Subclinical liver disease and incident cardiovascular events.

Authors

Le Li, Lingmin Wu, Zhicheng Hu, Limin Liu, Tao Zhang, Likun Zhou, Zhenhao Zhang, Yulong Xiong, Lihui Zheng, Ligang Ding, Yan Yao

Published in

European heart journal. Sep 07, 2026. Epub Sep 07, 2026.

Abstract

Quantifying the multidimensional risk that subclinical liver disease imposes on cardiovascular health remains a critical unmet need. This study aimed to investigate the independent and synergistic associations of hepatic steatosis, fibrosis, and functional decline with incident cardiovascular disease (CVD).
In this prospective cohort study of 318 308 participants free of clinical liver and CVD at baseline, this study evaluated the association of three non-invasive liver biomarkers-fatty liver index (FLI) for steatosis, fibrosis-4 index (FIB-4) for fibrosis, and albumin-bilirubin (ALBI) score for functional reserve-with major incident CVD events, including myocardial infarction, heart failure, atrial fibrillation, ischaemic stroke, and cardiovascular death.
Over a median follow-up of 14.0 years, 32 637 incident CVD events (10.3%) occurred. Each biomarker independently predicted CVD risk after multivariable adjustment: the highest quartile (Q4) of FLI (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] 1.40-1.52), FIB-4 (aHR 1.66, 95% CI 1.60-1.73), and ALBI (aHR 1.42, 95% CI 1.37-1.47) showed significantly elevated risks compared to Q1. Critically, participants with all three biomarkers in Q4 exhibited a substantially elevated synergistic risk (aHR 2.53, 95% CI 2.38-2.70). Sex-specific analyses revealed FLI was more strongly associated with CVD in women, whereas FIB-4 and ALBI showed greater risk in men. Results were consistent across sensitivity analyses and specific CVD endpoints.
These findings establish subclinical liver disease-through steatosis, fibrosis, and functional impairment-as an independent and synergistic determinant of CVD risk. Incorporation of these non-invasive biomarkers could refine CVD risk stratification and enable targeted prevention strategies.

PMID:
42702521
Bibliographic data and abstract were imported from PubMed on 07 Sep 2026.

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