THE COURSE OF CHRONIC HEART FAILURE IN PERSONS WITH POST-INFARCTION CARDIOSCLEROSIS AND TYPE 2 DIABETES MELLITUS AND OBESITY ACCORDING TO A NUMBER OF METABOLIC AND HORMONAL INDICATORS

Diseases of the cardiovascular system re­ main the leading cause of overall morbidity and mortality [1, 2]. Over the past three decades, some reduction in cardiovascular mortality has been associated with improved control of risk factors such as cholesterol, hypertension (AH), and smoking [3]. At the same time, there is an increase in obese people, type 2 diabetes mel­ litus (DM), the severity of metabolic shifts in which leads to vascular accidents [4]. The leading etiological factor in the deve­ lopment of chronic heart failure (CHF) is coro­ nary heart disease (CHD), which according to many studies develops in almost 70 % of cases [4, 5]. The pathogenesis of CHF is multifactorial and very complex, which includes the impact on the cardiovascular system of etiological factors and the activation of a complex of compensa­ tory mechanisms. Risk factors for CHF include: left ventricular myocardial hypertrophy, type 2 diabetes, obesity [6­9]. It should be noted that the evolution of views on the pathogenesis of CHF resembles a spiraling movement — at each new round of obtaining new knowledge there is a return to old truths with modern analysis and combining them with the current paradigm. To identify the stage of CHF, it is impor­ tant to search for non­invasive methods of early differential diagnosis, risk assessment, disease prognosis, treatment dynamics. Clusterin and fractalkin are among the bio­ markers that indicate a predisposition to the development of CHF and early diagnostic indi­ cators of the disease, especially in the asymp­ tomatic course. The role of clusterin in lipid transport and inhibition of inflammation has now been pro­ ven, making this molecule a potential candi­ ISSN 2518­1432 (Online); ISSN 2227­4782 (Print) https://doi.org/10.21856/j­PEP.2022.2.02

Diseases of the cardiovascular system re main the leading cause of overall morbidity and mortality [1,2]. Over the past three decades, some reduction in cardiovascular mortality has been associated with improved control of risk factors such as cholesterol, hypertension (AH), and smoking [3]. At the same time, there is an increase in obese people, type 2 diabetes mel litus (DM), the severity of metabolic shifts in which leads to vascular accidents [4].
The leading etiological factor in the deve lopment of chronic heart failure (CHF) is coro nary heart disease (CHD), which according to many studies develops in almost 70 % of cases [4,5].
The pathogenesis of CHF is multifactorial and very complex, which includes the impact on the cardiovascular system of etiological factors and the activation of a complex of compensa tory mechanisms. Risk factors for CHF include: left ventricular myocardial hypertrophy, type 2 diabetes, obesity [69].
It should be noted that the evolution of views on the pathogenesis of CHF resembles a spiraling movement -at each new round of obtaining new knowledge there is a return to old truths with modern analysis and combining them with the current paradigm.
To identify the stage of CHF, it is impor tant to search for noninvasive methods of early differential diagnosis, risk assessment, disease prognosis, treatment dynamics.
Clusterin and fractalkin are among the bio markers that indicate a predisposition to the development of CHF and early diagnostic indi cators of the disease, especially in the asymp tomatic course.
The role of clusterin in lipid transport and inhibition of inflammation has now been pro ven, making this molecule a potential candi date as a marker of cardiovascular disease, diabetes, and obesity [10][11][12].
There is evidence of fractalkin -the only chemokine that exists in soluble and fixed forms in the pathogenesis of cardiovascular disease [13][14][15][16], which allows us to consider it as a marker of activation of the inflammatory process associated with chemotaxis of various leukocytes, primarily monocytes and lympho cytes in the area of inflammation. It is possible that the results of further studies will prove the possibility of using fractalkin as a target for therapeutic effects in patients with CHF. Global studies demonstrate the uncertainty of a number of issues regarding the progression of CHF in patients with postinfarction cardioscle rosis and concomitant metabolic disorders and dictate the need to find new modern markers.
The aim: To determine the role of lipid me tabolism and fractalkin and clusterin in the progression of CHF in patients with postinfarc tion cardiosclerosis with concomitant type 2 diabetes and obesity.

MATERIALS AND METHODS
In accordance with the purpose of the work, a retrospective analysis of a comprehensive examination of 67 patients with postinfarc tion cardiosclerosis with concomitant type 2 diabetes obesity. The study has been carried out in compliance with the main bioethical The clusterin level was determined by en zymelinked immunosorbent assay using the Human Clusterin Elisa test system manufac tured by Bio Vender (Czech Republic).
Serum concentration of fractalkine was per formed by enzymelinked immunosorbent as say using a set of reagents Human Fractalkine Elisa Kit «RayBio ® » (Georgia).
The research was carried out in the bio chemical department of the Central Research Institute of Kharkiv National Medical Uni versity of the Ministry of Health of Ukraine Проблеми ендокринної патології № 2, 2022 Клінічна ендокринологія on the enzymelinked immunosorbent assay «Labline Go» (Austria). The obtained results are presented as the mean ± standard devia tion from the mean (M ± m). Statistical pro cessing of the obtained data was carried out using the statistical software package Statisti ca, 8.0 (Stat Soft Inc, USA), Microsoft office Excel2003. Evaluation of differences between groups in a distribution close to normal was performed using Pearson's test. Differences at p < 0.05 were considered statistically signifi cant.

RESULTS AND THEIR DISCUSSION
The analysis of the obtained data (Table 1) shows that with the progression of CHF from FC II to FC III there is a deterioration of lipid metabolism: a significant increase in choleste rol levels by 5.5 %, TG -by 15.7 %, LDL cho lesterol -by 74.4 %, VLDL cholesterol -by 15.9 %, reduction of HDL cholesterol -by 27.6 % (p < 0.05). These results demonstrate atherogenic progression of the blood lipid spec trum in patients with postinfarction cardioscle rosis and type 2 diabetes. At the same time, an increase in BMI by 8.8 % was noted, which in dicates a more pronounced obesity in the group of patients with CHF III FC.
It should be noted that the level of Hb1Ac was the same in all three groups of patients.
At the same time, with the progression of CHF III FC to FC IV there is a decrease in CH -by 8. Analysis of the level of fractalkin showed that in patients with CHF with an increase in its FC, it increases. On the contrary, the level of clusterin decreased: in patients with CHF II FC it was 14.0 % and 33.2 %, respectively, higher than in the groups of CHF III FC and CHF IV FC (p < 0.001).
The study shows the classic changes in pa tients with postinfarction cardiosclerosis with CHF and concomitant type 2 diabetes and obe sity, which are the formation of disorders of lipid metabolism of atherogenic nature, which are associated with body weight, as well as changes in new indicators such as fractalkin and clusterin, indicating the role of these mol ecules in the progression of CHF.
The striking effect of type 2 diabetes on the development and prognosis of CHF is due to a whole set of interrelated mechanisms. First of all, these are factors of high cardiovascu lar risk that make up the syndrome of insulin resistance: dyslipidemia, hypertension, obesity, inflammation [17]. Hyperglycemia is a leading link in heart disease and the presence of type 2 diabetes contributes to the development of coro nary atherosclerosis and realizes its negative impact on the progression of CHF due to the oc currence and severity of coronary heart disease [18,19].
This paper reflects the concept of the ef fect of chemokines on myocyte contractility, as evidenced by the results of other researchers who demonstrate that fractalkin causes a de crease in cardiomyocyte contractility through the CXCR4 receptor [20,21].
The obtained results suggest that type 2 diabetes, obesity, dyslipidemia, inflammation have common pathogenetic mechanisms of the development and progression of cardiovascular complications in patients with comorbid patho logy, lead to summation and potentiation of cardiovascular risk, which is consistent with the results obtained by other studies, reflected in subsequent works [22][23][24]. Клінічна ендокринологія tant type 2 diabetes mellitus and obesity is accompanied by an increase in the functional class of chronic heart failure.

Fractalkin and clusterin play a significant
role in the progression of chronic heart fai lure in patients with postinfarction cardio sclerosis with concomitant type 2 diabetes and obesity, so they can be used as biomar kers of the severity of heart failure.

I. P. Dunaieva, O. M. Bilovol, I. I. Knyazkova
Kharkiv National Medical University, Kharkiv, Ukraine; innadunaieva@gmail.com The aim of the study is to investigate the effect of lipid metabolism, biomarkers of fractalkin and clusterin inflammation on the development and progression of chronic heart failure (CHF) in patients with postinfarc tion cardiosclerosis, type 2 diabetes and obesity.
Materials and methods. A retrospective analysis of a comprehensive examination of 67 patients with postinfarction cardiosclerosis with concomitant type 2 diabetes and obesity. All patients were divided into 3 groups depending on the functional class (FC) of CHF: 1 group (n = 22) -patients with CHF II FC; Group 2 Проблеми ендокринної патології № 2, 2022 Клінічна ендокринологія (n = 23) -patients with CHF III FC; Group 3 (n = 22) -patients with CHF IV FC. All patients were examined clinically, they underwent instrumental, biochemical and hormonal examinations.
Results. With the progression of CHF from FC II to FC III there is a deterioration of lipid metabolism: a significant increase in cholesterol levels by 5.5 %, TG -by 15.7 %, LDL cholesterol -by 74.4 %, VLDL cholesterol -by 15.9 %, reduction of HDL cholesterol by 27.6 % (p < 0,05). An analysis of the fractal equation showing that ailing on CHF is advised by FC; and the level of clusterine -on the contrary decreases. Classical changes in patients with postinfarction cardiosclerosis with CHF and concomitant type 2 diabetes mellitus and obesity, which are the formation of atherogenic lipid metabolism disorders associated with body weight, as well as changes in the latest indicators such as fractalkin and clusterin, indicating the role of these molecules in the progression of CHF.
Conclusions. Due to the progression of chronic heart failure in patients with postinfarction cardiosclerosis and concomitant type 2 diabetes and obesity, an increase in all fractions of lipoproteins at stage III functional class was diagnosed, and then their decrease (at stage IV functional class), which may indicate a deterioration in this category of patients. , due to the progression of metabolic shifts, stagnation, dysfunction of the main parenchymal organs. Increased circulatory levels of fractalkin and decreased clusterin content in patients with postinfarction cardiosclerosis with concomitant type 2 diabetes mellitus and obesity is accompanied by an in crease in the functional class of chronic heart failure. Fractalkin and clusterin play a significant role in the pro gression of chronic heart failure in patients with postinfarction cardiosclerosis with concomitant type 2 diabetes and obesity, so they can be used as biomarkers of the severity of heart failure.