Integrating inflammation, insulin resistance, and visceral adiposity: the C-reactive protein–triglyceride–glucose-Chinese visceral adiposity (CTI–CVAI) index is associated with cardiovascular disease risk across CKM stages 0–3 in a nationwide prospective cohort

BACKGROUND: Early-stage (0-3) cardiovascular-kidney-metabolic (CKM) syndrome populations require urgent cardiovascular disease (CVD) prevention. Chronic inflammation, insulin resistance, and visceral adiposity are three core interactive CVD pathogenic pathways, while current biomarkers fail to integrate all three. This study aimed to explore the association of the novel three-dimensional composite index CTI-CVAI with incident CVD and its predictive value in Chinese adults with CKM stages 0-3. METHODS: This nationwide prospective cohort study used data from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2020), including 6728 participants aged ≥ 45 years with CKM stages 0-3. CTI-CVAI was calculated by combining the C-reactive protein-triglyceride-glucose index (CTI) and Chinese visceral adiposity index (CVAI). Cox regression, restricted cubic spline, survival analysis, ROC curves, and reclassification analysis were used to evaluate its value. Subgroup and multiple sensitivity analyses, including competing-risks models, were conducted to assess the robustness of the results. RESULTS: During a median follow-up of 9 years, the overall CVD incidence was 23.83%. CTI-CVAI elevation showed a linear, dose-dependent correlation with increased CVD risk (P < 0.001). After full confounder adjustment, per 1-SD CTI-CVAI increment increased CVD risk by 32% (HR = 1.32, 95% CI 1.26-1.39, P < 0.001), and the highest quartile exhibited 2.07-fold higher risk than the lowest (HR = 2.07, 95% CI 1.77-2.42, P < 0.001). Restricted cubic spline analysis revealed a linear association between CTI-CVAI and incident CVD (P for non-linearity > 0.05). CTI-CVAI demonstrated improved risk reclassification (NRI = 0.0566, P < 0.001) compared with single biomarkers. The association was stable across most subgroups. All sensitivity analyses yielded reliable, robust results. CONCLUSIONS: CTI-CVAI is independently and linearly associated with incident CVD risk in Chinese adults with CKM stage 0-3. As a low-cost, accessible biomarker integrating three key pathological pathways, it optimizes early CVD risk stratification and reclassification, providing a promising tool for targeted CVD prevention in CKM high-risk populations.