The cholesterol, high‐density lipoprotein, and glucose index and its derivatives related to obesity and inflammation as novel metabolic markers for predicting new‐onset cardiovascular‐liver‐metabolic multimorbidity: A prospective cohort study

BACKGROUND: Cardiovascular-liver-metabolic multimorbidity (CLMM), defined as the co-occurrence of at least two of cardiovascular disease, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease, is an increasing health burden. We evaluated the cholesterol, high-density lipoprotein, and glucose (CHG) index and its obesity- and inflammation-derived variants for predicting incident CLMM. METHODS: This prospective cohort included 6,534 adults aged ≥45 years from the China Health and Retirement Longitudinal Study. CHG, eight obesity-derived indices, and CHG-CRP were assessed, with the triglyceride-glucose index and TG/HDL-C ratio as comparators. Associations with incident CLMM were evaluated using logistic regression, restricted cubic splines, and threshold analysis. Predictive performance was compared using receiver operating characteristic analysis, the integrated discrimination improvement (IDI), and the net reclassification improvement (NRI), with additional joint-effect, interaction, subgroup, and sensitivity analyses. RESULTS: At the 2015 follow-up, 406 participants (6.2%) met the criteria for CLMM. Higher CHG was linearly associated with incident CLMM (highest vs lowest quartile: OR 1.64, 95% confidence interval [CI] 1.22-2.22). Obesity-derived variants showed stronger associations, particularly CHG-BMI (OR 3.13, 95% CI 2.21-4.43), which also had the highest discrimination (AUC 0.643, 95% CI 0.616-0.669) and continuous NRI (34.08%). Participants with both high CHG and high BMI had the greatest CLMM risk (OR 2.59, 95% CI 1.94-3.51). Results were robust in sensitivity analyses. CONCLUSIONS: The CHG index and its obesity-derived variants, particularly CHG-BMI, are accessible and inexpensive candidate metabolic markers for predicting new-onset CLMM. CHG-BMI showed the highest apparent discrimination among the evaluated indices, although its AUC was modest. External population validation is needed.