Fibroblast growth factor 21 (FGF-21), a key hepatokine regulating lipid metabolism, is related to several atherosclerotic diseases. But whether this relationship is mediated by nonalcoholic fatty liver disease (NAFLD) is not clear. Here we assessed the association of serum FGF-21 with atherosclerosis in non-NAFLD subjects and further investigated prospectively whether baseline FGF-21 could predict incident atherosclerotic cardiovascular disease (ASCVD) in a 7-year community study.Serum FGF-21 were measured in a cross-sectional cohort of 371 type 2 diabetic patients without NAFLD as determined by hepatic magnetic resonance spectroscopy, and a population-based prospective cohort of 7subjects from the Shanghai Diabetes Study. In the cross-sectional study, serum FGF-21 was significantly higher in those with subclinical carotid atherosclerosis (268.8 [139.0-415.2] vs. 188.3 [100.2-376.4] pg/ml, P=0.005). Multiple logistic regression analysis showed that serum FGF-21 was independently associated with atherosclerosis. In the prospective study, baseline serum FGF-21 was significantly higher in those who developed ischemic heart disease (479.5 [302.4-627.0] pg/ml, P=0.004) or cerebral infarction (401.6 [238.3-616.4] pg/ml, P=0.021) than those who did not (325.2 [189.0-498.9] pg/ml) during the follow-up. In multivariable Cox regression analysis, baseline serum FGF-21 independently predicted incident ASCVD events and significantly improved discriminatory and reclassifying abilities of the prediction model after adjustment for established cardiovascular risk factors.This study provides the first evidence that FGF-21 is elevated, independent of NAFLD, in subjects with subclinical atherosclerosis. Baseline FGF-21 is an independent predictor of incident ASCVD and could be utilized as a novel biomarker for primary prevention in general population.


L. Wu: None. L. Qian: None. H. Li: None. W. Jia: None.

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