Association between the cholesterol-high-density lipoprotein-glucose index and new-onset stroke in middle-aged and older adults with depressive symptoms: a longitudinal cohort analysis

BACKGROUND: Depression is a global disease that significantly increases the risk of stroke. The cholesterol, high-density lipoprotein, and glucose index (CHG index) as an emerging composite metabolic marker has shown value in cardiovascular diseases and diabetes, but its predictive role in new-onset stroke among depressed individuals remains unclear. METHODS: This study is based on the data from the Chinese Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018. A total of 5,138 participants aged 45 and above, who had depressive symptoms (CES-D score ≥ 10) at the baseline and had no history of stroke, were included. Sequential Cox proportional hazards regression models were used as the main analysis to evaluate the association between the CHG index and new-onset stroke, and multivariable logistic regression was used as a secondary analysis to verify the consistency of the direction. Multiple imputation (20 datasets) was used to handle missing values of covariates. Restricted cubic splines and two-stage Cox regression models were used to explore potential nonlinear relationships and threshold effects. RESULTS: During a total follow-up period of 35,554 person-years (with a median follow-up of 7 years), a total of 421 new-onset stroke events occurred. In the fully adjusted Cox model, for every 1-unit increase in the CHG index, the risk of new-onset stroke increased by 48% (HR = 1.48, 95% CI: 1.15-1.90, P = 0.003). However, the restricted cubic spline analysis revealed a significant non-linear relationship (D1 test P = 0.005), with the inflection point occurring at a CHG index of 5.59. When the CHG index was below 5.59, for every 1-unit increase, the risk of stroke increased by 117% (HR = 2.17, 95% CI: 1.37-3.44, P = 0.001); above this inflection point, no statistically significant association was observed (HR = 1.00, 95% CI: 0.62-1.62, P = 0.996). Multivariable logistic regression yielded a consistent significant association (OR = 1.53, 95% CI: 1.16-2.03, P = 0.003). Subgroup analysis and multiple sensitivity analyses (quartile analysis, exclusion of early stroke events, median binary classification analysis) all supported the robustness of the main findings. CONCLUSION: Among middle‑aged and older Chinese adults with depressive symptoms, the CHG index shows a significant non-linear positive association with the risk of new-onset stroke, and the risk increases sharply when the index is below 5.59. The CHG index may serve as a potential indicator for the early risk of stroke in this high-risk population.