Attributable burden of steatotic liver disease on cardiovascular outcomes in Asia.

Background & Aims: The associations between metabolic dysfunction-associated steatotic liver disease (MASLD) and specific cardiovascular events, as well as their attributable burdens, remain inconsistent and underexplored within a single population. This large-scale prospective cohort evaluated the associations between MASLD and various cardiovascular outcomes. Two additional steatotic liver disease (SLD) subtypes - MASLD with increased alcohol consumption (MetALD) and alcohol-related liver disease (ALD) - were also evaluated. Methods: We included 303,589 adults aged ≥30 years from Taiwan who underwent health examinations between 1997 and 2013. MASLD was defined by ultrasound-detected steatosis, limited alcohol intake, and ≥1 cardiometabolic risk factor. MetALD and ALD were defined based on alcohol intake thresholds and cardiometabolic profiles. Participants were followed until 2020, with outcomes and mortality ascertained via linkage to national registries. Cox proportional hazards models were used to estimate adjusted relative risks (RRs), and population attributable fractions (PAFs) were calculated. Results: Of the total population, 91,877 (30.3%) had MASLD, 7,490 (2.5%) had MetALD, 5,576 (1.8%) had ALD, and 198,646 (65.4%) did not have SLD. Over a median follow-up of 10.4 years, 162,959 cardiovascular events occurred. The adjusted RR of any cardiovascular diseases was 1.29 (95% CI 1.38-1.31) for MASLD, 1.38 (95% CI 1.34-1.42) for MetALD, and 1.48 (95% CI 1.43-1.53) for ALD. Among all SLD subtypes, MASLD showed the highest RR for myocardial infarction (RR 1.46, 95% CI 1.36-1.56). Findings remained consistent after accounting for liver-related deaths. The PAF for MASLD was 8.07% (95% CI 7.81-8.58). Despite higher risks, MetALD and ALD had lower PAFs due to lower prevalence. Conclusions: All major SLD subtypes - MASLD, MetALD, and ALD - were associated with increased long-term cardiovascular risk, underscoring the need for early detection and cardiometabolic risk management across the SLD spectrum. Impact and implications: This large-scale study of 303,589 individuals demonstrates that metabolic dysfunction-associated steatotic liver disease (MASLD) increases the risk of cardiovascular diseases by at least 29%. Cardiovascular risk further escalates across SLD subtypes with higher levels of alcohol consumption. Notably, MASLD was associated with the highest risk of myocardial infarction among all SLD subtypes. By quantifying population burden, we found that 8.07% of cardiovascular events may be preventable through effective MASLD prevention strategies, highlighting the critical role of cardiometabolic risk management. These findings emphasize the need to integrate MASLD identification and prevention into broader cardiometabolic care and public health frameworks. Clinical trial number: not applicable.