the general population, which persisted in both normal glucose regulation (NGR) and prediabetes mellitus (Pre-DM) patients. WQS regression analysis revealed that, in the general population, TG contributed the most to CVD risk in the CTI, while WC, BMI, and WHtR had greater weights in their modified indices. In the general population, all modified CTI indices demonstrated superior predictive ability than did the original CTI (C-index: CTI-WC 0.619, CTI-WHtR 0.616, CTI-BMI 0.614, and CTI 0.612). In the population with NGR, Pre-DM, and DM, the predictive capability of CTI-WC is superior to that of the original CTI, with its C-index being greater across all these populations. CONCLUSIONS: The CTI and its modified indices are effective in predicting CVD risk in the general population. The modified CTI indices, especially the CTI-WC, show superior predictive ability across different glycemic statuses. These findings suggest that incorporating obesity-related metrics into the CTI may enhance its utility for CVD risk prediction.