Fibrosis and Metabolic Markers in Relation to PREVENT Cardiovascular Risk in MASLD

Fibrosis Versus Metabolic Risk in MASLD: Age-Adjusted Associations With PREVENT Cardiovascular Risk

This retrospective observational study evaluates the relationship between non-invasive liver fibrosis and metabolic markers and estimated cardiovascular risk in adults with metabolic dysfunction-associated steatotic liver disease (MASLD). The primary objective is to assess the association between the Fibrosis-4 index (FIB-4) and 10-year cardiovascular disease risk estimated using the American Heart Association PREVENT equations, with particular attention to the effect of age on this association. Secondary analyses evaluate the Fibrosis-3 index (FIB-3), triglyceride-glucose index (TyG), and liver stiffness measurement (LSM) in relation to PREVENT-estimated risks of cardiovascular disease, atherosclerotic cardiovascular disease, and heart failure.

This is a retrospective, single-center, observational study of adults with metabolic dysfunction-associated steatotic liver disease (MASLD) evaluated between January 1, 2024 and April 30, 2026. MASLD was defined by hepatic steatosis on ultrasonography together with at least one cardiometabolic risk factor, after exclusion of alternative causes of chronic liver disease.

Clinical and laboratory data were obtained from electronic medical records. Non-invasive indices included the Fibrosis-4 index (FIB-4), Fibrosis-3 index (FIB-3), triglyceride-glucose index (TyG), and liver stiffness measurement (LSM) by transient elastography when available.

Cardiovascular risk was estimated using the American Heart Association Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) base equations. Ten-year estimates were calculated for total cardiovascular disease (PREVENT-CVD), atherosclerotic cardiovascular disease (PREVENT-ASCVD), and heart failure (PREVENT-HF).

The primary analysis examines the association between FIB-4 and PREVENT-CVD risk. FIB-3 and TyG are evaluated as secondary markers, while analyses involving PREVENT-ASCVD, PREVENT-HF, and LSM are supportive. Because age is incorporated into FIB-4 and is also a major determinant of cardiovascular risk, crude associations are compared with age-adjusted partial Spearman correlations. A sensitivity analysis is also performed in participants without diabetes.

Participants with prior cardiovascular disease were excluded from the primary prevention cohort. Analyses are based on complete cases, without imputation of missing data.

Inclusion Criteria:

• Adults aged 30 to 79 years. Metabolic dysfunction-associated steatotic liver disease (MASLD), defined by hepatic steatosis on ultrasonography together with at least one cardiometabolic risk factor.

Clinical data available for calculation of the PREVENT cardiovascular risk estimates within the supported input ranges.

Exclusion Criteria:

• Alternative causes of chronic liver disease. One or more required PREVENT input variables outside the supported ranges: systolic blood pressure 90-200 mmHg, total cholesterol 130-320 mg/dL, HDL cholesterol 20-100 mg/dL, eGFR 15-140 mL/min/1.73 m², or BMI 18.5-39.9 kg/m².

Prior cardiovascular disease, defined as a history of stroke, coronary artery disease, heart failure, atrial fibrillation, or peripheral arterial disease.