#NONALCOHOLIC FATTY LIVER DISEASE-RELATED RISK OF #CARDIOVASCULAR DISEASE AND OTHER CARDIAC COMPLICATIONS

Nonalcoholic fatty liver disease (NAFLD) affects approximately ~25% of the global adult population. The aim of this narrative review is to describe the associations between NAFLD and cardiovascular disease (CVD), arrhythmias, cardiac conduction defects, myocardial remodelling and heart failure. We also discuss the potential mechanisms that mediate or attenuate the strength of these associations, and briefly summarize the effect of treatments that both ameliorate NAFLD and decrease risk of CVD.

Methods
Searches of PubMed were performed by the two authors using the terms listed in the manuscript Appendix. We limited the timeframe to the last decade due to the vast amount of research in the field (up to April 2021) for meta-analyses, reviews and original papers. Only articles published in English were considered.

Results
NAFLD is associated with an increased risk of fatal/nonfatal CVD events and other cardiac and arrhythmic complications (left ventricular hypertrophy, aortic-valve sclerosis and certain arrhythmias), independently of common CVD risk factors. There are probably several underlying mechanisms, including hepatic/systemic insulin resistance, atherogenic dyslipidaemia, hypertension and pro-atherogenic, pro-coagulant and pro-inflammatory mediators released from the steatotic/inflamed liver that may be involved. Some genetic polymorphisms, such as PNPLA3 (rs738409 C > G) and TM6SF2 (rs58542926 C > T), may worsen liver disease, but also attenuate the strength of the association between NAFLD and CVD, possibly via their effects on lipoprotein metabolism. Of the currently tested drugs for treating NAFLD that also benefit the vasculature, pioglitazone and GLP-1 receptor agonists are the most promising.

Conclusions
The complex interplay between the liver and cardiometabolic risk factors contributes to CVD, arrhythmias and cardiac disease in NAFLD. There is an urgent need for a multidisciplinary approach to manage both liver disease and cardiometabolic risk, and to test the cardiovascular and cardiac effects of new drugs for NAFLD

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