A recent study published in Heart Rhythm demonstrated that an elevated Fatty Liver Index (FLI) is a strong independent predictor of sudden cardiac arrest (SCA) in adults without baseline cardiovascular disease (CVD), with a gradual increase in SCA risk corresponding to higher FLI levels. These findings underscore the importance of incorporating metabolic dysfunction-associated steatotic liver disease (MASLD) into cardiovascular risk assessment.
FLI is a practical, quantitative biomarker of metabolic liver injury that enables cost-effective risk stratification. Beyond liver-related outcomes, FLI independently predicts adverse cardiovascular events and is associated with increased mortality in high-risk populations. Notably, in young Korean adults, a high FLI (≥60) was linked to a 55% increased risk of SCA, particularly prominent in women. However, the ability of FLI to predict incident SCA in adults without baseline CVD or liver disease had not been validated. This study therefore aimed to determine whether FLI could independently predict SCA in a primary prevention cohort, potentially enabling early metabolic intervention.
Using the prospective UK Biobank cohort, the study enrolled 347,925 middle‑aged and older adults without CVD, liver disease, or prior SCA at baseline. Sudden cardiac arrest events were strictly defined using ICD‑10 codes. FLI was categorized into four tiers: <30, 30–59, 60–89, and ≥90. An FLI ≥30 plus at least one cardiometabolic risk factor was used to define MASLD. Models were systematically adjusted for age, sex, socioeconomic status, lifestyle, inflammatory markers, dysglycemia, and multiple chronic conditions. Robustness was verified using propensity score matching and multiple sensitivity analyses.
During a median follow‑up of 14.1 years, 1,843 incident SCA events were recorded. The incidence of SCA increased significantly across FLI categories.
In multivariable Cox regression models, SCA risk rose stepwise with higher FLI. After full adjustment for confounders, all higher FLI categories showed significantly increased SCA risk compared with FLI <30, confirming FLI as a robust and strong independent predictor in individuals without CVD. The association remained consistent in propensity score‑matched cohorts and in sensitivity analyses excluding participants with hypertension, diabetes, chronic kidney disease, or early follow‑up events, indicating high robustness.
Further analysis revealed that among individuals with FLI ≥30, SCA risk increased exponentially with the number of coexisting cardiometabolic abnormalities. Those with ≥4 abnormalities had an SCA incidence of 0.86%, with an adjusted 41% risk increase (HR = 1.41, 95% CI: 1.21–1.65), demonstrating a significant synergistic amplification effect between fatty liver and multiple metabolic disorders. Subgroup analyses showed a clear sex difference: women exhibited significantly elevated risk at FLI ≥60 (60–89: HR = 1.27; ≥90: HR = 1.69), whereas men only showed a significant increase at FLI ≥90 (HR = 1.42), suggesting that women enter a high-risk state for cardiac electrophysiological instability at a lower fatty liver burden.
Furthermore, the Fine–Gray competing risk model confirmed that the association between FLI and SCA remained stable after accounting for the competing risk of all‑cause mortality. Mediation analysis further indicated that systemic inflammation (high‑sensitivity C‑reactive protein) and fasting plasma glucose significantly mediated the relationship between FLI and SCA, suggesting that systemic inflammation and dysglycemia represent key biological pathways linking fatty liver to sudden cardiac arrest and providing a mechanistic rationale for early clinical intervention.