Liver fibrosis and sudden cardiac arrest: A prospective cohort study of 452,454 individuals

The bidirectional liver-heart axis is increasingly recognized. Although compelling evidence links liver fibrosis to adverse cardiovascular outcomes, its specific link to sudden cardiac arrest (SCA) in the general population remains less well elucidated.

We aimed to investigate the association between liver fibrosis and SCA.

This prospective analysis included 452,454 participants from the United Kingdom Biobank. Liver fibrosis was non-invasively assessed using the Fibrosis-4 (FIB-4) index, with participants categorized into low (<1.30), indeterminate (1.30-2.67), and high (>2.67) risk groups. The primary outcome was incident SCA. Associations were evaluated using Cox proportional hazards models, adjusted for comprehensive cardiovascular risk factors.

The analysis included participants with a median age of 58 years, and 45.8% were male. During a median follow-up of 13.8 years, 2889 incident SCA cases were documented. Participants with higher FIB-4 scores exhibited significantly higher cumulative incidence of SCA (log-rank P < .001). Compared with the low-risk group, the adjusted hazard ratios for SCA were 1.26 (95% confidential interval [CI]: 1.15-1.39) in the indeterminate-risk group and 1.69 (95% CI: 1.36-2.12) in the high-risk group. Dose-response analysis revealed a nonlinear yet positive association between continuous FIB-4 index and SCA risk. Each standard deviation increase in FIB-4 was associated with a 20% higher SCA risk (adjusted hazard ratios 1.20, 95% CI: 1.15-1.27).

Liver fibrosis, as assessed by the FIB-4 index, is an independent and graded predictor of SCA risk in the general population. This readily available biomarker could enhance SCA risk stratification and primary prevention strategies.