Risk of cardiovascular, cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) has emerged as a public health problem of epidemic proportions worldwide. Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease (CHD), abnormalities of cardiac function and structure (e.g., left ventricular dysfunction and hypertrophy, and heart failure), valvular heart disease (e.g., aortic valve sclerosis) and arrhythmias (e.g., atrial fibrillation). Experimental evidence suggests that NAFLD itself, especially in its more severe forms, exacerbates systemic/hepatic insulin resistance, causes atherogenic dyslipidemia, and releases a variety of pro-inflammatory, pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications. Collectively, these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications. The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular, cardiac and arrhythmic complications, to briefly examine the putative biological mechanisms underlying this association, and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications.

Keywords: Arrhythmias; Arrhythmic complications; Cardiac complications; Cardiovascular disease; Coronary heart disease; Myocardial dysfunction; Non-alcoholic fatty liver disease; Valvular heart disease.

Figure 1

Possible mechanisms leading to cardiac and arrhythmogenic complications in non-alcoholic fatty liver disease. The close and complex inter-relationships among non-alcoholic fatty liver disease (NAFLD), visceral obesity and insulin resistance make it extremely difficult to dissect out the specific role of the liver and the underlying mechanisms responsible for the association between NAFLD and the risk of developing coronary heart disease (CHD), aortic valve sclerosis, left ventricular (LV) dysfunction/hypertrophy and arrhythmias. NAFLD might be associated with such complications either as a consequence of shared cardiometabolic risk factors and co-morbidities or as a marker of ectopic fat accumulation in other organs. For instance, myocardial steatosis and increased pericardial fat volume might exert local adverse effects that result in functional and structural derangements of the myocardium. Such myocardial remodelling will likely also result in pro-arrhythmogenic effects. The occurrence of cardiac arrhythmias is likely facilitated in remodeled heart by (local) pro-inflammatory cytokines, chemokines and concurrent cardiac autonomic dysfunction occurring on this dysmetabolic milieu. However, in this dangerous scenario, which may potentially account for premature CHD and increased risk of arrhythmias, NAFLD seems to be not simply a marker of cardiac and arrhythmogenic complications but also may play a part in their pathogenesis possibly via atherogenic dyslipidemia and the hepatic secretion of several pathogenic mediators into the bloodstream. HDL-C: High-density lipoprotein cholesterol; LDL: Low-density lipoprotein; CRP: C reactive protein; IL: Interleukin; TNF: Tumor necrosis factor; PAI-1: Plasminogen activator inhibitor-1; TGF: Transforming growth factor.