Skip to main content
Clinical Cardiology logoLink to Clinical Cardiology
. 2006 Dec 5;28(10):454–458. doi: 10.1002/clc.4960281003

Anemia in heart failure—A concise review

Sujethra Vasu 1, Patricia Kelly 1, William E Lawson 2,
PMCID: PMC6653873  PMID: 16274092

Abstract

Heart failure affects 5 million persons in the United States, with 400,000 new cases occurring every year. Paradoxically, although advances in coronary angioplasty and effective drugs have increased survival post infarction, the myocardial damage and subsequent neurohormonal activation‐induced remodeling causes significant morbidity years later in the form of heart failure. Angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) together with beta blockers modify the neurohormonal activation associated with heart failure and are key treatments for improving cardiac function and survival. Anemia is a significant risk factor predicting morbidity and mortality in heart failure. This article describes the various etiologies of anemia in heart failure. Of particular importance is the fact that recent stem cell studies have shown that the drugs acting on the renin‐angiotensin system inhibit erythropoiesis in vivo and may cause anemia in patients with both normal renal function and end‐stage renal disease (ESRD). The role of angiotensin‐II as an erythropoietic growth factor and ACE in facilitating erythropoiesis is described in this article. Anemia has been shown to be a modifiable risk factor and its treatment correlates with improvement in clinical outcomes. Thus, anemia, its etiology (especially the contribution of ACEIs and ARBs), physiologic and prognostic impact, and treatment in the setting of heart failure are critical areas for investigation.

Keywords: anemia, heart failure, angiotensin‐II

Full Text

The Full Text of this article is available as a PDF (59.9 KB).

References

  • 1. Al‐Ahmad A, Rand WM, Manjunath G, Konstam MA, Salem DN, Levey AS, Sarnak MJ: Studies of Left Ventricular Dysfunction—SOLVD. Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction. J Am Coll Cardiol 2001; 38 (4): 955–962 [DOI] [PubMed] [Google Scholar]
  • 2. McClellan WM, Flanders WD, Langston RD, Jurkovitz C, 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 2002; 13 (7): 1928–1936 [DOI] [PubMed] [Google Scholar]
  • 3. 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 (11): 1933–1939 [DOI] [PubMed] [Google Scholar]
  • 4. Horwich TB, Fonarow GC, Hamilton MA, MacLellan WR, Borenstein 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 2002; 39 (11): 1780–1786 [DOI] [PubMed] [Google Scholar]
  • 5. 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 (2): 223–225 [DOI] [PubMed] [Google Scholar]
  • 6. Kalra PR, Bolger AP, Francis DP, Genth‐Zotz S, Sharma R, Ponikowski PP: Effect of anemia on exercise tolerance in chronic heart failure in men. Am J Cardiol 2003; 91 (7): 888–891 [DOI] [PubMed] [Google Scholar]
  • 7. Metivier F, Marchais SJ, Guerin AP, Pannier B, London GM: Pathophysiology of anaemia: Focus on the heart and blood vessels. Nephrol Dial Transplant 2000; 15 (suppl3): 14–18 [DOI] [PubMed] [Google Scholar]
  • 8. Iversen PO, Woldbaek PR, Tonnessen T, Christensen G: Decreased hematopoiesis in bone marrow of mice with congestive heart failure. Am J PhysiolRegul Integr Comp Physiol 2002; 282 (1): R166–172 [DOI] [PubMed] [Google Scholar]
  • 9. Rodgers KE, Xiong S, Steer R, diZerega GS: Effect of angiotensin II on hematopoietic progenitor cell proliferation. Stem Cells 2000; 18 (4): 287–294 [DOI] [PubMed] [Google Scholar]
  • 10. Mrug M, Stopka T, Julian BA, Prchal JF, Prchal JT: Angiotensin II stimulates proliferation of normal early erythroid progenitors. J Clin Invest 1997; 100 (9): 2310–2314 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. Naito M, Kawashima A, Akiba T, Takanashi M, Nihei H: Effects of an angiotensin II receptor antagonist and angiotensin‐converting enzyme in hibitors on burst forming units‐erythroid in chronic hemodialysis patients. Am J Nephrol 2003; 23 (5): 287–293 [DOI] [PubMed] [Google Scholar]
  • 12. Cole J, Ertoy D, Lin H, Sutliff RL, Ezan E, Guyene TT, Capecchi M, Corvol P, Bernstein KE: Lack of angiotensin II‐facilitated erythropoiesis causes anemia in angiotensin‐converting enzyme‐deficient mice. J Clin Invest 2000; 106 (11): 1391–1398 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Comte L, Lorgeot V, Volkov L, Alleglaud A, Aldigier JC, Praloran V: Effects of the ACEI enalapril on blood hematopoietic progenitors and acetyl‐N‐Ser‐Asp‐Lys‐Pro concentrations. Eur J Clin Invest 1997; 27: 788–790 [DOI] [PubMed] [Google Scholar]
  • 14. Macdougall IC: The role of ACE inhibitors and angiotensin II receptor blockers in the response to epoetin. Nephrol Dial Transplant 1999; 14 (8): 1836–1841 [DOI] [PubMed] [Google Scholar]
  • 15. Vlahakos DV, Balodimos C, Papachristopoulos V, Vassilakos P, Hinari E, Vlachojannis JG: Renin‐angiotensin system stimulates erythropoietin secretion in chronic hemodialysis patients. Clin Nephrol 1995; 43 (1): 53–59 [PubMed] [Google Scholar]
  • 16. Haznedaroglu IC, Ozturk MA: Towards the understanding of the local hematopoietic bone marrow renin‐angiotensin system. Int J Biochem Cell Bio 2003; 35 (6): 867–880 [DOI] [PubMed] [Google Scholar]
  • 17. Marusic‐Vrsalovic M, Dominis M, Jaksic B, Kusec R: Angiotensin I‐converting enzyme is expressed by erythropoietic cells of normal and myeloproliferative bone marrow. Br J Haematol 2003; 123 (3): 539–541 [DOI] [PubMed] [Google Scholar]
  • 18. Okunishi H, Oka Y, Shiota N, Kawamoto T, Song K, Miyazaki M: Marked species‐difference in the vascular angiotensin II‐forming pathways: Humans versus rodents. Jpn J Pharmacol 1993; 62: 207–210 [DOI] [PubMed] [Google Scholar]
  • 19. Hollenberg NK, Fisher NDL, Price DA: Pathways for angiotensin II generation in intact human tissue. Evidence from comparative pharmacological interruption of the renin system. Hypertension 1998; 32: 387–392 [DOI] [PubMed] [Google Scholar]
  • 20. Mrug M, Julian BA, Prchal JT: Angiotensin U receptor type 1 expression in erythroid progenitors: Implications for the pathogenesis of postrenal transplant erythrocytosis. Semin Nephrol 2004; 24 (2): 120–130 [DOI] [PubMed] [Google Scholar]
  • 21. Erturk S, Nergizoglu G, Ates K, Duman N, Erbay B, Karatan O, Ertug AE: The impact of withdrawing ACE inhibitors on erythropoietin responsiveness and left ventricular hypertrophy in haemodialysis patients. Nephrol Dial Transplant 1999; 14 (8): 1912–1916 [DOI] [PubMed] [Google Scholar]
  • 22. Ducloux D, Saint‐Hillier Y, Chalopin JM: Effect of losartan on haemoglobin concentration in renal transplant recipients—a retrospective analysis. Nephrol Dial Transplant 1997; 12 (12): 2683–2686 [DOI] [PubMed] [Google Scholar]
  • 23. Usalan C, Erdem Y, Caglar M, Altun B, Arici M, Bakkaloglu M, Yasavul U, Turgan C, Caglar S: Effect of enalapril on exaggerated erythropoietin response to phlebotomy in erythrocytosic renal transplant patients. Nephrol Dial Transplant 1998; 13 (11): 2884–2889 [DOI] [PubMed] [Google Scholar]
  • 24. Vlahakos DV, Marathias KP, Kosmas EN: Losartan reduces hematocrit in patients with chronic obstructive pulmonary disease and secondary erythrocytosis. Ann Intern Med 2001; 134 (5): 426–427 [DOI] [PubMed] [Google Scholar]
  • 25. Fakhouri F, Grunfeld JP, Hermine O, Delarue R: Angiotensin‐converting enzyme inhibitors for secondary erythrocytosis. Ann Intern Med 2004; 140 (6): 492–493 [DOI] [PubMed] [Google Scholar]
  • 26. Androne AS, Katz SD, Lund L, LaManca J, Hudaihed A, Hryniewicz K: Hemodilution is common in patients with advanced heart failure. Circulation 2003; 107 (2): 226–229 [DOI] [PubMed] [Google Scholar]
  • 27. Volpe M, Tritto C, Testa U, Rao MA, Martucci R, Mirante A, Enea I, Russo R, Rubattu S, Condorelli GL, Cangianiello S, Trimarco B, Peschle C, Condorelli M: Blood levels of erythropoietin in congestive heart failure and correlation with clinical, hemodynamic, and hormonal profiles. Am J Cardiol 1994; 74 (5): 468–473 [DOI] [PubMed] [Google Scholar]
  • 28. Biaggioni I, Robertson D, Krants S, Jones M, Haile V: The anemia of primary autonomic failure and its reversal with recombinant erythropoietin. Ann Intern Med 1994; 121: 181–186 [DOI] [PubMed] [Google Scholar]
  • 29. Obayashi K, Ando Y, Terazaki H, Yamashita T, Nakamura M, Ando M: Mechanism of anemia associated with autonomic dysfunction in rats. Autonomic Neuroscience: Basic and Clinical 2000; 82: 123–129 [DOI] [PubMed] [Google Scholar]
  • 30. Silverberg DS, Wexler D, Blum M, Keren G, Sheps D, Leibovitch E: 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 (7): 1737–1744 [DOI] [PubMed] [Google Scholar]
  • 31. Silverberg DS, Wexler D, Sheps D, Blum M, Keren G, Baruch R: 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 (7): 1775–1780 [DOI] [PubMed] [Google Scholar]
  • 32. Mancini DM, Katz SD, Lang CC, LaManca J, Hudaihed A, Androne AS: Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure. Circulation 2003; 107 (2): 294–299 [DOI] [PubMed] [Google Scholar]

Articles from Clinical Cardiology are provided here courtesy of Wiley

RESOURCES