Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging public health concern intricately linked to metabolic syndrome and cardiovascular diseases. Among its complications, MASLD is associated with progressive liver fibrosis and an elevated risk of adverse cardiovascular outcomes, including coronary artery disease (CAD), congestive heart failure (CHF), and peripheral artery disease (PAD). Patients with MASLD frequently present with multiple comorbidities, such as hypertension (HTN) and diabetes (DM), which may further compound their risk for these outcomes. Therapies commonly prescribed for these conditions, including statins, antihypertensives, and antidiabetic medications, may influence the interplay between liver fibrosis and cardiovascular events. However, the extent to which these medications modify outcomes in MASLD patients, particularly in the context of fibrosis progression, remains unclear. This study aimed to investigate the association between comorbidities and cardiovascular disease in MASLD patients. Furthermore, we explored the relationship between therapies for these comorbidities and cardiovascular outcomes, with a specific focus on how fibrosis severity influences these associations.
Methods: This cross-sectional retrospective study included 13,787 participants diagnosed with MASLD based on laboratory and imaging data, with FIB-4 scores calculated from January 2023 to March 2024 at Lincoln Medical Center, Bronx, NY. Demographic and clinical data were extracted from the electronic health records (EHR) using ICD codes. Patients were stratified into low-risk (FIB-4 < 1.3; n=9,344) and moderate-risk (FIB-4 ≥1.3; n=4,442) groups. Exclusion criteria were alcohol use disorder and insulin therapy. The primary outcome was the odds of combined endpoint events (CHF, CAD, and PAD), preliminary analyzed using multivariable logistic regression. Odds ratios (ORs) with 95% confidence interval (CI) were reported for each comorbidity (HTN, DM, dyslipidemia and obesity) and medication.
Results: HTN demonstrated the highest odds of an endpoint (OR 8.80, 95% CI: 6.50–12.18), followed by DM (OR 4.73, 95% CI: 3.76–5.97) and dyslipidemia (OR 2.98, 95% CI: 2.36–3.79). Among moderate-risk patients, only HTN (OR 3.52, 95% CI: 2.53–5.04) and DM (OR 1.80, 95% CI: 1.46–2.23) were significant, while obesity and dyslipidemia were not. In low-risk patients, statin use (OR 7.23, 95% CI: 5.51–9.61), ezetimibe use (OR 13.7, 95% CI: 8.63–21.13), and diabetic medications (OR 4.59, 95% CI: 3.64–5.80) were significantly associated with higher odds of an endpoint. In moderate-risk patients, statins (OR 3.50, 95% CI: 2.65–4.78), ezetimibe (OR 7.58, 95% CI: 4.61–12.35), and diabetic medications (OR 2.10, 95% CI: 1.70–2.60) remained significant.
Conclusions: Our study showed the significant association between comorbidities and cardiovascular outcomes in MASLD, with HTN and DM as the strongest predictors, in moderate-risk patients. Among pharmacologic interventions, statins, ezetimibe, and antidiabetic medications were strongly associated with increased OR of cardiovascular endpoints, especially in low-risk patients. These findings may prove the role of comorbidity management in MASLD patients and suggest that tailored therapeutic strategies may increase cardiovascular risk, particularly in those with varying fibrosis severity. Further studies are needed to explore cofounders, such as unadjusted analysis, in this high-risk population.