CORRESPONDENCE: LETTER TO THE EDITOR
Serum Erythropoietin Levels and Infarct Size
Erik Lipsic, MD*,
Adriaan A. Voors, MD, PhD and
Dirk J. van Veldhuisen, MD, PhD
* Department of Cardiology, University Medical Center, Hanzeplein 1, 9700 RB Groningen, the Netherlands (Email: e.lipsic{at}med.umcg.nl).
With great interest we read the recent study by Namiuchi et al. (1) showing an association between high serum erythropoietin levels and smaller infarct size in patients with acute myocardial infarction (MI) undergoing primary angioplasty.
Although originally considered a hematopoietic hormone, erythropoietin (EPO) has been shown to act as a pleiotropic survival and growth factor (2). There is accumulating evidence for a protective role of EPO in the heart. We and others have demonstrated that exogenous EPO administration in rodent ischemia-reperfusion models leads to reduced infarct size and inhibition of apoptosis (3,4).
Namiuchi et al. (1) suggested that endogenous EPO might also be protective against ischemia-reperfusion injury in humans. However, elevated EPO levels could also be a direct reflection of the disease severity. Serum EPO is elevated in chronic heart failure (CHF) patients, and this increase is related to the progression of the disease (5). Our group has shown that, in these patients, elevated plasma EPO levels are associated with an impaired prognosis, independent of hemoglobin levels and other established markers of CHF severity (6). Of note, in the study by Namiuchi et al. (1), MI patients with higher EPO levels were found to have significantly higher serum levels of B-type natriuretic peptide (BNP), a sign of hemodynamic impairment. Enhanced production of EPO could therefore also serve as a compensatory mechanism under ischemic conditions and reflect the severity of ischemic injury.
In the present study, patients with higher EPO levels and smaller infarct size also had lower hemoglobin levels. This is in contrast to previous findings, namely that a low hemoglobin concentration is associated with higher mortality in patients with stable coronary artery disease (7) and acute MI (8).
In addition, a very weak correlation between enzymatic infarct size and endogenous EPO levels should awake cautiousness as to the interpretation of the presumed effect of endogenous EPO on reducing the infarct size. Moreover, the serum EPO levels were measured almost 10 hours after the angioplasty and could thus reflect peri- and postprocedural blood loss, or ischemia-triggered EPO production.
Finally, we believe that the potential mechanism of protective EPO action in these patients might be different from that suggested by the investigators. In an acute ischemic situation, rescuing the cardiomyocytes from cell death (apoptosis) seems a more plausible explanation than increased neovascularization through progenitor cell stimulation. Further studies in larger cohorts of patients should elucidate the precise role of endogenous EPO in acute coronary syndromes. Moreover, therapy of patients with MI with exogenous EPO may be considered in the future.
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1. Namiuchi S, Kagaya Y, Ohta J, et al. High serum erythropoietin level is associated with smaller infarct size in patients with acute myocardial infarction who undergo successful primary percutaneous coronary intervention J Am Coll Cardiol 2005;45:1406-1412.[Abstract/Free Full Text]2. Henry DH, Bowers P, Romano MT, et al. Epoetin alfa. Clinical evolution of a pleiotropic cytokine Arch Intern Med 2004;164:262-276.[Abstract/Free Full Text] 3. Lipsic E, van der Meer P, Henning RH, et al. Timing of erythropoietin treatment for cardioprotection in ischemia/reperfusion J Cardiovasc Pharmacol 2004;44:473-479.[CrossRef][Web of Science][Medline] 4. Parsa CJ, Matsumoto A, Kim J, et al. A novel protective effect of erythropoietin in the infarcted heart J Clin Invest 2003;112:999-1007.[CrossRef][Web of Science][Medline] 5. Volpe M, Tritto C, Testa U, et al. Blood levels of erythropoietin in congestive heart failure and correlation with clinical, hemodynamic, and hormonal profiles Am J Cardiol 1994;74:468-473.[CrossRef][Web of Science][Medline] 6. van der Meer P, Voors AA, Lipsic E, et al. Prognostic value of plasma erythropoietin on mortality in patients with chronic heart failure J Am Coll Cardiol 2004;44:63-67.[Abstract/Free Full Text] 7. Reinecke H, Trey T, Wellmann J, et al. Haemoglobin-related mortality in patients undergoing percutaneous coronary interventions Eur Heart J 2003;24:2142-2150.[Abstract/Free Full Text] 8. Lipsic E, van der Horst IC, Voors AA, et al. Hemoglobin levels and 30-day mortality in patients after myocardial infarction Int J Cardiol 2005;100:289-292.[CrossRef][Web of Science][Medline]
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