Increased Cardiovascular and Cerebrovascular Events in Patients With Lean vs Non-lean MASLD: A Multicenter Analysis

INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a significant contributor to morbidity and mortality, linked to adverse cardiovascular outcomes. While extensive research highlights the cardiovascular burden in non-lean MASLD, lean MASLD remains comparatively understudied. To address this gap, our study evaluates cardiovascular outcomes in lean MASLD compared with non-lean MASLD. METHODS: This is a retrospective cohort study of patients with MASLD identified in the multi-institutional database, TriNetX. Lean MASLD was defined as a body mass index <25 kg/m 2 . Leveraging 1:1 propensity score matching, we balanced baseline characteristics, including age, sex, comorbidities, laboratory values, and medication use. Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for cardiovascular events, cerebrovascular outcomes, new-onset heart failure, and all-cause mortality over 1-, 3-, 5-, and 7-year follow-up. RESULTS: After matching, there were 67,519 patients in both groups. At 7-year follow-up, lean patients with MASLD demonstrated significantly higher rates of new onset heart failure compared with non-lean patients with MASLD (HR: 1.23, 95% CI: 1.16-1.31, P < 0.0001), composite cardiovascular events (HR: 1.21, 95% CI: 1.13-1.30, P < 0.0001), cerebrovascular events (HR: 1.33, 95% CI: 1.24-1.43, P < 0.0001), and all-cause mortality (HR: 1.48, 95% CI: 1.38-1.59, P < 0.0001). These increased risks were noted at 1-, 3-, and 5-year follow-up. DISCUSSION: Patients with lean MASLD are at significantly higher risks of cardiovascular events and all-cause mortality compared with non-lean patients with MASLD. Further research is needed to clarify the underlying pathophysiology and develop tailored interventions to improve outcomes for this growing population.