Abstract
Introduction:
Fibroblast growth factor 23 (FGF23), a hormone that regulates phosphate homeostasis, has recently been linked with mortality, cardiovascular events, and stroke. While limited evidence suggests that FGF23 is associated with arterial calcification in chronic kidney disease (CKD), data on the association between FGF23 and carotid plaque are lacking, especially in population-based studies. This study aimed to determine if relative elevations of FGF23 are associated with presence and area of carotid plaque in a race/ethnically diverse community-based sample.
Methods:
There were 1,512 stroke-free NOMAS participants with FGF23 levels and 2D carotid ultrasound data available (mean age, 68±9; 61% women; 62% Hispanic, 18% black, 18% white, 2% other). We evaluated the association of FGF23, continuously and by quintiles, with presence of carotid plaque using logistic regression models and with plaque area (cubic root transformed) using linear regression models, adjusting for age, sex, race/ethnicity, estimated glomerular filtration rate (eGFR), body mass index, smoking, alcohol use, blood pressure, fasting glucose, lipids, and hypertension, diabetes, and dyslipidemia medication use.
Results:
Participants with FGF23 levels in the top quintile had greater odds of having carotid plaque (OR=1.5 95% CI=1.0-2.2, p=0.04) and larger plaque area (beta=0.3, 95% CI=0.1-0.5, p=0.006) than those in the lowest quintile, adjusting for eGFR and demographic factors, although the association was attenuated after adjusting for vascular risk factors. Linear regression models also showed that log transformed FGF23 was associated with greater plaque area adjusting for eGFR and sociodemographic factors (beta=0.2, 95% CI=0.03-0.3, p=0.02), and this remained marginally significant after adjusting for vascular risk factors (beta=0.1, 95% CI=0.0-0.3, p=0.05).
Conclusions:
These data suggest that FGF23 is associated with the likelihood and burden of carotid atherosclerosis in a stroke-free community based sample. Our finding that the association between FGF23 and carotid plaque measures was weaker after adjusting for vascular risk factors suggests possible mediation and requires further study.