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2000
Volume 23, Issue 3
  • ISSN: 1871-5257
  • E-ISSN: 1875-6182

Abstract

Background

Iron Deficiency (ID) is common in patients with cardiovascular disease. More than 64 million patients are suffering from chronic heart failure. The prevalence of iron deficiency increases with the severity of cardiac and renal dysfunction and is probably more common amongst women.

Aims

This review article discusses multifactorial pathophysiology, the relationship between clinical characteristics, functional and absolute ID, and the advantages of medicinal intervention in chronic heart failure (CHF). It also covers how iron shortage affects other body parts.

Methods

The most recent publications that included substantial scientific data on the connection between CHF and ID, with or without anaemia, were selected.

Results and Discussion

Complex physiopathological interactions, including higher hepcidin levels, systemic inflammation, and activation of the renin-angiotensin-aldosterone system, have been identified in these patients. These mechanisms exacerbate the outcomes for patients by amplifying the severity of anemia, chronic heart failure (CHF), and Chronic kidney disease (CKD). Research in this area has been limited and has shown inconsistent findings. Still, it has also examined evidence-based treatment approaches and diagnostic guidelines, especially in relation to iron supplements and erythropoietin-stimulating medications.

Conclusion

Anemia is a frequent chronic heart failure consequence and a poor prognostic factor. We still don't completely understand the many complex causes of anemia. Iron deficiency screening is highly recommended for people with cardiac ailments because of its significance for their prognoses. Due to the paucity of research proving its effectiveness, the high incidence of unfavourable gastrointestinal side effects, and the prolonged length of time required for treatment to boost haemoglobin levels, an oral iron supplement is not advised for people with chronic heart failure. An insufficient amount of iron not only impacts the heart but also various other body components.

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References

  1. GebreA. MulugetaA. Prevalence of anemia and associated factors among pregnant women in North Western zone of Tigray, Northern Ethiopia: A cross-sectional study.J. Nutr. Metab.201520151710.1155/2015/16543026137321
    [Google Scholar]
  2. AttardS.M. HerringA.H. WangH. HowardA-G. ThompsonA.L. AdairL.S. Mayer-DavisE.J. Gordon-LarsenP. Implications of iron deficiency/anemia on the classification of diabetes using HbA1c.Nutr. Diabetes201556e166e16610.1038/nutd.2015.1626098445
    [Google Scholar]
  3. DunnL.L. RahmantoY.S. RichardsonD.R. Iron uptake and metabolism in the new millennium.Trends Cell Biol.20071729310010.1016/j.tcb.2006.12.00317194590
    [Google Scholar]
  4. CairoG. BernuzziF. RecalcatiS. A precious metal: Iron, an essential nutrient for all cells.Genes Nutr.200611253910.1007/BF0282993418850218
    [Google Scholar]
  5. AnandI.S. Anemia and chronic heart failure implications and treatment options.J. Am. Coll. Cardiol.200852750151110.1016/j.jacc.2008.04.04418687241
    [Google Scholar]
  6. AnandI.S. GuptaP. Anemia and iron deficiency in heart failure: Current concepts and emerging therapies.Circulation20181381809810.1161/CIRCULATIONAHA.118.03009929967232
    [Google Scholar]
  7. SiddiquiS.W. AshokT. PatniN. FatimaM. LamisA. AnneK.K. Anemia and heart failure: A narrative review.Cureus2022147e2716710.7759/cureus.2716736017290
    [Google Scholar]
  8. HorwichT.B. FonarowG.C. HamiltonM.A. MacLellanW.R. BorensteinJ. 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.200239111780178610.1016/S0735‑1097(02)01854‑512039491
    [Google Scholar]
  9. LippiG. Sanchis-GomarF. Global epidemiology and future trends of heart failure.AME Med. J.202051510.21037/amj.2020.03.03
    [Google Scholar]
  10. GeorgeP. The specific reactions of iron in some hemoproteins.Advances in catalysis.AmsterdamElsevier1952Vol. 436742810.1016/S0360‑0564(08)60619‑7
    [Google Scholar]
  11. CaugheyW.S. Porphyrin proteins and enzymes.Annu. Rev. Biochem.196736161164410.1146/annurev.bi.36.070167.00314318257732
    [Google Scholar]
  12. HoffbrandA.V. HershkoC. CamaschellaC. Iron metabolism, iron deficiency and disorders of haem synthesis.Postgrad. Haematol.20102010264610.1002/9781444323160.ch3
    [Google Scholar]
  13. BonkovskyH.L. Iron and the Liver.Am. J. Med. Sci.19913011324310.1097/00000441‑199101000‑000061847276
    [Google Scholar]
  14. GanzT. NemethE. Regulation of iron acquisition and iron distribution in mammals.Biochim. Biophys. Acta Mol. Cell Res.20061763769069910.1016/j.bbamcr.2006.03.01416790283
    [Google Scholar]
  15. CookJ.D. FlowersC.H. SkikneB.S. The quantitative assessment of body iron.Blood200310193359336310.1182/blood‑2002‑10‑307112521995
    [Google Scholar]
  16. RaoR. GeorgieffM.K. Perinatal aspects of iron metabolism.Acta Paediatr.200291s43812412910.1111/j.1651‑2227.2002.tb02917.x12477276
    [Google Scholar]
  17. ConradM.E. UmbreitJ.N. MooreE.G. Iron absorption and transport.Am. J. Med. Sci.1999318421322910.1016/S0002‑9629(15)40626‑310522550
    [Google Scholar]
  18. FrazerD.M. AndersonG.J. The regulation of iron transport.Biofactors201440220621410.1002/biof.114824132807
    [Google Scholar]
  19. JacobsA. WorwoodM. Iron absorption: Present state of the art.Br. J. Haematol.197531s18910110.1111/j.1365‑2141.1975.tb00902.x
    [Google Scholar]
  20. Hanna-RiveroN. TuS.J. ElliottA.D. PitmanB.M. GallagherC. LauD.H. SandersP. WongC.X. Anemia and iron deficiency in patients with atrial fibrillation.BMC Cardiovasc. Disord.202222120410.1186/s12872‑022‑02633‑635508964
    [Google Scholar]
  21. WeissG. GoodnoughL.T. Anemia of chronic disease.N. Engl. J. Med.2005352101011102310.1056/NEJMra04180915758012
    [Google Scholar]
  22. OkonkoD.O. MandalA.K.J. MissourisC.G. Poole-WilsonP.A. Disordered iron homeostasis in chronic heart failure: Prevalence, predictors, and relation to anemia, exercise capacity, and survival.J. Am. Coll. Cardiol.201158121241125110.1016/j.jacc.2011.04.04021903058
    [Google Scholar]
  23. NemethE. RiveraS. GabayanV. KellerC. TaudorfS. PedersenB.K. GanzT. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin.J. Clin. Invest.200411391271127610.1172/JCI20042094515124018
    [Google Scholar]
  24. EbnerN. von HaehlingS. Why is iron deficiency recognised as an important comorbidity in heart failure?Card. Fail. Rev.20195317317510.15420/cfr.2019.9.231768275
    [Google Scholar]
  25. JelkmannW. Proinflammatory cytokines lowering erythropoietin production.J. Interferon Cytokine Res.199818855555910.1089/jir.1998.18.5559726435
    [Google Scholar]
  26. LofrutheN. GallitzI. TraegerL. BäumerN. SchulzeI. KuhlmannT. Müller-TidowC. SteinbickerA.U. Intravenous iron carboxymaltose as a potential therapeutic in anemia of inflammation.PLoS One2016117e015859910.1371/journal.pone.015859927404499
    [Google Scholar]
  27. Van AelstL.N.L. MazureD. Cohen-SolalA. Towards Holistic Heart Failure Management—How to Tackle the Iron Deficiency Epidemic?Curr. Heart Fail. Rep.201714422323410.1007/s11897‑017‑0338‑828669000
    [Google Scholar]
  28. von HaehlingS. GremmlerU. KrummM. MibachF. SchönN. TaggeselleJ. DahmJ.B. AngermannC.E. Prevalence and clinical impact of iron deficiency and anaemia among outpatients with chronic heart failure: The PrEP Registry.Clin. Res. Cardiol.2017106643644310.1007/s00392‑016‑1073‑y28229219
    [Google Scholar]
  29. GroenveldH.F. JanuzziJ.L. DammanK. van WijngaardenJ. HillegeH.L. van VeldhuisenD.J. van der MeerP. Anemia and mortality in heart failure patients a systematic review and meta-analysis.J. Am. Coll. Cardiol.2008521081882710.1016/j.jacc.2008.04.06118755344
    [Google Scholar]
  30. AdamsK.F.Jr PiñaI.L. GhaliJ.K. WagonerL.E. DunlapS.H. SchwartzT.A. StoughW.G. MehraM.R. FelkerG.M. ChiongJ.R. PattersonJ.H. KimJ. ButlerJ. OrenR.M. Prospective evaluation of the association between hemoglobin concentration and quality of life in patients with heart failure.Am. Heart J.2009158696597110.1016/j.ahj.2009.10.01519958863
    [Google Scholar]
  31. TangY.D. KatzS.D. Anemia in chronic heart failure: Prevalence, etiology, clinical correlates, and treatment options.Circulation2006113202454246110.1161/CIRCULATIONAHA.105.58366616717164
    [Google Scholar]
  32. KlipI.T. Iron deficiency in chronic heart failure: An international pooled analysis.Am Heart J.20131654575582.e310.1016/j.ahj.2013.01.017
    [Google Scholar]
  33. SilverbergD.S. WexlerD. PalazzuoliA. IainaA. SchwartzD. The anemia of heart failure.Acta Haematol.20091222-310911910.1159/00024379519907148
    [Google Scholar]
  34. ToblliJ.E. LombrañaA. DuarteP. Di GennaroF. Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency.J. Am. Coll. Cardiol.200750171657166510.1016/j.jacc.2007.07.02917950147
    [Google Scholar]
  35. JankowskaE. A. Iron deficiency in chronic heart failure: An international pooled analysis.Eur Heart J2010311518728010.1093/eurheartj/ehq158
    [Google Scholar]
  36. SilverbergD. WexlerD. RozenfeldJ. The cardio renal anemia syndrome.J. Balk. Cities Assoc. Nephrol. Dial. Transplant. Artif. Organs.2003200324
    [Google Scholar]
  37. QaseemA. HumphreyL.L. FittermanN. StarkeyM. ShekelleP. Treatment of anemia in patients with heart disease: A clinical practice guideline from the American College of Physicians.Ann. Intern. Med.20131591177077910.7326/0003‑4819‑159‑11‑201312030‑0000924297193
    [Google Scholar]
  38. FelkerG.M. AdamsK.F.Jr GattisW.A. O’ConnorC.M. Anemia as a risk factor and therapeutic target in heart failure.J. Am. Coll. Cardiol.200444595996610.1016/j.jacc.2004.05.07015337204
    [Google Scholar]
  39. JankowskaE.A. von HaehlingS. AnkerS.D. MacdougallI.C. PonikowskiP. Iron deficiency and heart failure: Diagnostic dilemmas and therapeutic perspectives.Eur. Heart J.2013341181682910.1093/eurheartj/ehs22423100285
    [Google Scholar]
  40. SilverbergD. WexlerD. SchwartzD. Is correction of iron deficiency a new addition to the treatment of the heart failure?Int. J. Mol. Sci.2015166140561407410.3390/ijms16061405626096008
    [Google Scholar]
  41. LanasA. DumonceauJ.M. HuntR.H. FujishiroM. ScheimanJ.M. GralnekI.M. CampbellH.E. RostomA. VillanuevaC. SungJ.J.Y. Non-variceal upper gastrointestinal bleeding.Nat. Rev. Dis. Primers2018411802010.1038/nrdp.2018.2029671413
    [Google Scholar]
  42. NemethE. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization.Science200430657042090310.1126/science.1104742
    [Google Scholar]
  43. SingerC.E. VasileC.M. PopescuM. PopescuA.I.S. MargineanI.C. IacobG.A. PopescuM.D. MargineanC.M. Role of Iron Deficiency in Heart Failure—Clinical and Treatment Approach: An Overview.Diagnostics (Basel)202313230410.3390/diagnostics1302030436673114
    [Google Scholar]
  44. CappelliniM.D. MottaI. Anemia in clinical practice—definition and classification: Does hemoglobin change with aging?Seminars in hematology.AmsterdamElsevier201526126910.1053/j.seminhematol.2015.07.006
    [Google Scholar]
  45. CamaschellaC. New insights into iron deficiency and iron deficiency anemia.Blood Rev.201731422523310.1016/j.blre.2017.02.00428216263
    [Google Scholar]
  46. HarveyJ.W. FrenchT.W. MeyerD.J. Chronic iron deficiency anemia in dogs.J. Am. Anim. Hosp. Assoc.198218946960
    [Google Scholar]
  47. WoodsG.L. WalkerD.H. Detection of infection or infectious agents by use of cytologic and histologic stains.Clin. Microbiol. Rev.19969338240410.1128/CMR.9.3.3828809467
    [Google Scholar]
  48. ButtarelloM. PlebaniM. Automated blood cell counts: State of the art.Am. J. Clin. Pathol.2008130110411610.1309/EK3C7CTDKNVPXVTN18550479
    [Google Scholar]
  49. HughesD.A. Stuart-SmithS.E. BainB.J. How should stainable iron in bone marrow films be assessed?J. Clin. Pathol.200457101038104010.1136/jcp.2003.01583415452156
    [Google Scholar]
  50. Stuart-SmithS.E. HughesD.A. BainB.J. Are routine iron stains on bone marrow trephine biopsy specimens necessary?J. Clin. Pathol.200558326927210.1136/jcp.2004.01703815735158
    [Google Scholar]
  51. LeiteL.R. Ferritin Expression in Breast Cancer Infiltrating Lymphocytes.MedicinePhiladelphiaLippincott Williams & Wilkins2001
    [Google Scholar]
  52. PhiriK.S. Assessment of iron deficiency in Malawian children living in an area of high malaria and bacterial infection morbidity.Doctoral dissertation, University of Liverpool2006
    [Google Scholar]
  53. CappelliniM.D. MusallamK.M. TaherA.T. Iron deficiency anaemia revisited.J. Intern. Med.2020287215317010.1111/joim.1300431665543
    [Google Scholar]
  54. SwainJ.H. Dietary proteins that influence nonheme iron bioavailability, iron status, and plasma total antioxidant status.Iowa State University200010.31274/rtd‑180813‑13633
    [Google Scholar]
  55. AdelugbaA.O. The assessment of reticulocyte and erythrocyte haemoglobin contents, and their use in the evaluation of iron status in hospitalised patients.Doctoral dissertation, University of Portsmouth2012
    [Google Scholar]
  56. JoseA. Study on the Effect of Iron Deficiency on Glycated Haemoglobin in Non DiabeticsDoctoral dissertation, Rajiv Gandhi University of Health Sciences (India)2020
    [Google Scholar]
  57. DeLougheryT.G. Iron deficiency anemia.Med. Clin. North Am.2017101231933210.1016/j.mcna.2016.09.00428189173
    [Google Scholar]
  58. RymerJ.A. RaoS.V. Anemia and coronary artery disease.Coron. Artery Dis.201829216116710.1097/MCA.000000000000059829280914
    [Google Scholar]
  59. SilverbergD.S. The role of erythropoiesis stimulating agents and intravenous (IV) iron in the cardio renal anemia syndrome.Heart Fail. Rev.201116660961410.1007/s10741‑010‑9194‑220865450
    [Google Scholar]
  60. Johnson-WimbleyT.D. GrahamD.Y. Diagnosis and management of iron deficiency anemia in the 21st century.Therap. Adv. Gastroenterol.20114317718410.1177/1756283X1139873621694802
    [Google Scholar]
  61. LewisG.D. MalhotraR. HernandezA.F. McNultyS.E. SmithA. FelkerG.M. TangW.H.W. LaRueS.J. RedfieldM.M. SemigranM.J. GivertzM.M. Van BurenP. WhellanD. AnstromK.J. ShahM.R. Desvigne-NickensP. ButlerJ. BraunwaldE. Effect of oral iron repletion on exercise capacity in patients with heart failure with reduced ejection fraction and iron deficiency: The IRONOUT HF randomized clinical trial.JAMA2017317191958196610.1001/jama.2017.542728510680
    [Google Scholar]
  62. JankowskaE.A. RozentrytP. WitkowskaA. NowakJ. HartmannO. PonikowskaB. Borodulin-NadziejaL. von HaehlingS. DoehnerW. BanasiakW. PolonskiL. FilippatosG. AnkerS.D. PonikowskiP. Iron deficiency predicts impaired exercise capacity in patients with systolic chronic heart failure.J. Card. Fail.2011171189990610.1016/j.cardfail.2011.08.00322041326
    [Google Scholar]
  63. AvniT. LeiboviciL. Gafter-GviliA. Iron supplementation for the treatment of chronic heart failure and iron deficiency: Systematic review and meta-analysis.Eur. J. Heart Fail.201214442342910.1093/eurjhf/hfs01722348897
    [Google Scholar]
  64. AnkerS.D. Comin ColetJ. FilippatosG. WillenheimerR. DicksteinK. DrexlerH. LüscherT.F. BartB. BanasiakW. NiegowskaJ. KirwanB.A. MoriC. von Eisenhart RotheB. PocockS.J. Poole-WilsonP.A. PonikowskiP. Ferric carboxymaltose in patients with heart failure and iron deficiency.N. Engl. J. Med.2009361252436244810.1056/NEJMoa090835519920054
    [Google Scholar]
  65. OkonkoD.O. GrzesloA. WitkowskiT. MandalA.K.J. SlaterR.M. RoughtonM. FoldesG. ThumT. MajdaJ. BanasiakW. MissourisC.G. Poole-WilsonP.A. AnkerS.D. PonikowskiP. 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.200851210311210.1016/j.jacc.2007.09.03618191732
    [Google Scholar]
  66. QianC. WeiB. DingJ. WuH. WangY. The Efficacy and Safety of Iron Supplementation in Patients With Heart Failure and Iron Deficiency: A Systematic Review and Meta-analysis.Can. J. Cardiol.201632215115910.1016/j.cjca.2015.06.00926454467
    [Google Scholar]
  67. PonikowskiP. van VeldhuisenD.J. Comin-ColetJ. ErtlG. KomajdaM. MareevV. McDonaghT. ParkhomenkoA. TavazziL. LevesqueV. MoriC. RoubertB. FilippatosG. RuschitzkaF. AnkerS.D. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency.Eur. Heart J.2015361165766810.1093/eurheartj/ehu38525176939
    [Google Scholar]
  68. ToblliJ.E. Di GennaroF. RivasC. Changes in Echocardiographic Parameters in Iron Deficiency Patients with Heart Failure and Chronic Kidney Disease Treated with Intravenous Iron.Heart Lung Circ.201524768669510.1016/j.hlc.2014.12.16125666998
    [Google Scholar]
  69. AnkerS.D. KirwanB.A. van VeldhuisenD.J. FilippatosG. Comin-ColetJ. RuschitzkaF. LüscherT.F. ArutyunovG.P. MotroM. MoriC. RoubertB. PocockS.J. PonikowskiP. Effects of ferric carboxymaltose on hospitalisations and mortality rates in iron-deficient heart failure patients: An individual patient data meta-analysis.Eur. J. Heart Fail.201820112513310.1002/ejhf.82328436136
    [Google Scholar]
  70. McDonaghT. DamyT. DoehnerW. LamC.S.P. SindoneA. van der MeerP. Cohen-SolalA. KindermannI. ManitoN. PfisterO. Pohjantähti-MaaroosH. TaylorJ. Comin-ColetJ. Screening, diagnosis and treatment of iron deficiency in chronic heart failure: Putting the 2016 European Society of Cardiology heart failure guidelines into clinical practice.Eur. J. Heart Fail.201820121664167210.1002/ejhf.130530311713
    [Google Scholar]
  71. AvniT. BieberA. GrossmanA. GreenH. LeiboviciL. Gafter-GviliA. The safety of intravenous iron preparations: Systematic review and meta-analysis.Mayo Clin. Proc.2015901122310.1016/j.mayocp.2014.10.00725572192
    [Google Scholar]
  72. BrillJ.R. BaumgardnerD.J. Normocytic anemia.Am. Fam. Physician200062102255226411126852
    [Google Scholar]
  73. YilmazG ShaikhH. Normochromic Normocytic Anemia.Treasure Island, FLStatPearls Publishing
    [Google Scholar]
  74. TohB.H. van DrielI.R. GleesonP.A. Pernicious Anemia.N. Engl. J. Med.1997337201441144810.1056/NEJM1997111333720079358143
    [Google Scholar]
  75. DavenportJ. SallisR. Macrocytic anemia.Am. Fam. Physician19965311551628546042
    [Google Scholar]
  76. GehrsB.C. FriedbergR.C. Autoimmune hemolytic anemia.Am. J. Hematol.200269425827110.1002/ajh.1006211921020
    [Google Scholar]
  77. LiebmanH.A. WeitzI.C. Autoimmune hemolytic anemia.Med. Clin. North Am.2017101235135910.1016/j.mcna.2016.09.00728189175
    [Google Scholar]
  78. SteiberA. Multicenter study of the validity and reliability of subjective global assessment in the hemodialysis population.J. Ren. Nutr.20071753364210.1053/j.jrn.2007.05.004
    [Google Scholar]
  79. FalkinghamM. AbdelhamidA. CurtisP. Fairweather-TaitS. DyeL. HooperL. The effects of oral iron supplementation on cognition in older children and adults: A systematic review and meta-analysis.Nutr. J.201091410.1186/1475‑2891‑9‑420100340
    [Google Scholar]
  80. AndroM. Le SquereP. EstivinS. GentricA. Anaemia and cognitive performances in the elderly: A systematic review.Eur. J. Neurol.20132091234124010.1111/ene.1217523647493
    [Google Scholar]
  81. BrownlieT.IV UtermohlenV. HintonP.S. GiordanoC. HaasJ.D. Marginal iron deficiency without anemia impairs aerobic adaptation among previously untrained women.Am. J. Clin. Nutr.200275473474210.1093/ajcn/75.4.73411916761
    [Google Scholar]
  82. HaasJ.D. BrownlieT.IV Iron deficiency and reduced work capacity: A critical review of the research to determine a causal relationship.J. Nutr.20011312676S690S10.1093/jn/131.2.676S11160598
    [Google Scholar]
  83. WangW. BourgeoisT. KlimaJ. BerlanE.D. FischerA.N. O’BrienS.H. Iron deficiency and fatigue in adolescent females with heavy menstrual bleeding.Haemophilia201319222523010.1111/hae.1204623106971
    [Google Scholar]
  84. KhanA. ChawlaR.K. GuoM. WangC. Risk factors associated with anaemia among adolescent girls: A cross sectional study in District Peshawar.PakistanJPMA201910.5455/JPMA.295006
    [Google Scholar]
  85. MusallamK.M. TaherA.T. Iron deficiency beyond erythropoiesis: Should we be concerned?Curr. Med. Res. Opin.2018341819310.1080/03007995.2017.139483329050512
    [Google Scholar]
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