Fibrosis-4 –defined liver fibrosis, traditional risk factors, and cardiovascular events in patients with acute coronary syndrome

Background Liver fibrosis and cardiovascular disease share common metabolic risk factors. However, the relationship between liver fibrosis and traditional cardiovascular risk factors and their combined prognostic impact in patients with acute coronary syndrome (ACS) remains incompletely understood. Objective This study aimed to investigate the association between traditional cardiovascular risk factors and liver fibrosis, as assessed by the Fibrosis-4 (FIB-4) index, in patients with acute coronary syndrome (ACS), and to evaluate their independent and combined effects on cardiovascular outcomes. Methods This was a post-hoc analysis of the OSA-ACS study. Patients were stratified into three groups based on FIB-4 cut-offs: <1.3 (minimal fibrosis), 1.3–2.67 (moderate fibrosis), and ≥2.67 (advanced fibrosis). Standardized modifiable cardiovascular risk factors (SMuRFs), including hypertension, dyslipidemia, diabetes mellitus, and smoking, were assessed. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), defined as a composite of hospitalization for ACS, cardiovascular death, ischemia-driven revascularization, stroke, or hospitalization for heart failure. Results A total of 1,909 patients with a median follow-up of 2.9 years were analyzed. Of these, 912 (47.8%) had low FIB-4 scores, 663 (34.7%) had intermediate scores, and 334 (17.5%) had high scores. After multivariable adjustment for traditional cardiovascular confounders including obesity, hypertension, diabetes, dyslipidemia, smoking, drinking, a high FIB-4 level remained the strongest independent predictor of MACCE (HR 1.60, 95% CI 1.23–2.08, P<0.001). Notably, the coexistence of elevated FIB-4 with more than one SMuRF was associated with a markedly increased MACCE risk (P=0.02 for intermediate fibrosis; P<0.001 for advanced fibrosis). Conclusions Advanced liver fibrosis, as staged by the FIB-4 index, is independently associated with an increased risk of MACCE in patients with ACS. Furthermore, the combination of liver fibrosis with multiple traditional cardiovascular risk factors confers a synergistic, markedly higher risk. These findings suggest that integrating FIB-4 into routine risk stratification may improve the identification of high-risk ACS patients.