People with metabolic dysfunction-associated steatotic liver disease (MASLD) who show higher scores on a common liver fibrosis measure also face a substantially greater risk of heart attack, stroke and heart failure, according to a cohort study drawing on UK Biobank data. The new analysis suggests the index carries information relevant well beyond the liver.
The study included UK Biobank participants classified as having MASLD using a Fatty Liver Index of 60 or higher in the absence of significant alcohol consumption or other liver diseases. Researchers divided participants into three FIB-4 risk categories: low risk below 1.30, intermediate risk between 1.30 and 2.67, and high risk above 2.67. The primary outcome was a composite of heart failure, myocardial infarction and stroke, and the team used Cox proportional hazards models to test associations between fibrosis risk category and cardiovascular events.
The results showed a clear gradient. Compared with participants in the low-risk group, those at intermediate FIB-4 risk had an adjusted hazard ratio of 1.57 for cardiovascular events (95% confidence interval, 1.49 to 1.66), while those in the high-risk group had an adjusted hazard ratio of 2.31 (95% confidence interval, 2.00 to 2.66). Participants who experienced cardiovascular events during follow-up tended to be older, more often male, and to have less favorable cardiometabolic profiles than those who did not.
Because MASLD is closely tied to cardiovascular disease, the researchers also probed the metabolic features that might underlie the association. Using nuclear magnetic resonance metabolomics, they screened for metabolites associated with cardiovascular events within each FIB-4 group, using a nominal significance threshold of P below 0.05 for this exploratory analysis and examining false discovery rate-corrected results in sensitivity analyses. Sixty-four nominally associated metabolites were shared across all three FIB-4 groups, and these predominantly involved cholesterol, lipids, lipoprotein particles and phospholipids. Spearman correlation networks and manual enrichment of metabolic categories pointed to shared features reflecting lipid transport and lipoprotein particle composition.
The team then tested whether this information improved risk prediction beyond an established tool. Using Cox-LASSO regression with 10-fold cross-validation, they selected a metabolite panel and compared discrimination, measured by area under the receiver operating characteristic curve, across three models: the Framingham score alone, the Framingham score plus FIB-4, and the Framingham score plus FIB-4 and metabolites. The AUC rose from 0.663 for the Framingham score alone to 0.668 after adding FIB-4 and to 0.684 after further adding metabolites, with differences assessed using DeLong tests.
The authors conclude that higher FIB-4 risk was associated with greater cardiovascular event risk among participants with MASLD, and that the shared metabolic signature suggests a common metabolic background rather than a causal pathway running from liver fibrosis to cardiovascular disease. As an observational cohort analysis, the study establishes associations rather than proven causal effects, and the modest gains in predictive discrimination indicate that metabolomics added incremental, not transformative, value on top of conventional risk scoring. The work was published open access in BMC Cardiovascular Disorders on 29 October 2026.
Subject of Research: Associations between liver fibrosis risk categories and cardiovascular events in metabolic dysfunction-associated steatotic liver disease
Article Title: FIB-4 risk categories and cardiovascular events in metabolic dysfunction-associated steatotic liver disease: metabolomic insights from a UK Biobank cohort study
Article References: Wei, X., Jin, A., Ye, Z., Xu, H., Hou, Y., & Xu, J. (2026). FIB-4 risk categories and cardiovascular events in metabolic dysfunction-associated steatotic liver disease: metabolomic insights from a UK Biobank cohort study. BMC Cardiovascular Disorders. https://doi.org/10.1186/s12872-026-06890-7
Image Credits: AI Generated
DOI: 10.1186/s12872-026-06890-7
Keywords: MASLD, FIB-4, cardiovascular events, UK Biobank, metabolomics, lipoproteins, heart failure, myocardial infarction, stroke, risk prediction, risk, categories
News Source: Ophelia Keating. (October 29, 2026). Liver Fibrosis Score Tied to Higher Cardiovascular Risk in Fatty Liver Disease. Scienmag.
