NAFLD and Atherosclerosis: Two Sides of the Same Dysmetabolic Coin?

• Published in: Trends in endocrinology and metabolism Vol. 30; no. 12; pp. 891 - 902
• Main Authors: Stols-Gonçalves, Daniela, Hovingh, G. Kees, Nieuwdorp, Max, Holleboom, Adriaan G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.12.2019
• Subjects: atherosclerosis; cardiovascular disease; dyslipidemia; NAFLD; NASH; type 2 diabetes mellitus; atherosclerosis; type 2 diabetes mellitus; cardiovascular disease; NAFLD; NASH; dyslipidemia
• ISSN: 1043-2760; 1879-3061
• DOI: 10.1016/j.tem.2019.08.008

The prevalence of non-alcoholic fatty liver disease (NAFLD) is strongly increasing and may put patients at increased risk for atherosclerotic cardiovascular disease (asCVD). Both disease phenotypes often co-occur, in the case of obesity, insulin resistance, diabetes mellitus type 2, and the metabolic syndrome. We explore the pathogenesis of NAFLD, the epidemiology of asCVD in NAFLD patients, shared drivers of both phenotypes, and factors caused by NAFLD that contribute to asCVD. Genetic studies support that NAFLD may drive asCVD through mixed hyperlipidemia. Next, we discuss the prospects of lifestyle improvement and pharmacological treatment of NAFLD for asCVD risk reduction. Finally, we point out that earlier identification of patients with NAFLD should be pursued by increasing awareness of the association of these two phenotypes and collaboration between the involved physicians. Non-alcoholic Fatty Liver Disease (NAFLD) and atherosclerotic cardiovascular disease (asCVD) often co-occur.Large epidemiological studies, genetics studies, and studies of subclinical atherosclerosis, support the relation between NAFLD and asCVD.NAFLD–non-alcoholic steatohepatitis (NASH) may directly contribute to asCVD and atherothrombotic events in the hepatic secretion of atherogenic lipoproteins and procoagulant factors.Genetic studies support the relationship between NAFLD and asCVD, notably via increased VLDL secretion. In particular, they support that genetic variants affecting both liver fat and plasma lipid levels have an effect on asCVD risk, while variants with an effect on liver fat only do not affect asCVD.Factors that may drive both NAFLD and asCVD are insulin resistance, hypertension, and potentially chronic periodic hypoxia, as observed in obstructive sleep apnea, and intestinal dysbiosis and chronic low grade inflammation.