Association between the C-reactive protein–triglyceride–glucose Index and risks of all-cause and cardiovascular mortality in USA adults: a prospective cohort study

INTRODUCTION: The C-reactive protein-triglyceride-glucose index (CTI) is an emerging composite biomarker reflecting insulin resistanceand systemic inflammation. Research regarding the relationship between CTI and risks of all-cause and cardiovascular mortality remainslimited and inconsistent. MATERIAL AND METHODS: Data from 9,264 USA adults aged ≥ 20 years were obtained from the National Health and Nutrition Examination Survey (1999-2010). Mortality status was determined through linkage to the National Death Index through 31 December 2019. Hazardratios (HRs) for all-cause and cardiovascular mortality were estimated using weighted Kaplan-Meier methods, restricted cubic spline(RCS) models, and multivariable Cox proportional hazards regression models. Prespecified subgroup analyses and sensitivity analyseswere conducted to assess the robustness of the findings. RESULTS: Over a median follow-up of 12.8 years, 2,644 deaths occurred, including 2,009 attributable to all causes and 635 to cardiovascular causes. After adjustment for potential confounders, each one-unit increment in CTI was associated with a 26% higher risk of all-causemortality [HR, 1.26; 95% confidence interval (CI), 1.15-1.38; p < 0.001) and a 25% higher risk of cardiovascular mortality (HR, 1.25; 95% CI,1.03-1.51; p = 0.021). Participants in the highest CTI quartile demonstrated a 33% higher risk of all-cause mortality compared with thosein the lowest quartile (HR, 1.33; 95% CI, 1.07-1.64; p = 0.010). RCS analyses indicated a nonlinear association between CTI and all-causemortality (p for nonlinearity = 0.018), with an inflection point at a CTI value of 9.25, whereas a linear association was observed for cardiovascular mortality (p for nonlinearity = 0.072). No statistically significant interactions were identified across prespecified subgroups. The results remained consistent after exclusion of early deaths (≤ 2 years) and after exclusion of participants with neoplasms. CONCLUSIONS: Higher CTI levels were independently associated with increased risks of all-cause and cardiovascular mortality among USA adults. These findings suggest that CTI may serve as a clinically relevant biomarker for early identification of individuals at elevated mortality risk, with potential implications for risk stratification, targeted prevention strategies, and healthcare resource allocation.