Association of the cholesterol, high-density lipoprotein, and glucose index with stroke risk in individuals with cardiovascular-kidney-metabolic syndrome stages 0-3: a national prospective cohort study

BACKGROUND: The association between the cholesterol, high-density lipoprotein, and glucose (CHG) index and stroke risk among individuals with cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 remains unclear. OBJECTIVE: This study aimed to assess the associations of dynamic and cumulative CHG indices with stroke risk. METHODS: This study used data from the China Health and Retirement Longitudinal Study (CHARLS) among individuals aged ≥45 years with CKM stages 0-3. The outcome was self-reported incident stroke during a 5-year follow-up. CHG changes were clustered into four groups via K-means; cumulative CHG was divided into quartiles. Multivariable logistic regression analyses were used to assess the associations of CHG changes and cumulative CHG with stroke risk. RESULTS: During follow-up, 358 participants (7.95%) with CKM syndrome stages 0-3 experienced stroke. In the fully adjusted model, each 1-SD increase in the CHG index was linked to a 21.2% higher stroke risk (OR 1.212; 95% CI 1.072-1.366). Compared with cluster 1, risk increased across clusters 2-4, with odds ratios of 1.376 (95% CI 0.998-1.908), 1.647 (95% CI 1.194-2.285), and 1.773 (95% CI 1.168-2.677), respectively. Restricted cubic spline (RCS) regression supported a linear relationship. Adding CHG improved receiver operating characteristic (ROC) performance: area under the curve (AUC) increased from 0.634 to 0.642, with significant net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Mediation analysis indicated partial effects via systolic blood pressure (SBP, 13.6%), diastolic blood pressure (DBP, 8.3%), and estimated pulse wave velocity (ePWV, 6.8%). CONCLUSIONS: In CKM syndrome stages 0-3, elevated CHG and cumulative CHG are associated with higher stroke risk, highlighting the potential value of CHG monitoring for prevention.