Cumulative exposure and patterns of the cholesterol–HDL-C–glucose index and risk of new-onset cardiometabolic multimorbidity: 9-year longitudinal evidence from CHARLS

Background: The cholesterol-HDL-C-glucose (CHG) index has been proposed as an integrated marker of glucose-lipid metabolic dysfunction. However, the associations of long-term CHG exposure and its temporal patterns with new-onset cardiometabolic multimorbidity (CMM) remain unclear, particularly among middle-aged and older adults. Methods: We used data from the China Health and Retirement Longitudinal Study (CHARLS) and included participants aged 45 years or older without baseline CMM. Cumulative CHG (cuCHG) was calculated as a cumulative exposure metric based on CHG measured in 2012 and 2015. K-means clustering was applied to identify broad CHG patterns based on the two repeated measurements. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and restricted cubic spline (RCS) analyses were performed to examine the dose-response relationship. Results: Among 6,515 participants, 593 new-onset CMM events (9.1%) occurred over a median follow-up of 9 years. In the fully adjusted model, participants in the highest quartile of cuCHG had a 78% higher risk of new-onset CMM than those in the lowest quartile (HR 1.78, 95% CI 1.39-2.29), and each 1-unit increase in cuCHG was associated with a 23% higher risk (HR 1.23, 95% CI 1.15-1.32). Three distinct CHG patterns based on two repeated measurements were identified, and only the persistently high CHG pattern group was significantly associated with an increased risk of new-onset CMM (HR 2.05, 95% CI 1.61-2.61). RCS and piecewise Cox analyses suggested a non-linear association, with a potential threshold at a cuCHG value of 14.92. These findings remained robust across subgroup and sensitivity analyses. Compared with baseline CHG, the triglyceride-glucose index, and the atherogenic index of plasma, cuCHG and CHG pattern groups showed better discriminatory performance. Conclusions: Higher cumulative CHG exposure and a persistently high CHG pattern group were independently associated with an increased risk of new-onset CMM in middle-aged and older Chinese adults. Compared with a single baseline CHG measurement, cumulative CHG exposure and CHG patterns based on repeated measurements may provide additional information for CMM risk stratification.