Nonalcoholic fatty liver disease and vascular disease: State-of-the-art

Abstract

Nonalcoholic fatty liver disease (NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis (NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis (increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific life-style modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular disease improving overall prognosis and survival.

Keywords: Intima-media thickness; Steatosis; Nonalcoholic fatty liver disease; Non-alcoholic steatohepatitis; Early atherosclerosis; Cardiovascular risk; Inflammation; Epicardic fat

Core tip: Nonalcoholic fatty liver disease (NAFLD) is emerging as an independent risk factor for the occurrence and progression of cardiovascular disease. In this review we have systematically analyzed the correlation between NAFLD and cardiovascular diseases (CVD) focusing on the different aspects of CVD (increased carotid intima media thickness, increased arterial stiffness, endhotelial dysfunction, impaired left ventricular function, coronary calcification, epicardic fat), on the clinical manifestations (obstructive sleep apnea syndrome, clinical consequences of microangiopathy), and on the underlying physiopathogenic mechanisms (insulin resistance, atherogenic dyslipidemia, inflammation, oxidative stress, adipokynes imbalance, coagulation imbalance, increased assumption of fructose). Furthermore, we emphasized that NAFLD, by itself, is probably an independent risk factor for the occurrence of CVD.