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Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): фГБ ОУ ВО СЗГМУ им. И.И. Мечникова Introduction. The pathogenesis of microvascular angina pectoris (MVA) is not completely clear to the end, some authors consider the violation of pain (nociceptive) sensitivity to be an important cause of this disease. The purpose of this study was to study the perception of pain and serum endothelin-1 in patients with MVA. Materials and methods. The criteria for inclusion in the group with MVA (49 patients): chest pain, positive stress test, unchanged coronary artery  according to coronary angiography, the presence of a violation of myocardial perfusion and a decrease in the coronary reserve according to the positron emission tomography (PET) of the myocardium in rest, with a sample with adenosine and a cold test. Pain in the chest was noted in all 49 patients. Assessment of the nature of the pain syndrome was carried out using a 10-point visual-analogue scale (VAS), verbal rank scale (VRS). All subjects underwent a study of the functional activity of nociceptive and antinociceptive systems using the nociceptive flexor reflex method on the Nicolet VikingSelect expert class equipment, the pain threshold (Pb), the threshold of the reflex (Pr), and ratio coefficient (Pb / Pr), which in healthy people is approximately 0.9-1.0. The content of endothelin-1 in the serum of peripheral blood was determined by the method of enzyme immunoassay using test systems "Endotelin 1-21" (the normal values are up to 0.26 fmol / l) Fresh samples immediately after collection of blood were placed on ice and centrifuged during the day. Results. The intensity of pain in the usual attacks in patients with MVA according to the VAS data (5.51 ± 0.2) in most cases was moderate and none of the subjects reached the maximum possible values. According to VRS, moderate pain was described by 60% of patients with MVA, strong - 34.3%.In the study of NFR in patients with MVA, the group as a whole showed a decrease in the pain threshold, the threshold of the reflex, and the ratio coefficient (Pb / Pr) as compared with normal values. In the MVA group, Pb was equal to 9.5 ± 0.58 mA; Pr = 12.1 ± 0.58 mA; Pb / Pr = 0.78 ± 0.02. When studying the level of endothelin-1 in patients with MVA  the level of this peptide was raised to 2.9 ± 0.82 fmol / l. According to the correlation analysis between endothelin-1 and the parameters of NFR, an inverse correlation was observed: between endothelin-1 and pain threshold (r = -0.4; p <0.01); between the level of endothelin-1 and the ratio coefficient of PB / PR (r = -0.9; p <0.01). Based on the results of the correlation analysis of the pain intensity index on the VAS scale and endothelin-1 level in patients with MVA, a significant relationship was found (r = 0.6, p <0.01) Conclusions. In patients with MVA, a decrease in the pain threshold and an elevated level of endothelin-1 were found. Thus, the severity of endothelial dysfunction in patients with MVA was interrelated with the process of perception of pain.

Funding Acknowledgements Type of funding sources: None. Introduction Bisoprolol is one of the most effective and frequently prescribed beta-blockers. The widespread use of bisoprolol is due to its high efficiency in the treatment of patients with various cardiological pathologies: arterial hypertension, ischemic heart disease, chronic heart failure. Bisoprolol, like all members of the group of beta-adrenergic blockers, is effective in the treatment of patients with acute myocardial infarction, reducing the risk of complications such as rhythm disturbances and sudden cardiac death. In vitro studies indicate that bisoprolol is a substrate for two isoforms of cytochrome P450 - 3A4 and 2D6. Purpose The purpose of this work was to analyze the effect of CYP2D6 activity on the chronotropic effect of bisoprolol therapy in patients with acute coronary syndrome (ACS). Materials and methods The study included patients with ACS who was assigned bisoprolol according to clinical indications. All patients included in the study were Holter monitor on the 10th day of hospitalization - the minimum, mean, maximum heart rate during the day and the maximum heart rate were assessed at the time of exercise was evaluated against the background of the current therapy. All patients included in the study also underwent molecular genetic testing. The detection of polymorphic variants of СYP2D6 (*3/*4) gene was carried out by real-time PCR. Results A total of 93 patients, 58 males and 35 females were included in the study. The average age of patients is 63 years.  In the studied population, CYP2D6 * 3 was not detected. The CYP2D6 * 4 mutation occurred with a frequency of 15%, which is comparable to previously published data on the Russian population. The distribution of alleles corresponded to the Hardy-Weinberg law (Chi square, p> 0.05). In order to determine the effect of genetically determined CYP2D6 activity on the effectiveness of bisoprolol therapy in patients with ACS, we identified a group of patients - carriers of the allelic CYP2D6 * 4 variant in homozygous or heterozygous form (AA / AG) (group with a reduced metabolic rate), and a group with the CYP2D6 genotype GG (group with normal and increased metabolic rate). In the correlation analysis, carriage of CYP2D6 * 4 in heterozygous or homozygous form was associated with a lower maximum heart rate during exercise (r-0.21; p <0.05). Maximum heart rate during exercise in carriers of CYP2D6 * 4 was 107 [105; 119], in the comparison group - 114 [108; 120]. The difference was significant with p <0.05 (values are expressed as median [25%; 75%]). Conclusion In this study, for the first time, the role of the influence of allelic variants of the CYP2D6 gene on the achievement of maximum heart rate during exercise was revealed when using bisoprolol in patients with ACS. These data may have promising implications for maximizing the personalization of therapy for patients, including those with ACS.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Northwestern State Medical University named after I.I. Mechnikov Introduction. The syndrome of senile asthenia (ASA) ("fragility") in combination with anxiety-depressive symptoms in patients contributes to an increase in the frequency of hospitalizations, reduces the effectiveness of treatment and the quality of life. To study the relationship of SSA with anxiety-depressive disorders in elderly patients after acute coronary syndrome (ACS). Materials and methods. The study included patients with acute coronary syndrome. The inclusion criterion was also a signed voluntary informed consent to participate in the study. A total of 76 patients, 44 men and 32 women hospitalized for ACS were included in this prospective observational study. The average age of the patients is 73.2 years. A questionnaire was conducted with a validated questionnaire "Age is not a hindrance", and the hospital anxiety and depression scale (HADS) was also used. Results. SSA was found in 32% (p = 0.01) of hospitalized elderly patients, in the majority of women (71%) than men (29%). The average overall score according to the questionnaire "Age is not a hindrance" in elderly patients with ACS was 4.58. The results of the HADS survey showed that anxiety and depressive symptoms in fragile elderly patients occurred in 53.7% and 46.8%, respectively. There was a pronounced relationship between the occurrence of SSA and the symptoms of anxiety according to HADS (p <0.001), however, the more severe depressive symptoms were, the less frequent was SSA (p = 0.007). Conclusions. "Fragility" in elderly hospitalized patients with ACS is associated with increased anxiety and depressive symptoms. In addition, a significant relationship was demonstrated between high scores on «the age is not a hindrance» questionnaire and the presence of anxiety, but not depression.