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The journal "Ateroskleroz"

2021 year, number 1

1.
ASSOCIATION OF SINGLE-NUCLEOTIDE POLYMORPHISMS RS10867772, RS4700290 WITH SUDDEN CARDIAC DEATH

A.A. Ivanova1, S. K. Malyutina1, V. P. Novoselov2, A Rodina. I.3, O. V.. Khamovich3, V. N. Maximov1
1Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
2Novosibirsk State Medical University of Minzdrav of Russi, Novosibirsk, Russia
3Novosibirsk regional clinical bureau of forensic medical examination, Novosibirsk, Russia
Keywords: sudden cardiac death, single nucleotide polymorphism, genome- wide allelotyping

Abstract >>
The aim of the research is to verify the association with sudden cardiac death (SCD) of single nucleotide polymorphisms rs10867772 and rs4700290, identified as new molecular genetic markers of SCD in the own genome-wide pooled allelotyping. Material and methods. Case-control study. The SCD group is formed using the criteria of the European Society of Cardiology from the DNA bank of suddenly deceased residents of the Oktyabrsky district of Novosibirsk (n = 437, average age - 53.1 9.0 years, men - 73.5%, women - 26.5%) The control group (n = 405, average age 53.2 9.2 years, men - 70.0%, women - 30.0%) is formed from the DNA bank of participants of MONICA and HAPIEE projects. DNA was isolated by phenol-chloroform extraction from myocardial tissue in the SCD group and venous blood in the control group. Genotyping was performed by the PCR-RFLP method. Results. No statistical significance was found in allele and genotype frequencies of rs10867772 and rs4700290 between groups, even in separating in sex and age (p> 0.05). Conclusion. Single nucleotide polymorphism rs10867772 and rs4700290 are not associated with SCD.
																								



2.
DYNAMICS OF BLOOD PRESSURE INDICATORS IN PATIENTS WITH DIABETES MELLITUS AFTER PLANNED PERCUTANEOUS CORONARY INTERVENTION

A. M. Kochergina, O. L. Barbarash
Research Institute for Complex Issues of Cardiovascular Disease, Kemerovo, Russia
Keywords: arterial hypertension, adherence, daily blood pressure monitoring, coronary heart disease, diabetes mellitus, percutaneous coronary intervention

Abstract >>
Arterial hypertension (AH) is a common modifiable cardiovascular risk factor. Despite the wide choice of antihypertensive drugs, according to epidemiological studies, just over 20% of patients demonstrate effective control of hypertension. Failure to achieve the target values of blood pressure (BP) determines a high probability of developing cardiovascular events, which is also true for patients undergoing percutaneous coronary interventions (PCI). However, there is evidence that individuals who have undergone PCI show a higher percentage of achieving the target blood pressure levels. Aim of the study was to evaluate the dynamics of blood pressure indicators in patients with stable coronary artery disease (CAD) and diabetes mellitus, depending on the fact of performing PCI. Material and methods. The study was conducted at federal state budgetary scientific institution research institute of complex issues of cardiovascular diseases as a prospective, open, not comparative. The study included 75 patients with stable CAD and type 2 diabetes who regularly received therapy for at least 1 month prior to the start of participation in this study. The majority of patients 45 (60%) are represented by males. The median age was 52.646.96 years. 44 patients (58.81%) had a history of myocardial infarction, and 46 patients (61.33%) had previously undergone myocardial revascularization, history of stroke had 5 patients (6.66%). All patients according to the daily blood pressure monitoring at the 1st visit had average daily blood pressure values above 130/80 mmHg. Participants were divided into 2 groups: 43 patients had indications for routine PCI at the time of inclusion in the study, 32 patients had no indications for revascularization. The groups did not have significant differences in clinical and anamnestic characteristics, and regular significant differences were noted in relation to previously undergone revascularization (46.51 and 81.25%, respectively, p=0.0022) and the SYNTAX Score (14.399.20 and 6.138.28, respectively, p=0.0001). During 4 visits (1 visit, 1 month, 3 months, 6 months), ambulatory blood pressure monitoring (ABPM) was performed using the BiPiLAB system. Results. Initially according ABPM parameters group without the alleged PCI had greater variability in systolic blood pressure (SBP) in the daytime, higher values of mean diastolic blood pressure (DBP) at night, more time index of hypertension DBP at night. After 1 month of follow - up (for the group with PCI 1 month after the procedure), there were significant differences in the average daily SBP and DBP, the index of the time of hypertension DBP in the daytime, and the average daily SBP. Patients who underwent revascularization had lower ABPM values. The previously described differences in the night time DBP and the index of hypertension time at night were preserved. After 3 months of follow-up, significant differences were observed only in the indicators of night time SAD and DBP. At the end of the study (6 months of follow-up), the groups had differences only in the indicators of mean diastolic pressure at night. Conclusion. Patients who underwent PCI for 1 month after the procedure have a significant tendency to normalize (compared to the group without revascularization) blood pressure indicators. However, over time, the effect «escapes. Most likely, the short-term improvement in blood pressure is due to a temporary improvement in treatment adherence after an invasive procedure
																								



3.
LEVELS OF MARKER LYSOSOMAL HYDROLASES IN WOMEN WITH CORONARY HEART DISEASE DEPENDING ON AGE AND SEX HORMONE LEVEL

O. V. Tsygankova1,2, N. E. Evdokimova2, Yu.I. Ragino2, L. D. Latyntseva2, V. V. Veretyuk1, A.A. Starichkova1
1Novosibirsk State Medical University, Novosibirsk, Russia
2Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
Keywords: women, coronary heart disease, follicle-stimulating hormone, testosterone, cathepsin D, acid phosphatase, acid DNase

Abstract >>
Aim of the study was to evaluate the serum concentrations of three marker lysosomal hydrolases (cathepsin D, acid phosphatase (AP) and acid DNase (aDNAase)) in women with coronary heart disease (CHD) depending on the level of follicle-stimulating hormone (FSH), testosterone (T), age and find if those parameters associated with anthropometric parameters, glycemia, insulinemia and HOMA-IR index, biomarkers of atherosclerosis. The study included 285 women aged 35-65 years (median age was 54.4 years (25% and 75% percentiles - 43.2 and 61.3 years, respectively) who had had myocardial infarction no earlier than 30 days before the examination. Patients were divided into the following age groups: 35-55 and 56-65 years (first and second age groups, respectively), and into groups according to the levels of sex hormones: FSH ≥ and <30 mIU/mL and testosterone ≥ and <3 nmol/L. Results of comparative and correlation analyzes demonstrates that in women 35-65 years old with FSH ≥30 mIU/mL, the levels of cathepsin D are higher (p <0.05) than in patients with FSH <30 mIU/mL, and in women 35-55 years old, the content of AP was also higher (p=0.025). Associations of a high level of androgen with lysosomal hyperenzymemia were demonstrated only in the second age group, where at a level of T ≥3 nmol/L, higher values of all three lysosomal enzymes were recorded. Multivariate analysis in both age groups is confirmed direct impact of peri- and postmenopausal periods on the levels of lysosomal enzymemia and, accordingly, a negative effect on the state of lysosomal membranes. Thus, FSH levels directly determined the concentrations of AP and cardiotropic cathepsin D. The levels of aDNAase in women with CHD of 56-65 years of age were positively correlated with indicators that determine insulin-glucose homeostasis: glycemia (p <0.001), HOMA-IR index (p <0.001). Such associations of three marker lysosomal enzymes demonstrate the primary contribution of FSH ≥30 mIU/mL to an increase in the concentration of lysosomal hydrolases in women with CHD35-65 years old and the correlation of aDNAase with the processes triggered by insulin resistance.
																								



4.
ANALYSIS OF F5 GENE POLYMORPHISM IN MEN WITH CORONARY ATHEROSCLEROSIS USING WHOLE EXOME SEQUENCING

E. S. Striukova1, E. V. Shakhtshneider1,2, D. E. Ivanoshchuk1,2, Yu.I. Ragino1, Ya.V. Polonskaya1, I. S. Murashov3, A. M. Volkov3, A. V. Kurguzov3, A. M. Chernyavsky3, E. S. Valeev2, V. N. Maksimov1, E. V. Kashtanova1
1Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
2Federal State Autonomous Educational Institution for Higher Education «Novosibirsk State University, Novosibirsk, Russia
3The Federal State Budgetary Institution «National Medical Research Center named academician E. N. Meshalkin of the Ministry of Health of the Russian Federation, Novosibirsk, Russia
Keywords: F5 gene, factor V, coronary atherosclerosis

Abstract >>
Factor V, encoded by the F5 gene, is a procoagulant blood clotting factor that increases the production of thrombin, the central enzyme that converts fibrinogen to fibrin, which leads to the formation of a blood clot. The F5 gene is localized to 1q24.2 chromosome and consists of 25 exons. There are various mutations in the F5 gene that lead to resistance of activated protein C (APC) (elimination of the AP cleavage site in factor V and factor Va), which can lead to arterial and venous thrombosis. The aim of the present study was to analyze variants of the F5 gene in patients diagnosed with coronary atherosclerosis without acute coronary syndrome with stable functional class II-IV angina pectoris, confirmed by coronary angiography data, using the method of whole exome sequencing. Material and methods. The study was conducted in the framework of the Program of joint research work IIPM - branch of the ICG SB RAS and the FSBI «Research Institute of Circulation Pathology named after E. N. Meshalkin Ministry of Health of Russian Federation. The study included 30 men aged 40-70 years with coronary angiography-verified coronary atherosclerosis, without ACS, with stable angina pectoris of the II-IV FC. Patients were admitted for coronary bypass surgery, and endarteriaectomy from the coronary artery (s) was performed during the operation according to intraoperative indications. Whole exome sequencing (SureSelectXT Human All Exon v.6+UTR) was carried out on an Illumina NextSeq 500 instrument (USA). Results. In 30 patients, 29 single-nucleotide variants were found in the F5 gene. In patients with coronary atherosclerosis, rs9332701 of the F5 gene is 3.33 times more common, and rs6027 is 1.67 times more common than in the population. And rs184663825 was found in 3.33% of cases, while its occurrence in the population is 0.05%. For variants rs6034 and rs144979314, a possible damaging effect on the protein product is shown. Conclusion. The single-nucleotide variants rs9332701, rs6027, rs184663825, rs6034, rs144979314 of the F5 gene are of interest for inclusion in the genetic panels for the analysis of risk factors for the development of acute coronary syndrome.
																								



5.
LIPID AND ENDOCRINE STATUS OF PARTICIPANTS OF LONG SKI CROSSINGS IN THE RCTIC

A.A. Rozumenko, L. M. Polyakov
Institute of Biochemistry of Federal Research Center for Fundamental and Translational Medicine, Novosibirsk, Russia
Keywords: blood serum, lipoproteins, cortisol, insulin, Arctic, long ski crossings

Abstract >>
The paper presents the lipid and endocrine status of athletes - members of the two Arctic long ski crossings. The aim of the study was to study the main indicators of lipid metabolism, cortisol and insulin content in athletes during long skiing in the Arctic. Material and methods. A survey of sportsmen-participants of two polar long ski crossings. Results. A significant decrease in the concentration of the total fraction of low and very low density lipoproteins in the blood serum was revealed in male athletes - participants of two long Arctic ski crossings. At the same time, a shift in the lipoprotein spectrum of blood towards an increase in the content of high density lipoproteins due to the second type of subfraction was revealed. The dynamics of the concentration of free fatty acids in the blood of participants in ski crossings in the Arctic was of a multidirectional nature, expressed in an increase in the level of free fatty acids compared to the initial level in the training trip and in a decrease in the level of free fatty acids at all stages of the trip to the North Pole of relative inaccessibility. During the training hike an increase in the level of cortisol in the blood was revealed, as well as an increase in the insulin content after the end of the hike. During the transition to the North Pole of relative inaccessibility a significant decrease in blood cortisol concentration compared with the preparatory period was revealed, as well as the absence of significant changes in insulin content at all stages of the transition.
																								



6.
EFFICIENCY OF CONDUCTING CARDIOBIOFEEDBACK IN HEALTHY ADOLESCENTS AND ADOLESCENTS WITH ESSENTIAL HYPERTENSION

A. M. Nesterets1, O. V. Sorokin2, Z. V. Nefedova3, V. G. Kainara4, L. M. Panasenko3, V. N. Maksimov1
1Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
2NCO National Ayurvedic Medical Association, Novosibirsk, Russia
3Novosibirsk State Medical University, Novosibirsk, Russia
4City Children Clinical Hospital, Novosibirsk, Russia
Keywords: adolescents, cardiointervalography, cardiorespiratory synchronization, cognitive visceral cardiobiofeedback, essential hypertension, non-drug method

Abstract >>
Introduction. The article discusses the problem of using cognitive visceral cardiobiofeedback as a preventive and non-drug method for correcting disturbed regulation mechanisms associated with an increase in blood pressure in adolescents with essential hypertension (EH) against the background of standard antihypertensive therapy with enalapril. Aim of the study was to investigate the indices of the cardiointervalogram (CIG) during a biofeedback session and to evaluate the effectiveness of cardiobiofeedback in healthy adolescents and adolescents with EH living in Novosibirsk. Material and methods. Each participant underwent a 5-minute CIG recording using the hardware and software complex VedaPulse under physiological rest and during biofeedback session. In the course of biofeedback, the subject was asked to lengthen the expiration phase of the respiratory cycle with parallel relaxation of muscle tone and visual feedback on the dynamics of a multimedia plot reflecting changes in the duration of the cardiac cycle. Results and discussion. We found that the effectiveness of cardiorespiratory synchronization (CRS) is characterized by an increase in SDNN indicators by 8.3% and the total power of spectral influences (TP) by 23.6% due to a significant increase in the parasympathetic spectral index of HF by 29.4%. An increase in the power index of the spectrum of low-frequency oscillations (LF) by 51.3% can be considered as an element of CRS within 0,1 Hz. In healthy adolescents, the reactivity of the suprasegmental levels of regulation (IC) is preserved and their growth is noted by 7.6%. In adolescents with EH, an increase in the duration of the cardiac cycle by 5.2% and TP by 31.2% was recorded in the course of cardiobiofeedback, which is associated with an increase in the power of the spectrum of high-frequency oscillations (HF) by 2.4%. This phenomenon should be considered as a positive pathophysiological response of the autonomic link of the nervous system, which is recorded by a decrease in blood pressure. Conclusion. We assume that the test with cognitive visceral cardiobiofeedback can serve as an effective marker for the analysis of the rigidity of autonomic mechanisms of regulation in adolescents with essential hypertension. Conscious regulation of the heart rate through the mechanism of controlled respiration (biofeedback) can be an effective non-drug method for correcting autonomic regulation disorders in adolescents with arterial hypertension, which is manifested by a significant decrease in blood pressure.
																								



7.
CARDIOMETABOLIC RISK FACTORS IN OBESE INDIVIDUALS AND THE RISK OF INCIDENT DIABETES MELLITUS IN 12-YEAR PROSPECTIVE STUDY

S. V. Mustafina1, D.A. Vinter1, O. D. Rymar1, L. V. Scherbakova1, O. V. Sazonova2, S. K. Malutina1
1Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
2Novosibirsk State Medical University of Minzdrav of Russia, Novosibirsk, Russia
Keywords: Type 2 diabetes mellitus, metabolically healthy obesity, obesity, cohort

Abstract >>
Aim of the study was to investigate the risk of developing type 2 diabetes mellitus (T2DM) in individuals with metabolically healthy and unhealthy obesity phenotypes (MHO and MUO) and evaluate the contribution of metabolic syndrome (MS) components to the 12-year risk of developing T2DM according to a prospective study. Material and methods. The study included 1958 people with a BMI ≥30 kg/m² and no T2DM, from among those examined at the baseline screening in 2003- 2005 of the HAPPIE project. New cases of T2DM were diagnosed between 2003 and 2018 according to the register of diabetes mellitus and repeated screenings. The median follow-up period was 12.1 years. Were used to define MHO: criteria of the NCEPATP III, 2001 and IDF, 2005. Results . The incidence of T2DM in the MHO group according to all studied criteria is on 1,5 times lower than in persons with MUO, p <0,001. According to the results of Cox regression multivariate analysis, the risk of developing T2DM in individuals with MHO is 2.3 times lower according to the IDF criteria, 2005 and 2,2 times lower according to the NCEP ATP III, 2001 criteria, compared with persons with MUO. The risk of developing T2DM increases in direct proportion to the number of MS components: 3 components - OR = 3,1 (95% CI: 1.0; 9.9), p = 0.048, 4 components - OR = 4.4 (95% CI: 1.4; 14.0), p = 0.011. However, the presence of obesity in a person with one risk factor does not lead to the development of T2DM within 12 years, p > 0.05. When analyzing obese individuals who had abdominal obesity (AO), the risk of developing T2DM is 2 times higher compared to individuals with normal waist circumference (WC), and people without AO demonstrate no risk of developing T2DM, with an increase in the number of MS components, p > 0.05. Conclusions . The incidence of first-onset T2DM during 12 years in the MHO group by any used criteria is on 1.5 times lower than in the MUO group. In individuals with obesity, regardless of its phenotype, the most significant independent predictors of the risk of incident T2DM are AO and fasting hyperglycaemia. In individuals without AO, the risk of developing T2DM does not increase, even with an increase in the number of MS components. In the presence of AO, the risk of developing T2DM increases 2 times already with the appearance of any other component.
																								



8.
FACTORS ASSOCIATED WITH POST-INFARCTION MYOCARDIAL REMODELING

N. G. Lozhkina, I. R. Mukaramov
Novosibirsk State Medical University of Minzdrav of Russia, Novosibirsk, Russia
Keywords: postinfarction myocardial remodeling, chronic heart failure, remodeling factors

Abstract >>
This article analyzes the problem of postinfarction myocardial remodeling in the current availability of high-tech methods of coronary revascularization in most countries. The authors discuss both well- studied factors that determine the transformation of acute myocardial injury into chronic heart failure syndrome and new fundamental ones that determine prognosis and treatment. Used information on the topic from publications over the past five years, based on the PubMed, Google Scholar and Russian Science Citation Index databases.
																								



9.
CURRENT ASPECTS OF STABLE ISCHEMIC HEART DISEASE. ISHEMIA STUDY: BREAKTHROUGH OR CONSTANT OPTIMISM IN APPROACHES TO TREATMENT. MYOCARDIAL ISCHEMIA IN NON-OBSTRUCTIVE CORONARY ARTERIES (INOCA)

D.A. Yakhontov, Yu.O. Ostanina, A. V. Zvonkova
Novosibirsk State Medical University, Novosibirsk, Russia
Keywords: coronary artery disease, non-obstructive coronary artery disease, ISHEMIA study

Abstract >>
Approaches to stable coronary artery disease (CD) treatment have been subject to debate for a long time. One of the first and fundamental studies in stable coronary artery disease patients treatment is the COURAGE study, which showed the advantage of rational drug therapy in comparison with percutaneous intervention in such patients. However, CAD high prevalence with medical and social significance cause the need for future development of relationship between conservative and invasive approaches in the problem of this disease treatment. It was particularly the focus of recently completed multicentre ISCHEMIA trail. The aim of review is to analyze the available data on the management of stable coronary artery disease patients based on the ISCHEMIA study data. Results. In the largest multicenter randomized clinical trial ISCHEMIA, the primary outcome (cardiovascular death, myocardial infarction, cardiac arrest with effective resuscitation, hospitalization due to heart failure) rate was 13.3% in the routine invasive strategy group and 15.5% in the conservative strategy group (p = 0.34). The main secondary outcome rate also does not differ between groups significantly. Quality of life in the non-invasive group was higher only in those patients who had angina at baseline. Study subanalysis demonstrated that left coronary artery borderline stenosis accompanied by a poor prognosis, and an invasive strategy improves angina symptoms. Also, low density lipoprotein cholesterol target values achievement predictors were determined. In addition, women, participated in ISCHEMIA study had more frequent angina episodes, regardless less extensive coronary artery damage, and less severe ischemia manifestations than men. Among stable CAD accompanied moderate to severe ischemia and severe chronic kidney disease patients, no evidence initial invasive strategy, compared initial conservative strategy, in relation of death or non-fatal myocardial infarction risk reduction was found. Conclusion: ISCHEMIA trial data demonstrated necessity more carefully stable coronary artery disease patients selection for invasive treatment, taking into account angina pectoris severity and modern antianginal therapy possibilities.