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
FGF21 levels and
atherosclerosis in patients without
nonalcoholic fatty liver disease, and investigated whether baseline
FGF21 could predict incident atherosclerotic
cardiovascular disease in a 7-year prospective cohort. Methods and Results Baseline serum
FGF21 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,
FGF21 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
FGF21 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
FGF21 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
FGF21 levels are elevated in patients without
nonalcoholic fatty liver disease with subclinical
atherosclerosis. Baseline
FGF21 is an independent predictor of atherosclerotic
cardiovascular disease and represents a novel
biomarker for primary prevention in the general population.