Abstract / Summary
Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a globally prevalent chronic liver disease. Accumulating evidence indicates that MASLD is closely linked to coronary artery disease (CAD) through the liver-heart axis, with insulin resistance, chronic systemic inflammation and lipid disorders as core shared mechanisms. Invasive coronary angiography remains an important reference method for defining luminal coronary stenosis, while contemporary CAD assessment increasingly incorporates coronary CT angiography and lesion-specific physiological indices such as FFR/iFR; its invasiveness and cost nevertheless restrict its role in large-scale population screening and primary care. However, optimal non-invasive strategies for CAD risk stratification specific to MASLD populations, particularly across different liver fibrosis stages, remain inadequately defined. Methods Based on a development cohort (n = 423) and an independent validation cohort (n = 212) of patients with MASLD fulfilling the cardiometabolic criteria of the current consensus definition, recruited under a single protocol and undergoing coronary angiography, we prespecified three primary biomarkers — TyG, LLCI, and FIB-4 — and additionally screened ten exploratory composite inflammatory/lipid indices, evaluating their discrimination for prevalent CAD and lesion severity via regression and ROC analyses. Patients were stratified by clinical presentation (non-CAD, SAP, UAP, AMI) and FIB-4-based fibrosis risk category (low risk, FIB-4 <1.3; intermediate risk, 1.3–2.67; high risk, ≥2.67; no second-line fibrosis assessment was performed). Multivariable logistic regression and receiver operating characteristic analysis were performed; bootstrap resampling was used to derive confidence intervals for subgroup AUC estimates. Results LLCI was independently associated with CAD (adjusted OR per 1-SD increase 1.33, 95% CI 1.21–1.46, P = 0.006), but its discrimination was poor and similar across cohorts (AUC 0.561 in the development cohort, 95% CI 0.506–0.615; AUC 0.562 in the validation cohort, 95% CI 0.475–0.650). Exploratory stratification by FIB-4 risk category did not identify any subgroup in which discrimination was reliably enhanced, and an apparent difference observed in the small high-risk stratum of the development cohort was not reproduced upon external validation. FIB-4 was independently associated with CAD severity (OR 1.445, 95% CI 1.070–1.950, P=0.016). Subgroup analyses were exploratory, and formal interaction tests were not significant (all P for interaction >0.05); no subgroup-specific effect modification could be demonstrated. After re-computation of the neutrophil-to-monocyte ratio (NMR) from raw leukocyte counts, NMR was not associated with ACS (OR 0.99 per 1-SD increase, 95% CI 0.69–1.41, P=0.94; sex-NMR combined AUC 0.51, close to chance), and the previously proposed sex-NMR model was withdrawn. Conclusion Routine laboratory indices showed limited and largely overlapping discrimination for angiographic CAD in MASLD, and none supported population-specific risk-stratification strategies. These findings underscore the limited incremental value of routine laboratory biomarkers for CAD risk assessment in MASLD and highlight the need for validated, prospectively evaluated markers. Clinical trial number Not applicable.