Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease

Abstract Nonalcoholic fatty liver disease (NAFLD) is systematically associated with features of metabolic syndrome, a condition carrying a high risk of cardiovascular events. We measured the percent vasodilation of brachial artery in response to ischemia (a test of endothelial function)(FMV) and cardiovascular risk profile in 52 NAFLD cases and 28 age- and gender-matched controls. The 10-year risk of coronary events was calculated according to the Framingham equation and the scores derived from the PROCAM study and NCEP-ATPIII proposals. FMV was 6.33 ± SD 5.93% in NAFLD vs. 12.22 ± 5.05% in controls (P < 0.0001), and higher in pure fatty liver (9.93%) compared with nonalcoholic steatohepatitis (4.94%)(P = 0.010). No differences were observed in flow-independent vasodilation (response to sublingual nitroglycerin). Percent FMV was negatively associated with insulin resistance (homeostasis model assessment) in the whole population (r = -0.243; P = 0.030). In logistic regression analysis, NAFLD was associated with a percent FMV in the lower tertile (odds ratio, 6.7; 95% confidence interval, 1.26-36.1), after adjustment for age, gender, BMI and insulin resistance. Among NAFLD patients, low FMV was associated with nonalcoholic steatohepatitis (adjusted-odds ratio, 6.8; 1.2-40.2). The 10-year probability of cardiovascular events was moderately increased in NAFLD, and particularly in nonalcoholic steatohepatitis. Our study provides evidence of endothelial dysfunction and increased risk of cardiovascular events in NAFLD. The risk of advanced liver disease is well-recognized in NAFLD patients, but the large majority of cases might probably experience cardiovascular disease in the long-term, indirectly limiting the burden of liver failure.