Prognostic value of erythropoietin in elderly and senile patients with heart failure and anemia

Prognostic value of erythropoietin in elderly and senile patients with heart failure and anemia

OBJECTIVE: to study the prognostic value of erythropoietin (EPO) levels in elderly and senile patients with chronic heart failure (CHF) and anemia.

MATERIAL AND METHODS. EPO levels in blood serum were determined once in 105 patients with CHF and anemia aged 65 to 90 years. The follow-up period was 24 months. The primary endpoint was death from all causes. The adequacy of endogenous EPO production was assessed by the ratio «observed EPO / predicted EPO» (O/P), calculated on the basis of EPO and hemoglobin levels in patients of the control group with iron deficiency anemia without CHF – [HR 1.004 ± 0.004 [95 % CI; (0.919–1.080)]. The value of O/P < 0.9 was considered insufficient production of EPO, O/P > 1.1 – excessive, O/P = 1.0 – adequate. The Kaplan – Meyer method was used to compare survival rates depending on the value of O/P levels of EPO. Regression analysis of proportional hazards of Cox was used to assess the effect of the value of O/P levels of EPO on the risk of death.

RESULTS. In patients with CHF and anemia, the average EPO level was (35.900 ± 2.537) mIU/ml [8.46; 154.00]. According to the obtained ratio of O/P levels of EPO, 59 % of patients showed signs of excessive production of EPO (O/P > 1.1), 18 % – insufficient production (O/P < 0.9) and adequate – in 23 % (O/P = 1.0). The Kaplan – Mayer method showed significantly higher mortality in patients with O/P > 1.1 than in patients with O/P < 0.9  and O/P = 1 (p = 0.00418). The analysis of proportional hazards of Cox revealed an effect on the risk of death of the ratio O/P > 1.1 at the trend level in a single-factor analysis [HR 0.947 (95 % CI; 0.893–1.004), p = 0.069] and significant in a multifactorial [HR 0.924 (95 % CI; 0.859–0.994), p = 0.034].

CONCLUSION. Elderly and senile patients with CHF and anemia are characterized by marked variability in EPO levels, while there may be excessive, insufficient or adequate EPO production. The prognostic value of O/P levels of EPO as a marker of the discrepancy between the degree of anemia and the actual production of EPO was revealed, while the O/P value >1.1 indicates an unfavorable prognosis, since it correlates with an increased risk of death.

1. Fomin I. V. Chronic heart failure in Russian Federation: what do we know and what to do. Russian journal of cardiology. 2016 ; (8) : 7–13. (In Russ.). doi: 10.15829/1560-4071-2016-8-7-13.

2. Beguin Y., Clemons G. K., Pootrakul P., et al. Quantitative assessment of erythropoiesis and functional classification of anemia based on measurements of serum transferrin receptor and erythropoietin. Blood. 1993 ; 81 (4) : 1067–1076.

3. Spivak J. L. Serum immunoreactive erythropoietin in health and disease. J Perinat Med. 1995 ; 23 (1–2) : 13–17. doi: 10.1515/jpme.1995.23.1-2.13.

4. van der Meer P., Lok D. J., Januzzi J. L., et al. Adequacy of endogenous erythropoietin levels and mortality in anaemic heart failure patients. Eur Heart J. 2008 ; 29 (12) : 1510–1515. doi: 10.1093/eurheartj/ehn205.

5. Grote Beverborg N., van der Wal H. H., Klip I. T., et al. High serum erythropoietin levels are related to heart failure development in subjects from the general population with albuminuria: data from PREVEND. Eur J Heart Fail. 2016 ; 18 (7) : 814–821. doi: 10.1002/ejhf.484.

6. Garimella P. S., Katz R., Patel K. V., et al. Health ABC study. Association of serum erythropoietin with cardiovascular events, kidney function decline, and mortality: the health aging and body composition study. Circ Heart Fail. 2016 ; 9 (1) : e002124. doi: 10.1161/CIRCHEARTFAILURE.115.002124.

7. Nagai T., Nishimura K., Honma T., et al. Prognostic significance of endogenous erythropoietin in longterm outcome of patients with acute decompensated heart failure. Eur J Heart Fail. 2016 ; 18 (7) : 803–813. doi: 10.1002/ejhf.537.

8. Tkaczyszyn M., Comín-Colet J., Voors A. A., et al. Iron deficiency contributes to resistance to endogenous erythropoietin in anaemic heart failure patients. Eur J Heart Fail. 2021 ; 23 (10) : 1677–1686. doi: 10.1002/ejhf.2253.

9. Montero D., Haider T., Flammer A. J. Erythropoietin response to anaemia in heart failure. Eur J Prev Cardiol. 2019 ; 26 (1) : 7–17. doi: 10.1177/2047487318790823.

10. Efremova E. V., Shutov A. M., Podusov A. S. The prognostic value of endogenous erythropoietin in chronic heart failure. Nephrology and Dialysis. 2021;23(1):90-97. (In Russ.)]. doi: 10.28996/2618-9801-2021-1-90-97.

11. Chatterjee B., Nydegger U. E., Mohacsi P. Serum erythropoietin in heart failure patients treated with ACE-inhibitors or AT(1) antagonists. Eur J Heart Fail. 2000 ; 2 (4) : 393–398. doi: 10.1016/s1388-9842(00)00110-0.

12. Girelli D., Marchi G., Camaschella C. Anemia in the Elderly. Hemasphere. 2018 ; 2 (3) : e40. doi: 10.1097/HS9.0000000000000040.

13. Bulgakova S. V., Zakharova N. O., Treneva E. V., Lobinskaya M. A. Current understanding of anemic syndrome in older age groups (literature review). Current problems of health care and medical statistics. 2020 ; (2) ; 45–68. (In Russ.). doi: 10.24411/2312-2935-2020-10031.

14. Belonje A. M., Voors A. A., van der Meer P., et al. Endogenous erythropoietin and outcome in heart failure. Circulation. 2010 ; 121 (2) : 245–251. doi: 10.1161/CIRCULATIONAHA.108.844662.

15. 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. 2005 ; 26 (21) : 2232–2237. doi: 10.1093/eurheartj/ehi388.

16. McDonagh T. A., Metra M., Adamo M., et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 ; 42 (36) : 3599–3726. doi: 10.1093/eurheartj/ehab368.

17. Mareev V. Y., Fomin I. V., Ageev F. T. et al. Russian Heart Failure Society, Russian Society of Cardiology. Russian Scientific Medical Society of Internal Medicine Guidelines for Heart failure: chronic (CHF) and acute decompensated (ADHF). Diagnosis, prevention and treatment. Kardiologia. 2018 ; 58 (6S) : 8–158. (In Russ.). doi.org/10.18087/cardio.2475.

18. Gurkina A. A., Stuklov N. I., Kisly N. D., et al. Characteristics of anemia in heart failure: iron metabolism, erythropoietic activity and markers of inflammation. Cardiovascular Therapy and Prevention. 2023 ; 22 (1) : 3332 (In Russ.). doi: 10.15829/1728-8800-2023-3332.

19. Zahidova K. K. Indexes of the erythropoietin level in the blood plasma of chronic heart failure patients with anemia. J Basic Clin Physiol Pharmacol. 2018 ; 29 (1) : 11–17. doi: 10.1515/jbcpp-2016-0102.

20. Makarova N. A. Present ways of iron deficiency correction in chronic heart failure. Nepreryvnoe medicinskoe obrazovanie i nauka. 2023 ; 18 (1) : 23–28. (In Russ.).

21. Smith K. J., Bleyer A. J., Little W. C., Sane D. C. The cardiovascular effects of erythropoietin. Cardiovasc Res. 2003 ; 59 (3) : 538–548. doi: 10.1016/s0008-6363(03)00468-1.

22. Markousis-Mavrogenis G., Tromp J., Ouwerkerk W., et al. The clinical significance of interleukin-6 in heart failure: results from the BIOSTAT-CHF study. Eur J Heart Fail. 2019 ; 21 (8) : 965–973. doi: 10.1002/ejhf.1482.

23. Weiss G., Ganz T., of inflammation. Blood. 2019 ; 133 (1) : 40–50. doi: 10.1182/blood-2018-06-856500.

24. Lykov A. P. Erythropoietin: function and therapeutic potential. Sibirskij nauchnyj medicinskij zhurnal = Siberian Scientific Medical Journal. 2023 ; 43 (3) : 29–39. (In Russ.). doi: 10.18699/SSMJ20230203.

25. Swedberg K., Young J. B., Anand I. S., et al. Treatment of anemia with darbepoetin alfa in systolic heart failure. N Engl J Med. 2013 ; 368 (13) : 1210–1219. doi: 10.1056/NEJMoa1214865.

26. Docherty K. F., Welsh P., Verma S., et al. Iron Deficiency in Heart Failure and Effect of Dapagliflozin: Findings From DAPA-HF. Circulation. 2022 ; 146 (13) : 980–994. doi: 10.1161/CIRCULATIONAHA.122.060511.

27. Szczech L. A., Barnhart H. X., Inrig J. K., et al. Secondary analysis of the CHOIR trial epoetin-alpha dose and achieved hemoglobin outcomes. Kidney Int. 2008 ; 74 (6) : 791–798. doi: 10.1038/ki.2008.295.