Comparative associations of cumulative cholesterol-HDL-glucose index and triglyceride-glucose index with risk of cardiovascular disease in individuals with cardiovascular-kidney-metabolic syndrome stages 0-3: a prospective cohort study.

Background: The American Heart Association recently introduced Cardiovascular-kidney-metabolic (CKM) syndrome as an integrated clinical construct. Evidence based on a single assessment suggests that the novel composite biomarker, Cholesterol, High-density lipoprotein, and Glucose (CHG) index, is associated with cardiovascular disease (CVD) risk. To data, the association between cumulative CHG index and risk of CVD has not been sufficiently investigated, particularly in individuals with CKM syndrome stages 0-3. Thus, we aimed to investigate the impact of cumulative CHG index on CVD development in individuals with CKM syndrome stages 0-3 and compared the predictive performances of triglyceride-glucose (TyG) index and CHG index for CVD. Methods: Participants were recruited from the Kailuan Study, a large-scale prospective cohort. The cumulative exposure was assessed using the time-weighted average (TWA) and exposure duration. The optimal cut-off values for TyG_TWA and CHG_TWA associated with CVD were derived using a survival-time method and were used to assess exposure duration of high TyG index/CHG index. Multivariable Cox proportional hazard regression model was used to assess hazard ratio (HR) and 95% confidence interval (95% CI) for CVD incident in individuals with CKM syndrome stages 0-3. Results: We included 46,827 participants, of these, the mean age was 52.71 years, 76.80% were males. All participants were divided into four groups according to the quartiles (Q) of TyG_TWA and CHG_TWA (Q1-Q4), and exposure duration of high TyG index/CHG index was quantified as 0 (reference), 2, 4, or 6 years. Over a mean follow-up of 11.08 years, 4,639 participants developed CVD. Compared with participants in Q1 group of CHG_TWA, the HRs (95% CIs) of CVD were 1.04 (0.95-1.14) for those in Q2 group, 1.13 (1.04-1.24) for those in Q3 group, and 1.23 (1.12-1.36) for those in Q4 group; compared with participants without exposure of high CHG index, the HR (95% CI) of CVD was increased by 41% (1.25-1.59) for those with 6 years exposure. Similar findings were observed in the analysis of cumulative exposure to TyG index with CVD. The association between TyG_TWA and CVD was linear, whereas the association of CHG_TWA with CVD was non-linear. The result of receiver operating characteristic curve analysis showed that CHG_TWA had a modestly higher discriminatory ability for CVD risk compared with TyG_TWA. Conclusions: In individuals with CKM syndrome stages 0-3, there was a significant association of high CHG_TWA/TyG_TWA with the risk of CVD, with these associations being stronger with longer exposure duration to high TyG index and CHG index. CHG_TWA demonstrated a modestly higher discriminatory ability for CVD risk compared with TyG_TWA. Our findings suggest that longitudinal monitoring of CHG index and TyG index may provide additional information for CVD risk stratification in individuals with CKM syndrome stages 0-3.