Association of cumulative cholesterol-HDL-glucose index with cardiovascular disease risk in individuals with cardiovascular-kidney-metabolic syndrome stages 0–3: a nationwide prospective cohort study

Abstract

Cardiovascular–kidney–metabolic (CKM) syndrome integrates cardiovascular disease, chronic kidney disease, and metabolic risk factors, highlighting their interaction and shared progression. The cholesterol–HDL–glucose (CHG) index is a composite lipid–glucose index that may reflect metabolic dysfunction related to insulin resistance, although it is not a direct measure of insulin sensitivity. However, the association between cumulative CHG exposure and cardiovascular disease risk in the CKM stages 0–3 population remains unclear. Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS). A total of 3,002 participants with CKM stages 0–3 were included. Cumulative CHG exposure was assessed using CHG values measured at Wave 1 and Wave 3. K-means clustering was applied to identify clusters representing two-point repeated CHG exposure patterns. Multivariable Cox proportional hazards regression models and restricted cubic spline (RCS) analyses were used to evaluate the association between cumulative CHG and incident cardiovascular disease (CVD). Receiver operating characteristic (ROC) curve analyses were performed to assess the discrimination ability of cumulative CHG for 3-year and 5-year CVD occurrence. Subgroup and sensitivity analyses were conducted to examine the robustness of the results. Among the 3,002 participants included in the analysis, 569 (19%) developed incident CVD during a median follow-up of 5 years. In the main confounder-adjusted model, each one-unit increase in cumulative CHG was associated with a higher risk of incident CVD (HR = 1.19, 95% CI: 1.11–1.27). Compared with participants in the lowest quartile, those in the highest quartile had an increased risk of CVD (HR = 1.67, 95% CI: 1.31–2.12). Restricted cubic spline analysis indicated a linear association between cumulative CHG and CVD risk. Among the three clusters representing two-point repeated CHG exposure patterns, participants in Cluster 2 and Cluster 3 had higher risks of CVD compared with Cluster 1, with HRs of 1.32 (95% CI: 1.10–1.58) and 1.69 (95% CI: 1.29–2.21), respectively. ROC analyses showed that cumulative CHG had limited discrimination ability when used alone for incident CVD, with AUC values of 0.560 at 3 years and 0.569 at 5 years. In individuals with CKM stages 0–3, elevated cumulative CHG is associated with an increased risk of CVD. Repeated CHG measurements may provide a more comprehensive characterization of long-term metabolic exposure, although cumulative CHG showed limited discrimination ability when used alone.