Fibroblast Growth Factor 23 Is Associated With Subclinical Cerebrovascular Damage

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphate homeostasis and when elevated increases cardiovascular disease and stroke risk and mortality. However, most studies of FGF23 have focused on those with chronic kidney disease (CKD). Less data are available from the general population, especially with respect to stroke. We previously reported elevated FGF23 increased stroke risk independent of CKD in the race/ethnically diverse community–based Northern Manhattan Study (NOMAS). The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study reported an association between FGF23 and cardioembolic stroke. We also reported that FGF23 was positively associated with carotid plaque presence and area, but FGF23’s role in subclinical cerebrovascular damage (SCVD), especially cerebral small vessel disease, is still unknown. Background and Purpose—Elevated fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis and is linked with mortality, cardiovascular events, and stroke. However, the role of FGF23 as a risk factor for subclinical cerebrovascular damage is unclear. Methods—We used multivariable linear and logistic regression to evaluate associations between FGF23, continuously and by quartiles, with white matter hyperintensity volume, expressed as percent intracranial volume (%ICV), and subclinical brain infarction (SBI) in a community-based stroke-free sample. Results—There were 1170 stroke-free Northern Manhattan Study (NOMAS) participants with FGF23 levels and quantitative magnetic resonance imaging data on white matter hyperintensity volume and SBI. Participants with FGF23 levels in the top quartile (range=85–1425 RU/mL) had greater white matter hyperintensity volume (β=0.19 %ICV; 95% CI, 0.04–0.33 %ICV; P=0.01) compared with those in the lowest quartile (range=15–49 RU/mL), adjusted for demographics, vascular risk factors, and estimated glomerular filtration rate. These findings remained significant in those without evidence of chronic kidney disease (estimated glomerular filtration rate <60 mL/min per 1.73 m). Elevated FGF23 was not associated with SBI overall after adjusting for demographic factors and estimated glomerular filtration rate, but sex modified the effect of FGF23 on odds of SBI (P for interaction=0.03). FGF23 was associated with significantly greater odds of SBI only in men (odds ratio, 1.7; 95% CI, 1.1–2.7; P=0.03) after full adjustment. Conclusions—These cross-sectional community-based data from a diverse urban sample show an association between elevated FGF23 and small vessel disease and magnetic resonance imaging–defined brain infarction in men, independent of chronic kidney disease. Data on elevated FGF23 and subclinical cerebrovascular damage progression are needed. (Stroke. 2016;47:923-928. DOI: 10.1161/STROKEAHA.115.012379.)