Atherosclerosis 191 (2007) 235–240 Review Non-alcoholic fatty liver disease and increased risk of cardiovascular disease Giovanni Targher * , Guido Arcaro Division of Internal Medicine, “Sacro Cuore” Hospital of Negrar (VR), Italy Received 21 June 2006; received in revised form 26 July 2006; accepted 8 August 2006 Available online 12 September 2006 Abstract Non-alcoholic fatty liver disease (NAFLD) is present in up to one-third of the general population and in the majority of patients with cardio-metabolic risk factors such as abdominal obesity, type 2 diabetes and other components of the metabolic syndrome (MetS). Currently, the importance of NAFLD and its relationship to the MetS is increasingly recognized, and this has stimulated an interest in the possible role of NAFLD in the development of cardiovascular disease (CVD). Indeed, the impact of NAFLD on CVD risk deserves particular attention in view of the implications for screening/surveillance strategies in this growing number of patients. Recent evidence suggests that the severity of liver histology in NAFLD patients is closely associated with markers of early atherosclerosis such as greater carotid artery wall thickness and lower endothelial flow-mediated vasodilation independently of classical risk factors and components of the MetS. Moreover, NAFLD is associated with greater overall mortality and independently predicts the risk of future CVD events. Overall, the current body of evidence strongly suggests that NAFLD is likely to be associated with increased CVD risk, and raises the possibility that NAFLD may be not only a marker but also an early mediator of atherosclerosis. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Non-alcoholic fatty liver disease; Atherosclerosis; Risk factors; Metabolic syndrome Contents 1. Introduction ........................................................................................................ 235 1.1. Associations between NAFLD and markers of subclinical atherosclerosis .......................................... 236 1.2. Associations between NAFLD and increased CVD prevalence .................................................... 236 1.3. Associations between NAFLD and increased CVD incidence ..................................................... 237 1.4. Possible biological mechanisms linking NAFLD and accelerated atherosclerosis .................................... 238 2. Conclusions ........................................................................................................ 238 References ......................................................................................................... 239 1. Introduction For a long time, the presence of hepatic steatosis was con- sidered as a benign manifestation with scarce or no clinical significance. However, recent results indicate a broad spec- * Corresponding author at: Division of Internal Medicine and Diabetes Unit, Ospedale “Sacro Cuore – don Calabria”, Via Sempreboni, 5, 37024 Negrar (VR), Italy. Tel.: +39 045 6013713; fax: +39 045 6013713. E-mail address: targher@sacrocuore.it (G. Targher). trum of clinical and pathological manifestations that individ- uals with non-alcoholic hepatic steatosis develop, which are termed as non-alcoholic fatty liver disease (NAFLD). Inter- estingly, the manifestations of NAFLD are very similar to those observed in patients with alcoholic liver disease, and range from simple steatosis, steatohepatitis (NASH), liver fibrosis to cirrhosis and, rarely, to hepatocellular carcinoma [1,2]. The prevalence of NAFLD in Western countries is high and there is a trend towards a further increase, with millions 0021-9150/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2006.08.021