Association of M2BPGi with Subclinical Atherosclerosis in Metabolic Dysfunction-Associated Steatotic Liver Disease

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic metabolic disorder associated with an elevated risk of cardiovascular disease. Mac-2 binding protein glycosylation isomer (M2BPGi), a noninvasive serum biomarker of hepatic fibrosis, has also been linked to adverse metabolic and cardiovascular outcomes. However, the association between serum M2BPGi levels and subclinical coronary atherosclerosis in individuals with MASLD remains unclear. We investigated the association between serum M2BPGi levels and coronary artery calcium score (CACS), an established imaging marker of subclinical atherosclerosis, in individuals with MASLD. Methods: This retrospective cross-sectional study included 6514 adults with MASLD who underwent health screening examinations between 2020 and 2025. Participants were categorized into quartiles according to serum M2BPGi levels: Q1 (<0.48), Q2 (0.48-0.61), Q3 (0.62-0.80), and Q4 (≥0.81). Coronary artery calcification (CAC) was defined as CACS > 0. Multivariable logistic regression analysis was performed after adjustment for age, sex, smoking status, liver enzymes, adiposity, dysglycemia, blood pressure, and lipid profile. Multivariable ordinal logistic regression analysis was additionally performed to evaluate the association between M2BPGi levels and CAC severity. Results: The prevalence of CAC increased progressively across M2BPGi quartiles (39.4%, 45.3%, 48.5%, and 57.4% for Q1-Q4, respectively; p < 0.001). In multivariable logistic regression analysis, participants in the highest M2BPGi quartile had significantly higher odds of CAC presence than those in the lowest quartile (OR, 1.32; 95% CI, 1.10-1.58; p = 0.0035). Higher M2BPGi quartiles were also independently associated with greater CAC severity in multivariable ordinal logistic regression analysis (OR, 1.33; 95% CI, 1.13-1.57; p = 0.0007 for Q4 vs. Q1). Conclusions: Higher serum M2BPGi levels were independently associated with both the presence and severity of CAC in individuals with MASLD. These findings suggest that M2BPGi may serve as a potential biomarker for identifying individuals with MASLD at increased risk of subclinical atherosclerosis and may complement conventional cardiovascular risk assessment.