Abstract P222: Serum fibroblast growth factor-23 and risk of incident stroke: The Atherosclerosis Risk in Communities Study (ARIC)

Abstract

Background: Fibroblast growth factor-23 (FGF23), a hormone involved in phosphorous regulation and vitamin D metabolism, has been associated with risk of coronary heart disease and heart failure and is a potential target for intervention. FGF23 may influence stroke risk through several pathways: suboptimal vitamin D levels, impaired kidney function, endothelial dysfunction, and/or inflammation. We tested whether elevated FGF23 is associated with increased risk of incident stroke, independent of traditional stroke risk factors and kidney function. Methods: Biologically active intact FGF23 was measured in stored samples collected at baseline, in 1990-1992, from 12,432 stroke-free ARIC participants. Participants were followed through 2010. Incident stroke events (both ischemic and hemorrhagic) were identified during follow-up and adjudicated using medical chart review. Multivariable Cox proportional hazards regression models were used to evaluate the independent association of baseline serum FGF23 with risk of incident stroke. Results: Over a median follow-up of 19 years, 766 participants (median age 56, 24% black) developed incident stroke. A significant association of baseline FGF23 with incident stroke was only observed in the highest quintile of serum FGF23. Compared to those in the lowest quintile of FGF23, those in the highest quintile were at 37% greater risk of incident stroke (Table), after adjustment for demographics, behaviors, and body mass index. Additional adjustment for cardiovascular risk factors and eGFR categories completely attenuated the association. There was no evidence of interaction by age, sex, race, or eGFR category. Conclusions: Elevated levels of serum FGF23 were associated with modestly increased risk of incident stroke in this large, biracial, community-based cohort in minimally-adjusted models, however this association was not independent of cardiovascular risk factors and kidney function.