Association between C-reactive protein-triglyceride glucose related indices and all-cause and cardiovascular mortality in individuals with cardiovascular-kidney-metabolic syndrome

BACKGROUND: The C-reactive protein-triglyceride glucose index (CTI) has been proposed as a biomarker for insulin resistance and inflammation, which contribute to the development of cardiovascular-kidney-metabolic (CKM) syndrome. Waist- circumference-based anthropometric indices have been extensively studied as measures of abdominal obesity, which is strongly associated with mortality risk. This study evaluates the association with mortality of CTI and its combination with several waist circumference based anthropometric indices across stages of CKM. METHODS: A total of 10,941 participants were included from NHANES database. CTI and its derivatives (CTI-waist-to-height ratio CTI-WHtR, CTI-weight-adjusted waist index CTI-WWI, and CTI-a body shape index CTI-ABSI) were calculated. Study outcomes were all-cause and cardiovascular mortality. Cox regression model and restricted cubic spline (RCS) were used to assess the association between the CTI-related indices and outcomes. Receiver operating characteristic (ROC) analyses were performed to show their predictive ability for outcomes. Subgroup analyses were conducted to verify the robustness. RESULTS: During a median follow-up of 12.83 years, 20.3% of patients (n = 2223) died, including 6.3% (n = 693) from cardiovascular causes. After adjustment, higher CTI-related indices were associated with higher risk of all-cause mortality (CTI: HR = 1.21, 95%CI 1.14-1.28; CTI-WHtR: HR = 1.14, 95%CI 1.08-1.21; CTI-WWI: HR = 1.25, 95%CI 1.18-1.33; CTI-ABSI: HR = 1.29, 95%CI 1.22-1.37) and cardiovascular mortality (CTI: sHR = 1.31, 95%CI 1.18-1.45; CTI-WHtR: sHR = 1.29, 95%CI 1.16-1.42; CTI-WWI: sHR = 1.39, 95%CI 1.25-1.55; CTI-ABSI: sHR = 1.40, 95%CI 1.26-1.55). RCS analysis showed that CTI was nonlinearly associated with both all-cause and cardiovascular mortality, whereas CTI-WWI and CTI-ABSI showed linear associations with both outcomes; CTI-WHtR was nonlinearly associated with all-cause mortality but linearly with cardiovascular mortality. ROC analyses revealed that CTI-ABSI had the highest predictive efficacy for all-cause mortality (AUC = 0.711) and cardiovascular mortality (AUC = 0.690). Notably, subgroup analyses revealed that the association between CTI-related indices and mortality was more pronounced in early CKM stages (stages 0-2) than in advanced stages (stages 3-4). CONCLUSION: Higher CTI-related indices were significantly associated with a higher risk of all-cause and cardiovascular mortality in individuals with CKM syndrome. Among these indices, CTI-ABSI exhibits superior predictive performance, suggesting its potential as practical prognostic biomarkers for CKM patients.