American Heart Journal
Volume 157, Issue 1 , Pages 91-96 , January 2009

Erythropoietin levels in heart failure after an acute myocardial infarction: Determinants, prognostic value, and the effects of captopril versus losartan

  • Anne M.S. Belonje, MD

      Affiliations

    • Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands
  • ,
  • B. Daan Westenbrink, MD

      Affiliations

    • Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands
  • ,
  • Adriaan A. Voors, MD, PhD

      Affiliations

    • Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands
    • Corresponding Author InformationReprint requests: Adriaan A. Voors, MD, PhD, Department of Cardiology, Thoraxcenter, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB Groningen, The Netherlands.
  • ,
  • Stephan von Haehling, MD

      Affiliations

    • Department of Cardiology, Applied Cachexia Research, Charité, Campus Virchow-Klinikum, Berlin, Germany
  • ,
  • Pjotr Ponikowski, MD, PhD

      Affiliations

    • Department of Cardiology, Military Hospital, Wroclaw, Poland
  • ,
  • Stefan D. Anker, MD, PhD

      Affiliations

    • Department of Cardiology, Applied Cachexia Research, Charité, Campus Virchow-Klinikum, Berlin, Germany
  • ,
  • Dirk J. van Veldhuisen, MD, PhD

      Affiliations

    • Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands
  • ,
  • Kenneth Dickstein, MD, PhD

      Affiliations

    • Department of Cardiology, University of Bergen, Stavanger University Hospital, Stavanger, Norway

Received 2 May 2008 ,Accepted 21 August 2008.

References 

  1. 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
  2. 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
  3. George J, Patal S, Wexler D, et al. Circulating erythropoietin levels and prognosis in patients with congestive heart failure: comparison with neurohormonal and inflammatory markers. Arch Intern Med. 2005;165:1304–1309
  4. Roque ME, Sandoval MJ, Aggio MC. Serum erythropoietin and its relation with soluble transferrin receptor in patients with different types of anaemia in a locally defined reference population. Clin Lab Haematol. 2001;23:291–295
  5. Fehr T, Ammann P, Garzoni D, et al. Interpretation of erythropoietin levels in patients with various degrees of renal insufficiency and anemia. Kidney Int. 2004;66:1206–1211
  6. Belonje AM, Voors AA, van Gilst WH, et al. Erythropoietin in chronic heart failure. Congest Heart Fail. 2007;13:289–292
  7. Lipsic E, van der Meer P, Voors AA, et al. A single bolus of a long-acting erythropoietin analogue darbepoetin alfa in patients with acute myocardial infarction: a randomized feasibility and safety study. Cardiovasc Drugs Ther. 2006;20:135–141
  8. 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
  9. Ferrario M, Massa M, Rosti V, et al. Early haemoglobin-independent increase of plasma erythropoietin levels in patients with acute myocardial infarction. Eur Heart J. 2007;28:1805–1813
  10. Freudenthaler SM, Schreeb K, Korner T, et al. Angiotensin II increases erythropoietin production in healthy human volunteers. Eur J Clin Invest. 1999;29:816–823
  11. Gossmann J, Burkhardt R, Harder S, et al. Angiotensin II infusion increases plasma erythropoietin levels via an angiotensin II type 1 receptor–dependent pathway. Kidney Int. 2001;60:83–86
  12. Kato H, Ishida J, Imagawa S, et al. Enhanced erythropoiesis mediated by activation of the renin-angiotensin system via angiotensin II type 1a receptor. FASEB J. 2005;19:2023–2025
  13. Fyhrquist F, Karppinen K, Honkanen T, et al. High serum erythropoietin levels are normalized during treatment of congestive heart failure with enalapril. J Intern Med. 1989;226:257–260
  14. Robles NR, Angulo E, Grois J, et al. Comparative effects of fosinopril and irbesartan on hematopoiesis in essential hypertensives. Ren Fail. 2004;26:399–404
  15. Wang AY, Yu AW, Lam CW, et al. Effects of losartan or enalapril on hemoglobin, circulating erythropoietin, and insulin-like growth factor-1 in patients with and without posttransplant erythrocytosis. Am J Kidney Dis. 2002;39:600–608
  16. Durmus A, Dogan E, Erkoc R, et al. Effect of valsartan on erythropoietin and hemoglobin levels in stage III-IV chronic kidney disease patients. Int J Clin Pract. 2005;59:1001–1004
  17. Dickstein K, Kjekshus J. Comparison of the effects of losartan and captopril on mortality in patients after acute myocardial infarction: the OPTIMAAL trial design. Optimal Therapy in Myocardial Infarction with the Angiotensin II Antagonist Losartan. Am J Cardiol. 1999;83:477–481
  18. Dickstein K, Kjekshus J. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan. Lancet. 2002;360:752–760
  19. Squire IB, Orn S, Ng LL, et al. Plasma natriuretic peptides up to 2 years after acute myocardial infarction and relation to prognosis: an OPTIMAAL substudy. J Card Fail. 2005;11:492–497
  20. Benson EW, Hardy R, Chaffin C, et al. New automated chemiluminescent assay for erythropoietin. J Clin Lab Anal. 2000;14:271–273
  21. Mengozzi M, Latini R, Salio M, et al. Increased erythropoietin production after myocardial infarction in mice. Heart. 2006;92:838–839
  22. van der Meer P, Lipsic E, Henning RH, et al. Erythropoietin induces neovascularization and improves cardiac function in rats with heart failure after myocardial infarction. J Am Coll Cardiol. 2005;46:125–133
  23. van der Meer P, Lipsic E, Henning RH, et al. Erythropoietin improves left ventricular function and coronary flow in an experimental model of ischemia-reperfusion injury. Eur J Heart Fail. 2004;6:853–859
  24. 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
  25. 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
  26. Bahlmann FH, Song R, Boehm SM, et al. Low-dose therapy with the long-acting erythropoietin analogue darbepoetin alpha persistently activates endothelial Akt and attenuates progressive organ failure. Circulation. 2004;110:1006–1012
  27. Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006;355:2085–2098
  28. Drueke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006;355:2071–2084
  29. van Veldhuisen DJ, McMurray JJ. Are erythropoietin stimulating proteins safe and efficacious in heart failure? Why we need an adequately powered randomised outcome trial. Eur J Heart Fail. 2007;9:110–112
  30. Belonje AM, Voors AA, van Gilst WH, et al. Effects of erythropoietin after an acute myocardial infarction: rationale and study design of a prospective, randomized, clinical trial (HEBE III). Am Heart J. 2008;155:817–822
  31. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352:1011–1023
  32. 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
  33. van der Meer P, Lok DJ, Januzzi JL, et al. Adequacy of endogenous erythropoietin levels and mortality in anaemic heart failure patients. Eur Heart J. 2008;29:1510–1515
  34. Voors AA, Pinto YM, Buikema H, et al. Dual pathway for angiotensin II formation in human internal mammary arteries. Br J Pharmacol. 1998;125:1028–1032
  35. Swedberg K. Exploring new treatment strategies in heart failure. Blood Press Suppl. 2000;1:44–48
  36. Roig E, Perez-Villa F, Morales M, et al. Clinical implications of increased plasma angiotensin II despite ACE inhibitor therapy in patients with congestive heart failure. Eur Heart J. 2000;21:53–57
  37. van der Meer P, Lipsic E, Westenbrink BD, et al. Levels of hematopoiesis inhibitor N-acetyl-seryl-aspartyl-lysyl-proline partially explain the occurrence of anemia in heart failure. Circulation. 2005;112:1743–1747
  38. Hornig B, Arakawa N, Drexler H. Effect of ACE inhibition on endothelial dysfunction in patients with chronic heart failure. Eur Heart J. 1998;19(Suppl G):G48–G53

 D.J. van Veldhuisen and A.A. Voors are Clinical Established Investigators of the Netherlands Heart Foundation (D97-017 and 2006T37).

PII: S0002-8703(08)00735-7

doi: 10.1016/j.ahj.2008.08.020

American Heart Journal
Volume 157, Issue 1 , Pages 91-96 , January 2009