Journal
ATHEROSCLEROSIS
Volume 299, Issue -, Pages 38-44Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2020.03.009
Keywords
Biomarker; Computed tomography; Fibroblast growth factor 21; Inflammation; Lipoproteins; Non-alcoholic fatty liver disease
Funding
- Australian National Health and Medical Research Council Career Development Fellowship [1122854]
- NSW CVRN Research Development Project from the National Heart Foundation of Australia [100715]
- National Heart, Lung, and Blood Institute [R01 HL071739, HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]
- National Center for Advancing Translational Sciences [UL1-TR-000040, UL1-TR-001079, UL1-TR-001420]
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Background and aims: Non-alcoholic fatty liver disease (NAFLD) is associated with inflammation and atherogenic lipoprotein abnormalities. Previous studies suggest an association of fibroblast growth factor 21 (FGF21) with NAFLD. Therefore, we assessed the association of circulating FGF21 levels with inflammatory markers, lipoprotein profile and NAFLD in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: Among 6814 participants free of apparent cardiovascular disease at baseline (2000-2002), 3634 participants had valid data on variables of interest. After excluding participants with excessive alcohol consumption, 3446 participants were included in the analysis. NAFLD was defined using non-contrast cardiac computed tomography with a liver-to-spleen ratio (LSR) < 1 or liver attenuation < 40 Hounsfield units (HU). Results: The mean age of the participants was 63.5 years with 54% females, 36% Caucasian, 10% Chinese American, 31% African American and 23% Hispanic. 17% of the participants had NAFLD. After adjustment for demographic, socioeconomic and other confounders, a 1-SD increment in ln-transformed FGF21 level was associated with a 5.1% higher IL-6 level, a 0.31 nm larger very-low-density lipoprotein particle diameter, a 0.014 nm smaller high-density lipoprotein particle diameter, and a 5.25 nmol/L lower intermediate-density lipoprotein particle concentration (all p < 0.05). A 1-SD increment in ln-transformed FGF21 level was associated with LSR< 1 and liver attenuation < 40 HU (OR = 1.38 and 1.48; both p < 0.01), even after adjusting for the aforementioned inflammation and lipoprotein parameters. Conclusions: This study suggests an association between FGF21 and NAFLD, independent of inflammation and atherogenic lipoprotein abnormalities. Further studies are needed to assess FGF21 as a biomarker for future NAFLD risk.
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