The role of non-alcoholic fatty liver disease in cardiovascular disease.

BACKGROUND/AIMS Fatty liver is the hepatic component of the metabolic syndrome. Insulin resistance, the pathogenic driver of the metabolic syndrome, refers to a constellation of features such as overweight/obesity, glucose intolerance, dyslipidemia and hypertension, all of which are important risk factors for cardiovascular disease (CVD). The aim of this article is to summarize the available data linking non-alcoholic fatty liver disease (NAFLD) with CVD. METHODS Two approaches were used to address this issue. First, data in support of the presence of the typical in vivo pathogenic features of atherosclerosis in individuals with NAFLD were described to confirm whether or not the association between NAFLD and CVD is plausible. Second, epidemiological data linking NAFLD with CVD outcome was reviewed. RESULTS Individuals with NAFLD are characterized by abnormal endothelial function. Data about the carotid intima-media thickness, which as a surrogate marker of atherosclerosis, are controversial, as is higher CAD even if altered myocardial perfusion has been described. Data in support of altered cardiac intermediary metabolism and energy metabolism are more robust. Low-grade inflammation is typically linked to NAFLD and animal studies, suggested that NAFLD may represent a potential mediator of the systemic inflammation. Epidemiologic studies support a causal link between fatty liver and type 2 diabetes but the causal association between NAFLD and CVD is rather weak. CONCLUSION NAFLD is characterized by the early onset of the typical metabolic and vascular pathogenic alterations of atherosclerosis. In spite of this background, the evidence for the association between NAFLD and CVD is weak.