Ten-Year Atherosclerotic Cardiovascular Disease Risk in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Separate Analyses from Romanian and Italian Cohorts Integrating Metabolic, Hepatic, and Gut–Liver Axis Markers

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Abstract
Background/Objectives: Metabolic dysfunction–associated steatotic liver disease (MASLD) is closely linked to atherosclerotic cardiovascular disease (ASCVD), but the prognostic value of liver fibrosis and gut–liver axis alterations remains uncertain. Methods: We conducted a prospective, observational study in two tertiary centers (in Romania and Italy) and compared the outcomes with different tests available for fibrosis (FibroTest in Romania or acoustic radiation force impulse (ARFI) elastography in Italy) and intestinal permeability (IP) (by fecal zonulin in Romania or lactulose/mannitol ratio in Italy). Liver steatosis was confirmed at ultrasonography. Analyses followed a within-cohort strategy. Ten-year ASCVD categories were summarized separately per cohort, and within-cohort associations with elevated ASCVD risk (≥7.5%) were explored using univariate logistic regression with age-adjusted two-parameter checks. A pooled robustness analysis (n = 132) was then performed using multivariable logistic regression models for intermediate–high ASCVD risk (≥7.5%), adjusted for age (per 5 years), waist circumference (per 5 cm), total cholesterol (per 10 mg/dL), diabetes, and hypertension. A higher threshold (≥20%) yielded the same qualitative interpretation. Results: ASCVD was computable for 52 Romanian (low 78.8%, borderline 5.8%, intermediate 7.7%, high 7.7%) and 80 Italian participants (low 80.0%, borderline 6.2%, intermediate 12.5%, high 1.2%). In both cohorts, age was associated with higher ASCVD. Fibrosis severity (FibroTest or ARFI) and IP (zonulin or LA/MA) showed no associations with ASCVD. In pooled adjusted models, neither significant fibrosis nor high intestinal permeability was independently associated with ASCVD, whereas age and cardiometabolic comorbidities remained the dominant correlates. Conclusions: Across both cohorts, 10-year ASCVD risk was mainly determined by age and major cardiometabolic comorbidities. Neither liver fibrosis nor intestinal permeability contributed additional prognostic value in this setting, regardless of the assessment method. These data support prioritizing aggressive metabolic risk management and call for harmonized, longitudinal studies to clarify gut–liver contributions to cardiovascular outcomes.

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