Author + information
- 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
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 exogenousEPO administration in rodent ischemia-reperfusion models leads to reduced infarct size and inhibition of apoptosis (3,4).
Namiuchi et al. (1) suggested that endogenousEPO 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 endogenousEPO in acute coronary syndromes. Moreover, therapy of patients with MI with exogenousEPO may be considered in the future.
- American College of Cardiology Foundation
- Namiuchi S.,
- Kagaya Y.,
- Ohta J.,
- et al.
- van der Meer P.,
- Voors A.A.,
- Lipsic E.,
- et al.
- Reinecke H.,
- Trey T.,
- Wellmann J.,
- et al.