Byrne CD, Targher G, et al. - Cardiovascular disease (CVD), arrhythmias, and cardiac disease are all linked to the complex interplay between the liver and cardiometabolic risk factors in nonalcoholic fatty liver disease (NAFLD). A multidisciplinary approach to managing both liver disease and cardiometabolic risk, as well as testing the cardiovascular and cardiac effects of new NAFLD drugs, is urgently needed.

• Independent of common CVD risk factors, NAFLD is associated with an increased risk of fatal/nonfatal CVD events as well as other cardiac and arrhythmic complications (left ventricular hypertrophy, aortic-valve sclerosis and certain arrhythmias).

• Hepatic/systemic insulin resistance, atherogenic dyslipidaemia, hypertension, and pro-atherogenic, pro-coagulant, and pro-inflammatory mediators generated by a steatotic/inflamed liver are all possible underlying mechanisms.

• Some genetic polymorphisms like PNPLA3 (rs738409 C > G) and TM6SF2 (rs58542926 C > T) may worsen liver disease while also weakening the link between NAFLD and CVD, possibly through effects on lipoprotein metabolism.

• Pioglitazone and GLP-1 receptor agonists are the most promising of the currently tested drugs for treating NAFLD that also benefit the vasculature.