Incidence of major cardiovascular events in patients with metabolic dysfunction-associated steatotic liver disease in the general population.

AIMS Major adverse cardiovascular events (MACE) related to cardiovascular disease are a major cause of death in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We explored the impact of MASLD on incident MACE and overall mortality in the general population in Germany. METHODS AND RESULTS A total of 14 575 patients were included for the analysis. Elevated liver enzymes were present in 21.7% and MASLD, defined with a positive fatty liver index (FLI) in the absence of relevant alcohol use, was detected in 37% of participants. MACE were defined as a three-item composite endpoint of acute myocardial infarction (AMI), stroke and cardiovascular mortality (3-point MACE) and extended MACE (eMACE) including MACE criteria, incident atrial fibrillation and pulmonary embolism. In the group with a positive FLI (≥60) a higher rate of male sex and a higher age as well as a higher prevalence of metabolic and cardiovascular risk factors compared to the group with a negative FLI (<30) were present. At 5 years of follow-up, 475 patients (3.7%) developed 3-point MACE and 577 (4.9%) developed eMACE. In the subgroup with MASLD, the incidence of eMACE was higher (7.1% vs. 3.7%; p < 0.0001). Using Cox regression analysis with a stepwise adjustment strategy, we were able to show an independent prediction of MACE and eMACE by hepatic steatosis under consideration of various confounders. The presence of MASLD was associated with an increased risk of developing MACE by 62.3% (p < 0.0001) and eMACE by 44.0% (p < 0.0001). Importantly, MASLD was associated with an increased risk for all-cause mortality (hazard ratio 1.55; p < 0.0001). CONCLUSIONS Metabolic dysfunction-associated steatotic liver disease is an independent risk factor for MACE and is associated with a significantly increased risk of all-cause mortality. In the management of patients with cardiovascular risk, identification of MASLD can potentially refine their disease trajectory.