title: Fibroblast Growth Factor 23 Is Associated With Carotid Plaque Presence and Area: The Northern Manhattan Study.
abstract: OBJECTIVE
  Elevated fibroblast growth factor 23 (FGF23), a hormone that regulates phosphate homeostasis, has been associated with mortality, cardiovascular events, and stroke, and to arterial calcification in chronic kidney disease, but its role in atherosclerosis is unclear and population-based studies are lacking. We hypothesized that elevated FGF23 would associate with carotid plaque presence, area, and echogenicity in the race/ethnically diverse community-based Northern Manhattan Study (NOMAS) sample.
  
  
  RESULTS
  There were 1512 stroke-free NOMAS participants with FGF23 and 2-dimensional carotid ultrasound data (mean age, 68±9 years; 61% women; 62% Hispanic, 18% black, and 18% white). We used multivariable linear and logistic regression to evaluate FGF23, continuously and by quintiles, as a correlate of carotid plaque, plaque area (cubic root transformed), and echogenicity adjusting for sociodemographic and vascular risk factors. Participants with FGF23 levels in the top quintile were more likely to have carotid plaque (odds ratio, 1.49; 95% confidence interval, 1.02-2.19; P=0.04) and larger plaque area (β=0.32 mm(2), 95% confidence interval, 0.10-0.53 mm(2); P=0.004) than those in the lowest quintile, adjusting for estimated glomerular filtration rate, demographics, and vascular risk factors. Linear regression models also showed that log transformed FGF23 (LnFGF23) associated with greater odds of plaque presence (odds ratio, 1.26 per LnFGF23; 95% confidence interval, 1.01-1.58; P=0.04), and plaque area (β=0.19 mm(2) per LnFGF23; 95% confidence interval, 0.07-0.31 mm(2); P=0.002).
  
  
  CONCLUSIONS
  Higher FGF23 associated with greater likelihood and burden of carotid atherosclerosis independent of CKD. Atherosclerosis may be a mechanism through which FGF23 increases cardiovascular events and stroke.
authors.affiliation: From the Evelyn F. McKnight Brain Institute (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Neurology (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Public Health Sciences (R.L.S., T.R., C.B.W.), Department of Human Genomics (R.L.S., T.R.), Department of Medicine (A.J.M.), The Neuroscience Program (R.L.S., C.B.W.), and Division of Endocrinology, Diabetes and Metabolism (B.I.H.), Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, FL; Center for Translational Metabolism and Health (M.W.), Institute for Public Health and Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (B.I.H., M.W.); and Department of Neurology (M.S.V.E.), Department of Medicine, College of Physicians and Surgeons (S.S.), and Department of Epidemiology, Mailman School of Public Health (M.S.V.E.), Columbia University, New York, NY.
authors.forename: Nirav H
authors.initials: NH
authors.lastname: Shah
authors.affiliation: From the Evelyn F. McKnight Brain Institute (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Neurology (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Public Health Sciences (R.L.S., T.R., C.B.W.), Department of Human Genomics (R.L.S., T.R.), Department of Medicine (A.J.M.), The Neuroscience Program (R.L.S., C.B.W.), and Division of Endocrinology, Diabetes and Metabolism (B.I.H.), Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, FL; Center for Translational Metabolism and Health (M.W.), Institute for Public Health and Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (B.I.H., M.W.); and Department of Neurology (M.S.V.E.), Department of Medicine, College of Physicians and Surgeons (S.S.), and Department of Epidemiology, Mailman School of Public Health (M.S.V.E.), Columbia University, New York, NY.
authors.forename: Chuanhui
authors.initials: C
authors.lastname: Dong
authors.affiliation: From the Evelyn F. McKnight Brain Institute (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Neurology (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Public Health Sciences (R.L.S., T.R., C.B.W.), Department of Human Genomics (R.L.S., T.R.), Department of Medicine (A.J.M.), The Neuroscience Program (R.L.S., C.B.W.), and Division of Endocrinology, Diabetes and Metabolism (B.I.H.), Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, FL; Center for Translational Metabolism and Health (M.W.), Institute for Public Health and Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (B.I.H., M.W.); and Department of Neurology (M.S.V.E.), Department of Medicine, College of Physicians and Surgeons (S.S.), and Department of Epidemiology, Mailman School of Public Health (M.S.V.E.), Columbia University, New York, NY.
authors.forename: Mitchell S V
authors.initials: MS
authors.lastname: Elkind
authors.affiliation: From the Evelyn F. McKnight Brain Institute (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Neurology (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Public Health Sciences (R.L.S., T.R., C.B.W.), Department of Human Genomics (R.L.S., T.R.), Department of Medicine (A.J.M.), The Neuroscience Program (R.L.S., C.B.W.), and Division of Endocrinology, Diabetes and Metabolism (B.I.H.), Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, FL; Center for Translational Metabolism and Health (M.W.), Institute for Public Health and Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (B.I.H., M.W.); and Department of Neurology (M.S.V.E.), Department of Medicine, College of Physicians and Surgeons (S.S.), and Department of Epidemiology, Mailman School of Public Health (M.S.V.E.), Columbia University, New York, NY.
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Sacco
authors.affiliation: From the Evelyn F. McKnight Brain Institute (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Neurology (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Public Health Sciences (R.L.S., T.R., C.B.W.), Department of Human Genomics (R.L.S., T.R.), Department of Medicine (A.J.M.), The Neuroscience Program (R.L.S., C.B.W.), and Division of Endocrinology, Diabetes and Metabolism (B.I.H.), Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, FL; Center for Translational Metabolism and Health (M.W.), Institute for Public Health and Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (B.I.H., M.W.); and Department of Neurology (M.S.V.E.), Department of Medicine, College of Physicians and Surgeons (S.S.), and Department of Epidemiology, Mailman School of Public Health (M.S.V.E.), Columbia University, New York, NY.
authors.forename: Armando J
authors.initials: AJ
authors.lastname: Mendez
authors.affiliation: From the Evelyn F. McKnight Brain Institute (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Neurology (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Public Health Sciences (R.L.S., T.R., C.B.W.), Department of Human Genomics (R.L.S., T.R.), Department of Medicine (A.J.M.), The Neuroscience Program (R.L.S., C.B.W.), and Division of Endocrinology, Diabetes and Metabolism (B.I.H.), Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, FL; Center for Translational Metabolism and Health (M.W.), Institute for Public Health and Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (B.I.H., M.W.); and Department of Neurology (M.S.V.E.), Department of Medicine, College of Physicians and Surgeons (S.S.), and Department of Epidemiology, Mailman School of Public Health (M.S.V.E.), Columbia University, New York, NY.
authors.forename: Barry I
authors.initials: BI
authors.lastname: Hudson
authors.affiliation: From the Evelyn F. McKnight Brain Institute (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Neurology (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Public Health Sciences (R.L.S., T.R., C.B.W.), Department of Human Genomics (R.L.S., T.R.), Department of Medicine (A.J.M.), The Neuroscience Program (R.L.S., C.B.W.), and Division of Endocrinology, Diabetes and Metabolism (B.I.H.), Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, FL; Center for Translational Metabolism and Health (M.W.), Institute for Public Health and Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (B.I.H., M.W.); and Department of Neurology (M.S.V.E.), Department of Medicine, College of Physicians and Surgeons (S.S.), and Department of Epidemiology, Mailman School of Public Health (M.S.V.E.), Columbia University, New York, NY.
authors.forename: Shonni
authors.initials: S
authors.lastname: Silverberg
authors.affiliation: From the Evelyn F. McKnight Brain Institute (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Neurology (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Public Health Sciences (R.L.S., T.R., C.B.W.), Department of Human Genomics (R.L.S., T.R.), Department of Medicine (A.J.M.), The Neuroscience Program (R.L.S., C.B.W.), and Division of Endocrinology, Diabetes and Metabolism (B.I.H.), Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, FL; Center for Translational Metabolism and Health (M.W.), Institute for Public Health and Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (B.I.H., M.W.); and Department of Neurology (M.S.V.E.), Department of Medicine, College of Physicians and Surgeons (S.S.), and Department of Epidemiology, Mailman School of Public Health (M.S.V.E.), Columbia University, New York, NY.
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
authors.affiliation: From the Evelyn F. McKnight Brain Institute (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Neurology (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Public Health Sciences (R.L.S., T.R., C.B.W.), Department of Human Genomics (R.L.S., T.R.), Department of Medicine (A.J.M.), The Neuroscience Program (R.L.S., C.B.W.), and Division of Endocrinology, Diabetes and Metabolism (B.I.H.), Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, FL; Center for Translational Metabolism and Health (M.W.), Institute for Public Health and Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (B.I.H., M.W.); and Department of Neurology (M.S.V.E.), Department of Medicine, College of Physicians and Surgeons (S.S.), and Department of Epidemiology, Mailman School of Public Health (M.S.V.E.), Columbia University, New York, NY.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Rundek
authors.affiliation: From the Evelyn F. McKnight Brain Institute (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Neurology (N.H.S., C.D., R.L.S., T.R., C.B.W.), Department of Public Health Sciences (R.L.S., T.R., C.B.W.), Department of Human Genomics (R.L.S., T.R.), Department of Medicine (A.J.M.), The Neuroscience Program (R.L.S., C.B.W.), and Division of Endocrinology, Diabetes and Metabolism (B.I.H.), Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, FL; Center for Translational Metabolism and Health (M.W.), Institute for Public Health and Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL (B.I.H., M.W.); and Department of Neurology (M.S.V.E.), Department of Medicine, College of Physicians and Surgeons (S.S.), and Department of Epidemiology, Mailman School of Public Health (M.S.V.E.), Columbia University, New York, NY. c.wright21@med.miami.edu.
authors.forename: Clinton B
authors.initials: CB
authors.lastname: Wright
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D003430:Cross-Sectional Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009519:New York City / Q000453:epidemiology; D016017:Odds Ratio; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D012372:ROC Curve; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D014463:Ultrasonography; D014505:Urban Population
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: atherosclerosis; epidemiology; fibroblast growth factors; glomerular filtration rate; risk factors