title: Fibroblast Growth Factor 23 Is Associated With Subclinical Cerebrovascular Damage: The Northern Manhattan Study.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Clinton B
authors.initials: CB
authors.lastname: Wright
authors.affiliation: 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.).
authors.forename: Nirav H
authors.initials: NH
authors.lastname: Shah
authors.affiliation: 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.).
authors.forename: Armando J
authors.initials: AJ
authors.lastname: Mendez
authors.affiliation: 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.).
authors.forename: Janet T
authors.initials: JT
authors.lastname: DeRosa
authors.affiliation: 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.).
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshita
authors.affiliation: 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.).
authors.forename: Mitchell S V
authors.initials: MS
authors.lastname: Elkind
authors.affiliation: 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.).
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Sacco
authors.affiliation: 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.).
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.affiliation: 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.).
authors.forename: Tatjana
authors.initials: T
authors.lastname: Rundek
authors.affiliation: 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.).
authors.forename: Shonni
authors.initials: S
authors.lastname: Silverberg
authors.affiliation: 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.).
authors.forename: Chuanhui
authors.initials: C
authors.lastname: Dong
authors.affiliation: 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.).
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000473:pathology; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D066127:White Matter / Q000473:pathology
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: chronic kidney disease; cohort studies; fibroblast growth factor 23; leukoaraiosis; magnetic resonance imaging (MRI)