The Role of Hepcidin in Formation of Anemia of Chronic Disease and Iron Deficiency Anemia in Elderly and Old Patients With Chronic Heart Failure

Background. Literature data on hepcidin (H) level - the main regulator of systemic iron homeostasis in patients with chronic heart failure (CHF) - are contradictory. Relationships of H with markers of inflammation elevated level of which is characteristic of CHF are insufficiently studied. The latter problem remains practically unexplored in elderly and very old patients with CHF. Aim: to study the role of H in formation of anemia of chronic disease (ACD) and iron deficiency anemia (IDA) in elderly and very old patients with CHF. Material and methods. We examined 65 elderly and very old patients with ischemic heart disease (IHD) (35 with CHF and ACD, 10 with CHF and IDA, 20 without CHF, ACD, and IDA [control group]). H level in blood serum was measured using competitive solid-phase immunoenzyme assay. Results and discussion. In patients with CHF and ACD mean H levels were significantly high relative to those in patients with CHF and IDA, while in the latter group H levels were insignificantly low relative to those in patients of control group. High H level, high level of inflammatory tests as well as positive correlations between them, and negative correlation between H and hemoglobin (Hb) are indicative of inflammation as a cause of H level elevation, which in turn facilitates development of anemia in elderly and very old patients with CHF and ACD. Low H level, normal levels of inflammatory tests, absence of links between them, as well as absence of correlation between H and Hb are indicative of lack of H role in development of anemia in these patients with CHF and IDA. We did not study influence on development of anemia of each of possible causes (inflammation, decompensation of CHF) separately, therefore contribution of each of them is unknown. The data obtained also do not exclude effect of other not investigated in this work and presently unknown factors. Received by us data indicate to necessity of precise identification of origin of anemia in every case in an elderly or very old patient with CHF with the aim of elimination of its cause and conduct of pathogenetically valid therapy.

хроническая сердечная недостаточность, анемия хронических заболеваний, железодефицитная анемия, гепсидин, hepcidin, chronic heart failure, anemia of chronic disease, iron deficiency anemia, old age

1. Park C. H., Valore E. V., Waring A.J. et al. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. Journal of Biological Chemistry 2001;276 (11):7806-7810.

2. Кетпа Е. Н., Tjalsma Н., Willems H. L. et al. Hepcidin: from discovery to differential diagnosis. Haematologica 2008;93 (1):90-97.

3. Finberg K. E. Regulation of systemic iron homeostasis. Curr Opin Hematol 2013; 20:208-214.

4. Nairz M., Theurl I., Wolf D. еt al. Iron deficiency or anemia of inflammation? Differential diagnosis and mechanisms of anemia of inflammation 2016;166 (13):411.

5. Arezes J., Nemeth E. Hepcidin and iron disorders: new biology and clinical approaches. International Journal of Laboratory Hematology 2015;37 (S1):92-98.

6. DAngelo G. Role of hepcidin in the pathophysiology and diagnosis of anemia. Blood Res 2013;48 (1):10-15.

7. Camaschella C. Iron and hepcidin: a story of recycling and balance. Hematol Am Soc Hematol Educ Program 2013; 2013:1-8.

8. Nanas J., Matsouka C., Karageorgopoulos D. et al. Etiology of anemia in patients with advanced heart failure. J Am Coll Cardiol 2006;48 (12):2485-2489.

9. Ezekowitz J. A., McDister F. А., Armstrong P. W. Anemia is соmmоn in heart fаiturе and is associated with poor outcomes: in sights from а cohort of l2065 patients with new-onset heart failure. Circulation 2003;107 (2):223-225.

10. Levin A. A., Kazakova T. V., Tsvetaeva, N. V. et al. Hepcidin as a regulator of iron homeostasis. Pediatrics 2008;87 (1):67-74. Russian (Левина А. А., Казюкова Т. В., Цветаева, Н. В. и др. Гепсидин как регулятор гомеостаза железа. Педиатрия 2008;87 (1):67-74).

11. Leong W., Lonnerdal B. Hepcidin the recently identified peptide that appears to regulate iron absorption. J Nutr 2004;134:1-4.

12. Van der Put-ten K., Jie K. E., van den Broek D. et al. Hepcidin-25 is a marker of the response rather than resistance to exogenous erythropoietin in chronic kidney disease chronic heart failure patients. EurJ Heart Fail 2010;12 (9):943-950.

13. Divakaran V., Mehta S., Yao D. et al. Hepcidin in anemia of chronic heart failure. Am J Hematol 2011;86 (1):107-109.

14. Hunter H. N., Fulton D. B., Ganz T. et al. The solution structure of human hepcidin, a peptide hormone with antimicrobial activity that is involved in iron uptake and hereditary hemochromatosis. Journal of Biological Chemistry 2002;277 (40):37597-37603.

15. Kemna E., Pickkers P., Nemeth E. et al. Time course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. Blood 2005;106 (5):1864-1866.

16. Nemeth E., Rivera S., Gabayan V. et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 2004; 113:1271-1276.

17. Muzzarelli S., Pfisterer M. TIME Investigators. Anemia as independent predictor of major events in elderly patients with chronic angina. Am Heart J 2006;152 (5):991-996.

18. Jankowska E. A., Anker S. D., Macdougall I. C. et al. Iron deficiency and heart failure: diagnostic dilemmas and therapeutic perspectives. European Heart Journal 2012;34 (11):816-829.

19. Nicolas G., Bennoun M., Porteu A. et al. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci USA 2002;99 (7):4596-4601.

20. Rebrov A. P., Sazhina E. Y. Endothelial dysfunction and features of changes in the level of cytokines and C-reactive protein in patients with chronic heart failure. Russian journal of cardiology 2005; 2:26

21. Finberg K. E. Regulation of systemic iron homeostasis. Curr Opin Hematol 2013; 20:208-214.