Association Between Cholesterol–HDL–Glucose Index and Stroke Risk in Middle-Aged and Elderly Adults Without Diabetes: Evidence From Two National Cohort Studies

Background: The cholesterol–HDL–glucose (CHG) index has emerged as a novel indicator for metabolic disorders, but its association with stroke risk, especially in nondiabetic individuals, remains unclear. This study aimed to investigate the relationship between the CHG index and stroke risk in middle-aged and elderly adults without diabetes. Methods: Data were derived from two cohorts: the China Health and Retirement Longitudinal Study (CHARLS) database (2011–2020) and the National Health and Nutrition Examination Survey (NHANES) database (2011–2018), respectively. The incidence of stroke events was the primary outcome. Cox proportional hazard regression models and restricted cubic spline (RCS) analysis were employed to examine the association between the CHG index and the risk of stroke. Receiver operating characteristic (ROC) curve was established to assess the diagnostic performance of the CHG index. Mediation analysis was conducted to reveal potential mediators of this association. Sensitivity and subgroup analyses were used to validate the robustness of the main findings. Results: In CHARLS cohort, a total of 651 participants (n = 8,376, 7.77%) developed stroke during the 9.0 years follow-up period. The multivariable adjusted hazard ratios for participants in the quartile 2 to quartile 4 groups compared with those in the quartile 1 group were 1.378 (95% confidence interval (CI) 1.073–1.771), 1.447 (95% CI 1.137–1.842), and 1.463 (95% CI 1.147–1.868), respectively. RCS analysis demonstrated a significant linear relationship between the CHG index and stroke risk (all P for nonlinear > 0.05). The ROC curve revealed that the CHG index had a comparable predictive performance with the triglyceride–glucose (TyG) index. Mediation analysis showed that glycated hemoglobin A1c (HbA1c) mediated 13.33% of the association between the CHG index and the stroke. Subgroup and sensitivity analyses further confirmed the robustness of the main findings, showing consistent results across different demographic and clinical groups. Additionally, analyses of the NHANES database (n = 5,057) indicated a significant positive correlation between the CHG index and stroke risk, as well as a notable predictive capacity of the CHG index for stroke. Conclusions: These findings suggest that the CHG index may serve as a novel and promising indicator for stroke.