Abstract
BACKGROUND: Emerging triglyceride-glucose (TyG)-related indices, such as the TyG-related body roundness index (TyG-BRI), a body shape index (TyG-ABSI), weight-adjusted waist index (TyG-WWI), and Chinese visceral adiposity index (TyG-CVAI), have gained attention as promising predictors of diverse cardiometabolic conditions. Nevertheless, their prospective associations with stroke onset remain insufficiently characterized, especially in individuals affected by cardiovascular-kidney-metabolic (CKM) syndrome. METHODS: This prospective cohort study included 7,503 middle-aged and older adults with CKM syndrome stages 0-3 (see Methods: Definition of CKM Stages 0 to 4) from the China Health and Retirement Longitudinal Study (CHARLS). Cox proportional hazards models were used to evaluate the associations between TyG-related indices and incident stroke, with potential non-linear relationships examined via restricted cubic splines (RCS). Discriminative performance was compared using receiver operating characteristic (ROC) curves. Mediation analysis was conducted to assess whether systolic blood pressure (SBP) mediated the associations. Subgroup and sensitivity analyses were also performed to verify robustness. RESULTS: Over a median follow-up of 5.2 years, 625 participants (8.33%) experienced a first stroke (incidence rate 102.18 per 10,000 person-years). In fully adjusted models, each 1-SD increase in TyG-BRI, TyG-ABSI, TyG-WWI, and TyG-CVAI was associated with stroke hazards of 1.16 (95% CI, 1.06-1.27), 1.10 (1.01-1.21), 1.13 (1.03-1.25), and 1.20 (1.10-1.31), respectively. Participants in the highest TyG-CVAI quartile had a 67% higher risk than those in the lowest (HR, 1.67; 95% CI, 1.28-2.18). Nonlinear thresholds were identified at TyG-BRI 18.16 and TyG-WWI 78.93. ROC analysis indicated that TyG-CVAI had the greatest discriminative ability for predicting stroke. SBP mediated 26.3-32.9% of these associations. The findings were consistent across multiple subgroup and sensitivity analyses. CONCLUSION: Novel TyG-related indices, particularly TyG-CVAI, showed significant and incremental predictive value for stroke risk among individuals with CKM syndrome stages 0-3. Their incorporation into risk stratification frameworks may enhance early detection and prevention of cerebrovascular events in metabolically vulnerable populations.