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Anemia and heart failure

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Abstract

Over the past few years, anemia has emerged as a powerful independent predictor of adverse outcomes in chronic heart failure (CHF). It affects up to 50% of patients with CHF, depending on the definition of anemia used and on the population studied. Even small reductions in hemoglobin are associated with worse outcome. However, the causes of anemia in CHF remain unclear, although impairment of renal function and inflammatory cytokines are proposed mechanisms. Both may act through impairment of the synthesis or action of erythropoietin. Preliminary studies have demonstrated improvement in symptoms, exercise tolerance, quality of life, and reductions in hospitalizations when patients with severe CHF were treated with erythropoietin. The benefits and the potential risks of such therapies will be further addressed in upcoming larger randomized trials. The recent interest in anemia reflects a new perspective in heart failure therapy, focusing on noncardiovascular comorbidities.

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References and Recommended Reading

  1. Mozaffarian D, Nye R, Levy WC: Anemia predicts mortality in severe heart failure. The Prospective Randomized Amlodipine Survival Evaluation (PRAISE). J Am Coll Cardiol 2003, 41:1933–1939. This is an in-depth multivariable analysis showing the independent prognostic effect of hemoglobin (and hematocrit) on mortality in severe CHF. The relationship between hemoglobin and cause of death in CHF is also examined.

    Article  PubMed  Google Scholar 

  2. CIBIS II Investigators and Committees: The Cardiac Insufficiency Bisoprolol Study II (CIBIS II). Lancet 1999, 353:9–13.

    Article  Google Scholar 

  3. Hjalmarson A, Goldstein S, Fagerberg B, et al.: Effects of controlled-release metoprolol in total mortality, hospitalizations, and well-being in patients with heart failure. JAMA 2000, 283:1295–1302.

    Article  PubMed  CAS  Google Scholar 

  4. Packer M, Coats AJS, Fowler MB, et al.: Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001, 344:1651–1658.

    Article  PubMed  CAS  Google Scholar 

  5. Pitt B, Zannad F, Remme WJ, et al.: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999, 341:709–717.

    Article  PubMed  CAS  Google Scholar 

  6. Granger CB, McMurray JJ, Yusuf S, et al.: Effects of candesartan in patients with chronic heart failure and reduced leftventricular systolic function intolerant to angiotensinconverting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003, 362:772–776.

    Article  PubMed  CAS  Google Scholar 

  7. McMurray JJ, Ostergren J, Swedberg K, et al.: Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003, 362:767–771.

    Article  PubMed  CAS  Google Scholar 

  8. Yusuf S, Pfeffer MA, Swedberg K, et al.: Effects of candesartan in patients with chronic heart failure and preserved leftventricular ejection fraction: the CHARM-Preserved trial. Lancet 2003, 362:777–781.

    Article  PubMed  CAS  Google Scholar 

  9. Pfeffer MA, Swedberg K, Granger CB, et al.: Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003, 362:759–766.

    Article  PubMed  CAS  Google Scholar 

  10. McMurray J, Östergren J, Pfeffer M, et al.: Clinical features and contemporary management of patients with low and preserved ejection fraction heart failure: baseline characteristics of patients in the Candesartan in Heart Failure--Assessment of Reduction in Mortality and Morbidity (CHARM) programme. Eur J Heart Fail 2003, 5:261–270.

    Article  PubMed  CAS  Google Scholar 

  11. Silverberg D, Wexler D, Sheps D, et al.: Prevalence of anemia in patients admitted to hospital with a primary diagnosis of congestive heart failure. Int J Cardiol 2004, 96:79–87.

    Article  PubMed  Google Scholar 

  12. Horwich TB, Fonarow GC, Hamilton MA, et al.: Anemia is associated with worse symptoms, greater impairment in functional capacity and a significant increase in mortality in patients with advanced heart failure. J Am Coll Cardiol 2002, 39:1780–1786. In this study, a large cohort of patients (1061) was referred for heart transplant evaluation. Factors associated with decreased hemoglobin were examined. Even slight reductions in hemoglobin are associated with more CHF symptoms, poorer functional status, and reduced survival.

    Article  PubMed  Google Scholar 

  13. Anker SD, Sharma R, Fracis D, et al.: Anemia and survival in 3044 patients with chronic heart failure (CHF) in the ELITE II study [abstract]. Circulation 2002, 106(Suppl):2335A.

    Google Scholar 

  14. Al-Ahmad A, Rand WM, Manjunath G, et al.: Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction. J Am Coll Cardiol 2001, 38:955–962. This is an important study of patients with symptomatic and asymptomatic LVSD (from the SOLVD prevention and treatment trials). It demonstrates that reduced renal function and anemia are independent predictors of mortality in CHF.

    Article  PubMed  CAS  Google Scholar 

  15. Kalra PR, Bolger AP, Francis DP, et al.: Effect of anemia on exercise tolerance in chronic heart failure in men. Am J Cardiol 2003, 91:888–891.

    Article  PubMed  Google Scholar 

  16. Kosiborod M, Smith GL, Radford MJ, et al.: The prognostic importance of anemia in patients with heart failure. Am J Med 2003, 114:112–119. This is a large (2281 patients) retrospective analysis of an administrative database of patients (aged older than 65 years) with heart failure who had been admitted to 18 different hospitals in Connecticut. In a multivariate analysis, anemia, defined as a hematocrit of 37% or less, is an independent predictor of death and 1-year readmission in elderly patients.

    Article  PubMed  Google Scholar 

  17. Felker GM, Gattis WA, Leimberger JD, et al.: Usefulness of anemia as a predictor of death and rehospitalization in patients with decompensated heart failure. Am J Cardiol 2003, 92:625–628.

    Article  PubMed  Google Scholar 

  18. McClellan WM, Flanders WD, Langston RD, et al.: Anemia and renal insufficiency are independent risk factors for death among patients with congestive heart failure admitted to community hospitals: a population-based study. J Am Soc Nephrol 2002, 13:1928–1936.

    Article  PubMed  Google Scholar 

  19. Ezekowitz JA, McAlister FA, Armstrong PW: Anemia is common in heart failure and is associated with poor outcomes. Insights from a cohort of 12,065 patients with new-onset heart failure. Circulation 2003, 107:223–225. In this study, the prevalence of anemia and its predictors were examined in a very large, state-wide, administrative database of patients hospitalized with heart failure in Alberta, Canada. Anemia also independently predicts mortality in this population setting.

    Article  PubMed  Google Scholar 

  20. Silverberg DS, Wexler D, Blum M, et al.: The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations. J Am Coll Cardiol 2000, 35:1737–1744. This is a pioneering study of erythropoietin therapy in a small group of patients with severe CHF that shows improvement in NYHA functional class and renal function, and reduction of hospitalizations and use of diuretics. However, it is limited by an open-label, uncontrolled design and a small sample size.

    Article  PubMed  CAS  Google Scholar 

  21. Tanner H, Moschovitis G, Kuster GM, et al.: The prevalence of anemia in chronic heart failure. Int J Cardiol 2002, 86:115–121.

    Article  PubMed  Google Scholar 

  22. Wexler D, Silverberg D, Sheps D, Iaina A: The importance of correction of anemia with erythropoietin and intravenous iron in severe resistant congestive heart failure. Eur J Heart Fail 2003, 5(Suppl 2):225–230.

    Article  Google Scholar 

  23. Androne AS, Katz SD, Lund L, et al.: Hemodilution is common in patients with advanced heart failure. Circulation 2003, 107:226–229. This is an important study addressing the contribution of hemodilution to the anemia associated with CHF.

    Article  PubMed  Google Scholar 

  24. Hillege HL, Girbes ARJ, de Kam PJ, et al.: Renal function, neurohormonal activation, and survival in patients with chronic heart failure. Circulation 2000, 102:203–210.

    PubMed  CAS  Google Scholar 

  25. Dries DL, Exner DV, Domanski MJ, et al.: The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction. J Am Coll Cardiol 2000, 35:681–689.

    Article  PubMed  CAS  Google Scholar 

  26. Pennell JP: Optimizing medical management of patients with pre-end-stage renal disease. Am J Med 2001, 111:559–568.

    Article  PubMed  CAS  Google Scholar 

  27. Levey AS, Coresh J, Balk E, et al.: National Kidney Foundation Practice Guidelines for Chronic Kidney Disease: evaluation, classification, and stratification. Ann Intern Med 2003, 139:137–147.

    PubMed  Google Scholar 

  28. Redfield MM, Aarhus LL, Wright RS, et al.: Cardiorenal and neurohormonal function in a canine model of early left ventricular dysfunction. Circulation 1993, 87:2016–2022.

    PubMed  CAS  Google Scholar 

  29. Silverberg DS, Wexler D, Blum M, et al.: Erythropoietin should be part of congestive heart failure management. Kid Int 2003, 64(Suppl 87):S40-S47.

    Article  Google Scholar 

  30. Anand IS, Chandrahekhar Y, Ferrari R, et al.: Pathogenesis of edema in chronic anemia: studies of body water and sodium, renal function, hemodynamics and plasma hormones. Br Heart J 1993, 70:357–362.

    PubMed  CAS  Google Scholar 

  31. Levey AS, Bosch JP, Lewis JB, et al.: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 1999, 130:461–470.

    PubMed  CAS  Google Scholar 

  32. Lin J, Knight EL, Hogan ML, et al.: A comparison of prediction equations for estimating glomerular filtration rate in adults without kidney disease. J Am Soc Nephrol 2003, 14:2573–2580.

    Article  PubMed  Google Scholar 

  33. Lamb EJ, Webb MC, Simpson DE, et al.: Estimation of glomerular filtration rate in older patients with chronic renal insufficiency: is the modification of diet in renal disease formula an improvement? J Am Geriatr Soc 2003, 51:1012–1017.

    Article  PubMed  Google Scholar 

  34. Spivak JL: The blood in systemic disorders. Lancet 2000, 355:1707–1712.

    Article  PubMed  CAS  Google Scholar 

  35. Jelkman W, Paget H, Wolff M, et al.: Monokines inhibiting erythropoietin production in human hepatoma cultures and in isolated perfused rat kidneys. Life Sci 1991, 50:301–308.

    Article  Google Scholar 

  36. Means RT, Krantz SB: Progress in understanding the pathogenesis of the anemia of chronic disease. Blood 1992, 80:1639–1647.

    PubMed  Google Scholar 

  37. Pincus T, Olsen N, Russel IJ: Multicenter study of recombinant human erythropoietin in correction of anemia in rheumatoid arthritis. Am J Med 1990, 89:161–168.

    Article  PubMed  CAS  Google Scholar 

  38. 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.

    Article  PubMed  CAS  Google Scholar 

  39. Mancini DM, Katz SD, Lang CC, et al.: Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure. Circulation 2003, 107:294–299. This is an important prospective, randomized, controlled, singleblind study showing a favorable effect of erythropoietin therapy on exercise capacity (and peak oxygen consumption) in a small group of patients with severe CHF and anemia.

    Article  PubMed  CAS  Google Scholar 

  40. Chatterjee B, Nydegger UE, Mohacsi P: Serum erythropoietin in heart failure patients treated with ACE-inhibitors or AT1 antagonists. Eur J Heart Fail 2000, 2:393–398.

    Article  PubMed  CAS  Google Scholar 

  41. Torre-Amione G, Bozkurt B, Deswal A, et al.: An overview of tumor necrosis factor and the failing human heart. Curr Opin Cardiol 1999, 14:206–210.

    Article  PubMed  CAS  Google Scholar 

  42. Rauchhaus M, Doehner W, Francis DP, et al.: Plasma cytokine parameters and mortality in patients with chronic heart failure. Circulation 2000, 102:3060–3067.

    PubMed  CAS  Google Scholar 

  43. Silverberg DS, Wexler D, Iaina A: The importance of anemia and its correction in the management of severe congestive heart failure. Eur J Heart Fail 2002, 4:681–686.

    Article  PubMed  Google Scholar 

  44. Albitar S, Genin R, Fen-Chong M, et al.: High dose enalapril impairs the response to erythropoietin treatment in haemodialysis patients. Nephrol Dial Transplant 1998, 13:1206–1210.

    Article  PubMed  CAS  Google Scholar 

  45. Nomura S, Sasaki T, Kitano Y, et al.: Effects of ACE inhibitor on renal anemia in predialysis patients. Nephron 1996, 73:336–337.

    Article  PubMed  CAS  Google Scholar 

  46. Altun B, Aric M, Yasuval U, et al.: Role of erythropoietin in pathogenesis of post transplant erythrocytosis (PTE) and mechanism of losartan’s efficiency. Nephrol Dial Transplant 1997, 12:626–627.

    Article  PubMed  CAS  Google Scholar 

  47. Julian BA, Brantley RRJ, Barker CV, et al.: Losartan, an angiotensin II type 1 receptor antagonist, lowers hematocrit in post-transplant erythrocytosis. J Am Soc Nephrol 1998, 6:1104–1108.

    Google Scholar 

  48. Ducloux D, Fournier V, Bresson VC, et al.: Long-term follow-up of renal transplant recipients treated with losartan for posttransplant erythrocytosis. Transplant Int 1998, 11:312–315.

    Article  CAS  Google Scholar 

  49. Klaassen RJ, Van Gelder T, Rischen VJ, et al.: Losartan, an angiotensin-II receptor antagonist, reduces hematocrits in kidney transplant recipients with post-transplant erythrocytosis. Transplantation 1997, 64:780–782.

    Article  PubMed  CAS  Google Scholar 

  50. Shiffl H, Lang SM: Angiotensin-converting enzyme inhibitors but not angiotensin II AT1 receptor antagonists affect erythropoiesis in patients with anemia of end-stage renal disease. Nephron 1999, 81:106–108.

    Article  Google Scholar 

  51. Lang SM, Shiffl H: Losartan and anemia of end-stage renal disease. Lancet 1998, 352:1708.

    Article  PubMed  CAS  Google Scholar 

  52. Macdougall IC: The role of ACE inhibitors and angiotensin II receptor blockers in the response to epoietin. Nephrol Dial Transplant 1999, 14:1836–1841.

    Article  PubMed  CAS  Google Scholar 

  53. Metivier F, Marchais SJ, Guerin AP, et al.: Pathophysiology of anemia: focus on the heart and blood vessels. Nephrol Dial Transplant 2000, 15(Suppl 3):14–18.

    PubMed  Google Scholar 

  54. Foley RN, Parfrey PS, Harnett JD, et al.: The impact of anemia on cardiomyopathy, morbidity and mortality in end-stage renal disease. Am J Kidney Dis 1996, 28:53–61.

    PubMed  CAS  Google Scholar 

  55. Levin A, Singer J, Thompson CR, et al.: Prevalent left ventricular hypertrophy in the predialysis population: identifying opportunities for intervention. Am J Kidney Dis 1996, 17:347–354.

    Google Scholar 

  56. Pereira AA, Sarnak MJ: Anemia as a risk factor for cardiovascular disease. Kid Int 2003, 64(Suppl 87):S32-S39.

    Article  Google Scholar 

  57. Stevenson LW, Steimle AE, Fonarow GC, et al.: Improvement in exercise capacity of candidates awaiting heart transplantation. J Am Coll Cardiol 1995, 25:163–170.

    Article  PubMed  CAS  Google Scholar 

  58. Mancini DM, Kunavarapu C: Effect of erythropoietin on exercise capacity in anemic patients with advanced heart failure. Kid Int 2003, 64(Suppl 87):S48-S52.

    Article  Google Scholar 

  59. Silverberg DS, Wexler D, Sheps D, et al.: The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study. J Am Coll Cardiol 2001, 37:1775–1780.

    Article  PubMed  CAS  Google Scholar 

  60. Silverberg DS, Wexler D, Blum M, et al.: The correction of anemia in severe resistant heart failure with erythropoietin and intravenous iron prevents the progression of both the heart and renal failure and markedly reduces hospitalization. Clin Nephrol 2002, 58(Suppl 1):S37-S45.

    PubMed  CAS  Google Scholar 

  61. Silverberg DS, Wexler D, Blum M, et al.: The effect of correction of anemia in diabetic and non diabetics with severe resistant congestive heart failure and chronic renal failure by subcutaneous erythropoietin and intravenous iron. Nephrol Dial Transplant 2003, 18:141–146. This important study suggests that correcting anemia in patients with CHF is beneficial in diabetic and in nondiabetic patients. This is an important finding because anemia is frequent in diabetes and its pathophysiology may not be the same as in CHF.

    Article  PubMed  CAS  Google Scholar 

  62. St Peter WL, Xue J, Ebben J, et al.: Pre-end stage renal disease erythropoietin use predicts hospitalization in the periods before and after end-stage renal disease diagnosis [abstract]. J Am Soc Nephrol 2001, 12(Suppl):1274A.

    Google Scholar 

  63. Rossert J, Fouqueray B, Boffa JJ: Anemia management and the delay of chronic renal failure progression. J Am Soc Nephrol 2003, 14:S173-S177.

    Article  PubMed  Google Scholar 

  64. Smith KJ, Bleyer AJ, Little WC, Sane DC: The cardiovascular effects of erythropoietin. Cardiovasc Res 2003, 59:538–548.

    Article  PubMed  CAS  Google Scholar 

  65. Besarab A, Kline Bolton W, Browne JK, et al.: The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoietin. N Engl J Med 1998, 339:584–590.

    Article  PubMed  CAS  Google Scholar 

  66. Abramowicz M: Darbepoietin (Aranesp)—a long-acting erythropoietin. Med Lett 2001, 43:109–110.

    Google Scholar 

  67. Muirhead N, Laupacis A, Wong C: Erythropoietin for anemia in haemodialysis patients: results of a maintenance study (the Canadian Erythropoietin Study Group). Nephrol Dial Transplant 1992, 7:811–816.

    PubMed  CAS  Google Scholar 

  68. Stohlawetz PJ, Dzirio L, Hergovich N, et al.: Effects of erythropoietin on platelet reactivity and thrombopoiesis in humans. Blood 2000, 95:2983–2989.

    PubMed  CAS  Google Scholar 

  69. Rao M, Pereira BJG: Prospective trials on anemia of chronic disease: the Trial to Reduce Cardiovascular Events with Aranesp (TREAT). Kid Int 2003, 64(Suppl 87):S12-S19.

    Article  Google Scholar 

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  1. Department of Cardiology, Western Infirmary, G11 6NT, Glasgow, UK

    John J. V. McMurray MD

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  1. Eileen O’Meara MD
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  2. Clare Murphy MBChB
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  3. John J. V. McMurray MD
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O’Meara, E., Murphy, C. & McMurray, J.J.V. Anemia and heart failure. Curr Heart Fail Rep 1, 176–182 (2004). https://doi.org/10.1007/s11897-004-0006-7

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