Cardiovascular risk in MASLD: What multiple lines of evidence reveal

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with increased cardiovascular risk, yet whether it independently confers risk beyond established cardiometabolic factors remains debated. Herein, we critically appraise epidemiological, genetic, mechanistic, and large-cohort evidence. Many studies reporting independent associations are limited by small sample sizes, heterogeneous cardiovascular outcomes, potential selection and publication bias, and perhaps most importantly, incomplete adjustment for established continuous cardiovascular risk factors. Mendelian randomisation and large-scale cohort data suggest that excess liver fat per se is not independently atherogenic; rather, accompanying abnormalities in lipid profiles mediate the observed risk. Notably, no current cardiovascular risk model includes MASLD as an independent variable. Clinically, MASLD identifies individuals with higher than average cardiovascular risk who are frequently undertreated with preventive therapies. Thus, the priority for primary care physicians, hepatologists, endocrinologists, and cardiologists, among others, should be to adequately determine (using risk scores), communicate on and address the cardiovascular and related multimorbidity challenges inherent in MASLD care.