Anemia and Chronic Heart Failure. Implications and Treatment Options

Journal of the American College of Cardiology

Volumn 52, Issue 7, 2008, Pages 501-511

  Anand, Inder S ^a  

^a UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

Author keywords

anemia; chronic kidney disease; erythropoietin; heart failure

Indexed keywords

DIURETIC AGENT; FERRIC HYDROXIDE SUCROSE; FOLIC ACID; HEMOGLOBIN; IRON; NOVEL ERYTHROPOIESIS STIMULATING PROTEIN; RECOMBINANT ERYTHROPOIETIN;

ANEMIA; BLOOD TRANSFUSION; BONE MARROW DEPRESSION; CHRONIC DISEASE; CHRONIC KIDNEY DISEASE; CLINICAL TRIAL; COMORBIDITY; DISEASE COURSE; DISEASE SEVERITY; DRUG MEGADOSE; HEART FAILURE; HEART INFARCTION; HEMODILUTION; HUMAN; HYPERTENSION; KIDNEY DISEASE; NONHUMAN; OUTCOME ASSESSMENT; PATHOPHYSIOLOGY; PREVALENCE; PRIORITY JOURNAL; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; RISK ASSESSMENT;

ANEMIA; BIOLOGICAL MARKERS; BONE MARROW; ERYTHROPOIETIN; FEMALE; HEART FAILURE; HUMANS; INFLAMMATION; IRON COMPOUNDS; KIDNEY FAILURE, CHRONIC; MALE; RECEPTORS, ERYTHROPOIETIN; RISK FACTORS;

EID: 43749089210     PISSN: 07351097     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jacc.2008.04.044     Document Type: Review

References (104)

1. Bardy G.H., Lee K.L., Mark D.B., et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 352 (2005) 225-237
2. Rosamond W., Flegal K., Friday G., et al. Heart disease and stroke statistics-2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 115 (2007) e69-e171
3. Dallman P.R. Iron Nutrition in Health and Disease (1996), John Libbey & Co, Eastleigh, UK
4. Sarnak M.J., Tighiouart H., Manjunath G., et al. Anemia as a risk factor for cardiovascular disease in The Atherosclerosis Risk in Communities (ARIC) study. J Am Coll Cardiol 40 (2002) 27-33
5. Beutler E., and Waalen J. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration?. Blood 107 (2006) 1747-1750
6. Komajda M. Prevalence of anemia in patients with chronic heart failure and their clinical characteristics. J Card Fail 10 (2004) S1-S4
7. Anand I.S. Pathogenesis of anemia in cardiorenal disease. Rev Cardiovasc Med 6 Suppl 3 (2005) S13-S21
8. Tang Y.-D., and Katz S.D. The prevalence of anemia in chronic heart failure and its impact on clinical outcomes. Heart Fail Rev 13 (2008) 387-392
9. Ishani A., Weinhandl E., Zhao Z., et al. Angiotensin-converting 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 45 (2005) 391-399
10. Anand I.S., Kuskowski M.A., Rector T.S., 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 112 (2005) 1121-1127
11. Komajda M., Anker S.D., Charlesworth A., et al. The impact of new onset anaemia on morbidity and mortality in chronic heart failure: results from COMET. Eur Heart J 27 (2006) 1440-1446
12. Nair D., Shlipak M.G., Angeja B., Liu H.H., Schiller N.B., and Whooley M.A. Association of anemia with diastolic dysfunction among patients with coronary artery disease in the Heart and Soul Study. Am J Cardiol 95 (2005) 332-336
13. Felker G.M., Shaw L.K., Stough W.G., and O'Connor C.M. Anemia in patients with heart failure and preserved systolic function. Am Heart J 151 (2006) 457-462
14. Berry C., Norrie J., Hogg K., Brett M., Stevenson K., and McMurray J.J. The prevalence, nature, and importance of hematologic abnormalities in heart failure. Am Heart J 151 (2006) 1313-1321
15. O'Meara E., Clayton T., McEntegart M.B., 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 113 (2006) 986-994
16. Ezekowitz J.A., McAlister F.A., and Armstrong P.W. 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 107 (2003) 223-225
17. 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 26 (2005) 2232-2237
18. Anand I.S., Rector T., Deswal A., et al. Relationship between proinflammatory cytokines and anemia in heart failure. Eur Heart J 27 Suppl 1 (2006) 485
19. Anand I., McMurray J.J., Whitmore J., et al. Anemia and its relationship to clinical outcome in heart failure. Circulation 110 (2004) 149-154
20. Al-Ahmad A., Rand W.M., Manjunath G., et al. Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction. J Am Coll Cardiol 38 (2001) 955-962
21. Horwich T.B., Fonarow G.C., Hamilton M.A., MacLellan W.R., and zjaBorenstein J. 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 39 (2002) 1780-1786
22. McMahon L.P., Mason K., Skinner S.L., Burge C.M., Grigg L.E., and Becker G.J. Effects of haemoglobin normalization on quality of life and cardiovascular parameters in end-stage renal failure. Nephrol Dial Transplant 15 (2000) 1425-1430
23. Witte K.K., Desilva R., Chattopadhyay S., Ghosh J., Cleland J.G., and Clark A.L. Are hematinic deficiencies the cause of anemia in chronic heart failure?. Am Heart J 147 (2004) 924-930
24. Cromie N., Lee C., and Struthers A.D. Anaemia in chronic heart failure: what is its frequency in the UK and its underlying causes?. Heart 87 (2002) 377-378
25. Westenbrink B.D., Visser F.W., Voors A.A., 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 28 (2007) 166-171
26. Felker G.M., Gattis W.A., Leimberger J.D., et al. Usefulness of anemia as a predictor of death and rehospitalization in patients with decompensated heart failure. Am J Cardiol 92 (2003) 625-628
27. de Silva R., Rigby A.S., Witte K.K., et al. Anemia, renal dysfunction, and their interaction in patients with chronic heart failure. Am J Cardiol 98 (2006) 391-398
28. Nanas J.N., Matsouka C., Karageorgopoulos D., et al. Etiology of anemia in patients with advanced heart failure. J Am Coll Cardiol 48 (2006) 2485-2489
29. Weiss G., and Goodnough L.T. Anemia of chronic disease. N Engl J Med 352 (2005) 1011-1023
30. Bauer C., and Kurtz A. Oxygen sensing in the kidney and its relation to erythropoietin production. Annu Rev Physiol 51 (1989) 845-856
31. Anand I.S., Ferrari R., Kalra G.S., Wahi P.L., Poole-Wilson P.A., and Harris P.C. Edema of cardiac origin. Studies of body water and sodium, renal function, hemodynamic indexes, and plasma hormones in untreated congestive cardiac failure. Circulation 80 (1989) 299-305
32. McClellan W.M., Flanders W.D., Langston R.D., Jurkovitz C., and Presley R. 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 13 (2002) 1928-1936
33. 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 74 (1994) 468-473
34. van der Meer P., Voors A.A., Lipsic E., Smilde T.D., van Gilst W.H., and van Veldhuisen D.J. Prognostic value of plasma erythropoietin on mortality in patients with chronic heart failure. J Am Coll Cardiol 44 (2004) 63-67
35. Jensen J.D., Eiskjaer H., Bagger J.P., and Pedersen E.B. Elevated level of erythropoietin in congestive heart failure relationship to renal perfusion and plasma renin. J Intern Med 233 (1993) 125-130
36. Pham I., Andrivet P., Sediame S., et al. Increased erythropoietin synthesis in patients with COLD or left heart failure is related to alterations in renal haemodynamics. Eur J Clin Invest 31 (2001) 103-109
37. Mrug M., Stopka T., Julian B.A., Prchal J.F., and Prchal J.T. Angiotensin II stimulates proliferation of normal early erythroid progenitors. J Clin Invest 100 (1997) 2310-2314
38. Albitar S., Genin R., Fen-Chong M., Serveaux M.O., and Bourgeon B. High dose enalapril impairs the response to erythropoietin treatment in haemodialysis patients. Nephrol Dial Transplant 13 (1998) 1206-1210
39. Fyhrquist F., Karppinen K., Honkanen T., Saijonmaa O., and Rosenlof K. High serum erythropoietin levels are normalized during treatment of congestive heart failure with enalapril. J Intern Med 226 (1989) 257-260
40. van der Meer P., Lipsic E., Westenbrink B.D., et al. Levels of hematopoiesis inhibitor N-acetyl-seryl-aspartyl-lysyl-proline partially explain the occurrence of anemia in heart failure. Circulation 112 (2005) 1743-1747
41. Deswal A., Petersen N.J., Feldman A.M., Young J.B., White B.G., and Mann D.L. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation 103 (2001) 2055-2059
42. Anand I.S., Latini R., Florea V.G., et al. C-reactive protein in heart failure: prognostic value and the effect of valsartan. Circulation 112 (2005) 1428-1434
43. Jelkmann W. Proinflammatory cytokines lowering erythropoietin production. J Interferon Cytokine Res 18 (1998) 555-559
44. Macdougall I.C., and Cooper A.C. Erythropoietin resistance: the role of inflammation and pro-inflammatory cytokines. Nephrol Dial Transplant 17 Suppl 11 (2002) 39-43
45. Iversen P.O., Woldbaek P.R., Tonnessen T., and Christensen G. Decreased hematopoiesis in bone marrow of mice with congestive heart failure. Am J Physiol Regul Integr Comp Physiol 282 (2002) R166-R172
46. Androne A.S., Katz S.D., Lund L., et al. Hemodilution is common in patients with advanced heart failure. Circulation 107 (2003) 226-229
47. Anand I.S., Veall N., Kalra G.S., et al. Treatment of heart failure with diuretics: body compartments, renal function and plasma hormones. Eur Heart J 10 (1989) 445-450
48. Metivier F., Marchais S.J., Guerin A.P., Pannier B., and London G.M. Pathophysiology of anaemia: focus on the heart and blood vessels. Nephrol Dial Transplant 15 (2000) 14-18
49. Anand I.S., Chandrashekhar Y., Ferrari R., Poole-Wilson P.A., and Harris P.C. Pathogenesis of oedema in chronic severe anaemia: studies of body water and sodium, renal function, haemodynamic variables, and plasma hormones. Br Heart J 70 (1993) 357-362
50. Ni Z., Morcos S., and Vaziri N.D. Up-regulation of renal and vascular nitric oxide synthase in iron-deficiency anemia. Kidney Int 52 (1997) 195-201
51. Anand I.S., Chandrashekhar Y., Wander G.S., and Chawla L.S. Endothelium-derived relaxing factor is important in mediating the high output state in chronic severe anemia. J Am Coll Cardiol 25 (1995) 1402-1407
52. Anand I.S., Ferrari R., Kalra G.S., Wahi P.L., Poole-Wilson P.A., and Harris P.C. Pathogenesis of edema in constrictive pericarditis. Studies of body water and sodium, renal function, hemodynamics, and plasma hormones before and after pericardiectomy. Circulation 83 (1991) 1880-1887
53. Varat M.A., Adolph R.J., and Fowler N.O. Cardiovascular effects of anemia. Am Heart J 83 (1972) 415-426
54. Go A.S., Yang J., Ackerson L.M., 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 113 (2006) 2713-2723
55. Sharma R., Francis D.P., Pitt B., Poole-Wilson P.A., Coats A.J., and Anker S.D. Haemoglobin predicts survival in patients with chronic heart failure: a substudy of the ELITE II trial. Eur Heart J 25 (2004) 1021-1028
56. Gagnon D.R., Zhang T.J., Brand F.N., and Kannel W.B. Hematocrit and the risk of cardiovascular disease-the Framingham study: a 34-year follow-up. Am Heart J 127 (1994) 674-682
57. Brown D.W., Giles W.H., and Croft J.B. Hematocrit and the risk of coronary heart disease mortality. Am Heart J 142 (2001) 657-663
58. Sabatine M.S., Morrow D.A., Giugliano R.P., et al. Association of hemoglobin levels with clinical outcomes in acute coronary syndromes. Circulation 111 (2005) 2042-2049
59. Datta B.N., and Silver M.D. Cardiomegaly in chronic anemia in rats and man experimental study including ultrastructural, histometric, and stereologic observations. Lab Invest 32 (1975) 503-514
60. Olivetti G., Quaini F., Lagrasta C., et al. Myocyte cellular hypertrophy and hyperplasia contribute to ventricular wall remodeling in anemia-induced cardiac hypertrophy in rats. Am J Pathol 141 (1992) 227-239
61. Levin A. The treatment of anemia in chronic kidney disease: understandings in 2006. Curr Opin Nephrol Hypertens 16 (2007) 267-271
62. Collins A.J. The hemoglobin link to adverse outcomes. Adv Stud Med 3 (2003) S194-S197
63. Anker S.D., and Coats A.J. Cardiac cachexia: a syndrome with impaired survival and immune and neuroendocrine activation. Chest 115 (1999) 836-847
64. Demetri G.D. Anaemia and its functional consequences in cancer patients: current challenges in management and prospects for improving therapy. Br J Cancer 84 Suppl 1 (2001) 31-37
65. Silverberg D.S., 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 35 (2000) 1737-1744
66. Silverberg D.S., 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 37 (2001) 1775-1780
67. Mancini D.M., Katz S.D., Lang C.C., LaManca J., Hudaihed A., and Androne A.S. Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure. Circulation 107 (2003) 294-299
68. Palazzuoli A., Silverberg D.S., 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 anemia syndrome. Am Heart J 154 (2007) 645e9-645e15
69. Ponikowski P., Anker S.D., 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 49 (2007) 753-762
70. van Veldhuisen D.J., 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 28 (2007) 2208-2216
71. Ghali J.K., Anand I.S., Abraham W.T., et al. Randomized double-blind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia. Circulation 117 (2008) 526-535
72. van Veldhuisen D.J., and McMurray J.J. Are erythropoietin stimulating proteins safe and efficacious in heart failure?. Why we need an adequately powered randomised outcome trial. Eur J Heart Fail 9 (2007) 110-112
73. Phrommintikul A., Haas S.J., Elsik M., and Krum H. Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis. Lancet 369 (2007) 381-388
74. Fishbane S., Ragolia L., Palaia T., Johnson B., Elzein H., and Maesaka J.K. Cytoprotection by darbepoetin/epoetin alfa in pig tubular and mouse mesangial cells. Kidney Int 65 (2004) 452-458
75. Besarab A., Bolton W.K., Browne J.K., 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 339 (1998) 584-590
76. Drueke T.B., Locatelli F., Clyne N., et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 355 (2006) 2071-2084
77. Singh A.K., Szczech L., Tang K.L., et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 355 (2006) 2085-2098
78. Levin A. Understanding recent haemoglobin trials in CKD: methods and lesson learned from CREATE and CHOIR. Nephrol Dial Transplant 22 (2007) 309-312
79. Mix T.C., Brenner R.M., Cooper M.E., et al. Rationale-Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT): evolving the management of cardiovascular risk in patients with chronic kidney disease. Am Heart J 149 (2005) 408-413
80. Pfeffer M.A. An ongoing study of anemia correction in chronic kidney disease. N Engl J Med 356 (2007) 959-961
81. Food and Drug Administration. Information for Healthcare Professionals Erythropoiesis Stimulating Agents (ESA) [Aranesp (darbepoetin), Epogen (epoealfa)], November 8, 2007. http://www.fda.gov/cder/drug/InfoSheets/HCP/RHE200711HCP.htm Accessed June 9, 2008
82. Vaziri N.D. Cardiovascular effects of erythropoietin and anemia correction. Curr Opin Nephrol Hypertens 10 (2001) 633-637
83. Rodrigue M.E., Moreau C., Lariviere R., and Lebel M. Relationship between eicosanoids and endothelin-1 in the pathogenesis of erythropoietin-induced hypertension in uremic rats. J Cardiovasc Pharmacol 41 (2003) 388-395
84. Eggena P., Willsey P., Jamgotchian N., et al. Influence of recombinant human erythropoietin on blood pressure and tissue renin-angiotensin systems. Am J Physiol 261 (1991) E642-E646
85. Tobu M., Iqbal O., Fareed D., et al. Erythropoietin-induced thrombosis as a result of increased inflammation and thrombin activatable fibrinolytic inhibitor. Clin Appl Thromb Hemost 10 (2004) 225-232
86. Brines M., and Cerami A. Emerging biological roles for erythropoietin in the nervous system. Nat Rev Neurosci 6 (2005) 484-494
87. Parsa C.J., Matsumoto A., Kim J., et al. A novel protective effect of erythropoietin in the infarcted heart. J Clin Invest 112 (2003) 999-1007
88. Calvillo L., Latini R., Kajstura J., et al. Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci U S A 100 (2003) 4802-4806
89. Westenbrink B.D., 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 28 (2007) 2018-2027
90. REVEAL. Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction(ClinicalTrials.gov Identifier: NCT00378352). http://clinicaltrials.gov/show/NCT00378352 Accessed June 9, 2008
91. HEBEIII. Clinical Study to Examine the Effects of Erythropoietin on Left Ventricular Function After Acute Myocardial Infarction (ClinicalTrials.gov Identifier: NCT00449488). http://clinicaltrials.gov/ct2/show/NCT00449488 Accessed June 9, 2008
92. Brines M., Grasso G., Fiordaliso F., et al. Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor. Proc Natl Acad Sci U S A 101 (2004) 14907-14912
93. Leist M., Ghezzi P., Grasso G., et al. Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science 305 (2004) 239-242
94. Fiordaliso F., Chimenti S., Staszewsky L., et al. A nonerythropoietic derivative of erythropoietin protects the myocardium from ischemia-reperfusion injury. Proc Natl Acad Sci U S A 102 (2005) 2046-2051
95. Dunn L.L., Rahmanto Y.S., and Richardson D.R. Iron uptake and metabolism in the new millennium. Trends Cell Biol 17 (2007) 93-100
96. Brownlie T., Utermohlen V., Hinton P.S., and Haas J.D. Tissue iron deficiency without anemia impairs adaptation in endurance capacity after aerobic training in previously untrained women. Am J Clin Nutr 79 (2004) 437-443
97. Dong F., Zhang X., Culver B., Chew Jr. H.G., Kelley R.O., and Ren J. Dietary iron deficiency induces ventricular dilation, mitochondrial ultrastructural aberrations and cytochrome c release: involvement of nitric oxide synthase and protein tyrosine nitration. Clin Sci (Lond) 109 (2005) 277-286
98. Bolger A.P., Bartlett F.R., Penston H.S., et al. Intravenous iron alone for the treatment of anemia in patients with chronic heart failure. J Am Coll Cardiol 48 (2006) 1225-1227
99. Toblli J.E., Lombrana A., Duarte P., and 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 50 (2007) 1657-1665
100. Okonko D.O., 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 51 (2008) 103-112
101. Beck-da-Silva L., Luís Eduardo Rohde L., Pereira-Barretto A.C., 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 13 (2007)
102. Weinberg E.D. Iron loading and disease surveillance. Emerg Infect Dis 5 (1999) 346-352
103. Sullivan J.L. Long-term risks of increased use of intravenous iron. Lancet 370 (2007) 481-482 author reply 482-3
104. National Kidney Foundation Kidney Disease Outcomes Quality Initiative. KDOQI clinical practice guideline and clinical practice recommendations for anemia in chronic kidney disease: 2007 update of hemoglobin target. http://www.kidney.org/professionals/KDOQI/ Accessed June 9, 2008