title: Endogenous erythropoietin and outcome in heart failure.
abstract: BACKGROUND
  Endogenous erythropoietin is increased in patients with heart failure (HF). Previous small-scale data suggest that these erythropoietin levels are related to prognosis. This study aims to analyze the clinical and prognostic value of erythropoietin levels in relation to hemoglobin in a large cohort of HF patients.
  
  
  RESULTS
  In patients hospitalized for HF, endogenous erythropoietin levels were measured at discharge and after 6 months. In anemic patients, the relation between erythropoietin and hemoglobin levels was determined by calculating the observed/predicted ratio of erythropoietin levels. We studied data from 605 patients with HF. Mean age was 71+/-11 years; 62% were male; and mean left ventricular ejection fraction was 0.33+/-0.14. Median erythropoietin levels were 9.6 U/L at baseline and 10.5 U/L at 6 months. Higher erythropoietin levels at baseline were independently related to an increased mortality at 18 months (hazard ratio, 2.06; 95% confidence interval, 1.40 to 3.04; P<0.01). In addition, persistently elevated erythropoietin levels (higher than median at baseline and at 6 months) were related to an increased mortality risk (hazard ratio, 2.24; 95% confidence interval, 1.02 to 4.90; P=0.044). The observed/predicted ratio was determined in a subset of anemic patients, 79% of whom had erythropoietin levels lower than expected and 9% had levels higher than expected on the basis of their hemoglobin. Multivariate Cox regression analysis revealed that a higher observed/predicted ratio was related to an increased mortality risk (hazard ratio, 3.52; 95% confidence interval, 1.53 to 8.12; P=0.003).
  
  
  CONCLUSIONS
  Erythropoietin levels predict mortality in HF patients, and persistently elevated levels have an independent prognostic value. In anemic HF patients, the majority had a low observed/predicted ratio. However, a higher observed/predicted ratio may be related to an independent increased mortality risk.
authors.affiliation: Departments of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Anne M S
authors.initials: AM
authors.lastname: Belonje
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.forename: Peter
authors.initials: P
authors.lastname: van der Meer
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
authors.forename: Tiny
authors.initials: T
authors.lastname: Jaarsma
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood; D015331:Cohort Studies; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D006333:Heart Failure / Q000175:diagnosis* / Q000453:epidemiology / Q000401:mortality; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D011237:Predictive Value of Tests; D011379:Prognosis; D013318:Stroke Volume
chemical_list: D006454:Hemoglobins; D004921:Erythropoietin