CC BY
14
Turakulov Rustam Ismatullaevich, doctor, cardiologist at the 3rd clinic of the Tashkent Medical Academy, Gadayev Abdugaffar Gadayevich, professor, Department of Internal Medicine No. 3, Tashkent Medical Academy, Uzbekistan E-mail: [email protected]
DYNAMICS OF CYTOKINES AND LEVEL OF HEPSIDINE IN PATIENTS WITH CHRONIC HEART FAILURE WITH ANEMIA
Abstract: the study examined the dynamics of cytokines and hepcidin level in patients with chronic heart failure, depending on the presence or absence of anemia in them. At the beginning of the study, Hepsidine was raised in the second subgroup of 23.3 ± 3.5 ng/ml, in the first subgroup and in the hanging comparison group, these indices were not noted. After 6 months there was a decrease in the level of Gepsidin in the second subgroup to 19.2 ± 0.06 ng/ml (p > 0.05). Correlation analysis of hepcidin and cytokine indices in patients with CHF with anemia revealed a direct weak correlation between hepcidin and IL-6 concentration in the second subgroup.
Keywords: chronic heart failure, iron deficiency anemia, anemia of a chronic disease, hepcidin, interleukins.
Chronic heart failure (CHF) - occupies one of the leading places in the structure of morbidity and disability among the world's population. This syndrome is still one of the most common, severe, and also prognostically unfavorable complications of all diseases of the cardiovascular system and affects 1.5-2% of the entire world population, the incidence is 5-10 cases per 1000 people annually [4].
In the past decade, the possibilities of treating anemia in patients with CHF have been actively studied [6]. Anemia is an independent predictor of the high risk of adverse events in patients with CHF.
At present, the etiology and pathogenesis of anemia developing in patients with CHF is quite diverse. The following are considered as the main ones: hemodilution, renal dysfunction (the so-called cardiorenal anemia syndrome), iron metabolism disorders and a number of other factors. The development of anemia of chronic diseases (AChS) in patients with CHF as a consequence of neurohumoral reactions characteristic of them, including the activation ofpro-inflammatory cytokines (tumor necrosis factor, interleukin-6, etc.) is also not excluded. Special attention should be paid to the possibility of oppression of erythropoiesis against the background of taking ACE in-
hibitors and angiotensin II receptor blockers, which need to be used in the treatment of patients with CHF [5].
Recently, when discussing the problems of the pathogenesis of ACh, special attention is paid to hepcidin, an acute-phase protein with the properties of a regulator of iron metabolism in the body, blocking the transport of iron in various places (including enterocytes and macrophages). The level of hepcidin correlates with the iron content in the liver and the level of hemoglobin. Synthesis of hepcidin is enhanced by inflammation (under the influence of IL-6) and under conditions of iron overload. ACh are very heterogeneous in nature [1, 3], differ in their origin and simultaneous participation of many factors that regulate erythropoiesis.
To date, only a few studies have examined the role of hepcidin in CHF and AChS, and these data are contradictory [2, 7].
Objective: to assess the relationship between inflammatory markers and the hepcidin level in patients with chronic heart failure and anemia. MATERIALS AND METHODS: The study included 115 patients with CHF, the main cause ofhospitalization was heart failure. The etiological factor of CHF in all patients was CHD.
Section 7. Medicine
The patients were divided into two groups: The main group of 75 CHF patients with anemia was divided into two subgroups, which included patients with CHF of iron deficiency anemia (CHD) and patients with CHF of chronic anemia (ACH), respectively. The second control group included patients with CHF without anemia. The first subgroup included 40 CHF patients with IDA with an average age of 64.8 ± 1.08 years; The second subgroup included 35 patients with CHF with ACH with an average age of 65.3 ±1.48 years; The second group included 40 patients with CHF without anemia with an average age of 61.4 ± 1.13 years.
The first group was treated with intravenous iron against the background of standard therapy ofCHF during hospitalization, in the comparison group patients received standard therapy for decompensated chronic insufficiency.
Patients were observed for 6 months. Clinical status, laboratory parameters, quality of life and ECHO-cardiography were evaluated initially, 6 months after the start of treatment.
Results of the study
Since the inclusion criterion was hospitalization
FC CHF on NUNA. In the first subgroup there were 14(34.4%) patients of II FC and 26(65.6%) of III FC, in the second 10 (28.5%) and 25(71.5%) patients, respectively. In the control group there were 16 (40.0%) patients of II FC and 24(60.0%) of III FC.
To determine the clinical and laboratory features of anemia in patients with CHF, a comparative analysis was performed depending on the presence or absence of anemia in them.
The mean hemoglobin level was 101.4 ± 0.48 g /L in the IDA group, 104.3 ± 0.8 g / L in the ACS group and 126.0 ± 0.58 g / L in the comparison group, the mean ferritin- 102.9 ± 8.5 mg/l, 267.5 ± 8.54 and 389.5 ± 11.6 mg/l, respectively. The serum iron values before the start of treatment were only slightly below the norm in the IDA and ACH groups 7.94 ± 0.21 mol/L and 6.14 ± 4.12 mol/L. The mean level of hepcidin was significantly higher in the AChS group 23.3 ± 3.5. In the IDA group and the control group, the same indicator was 7.6 ± 1.3 and 5.7 ± 1.02. For the rest of the laboratory parameters, the patients of both groups did not differ significantly.
due to CHF, the study included patients with II-III
Table 1. - Dynamics of proinflammatory cytokines in blood plasma in patients before and after treatment
Indicators Treatment period A group Control group
CHF FC II, n = 14 CHF FC III, n = 26 CHF FC II, n = 16 CHF FC III, n = 24
IL-1 Before 17.9 ± 2.1 20.8 ± 1.3 16.4 ± 0.72 18.6 ± 1.93
After 9.6 ± 1.2AA 10.8 ± 1.23AAA 7.4 ± 1.3 8.7 ± 0.92
IL -6 Before 20.4 ± 1.8 22.6 ± 1.3* 17.2 ± 1.78 18.9 ± 1.3
After 10.3 ± 0.98AAA 12.2 ± 1.43AAA 7.7 ± 1.43 8.6 ± 1.2
TNF-a Before 19.6 ± 0.62*** 21.8 ± 1.64 15.9 ± 0.72 17.4 ± 1.93
After 9.2 ± 1.33AAA 11.4 ± 1.67AAA 6.8 ± 2.1 8.2 ± 2.3
Indicators Treatment period B group Control group
CHF FC II. n = 10 CHF FC III. n = 25 CHF FC II. n =16 CHF FC III. n = 24
IL-1 After 18.2 ± 0.72 21.1 ± 1.93 16.4 ± 0.72 18.6 ± 1.93
Before 16.2 ± 1.12*** 18.3 ± 1.21*** 7.4 ± 1.3 8.7 ± 0.92
IL -6 After 26.6 ± 1.7*** 29.7 ± 1.3*** 17.2 ± 1.78 18.9 ± 1.3
Before 19.7 ± 0.98***AA 22.8 ± 1.32***AAA 7.7 ± 1.43 8.6 ± 1.2
TNF-a After 20.2 ± 0.72*** 24.7 ± 1.93** 15.9 ± 0.72 17.4 ± 1.93
Before 15.6 ± 1.42**AA 19.3 ± 0.89***A 6.8 ± 2.1 8.2 ± 2.3
Note: * - differences relative to the control group of the group are significant (* - P < 0.05, ** - P < 0.01, *** - P < 0.001); a - the differences with respect to indicators before treatment are significant (A - P < 0.05, AA - P < 0.01, AAA - P <0.001)
Six months after the start of treatment, the patients in the first subgroup had a significant change in hematologi-cal parameters compared to the baseline: the mean hemoglobin level increased 126.6 ± 0.78 g / l (P < 0.001), hematocrit up to 40.1 ± 0.19% (P < 0.001). In the second ACS subgroup, hemoglobin and hematocrit levels varied 120.1 ± 1.79 g/l (P < 0.001), and 39.7 ± 0.17%, respectively, during the study.
Against the background of intravenous therapy in the first subgroup, there was a significant increase in serum iron, ferritin, transferrin saturation, and a decrease in transferrin level, which shows the effectiveness of Venofer in correction of iron deficiency. In the second subgroup, the change in these indicators was statistically unreliable.
Indicators of levels of tumor necrosis factor, interleu-kin 1, interleukin 6 were investigated. At the beginning of the study, the level of IL-1 in patients in the control group with CHF without anemia with FC II-III was 16.4 ± ± 0.72, 18.6 ± 1.93 ng/ml, IL-6-17.2 ± 1.78-18.9 ± 1.3 ng/ml, and the level of TNF-a was 15.9 ± 0.72, 17.4 ± ± 1.93 ng/ml, respectively.
In the I-A group of patients with the presence of CHF with ZDA with FC II-III IL-1 was equal to 17.9 ± ± 2.1-20.8 ± 1.3 ng/ml, IL-6-20.4 ± 1.8-22.6 ± 1.3 ng/ ml, and the level of TNF-a was 15.9 ± 0.72, 17.4 ± 1.93 ng/ml, respectively.
In group I-B patients with CHF with AChS with FC II-III IL-1 was 18.2 ± 0.72-21.1 ± 1.93 ng/ml, IL-6-
-26.6 ± 1.7-29.7 ± 1.3 ng/ml, and the level of TNF-a was 20.2 ± 0.72,- 24.7 ± 1.93 ng/ml, respectively.
In comparison with the control group, the level of in-terleukin-1 in the I-A group of patients is higher by 9.111.8% (P < 0.05), interleukin-6 is 18.6-19.5% (P < 0.01), and TNF-a - 27.1-41.0 (P < 0.01)%, respectively.
In the I-B group of patients, the level of interleukin-1 is higher by 10.9-13.4%(P < 0.05), interleukin-6 is 54.6--57.1(P < 0.001)%, TNF-27, 1 - 41.0(P < 0.01)% than in the control group.
The correlation between hepcidin and proinflammatory cytokines has been studied in not many studies and conflicting data have been obtained. When studying the correlation between a statistically significant high level of proinflammatory cytokines and playing an important role in the pathogenesis of chronic anemia with hepcidin, a weakly positive relationship was established between hepcidin in patients with CHF C AChS (I-B Guppa) and IL-1 (r = 0.24 P < 0.05), and between IL-6 there is a strong positive relationship (r = 0.49, P < 0.05), between TNF-a- a medium-positive bond (r = 0.37, P < 0.05).
Conclusion: The results of our study showed that the level of hepcidin was significantly higher in patients with CHF and AChZ, as well as in patients with CHF with anemia, a correlation between hepcidin and IL-6 in the AChS group was found.
In both subgroups ofpatients with anemia, there was an increase in the level of cytokines IL-1, IL-6, TNF-a.
References:
1. Divakaran V., Mehta S., Yao D., Hassan S. et al. Hepcidin in anemia of chronic heart failure // Am J Hematol.-2011.- Vol. 86 (1).- P. 107-9.
2. Martinez-Ruiz A., Tornel-Osorio P.L., Sanchez-Mas J. Soluble TNF-a receptor type I and hepcidin as determinants of development of anemia in the long-term follow-up of heart failure patients // Clin Biochem.- 2012.-Vol. 45.- P. 1455-8.
3. Matsumoto M., Tsujino T., Lee-Kawabata M. et al. Iron regulatory hormone hepcidin decreases in chronic heart failure patients with anemia // Circ J.- 2010.- Vol. 74 (2).- P. 301-6.
4. Mosterd A., Hoes A. W. Clinical epidemiology of heart failure // Heart. - 2007.- Vol. 93.- P. 1137-1146.
5. Nemeth E., Rivera S., Gabayan V.et al. IL-6 mediates hypoferremia in inflammation by inducing the synthesis of the iron regulatory hormone hepcidin // J Clin Invest.- 2004.- Vol. 113 (9).- P. 1271-6.
6. Silverberg D. S. The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoitin and intravenous iron: randomized controlled study [Text] / D. S. Silverberg, D. Wexler, D. Sheps // J. Am. Coll. Cardiol.- 2001.- Vol. 37.- P. 1775-1780.
7. Van der Putten 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 // Eur J Heart Fail.- 2010.-Vol. 12 (9).- P. 943-50.
