title: Iron status in patients with chronic heart failure.
abstract: OBJECTIVE
  The changes in iron status occurring during the course of heart failure (HF) and the underlying pathomechanisms are largely unknown. Hepcidin, the major regulatory protein for iron metabolism, may play a causative role. We investigated iron status in a broad spectrum of patients with systolic HF in order to determine the changes in iron status in parallel with disease progression, and to associate iron status with long-term prognosis.
  
  
  RESULTS
  Serum concentrations of ferritin, transferrin saturation (Tsat), soluble transferrin receptor (sTfR), and hepcidin were assessed as the biomarkers of iron status in 321 patients with chronic systolic HF [age: 61 ± 11 years, men: 84%, left ventricular ejection fraction: 31 ± 9%, New York Heart Association (NYHA) class: 72/144/87/18] at a tertiary cardiology centre and 66 age- and gender-matched healthy subjects. Compared with healthy subjects, asymptomatic HF patients had similar haematological status, but increased iron stores (evidenced by higher serum ferritin without distinct inflammation, P < 0.01) with markedly elevated serum hepcidin (P < 0.001). With increasing HF severity, patients in advanced NYHA classes had iron deficiency (ID) (reduced serum ferritin, low Tsat, high sTfR), iron-restricted erythropoiesis (reduced haemoglobin, high red cell distribution width), and inflammation (high serum high-sensitivity-C-reactive protein and interleukin 6), which was accompanied by decreased circulating hepcidin (all P < 0.001). In multivariable Cox models, low hepcidin was independently associated with increased 3-year mortality among HF patients (P < 0.001).
  
  
  CONCLUSIONS
  Increased level of circulating hepcidin characterizes an early stage of HF, and is not accompanied by either anaemia or inflammation. The progression of HF is associated with the decline in circulating hepcidin and the development of ID. Low hepcidin independently relates to unfavourable outcome.
authors.affiliation: Laboratory for Applied Research of Cardiovascular System, Department of Heart Diseases, Faculty of Health Sciences, Wroclaw Medical University, ul. Weigla 5, 50-981 Wroclaw, Poland. ewa.jankowska@am.wroc.pl
authors.forename: Ewa A
authors.initials: EA
authors.lastname: Jankowska
authors.forename: Jolanta
authors.initials: J
authors.lastname: Malyszko
authors.forename: Hossein
authors.initials: H
authors.lastname: Ardehali
authors.forename: Ewa
authors.initials: E
authors.lastname: Koc-Zorawska
authors.forename: Waldemar
authors.initials: W
authors.lastname: Banasiak
authors.forename: Stephan
authors.initials: S
authors.lastname: von Haehling
authors.forename: Iain C
authors.initials: IC
authors.lastname: Macdougall
authors.forename: Guenter
authors.initials: G
authors.lastname: Weiss
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000209:etiology / Q000401:mortality; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D005293:Ferritins / Q000378:metabolism; D054143:Heart Failure, Systolic / Q000097:blood / Q000209:etiology* / Q000401:mortality; D064451:Hepcidins; D006801:Humans; D000090463:Iron Deficiencies; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014168:Transferrin / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; C578702:HAMP protein, human; D064451:Hepcidins; D014168:Transferrin; D005293:Ferritins