CORRESPONDENCE: LETTER TO THE EDITOR
Is Anemia in Chronic Heart Failure Caused by Iron Deficiency?
B. Daan Westenbrink, MD*,
Adriaan A. Voors, MD, PhD and
Dirk J. van Veldhuisen, MD, PhD, FACC
* Department of Cardiology, Thoraxcenter, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB Groningen, the Netherlands (Email: b.d.westenbrink{at}thorax.umcg.nl).
With great interest we read the recent study in JACC by Nanas et al. (1), which provides important insight into the etiology of anemia in patients with advanced heart failure. Anemia is prevalent in chronic heart failure (CHF) patients and is associated with an impaired prognosis (2). The etiology of anemia is likely to be multifactorial (3) although prospective studies on the etiology of anemia in CHF are sparse. The main finding of the study by Nanas et al. (1) was that, although serum iron and ferritin levels were normal, iron stores in the bone marrow were significantly depleted. The investigators therefore concluded that anemia in these patients is predominantly caused by iron deficiency, which is masked by inflammation-associated up-regulation of ferritin, thereby disqualifying ferritin as a diagnostic modality in CHF. Regretfully, Nanas et al. (1) do not provide mechanistic insight into the cause of iron deficiency, as it is questionable whether the depleted iron stores in the bone marrow truly indicate systemically depleted iron stores.
One of the hallmarks of anemia of chronic disease is the marked dysregulation of iron homeostasis (4). Proinflammatory cytokines such as interleukin (IL)-6, IL-1, and tumor necrosis factor-alpha divert iron from the circulation to the reticuloendothelial system in the lymph nodes and the spleen. This is facilitated through increased erythrophagocytosis, increased production of ferritin, increased uptake of ferrous iron, and reduced release of iron by macrophages, resulting in a "reticuloendothelial block" (5). Accumulation of iron in storage sites of the reticuloendothelial system results in reduced serum iron levels and depleted iron stores in the bone marrow, thereby limiting the availability of iron for erythropoiesis. Thus, although anemia of chronic disease is associated with iron-restricted erythropoiesis, systemic iron stores may be adequate or even slightly elevated. As CHF is associated with up-regulation of these cytokines, the depleted iron stores in the bone marrow aspirates of the patients presented by Nanas et al. (1) might therefore result from a "reticuloendothelial block" rather than true iron deficiency. Thus, the implementation of bone marrow aspiration to evaluate iron stores in anemic CHF patients, as suggested by the researchers, will fail to differentiate between nutritional iron deficiency and anemia of chronic disease.
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1. Nanas JN, Matsouka C, Karageorgopoulos D, et al. Etiology of anemia in patients with advanced heart failure J Am Coll Cardiol 2006;48:2485-2489.[Abstract/Free Full Text]2. van der Meer P, Voors AA, Lipsic E, van Gilst WH, van Veldhuisen DJ. Erythropoietin in cardiovascular diseases Eur Heart J 2004;25:285-291.[Abstract/Free Full Text] 3. Westenbrink BD, Visser FW, Voors AA, et al. Anaemia in chronic heart failure is not only related to impaired renal perfusion and blunted erythropoietin production, but to fluid retention as well Eur Heart J 2007;28:166-171.[Abstract/Free Full Text] 4. Weiss G. Pathogenesis and treatment of anaemia of chronic disease Blood Rev 2002;16:87-96.[CrossRef][Web of Science][Medline] 5. Weiss G, Goodnough LT. Anemia of chronic disease N Engl J Med 2005;352:1011-1023.[CrossRef][Web of Science][Medline]
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