Joint association of the C-reactive protein-triglyceride-glucose index and frailty with incident stroke: a nationwide prospective cohort study

Frail individuals frequently present with chronic inflammation and metabolic dysfunction, both of which are closely associated with increased stroke risk. Therefore, the joint contribution of the C-reactive protein–triglyceride-glucose index (CTI) and frailty to incident stroke appears biologically plausible but has not yet been investigated. We therefore examined the independent and combined associations of CTI and the frailty index (FI) with incident stroke in a nationwide prospective cohort. This prospective cohort study included 8,755 participants without baseline stroke from the China Health and Retirement Longitudinal Study (CHARLS). Participants were classified according to CTI level and frailty status. Cox proportional hazards models were used to evaluate the independent and joint associations of CTI and the frailty index (FI) with incident stroke. Additive and multiplicative interactions between CTI and FI were further evaluated. During follow-up, 515 participants developed an incident stroke. In the fully adjusted model, high CTI and high FI were independently associated with increased stroke risk, with hazard ratios (HRs) of 1.62 (95% CI: 1.35–1.95) and 1.53 (95% CI: 1.25–1.87), respectively. Compared with participants with low CTI and low FI, those with high CTI and low FI, low CTI and high FI, and high CTI and high FI exhibited progressively increased stroke risks, with HRs of 1.88 (95% CI: 1.51–2.35), 2.05 (95% CI: 1.51–2.79), and 2.42 (95% CI: 1.81–3.24), respectively. No significant additive interaction was observed, whereas a significant multiplicative interaction was identified. The combined CTI + FI model showed better predictive performance for incident stroke than either indicator alone. These associations remained stable across subgroup and sensitivity analyses. Elevated CTI and FI were independently and jointly associated with increased risks of incident stroke. The combined assessment of metabolic-inflammatory status and frailty may improve stroke risk stratification in middle-aged and older adults.