Elevated fibroblast growth factor-21 is associated with increased carotid intima media thickness

Abstract

OBJECTIVE: Elevated circulating concentrations of fibroblast growth factor-21 (FGF21), a recently recognised regulator of glucose and lipid metabolism, have been reported in type 2 diabetes, coronary artery disease, and in dialysis-dependent patients with end-stage renal failure. In this study, we investigated the relationship of serum FGF21 levels with carotid atherosclerosis in subjects with normal serum creatinine level. Design and METHODS: In 670 Chinese subjects, anthropometric and biochemical parameters, serum FGF21 concentrations and carotid intima media thickness (IMT) were measured. The relationships between serum FGF21 concentrations, various cardiometabolic risk factors, and IMT were analysed. RESULTS: Carotid IMT was measured in 285 men and 385 women mean age 58.2±12.9 years). Men had higher IMT (0.73±0.17 mm vs. 0.68±0.14 mm, p<0.001). Serum FGF21 was similar between men and women, being 248[159.6-368.2] ng/l and 251 [136.8-415.2] ng/l, median [Inter-quartile range] respectively, and correlated positively with age (p<0.001), anthropometric parameters (p<0.05), blood pressure, LDL, triglycerides, serum creatinine level, and negatively with HDL and estimated glomerular filtration rate (eGFR) (all p<0.001). A significant positive correlation was found between serum FGF21 concentration and carotid IMT (r=0.32; p<0.001) in women but not in men. This relationship remained significant even after adjusting for age, waist circumference, hypertension, fasting glucose, serum creatinine level, dyslipidaemia and smoking status (standardized beta=0.103; p=0.021). Using eGFR instead of serum creatinine level in the regression model did not alter the finding. CONCLUSIONS: Our results suggested a positive correlation between circulating levels of FGF21 and carotid IMT, a marker of carotid atherosclerosis, being demonstrable in women. This relationship was independent of various cardiometabolic risk factors. These observations would support a role for FGF21 or FGF21 resistance in the pathogenesis of atherosclerosis.