Skip to main content

Advertisement

SpringerLink
Log in

Anemia and the potential role of erythropoiesis-stimulating agents in heart failure

  • Published:
Current Heart Failure Reports Aims and scope Submit manuscript

Abstract

The recognition of the high prevalence and the independent prognostic role of anemia in heart failure (HF) has contributed to intensification of the search for an effective treatment. A central role of erythropoietin in cardiorenal anemia syndrome has been proposed. Several clinical trials have established the safety and efficacy of erythropoiesis-stimulating agents in correcting anemia in patients with HF. The recognition of the pleiotropic effect of erythropoietin has expanded targets of therapy. The ongoing outcomes trial with darbepoetin alfa will determine the role of this novel therapy in the treatment of HF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Rosamond W, Flegal K, Furie K, et al.: Heart disease and stroke statistics—2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2008, 117:e25–e146.

    Article  PubMed  Google Scholar 

  2. Lang CC, Mancini DM: Non-cardiac comorbidities in chronic heart failure. Heart 2007, 93:665–671.

    Article  PubMed  Google Scholar 

  3. Lindenfeld J: Prevalence of anemia and effects on mortality in patients with heart failure. Am Heart J 2005, 149:391–401.

    Article  PubMed  Google Scholar 

  4. Tang WH, Tong W, Jain A, et al.: Evaluation and long-term prognosis of new-onset, transient, and persistent anemia in ambulatory patients with chronic heart failure. J Am Coll Cardiol 2008, 51:569–576.

    Article  PubMed  Google Scholar 

  5. Valeur N, Nielsen OW, McMurray JJ, et al.: Anaemia is an independent predictor of mortality in patients with left ventricular systolic dysfunction following acute myocardial infarction. Eur J Heart Fail 2006, 8:577–584.

    Article  PubMed  Google Scholar 

  6. Berry C, Norrie J, Hogg K, et al.: The prevalence, nature, and importance of hematologic abnormalities in heart failure. Am Heart J 2006, 151:1313–1321.

    Article  PubMed  Google Scholar 

  7. Philipp S, Ollmann H, Schink T, et al.: The impact of anaemia and kidney function in congestive heart failure and preserved systolic function. Nephrol Dial Transplant 2005, 20:915–919.

    Article  PubMed  Google Scholar 

  8. Young JB, Abraham WT, Albert NM, et al.: Relation of low hemoglobin and anemia to morbidity and mortality in patients hospitalized with heart failure (insight from the OPTIMIZE-HF registry). Am J Cardiol 2008, 101:223–230.

    Article  PubMed  CAS  Google Scholar 

  9. Grigorian Shamagian L, Varela Roman A, Garcia-Acuna JM, et al.: Anaemia is associated with higher mortality among patients with heart failure with preserved systolic function. Heart 2006, 92:780–784.

    Article  PubMed  CAS  Google Scholar 

  10. Nair D, Shlipak MG, Angeja B, et al.: Association of anemia with diastolic dysfunction among patients with coronary artery disease in the Heart and Soul Study. Am J Cardiol 2005, 95:332–336.

    Article  PubMed  Google Scholar 

  11. Felker GM, Shaw LK, Stough WG, O’Connor CM: Anemia in patients with heart failure and preserved systolic function. Am Heart J 2006, 151:457–462.

    Article  PubMed  Google Scholar 

  12. O’Meara E, Clayton T, McEntegart MB, et al.: Clinical correlates and consequences of anemia in a broad spectrum of patients with heart failure: results of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program. Circulation 2006, 113:986–994.

    Article  PubMed  Google Scholar 

  13. Kosiborod M, Curtis JP, Wang Y, et al.: Anemia and outcomes in patients with heart failure: a study from the National Heart Care Project. Arch Intern Med 2005, 165:2237–2244.

    Article  PubMed  Google Scholar 

  14. Maggioni AP, Opasich C, Anand I, et al.: Anemia in patients with heart failure: prevalence and prognostic role in a controlled trial and in clinical practice. J Card Fail 2005, 11:91–98.

    Article  PubMed  Google Scholar 

  15. Anand IS, Kuskowski MA, Rector TS, et al.: Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure: results from Val-HeFT. Circulation 2005, 112:1121–1127.

    Article  PubMed  CAS  Google Scholar 

  16. Ishani A, Weinhandl E, Zhao Z, et al.: Angiotensinconverting enzyme inhibitor as a risk factor for the development of anemia, and the impact of incident anemia on mortality in patients with left ventricular dysfunction. J Am Coll Cardiol 2005, 45:391–399.

    Article  PubMed  CAS  Google Scholar 

  17. Komajda M, Anker SD, Charlesworth A, et al.: The impact of new onset anaemia on morbidity and mortality in chronic heart failure: results from COMET. Eur Heart J 2006, 27:1440–1446.

    Article  PubMed  Google Scholar 

  18. Go AS, Yang J, Ackerson LM, et al.: Hemoglobin level, chronic kidney disease, and the risks of death and hospitalization in adults with chronic heart failure: the Anemia in Chronic Heart Failure: Outcomes and Resource Utilization (ANCHOR) Study. Circulation 2006, 113:2713–2723.

    Article  PubMed  CAS  Google Scholar 

  19. Latado AL, Passos LC, Darze ES, Lopes AA: Comparison of the effect of anemia on in-hospital mortality in patients with versus without preserved left ventricular ejection fraction. Am J Cardiol 2006, 98:1631–1634.

    Article  PubMed  Google Scholar 

  20. Varadarajan P, Gandhi S, Sharma S, et al.: Prognostic significance of hemoglobin level in patients with congestive heart failure and normal ejection fraction. Clin Cardiol 2006, 29:444–449.

    Article  PubMed  Google Scholar 

  21. Tada T, Shiba N, Watanabe J, et al.: Prognostic value of anemia in predicting sudden death of patients with diastolic heart failure. Int J Cardiol 2007 Jul 20 (Epub ahead of print).

  22. Schou M, Gustafsson F, Kistorp CN, et al.: Prognostic usefulness of anemia and N-terminal pro-brain natriuretic peptide in outpatients with systolic heart failure. Am J Cardiol 2007, 100:1571–1576.

    Article  PubMed  CAS  Google Scholar 

  23. Desai AS, Bibbins-Domingo K, Shlipak MG, et al.: Association between anaemia and N-terminal pro-B-type natriuretic peptide (NT-proBNP): findings from the Heart and Soul Study. Eur J Heart Fail 2007, 9:886–891.

    Article  PubMed  CAS  Google Scholar 

  24. Baggish AL, van Kimmenade R, Bayes-Genis A, et al.: Hemoglobin and N-terminal pro-brain natriuretic peptide: independent and synergistic predictors of mortality in patients with acute heart failure: Results from the International Collaborative of NT-proBNP (ICON) Study. Clin Chim Acta 2007, 381:145–150.

    Article  PubMed  CAS  Google Scholar 

  25. Fukuta H, Ohte N, Mukai S, et al.: Anemia is an independent predictor for elevated plasma levels of natriuretic peptides in patients undergoing cardiac catheterization for coronary artery disease. Circ J 2008, 72:212–217.

    Article  PubMed  CAS  Google Scholar 

  26. Hogenhuis J, Voors AA, Jaarsma T, et al.: Anaemia and renal dysfunction are independently associated with BNP and NT-proBNP levels in patients with heart failure. Eur J Heart Fail 2007, 9:787–794.

    Article  PubMed  CAS  Google Scholar 

  27. Ralli S, Horwich TB, Fonarow GC: Relationship between anemia, cardiac troponin I, and B-type natriuretic peptide levels and mortality in patients with advanced heart failure. Am Heart J 2005, 150:1220–1227.

    Article  PubMed  CAS  Google Scholar 

  28. van der Putten K, Braam B, Jie KE, Gaillard CA: Mechanisms of disease: erythropoietin resistance in patients with both heart and kidney failure. Nat Clin Pract Nephrol 2008, 4:47–57.

    Article  PubMed  Google Scholar 

  29. Weiss G, Goodnough LT: Anemia of chronic disease. N Engl J Med 2005, 352:1011–1023.

    Article  PubMed  CAS  Google Scholar 

  30. Theurl I, Mattle V, Seifert M, et al.: Dysregulated monocyte iron homeostasis and erythropoetin formation in patients with anemia of chronic disease. Blood 2006, 107:4142–4148.

    Article  PubMed  CAS  Google Scholar 

  31. Wrighting DM, Andrews NC: Interleukin-6 induces hepcidin expression through STAT3. Blood 2006, 108:3204–3209.

    Article  PubMed  CAS  Google Scholar 

  32. Opasich C, Cazzola M, Scelsi L, et al.: Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure. Eur Heart J 2005, 26:2232–2237.

    Article  PubMed  CAS  Google Scholar 

  33. 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.

    Article  PubMed  CAS  Google Scholar 

  34. 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.

    Article  PubMed  Google Scholar 

  35. Terrovitis JV, Anastasiou-Nana MI, Alexopoulos GP, et al.: Prevalence and prognostic significance of anemia in patients with congestive heart failure treated with standard vs high doses of enalapril. J Heart Lung Transplant 2006, 25:333–338.

    Article  PubMed  Google Scholar 

  36. van der Meer P, Lipsic E, Westenbrink BD, et al.: Levels of hematopoiesis inhibitor N-acetyl-seryl-aspartyl-lysylproline partially explain the occurrence of anemia in heart failure. Circulation 2005, 112:1743–1747.

    Article  PubMed  Google Scholar 

  37. Tang YD, Katz SD: Anemia in chronic heart failure: prevalence, etiology, clinical correlates, and treatment options. Circulation 2006, 113:2454–2461.

    Article  PubMed  Google Scholar 

  38. Damman K, Navis G, Voors AA, et al.: Worsening renal function and prognosis in heart failure: systematic review and meta-analysis. J Card Fail 2007, 13:599–608.

    Article  PubMed  Google Scholar 

  39. Bongartz LG, Cramer MJ, Doevendans PA, et al.: The severe cardiorenal syndrome: ‘Guyton revisited’. Eur Heart J 2005, 26:11–17.

    Article  PubMed  Google Scholar 

  40. Palazzuoli A, Gallotta M, Iovine F, et al.: Anaemia in heart failure: a common interaction with renal insufficiency called the cardio-renal anaemia syndrome. Int J Clin Pract 2008, 62:281–286.

    PubMed  CAS  Google Scholar 

  41. Jie KE, Verhaar MC, Cramer MJ, et al.: Erythropoietin and the cardiorenal syndrome: cellular mechanisms on the cardiorenal connectors. Am J Physiol Renal Physiol 2006, 291:F932–F944.

    Article  PubMed  CAS  Google Scholar 

  42. Depping R, Kawakami K, Ocker H, et al.: Expression of the erythropoietin receptor in human heart. J Thorac Cardiovasc Surg 2005, 130:877–878.

    Article  PubMed  Google Scholar 

  43. Westenbrink BD, Lipsic E, van der Meer P, et al.: Erythropoietin improves cardiac function through endothelial progenitor cell and vascular endothelial growth factor mediated neovascularization. Eur Heart J 2007, 28:2018–2027.

    Article  PubMed  CAS  Google Scholar 

  44. Lipsic E, Westenbrink BD, van der Meer P, et al.: Low-dose erythropoietin improves cardiac function in experimental heart failure without increasing haematocrit. Eur J Heart Fail 2008, 10:22–29.

    Article  PubMed  CAS  Google Scholar 

  45. Nishiya D, Omura T, Shimada K, et al.: Effects of erythropoietin on cardiac remodeling after myocardial infarction. J Pharmacol Sci 2006, 101:31–39.

    Article  PubMed  CAS  Google Scholar 

  46. Li Y, Takemura G, Okada H, et al.: Reduction of inflammatory cytokine expression and oxidative damage by erythropoietin in chronic heart failure. Cardiovasc Res 2006, 71:684–694.

    Article  PubMed  CAS  Google Scholar 

  47. Lipsic E, Schoemaker RG, van der Meer P, et al.: Protective effects of erythropoietin in cardiac ischemia: from bench to bedside. J Am Coll Cardiol 2006, 48:2161–2167.

    Article  PubMed  CAS  Google Scholar 

  48. Asaumi Y, Kagaya Y, Takeda M, et al.: Protective role of endogenous erythropoietin system in nonhematopoietic cells against pressure overload-induced left ventricular dysfunction in mice. Circulation 2007, 115:2022–2032.

    Article  PubMed  CAS  Google Scholar 

  49. 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.

    Article  PubMed  CAS  Google Scholar 

  50. Jelkmann W: Erythropoietin after a century of research: younger than ever. Eur J Haematol 2007, 78:183–205.

    Article  PubMed  CAS  Google Scholar 

  51. Palazzuoli A, Silverberg D, Iovine F, et al.: Erythropoietin improves anemia exercise tolerance and renal function and reduces B-type natriuretic peptide and hospitalization in patients with heart failure and anemia. Am Heart J 2006, 152:1096.e9–1096.e15.

    Article  Google Scholar 

  52. Palazzuoli A, Silverberg DS, Iovine F, et al.: Effects of betaerythropoietin treatment on left ventricular remodeling, systolic function, and B-type natriuretic peptide levels in patients with the cardiorenal anemia syndrome. Am Heart J 2007, 154:645.e9–645.e15.

    Article  Google Scholar 

  53. Zilberman M, Silverberg DS, Bits I, et al.: Improvement of anemia with erythropoietin and intravenous iron reduces sleep-related breathing disorders and improves daytime sleepiness in anemic patients with congestive heart failure. Am Heart J 2007, 154:870–876.

    Article  PubMed  CAS  Google Scholar 

  54. Kourea K, Parissis JT, Farmakis D, et al.: Effects of darbepoetin-alpha on plasma pro-inflammatory cytokines, anti-inflammatory cytokine interleukin-10 and soluble Fas/Fas ligand system in anemic patients with chronic heart failure. Atherosclerosis 2007 Nov 6 (Epub ahead of print).

  55. van Veldhuisen DJ, Dickstein K, Cohen-Solal A, et al.: Randomized, double-blind, placebo-controlled study to evaluate the effect of two dosing regimens of darbepoetin alfa in patients with heart failure and anaemia. Eur Heart J 2007, 28:2208–2216.

    Article  PubMed  Google Scholar 

  56. Ponikowski P, Anker SD, Szachniewicz J, et al.: Effect of darbepoetin alfa on exercise tolerance in anemic patients with symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol 2007, 49:753–762.

    Article  PubMed  CAS  Google Scholar 

  57. Ghali JK, Anand IS, Abraham WT, et al.: Randomized double-blind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia. Circulation 2008, 117:526–535.

    Article  PubMed  CAS  Google Scholar 

  58. Young JB, Anand IS, Diaz R, et al.: Reduction of Events With Darbepoetin Alfa in Heart Failure (RED-HF) trial [abstract]. J Card Fail 2006, 12(Suppl 1):S77.

    Article  Google Scholar 

  59. Okonko DO, Grzeslo A, Witkowski T, et al.: Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency: FERRIC-HF: a randomized, controlled, observer-blinded trial. J Am Coll Cardiol 2008, 51:103–112.

    Article  PubMed  CAS  Google Scholar 

  60. Bolger AP, Bartlett FR, Penston HS, et al.: Intravenous iron alone for the treatment of anemia in patients with chronic heart failure. J Am Coll Cardiol 2006, 48:1225–1227.

    Article  PubMed  CAS  Google Scholar 

  61. Toblli JE, Lombrana A, Duarte P, Di Gennaro F: Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency. J Am Coll Cardiol 2007, 50:1657–1665.

    Article  PubMed  CAS  Google Scholar 

  62. Beck-da-Silva L, Rohde LE, Pereira-Barretto AC, et al.: Rationale and design of the IRON-HF study: a randomized trial to assess the effects of iron supplementation in heart failure patients with anemia. J Card Fail 2007, 13:14–17.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University Health Center, Wayne State University, 2E, 4201 St. Antoine, Detroit, MI, 48201, USA

    Jalal K. Ghali

Authors
  1. Haroon A. Faraz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Syed F. Zafar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jalal K. Ghali
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jalal K. Ghali.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Faraz, H.A., Zafar, S.F. & Ghali, J.K. Anemia and the potential role of erythropoiesis-stimulating agents in heart failure. Curr Heart Fail Rep 5, 83–90 (2008). https://doi.org/10.1007/s11897-008-0014-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11897-008-0014-0

Keywords

Search

Navigation