Plasma fetuin‐A is associated with endothelial dysfunction and subclinical atherosclerosis in subjects with nonalcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome (MetS) is closely associated with an increased risk of cardiovascular disease. Fetuin-A is associated with MetS and NAFLD. We investigated the relationship of circulating fetuin-A level with markers of endothelial dysfunction and presence of carotid atherosclerosis in subjects with NAFLD. The consecutive 115 patients with NAFLD and age-matched 74 healthy subjects were enrolled. Plasma levels of fetuin-A and markers of endothelial dysfunction [asymmetric dimethyl arginine (ADMA) and adiponectin] were measured by ELISA method. Insulin sensitivity was determined by homeostasis model assessment of insulin resistance (HOMA-IR) index. Carotid artery intima-media thickness (cIMT) was assessed by high-resolution ultrasonography. Fetuin-A and ADMA were higher and, adiponectin was lower in NAFLD group than the control group (P=0·004, P<0·001 and P<0·001, respectively). In addition, NAFLD group had greater cIMT measurements than the controls (P<0·001). However, no difference was found for fetuin-A, ADMA, adiponectin and cIMT between two groups when the findings were adjusted according to the glucose, lipids and HOMA-IR index. In correlation analysis, fetuin-A was found to be positively correlated with triglyceride (r=0·23, P=0·001), HOMA-IR (r=0·29, P<0·001), ADMA (r=0·24, P=0·001), cIMT (r=0·3, P=0·003) and, negatively correlated with HDL-C (r=-0·17, P=0·02) and adiponectin (r=-0·19, P=0·01) levels. Multiple linear regression analysis showed that fetuin-A was independently associated with ADMA and cIMT levels. This study demonstrated for the first time that circulating fetuin-A in NAFLD is independently associated with endothelial dysfunction and subclinical atherosclerosis.