Background: Cardiovascular disease (CVD) is the leading cause of mortality among adults with nonalcoholic fatty liver disease (NAFLD), however accurate tools for identifying NAFLD patients at highest CVD risk are lacking.
Methods: Using a validated algorithm, we identified a retrospective cohort of 914 NAFLD patients without known CVD. Fibrosis severity was estimated using the FIB-4 index. Patients were followed for 5 years for the development of a major adverse cardiovascular event (MACE), a composite of cardiovascular (CV) death, myocardial infarction (MI) or unstable angina, urgent coronary revascularization or stroke. Using an adjusted Cox proportional hazard regression model, NAFLD-specific biomarkers of CVD risk were identified. Discrimination was compared to that of the Framingham Risk Score (FRS) using the area under the receiver operating characteristic curve (AUROC).
Results: Among 914 patients, the mean age was 53.4 years and 60.6% were female. Over 5 years, 288 (31.5%) experienced MACE. After adjustment for traditional cardiometabolic risk factors and underlying FIB-4 score, each 1-point increase in MELD-Na was associated with a 4.2% increased risk of MACE (HR 1.042 [95% CI 1.009-1.075]; p=0.011). Compared to patients in the lowest MELD-Na quartile (<7.5), those in the highest quartile (≥13.2) had a 2.2-fold increased risk of MACE (adjusted HR = 2.21, 95% CI 1.11-4.40, p=0.024; p-trend=0.004). Incorporating MELD-Na with the FRS significantly improved discrimination of future CVD risk (combined c-statistic 0.703 vs. 0.660 for the FRS alone; p=0.040).
Conclusion: Among patients with NAFLD, the MELD-Na score accurately risk stratifies patients according to future CVD event risk. The addition of the MELD-Na score to the FRS may further improve discrimination of NAFLD-related CVD risk.
Keywords: NAFLD; biomarker; cardiovascular disease; fibrosis; inflammation; prevention; risk prediction.