title: Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relation to anemia, exercise capacity, and survival.
abstract: OBJECTIVE
  The aim of this study was to comprehensively delineate iron metabolism and its implications in patients with chronic heart failure (CHF).
  
  
  BACKGROUND
  Iron deficiency is an emerging therapeutic target in CHF.
  
  
  METHODS
  Iron and clinical indexes were quantified in 157 patients with CHF.
  
  
  RESULTS
  Several observations were made. First, iron homeostasis was deranged in anemic and nonanemic subjects and characterized by diminished circulating (transferrin saturation) and functional (mean cell hemoglobin concentration) iron status in the face of seemingly adequate stores (ferritin). Second, while iron overload and elevated iron stores were rare (1%), iron deficiency (transferrin saturation <20%) was evident in 43% of patients. Third, disordered iron homeostasis related closely to worsening inflammation and disease severity and strongly predicted lower hemoglobin levels independently of age, sex, erythrocyte sedimentation rate, New York Heart Association (NYHA) functional class, and creatinine. Fourth, the etiologies of anemia varied with disease severity, with an iron-deficient substrate (anemia of chronic disease and/or iron-deficiency anemia) evident in 16%, 72%, and 100% of anemic NYHA functional class I or II, III, and IV patients, respectively. Although anemia of chronic disease was more prevalent than iron-deficiency anemia, both conditions coexisted in 17% of subjects. Fifth, iron deficiency was associated with lower peak oxygen consumption and higher ratios of ventilation to carbon dioxide production and identified those at enhanced risk for death (hazard ratio: 3.38; 95% confidence interval: 1.48 to 7.72; p = 0.004) independently of hemoglobin. Nonanemic iron-deficient patients had a 2-fold greater risk for death than anemic iron-replete subjects.
  
  
  CONCLUSIONS
  Disordered iron homeostasis in patients with CHF relates to impaired exercise capacity and survival and appears prognostically more ominous than anemia.
authors: Clinical Cardiology, National Heart & Lung Institute, Imperial College London, London, United Kingdom.
authors: Darlington O
authors: DO
authors: Okonko
authors: Amit K J
authors: AK
authors: Mandal
authors: Constantinos G
authors: CG
authors: Missouris
authors: Philip A
authors: PA
authors: Poole-Wilson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000378:metabolism*; D018798:Anemia, Iron-Deficiency / Q000378:metabolism / Q000401:mortality; D002908:Chronic Disease; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000378:metabolism* / Q000401:mortality; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019189:Iron Metabolism Disorders / Q000150:complications / Q000453:epidemiology / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D007501:Iron