Abstract
BACKGROUND: The C-reactive protein-triglyceride glucose index (CTI) has been associated with stroke risk in prior studies. However, its relevance among individuals with cardiovascular-kidney-metabolic (CKM) syndrome remains uncertain. METHODS: This study included 5767 participants with CKM syndrome stages 0-3 from the China Health and Retirement Longitudinal Study. CTI was calculated as: CTI = 0.412 × ln[hs-CRP (mg/L)] + ln[(triglyceride (mg/dL) × fasting glucose (mg/dL)) / 2]. The primary outcome was incident stroke, assessed via self-reported questionnaires, with follow-up spanning 2011 to 2020. Cox proportional hazards models, restricted cubic spline (RCS) analysis, and subgroup analyses were used to examine the association between CTI and stroke risk. Time-dependent receiver operating characteristic (ROC) curve analysis was performed to compare the predictive performance of CTI with the triglyceride-glucose index (TyG) and the metabolic score for insulin resistance. Multiple testing correction was performed using the false discovery rate approach. RESULTS: After adjustment for potential confounders, higher CTI levels were significantly associated with increased stroke risk (HR 1.33, 95% CI 1.18-1.51). RCS analysis indicated a linear association, with no evidence of nonlinearity (P for nonlinearity = 0.182). Subgroup analyses indicated that elevated CTI was significantly associated with higher stroke risk in individuals at CKM stages 2 (HR 1.27, 95% CI 1.04-1.56; P = 0.019, adjusted P = 0.023) and 3 (HR 1.25, 95% CI 1.04-1.50; P = 0.022, adjusted P = 0.025), but no significant association was observed at stages 0-1. ROC analysis revealed that CTI consistently outperformed TyG in predicting stroke at years 5 and 7, as confirmed by DeLong's test (adjusted P = 0.028 for both). CONCLUSION: CTI is positively and linearly associated with stroke risk in individuals with CKM syndrome, particularly in stages 2 and 3. Furthermore, CTI provides superior predictive accuracy compared to TyG.