Abstract
BACKGROUND: Stroke is a significant public health issue, with its risk influenced by various metabolic factors. The Cholesterol, High-Density Lipoprotein, Glucose (CHG) index has been identified as a valid stroke predictor. However, the impact of glucose-metabolic states on the relationship between CHG index and stroke risk remains unclear. AIMS: This study aimed to investigate how baseline, cumulative, and longitudinal changes in CHG index are associated with incident stroke risk across different glucose-metabolic states: normal glucose regulation (NGR), pre-diabetes (Pre-DM), and diabetes (DM). METHODS: We analyzed data from 8,728 adults aged 45 and older, collected through five waves of the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2020. We assessed baseline, cumulative, and changes in the CHG index, with incident stroke as the primary outcome. Cox proportional hazards models quantified associations, and restricted cubic splines explored dose-response patterns. RESULTS: Over follow-up, 9.51% of participants had a stroke. The stroke incidence increased with higher CHG quartiles, except in individuals with DM. The highest CHG quartile (Q4) showed a 1.7-fold increased stroke risk (adjusted HR = 2.21 for NGR, adjusted HR = 2.02 for Pre-DM). No significant association was found in individuals with DM. Cumulative and longitudinal CHG index changes were positively associated with stroke risk, particularly in Pre-DM. CONCLUSIONS: Elevated CHG index is linked to higher stroke risk, especially in individuals with NGR and Pre-DM, highlighting the importance of early monitoring and intervention for metabolic dysregulation-related stroke risk.