Clinton B Wright1, Nirav H Shah2, Armando J Mendez2, Janet T DeRosa2, Mitsuhiro Yoshita2, Mitchell S V Elkind2, Ralph L Sacco2, Charles DeCarli2, Tatjana Rundek2, Shonni Silverberg2, Chuanhui Dong2, Myles Wolf2. 1. From the Evelyn F. McKnight Brain Institute (C.B.W., N.H.S., R.L.S., T.R., C.D.) and the Departments of Neurology (C.B.W., R.L.S., T.R., C.D.), Public Health Sciences (C.B.W., R.L.S., T.R.), Human Genomics (R.L.S., T.R.), Medicine (A.J.M.), and the Neuroscience Program (C.B.W., R.L.S.), Leonard M. Miller School of Medicine, University of Miami, FL; Department of Neurology, University of California, San Francisco (N.H.S.); Department of Neurology, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY (J.T.D., M.S.V.E., S.S.); National Hospital Organization, Hokuriku National Hospital, Japan (M.Y.); Department of Neurology, University of California at Davis Health System, Sacramento (C.D.); Department of Medicine and Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.W.). wright.clinton@gmail.com. 2. From the Evelyn F. McKnight Brain Institute (C.B.W., N.H.S., R.L.S., T.R., C.D.) and the Departments of Neurology (C.B.W., R.L.S., T.R., C.D.), Public Health Sciences (C.B.W., R.L.S., T.R.), Human Genomics (R.L.S., T.R.), Medicine (A.J.M.), and the Neuroscience Program (C.B.W., R.L.S.), Leonard M. Miller School of Medicine, University of Miami, FL; Department of Neurology, University of California, San Francisco (N.H.S.); Department of Neurology, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY (J.T.D., M.S.V.E., S.S.); National Hospital Organization, Hokuriku National Hospital, Japan (M.Y.); Department of Neurology, University of California at Davis Health System, Sacramento (C.D.); Department of Medicine and Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (M.W.).
Abstract
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(2)). 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.
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(2)). 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.
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