Increased Cardiovascular and Cerebrovascular Events in Patients with Lean vs. Non-Lean MASLD: A Multi-Center Analysis

Background: 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 to 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 BMI <25 kg/m2. Leveraging 1:1 propensity score matching, we balanced baseline characteristics, including age, gender, 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 to 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. Conclusion: Patients with lean MASLD are at significantly higher risks of cardiovascular events and all-cause mortality compared to 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.