Fibroblast Growth Factor 23 Is Associated With Subclinical Cerebrovascular Damage: The Northern Manhattan Study

Clinton B Wright; Nirav H Shah; Armando J Mendez; Janet T DeRosa; Mitsuhiro Yoshita; Mitchell S V Elkind; Ralph L Sacco; Charles DeCarli; Tatjana Rundek; Shonni Silverberg; Chuanhui Dong; Myles Wolf

doi:10.1161/STROKEAHA.115.012379

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Fibroblast Growth Factor 23 Is Associated With Subclinical Cerebrovascular Damage: The Northern Manhattan Study

Journal article

Open access

Peer reviewed

Fibroblast Growth Factor 23 Is Associated With Subclinical Cerebrovascular Damage: The Northern Manhattan Study

Clinton B Wright, Nirav H Shah, Armando J Mendez, Janet T DeRosa, Mitsuhiro Yoshita, Mitchell S V Elkind, Ralph L Sacco, Charles DeCarli, Tatjana Rundek, Shonni Silverberg, …

Stroke (1970), Vol.47(4), pp.923-928

2016-04

DOI: https://doi.org/10.1161/STROKEAHA.115.012379

PMCID: PMC4811730

PMID: 26956260

Abstract

Severity of Illness Index

Cross-Sectional Studies

Humans

Middle Aged

Risk Factors

Male

Renal Insufficiency, Chronic - pathology

White Matter - pathology

Renal Insufficiency, Chronic - blood

Magnetic Resonance Imaging

Cerebrovascular Disorders - diagnosis

Fibroblast Growth Factors - blood

Cerebrovascular Disorders - blood

Sex Factors

Aged, 80 and over

Brain - pathology

Female

Aged

Cerebrovascular Disorders - pathology

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. 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. 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. 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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Web Of Science research areas: Clinical Neurology; Peripheral Vascular Disease
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Title: Fibroblast Growth Factor 23 Is Associated With Subclinical Cerebrovascular Damage: The Northern Manhattan Study
Creators: Clinton B Wright - 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
Nirav H Shah - 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.)
Armando J Mendez - 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.)
Janet T DeRosa - 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.)
Mitsuhiro Yoshita - 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.)
Mitchell S V Elkind - 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.)
Ralph L Sacco - 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.)
Charles DeCarli - 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.)
Tatjana Rundek - 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.)
Shonni Silverberg - 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.)
Chuanhui Dong - 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.)
Myles Wolf - 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.)
Publication Details: Stroke (1970), Vol.47(4), pp.923-928
Publisher: United States
Grant note: K24 NS062737 / NINDS NIH HHS K24DK093723 / NIDDK NIH HHS R37 NS29993 / NINDS NIH HHS K24 NS 062737 / NINDS NIH HHS R01 NS017950 / NINDS NIH HHS R01 HL108623 / NHLBI NIH HHS P30 AG010129 / NIA NIH HHS R37 NS029993 / NINDS NIH HHS K24 DK093723 / NIDDK NIH HHS R01 NS029993 / NINDS NIH HHS
Academic Unit: Leadership Department; Miller School of Medicine; Diabetes Research Institute (DRI); UMMG Department of Neurology
Language: English
Resource Type: Journal article
PMID: 26956260
PMCID: PMC4811730
Record Identifier: 991031559795302976