title: Association of Serum Erythropoietin With Cardiovascular Events, Kidney Function Decline, and Mortality: The Health Aging and Body Composition Study.
abstract: BACKGROUND
  Studies suggest that in patients with heart failure (HF), high serum erythropoietin is associated with risk of recurrent HF and mortality. Trials of erythropoietin-stimulating agents in persons with kidney disease have also suggested an increased incidence of adverse clinical events. No large studies of which we are aware have evaluated the association of endogenous erythropoietin levels with clinical outcomes in the community-living older adults.
  
  
  RESULTS
  Erythropoietin concentration was measured in 2488 participants aged 70-79 years in the Health, Aging and Body Composition Study. Associations of erythropoietin with incident HF, coronary heart disease, stroke, mortality, and ≥ 30% decline in estimated glomerular filtration rate were examined using Cox proportional hazards and logistic regression over 10.7 years of follow-up. Mean (SD) age was 75 (3) years and median (quartile 1, quartile 3) erythropoietin was 12.3 (9.0, 17.2) mIU/mL. There were 503 incident HF events, and each doubling of serum erythropoietin was associated with a 25% increased risk of incident HF 1.25 (95% confidence interval 1.13, 1.48) after adjusting for demographics, prevalent cardiovascular disease, cardiovascular disease risk factors, kidney function, and serum hemoglobin. There was no interaction of serum erythropoietin with chronic kidney disease or anemia (P > 0.50). There were 330 incident coronary heart disease events, 161 strokes, 1112 deaths, and 698 outcomes of ≥ 30% decline in estimated glomerular filtration rate. Serum erythropoietin was not significantly associated with these outcomes.
  
  
  CONCLUSIONS
  Higher levels of endogenous erythropoietin are associated with incident HF in older adults. Studies need to elucidate the mechanisms through which endogenous erythropoietin levels associate with specific outcomes.
authors.affiliation: From the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA (P.S.G., M.J.S.); Kidney Research Institute (R.K.) and Department of Anesthesiology and Pain Medicine (K.V.P.), University of Washington, Seattle; Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC (S.B.K.); Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT (C.R.P.); Nephrology Section, Veterans Affairs San Diego Healthcare System and Division of Nephrology and Preventive Medicine, University of California, San Diego (J.H.I.); Renal Section, VA Pittsburgh Healthcare System (L.F.F.) and Department of Epidemiology, Graduate School of Public Health (A.B.N.), University of Pittsburgh, PA; Department of Epidemiology, Biostatistics, and Medicine, University of California, San Francisco (M.G.S.); Department of General Internal Medicine, San Francisco VA Medical Center, CA (M.G.S.); and Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MA (T.B.H.).
authors.forename: Pranav S
authors.initials: PS
authors.lastname: Garimella
authors.affiliation: From the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA (P.S.G., M.J.S.); Kidney Research Institute (R.K.) and Department of Anesthesiology and Pain Medicine (K.V.P.), University of Washington, Seattle; Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC (S.B.K.); Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT (C.R.P.); Nephrology Section, Veterans Affairs San Diego Healthcare System and Division of Nephrology and Preventive Medicine, University of California, San Diego (J.H.I.); Renal Section, VA Pittsburgh Healthcare System (L.F.F.) and Department of Epidemiology, Graduate School of Public Health (A.B.N.), University of Pittsburgh, PA; Department of Epidemiology, Biostatistics, and Medicine, University of California, San Francisco (M.G.S.); Department of General Internal Medicine, San Francisco VA Medical Center, CA (M.G.S.); and Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MA (T.B.H.).
authors.forename: Ronit
authors.initials: R
authors.lastname: Katz
authors.affiliation: From the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA (P.S.G., M.J.S.); Kidney Research Institute (R.K.) and Department of Anesthesiology and Pain Medicine (K.V.P.), University of Washington, Seattle; Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC (S.B.K.); Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT (C.R.P.); Nephrology Section, Veterans Affairs San Diego Healthcare System and Division of Nephrology and Preventive Medicine, University of California, San Diego (J.H.I.); Renal Section, VA Pittsburgh Healthcare System (L.F.F.) and Department of Epidemiology, Graduate School of Public Health (A.B.N.), University of Pittsburgh, PA; Department of Epidemiology, Biostatistics, and Medicine, University of California, San Francisco (M.G.S.); Department of General Internal Medicine, San Francisco VA Medical Center, CA (M.G.S.); and Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MA (T.B.H.).
authors.forename: Kushang V
authors.initials: KV
authors.lastname: Patel
authors.affiliation: From the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA (P.S.G., M.J.S.); Kidney Research Institute (R.K.) and Department of Anesthesiology and Pain Medicine (K.V.P.), University of Washington, Seattle; Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC (S.B.K.); Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT (C.R.P.); Nephrology Section, Veterans Affairs San Diego Healthcare System and Division of Nephrology and Preventive Medicine, University of California, San Diego (J.H.I.); Renal Section, VA Pittsburgh Healthcare System (L.F.F.) and Department of Epidemiology, Graduate School of Public Health (A.B.N.), University of Pittsburgh, PA; Department of Epidemiology, Biostatistics, and Medicine, University of California, San Francisco (M.G.S.); Department of General Internal Medicine, San Francisco VA Medical Center, CA (M.G.S.); and Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MA (T.B.H.).
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Kritchevsky
authors.affiliation: From the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA (P.S.G., M.J.S.); Kidney Research Institute (R.K.) and Department of Anesthesiology and Pain Medicine (K.V.P.), University of Washington, Seattle; Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC (S.B.K.); Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT (C.R.P.); Nephrology Section, Veterans Affairs San Diego Healthcare System and Division of Nephrology and Preventive Medicine, University of California, San Diego (J.H.I.); Renal Section, VA Pittsburgh Healthcare System (L.F.F.) and Department of Epidemiology, Graduate School of Public Health (A.B.N.), University of Pittsburgh, PA; Department of Epidemiology, Biostatistics, and Medicine, University of California, San Francisco (M.G.S.); Department of General Internal Medicine, San Francisco VA Medical Center, CA (M.G.S.); and Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MA (T.B.H.).
authors.forename: Chirag R
authors.initials: CR
authors.lastname: Parikh
authors.affiliation: From the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA (P.S.G., M.J.S.); Kidney Research Institute (R.K.) and Department of Anesthesiology and Pain Medicine (K.V.P.), University of Washington, Seattle; Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC (S.B.K.); Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT (C.R.P.); Nephrology Section, Veterans Affairs San Diego Healthcare System and Division of Nephrology and Preventive Medicine, University of California, San Diego (J.H.I.); Renal Section, VA Pittsburgh Healthcare System (L.F.F.) and Department of Epidemiology, Graduate School of Public Health (A.B.N.), University of Pittsburgh, PA; Department of Epidemiology, Biostatistics, and Medicine, University of California, San Francisco (M.G.S.); Department of General Internal Medicine, San Francisco VA Medical Center, CA (M.G.S.); and Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MA (T.B.H.).
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.affiliation: From the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA (P.S.G., M.J.S.); Kidney Research Institute (R.K.) and Department of Anesthesiology and Pain Medicine (K.V.P.), University of Washington, Seattle; Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC (S.B.K.); Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT (C.R.P.); Nephrology Section, Veterans Affairs San Diego Healthcare System and Division of Nephrology and Preventive Medicine, University of California, San Diego (J.H.I.); Renal Section, VA Pittsburgh Healthcare System (L.F.F.) and Department of Epidemiology, Graduate School of Public Health (A.B.N.), University of Pittsburgh, PA; Department of Epidemiology, Biostatistics, and Medicine, University of California, San Francisco (M.G.S.); Department of General Internal Medicine, San Francisco VA Medical Center, CA (M.G.S.); and Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MA (T.B.H.).
authors.forename: Linda F
authors.initials: LF
authors.lastname: Fried
authors.affiliation: From the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA (P.S.G., M.J.S.); Kidney Research Institute (R.K.) and Department of Anesthesiology and Pain Medicine (K.V.P.), University of Washington, Seattle; Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC (S.B.K.); Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT (C.R.P.); Nephrology Section, Veterans Affairs San Diego Healthcare System and Division of Nephrology and Preventive Medicine, University of California, San Diego (J.H.I.); Renal Section, VA Pittsburgh Healthcare System (L.F.F.) and Department of Epidemiology, Graduate School of Public Health (A.B.N.), University of Pittsburgh, PA; Department of Epidemiology, Biostatistics, and Medicine, University of California, San Francisco (M.G.S.); Department of General Internal Medicine, San Francisco VA Medical Center, CA (M.G.S.); and Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MA (T.B.H.).
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
authors.affiliation: From the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA (P.S.G., M.J.S.); Kidney Research Institute (R.K.) and Department of Anesthesiology and Pain Medicine (K.V.P.), University of Washington, Seattle; Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC (S.B.K.); Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT (C.R.P.); Nephrology Section, Veterans Affairs San Diego Healthcare System and Division of Nephrology and Preventive Medicine, University of California, San Diego (J.H.I.); Renal Section, VA Pittsburgh Healthcare System (L.F.F.) and Department of Epidemiology, Graduate School of Public Health (A.B.N.), University of Pittsburgh, PA; Department of Epidemiology, Biostatistics, and Medicine, University of California, San Francisco (M.G.S.); Department of General Internal Medicine, San Francisco VA Medical Center, CA (M.G.S.); and Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MA (T.B.H.).
authors.forename: Michael G
authors.initials: MG
authors.lastname: Shlipak
authors.affiliation: From the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA (P.S.G., M.J.S.); Kidney Research Institute (R.K.) and Department of Anesthesiology and Pain Medicine (K.V.P.), University of Washington, Seattle; Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC (S.B.K.); Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT (C.R.P.); Nephrology Section, Veterans Affairs San Diego Healthcare System and Division of Nephrology and Preventive Medicine, University of California, San Diego (J.H.I.); Renal Section, VA Pittsburgh Healthcare System (L.F.F.) and Department of Epidemiology, Graduate School of Public Health (A.B.N.), University of Pittsburgh, PA; Department of Epidemiology, Biostatistics, and Medicine, University of California, San Francisco (M.G.S.); Department of General Internal Medicine, San Francisco VA Medical Center, CA (M.G.S.); and Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MA (T.B.H.).
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.affiliation: From the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA (P.S.G., M.J.S.); Kidney Research Institute (R.K.) and Department of Anesthesiology and Pain Medicine (K.V.P.), University of Washington, Seattle; Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC (S.B.K.); Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT (C.R.P.); Nephrology Section, Veterans Affairs San Diego Healthcare System and Division of Nephrology and Preventive Medicine, University of California, San Diego (J.H.I.); Renal Section, VA Pittsburgh Healthcare System (L.F.F.) and Department of Epidemiology, Graduate School of Public Health (A.B.N.), University of Pittsburgh, PA; Department of Epidemiology, Biostatistics, and Medicine, University of California, San Francisco (M.G.S.); Department of General Internal Medicine, San Francisco VA Medical Center, CA (M.G.S.); and Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MA (T.B.H.). msarnak@tuftsmedicalcenter.org.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Sarnak
mesh_terms: D000367:Age Factors; D000368:Aged; D000375:Aging / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001823:Body Composition; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000503:physiopathology*; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D015999:Multivariate Analysis; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality / Q000503:physiopathology; D012307:Risk Factors; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C554270:EPO protein, human; D004921:Erythropoietin
keywords: cardiovascular outcomes chronic kidney disease death erythropoietin heart failure