LETTERS TO THE EDITOR
Further Aspects of Anemia, Heart Failure, and Erythropoietin
Jason C. Kovacic, BMedSc, MBBS, FRACP*
* Cardiology Department, St. Vincent’s Hospital, Victoria St., Darlinghurst, NSW 2010, Australia (Email: jkovacic{at}netline.net.au).
A routine laboratory hemoglobin measurement reflects "hemoglobin concentration." This approximates the total-body circulating hemoglobin (TBH) to plasma volume (PV) ratio, but provides no absolute quantitative information about either TBH or PV. Anemia arises when the TBH:PV ratio falls. This occurs with either decreased TBH or increased PV. This distinction is important: in a recent study, 46% of anemic patients with heart failure had a normal total red cell volume, with anemia attributable to excess PV (1).
In their review, Felker et al. (2) raise several issues concerning anemia and heart failure that warrant further consideration. They adopt the term "true anemia" to describe a decrease in TBH (2). This begs the question: is a reduced hemoglobin concentration any truer if it arises from decreased TBH rather than increased PV? Undoubtedly not, and the term "true anemia" should probably be avoided as it is imprecise. Felker et al. also indicate that "anemia results in decreased oxygen-carrying capacity" (2). Again, this statement is imprecise. It is a decrease in TBH that results in decreased oxygen-carrying capacity.
Felker et al. (2) do not consider that anemia can be a normal adaptation to increased cardiovascular demand. Both athletic training (3–5) and pregnancy (6) cause a simultaneous increase in TBH and PV, with the increase in PV being relatively greater than the increase in TBH (3–6). This results in an increased total blood volume, reduced blood viscosity, and anemia—an adaptation that potentially enhances total-blood oxygen-carrying capacity, while concurrently decreasing blood viscosity (6,7).
Although not widely studied in heart failure, the importance of blood viscosity was given little consideration by Felker et al. (2). At a fixed hematocrit, cardiac output is enhanced as blood viscosity decreases (8). Blood viscosity is also inversely related to physical performance in athletes (7). Anemia in heart failure is undoubtedly the end result of multiple pathological pathways (2). However, a possible physiologic benefit (reduced blood viscosity) should not be discounted, and the broader consequences of increased blood viscosity from erythropoietin (EPO) therapy require careful consideration.
Felker et al. (2) provided little information on the impressive direct cardioprotective actions of EPO (9). Furthermore, research published after the Felker et al. (2) study appeared suggests that, from an evolutionary perspective, cardioprotection was one of EPO’s original functions (10), and derivatives of EPO, devoid of an erythropoietic action, retain tissue-protective effects (11).
Despite positive results in small studies (2), the large, randomized Normal Hematocrit Treatment trial of EPO in anemic dialysis patients with cardiac disease was largely negative (12). This should serve as a cautionary note, and the notion that the appropriate attitude toward EPO therapy in heart failure is "a mixture of optimism and caution" (2) needs expanding. It is difficult to reconcile EPO therapy in anemic patients with normal TBH but with expanded PV. Given the potentially adverse consequences of EPO (increased blood viscosity and other detrimental sequelae [2]) it would seem prudent to initially restrict human trials of EPO in heart failure to patients with decreased TBH.
Finally, EPO or its derivatives are a promising potential adjunctive therapy for heart failure, but to realize this potential a meticulous and rigorous approach is imperative.
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References
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- Felker GM, Adams Jr KF, Gattis WA, O’Connor CM. Anemia as a risk factor and therapeutic target in heart failure J Am Coll Cardiol 2004;44:959-966.[Abstract/Free Full Text]
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- Beischer NA, Mackay EV, Colditz P. The bloodanaemia, thromboembolism, coagulation. In: Beischer NA, Mackay EV, Colditz P, editors. Obstetrics and the Newborn. 3rd edition. London: W. B. Saunders; 1997. pp. 353-364.
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- Bogoyevitch MA. An update on the cardiac effects of erythropoietin cardioprotection by erythropoietin and the lessons learnt from studies in neuroprotection Cardiovasc Res 2004;63:208-216.[Abstract/Free Full Text]
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- Leist M, Ghezzi P, Grasso G, et al. Derivatives of erythropoietin that are tissue protective but not erythropoietic Science 2004;305:239-242.[Abstract/Free Full Text]
- Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin N Engl J Med 1998;339:584-590.[Abstract/Free Full Text]
Related Article
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Reply
- G. Michael Felker, Wendy A. Gattis, Kirkwood F. Adams, and Christopher M. O’Connor
J. Am. Coll. Cardiol. 2005 45: 1550-1551.
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