WHY DOES NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) CONTRIBUTE TO CARDIOVASCULAR OUTCOMES?

DOI

10.1016/j.artres.2016.10.151How to use a DOI?

Abstract

Take home messages

1. 1.

   Both ‘Metabolic NAFLD’ and the features of insulin resistance/the metabolic syndrome (MetS) increase the risk of cardiovascular disease (CVD), even independent of obesity

2. 2.

   ‘Metabolic NAFLD’ and insulin resistance share common pathophysiology, which may explain their link with CVD

3. 3.

   ‘Metabolic NAFLD’ may be even a better predictor of CVD as it measures more directly abnormal metabolism than the MetS

4. 4.

   Carriers of the I148M gene variant in PNPLA3 with NAFLD have steatosis but not features of insulin resistance implying that steatosis and insulin resistance and the risk for CVD dissociate

Features of insulin resistance/the metabolic syndrome (MetS) predict cardiovascular disease (CVD), even independent of obesity. NAFLD, diagnosed by liver enzymes, ultrasound or a liver biopsy, has also been shown in at least 14 prospective studies to predict CVD independent of obesity.

The MetS and NAFLD share common pathophysiology. The liver is the site of production of two of the key components of the MetS, fasting serum glucose and very-low density lipoprotein. In subjects with NAFLD, the ability of insulin to normally suppress production of glucose and VLDL is impaired resulting in hyperglycemia and hyperinsulinemia and hypertriglyceridemia combined with low HDL cholesterol. The liver, once fatty, also overproduces many other markers of cardiovascular risk such as C-reactive protein, fibrinogen, coagulation factors and plasminogen activator inhibitor-1.

The increases in markers of insulin resistance and of cardiovascular risk in NAFLD are associated with endothelial vascular dysfunction and could in part explain why NAFLD predicts CVD. NAFLD may be an even better predictor of the risk of CVD than the MetS. Whether this is because measurement of liver fat content provides a more direct estimate of the risk of CVD than the MetS, which can be diagnosed using 10 different combinations of its 5 components or other mechanisms is unclear.

Common genetic forms of NAFLD such as the I148M variant in PNPLA3 (‘PNPLA3 NAFLD’) are characterized by steatosis but not insulin resistance or an increased risk of CVD or diabetes. The molecular mechanisms underlying this dissociation in the human liver and its implications for CVD will be discussed.

Open Access

This is an open access article distributed under the CC BY-NC license.

TY  - JOUR
AU  - Hannele Yki-Järvinen
PY  - 2016
DA  - 2016/11/24
TI  - WHY DOES NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) CONTRIBUTE TO CARDIOVASCULAR OUTCOMES?
JO  - Artery Research
SP  - 46
EP  - 47
VL  - 16
IS  - C
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2016.10.151
DO  - 10.1016/j.artres.2016.10.151
ID  - Yki-Järvinen2016
ER  -