title: Fibroblast growth factor 23 and sudden versus non-sudden cardiac death: the Cardiovascular Health Study.
abstract: BACKGROUND
  Elevated fibroblast growth factor 23 (FGF-23) concentrations are associated with greater risk of cardiovascular events and mortality, especially among people with chronic kidney disease (CKD). Because individuals with CKD are at an increased risk of sudden cardiac death (SCD), we sought to understand whether FGF-23 level is a stronger risk factor for SCD versus non-SCD.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  3,244 participants 65 years or older in the community-based Cardiovascular Health Study.
  
  
  METHODS
  Plasma FGF-23 concentrations.
  
  
  RESULTS
  We assessed SCD and non-SCD in these analyses. SCD was adjudicated rigorously and was defined as a sudden pulseless condition of cardiac origin in a previously stable person occurring out of hospital or in the emergency department.
  
  
  METHODS
  We estimated associations of baseline FGF-23 concentrations with SCD and non-SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, comorbid conditions, and kidney function. We also tested whether associations differed by CKD status.
  
  
  RESULTS
  During a median follow-up of 8.1 years, there were 118 adjudicated SCD and 570 non-SCD events. After multivariable adjustment for demographics, cardiovascular risk factors, comorbid conditions, and parameters of kidney function, higher FGF-23 concentrations were an independent risk factor for non-SCD (HR [per doubling], 1.17; 95% CI, 1.06-1.30). However, elevated FGF-23 concentrations were not associated independently with SCD (HR [per doubling], 1.07; 95% CI, 0.85-1.35). In stratified analysis by CKD status (36.5% of cohort), doubling of FGF-23 concentrations was associated independently with non-SCD (adjusted HR, 1.26; 95% CI, 1.10-1.45). A similar magnitude of association was observed between FGF-23 level and SCD in the CKD subgroup; however, it was not significant (HR, 1.20; 95% CI, 0.89-1.62).
  
  
  CONCLUSIONS
  Limited power to detect moderate-sized effects between FGF-23 level and SCD in both the primary and stratified analyses.
  
  
  CONCLUSIONS
  In this population-based study, FGF-23 level elevations were associated independently with non-SCD. Among individuals with CKD, the associations between FGF-23 level and SCD and non-SCD were similar.
authors.affiliation: Section of Electrophysiology, Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia, PA. Electronic address: rajat.deo@uphs.upenn.edu.
authors.forename: Rajat
authors.initials: R
authors.lastname: Deo
authors.affiliation: Kidney Research Institute, University of Washington, Seattle, WA.
authors.forename: Ronit
authors.initials: R
authors.lastname: Katz
authors.affiliation: Kidney Research Institute, University of Washington, Seattle, WA; Division of Nephrology, University of Washington, Seattle, WA.
authors.forename: Ian H
authors.initials: IH
authors.lastname: de Boer
authors.affiliation: Division of Cardiology, University of Washington, Seattle, WA.
authors.forename: Nona
authors.initials: N
authors.lastname: Sotoodehnia
authors.affiliation: Kidney Research Institute, University of Washington, Seattle, WA; Division of Nephrology, University of Washington, Seattle, WA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Kestenbaum
authors.affiliation: Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Mukamal
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado Denver Health Sciences Center, Aurora, CO.
authors.forename: Michel
authors.initials: M
authors.lastname: Chonchol
authors.affiliation: Division of Nephrology, Tufts Medical Center, Boston, MA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Sarnak
authors.affiliation: Cardiovascular Health Research Unit, University of Washington, Seattle, WA; Department of Medicine, University of Washington, Seattle, WA; Department of Epidemiology, University of Washington, Seattle, WA; Department of Health Services, University of Washington, Seattle, WA; Center for Health Studies, Group Health, Seattle, WA.
authors.forename: David
authors.initials: D
authors.lastname: Siscovick
authors.affiliation: General Internal Medicine Section, Veterans Affairs Medical Center, San Francisco, CA; Department of Medicine, University of California, San Francisco, CA; Department of Epidemiology, University of California, San Francisco, CA; Department of Biostatistics, University of California, San Francisco, CA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Shlipak
authors.affiliation: Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, San Diego, CA; Division of Nephrology and Preventive Medicine, University of California, San Diego, San Diego, CA.
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D015897:Comorbidity; D016757:Death, Sudden, Cardiac; D004562:Electrocardiography; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005500:Follow-Up Studies; D006323:Heart Arrest / Q000097:blood; D006331:Heart Diseases / Q000097:blood* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000453:epidemiology; D012307:Risk Factors; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: Cardiovascular Health Study (CHS); Fibroblast growth factor 23 (FGF-23); cardiovascular event; cardiovascular mortality; chronic kidney disease (CKD); cohort study; fatal arrhythmic event; non-SCD; renal function; sudden cardiac death (SCD)