Abstract
INTRODUCTION:
Elevated fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis and has been linked with mortality, cardiovascular events, and stroke. However, the role of FGF23 as a risk factor for subclinical cerebrovascular damage (SCVD) is not known.
METHODS:
We used multivariable linear and logistic regression to evaluate associations between FGF23, continuously and by quartiles, with white matter hyperintensity volume (WMHV), expressed as percent intracranial volume (%ICV), and subclinical brain infarction (SBI) in a race/ethnically diverse communitybased sample.
RESULTS:
There were 1,170 strokefree NOMAS participants with FGF23 levels and quantitative MRI data on WMHV and SBI. Participants with FGF23 levels in the top quartile (range=84.98 to1424.59 RU/mL) had greater WMHV (β=0.19 %ICV, 95% CI=0.04 to 0.33 %ICV, p=0.01) compared to those in the lowest quartile (range=15.41 to 48.96 RU/mL), adjusted for demographics, vascularrisk factors, and estimated glomerular filtration rate (eGFR). These findings remained significant in those without evidence of chronic kidney disease (CKD). The highest quartile of FGF23 also associated with greater odds of SBI, but this effect was not significant after adjusting for demographic factors and eGFR. However, sex was an effect modifier ofFGF23 in relation to odds of SBI (p for interaction=0.03). Stratified by sex, FGF23 was associated with greater odds of SBI in men (OR=1.7, 95% CI=1.0 to 2.6, p=0.03) after adjusting for demographics, vascular risk factors, and eGFR, but not among women.
CONCLUSIONS:
These crosssectional communitybased data from a diverse urban sample suggest elevated FGF23 may be a risk factor for small vessel disease, as well as MRIdefined brain infarction in men, independent of CKD. Prospective data on elevated FGF23 and SCVD are needed.