Abstract
BACKGROUND: Stroke is one of the advanced outcomes of cardiovascular kidney metabolic syndrome (CKM). The combined effects of inflammation, insulin resistance, and hypertension in stroke remain to be fully elucidated in population studies. This study investigates the association between the composite TyG inflammation index (c-reactive protein-triglyceride glucose index, CTI) and hypertension with long-term stroke. METHODS: This longitudinal cohort study included 9082 participants from the China Health and Retirement Longitudinal Study (CHARLS). The associations with stroke risk were assessed using Cox proportional hazards models and Kaplan-Meier analysis, while predictive performance was evaluated using ROC curves and time-dependent AUC. The contribution of each component was determined by Weighted Quantile Sum (WQS) regression. Subgroup analysis and sensitivity analysis were also conducted. RESULTS: Over a median 9-year follow-up, 811 (8.9%) incident stroke cases occurred. A significant dose-response relationship was observed, with the highest CTI-hypertension group exhibiting a fully adjusted hazard ratio of 3.19 (95% CI 2.62-3.88) for stroke compared to the lowest group. The combined CTI-hypertension model demonstrated superior predictive performance (AUC = 0.672) versus hypertension-alone (AUC = 0.661) or CTI-alone (AUC = 0.651) models. WQS analysis identified C-reactive protein (38.8%) and hypertension (31.7%) as the predominant risk factors. CONCLUSION: Integrating CTI with hypertension significantly improves stroke risk stratification in CKM stage 0-3 populations, supporting its potential for early identification of high-risk individuals.