The prognostic significance of cholesterol, high-density lipoprotein and glucose (CHG) index in evaluating all-cause mortality risk in metabolic dysfunction-associated steatotic liver disease (MASLD) individuals: evidence from two cohort studies

The prognostic assessment of metabolic dysfunction-associated steatotic liver disease (MASLD) is of critical importance. Although previous international studies have suggested an association between the cholesterol, high-density lipoprotein, and glucose (CHG) index and mortality in MASLD patients, its generalizability in the Chinese population remains unclear, and there is a lack of predictive tools directly applicable for individual risk stratification. A total of 6936 participants with MASLD were sourced from the China Health and Retirement Longitudinal Study (CHARLS) database from 2011 to 2020. Survival differences were visualized using the Kaplan-Meier method. Multivariate Cox regression was employed to assess the association between the CHG index and mortality risk. Smooth curve fitting analysis was conducted to examine the nonlinear relationship between them. Mediation analysis was performed to explore the mediating roles of C-reactive protein (CRP) and triglyceride glucose-weight-adjusted waist index (TyG-WWI). To evaluate the predictive value of the CHG index, we implemented a set of eight distinct machine learning (ML) models. Subgroup and sensitivity analyses were conducted to verify the robustness of the results. Concurrently, the National Health and Nutrition Examination Survey (NHANES) database (1999–2018) was utilized for external validation. The median follow-up duration was 7.44 years. A total of 615 mortality events were recorded. After adjusting for multiple confounding factors, an elevated CHG index was significantly associated with an increased risk of mortality (highest vs. lowest tertile, HR = 1.49, 95% CI [1.21–1.84], P = 0.0002). Kaplan-Meier curves demonstrated that higher CHG index levels were significantly associated with reduced survival (P < 0.0001). Smooth curve fitting and threshold effect analysis revealed a nonlinear relationship between them. Mediation analysis indicated that CRP and TyG-WWI mediated 13.36% and 45.33% of the effect of CHG index on mortality, respectively (all P < 0.05). Logistic Regression model showed superior discrimination. Decision curve analysis confirmed that the Logistic Regression model provided significant clinical net benefit across a wide range of risk thresholds. The primary analyses were replicated using data from the representative NHANES cohort, revealing a significant positive association between CHG index and mortality. Elevated CHG index is significantly associated with an increased risk of mortality in the Chinese MASLD population, demonstrating a nonlinear relationship. Furthermore, indicators related to inflammation and insulin resistance (IR) significantly mediate these associations. The CHG index serves as an important tool for predicting long-term adverse outcomes in this population. What is currently known about this topic? What is the key research question? What is new? How might this study influence clinical practice?