Severe NAFLD Associated With High Subclinical Atherosclerosis Risk

Fatty liver, conceptual illustration. Fatty liver is commonly associated with alcohol or metabolic syndrome (diabetes, hypertension and obesity), but can also be due to any one of many causes. Fatty liver disease is a reversible condition wherein large vacuoles of fat (pale yellow circles) accumulate in liver cells.
The goal of this study was to determine the relationship between subclinical coronary artery disease and the severity of nonalcoholic fatty liver disease.

Severe nonalcoholic fatty liver disease (NAFLD) is associated with a high risk for subclinical atherosclerosis independent of Framingham risk score and body fat percentage, according to research results published in BMC Cardiovascular Disorders. 

Recently published systematic reviews and meta-analyses have evaluated the relationship between NAFLD and coronary artery disease (CAD), particularly obstructive CAD and coronary artery calcification. Data, however, were limited about the relationship between NAFLD severity and subclinical CAD.

In a retrospective study, researchers sought to clarify the relationship between subclinical CAD and NAFLD severity in a population of Asian patients in a real-world setting. Participants included 972 adults who underwent routine health checkups, abdominal sonograms, and coronary computed tomography (CT) angiography in 2018.

NAFLD severity was determined via ultrasonographic findings based on American Gastroenterology Association practice guidelines. Disease was classified as either normal, mild, moderate, or severe based on results of a hepatic ultrasound. All patients also underwent initial coronary artery calcium (CAC) scans and sequential coronary CT angiography; results were classified based on degree of calcification (minimal, mild, moderate, or severe).

The final cohort included 817 adults (mean age, 54.20±10.02 years; 60.02% men), 73.43% of whom had some degree of NAFLD. Following classification based on NAFLD severity, investigators noted statistically significant differences in certain baseline characteristics, including anthropometric and laboratory measurements and coronary artery findings.

Subclinical coronary atherosclerosis and the presence of vulnerable plaques increased significantly as NALFD severity increased. A post hoc analysis revealed no significant differences in those with mild vs moderate NAFLD and normal vs mild NAFLD in terms of subclinical coronary atherosclerosis.

A multivariate logistic regression analysis was performed to determine predictors of subclinical coronary atherosclerosis in terms of CAC ≥ 100, CAC ≥ 400, and Coronary Artery Diseases Reporting and Data System (CAD-RADS) ≥ 3, as well as the presence of vulnerable plaques with adjustments for both Framingham risk score and body fat percentage. After adjustment for Framingham risk score and body fat percentage, severe NAFLD was found to be an independent predictor of CAC ≥ 100 (odds ratio [OR], 2.946; 95% CI, 1.017-8.530).

Severe NAFLD was also an independent predictor of severe NAFLD (OR, 4.402; 95% CI, 1.149-16.862) as well as CAD-RADS ≥ 3 (OR, 4.091, 95% CI, 1.396-11.993).

Study limitations include those inherent to retrospective research and the cross-sectional design, a lack of data on C-reactive protein levels and medication history, and the use of self-referred participants, as well as the operator-dependent and subjective evaluation of NAFLD through ultrasonography. Study results may not be generalizable outside of the study population.

“[The] severity of NAFLD is closely associated with subclinical coronary atherosclerosis, as assessed by coronary CT [angiography] and CAC scan, regardless of [Framingham risk score] score and body fat percentage,” the researchers concluded. “We recommend that physicians should actively care for [patients] with severe degree NAFLD and offer information about [the] high risk of coronary atherosclerosis in the real-world ultrasound health-checkup setting.”


Hsiao CC, Teng PH, Wu YJ, Shen YW, Mar GY, Wu FZ. Severe, but not mild to moderate, non-alcoholic fatty liver disease associated with increased risk of subclinical coronary atherosclerosis. BMC Cardiovasc Disord. 2021;21(1):244. doi:10.1186/s12872-021-02060-z