Association of cumulative exposure to cholesterol, high‐density lipoprotein, and glucose index with the risk of cardiovascular disease and all‐cause mortality: A longitudinal cohort study

BACKGROUND: An innovative insulin resistance (IR)-related index of cholesterol, high-density lipoprotein, and glucose (CHG) has been linked to cardiovascular disease (CVD) risk, but there is limited evidence for the effect of a long-term pattern of CHG on CVD and all-cause mortality. This study aimed to examine the associations between cumulative CHG and the occurrence of CVD and all-cause mortality. METHODS: We incorporated 53 700 participants from the Kailuan cohort. Cumulative CHG was computed using data from the 2006 to 2010 surveys and was defined as the average CHG for each pair of subsequent surveys, multiplied by the time intervals between these surveys. A multivariate Cox proportional hazards regression model was employed to evaluate the risk of CVD and all-cause mortality from 2010 to 2021, reporting hazard ratios (HR) and 95% confidence intervals (95% CI). All participants were divided into four groups according to the quartiles of cumulative CHG, and the exposure duration of high CHG was quantified as 0, 2, 4, and 6 years. RESULTS: A total of 3739 CVD and 4853 all-cause mortality events occurred during a median follow-up of 11.06 years. After adjusting for potential covariates, participants in the highest quartile exhibited significantly increased risks of incident CVD (HR, 1.70; 95% CI: 1.55-1.88) and all-cause mortality (HR, 1.22; 95% CI: 1.13-1.33) compared to those in the lowest quartile. Participants in the 6-year exposure to high CHG exhibited significantly increased risks of incident CVD (HR, 1.79; 95% CI: 1.61-1.98) and all-cause mortality (HR, 1.23; 95% CI: 1.13-1.34) compared to those without exposure to high CHG. Receiver operating characteristic curve analysis revealed that cumulative CHG had superior predictive value for CVD and all-cause mortality compared to baseline CHG, outperforming other indices of IR. CONCLUSIONS: The high cumulative CHG was associated with an increased risk of CVD and all-cause mortality, demonstrating superior predictive performance compared to both baseline CHG and other cumulative metabolic indices. The study highlights the significance of the long-term monitoring of the CHG index in clinical practice.