title: High serum erythropoietin levels are related to heart failure development in subjects from the general population with albuminuria: data from PREVEND.
abstract: In patients with heart failure (HF), serum erythropoietin (EPO) levels are elevated and associated with disease severity and outcome. Whether endogenous EPO levels are prospectively associated with the development of HF or cardiovascular events in the general population is unknown.
  
  
  
  Serum EPO levels were measured at baseline in 6686 subjects enrolled in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study. Mean age (±SD) was 53 ± 12 years, 49.8% were male, and the median (interquartile range) EPO level was 7.7 (5.9-10.2) IU/L. During a median follow-up of 8.3 (7.7-8.8) years, 209 (3.1%) subjects were newly diagnosed with HF, 97 (1.5%) died of a cardiovascular cause, and 386 (6.0%) subjects had a non-fatal cardiovascular event (277 cardiac events and 93 strokes). Each doubling of EPO level was multivariably associated with new-onset HF [hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.03-1.69, P = 0.031]. EPO levels showed interaction with urinary albumin excretion (P = 0.006) and were only associated with HF in subjects with albuminuria (HR 1.51, 95% CI 1.13-2.03, P = 0.005). There was an independent association of EPO levels with stroke in women (HR 1.82, 95% CI 1.24-2.65, P = 0.002), but not in men. No association was observed for EPO levels with other cardiovascular events or cardiovascular mortality.
  
  
  
  High serum EPO levels are independently associated with an increased risk of new-onset HF in subjects with albuminuria. More research into the pathophysiological mechanisms linking EPO levels to HF is needed to understand this association.
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Niels
authors.initials: N
authors.lastname: Grote Beverborg
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Haye H
authors.initials: HH
authors.lastname: van der Wal
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: IJsbrand T
authors.initials: IT
authors.lastname: Klip
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Hans L
authors.initials: HL
authors.lastname: Hillege
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: van der Harst
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van der Meer
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000097:blood / Q000453:epidemiology*; D002318:Cardiovascular Diseases / Q000401:mortality*; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D006333:Heart Failure / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000453:epidemiology*; D017202:Myocardial Ischemia / Q000453:epidemiology; D009204:Myocardial Revascularization / Q000706:statistics & numerical data*; D009426:Netherlands / Q000453:epidemiology; D011379:Prognosis; D016016:Proportional Hazards Models; D012737:Sex Factors; D020521:Stroke / Q000453:epidemiology*
chemical_list: C554270:EPO protein, human; D004921:Erythropoietin
keywords: Albuminuria; Erythropoietin; General population; Heart failure; Stroke