Atherosclerosis burden across subtypes of steatotic liver disease: a European cohort analysis

Steatotic liver disease (SLD) affects over 30% of adults and is classified into metabolic dysfunction-associated (MASLD), alcohol-related (ALD), and metabolic dysfunction and alcohol-associated (MetALD) subtypes. Cardiovascular disease is the leading cause of death in SLD, yet the differential atherosclerotic risk across subtypes remains uncertain.

We conducted a cross-sectional analysis of 7820 participants from the population-based Paracelsus 10,000 cohort. SLD was defined by the Fatty Liver Index according to international consensus criteria. Atherosclerosis was assessed by carotid ultrasonography (n = 7820), coronary artery calcium (CAC) scoring by computed tomography (n = 1434), and polygenic risk scores (PGS, n = 1652). Primary outcomes were carotid plaque presence and CAC burden (Agatston score). Multivariable logistic regression adjusted for age, sex, and SCORE2 cardiovascular risk. We identified 5448 controls (69.7%), 2098 MASLD (26.8%), 201 ALD (2.6%), and 73 MetALD (0.9%). Carotid plaque prevalence increased stepwise: 30% in controls, 47% in MASLD, 53% in MetALD, and 62% in ALD (p<0.001). High-risk CAC (Agatston >300) was present in 4% of controls, 7% of MASLD, and 18% of both MetALD and ALD (p<0.001). Unadjusted odds ratios for plaque were 2.10 (95% CI, 1.89-2.33) for MASLD, 2.69 (1.69-4.28) for MetALD, and 3.86 (2.89-5.16) for ALD. After SCORE2 adjustment, associations attenuated and lost statistical significance. CAD-PGS differed modestly across subtypes (p=0.019) and inclusion further attenuated associations.

All SLD subtypes were associated with increased atherosclerotic burden, with ALD showing the highest risk. Associations were attenuated after adjustment for established cardiovascular risk factors, indicating shared cardiometabolic rather than liver-specific pathways.