clinmedКлиническая медицинаClinical Medicine (Russian Journal)0023-21492412-1339ООО «Медицинское информационное агентство»10.30629/0023-2149-2020-98-2-122-129clinmed-21Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL INVESTIGATIONSЦитокин-индуцированное воспаление при анемии у больных хронической сердечной недостаточностьюCytokine-induced inflammation in anemia in patients with chronic heart failurehttps://orcid.org/0000-0003-4767-4945ТкаченкоЕ. И.TkachenkoE. I.

Ткаченко Екатерина Игоревна — аспирант кафедры госпитальной терапии и общей врачебной практики им. В.Г. Вогралика 

603950, Нижний Новгород

etkachenko.doc@gmail.comБоровковаН. Ю.BorovkovaN. Y.

603950, Нижний Новгород

603950, Nizhny Novgorod

БуяноваМ. В.BuyanovaM. V.

603950, Нижний Новгород

603950, Nizhny Novgorod

БоровковН. Н.BorovkovN. N.

603950, Нижний Новгород

603950, Nizhny Novgorod

ФГБОУ ВО «Приволжский исследовательский медицинский университет» Минздрава РоссииРоссияPrivolzhsky Research Medical UniversityRussian Federation202015072020982122129Copyright © Ткаченко Е.И., Боровкова Н.Ю., Буянова М.В., Боровков Н.Н., 20202020Ткаченко Е.И., Боровкова Н.Ю., Буянова М.В., Боровков Н.Н.Tkachenko E.I., Borovkova N.Y., Buyanova M.V., Borovkov N.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.clinmedjournal.com/jour/article/view/21

Анемический синдром (АС) является частым патологическим состоянием среди пациентов с хронической сердечной недостаточностью (ХСН). Он признан независимым предиктором неблагоприятного прогноза. Особый вклад в течение ХСН вносит патогенетически связанная с ХСН анемия. Механизмы ее возникновения находятся в стадии изучения. Важную роль имеет системное воспаление, участвующее в формировании анемии хронических заболеваний (АХЗ). Однако вклад цитокин-индуцированного воспаления у больных ХСН в генез АС до настоящего времени до конца не изучен. Цель: проанализировать патогенетические особенности цитокин-индуцированного воспаления (по показателям интерлейкина-1β (ИЛ-1β), интерлейкина-6 (ИЛ-6), фактора некроза опухоли (ФНОα) и гепсидина) в генезе анемии у больных ХСН. Материал и методы. На базе кардиологического отделения ГБУЗ НО «НОКБ» (Нижний Новгород) проспективно проанализировано 873 случая больных ХСН. Основную группу составили пациенты с анемией, патогенетически связанной с ХСН (n = 96), контрольную группу (КГ) (n = 35) — пациенты с ХСН без анемии. Производилось оценка показателей феррокинетики и сравнение системного воспаления по показателям ИЛ-1β, ИЛ-6, ФНОα и гепсидина сыворотки крови. Результаты. У пациентов основной группы выявлены признаки функционального дефицита железа (ДЖ) и более высокие значения цитокинов и гепсидина по сравнению с группой контроля. Выявлена взаимосвязь уровня этих показателей со степенью тяжести ХСН, гемоглобином и хронической болезнью почек (ХБП). Заключение. Увеличение концентрации провоспалительных цитокинов и гепсидина у пациентов с АС при декомпенсации ХСН взаимосвязано с формированием функционального ДЖ и снижением уровня гемоглобина. Это указывает на роль цитокин-индуцированного воспаления в генезе анемии при ХСН. Особый вклад в эти механизмы вносит функциональное состояние почек, так как по мере нарастания ХБП увеличиваются уровни воспалительных цитокинов и гепсидина у этих пациентов и их взаимосвязь с маркерами (ХБП).

Introduction. Anemic syndrome (AS) is a common pathological condition in patients with chronic heart failure (CHF) and is recognized as an independent predictor of poor prognosis. A particular role is played by pathogenetically associated with CHF anemia. Mechanisms of its occurrence are being studied. An important role belongs to systemic inflammation, which is involved in the pathogenesis of anemia of chronic diseases (ACD). However, the contribution of cytokine-induced inflammation in patients with heart failure has not yet been fully investigated. Material and methods. A total of 873 cases of patients with CHF were prospectively analyzed on the basis of the cardiology department of the SBHCI NNR «Nizhny Novgorod Regional Clinical Hospital n.a. N.A. Semashko». The main group consisted of patients with anemia pathogenetically associated with heart failure (n = 96), the control group (CG) (n = 35) patients with heart failure without anemia. The indicators of ferrokinetics were assessed and the systemic inflammation was compared by indicators of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and serum hepсidin. Results. Patients of the main group had signs of functional iron deficiency (ID) and significantly higher values of cytokines and hepsidin compared with the CG. The relationship between the level of cytokines and hepsidin with the severity of CHF, hemogobin and chronic kidney disease was revealed. Conclusion. An increase in the concentration of pro-inflammatory cytokines and hepcidin in patients with AS with decompensation of CHF is interrelated with functional ID and a decrease in hemoglobin level. This shows the role of cytokine-induced inflammation in the genesis of anemia in heart failure. The functional state of the kidneys makes a special contribution to these mechanisms. As CKD increases, the levels of inflammatory cytokines and hepcidin in these patients and their relationship with markers (CKD) increase.

хроническая сердечная недостаточностьанемияпровоспалительные цитокиныинтерлейкин-1βинтерлейкин-6фактор некроза опухоли αгепсидинхроническая болезнь почекchronic heart failureanemiapro-inflammatory cytokinesinterleukin-1βinterleukin-6tumor necrosis factor-αhepсidinchronic kidney diseaseReferencesPonikowski P., Voors A.A., Anker S.D., Bueno H., Cleland J.G.F., Coats A.J.S. et al. Рекомендации ESK по диагностике и лечению острой и хронической сердечной недостаточности 2016. Российский. кардиологический журнал. 2017;1(141):7–81.Ponikowski P., Voors A.A., Anker S.D., Bueno H., Cleland J.G.F., Coats A.J. S. et al. 2016 ESK guidelines for the diagnosis and treatment of acute and chronic heart failure. Rossiyskiy kardiologicheskiy zhurnal. 2017;1(141):7–81. (in Russian)Ezekowitz J.A., McAlister F.A., Armstrong P.W. 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):223–5.Ezekowitz J.A., McAlister F.A., Armstrong P.W. 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):223–5.Tang W.H., Tong W., Jain A., Francis G.S., Harris C.M., Young J.B. Evaluation and long-term prognosis of new-onset, transient, and persistent anemia in ambulatory patients with chronic heart failure. J. Am. Coll. Cardiol. 2008;51:569–76.Tang W.H., Tong W., Jain A., Francis G.S., Harris C.M., Young J.B. Evaluation and long-term prognosis of new-onset, transient, and persistent anemia in ambulatory patients with chronic heart failure. J. Am. Coll. Cardiol. 2008;51:569–76.Сaughey M.C., Avery C.L., Ni H., Solomon S.D., Matsushita K., Wruck L.M. et al. Outcomes of patients with anemia and acute decompensated heart failure with preserved versus reduced ejection fraction (from the ARIC study community surveillance). Am. J. Cardiol. 2014;114(12):1850–4.Сaughey M.C., Avery C.L., Ni H., Solomon S.D., Matsushita K., Wruck L.M. et al. Outcomes of patients with anemia and acute decompensated heart failure with preserved versus reduced ejection fraction (from the ARIC study community surveillance). Am. J. Cardiol. 2014;114(12):1850–4.Núñez J., Comín-Colet J., Miñana G., Núñez E., Santas E., Mollar A. et al. Iron deficiency and risk of early readmission following a hospitalization for acute heart failure: Iron deficiency and rehospitalization. Eur. J. Heart Failure. 2016;18(7):798–802 .Núñez J., Comín-Colet J., Miñana G., Núñez E., Santas E., Mollar A. et al. Iron deficiency and risk of early readmission following a hospitalization for acute heart failure: Iron deficiency and rehospitalization. Eur. J. Heart Failure. 2016;18 (7):798–802.Pozzo J., Fournier P., Delmas C., Vervueren P-L., Roncalli J., Elbaz M. et al. Absolute iron deficiency without anemia in patients with chronic systolic heart failure is associated with poorer functional capacity. Arch. Cardiovasc. Dis. 2017;110(2):99–105.Pozzo J., Fournier P., Delmas C., Vervueren P-L., Roncalli J., Elbaz M. et al. Absolute iron deficiency without anemia in patients with chronic systolic heart failure is associated with poorer functional capacity. Arch. Cardiovasc. Dis. 2017;110(2):99–105.Ebner N., Jankowska E.A., Ponikowski P., Lainscak M., Elsner S., Sliziuk V. et al. The impact of iron deficiency and anaemia on exercise capacity and outcomes in patients with chronic heart failure. Results from the studies investigating co-morbidities aggravating heart failure. Int. J. Cardiol. 2016;205:6–12.Ebner N., Jankowska E.A., Ponikowski P., Lainscak M., Elsner S., Sliziuk V. et al. The impact of iron deficiency and anaemia on exercise capacity and outcomes in patients with chronic heart failure. Results from the studies investigating co-morbidities aggravating heart failure. Int. J. Cardiol. 2016;205:6–12.Karla P.R., Collier T., Cowie M.R., Fox K.F., Wood D.A., PooleWilson P.A. et al. Haemoglobin concentration and prognosis in new cases of heart failure. Lancet. 2003;362(9379):211–2.Karla P.R., Collier T., Cowie M.R., Fox K.F., Wood D.A., PooleWilson P.A. et al. Haemoglobin concentration and prognosis in new cases of heart failure. Lancet. 2003;362 (9379):211–12.Enjuanes C., Bruguera J., Grau M., Cladellas M., Gonzalez G., Meroño O. et al. Iron status in chronic heart failure: impact on symptoms, functional class and submaximal exercise capacity. Rev. Esp. Cardiol. 2016;69(3):247–55.Enjuanes C., Bruguera J., Grau M., Cladellas M., Gonzalez G., Meroño O. et al. Iron status in chronic heart failure: impact on symptoms, functional class and submaximal exercise capacity. Rev. Esp. Cardiol. 2016;69(3):247–55.Стуклов Н.И. Дефицит железа и анемия у больных хронической сердечной недостаточностью. Рациональная фармакотерапия в кардиологии. 2017;13(5):651–60.Stuklov N.I. Iron deficiency and anemia in patients with chronic heart failure. Ratsionalnaya farmakoterapiya v kardiologii. 2017;13(5):651–60. (in Russian)Marazia S., Loderini S., Magliari F., Sarullo F.M., Di Mauro M. Sucrosomial iron supplementation can be a useful support treatment in patients with heart failure and anemia. In: Materials of 5th International Multidisciplinary Course on Iron Anemia. Florence, Italy. March 31 — April 1, 2017.Marazia S., Loderini S., Magliari F., Sarullo F.M., Di Mauro M. Sucrosomial iron supplementation can be a useful support treatment in patients with heart failure and anemia. In: Materials of 5th International Multidisciplinary Course on Iron Anemia. Florence, Italy. March 31 — April 1, 2017.Захидова К.Х. Выбор оптимальной терапии при коррекции анемического синдрома у больных с хронической сердечной недостаточностью. Кардиология. 2018;58(1):25–31.Zakhidova K.Kh. The choice of optimal therapy for the correction of anemic syndrome in patients with chronic heart failure. Kardiologiya. 2018;58(1):25–31. (in Russian)Соломахина Н.И., Находнова Е.С., Беленков Ю.Н. Анемия хронических заболеваний и железодефицитная анемия: сравнительная характеристика показателей феррокинетики и их связь с воспалением у больных ХСН в пожилом и старческом возрасте. Кардиология. 2018;58(S8):58–64.Solomakhina N.I., Nakhodnova E.S., Belenkov Y.N. Anemia of chronic disease and iron deficiency anemia: Comparative characteristics of ferrokinetic parameters and their relationship with inflammation in late middle-aged and elderly patients with CHF. Kardiologiia. 2018;58(S8):58–64. (in Russian)Hoes M.F., Grote Beverborg N., Kijlstra J.D, Kuipers J., Swinkels D.W., Giepmans B.N.G. et al. Iron deficiency impairs contractility of human cardiomyocytes through decreased mitochondrial function: Impaired contractility in iron-deficient cardiomyocytes. Eur. J. Heart Failure. 2018;20(5):910–9.Hoes M.F., Grote Beverborg N., Kijlstra J.D, Kuipers J., Swinkels D.W., Giepmans B.N.G. et al. Iron deficiency impairs contractility of human cardiomyocytes through decreased mitochondrial function: Impaired contractility in iron-deficient cardiomyocytes. Eur. J. Heart Failure. 2018;20(5):910–9.Сумароков А.Б., Бурячковская Л.И., Учитель И.А. Кровотечения у больных с ишемической болезнью сердца при проведении терапии антиагрегантами. Кардиосоматика. 2011;3:29–35 .Sumarokov A.B., Buryachkovskaya L.I., Uchitel’ I.A. Bleeding in patients with coronary heart disease during antiplatelet therapy. Kardiosomatika. 2015;3:29–35. (in Russian)Atkinson M.A. Anemia in children with chronic kidney disease. Nat. Rev. Nephrol. 2011;7:635–41.Atkinson M.A. Anemia in children with chronic kidney disease. Nat. Rev. Nephrol. 2011;7:635–41.Lipsic, E., van der Meer P. Erithropoietin, iron, or both in heart failure: FAIR-HF in perspective. Eur. J. Heart Failure. 2010;12: 104–5.Lipsic E., van der Meer P. Erithropoietin, iron, or both in heart failure: FAIR-HF in perspective. Eur. J. Heart Failure. 2010;12:104–5.Элмурадов Ф.Х., Разиков А.А., Рахимова М.Э., Салихова М.Ф., Гадаев А.Г. Риск нарушения почечной функции при хронической сердечной недостаточности. В сб.: Материалы III Междунар. науч.-практ. конференции. Улан-Удэ: Восточно-Сибирский государственный университет технологий и управления; 2015:348–351.Elmuradov F.Kh., Razikov A.A., Rakhimova M.E., Salikhova M.F., Gadaev A.G. The risk of impaired renal function in chronic heart failure. Сollection of materials of the third international scientific-practical conference. [Materialy III Mezhdunar. nauch.-prakt. konferentsii]. Ulan-Ude: VostochnoSibirskii gosudarstvennyi universitet tekhnologii i upravleniya]; 2015: 348–51. (in Russian)Androne A.S., Katz S.D., Lund L. Hemodilution is common in patients with advanced heart failure. Circulation. 2003;107(2): 226–9.Androne A.S., Katz S.D., Lund L. Hemodilution is common in patients with advanced heart failure. Circulation. 2003;107(2):226–9.Ishani A., Weinhandl E., Zhao Z., Gilbertson D.T., Collins A.J., Yusuf S., Herzog C.A. Angiotensin converting enzyme inhibitor as a risk factor for the development of anemia, and the impact of incident anemia on mortality in patients with left ventricular dysfunction. J. Am. Coll. Cardiol. 2005;45:391–9.Ishani A., Weinhandl E., Zhao Z., Gilbertson D.T., Collins A.J., Yusuf S., Herzog C.A. Angiotensinconverting enzyme inhibitor as a risk factor for the development of anemia, and the impact of incident anemia on mortality in patients with left ventricular dysfunction. J. Am. Coll. Cardiol. 2005;45:391–9.Ross R. Atherosclerosis — an inflammatory disease. N. Engl. J. Med. 1999;34:115–26.Ross R. Atherosclerosis — an inflammatory disease. N. Engl. J. Med. 1999;34:115–26.Anand I.S. Relationship between proinflammatory cytokines and anemia in heart failure. Eur. Heart J. 2006;27(1):485–9.Anand I.S. Relationship between proinflammatory cytokines and anemia in heart failure. Eur. Heart J. 2006;27(1):485–9.Deswal A., Petersen N.J., Feldman A.M., Young J.B., White B.G., Mann D.L. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation. 2001;103:2055–9.Deswal A., Petersen N.J., Feldman A.M., Young J.B., White B.G., Mann D.L. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation. 2001;103:2055–9.Papathanasiou S., Rickelt S., Soriano M.E., Schips T.G., Maier H.J., Davos C.H., Varela A., Kaklamanis L., Mann D.L., Capetanaki Y. Tumor necrosis factor-α confers cardioprotection through ectopic expression of keratins K8 and K18. Nat. Med., 2015;21(9):1076–84.Papathanasiou S., Rickelt S., Soriano M.E., Schips T.G., Maier H.J., Davos C.H., Varela A., Kaklamanis L., Mann D.L., Capetanaki Y. Tumor necrosis factor-α confers cardioprotection through ectopic expression of keratins K8 and K18. Nat. Med., 2015;21(9):1076–84.Ruchala P., Nemeth E. The pathophysiology and farmacology of hepcidin. Trends Pharmacol. Sci. 2014;35(3):155–61.Ruchala P., Nemeth E. The pathophysiology and farmacology of hepcidin. Trends Pharmacol. Sci. 2014;35(3):155–61.Przybyszewska J., Zekanowska E. The role og hepcidin, ferroportin, HCP1 and DNT1 protein in iron absorbtion in human digestive tract. Prz. Gastroenterol. 2014;9(4):208–13.Przybyszewska J., Zekanowska E. The role og hepcidin, ferroportin, HCP1 and DNT1 protein in iron absorbtion in human digestive tract. Prz. Gastroenterol. 2014;9(4):208–13.Solomakhina N.I., Nakhodnova E.S., Gitel E.P., Belenkov Y.N. Hepcidin and its relationship with inflammation in old and older patients with anemia of chronic disease associated with CHF. Kardiologiia. 2018;17(2):4–11.Solomakhina N.I., Nakhodnova E.S., Gitel E.P., Belenkov Y.N. Hepcidin and its relationship with inflammation in old and older patients with anemia of chronic disease associated with CHF. Kardiologiia. 2018;17(2):4–11. (in Russian)Van der Pu-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. Am. J. Hematol. 2011;86(1):107–9.Van der Pu-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. Am. J. Hematol. 2011;86(1):107–9.Matsumoto M., Tsujino T., Lee-Kawabata M., Naito Y., Akahori H., Sakoda T. Iron regulatory hormone hepcidin decreases in chronic heart failure patients with anemia. Circ. J. 2010;74(2):301–6.Matsumoto M., Tsujino T., Lee-Kawabata M., Naito Y., Akahori H., Sakoda T. Iron regulatory hormone hepcidin decreases in chronic heart failure patients with anemia. Circ.J. 2010;74(2):301–6.Divakaran V. Hepcidin in anemia of chronic heart failure. Am. J. Hematol. 2011;86(1):107–9.Divakaran V. Hepcidin in anemia of chronic heart failure. Am. J. Hematol. 2011;86(1):107–9.WHO. Serum ferritin concentrations for the assessment of iron status and iron deficiency in populations. Vitamin and Mineral Nutrition Information System. Geneva, World Health Organization, 2011 (WHO/NMH/NHD/MNM/11.2WHO. Serum ferritin concentrations for the assessment of iron status and iron deficiency in populations. Vitamin and Mineral Nutrition Information System. Geneva, World Health Organization, 2011 (WHO/NMH/NHD/MNM/11.2Затонский С.А., Кастанян А.А. Патогенетическое значение цитокинов при хронической сердечной недостаточности ишемического генеза и влияние кардиоваскулярной терапии на иммунологические показатели. Современные проблемы науки и образования. 2013;6.Zatonskij S.A., Kastanjan A.A. The pathogenetic significance of cytokines in chronic heart failure of ischemic genesis and the effect of cardiovascular therapy on immunological parameters. Sovremennye problemy nauki i obrazovanija. 2013;6:107–9. (in Russian)Nicolas G., Bennoun M., Porteu A. et al. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc. Natl. Acad. Sci. 2002;99(7):4596–601.Nicolas G., Bennoun M., Porteu A. et al. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc. Natl. Acad. Sci. 2002;99(7):4596–601.

The authors declare that there are no conflicts of interest present.