Metabolic Dysfunction-Associated Fatty Liver Disease Better Predicts Incident Cardiovascular Disease

Abstract

Background/aims: Metabolic dysfunction (MD)-associated fatty liver disease is a new positive diagnostic criterion based on hepatic steatosis and MD. However, a comprehensive evaluation on the association of MD and hepatic steatosis with incident cardiovascular disease (CVD) has yet to be performed.

Methods: This retrospective cohort study included 333,389 participants from the Korean National Health Insurance Service database who received a health examination between 2009 and 2010. Hepatic steatosis was defined using the Korean National Health and Nutrition Examination Survey-derived nonalcoholic fatty liver disease scoring system. Cox proportional hazards regression was adopted to determine the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for CVD according to the presence of hepatic steatosis and MD, as well as the composite term.

Results: This study included 179,437 men and 153,952 women with a median age of 57 years. Hepatic steatosis with MD (aHR, 2.00; 95% CI, 1.89 to 2.13) and without MD (aHR, 1.30; 95% CI, 1.10 to 1.54) significantly increased the risk of CVD compared to no steatosis without MD (reference). However, steatosis revealed no significant difference in the risk of CVD compared to no steatosis among participants with one MD (aHR, 1.09; 95% CI, 0.91 to 1.30). In participants with steatosis, the presence of one and ≥2 MDs had aHR values of 1.25 (95% CI, 0.87 to 1.79) and 1.71 (95% CI, 1.22 to 2.41), respectively, compared to no MD.

Conclusions: Combined consideration of hepatic steatosis and MD was significantly associated with increased CVD risk and showed better predictive performance for CVD than hepatic steatosis or MD alone.

Keywords: Cardiometabolic risk factors; Cardiovascular diseases; Fatty liver; Liver diseases.

Fig. 1

Flowchart for the inclusion of study participants.

Fig. 2

Subgroup analysis of the effect of MAFLD on incident cardiovascular disease. aHR was calculated using the Cox proportional hazards model after adjustments for age, sex, insurance premium, body mass index, systolic blood pressure, fasting serum glucose, total cholesterol, alanine aminotransferase, smoking, alcohol consumption, physical activity, and Charlson comorbidity index. MAFLD was defined using the Korean National Health and Nutrition Survey nonalcoholic fatty liver disease score. MAFLD, metabolic dysfunction-associated fatty liver disease; PY, person-year; aHR, adjusted hazard ratio; CI, confidence interval.

Fig. 3

Joint effect of hepatic steatosis and metabolic dysfunction on incident cardiovascular disease. aHR was calculated using the Cox proportional hazards model after adjustments for age, sex, insurance premium, body mass index, alanine aminotransferase, smoking, alcohol consumption, physical activity, and Charlson comorbidity index. (A) Three-dimensional plotting of the composite effect of the K-NAFLD score and the number of metabolic dysfunctions on the risk of cardiovascular disease. (B) Two-dimensional plotting of the composite effect of the K-NAFLD score and the number of metabolic dysfunctions on the risk of cardiovascular disease. MAFLD, metabolic dysfunction-associated fatty liver disease; K-NAFLD, Korean National Health and Nutrition Examination Survey-derived nonalcoholic fatty liver disease; CI, confidence interval.