Bondarieva O. Clinical and pathogenetic features of the course of acute coronary syndrome on background of type 2 diabetes mellitus: optimization of prognosis-modifying therapy.

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0824U001338

Applicant for

Specialization

  • 222 - Медицина

10-03-2023

Specialized Academic Board

ДФ 20.601.041

Ivano-Frankivsk national medical university

Essay

The following research methods were used to achieve the goal: clinical, laboratory, instrumental and special research methods, as well as statistical analysis. The research work was carried out taking into account of ethical principles for research with the participation of people (Helsinki Declaration) and was conducted as an open, controlled, comparative study in parallel groups. Informed consent was signed with all participants of the study. The design of the study was approved by the Ivano-Frankivsk National Medical University Ethics Commission. 124 patients with ACS were examined, whose diagnosis was established on the basis of complaints, anamnesis, objective physical examination data and results of general clinical, laboratory, biochemical and instrumental methods of examination in accordance with the guidelines of the European Cardiological Society. Diagnosis of diabetes was made on the basis of the American Diabetological Association "Classification and Diagranosis of Diabetes: Standards of Medical Care in Diabetes-2021". The examined patients were randomized into following groups: the first group - 31 patients with ACS without type 2 diabetes; the second group is 93 patients with ACS and DM. The latter, in turn, was divided into three subgroups depending on the prescribed pharmacological strategy: using guideline directed medical therapy (GDMT); GDMT and Empagliflozin at a dose of 10 mg once a day; he combination of GDMT with empagliflozin and trimetazidine at a dose of 35 mg twice a day. Established that the course of ACS on the background of type 2 DM is characterized by a high probability of debut without a typical pain syndrome (φ =+0.25); greater frequency of detection of multi-vascular damage (3.86 times), the development of a severe class of AHF by Killip (φ =+0.27), higher risk of undesirable cardiovascular events on the Grace scale (18.8%); severe disorders of glucose and lipid metabolism, excretory function of the kidneys; frequent identification of concomitant CKD (3.47 times); lower quality of life (1.34 times). It was established that concomitant type 2 diabetes in patients with ACS is characterized by more pronounced manifestations of a chronic low-intensity inflammatory process, which is manifested, compared to patients without diabetes, by a higher of leukocytes count in the blood (by 1.25 times) due to neutrophils (by 1.32 times); the growth of a number of leukocyte indices: NLR (by 1.37 times), N/LMR (by 1.39 times); increased levels of highly sensitive C-reactive protein (by 1.23 times) and matrix metalloproteinase-9 (by 1.32 times). The leading role of the macrophage system in the development of low -grade inflammation in atherogenesis was investigated. Monocytes/macrophages in patients with ACS and DM are in a state of chronic activation, the manifestations of which are the imbalance of cytokine production in vitro towards increasing the secretion of proinflammatory molecules: interleukin-1β, Tumor necrosis factor - α (1.4 times), and decreased production of anti -inflammatory interleukin -10. The relationship between the risk of multivascular damage of the coronary arteries in patients with ACS and type 2 diabetes and blood content of LDL-C (φ =+0,35), the total count of leukocytes (φ =+0.34), NT-proBNP (φ =+0 0.27), and triacylglycerol-glucose index (φ =+0.39) was established. It is noted that the concomitant DM determines the structural and functional features of myocardial remodeling in ACS, which are manifested by higher LVEDD values (1.1 times) and LVESD (1.13 times), lower LVEF (1.14 times); higher levels in the blood of troponin and (1.16 times), NT-proBNP (1.14 times). It has been proven that the additional appointment of empagliflozin to GDMT in patients with ACS and type 2 DM leads to a faster reduction of manifestations of general weakness; decrease in blood levels of HbA1c, hs-CRP, MMP-9, NT-proBNP; improvement of the structural parameters of the heart according to echocardiography: a decrease in the diameter of the left atrium, the end-systolic and end-diastolic dimensions, the mass index of the myocardium of the left ventricle. It has been shown that the combined pharmacological therapy using empagliflozin and trimetazidine in patients with ACS and DM causes a more pronounced reduction of pain syndrome, a decrease in the need for short-acting nitrates; potentiates the decrease in blood levels of LDL-C; improves the quality of life of patients; reduces the manifestations of the inflammatory syndrome (decrease in the number of leukocytes, mainly due to neutrophils, and individual leukocyte indices - NLR, LMR and fibrosis phenomena (decrease in the content of galectin-3 in the blood). Key words: coronary artery disease, acute coronary syndrome, myocardial infarction, diabetes, fibrosis, myocardial remodeling, inflammation, monocytes, trimetazidine, empagliflozin. Branch-Medicine.

Research papers

1. Бондарєва ОО, Федоров СВ (2021). Маркери активації моноцитів у хворих на гострий коронарний синдром та цукровий діабет 2 типу. Вісник проблем біології і медицини 4(162):99-102 https://vpbm.com.ua/ua/vipusk-4-(162),-2021/15011 DOI 10.29254/2077-4214-2021-4-162-99-102

2. Bondareva OO, Fedorov SV (2021-2022). Markers of low-grade inflammation in patients with acute coronary syndrome and 2 type diabetes mellitus. Прикарпатський вісник наукового товариства імені Шевченка Пульс 16-17(61-62):110-118 https://pvntsh.nung.edu.ua/index.php/pulse/article/view/1743/1697 10.21802/2304-7437-2021-2022-16-17(61-62)-110-118

3. Бондарєва ОО (2022). Динаміка рівнів галектину-3 у хворих на гострі коронарні синдроми та цукровий діабет під впливом емпагліфлозину та триметазидину. Art of Medicine 3(23):18-21 https://art-of-medicine.ifnmu.edu.ua/index.php/aom/article/view/847 DOI: 10.21802/artm.2022.3.23.18

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