Iron deficiency states in cardiovascular diseases: impact on prognosis and features of correction
https://doi.org/10.21886/2712-8156-2023-4-1-7-18
Abstract
The article discusses the problem of comorbidity of iron deficiency conditions and cardiovascular diseases (CVD). Iron deficiency conditions (latent iron deficiency and iron deficiency anemia) significantly increase the risk of developing and progressing CVD. A number of studies have found that, regardless of the presence or absence of anemia, iron deficiency leads to the development of cardiovascular complications, a worsening of quality of life and an increase in mortality in patients with CVD. Currently, the most studied is the effect of iron deficiency on the prognosis of patients with chronic heart failure (CHF). The article discusses the etiology and pathogenesis of the development of iron deficiency in CHF, the mechanisms of the adverse effect of this condition on the quality of life, functional status, and life prognosis. The article presents an analysis of clinical studies on the treatment of iron deficiency conditions in CHF and excerpts from current clinical guidelines. Data are presented that describe the contribution of drugs for the treatment of CHF (guideline directed therapy) to the correction of anemia and iron deficiency. The article discusses the impact of iron deficiency conditions on the course and prognosis of life in atrial fibrillation (AF) and coronary heart disease (CHD). The negative contribution of iron deficiency states to the development of exacerbations of CVD, an increase in the number of hospitalizations and an increase in the risk of death in these categories of patients is emphasized. Despite the known negative impact of iron deficiency conditions on the functional status and prognosis of patients with CVD, there is still insufficient data on the efficacy and safety of iron deficiency correction in patients with CVD.
About the Authors
N. G. VinogradovaRussian Federation
Nadezhda G. Vinogradova, Dr. Sci. (Med.), Associate Professor of the Department of Therapy and Cardiology
Nizhny Novgorod
A. I. Chesnikova
Russian Federation
Anna I. Chesnikova, Dr. Sci. (Med.), Professor of the Department of Internal Medicine
Rostov-on-Don
References
1. Gorokhovskaya G.N., Martynov A.I., Yun V.L., Petina M.M. A modern view of the therapist on the problem of iron deficiency anemia in patients with cardiovascular pathology. Medical advice. 2020;(14):70-78. https://doi.org/10.21518/2079-701X-2020-14-70-78.
2. Astor B.C., Coresh J, Heiss G., Pettitt D., Sarnak M.J. Kidney function and anemia as risk factors for coronary heart disease and mortality: the AtheroscLerosis Risk in Communities (ARIC) Study. Am Heart J. 2006;151(2):492-500. https://doi.org/10.1016/j.ahj.2005.03.055.
3. Comin-Colet J, Enjuanes C, Gonzalez G et al. Iron deficiency is a key determinant of health-related quality of life in patients with chronic heart failure regardless of anemia status. Eur. J. Heart failure. 2013;15:1164–1172.
4. Jankowska E.A., Kasztura M., Sokolski M. et al. Iron deficiency defined as depleted iron stores accompanied by unmet cellular iron requirements identifies patients at the highest risk of death after an episode of acute heart failure. Eur. Heart J. 2014;35:2468–2476. doi: 10.1093/eurheartj/ehu235.
5. Iron deficiency and cardiovascular disease. von Haehling S, Jankowska EA, van Veldhuisen DJ, Ponikowski P, Anker SD. Nat Rev Cardiol. 2015 Nov;12(11):659-69. doi: 10.1038/nrcardio.2015.109.
6. Chopra VK, Anker SD. Anaemia, iron deficiency and heart failure in 2020: facts and numbers. ESC Heart Fail. 2020 Oct;7(5):2007-2011. doi: 10.1002/ehf2.12797.
7. Komajda M, Anker SD, Charlesworth A., et al. The impact of new onset anaemia on morbidity and mortality in chronic heart failure: results from COMET. Eur Heart J. 2006 Jun;27(12):1440-6. doi: 10.1093/eurheartj/ehl012.
8. Von Haehling S, Schefold JC, Hodoscek LM et al. Anaemia is an independent predictor of death in patients hospitalized for acute heart failure. Clin Res Cardiol. 2010;99:107–113. doi: 10.1007/s00392-009-0092-3.
9. Martens P, Minten L. Prevalence of underlying gastrointestinal malignancies in iron-deficient heart failure. ESC Heart Fail. 2019 Feb; 6:37–44. doi: 10.1002/ehf2.12379.
10. Jankowska EA, von Haehling S, Anker SD, Macdougall IC, Ponikowski P. Iron deficiency and heart failure: diagnostic dilemmas and therapeutic perspectives. Eur Heart J. 2013;34:816–29. doi: 10.1093/eurheartj/ehs224.
11. Mareev V.Yu., Gilyarevskii S.R., Mareev Yu.V. Consensus opinion of experts on the role of iron deficiency in patients with chronic heart failure, as well as modern approaches to its correction. Cardiology. 2020;60(1):99–106. doi: 10.18087/cardio.2020.1.n961.
12. Mistry R. H., Kohut A., Ford P. Correction of iron deficiency in hospitalized heart failure patients does not improve patient outcomes. Annals of Hematology. 2020;100(3),661–666. doi:10.1007/s00277-020-04338-2.
13. Núñez J, Comín-Colet J, Miñana G et al. Iron deficiency and risk of early readmission following a hospitalization for acute heart failure. Eur J Heart Fail. 2016;18:798–802. doi: 10.1002/ejhf.513.
14. Ponikowski P, Kirwan BA, Anker SD et al. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial. AFFIRM-AHF investigators. Lancet. 2020 Dec 12;396(10266):1895-1904. doi: 10.1016/S0140-6736(20)32339-4.
15. Melenovsky V, Petrak J, Mracek T et al. Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis. Eur J Heart Fail 2017;19:522–30. doi: 10.1002/ejhf.640.
16. Hoes MF, Grote Beverborg N, Kijlstra JD et al. Iron deficiency impairs contractility of human cardiomyocytes through decreased mitochondrial function. Eur J Heart Fail. 2018;20:910–19. doi: 10.1002/ejhf.1154.
17. Okonko D.O., Mandal A.K., Missouris C.G., Poole-Wilson P.A. Disordered iron homeostasis in chronic heart failure: Prevalence, predictors, and relation to anemia, exercise capacity, and survival. J. Am. Coll. cardiol. 2011;58:1241–1251. doi: 10.1016/j.jacc.2011.04.040.
18. Naito Y, Tsujino T, Matsumoto M et al. Adaptive response of the heart to long-term anemia induced by iron deficiency. Am J Physiol Heart Circ Physiol. 2009;296:H585-H593. doi: 10.1152/ajpheart.00463.2008.
19. Anand IS, Gupta P. Anemia and Iron Deficiency in Heart Failure. circulation. 2018;138(1):80-98. https://doi.org/10.1161/CIRCULATIONAHA.118.030099.
20. McDonagh T.A., et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021. doi: 10.1093/eurheartj/ehab368.
21. Tereshchenko S.N., Galyavich A.S., Uskach T.M. etc. Chronic heart failure. Clinical guidelines 2020. Russian Journal of Cardiology. 2020;25(11):311-374. doi: 10.15829/1560-4071-2020-4083.
22. Grote Beverborg N, Klip IT, Meijers WC, et al. Definition of iron deficiency based on the gold standard of bone marrow iron staining in heart failure patients. Circ Heart Fail. 2018;11:e004519. doi:10.1161/CIRCHEARTFAILURE.117.004519.
23. Robles NR, Campillejo RD, Valladares J, et al. Sacubitril-Valsartan Improves Anemia of Cardiorenal Syndrome (CRS). Cardiovasc Hematol Agents Med Chem. 2021;19(1):93-97. doi: 10.2174/1871525718666200506095537.
24. Docherty KF, Petrie MC. Sodium-glucose cotransporter 2 inhibitors as a treatment for heart failure. Heart 2021;0:1–9. doi:10.1136/heartjnl-2020-318658.
25. Mazer CD, Hare GM, Connelly PW, Gilbert RE, Shehata N, et al. Effect of empagliflozin on erythropoietin levels, iron stores, and red blood cell morphology in patients with type 2 diabetes mellitus and coronary artery disease. circulation. 2020;141:704–7. doi: 10.1161/CIRCULATIONAHA.119.044235.
26. Ghanim H, Abuaysheh S, Hejna J, Green K, Batra M, et al. Dapagliflozin Suppresses Hepcidin And Increases Erythropoiesis. J Clin Endocrinol Metab. 2020 Apr 1;105(4):dgaa057. doi: 10.1210/clinem/dgaa057.
27. Docherty, K. F., Curtain, J. P., Anand, I. S., Bengtsson, O., Inzucchi, S. E., et al. Effect of dapagliflozin on anemia in DAPA-HF. European Journal of Heart Failure. 2021;23(4), 617–628. doi:10.1002/ejhf.2132.
28. Ferreira JP, Anker SD., Butler J, Filippatos G, Iwata T et al. Impact of anemia and the effect of empagliflozin in heart failure with reduced ejection fraction: findings from EMPEROR-Reduced. European Journal of Heart Failure. 2022. doi:10.1002/ejhf.2409.
29. 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. Gregory D. Lewis, Rajeev Malhotra, Adrian F. Hernandez, Steven E. McNulty, Andrew Smith, G. Michael Felker, W.H. Wilson Tang, Shane J. LaRue, Margaret M. Redfield, Marc J. Semigran, Michael M. Givertz, Peter Van Buren, David Whellan, Kevin J. Anstrom, Monica R. Shah, Patrice Desvigne-Nickens, Javed Butler, Eugene Braunwald , for the NHLBI Heart Failure Clinical Research Network. JAMA. 2017 May 16; 317(19): 1958–1966. doi:10.1001/jama.2017.5427
30. Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, et al. FAIR-HF Trial Investigators. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009; 361:2436-2448. doi: 10.1056/NEJMoa0908355.
31. Veldhuisen DJ, Ponikowski P, van der Meer P, Metra M, Bohm M, et al. EFFECT-HF Investigators. Effect of ferric carboxymaltose on exercise capacity in patients with chronic heart failure and iron deficiency. Circulation 2017; 136:1374-1383. doi: 10.1161/CIRCULATIONAHA.117.027497.
32. Filippatos G, Farmakis D, Colet JC, Dickstein K, Luscher TF, et al. Intravenous ferric carboxymaltose in iron-deficient chronic heart failure patients with and without anaemia: a subanalysis of the FAIR-HF trial. Eur J Heart Fail 2013;15:12671276. doi: 10.1093/eurjhf/hft099.
33. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V et al.; CONFIRM-HF Investigators. Eur Heart J. 2015 Mar 14;36(11):657-68. doi: 10.1093/eurheartj/ehu385.
34. Anker SD, Kirwan BA, van Veldhuisen DJ, Filippatos G, Comin-Colet J, et al. 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 2018;20:125133. doi: 10.1002/ejhf.823.
35. Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial. Kalra PR, Cleland JGF, Petrie MC, Thomson EA, Kalra PA et al.; IRONMAN Study Group. Lancet. 2022 Nov 4:S0140-6736(22)02083-9. doi: 10.1016/S0140-6736(22)02083-9.
36. Minhas AMK, Sagheer S, Shekhar R et al. Trends and Inpatient Outcomes of Primary Atrial Fibrillation Hospitalizations with Underlying Iron Deficiency Anemia: An Analysis of The National Inpatient Sample Database from 2004 -2018. Curr Probl Cardiol. 2021 Sep 24;101001. doi: 10.1016/j.cpcardiol.2021.101001.
37. Takabayashi, K., Unoki, T., Ogawa, H. et al. Clinical characteristics of atrial fibrillation patients with anemia: from the Fushimi AF registry. European Heart Journal. 2013;34(suppl 1):389–P389. doi:10.1093/eurheartj/eht307.p389.
38. Tu SJ, Hanna-Rivero N, Elliott AD et al. Associations of anemia with stroke, bleeding, and mortality in atrial fibrillation: a systematic review and meta-analysis. J Cardiovasc Electrophysiol. 2021;32:686–94. doi: 10.1111/jce.14898.
39. Lee WH, Hsu PC, Chu CY et al. Anemia as an Independent Predictor of Adverse Cardiac Outcomes in Patients with Atrial Fibrillation. International Journal of Medical Sciences. 2015;12:618-624. doi: 10.7150/ijms.11924.
40. An Y, Ogawa H, Esato M et al. Cardiovascular Events and Mortality in Patients With Atrial Fibrillation and Anemia (from the Fushimi AF Registry). Registry Investigators. Am J Cardiol. 2020 Nov 1;134:74-82. doi: 10.1016/j.amjcard.2020.08.009.
41. Anemia and iron deficiency in patients with atrial fibrillation. Hanna-Rivero N, Tu SJ, Elliott AD, Pitman BM, Gallagher C, Lau DH, Sanders P, Wong CX. BMC Cardiovasc Discord. 2022 May 4;22(1):204. doi: 10.1186/s12872-022-02633-6.
42. Keskin M, Ural D, Altay S et al. Iron deficiency and hematinic deficiencies in atrial fibrillation: A new insight into comorbidities. Turk Kardiyol Dern Ars. 2018 Mar;46(2):103-110. doi: 10.5543/tkda.2018.51001.
43. He S, Feng R, Xu Z et al. Digoxin-induced anemia among patients with atrial fibrillation and heart failure: clinical data analysis and drug-gene interaction network. oncotarget. 2017 Jun 16;8(34):57003-57011. doi: 10.18632/oncotarget.18504.
44. Tu SJ, Elliott AD, Hanna-Rivero N et al. Rationale and design of the IRON-AF study: a double-blind, randomised, placebo-controlled study to assess the effect of intravenous ferric carboxymaltose in patients with atrial fibrillation and iron deficiency. BMJ Open. 2021 Aug 9;11(8):e047642. doi: 10.1136/bmjopen-2020-047642.
45. Rymer JA, Rao SV. Anemia and coronary artery disease: pathophysiology, prognosis, and treatment. Coron Artery Dis. 2018; 29:161-7. doi: 10.1097/MCA.0000000000000598.
46. Report on the work of the Expert Council "Topical issues of iron deficiency in the Russian Federation". Therapy. 2020; 5:10-19. https://dx.doi.org/10.18565/therapy.2020.5.10-19.
47. Anker SD, Colet JC, Filippatos G, et al. FAIRHF committees and investigators. Rationale and design of Ferinject Assessment in patients with IRon deficiency and chronic Heart Failure (FAIRHF) study: a randomized, placebo-controlled study of intravenous iron supplementation in patients with and without anaemia. Eur J Heart Fail. 2009;11:1084–91.
48. Benedikt Schrage1,2, Nicole Rübsamen1, Francisco M. Ojeda et al. Association of iron deficiency with incidentcardiovascular diseases and mortality in the generalpopulation. ESC Heart failure. 2021;8: 4584–4592]. doi:10.1002/ehf2.13589.
49. Collet JP, Thiele H, Barbato E et al. (ESC Scientific Document Group). 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2020; ehaa575. doi: 10.1093/eurheartj/ehaa575.
50. Ye SD, Wang SJ, Wang GG et al. Association between anemia and outcome in patients hospitalized for acute heart failure syndromes: findings from Beijing Acute Heart Failure Registry (Beijing AHF Registry). Intern Emerge Med. 2021;16(1):183–92. doi: 10.1007/s11739-020-02343-x.
51. Huynh R, Hyun K, D'Souza M et al. Outcomes of anemic patients presenting with acute coronary syndrome: An analysis of the Cooperative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events. Clinic Cardiol. 2019;42(9):791–96. doi:10.1002/clc. 23219.
52. McKechnie RS, Smith D, Montoye C et al. Prognostic implication of anemia on in-hospitaL outcomes after percutaneous coronary intervention. circulation. 2004;110(3):271-277.https://doi.org/10.1161/01.CIR.0000134964.01697.C7.
53. Zeller T, Waldeyer C, Ojeda F et al. Adverse outcome prediction of iron deficiency in patients with acute coronary syndrome. biomolecules. 2018;8(3):60. doi: 10.3390/biom8030060.
54. O. Meroño, M. Cladellas, N. Ribas-Barquet, et al. Iron Deficiency in patients with acute coronary syndrome: prevalence and predisposing factors. Rev Esp Cardiol. 2016; 69:615-617.
55. Budnevsky A.V., Ovsyannikov E.S., Red'ka A.V. Influence of anemia on the course of cardiovascular diseases. Cardiovascular therapy and prevention, 2016; 15(1): 64–68 http://dx.doi.org/10.15829/1728-8800-2016-1-64-68
56.
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For citations:
Vinogradova N.G., Chesnikova A.I. Iron deficiency states in cardiovascular diseases: impact on prognosis and features of correction. South Russian Journal of Therapeutic Practice. 2023;4(1):7-18. (In Russ.) https://doi.org/10.21886/2712-8156-2023-4-1-7-18