Mechanisms linking nonalcoholic fatty liver disease with coronary artery disease.

The most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) is coronary artery disease (CAD), not chronic liver disease. Fatty liver increases cardiovascular risk by classical (dyslipidemia, hypertension, diabetes) and by less conventional mechanisms. Common pathways involved in the pathogenesis of fatty liver and CAD includes hepatic insulin resistance and sub clinical inflammation. The hepatic insulin resistance state of fatty liver infiltration is characterized by increased FFA, which causes lipotoxicity and impairs endothelium-dependent vasodilatation, increases oxidative stress, and has a cardio toxic effect. Additional metabolic risk factors include leptin, adiponectin, pro inflammatory cytokines [such as IL-6, C-reactive protein and plasminogen activator inhibitor-1 (PAI-1)], which together lead to increased oxidative stress and endothelial dysfunction, finally promoting coronary artery disease (CAD). When classical risk factors are superimposed on fatty liver accumulation, they may further increase the new metabolic risk factors, exacerbating CAD. The clinical implication is that patients with NAFLD are at higher risk (steatohepatitis, diabetes, obesity, atherogenic dyslipidemia) and should undergo periodic cardiovascular risk assessment including the Framingham score, cardiac effort test, and measurement of intimae-media thickening of the carotids arteries. This may improve risk stratification for CAD.