Linking liver fibrosis to cardiac structure, function, and heart disease: a community-based fibrosis-4 index study

Background The Fibrosis-4 Index (FIB-4) is a non-invasive tool used to assess advanced liver fibrosis. Although liver fibrosis has been linked to heart disease, its relationship with cardiac structure and function remains unclear. Objectives This study examined associations of FIB-4 with incident heart disease and cardiac morpho-functional phenotypes and explored whether cardiac phenotypes statistically accounted for part of the association. Methods In this prospective cohort study using the UK Biobank, 416,001 participants without known heart or liver disease at baseline (mean age 56.15 ± 8.09 years; 55.78% female) were followed for up to 17 years. FIB-4, calculated from age, AST, ALT, and platelet count, was analyzed continuously and using a high-risk threshold of >2.67. Incident coronary heart disease, cardiac arrhythmias (CA), and heart failure (HF) were identified from linked records. A subset of 33,927 participants underwent cardiovascular magnetic resonance (CMR) imaging a median of 10.20 years after baseline. Results Over a median follow-up of 14.61 years, 57,207 participants (13.75%) developed heart disease. Higher FIB-4 was associated with CA (HR = 1.32, 95% CI 1.24–1.41), HF (HR = 1.29, 95% CI 1.14–1.47), greater LV mass ( β =0.014, 95% CI 0.0003–0.027), chamber dilation, reduced atrial ejection fractions, and LV remodeling. Exploratory pathway analysis indicated that LA ejection fraction statistically accounted for 36.38% of the FIB-4–CA/HF association; causal mediation cannot be inferred. Conclusion Elevated FIB-4 was associated with incident CA and HF and with adverse CMR phenotypes. Exploratory pathway results were consistent with indirect pathways through cardiac remodeling, but the observational design and single CMR assessment preclude causal or temporal interpretation. FIB-4 may help identify people at higher cardiovascular risk.