Nonalcoholic fatty liver disease (NAFLD) is closely associated with several metabolic syndrome features. We assessed whether NAFLD is associated with carotid artery intima-media thickness (IMT) as a marker of subclinical atherosclerosis and whether such an association is independent of classical risk factors, insulin resistance, and metabolic syndrome features. We compared carotid IMT, as assessed by ultrasonography, in 85 consecutive patients with biopsy-proven NAFLD and 160 age-, sex-, and BMI-matched healthy control subjects. NAFLD patients had a markedly greater carotid IMT (1.14 +/- 0.20 vs. 0.82 +/- 0.12 mm; P < 0.001) than control subjects. The metabolic syndrome (according to Adult Treatment Panel III criteria) and its individual components were more frequent in those with NAFLD (P < 0.001). The marked differences in carotid IMT observed between the groups were only slightly weakened after adjustment for age, sex, BMI, smoking history, LDL cholesterol, insulin resistance (by homeostasis model assessment), and metabolic syndrome components. Notably, carotid IMT was strongly associated with degree of hepatic steatosis, necroinflammation, and fibrosis among NAFLD patients (P < 0.001 for all). Similarly, by logistic regression analysis, the severity of histological features of NAFLD independently predicted carotid IMT (P < 0.001) after adjustment for all potential confounders. These results suggest that the severity of liver histopathology among NAFLD patients is strongly associated with early carotid atherosclerosis, independent of classical risk factors, insulin resistance, and the presence of metabolic syndrome.
