Associations of cumulative exposure and dynamic trajectories of the cholesterol–HDL–glucose index and its obesity-related derivatives with cardiovascular disease: a nationwide prospective cohort study

BACKGROUND: Integrating metabolic biomarkers with anthropometric indicators has been shown to enhance the discriminative capacity for cardiovascular disease (CVD). However, the impact of the cholesterol-HDL-glucose index (CHG) and its derivatives on CVD risk remains unclear. This study aimed to investigate the associations of CHG and its derivatives with CVD and to compare their discriminative performance. METHODS: This prospective study included 3,359 CVD-free participants from the China Health and Retirement Longitudinal Study (CHARLS). Repeated measurements obtained in 2011 and 2015 were used to derive cumulative exposure and longitudinal trajectory patterns of CHG and its derivatives. Associations of baseline values, cumulative exposure, and longitudinal trajectories of these indicators with incident CVD and stroke were examined using Cox proportional hazards regression models. RESULTS: During a median follow-up of 5 years, 466 participants (13.9%) developed CVD. Both CHG and its derivatives were significantly associated with CVD across baseline measurements, cumulative exposure, and longitudinal trajectories. Cumulative CHG derivatives showed significantly better discriminative power than isolated cumulative CHG (Delong's test P < 0.05), with the highest associations observed for cumulative CHG-waist circumference (HR = 1.29) and cumulative CHG-Chinese visceral adiposity index (HR = 1.28). Regarding trajectory patterns, participants with stably high CHG-CVAI exhibited the greatest risk compared with those maintaining stable low levels (HR = 1.79), followed by CHG-WC (HR = 1.65). Additionally, ascending and declining trajectories of both CHG-CVAI and CHG-WC were associated with increased CVD risk (ascending CHG-CVAI: HR = 1.79; declining CHG-CVAI: HR = 1.54; ascending CHG-WC: HR = 1.45; declining CHG-WC: HR = 1.54). CONCLUSIONS: CHG and its derivatives were strongly associated with incident CVD, with CHG-CVAI and CHG-WC exhibiting the most pronounced associations. Moreover, ascending and declining trajectories of CHG-CVAI and CHG-WC were linked to higher risk, highlighting the importance of tracking dynamic increases while also accounting for baseline metabolic status. These indicators may facilitate the identification of individuals at elevated risk for CVD.