A potential link between endothelial function, cardiovascular risk, and metabolic syndrome in patients with Non-alcoholic fatty liver disease

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthetase. Elevated ADMA reduces NO formation and is associated with endothelial dysfunction. The aims of this study were to evaluate endothelial function and the cardiovascular risk (CVR) profile in patients with non-alcoholic fatty liver disease (NAFLD), and to determine whether or not an association with metabolic syndrome (MS) increases these parameters. METHODS: A total of 100 consecutive patients with NAFLD, who were seen in Liver Disease Outpatient clinic and 45 age- and sex-matched controls were included. Endothelial function was evaluated based on the serum ADMA level measured using a validated ELISA kit (DLD Diagnostika GMBH, Hamburg, Germany) and flow-mediated vasodilatation (FMV) measured via high-resolution external ultrasonography. The CVR profile was calculated according to the Framingham equation. RESULTS: At baseline there weren’t any significant differences in brachial artery diameter between the NAFLD and control groups (3.7 ± 0.6 mm vs. 3.6 ± 0.6 mm, respectively). FMV and flow-independent vasodilatation in response to sublingual nitroglycerin did not differ between the NAFLD and control groups (mean: 16% ± 9.4% vs. 17.9% ± 12.4%, and 21.4% ± 14% vs. 17.8% ± 11.3%, respectively, p > 0.05). No significant difference in the serum ADMA concentration between the NAFLD and control groups was observed (mean: 0.8 ± 0.07 μmol L(-1) vs. 0.74 ± 0.2 μmol L(-1), respectively). The CVR profile was significantly higher in the NAFLD group than in the control group (mean: 9% ± 6.9% vs. 4.6% ± 3.8%, P = 0.000). MS associated with NAFLD significantly increased the CVR profile (mean: 11.2% ± 7.4%, P = 0.000). An abnormal serum alanine aminotransferase level (>37 IU L(-1)) and the presence of fibrosis did not increase the CVR profile (p > 0.05). CONCLUSIONS: The risk of cardiovascular events is increased in patients with NAFLD. The association with MS is further increased such risk.