title: Prognostic significance of endogenous erythropoietin in long-term outcome of patients with acute decompensated heart failure.
abstract: Although previous reports suggest that an elevated endogenous erythropoietin (EPO) level is associated with worse clinical outcomes in chronic heart failure (HF) patients, the prognostic implication of EPO in patients with acute decompensated HF (ADHF) and underlying mechanisms of the high EPO level in severe HF patients who have a poor prognosis remain unclear.
  
  
  
  We examined 539 consecutive ADHF patients with EPO measurement on admission from our registry. During a median follow-up period of 329 days, a higher EPO level on admission was independently associated with worse clinical outcomes [hazard ratio (HR) 1.25, 95% confidence interval (CI) 1.06-1.48, P = 0.008], and haemoglobin level was the strongest determinant of EPO level (P < 0.001), whereas estimated glomerular filtration rate (eGFR) was not significant in multivariate regression analysis. In the anaemic subgroup of 318 patients, a higher EPO level than expected on the basis of their haemoglobin level was related to increased adverse events (HR 1.63, 95% CI 1.05-2.49, P = 0.028). Moreover, estimated plasma volume excess rate was positively associated with EPO level (P = 0.003), and anaemic patients with a higher than expected EPO level tended to have a higher estimated plasma volume excess rate and plasma lactate level, and lower systemic oxygen saturation level with the preservation of the reticulocyte production index than those with a lower than expected EPO level.
  
  
  
  A high EPO level predicts long-term worse clinical outcomes in ADHF patients, independent of anaemia and impaired renal function. Anaemia and hypoxia due to severe congestion may synergistically contribute to a high EPO level in high-risk HF patients.
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Preventive Medicine and Epidemiology Informatics, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Honma
authors.affiliation: Preventive Medicine and Epidemiology Informatics, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Higashiyama
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sugano
authors.affiliation: Preventive Medicine and Epidemiology Informatics, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Michikazu
authors.initials: M
authors.lastname: Nakai
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Honda
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Naotsugu
authors.initials: N
authors.lastname: Iwakami
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okada
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Kawakami
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kanaya
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Asaumi
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Aiba
authors.affiliation: Foundation for Biomedical Research and Innovation, Hyogo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nishida
authors.affiliation: Department of Environmental and Preventive Medicine, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Kubota
authors.affiliation: Department of Preventive Medicine and Public Health, Keio University, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sugiyama
authors.affiliation: Department of Preventive Medicine and Public Health, Keio University, Tokyo, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Noguchi
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Kusano
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasuda
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Anzai
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood* / Q000150:complications; D002423:Cause of Death; D015331:Cohort Studies; D018450:Disease Progression; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000097:blood* / Q000150:complications; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D009026:Mortality; D015999:Multivariate Analysis; D010092:Oximetry; D010953:Plasma Volume; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D051437:Renal Insufficiency / Q000097:blood / Q000150:complications
chemical_list: C554270:EPO protein, human; D006454:Hemoglobins; D004921:Erythropoietin; D019344:Lactic Acid
keywords: Acute heart failure; Anaemia; Biomarker; Erythropoietin; Prognosis