Combined cholesterol, high-density lipoprotein, and glucose index and Frailty Index for Assessing Incident Stroke Risk in Middle-Aged and Older Adults: Based on Two Nationwide Prospective Cohorts

Background The cholesterol, high-density lipoprotein, and glucose (CHG) index is an emerging surrogate marker of insulin resistance (IR) and a recognised risk factor for stroke. Concurrently, the frailty index (FI) independently predicts the incidence of cerebrovascular events in ageing populations. However, the predictive value of a composite metric integrating these metabolic and biological ageing characteristics (namely, the combined CHG-FI) for incident stroke remains unexplored. The present study aims to elucidate the association between the novel CHG-FI and the risk of incident stroke among middle-aged and older populations. Methods Data from two national prospective cohorts, the China Health and Retirement Longitudinal Study (CHARLS) and the English Longitudinal Study of Ageing (ELSA), were analysed. Multivariable Cox proportional hazards models were employed to evaluate the longitudinal association between CHG-FI and incident stroke. Restricted cubic splines (RCS) were utilised to delineate the corresponding dose-response relationship. Furthermore, the discrimination and clinical utility of the predictive models were assessed via receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Results A total of 10,862 participants were included (8,825 in the CHARLS cohort; 2,037 in the ELSA cohort). Multivariable analyses indicated that CHG-FI is independently associated with incident stroke. Specifically, each 1-standard deviation (SD) increment in CHG-FI was associated with a 27.2% increase in the risk of incident stroke (HR, 1.272; 95% CI, 1.076–1.504; P = 0.005). RCS analysis confirmed a significant positive linear association between CHG-FI and stroke risk. Subgroup analyses demonstrated that this prognostic effect remained robust across different age and sex strata. Finally, ROC and DCA results from both cohorts confirmed that CHG-FI possesses reliable discriminative capacity and clear net clinical benefit. Conclusion An elevated combined CHG-FI is significantly and positively associated with an increased risk of incident stroke. This composite metric, integrating metabolic and frailty characteristics, may serve as a robust tool for early stroke risk stratification in middle-aged and older populations.