NAFLD and cardiovascular diseases: a clinical review

Abstract

Non-alcoholic fatty liver DISEASE (NAFLD) is the most common chronic liver disease in Western countries and affects approximately 25% of the adult population. Since NAFLD is frequently associated with further metabolic comorbidities such as obesity, type 2 diabetes mellitus, or dyslipidemia, it is generally considered as the hepatic manifestation of the metabolic syndrome. In addition to its potential to cause liver-related morbidity and mortality, NAFLD is also associated with subclinical and clinical cardiovascular disease (CVD). Growing evidence indicates that patients with NAFLD are at substantial risk for the development of hypertension, coronary heart disease, cardiomyopathy, and cardiac arrhythmias, which clinically result in increased cardiovascular morbidity and mortality. The natural history of NAFLD is variable and the vast majority of patients will not progress from simple steatosis to fibrosis and end stage liver disease. However, patients with progressive forms of NAFLD, including non-alcoholic steatohepatitis (NASH) and/or advanced fibrosis, as well as NAFLD patients with concomitant types 2 diabetes are at highest risk for CVD. This review describes the underlying pathophysiological mechanisms linking NAFLD and CVD, discusses the role of NAFLD as a metabolic dysfunction associated cardiovascular risk factor, and focuses on common cardiovascular manifestations in NAFLD patients.

Keywords: Cardiovascular disease; Diabetes; Hyperinsulinemia; Insulin resistance; Metabolic syndrome; NAFLD; Non-alcoholic fatty liver disease; Systemic inflammation.

Fig. 1

Pathophysiological mechanisms linking NAFLD and CVD (modified from: [12, 28, 29]). SFA saturated fatty acids, OSAS obstructive sleep apnea syndrome, carb. carbohydrates, n-3 FA omega-3 fatty acids, NAFLD non-alcoholic fatty liver disease; PNPLA3 patatin-like phospholipase domain-containing protein 3, TM6SF transmembrane 6 superfamily 2 human gene, HSD17B13 hydroxysteroid dehydrogenase 17beta 13, MARC1 mitochondrial amidoxime reducing component 1, PGC1α peroxisome proliferator-activated receptor gamma coactivator 1-alpha, miR micro-RNA, ADMA asymmetric dimethylarginine, eNOS endothelial nitric oxide synthase, VLDL very-low-density lipoprotein, IDL intermediate-density lipoprotein, LDL low-density lipoprotein, ApoB apolipoprotein B, ApoC III apolipoprotein C3, DNL de novo lipogenesis, HDL-C high-density lipoprotein cholesterol, sdLDL small dense low-density lipoprotein, LDL-P low-density lipoprotein particles, C16:0 palmitic acid, IL-1β interleukin-1β, IL-6 interleukin-6, CRP C-reactive protein, AGEs advanced glycation end products, FFAs free fatty acids, VEGF vascular endothelial growth factor, MAMPs microbe-associated molecular pattern, LPS lipopolysaccharide, SCFA short-chain fatty acids, TMA trimethylamine; ASCVD atherosclerotic cardiovascular disease. Down arrows (↓) indicate decreased levels, and up arrows (↑) indicate increased levels

Fig. 2

A proposed algorithm for management of cardiometabolic risk factors in NAFLD patients (modified from: [28, 29]). NAFLD non-alcoholic fatty liver disease, carb. carbohydrates, n-3 FA omega-3 fatty acids, EPA eicosapentaenoic acid, DHA docosahexaenoic acid, min minute, SGLT2 sodium-glucose linked transporter 2, ACEI angiotensin-converting-enzyme inhibitor, ARB angiotensin II receptor blocker, CCB calcium-channel blocker