S2781 Cardiovascular Disease Risk in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Multicenter Propensity-Matched Longitudinal Analysis

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic metabolic condition. While it has been associated with cardiovascular disease (CVD), the long-term real-world magnitude of this risk remains underexplored. We aimed to assess the incidence and predictors of major adverse cardiovascular events (MACE) in patients with MASLD compared to matched non-MASLD controls. Methods: We conducted a retrospective multicenter cohort study using TriNetX, a U.S.-based network of longitudinal electronic health records. Adults (≥18 years) diagnosed with MAFLD (International Classification of Diseases, Tenth Revision (ICD-10): K76.0) from Jan 1, 2010, to Dec 31, 2023, were included. Exclusion criteria: prior MI, stroke, cardiovascular procedures, alcohol-related liver disease, viral hepatitis, or cirrhosis at baseline. Controls were matched 1:1 for age, sex, BMI, diabetes, hypertension, dyslipidemia, tobacco use, and use of statins or antiplatelets. The primary outcome was 5-year incidence of MACE: MI, stroke (ischemic or hemorrhagic), and cardiovascular death. Adjusted hazard ratios (aHR) were estimated via Cox models controlling for metabolic syndrome, HbA1c, and medications. Kaplan-Meier analysis illustrated cumulative risk. Results: After matching, 48,552 patients (24,276 per group) were included. Mean age: 57.4 years; 52.8% woman. Median follow-up: 5.2 years. MASLD patients had significantly higher 5-year MACE incidence: MACE: 13.7% vs 8.4% (P < 0.001); MI: 5.9% vs 3.7%; aHR 1.56 (95% CI: 1.39–1.74). Stroke: 4.4% vs 2.9%; aHR 1.51 (95% CI: 1.32–1.73). CV death: 3.5% vs 1.9%; aHR 1.88 (95% CI: 1.55–2.29). Statin use was protective in both groups (aHR 0.67; 95% CI: 0.56–0.80). Sensitivity analyses confirmed findings across subgroups by diabetes, sex, LDL, and BMI. Kaplan-Meier curves showed divergence by 24 months, with sustained separation over 5 years. Conclusion: MASLD is independently linked to increased long-term risk of MI, stroke, and cardiovascular death. These real-world findings support classifying MASLD as a systemic disease and underscore the need for early cardiovascular screening, aggressive risk management, and statin therapy.