Sex differences in the association of the CRP-TyG index with coronary artery disease and long-term mortality in MASLD

Abstract

Background Metabolic dysfunction-associated steatotic liver disease (MASLD) increases cardiovascular risk, but non-invasive tools for risk stratification are limited. The C-reactive protein–triglyceride–glucose (CTI) index integrates metabolic and inflammatory pathways, but its value in MASLD is unclear. Methods We examined the association between CTI and obstructive coronary artery disease (CAD) in MASLD patients who underwent coronary computed tomography angiography. Machine-learning-assisted feature selection was used to assess the relative stability of CTI among candidate clinical variables, and multivariable logistic regression was used to evaluate its independent association with obstructive CAD. Discriminative performance was assessed using ROC curves, calibration analysis, clinical impact analysis, and restricted cubic spline analysis, with sex-stratified and sensitivity analyses. The prognostic relevance of CTI for all-cause and cardiovascular mortality was further evaluated in a population-based NHANES MASLD cohort. Results Higher CTI quartiles correlated with greater metabolic burden and CAD prevalence (P < 0.001). CTI was independently associated with obstructive CAD (OR = 1.68, 95% CI 1.33–2.12), with a graded association across quartiles. CTI showed moderate apparent discrimination for obstructive CAD, with higher AUCs than FIB-4, TyG-BMI, and TyG in the overall, male, and female populations. In the NHANES cohort, elevated CTI was associated with increased risks of all-cause and cardiovascular mortality, with the association for cardiovascular mortality being more evident in men than in women after full adjustment. Conclusion CTI was independently associated with CCTA-defined obstructive CAD in a high-risk MASLD cohort and showed prognostic relevance for long-term mortality in a population-based MASLD cohort.