Nonalcoholic fatty liver disease (NAFLD) is associated with a significant increase in the risk of carotid atherosclerosis that appears to be mediated by metabolic factors, according to a retrospective cohort study published in Gastroenterology.

The study of 8,020 adult Korean men without carotid atherosclerosis at baseline showed that men with persistent NAFLD had a 13% greater risk of subclinical carotid atherosclerosis compared with those without NAFLD, after adjustment for age, smoking, alcohol, body mass index, and weight change (95% confidence interval [CI], 1.13-1.35, P less than .001).

However, this increase in risk was entirely accounted for by metabolic variables including systolic blood pressure, fasting blood glucose, LDL and HDL cholesterol, and triglycerides (Gastroenterology 2016; ).

The analysis also showed a significant relationship between the degree of fibrosis and the risk of atherosclerosis; individuals with an NAFLD fibrosis score greater than –1.455 had a 29% higher risk of subclinical carotid atherosclerosis compared to those with a score less than –1.455. Those with a high FIB-4 score had a 43% greater risk of atherosclerosis than did those with a low FIB-4 score, even after adjustment for metabolic factors.

Individuals with a high gamma-glutamyl transferase level also had a higher risk of subclinical carotid atherosclerosis, but this became nonsignificant after adjustment for metabolic variables.

“Although the primary abnormality in NAFLD affects liver structure and function and may result in cirrhosis, liver failure, and hepatocellular carcinoma, the clinical burden of NAFLD is not confined to liver-related morbidity and mortality,” wrote Dong Hyun Sinn, MD, PhD, of Samsung Medical Center in Seoul, South Korea, and coauthors. “In our study, the association of persistent NAFLD with the development of carotid atherosclerosis was attenuated after adjusting for metabolic risk factors.”

Overall, 16.8% of individuals with persistent NAFLD developed subclinical carotid atherosclerosis over 3 years, compared to 11.4% of those with regressed NAFLD, 12.2% with developed NAFLD and 13.6% of those with no NAFLD.

The authors noted that regression of NAFLD appeared to reduce the risk of subclinical carotid atherosclerosis to a level that was comparable to that of individuals without NAFLD at baseline.

“This observation highlights the importance of persistent NAFLD as a risk factor and suggests that resolution of NAFLD may reduce the risk of atherosclerotic CVD,” they wrote. “Because lifestyle changes reduce CVD risk, it is possible that the reduced risk of CVD among participants with resolved NAFLD in the present study may be the consequence of lifestyle changes and not the direct consequence of NAFLD resolution.”

No conflicts of interest were declared.