Abstract
BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome represents an emerging notion focused on the interconnection among cardiovascular, renal, and metabolic disorders. The predictive value of the cholesterol-high-density lipoprotein-glucose (CHG) index for advanced CKM syndrome and its stage-stratified mortality risk across stages 0 to 3 remains uncertain. This research aims to examine the clinical importance of the CHG and the triglyceride-glucose (TyG) indices in characterizing the development of advanced CKM syndrome and predicting mortality within the 0–3 stage. METHODS: We processed the data from the National Health and Nutrition Examination Survey (NHANES) 2003–2018. Associations were evaluated using multivariate logistic regression for disease progression and Cox models with restricted cubic splines (RCS) for mortality outcomes, accompanied by threshold effect and mediation analyses. RESULTS: Using multivariable logistic regression models, we found that both the CHG index and the TyG index are positively related with advanced CKM syndrome. Multivariable-adjusted modeling showed a 44% increase in the threat of all-cause mortality for each 1-unit rise in the CHG index, while no association with cardiovascular mortality was found. RCS analysis revealed a J-curve pattern in the association of the CHG index with all-cause mortality and cardiovascular mortality, with thresholds of 5.16 and 5.27. Mediation analyses identified that alkaline phosphatase, neutrophils, and the systemic immune-inflammatory index mediated between 2.1% and 17.2% of the effect in the relationship between the CHG index and all-cause mortality. CONCLUSIONS: The CHG index demonstrates dual clinical utility: stratifying patients with advanced CKM syndrome and predicting nonlinear mortality across the early progressive continuum (stages 0–3). Its J-shaped association with mortality suggests complex pathophysiological relationships requiring further investigation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13098-025-02055-2.