Skip to content
BY-NC-ND 3.0 license Open Access Published by De Gruyter Open Access December 16, 2010

Anaemia and heart failure

Enrico Vizzardi, Tania Bordonali, Elena Tanghetti, Marco Metra and Livio Cas
From the journal Open Medicine

Abstract

Anaemia is one of the most frequent co-morbidities in patients with heart failure. Its prevalence increases from 4% to7% in subjects with asymptomatic left ventricular dysfunction to >30% in patients with severe heart failure. Renal insufficiency, activation of inflammatory mediators and treatment with renin-angiotensin antagonists seem to be its main determinants. The results of many studies agree in providing evidence that anaemia is a powerful independent determinant of survival in patients with heart failure. However, the mechanisms of this relation are still not fully understood. Moreover a favourable effect of the correction of anaemia on prognosis has not yet been shown. Also In addition to this, controlled studies assessing its effects on exercise tolerance have yielded controversial results. Further research is needed to assess the effect of correcting anaemia in chronic heart failure (CHF) patients; ongoing reduction of events with RED-HF (Darbepoetin alpha in heart failure) trial will help define the role.

[1] KDOQI; National Kidney Foundation. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anaemia in Chronic Kidney Disease. Am J Kidney Dis. 2006;47(5 Suppl 3):S11–145 10.1053/j.ajkd.2006.03.011Search in Google Scholar

[2] Felker GM, Adams KF Jr, Gattis WA, O’Connor CM. Anaemia as a risk factor and therapeutic target in heart failure. J Am Coll Cardiol. 2004;44:959–966 http://dx.doi.org/10.1016/j.jacc.2004.05.07010.1016/j.jacc.2004.05.070Search in Google Scholar

[3] Yi-Da Tang, Katz SD. Anaemia in chronic heart failure. Circulation 2006;113:2454–2461 http://dx.doi.org/10.1161/CIRCULATIONAHA.105.58366610.1161/CIRCULATIONAHA.105.583666Search in Google Scholar

[4] Go AS, Yang J, Ackerson LM, Lepper K, Robbins S, Massie BM, Shlipak MG. Hemoglobin level, chronic kidney disease, and the risks of death and hospitalization in adults with chronic heart failure: the Anaemia in Chronic Heart Failure: Outcomes and Resource Utilization (ANCHOR) Study. Circulation. 2006;113:2713–2723 http://dx.doi.org/10.1161/CIRCULATIONAHA.105.57757710.1161/CIRCULATIONAHA.105.577577Search in Google Scholar

[5] Young JB, Abraham WT, Albert NM, et al. Relation of low hamoglobin and anaemia to morbidity and mortality in patients hospitalized with heart failure (insight from the OPTIMIZE-HF registry). Am J Cardiol 2008; 101: 223–230 http://dx.doi.org/10.1016/j.amjcard.2007.07.06710.1016/j.amjcard.2007.07.067Search in Google Scholar

[6] Al-Ahmad A, Rand WM, Manjunath G, et al. Reduced kidney function and anaemia as risk factors for mortality in patients with left ventricular dysfunction. J Am Coll Cardiol 2001;38:955–962 http://dx.doi.org/10.1016/S0735-1097(01)01470-X10.1016/S0735-1097(01)01470-XSearch in Google Scholar

[7] Komajda M, Anker SD, Charleswoth 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 http://dx.doi.org/10.1093/eurheartj/ehl01210.1093/eurheartj/ehl012Search in Google Scholar

[8] O’Meara E, Clayton T, McEntegart MB, et al. Clinical correlates and consequences of anaemia 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 http://dx.doi.org/10.1161/CIRCULATIONAHA.105.58257710.1161/CIRCULATIONAHA.105.582577Search in Google Scholar

[9] Horwich TB, Fonarow GC, Hamilton MA, MacLeallan WR, Borenstein J. Anaemia is associated with worse symptoms, greater impairment in functional capacity and significant increase in mortality in patients with advanced heart failure. J Am Coll Cardiol 2002;39:1780–1786 http://dx.doi.org/10.1016/S0735-1097(02)01854-510.1016/S0735-1097(02)01854-5Search in Google Scholar

[10] Mozaffarian D, Nye R, Levy WC. Anaemia predicts mortality in severe heart failure: The prospective randomized amlodipine survival evaluation (PRAISE). J Am Coll Cardiol 2004; 93:1055–1057 Search in Google Scholar

[11] Anand IS, Kuskoski MA, Rector T, et al. Anaemia 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 http://dx.doi.org/10.1161/CIRCULATIONAHA.104.51298810.1161/CIRCULATIONAHA.104.512988Search in Google Scholar PubMed

[12] Tang WHW, Tong W, Jain A, et al. Evaluation and long-termprognosis of new onset, transient, and persistent anaemia in ambulatory patients with chronic heart failure. J Am Coll Cardiol 2008; 51:569–576 http://dx.doi.org/10.1016/j.jacc.2007.07.09410.1016/j.jacc.2007.07.094Search in Google Scholar PubMed

[13] Ishani A, Weinhandl E, Zhao Z, et al. Angiotensinconverting enzyme inhibitor as a risk factor for the development of anaemia, and the impact of incident anaemia on mortality in patients with left ventricular dysfunction. J Am Coll Cardiol 2005; 45:391–399 http://dx.doi.org/10.1016/j.jacc.2004.10.03810.1016/j.jacc.2004.10.038Search in Google Scholar PubMed

[14] Maggioni AP, Opasich C, Anand I et al. Anaemia in patients with heart failure: prevalence and prognostic role in a controlled trial and in clinical practice. J Card Fail 2005; 11(2): 91–98 http://dx.doi.org/10.1016/j.cardfail.2004.05.00410.1016/j.cardfail.2004.05.004Search in Google Scholar PubMed

[15] 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 http://dx.doi.org/10.1093/eurheartj/ehl41910.1093/eurheartj/ehl419Search in Google Scholar PubMed

[16] Androne AS, Katz SD, Lund L, LaManca J, Hudaihed A, Hryniewicz K, Mancini DM. Hemodilution is common in patients with advanced heart failure. Circulation. 2003;107:226–229 http://dx.doi.org/10.1161/01.CIR.0000052623.16194.8010.1161/01.CIR.0000052623.16194.80Search in Google Scholar

[17] Adlbrechtl C, Kommata S, Hülsmann M et all. Chronic heart failure leads to an expanded plasma volume and pseudoanaemia, but does not lead to a reduction in the body’s red cell volume. Eur Heart J (2008). 29: 2343–2350 http://dx.doi.org/10.1093/eurheartj/ehn35910.1093/eurheartj/ehn359Search in Google Scholar PubMed

[18] De Silva R, Rigby AS, Witte KK, et al. Anaemia, renal dysfunction, and their interaction in patients with chronic heart failure. Am J Cardiol 2006;98:391–398 http://dx.doi.org/10.1016/j.amjcard.2006.01.10710.1016/j.amjcard.2006.01.107Search in Google Scholar PubMed

[19] Nanas JN, Matsouka C, Karageorgopoulos D, et al. Etiology of anaemia in patients with advanced heart failure. J Am Coll Cardiol 2006;48:2485–2489 http://dx.doi.org/10.1016/j.jacc.2006.08.03410.1016/j.jacc.2006.08.034Search in Google Scholar PubMed

[20] Weiss G, Goodnough LT. Anaemia of chronic disease. N Engl J Med. 2005;352:1011–1023 http://dx.doi.org/10.1056/NEJMra04180910.1056/NEJMra041809Search in Google Scholar PubMed

[21] Westenbrink BD, Voors AA, van Veldhuisen DJ. Is anaemia in chronic heart failure caused by iron deficiency? J Am Coll Cardiol. 2007;49:2301–2302 http://dx.doi.org/10.1016/j.jacc.2007.04.00310.1016/j.jacc.2007.04.003Search in Google Scholar PubMed

[22] Bolger AP, Bartlett FR, Penston HS, O’Leary J, Pollock N, Kaprielian R, Chapman CM. Intravenous iron alone for the treatment of anaemia in patients with chronic heart failure. J Am Coll Cardiol. 2006;48:1225–1227 http://dx.doi.org/10.1016/j.jacc.2006.07.01510.1016/j.jacc.2006.07.015Search in Google Scholar

[23] Anand IS. Anaemia and Chronic Heart Failure J Am Coll Cardiol. 2008;52:501–511 http://dx.doi.org/10.1016/j.jacc.2008.04.04410.1016/j.jacc.2008.04.044Search in Google Scholar

[24] 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 http://dx.doi.org/10.1016/0002-9149(94)90905-910.1016/0002-9149(94)90905-9Search in Google Scholar

[25] Van der Meer P, Voors AA, Lipsic E, Smilde TD, van Gilst WH, van Veldhuisen DJ. Prognostic value of plasma erythropoietin on mortality in patients with chronic heart failure. J Am Coll Cardiol. 2004;44:63–67 http://dx.doi.org/10.1016/j.jacc.2004.03.05210.1016/j.jacc.2004.03.052Search in Google Scholar PubMed

[26] 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 http://dx.doi.org/10.1001/archinte.165.11.130410.1001/archinte.165.11.1304Search in Google Scholar PubMed

[27] 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 http://dx.doi.org/10.1093/eurheartj/ehi38810.1093/eurheartj/ehi388Search in Google Scholar PubMed

[28] MacDougall IC, Cooper AC. Erytropoietin resistance: the role of inflammation and proinflammatory cytokines. Nephrol Dial Transplant 2002;17(suppl11):39–43 10.1093/ndt/17.suppl_11.39Search in Google Scholar PubMed

[29] Mrug M, Stopka T, Julian BA, Prchal JF, Prchal JT. Angiotensin II stimulates proliferation of normal early erythroid progenitors. J Clin Invest. 1997;100:2310–2314 http://dx.doi.org/10.1172/JCI11976910.1172/JCI119769Search in Google Scholar PubMed PubMed Central

[30] Van der Meer P, Lipsic E, Westenbrink BD, et al. Levels of hematopoiesis inhibitor N-acetylseryl-aspartyl-lysyl-proline partially explain the occurrence of anaemia in heart failure. Circulation. 2005;112:1743–1747 http://dx.doi.org/10.1161/CIRCULATIONAHA.105.54912110.1161/CIRCULATIONAHA.105.549121Search in Google Scholar PubMed

[31] Mladenovic J, Adamson JW. Adrenergic modulation of erythropoiesis: in vitro studies of colony-forming cells in normal and polycythaemic man. Br J Haematol. 1984;56:323–332 http://dx.doi.org/10.1111/j.1365-2141.1984.tb03959.x10.1111/j.1365-2141.1984.tb03959.xSearch in Google Scholar PubMed

[32] Ni Z, Morcos S, Vaziri ND. Up-regulation of renal and vascular nitric oxide synthase in iron-deficiency anaemia. Kidney Int 1997;52: 195–201 http://dx.doi.org/10.1038/ki.1997.31910.1038/ki.1997.319Search in Google Scholar

[33] Anand IS, Chandrashekhar Y, Wander GS, Chawla LS. Endothelium-derived relaxing factor is important in mediating the high output state in chronic severe anaemia. J Am Coll Cardiol 1995;25:1402–1407 http://dx.doi.org/10.1016/0735-1097(95)00007-Q10.1016/0735-1097(95)00007-QSearch in Google Scholar

[34] Anand IS, Ferrari R, Kalra GS, Wahi PL, Poole-Wilson PA, Harris PC. Pathogenesis of edema in constrictive pericarditis. Studies of body water and sodium, renal function, hemodynamics, and plasma hormones before and after pericardiectomy. Circulation 1991;83: 1880–1887 10.1161/01.CIR.83.6.1880Search in Google Scholar

[35] Varat MA, Adollph RJ, Fowler NO, Cardiovascular effects of anaemia. Am Heart J 1972; 83:451–526 http://dx.doi.org/10.1016/0002-8703(72)90445-010.1016/0002-8703(72)90445-0Search in Google Scholar

[36] Anand IS, Chandrashekhar Y, Ferrari R, Poole-Wilson PA, Harris PC. Pathogenesis of oedema in chronic severe anaemia: studies of body water and sodium, renal function, haemodynamic variables, and plasma hormones. Br Heart J 1993;70:357–362 http://dx.doi.org/10.1136/hrt.70.4.35710.1136/hrt.70.4.357Search in Google Scholar PubMed PubMed Central

[37] Sharma R, Francis DP, Pitt B, Poole-Wilson PA, Coats AJS, Anker SD. Haemoglobin predicts survival in patients with chronic heart failure: a substudy of the ELITE II trial. Eur Heart J 2004;25:1021–1028 http://dx.doi.org/10.1016/j.ehj.2004.04.02310.1016/j.ehj.2004.04.023Search in Google Scholar PubMed

[38] Ezekowitz JA, McAlister FA, Armstrong PW. Anaemia 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 http://dx.doi.org/10.1161/01.CIR.0000052622.51963.FC10.1161/01.CIR.0000052622.51963.FCSearch in Google Scholar

[39] Brucks S, Little WC, Chao T, Rideman RL, Upadhya B, Wesley-Farrington D, Sane DC. Relation of anaemia to diastolic heart failure and the effect on outcome. Am J Cardiol. 2004;93:1055–10457 http://dx.doi.org/10.1016/j.amjcard.2003.12.06210.1016/j.amjcard.2003.12.062Search in Google Scholar PubMed

[40] Bansal N, Tighiouart H, Weiner D, Griffith J, Vlagopoulos P, Salem D, Levin A, Sarnak MJ. Anaemia as a risk factor for kidney function decline in individuals with heart failure. Am J Cardiol. 2007;99:1137–1142 http://dx.doi.org/10.1016/j.amjcard.2006.11.05510.1016/j.amjcard.2006.11.055Search in Google Scholar PubMed

[41] Valeur N, Nielsen OW, McMurray JJ, Torp-Pedersen C, Kober L; TRACE Study Group. 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 http://dx.doi.org/10.1016/j.ejheart.2005.11.01710.1016/j.ejheart.2005.11.017Search in Google Scholar PubMed

[42] Anand I, McMurray JJ, Whitmore J, Warren M, Pham A, McCamish MA, Burton PB. Anaemia and its relationship to clinical outcome in heart failure. Circulation. 2004;110:149–154 http://dx.doi.org/10.1161/01.CIR.0000134279.79571.7310.1161/01.CIR.0000134279.79571.73Search in Google Scholar

[43] Mancini DM, Katz SD, Lang CC, LaManca J, Hudaihed A, Androne A-S. Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure. Circulation 2003;107:294–299 http://dx.doi.org/10.1161/01.CIR.0000044914.42696.6A10.1161/01.CIR.0000044914.42696.6ASearch in Google Scholar

[44] Silverberg DS, Wexler D, Blum M, et al. The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anaemia 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 http://dx.doi.org/10.1016/S0735-1097(00)00613-610.1016/S0735-1097(00)00613-6Search in Google Scholar

[45] Witte KKA, Desilva R, Chattopadhyay S, Ghosh J, Cleland JGF, Clark AL. Are hematinic deficiencies the cause of anaemia in chronic heart failure? Am Heart J 2004;147:924–930 http://dx.doi.org/10.1016/j.ahj.2003.11.00710.1016/j.ahj.2003.11.007Search in Google Scholar

[46] Kosiborod M, Smith GL, Radford MJ et al. The prognostic importance of anaemia in patients with heart failure. Am J Med 2003; 114(2): 112–119 http://dx.doi.org/10.1016/S0002-9343(02)01498-510.1016/S0002-9343(02)01498-5Search in Google Scholar

[47] Sarnak MJ, Tighiouart H, Manjunath G, MacLeod B, Griffith J, Salem D, Levey AS. Anaemia as a risk factor for cardiovascular disease in the Atherosclerosis Risk in Communities (ARIC) study. J Am Coll Cardiol 2002;40:27–33 http://dx.doi.org/10.1016/S0735-1097(02)01938-110.1016/S0735-1097(02)01938-1Search in Google Scholar

[48] Pascual-Figal D.A., Bonaque J.C., Redondo B. et al. Red blood cell distribution width predicts longterm out come regardless of anaemia status in acute heart failure patients. Eur J Heart Fail 2009; 11: 840–846 http://dx.doi.org/10.1093/eurjhf/hfp10910.1093/eurjhf/hfp109Search in Google Scholar PubMed

[49] Amin MG, Tighiouart H, Weiner DE, Stark PC, Griffith JL, MacLeod B, Salem DN, Sarnak MJ. Hematocrit and left ventricular mass: the Framingham Heart Study. J Am Coll Cardiol 2004;43:1276–1282 http://dx.doi.org/10.1016/j.jacc.2003.10.04810.1016/j.jacc.2003.10.048Search in Google Scholar PubMed

[50] Parfrey PS, Foley RN, Wittreich BH, Sullivan DJ, Zagari MJ, Frei D. Double-blind comparison of full and partial anaemia correction in incident hemodialysis patients without symptomatic heart disease. J Am Soc Nephrol. 2005;16:2180–2189 http://dx.doi.org/10.1681/ASN.200412103910.1681/ASN.2004121039Search in Google Scholar PubMed

[51] Roger SD, McMahon LP, Clarkson A, et al. Effects of early and late intervention with epoetin alpha on left ventricular mass among patients with chronic kidney disease (stage 3 or 4): results of a randomized clinical trial. J Am Soc Nephrol. 2004;15:148–156 http://dx.doi.org/10.1097/01.ASN.0000102471.89084.8B10.1097/01.ASN.0000102471.89084.8BSearch in Google Scholar

[52] Levin A, Djurdjev O, Thompson C, et al. Canadian randomized trial of hemoglobin maintenance to prevent or delay left ventricular mass growth in patients with CKD. Am J Kidney Dis. 2005;46:799–811 http://dx.doi.org/10.1053/j.ajkd.2005.08.00710.1053/j.ajkd.2005.08.007Search in Google Scholar

[53] Ritz E, Laville M, Bilous RW, et al. Target level for hemoglobin correction in patients with diabetes and CKD: primary results of the Anaemia Correction in Diabetes (ACORD) Study. Am J Kidney Dis. 2007;49:194–207 http://dx.doi.org/10.1053/j.ajkd.2006.11.03210.1053/j.ajkd.2006.11.032Search in Google Scholar

[54] Drueke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anaemia. N Engl J Med. 2006;355:2071–2084 http://dx.doi.org/10.1056/NEJMoa06227610.1056/NEJMoa062276Search in Google Scholar

[55] O’Meara E, Clayton T, McEntegart MB, et al. Clinical correlates and consequences of anaemia 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 http://dx.doi.org/10.1161/CIRCULATIONAHA.105.58257710.1161/CIRCULATIONAHA.105.582577Search in Google Scholar

[56] Kalra PR, Bolger AP, Francis DP, et al. Effect of anaemia on exercise tolerance in chronic heart failure in men. Am J Cardiol. 2003;91:888–891 http://dx.doi.org/10.1016/S0002-9149(03)00030-410.1016/S0002-9149(03)00030-4Search in Google Scholar

[57] Rocca P, Metra M, Nodari S, et al. L’anaemia è associata con una ridotta capacità funzionale ed un’elevata incidenza d’ospedalizzazioni nei pazienti con insufficienza cardiaca. Ital Heart J 2003; 4(Suppl 6):80S Search in Google Scholar

[58] Metra M, Cannella G, La Canna G, Guaini T, Gaggiotti M, Movilli E, Dei Cas L. Improvement in exercise capacity after correction of anaemia in patients with end-stage renal failure. Am J Cardiol. 1991;68:1060–1066 http://dx.doi.org/10.1016/0002-9149(91)90496-810.1016/0002-9149(91)90496-8Search in Google Scholar

[59] 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 http://dx.doi.org/10.1016/j.jacc.2006.11.02410.1016/j.jacc.2006.11.024Search in Google Scholar PubMed

[60] Anker SD, Coats AJ. Cardiac cachexia: a syndrome with impaired survival and immune and neuroendocrine activation. Chest 1999;115: 836–847 http://dx.doi.org/10.1378/chest.115.3.83610.1378/chest.115.3.836Search in Google Scholar PubMed

[61] Practice Guidelines for blood component therapy: a report by the Am Society of Anesthesiologists Task Force on Blood Component Therapy. Anesthesiology 1996;84:732–747 10.1097/00000542-199603000-00032Search in Google Scholar

[62] Wu WC, Rathore SS, Wang Y, Radford MJ, Krumholz HM. Blood transfusion in elderly patients with acute myocardial infarction. N Engl J Med 2001;334:1230–1236 http://dx.doi.org/10.1056/NEJMoa01061510.1056/NEJMoa010615Search in Google Scholar PubMed

[63] Herbert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care: Critical Care Trials Group. N Engl J Med. 1999, 340:409–417 http://dx.doi.org/10.1056/NEJM19990211340060110.1056/NEJM199902113400601Search in Google Scholar

[64] Goodnough LT, Brecher ME, Kanter MH, Aubuchon JP. Transfusion medicine: first of two parts-blood transfusion. N Engl J Med 1999;340:438–447 http://dx.doi.org/10.1056/NEJM19990211340060610.1056/NEJM199902113400606Search in Google Scholar

[65] Drueke T, Witko-Sarsat V, Massy Z et al. Iron therapy, advanced oxidation protein products, and carotid artery intima-media thickness in end-stage renal disease. Circulation 2002; 106: 2212–2217 http://dx.doi.org/10.1161/01.CIR.0000035250.66458.6710.1161/01.CIR.0000035250.66458.67Search in Google Scholar

[66] Usmanov RI, Zueva EB, Silverberg DS, Shaked M. Intravenous iron without erythropoietin for the treatment of iron deficiency anaemia in patients with moderate to severe congestive heart failure and chronic kidney insufficiency. J Nephrol 2008; 21:236–242 Search in Google Scholar

[67] Toblli JE, Lombrana A, Duarte P, Di Gennaro F. Intravenous iron reduces NTpro- brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency. J Am Coll Cardiol 2007; 50:1657–1665 http://dx.doi.org/10.1016/j.jacc.2007.07.02910.1016/j.jacc.2007.07.029Search in Google Scholar

[68] 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: FERRICHF — a randomized, controlled, observer-blinded trial. J Am Coll Cardiol 2008; 51: 103–112 http://dx.doi.org/10.1016/j.jacc.2007.09.03610.1016/j.jacc.2007.09.036Search in Google Scholar

[69] Silverberg DS, Wexler D, Sheps D, et al. The effect of correction of mild anaemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study. J Am Coll Cardiol. 2001;37:1775–1780 http://dx.doi.org/10.1016/S0735-1097(01)01248-710.1016/S0735-1097(01)01248-7Search in Google Scholar

[70] Palazzuoli A, Silverberg DS, Iovine F, et al. Effects of beta-erythropoietin treatment on left ventricular remodeling, systolic function, and B-type natriuretic peptide levels in patients with the cardiorenal anaemia syndrome. Am Heart J 2007;154:645 e 9–645 e 15 http://dx.doi.org/10.1016/j.ahj.2007.07.02210.1016/j.ahj.2007.07.022Search in Google Scholar PubMed

[71] Van Veldhuisen DJ, McMurray JJ; RED-HF Executive Committee. 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 http://dx.doi.org/10.1016/j.ejheart.2007.01.00410.1016/j.ejheart.2007.01.004Search in Google Scholar PubMed

[72] 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 http://dx.doi.org/10.1093/eurheartj/ehm32810.1093/eurheartj/ehm328Search in Google Scholar PubMed

[73] Ghali JK, Anand IS, Abraham WT, et al. Randomized double-blind trial of darbepoetin alfa in patients with symptomatic heart failure and anaemia. Circulation 2008;117:526–535 http://dx.doi.org/10.1161/CIRCULATIONAHA.107.69851410.1161/CIRCULATIONAHA.107.698514Search in Google Scholar PubMed

[74] Singh AK, Szczech L, Tang KL, et al. Correction of anaemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006;355:2085–2098 http://dx.doi.org/10.1056/NEJMoa06548510.1056/NEJMoa065485Search in Google Scholar

[75] Drüeke TB, Locatelli F, Clyne N, et al.. Normalization of haemoglobin level in patients with chronic kidney disease and anaemia. N Engl J Med. 2006;355:2071–2084 http://dx.doi.org/10.1056/NEJMoa06227610.1056/NEJMoa062276Search in Google Scholar

[76] Fishbane S, Nissenson AR. The new FDA label for erythropoietin treatment: How does it affect hemoglobin target? Kidney Int advance online publication, 27 June 2007; doi:10.1038/sj.ki. 5002401 Search in Google Scholar

[77] Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 1998;339:584–590 http://dx.doi.org/10.1056/NEJM19980827339090310.1056/NEJM199808273390903Search in Google Scholar

[78] Fuste B, Serradell M, Escolar G, Cases A, Mazzara R, Castillo R, Ordinas A, Diaz-Ricard M. Erythropoietin triggers a signaling pathway in endothelial cells and increases the thrombogenicity of their extra-cellular matrices in vitro. Thromb Haemost 2002;88:678–685 10.1055/s-0037-1613275Search in Google Scholar

[79] Jin B., Luo X., Lin H., Li J.et al. A meta-analysis of erythropoiesis-stimulating agents in anaemic patients with chronic heart failure. European Journal of Heart Failure 2010, 12: 249–253 http://dx.doi.org/10.1093/eurjhf/hfp18210.1093/eurjhf/hfp182Search in Google Scholar

[80] Latini R., Brines M., Fiordaliso F. Do nonhemopoietic effects of erythropoietin play a beneficial role in heart failure? Heart Fail Rev (2008) 13:415–423 http://dx.doi.org/10.1007/s10741-008-9084-z10.1007/s10741-008-9084-zSearch in Google Scholar

[81] Al Ahmad A, Rand WM, Manjunath G, et al. Reduced kidney function and anaemia as risk factors for mortality in patients with left ventricular dysfunction. J Am Coll Cardiol 2001;38:955–962 http://dx.doi.org/10.1016/S0735-1097(01)01470-X10.1016/S0735-1097(01)01470-XSearch in Google Scholar

[82] Horwich TB, Fonarow GC, Hamilton MA, et al. Anaemia 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 http://dx.doi.org/10.1016/S0735-1097(02)01854-510.1016/S0735-1097(02)01854-5Search in Google Scholar

[83] Tanner H, Moschovitis G, Kuster GM, et al. The prevalence of anaemia in chronic heart failure. Int J Cardiol 2002;86:115–121 http://dx.doi.org/10.1016/S0167-5273(02)00273-510.1016/S0167-5273(02)00273-5Search in Google Scholar

[84] Ezekowitz JA, McAlister FA, Armstrong PW. Anaemia 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 http://dx.doi.org/10.1161/01.CIR.0000052622.51963.FC10.1161/01.CIR.0000052622.51963.FCSearch in Google Scholar PubMed

[85] Kosborod M, Smith GL, Radford MJ, et al. The prognostic importance of anaemia in patients with heart failure. Am J Med 2003;114:112–119 http://dx.doi.org/10.1016/S0002-9343(02)01498-510.1016/S0002-9343(02)01498-5Search in Google Scholar

[86] Mozaffarian D, Nye R, Levy WC. Anaemia predicts mortality in severe heart failure: the Prospective Randomized Amlodipine Survival Evaluation (PRAISE). J Am Coll Cardiol 2003;41:1933–1939 http://dx.doi.org/10.1016/S0735-1097(03)00425-X10.1016/S0735-1097(03)00425-XSearch in Google Scholar

[87] Felker GM, Gattis WA, Leimberger JD, et al. Usefulness of anaemia as a predictor of death and rehospitalization in patients with decompensated heart failure. Am J Cardiol 2003;92:625–628 http://dx.doi.org/10.1016/S0002-9149(03)00740-910.1016/S0002-9149(03)00740-9Search in Google Scholar

[88] McClellan WM, Flanders WD, Langston RD, et al. Anaemia 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 http://dx.doi.org/10.1097/01.ASN.0000018409.45834.FA10.1097/01.ASN.0000018409.45834.FASearch in Google Scholar

[89] Szachniewicz J, Petruk-Kowalczyk J, Majda J, et al. Anaemia is an independent predictor of poor outcome in patients with chronic heart failure. Int J Cardiol 2003;90:303–308 http://dx.doi.org/10.1016/S0167-5273(02)00574-010.1016/S0167-5273(02)00574-0Search in Google Scholar

[90] Brucks S, Little WC, Chao T, et al. Relation of anaemia to diastolic heart failure and the effect on outcome. Am J Cardiol 2004;93: 1055–1057. http://dx.doi.org/10.1016/j.amjcard.2003.12.06210.1016/j.amjcard.2003.12.062Search in Google Scholar PubMed

[91] Felker GM, Shaw LK, Stough WG, et al. Anaemia in patients with heart failure and preserved systolic function. Am Heart J 2006; 151: 45–62 10.1016/j.ahj.2005.03.056Search in Google Scholar PubMed

[92] Tehrani F, Phan A, Morrissey R, et al, Prognostic value of anaemia in patients with diastolic heart failure. Tex Heart Inst J 2009; 36: 220–225. 10.1002/clc.20615Search in Google Scholar PubMed PubMed Central

[93] Shamagian LG, Roman AV, 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 http://dx.doi.org/10.1136/hrt.2005.06439410.1136/hrt.2005.064394Search in Google Scholar PubMed PubMed Central

[94] Parsa CJ, Matsumoto A, Kim J, et al. A novel protective effect of erythropoietin in the infracted heart. J Clin Invest. 2003;112:999–1007 10.1172/JCI18200Search in Google Scholar PubMed PubMed Central

[95] 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 http://dx.doi.org/10.1016/j.jacc.2005.03.04410.1016/j.jacc.2005.03.044Search in Google Scholar PubMed

[96] Lipsic E, Schoemaker RG, van der Meer P, Voors AA, van Veldhuisen DJ, van Gilst WH. Protective effects of erythropoietin in cardiac ischemia: from bench to bedside. J Am Coll Cardiol. 2006;48:2161–2167 http://dx.doi.org/10.1016/j.jacc.2006.08.03110.1016/j.jacc.2006.08.031Search in Google Scholar PubMed

[97] 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; [Epub ahead of print] 10.1093/eurheartj/ehm177Search in Google Scholar PubMed

[98] Leist M, Ghezzi P, Grasso G, Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science. 2004 Jul 9;305(5681):239–242 http://dx.doi.org/10.1126/science.109831310.1126/science.1098313Search in Google Scholar PubMed

[99] Fiordaliso F, Chimenti S, Staszewsky L, et al. A nonerythropoietic derivative of erythropoietin protects the myocardium from ischemiareperfusion injury. Proc Natl Acad Sci U S A. 2005; 102:2046–2051 http://dx.doi.org/10.1073/pnas.040932910210.1073/pnas.0409329102Search in Google Scholar PubMed PubMed Central

Published Online: 2010-12-16
Published in Print: 2011-2-1

© 2010 Versita Warsaw

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Scroll Up Arrow