Abstract Body:
Background: The prevalence and prognostic impact of metabolic dysfunction-associated steatotic liver disease (MASLD), overall and across the cardiovascular-kidney-metabolic (CKM) spectrum, is uncertain.

Methods: In the prospective Coronary Artery Risk Development in Young Adults (CARDIA) study, abdominal computed tomography was performed at a follow-up examination in 2010. MASLD was defined as hepatic steatosis (≤51 Hounsfield units) and ≥1 cardiometabolic criteria, without other causes of hepatic steatosis. The association between MASLD (vs. no MASLD) and clinical outcomes was evaluated. Subgroup analyses were repeated by CKM stage.

Results: Among 2,600 participants with sufficient data (mean age, 50±10 years), 89% had CKM syndrome stage ≥1 (Figure, A); 24% had MASLD, with higher prevalence at higher CKM syndrome stages (Figure, B). After covariate adjustment, MASLD was associated with a higher rate of all-cause death (aHR, 1.90; 95% CI, 1.22-2.98), without heterogeneity across CKM stages (P_interaction=0.78) (Figure, C). MASLD was associated with a higher rate of incident cardiovascular events (aHR, 1.81; 95% CI, 1.23-2.65), observed primarily in those with CKM stages 0-1 (P_interaction=0.032) (Figure, C).

Conclusions: MASLD impacted 1 in 4 middle-aged adults and was associated with cardiovascular and mortality events, particularly at earlier CKM stages. These findings suggest early MASLD recognition and intervention across the CKM spectrum may reduce long-term adverse outcomes.