Open AccessFibroblast Growth Factor 21 is Related to Atherosclerosis Independent of Nonalcoholic Fatty Liver Disease and Predicts Atherosclerotic Cardiovascular Events
Author(s) -
Wu Liang,
Qian Lingling,
Zhang Lei,
Zhang Jing,
Zhou Jia,
Li Yuehua,
Hou Xuhong,
Fang Qichen,
Li Huating,
Jia Weiping
Publication year - 2020
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.119.015226
Subject(s) - medicine , nonalcoholic fatty liver disease , prospective cohort study , fgf21 , fatty liver , diabetes mellitus , population , cohort , risk factor , disease , cohort study , cardiology , gastroenterology , endocrinology , fibroblast growth factor , receptor , environmental health
Background FGF21 (fibroblast growth factor 21), a novel hepatokine regulating lipid metabolism, has been linked to atherosclerotic disease. However, whether this relationship exists in patients without nonalcoholic fatty liver disease is unclear. We assessed the association between serum FGF 21 levels and atherosclerosis in patients without nonalcoholic fatty liver disease, and investigated whether baseline FGF 21 could predict incident atherosclerotic cardiovascular disease in a 7‐year prospective cohort. Methods and Results Baseline serum FGF 21 was measured in a cross‐sectional cohort of 371 patients with type 2 diabetes mellitus without nonalcoholic fatty liver disease (determined by hepatic magnetic resonance spectroscopy), and in a population‐based prospective cohort of 705 patients from the Shanghai Diabetes Study. In the cross‐sectional study, FGF 21 was significantly higher in patients with than in those without subclinical carotid atherosclerosis ( P <0.01). The association remained significant after adjusting for demographic and traditional cardiovascular risk factors. In the prospective cohort, 80 patients developed atherosclerotic cardiovascular disease during follow‐up. Baseline FGF 21 was significantly higher in those who developed ischemic heart disease or cerebral infarction than in those who did not. Using a cutoff serum concentration of 232.0 pg/mL, elevated baseline FGF 21 independently predicted incident total atherosclerotic cardiovascular disease events, ischemic heart disease, and cerebral infarction in a nondiabetic population (all P <0.05), and significantly improved the discriminatory and reclassifying abilities of our prediction model after adjustment for established cardiovascular risk factors. Conclusions This study provides the first evidence that FGF 21 levels are elevated in patients without nonalcoholic fatty liver disease with subclinical atherosclerosis. Baseline FGF 21 is an independent predictor of atherosclerotic cardiovascular disease and represents a novel biomarker for primary prevention in the general population.