Background: Non-alcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome, a marker of increased cardiovascular risk. Aortic stiffness, flow-mediated dilation (FMD) and intima-media thickness (IMT) are markers of cardiovascular disease and independent predictors of the corresponding risk. We investigated whether the presence and the histological activity of NAFLD are associated with arterial function and early vascular changes.

Methods: A total of 51 subjects participated in this study, 23 patients (mean age 55±14 yrs, 48% males) with biopsy evidence of NAFLD but without cirrhosis, and 28 control subjects adjusted for age, gender and other cardiovascular risk factors. Carotid-femoral pulse wave velocity (PWV) was measured as index of aortic stiffness. FMD of the brachial artery, an index of endothelial function, and mean IMT of common carotid arteries, a marker of subclinical atherosclerosis, were measured using B-mode ultrasound imaging.

Results: NAFLD subjects had significantly higher PWV (8.2±1.3 m/sec vs. 6.9±1.3 m/sec, P=0.001), and higher carotid IMT (0.78±0.17 mm vs. 0.67±0.13 mm, P=0.01) compared to controls. NAFLD subjects had significantly reduced FMD (1.92±2.11% vs. 4.8±2.43%, P<0.001) compared to controls. Multivariable regression analysis, showed that histological activity was associated independently with FMD (β=–0.388, P=0.037). Leptin was an independent determinant of PWV (β=0.384, P=0.003). FMD was independently associated with both leptin (β=−0.294, P=0.035) and adiponectin (β=0.366, P=0.008).

Conclusions: Patients have higher PWV and IMT and lower FMD compared to controls, indicating both functional and structural impairment in large arteries. The histological activity of NAFLD and levels of adipokines predict the degree of arterial impairment.