Association between the C-reactive protein–triglyceride glucose index combined with waist circumference and incident cardiovascular disease across frailty states: a prospective cohort study from CHARLS

The C-reactive protein–triglyceride–glucose index combined with waist circumference (CTI-WC) integrates central adiposity, systemic inflammation, and metabolic dysfunction. It has been associated with incident cardiovascular disease (CVD), but whether this association differs across frailty states remains unclear. This prospective cohort study included 7,113 adults aged 45 years or older from the China Health and Retirement Longitudinal Study (CHARLS) who were free of cardiovascular disease at baseline and were followed from 2011 to 2020. CTI-WC was calculated using baseline C-reactive protein, triglyceride, fasting plasma glucose, and waist circumference. Incident CVD was defined as the first self-reported physician diagnosis of heart disease or stroke during follow-up. Frailty was assessed using a 30-item frailty index, and participants were classified as robust, prefrail, or frail. Cox proportional hazards models were used to examine the association between CTI-WC and incident CVD in the overall population and across frailty states, and interaction terms were used to evaluate heterogeneity by frailty status. During a median follow-up of 9 years, 1,701 participants (23.9%) developed incident CVD. Each 1-SD increase in CTI-WC was associated with a 14% higher risk of incident CVD [hazard ratio (HR) 1.14, 95% confidence interval (CI) 1.08–1.21]. The association differed significantly across frailty states ( P for interaction = 0.042). Higher CTI-WC was associated with incident CVD among robust participants (HR 1.15, 95% CI 1.04–1.27) and prefrail participants (HR 1.17, 95% CI 1.07–1.28), whereas no statistically significant association was detected among frail participants (HR 1.02, 95% CI 0.90–1.16). These findings remained consistent across multiple sensitivity analyses. Higher CTI-WC was independently associated with incident CVD, and this association differed across frailty states. These findings highlight the importance of considering frailty status when interpreting the cardiovascular relevance of CTI-WC.