Journal
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Volume 58, Issue 12, Pages 1241-1251Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2011.04.040
Keywords
anemia; heart failure; iron
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Funding
- British Heart Foundation (London, United Kingdom) [FS/03/104/16341]
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Objectives 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. (J Am Coll Cardiol 2011;58:1241-51) (C)2011 by the American College of Cardiology Foundation
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