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Rational Pharmacotherapy in Cardiology

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Scientific and practical peer-reviewed journal for cardiologists and internists "Rational Pharmacotherapy in Cardiology" has been coming out since 2005 with the support of the Russian Society of Cardiology and the National Medical Research Center for Preventive Medicine. It is All-Russian edition with a periodicity of 6 issues a year. The Journal is recommended for the publication of the results of master’s and doctor’s dissertations according to the List of editions of the State Commission for Academic Degrees and Titles. It is distributed by subscription and for free at special events.

The Editorial Board consists of leading Russian scientists in the field of cardiology, preventive cardiology, internal medicine, clinical pharmacology and preventive pharmacotherapy, including 26 Doctors of Science and 6 Academicians of the Russian Academy of Sciences. The Editorial Board consists of well-known National and International cardiologists.

The Journal mainly contains original study articles, scientific reviews, lectures, analysis of clinical practice. The Journal highlights the problems of early diagnosis, primary and secondary prevention of cardiovascular diseases, associated conditions, effective pharmacotherapy, and current questions of experimental and clinical pharmacology.

All manuscripts are published for free. They are subject to a thorough scientific expertise: double-blind review, plagiarism check, multi-stage editing. Authors are required to submit a statement of disclosure of conflict of interest associated with the publication. Reviewers are experts on the subject of peer-reviewed material. In each issue the best original articles are translated and published in Russian and English languages.

The Journal has website (www.rpcardio.com) in English and Russian where the full texts of published materials for all years are available in open access. The Journal is also available in open access on the website of the Scientific Electronic Library (SEL) and has a high impact factor of the Russian Science Citation Index (RSCI). Full-text electronic versions of all published materials are also available on the website of the Russian Scientific Electronic Library CyberLeninka and international open access website DOAJ. Published materials are presented in the international electronic databases Scopus, Web of Science, EMBASE, Index Copernicus, Ulrich's Periodicals Directory.

SCImago Journal & Country Rank

Current issue

Vol 15, No 3 (2019)
View or download the full issue PDF (Russian)

ORIGINAL STUDIES

294-304 46
Abstract

Aim. To evaluate the prevalence of smoking in 41-43-year-old men living in Moscow and its association with other chronic non-communicable diseases risk factors.
Material and methods. People of male sex were prospectively followed up during 32 years since childhood (11-12 years). Only 301 (30%) representatives of 1005 initially enrolled people were examined after 32 years. The examination included: survey by a standard questionnaire (the passport data, the level of physical activity, bad habits – smoking, alcohol consumption); three-time blood pressure measurement; assessment of heart rate; measurement of weight and height, thickness of skin folds (over the triceps, under the scapula and on the abdomen); waist circumference.
Results. Almost 50% of 41-44-year-old males smoked every day; less than a third of the study participants had never smoked. Every fifth of the smokers smoked less than 10 cigarettes per day while more than a half of them – a pack and more. The vast majority of the past smokers (85.2%) had stopped smoking at their own will and only very few (1.2%) by doctor’s advice. The intensity of smoking according to the pack/year index was >10 in almost 81.9% of the current smokers. The past smokers had abdominal obesity significantly more often than the non-smokers and the current smokers (57.5% vs 37% and 50.7%, respectively). The current smokers revealed the significantly higher risk of hypertension. The past smokers had 2.5 times higher risk of general obesity and 2.3 times higher one – of abdominal obesity as compared to the non-smokers. The intensity of smoking at the present time correlated with heart rate (HR). The past smokers (who smoked ≥20 cigarettes/day) as compared to the non-smokers had significantly higher HR, the Quetelet index, thickness of skin fold over the triceps and on the abdomen. The currents smokers revealed correlation of the status of smoking with HR, while the past smokers – with such parameters as the Quetelet index, waist circumference, thickness of skin fold under the scapula and over the triceps and no correlation with HR. The current smokers had significantly higher the 10-year risk of death as compared to the
past smokers and the non-smokers. 
Conclusion. Smoking is one of the most important risk factors of development of chronic non-communicable diseases. The struggle against smoking must be promoted, while close attention should be paid to people who had stopped smoking as a group of risk of cardiovascular disease onset. 

305-314 38
Abstract

Aim. To investigate the impact of amlodipine/valsartan single-pill combination (A/V SPC) on left ventricular hypertrophy (LVH) and left ventricular (LV) myocardial strain and stiffness parameters in naїve middle-aged patients with stage II grade 1-2 essential arterial hypertension (EAH).
Material and methods. A group of patients with stage II grade 1-2 EAH who had not previously received regular antihypertensive treatment (AHT) [n=38; mean age 49.7±7.0 years] was retrospectively formed. All the patients were treated with A/V SPC and all of them achieved target office blood pressure (BP) (less than 140/90 mm Hg). And after 12 weeks follow-up (since the time of reaching the target BP) the AHT effectiveness assessment, its impact on LVH and LV myocardial strain and stiffness parameters (general clinical data, ambulatory blood pressure monitoring, conventional and 2D-speckle tracking echocardiography) were performed in all included patients.
Results. The number of patients with LVH significantly (p=0.039) decreased from 25 individuals (65.8%) at baseline to 15 patients (39.5%) at the end of follow-up. Among patients with LVH at baseline after the treatment with A/V SPC significantly decreased (p<0.001 for all) interventricular septum thickness (from 1.36±0.19 to 1.28±0.18 cm), LV posterior wall thickness (from 1.08±0.09 to 0.97±0.11 cm) and the LV myocardial mass index (from 123.3±19.3 to 110.8±20.8 g/m2). At the end of follow-up end-systolic elastance significantly (p<0.001) decreased from 4.01±1.12 to 3.46±0.88 mm Hg/ml. In the subgroup of patients with reduced (in absolute value) LV longitudinal 2D-strain (n=27) at baseline, there was a significantly (p=0.005) increasing in this parameter at the end of the study (from -16.14±2.21% to -17.30±2.13%, Δ%=8.45±13.35).
Conclusion. In naive patients 40-65 years old with stage II grade 1-2 EAH AHT with A/V SPC provides effective 24 hours BP control, significantly reduced LVH and improves LV strain parameters, which indicates decreasing of LV myocardial stiffness.

315-321 35
Abstract

Aim. To study the frequency and characteristics of the development of thromboembolic and hemorrhagic complications in patients with atrial fibrillation (AF) during planned surgical interventions.
Material and methods. Preoperative examination and postoperative observation of 214 patients with AF (139 men and 75 women) who received anticoagulant therapy (ACT) and underwent planned surgery was carried out. The consistency of the used perioperative ACT regimens when performing interventions with current international recommendations was analyzed.
Results. Complications developed in 33 patients (15.4%) from the total sample of 214 patients: in 14 (6.5%) thromboembolism, in 19 (8.9%) hemorrhagic complications. Analysis of the complication frequency in various types of surgical interventions showed that the frequency of thromboembolism during heart and vascular operations was 9.8% (4 cases), with interventions for malignant tumors – 7 (6.2%), while performing general surgical abdominal tumors operations – 3 (5.0%). The frequency of bleeding was maximum during operations for cancer 18.6%, this value was significantly higher compared with the frequency of these complications when performing general surgical abdominal operations – 3 cases (5.0%), and during interventions on the heart and vascular vessels bleedings were not observed. The total frequency of complications was also maximal when performing interventions for malignant tumors – 24.8%. This value was significantly higher than in the groups of patients who underwent general surgical abdominal operations – 10.0%, and interventions on the heart and vessels – 9.8%. Analysis of the frequency of compliance with the recommendations of the European Society of Cardiology in terms of ACT usage in patients with AF in the perioperative period and the structure of errors in choosing the ACT regimen showed that among the examined patients the recommendations were followed only in 102 (47.7%), while the frequency of non-recommended regimens use reached 52.3% (112 patients). The most frequently incorrectly used scheme was “bridge therapy” with the possibility of canceling oral anticoagulants in 107 (50.0%) patients.
Conclusion. A significantly higher frequency of complications was found in patients, whose management did not follow the recommendations for perioperative ACT.

322-327 27
Abstract

Aim. To study the effect of hyperglycemia on the total surface charge of the erythrocyte membrane (SCEM) in patients with metabolic syndrome (MS).
Material and methods. 112 MS patients were examined (45 men and 67 women) (mean age 61.4±7.2 years, average MS duration 8.7±5.2 years). The level of SCEM was determined by adsorption of a positive cationic dye (cationic blue O) on the surface of the plasma membrane of erythrocytes to completely neutralize their negative charge, followed by photometry of the solution and calculation of the number of charges on the cell surface of erythrocytes.
Results. In the main group of patients with MS, abdominal obesity was observed in 100% of patients, arterial hypertension – in 73%, hyperglycemia – in 75%, dyslipidemia – in 80%. The level of glycated hemoglobin (HbA1c) was determined in all patients with MS, which was 7.3±1.9%. Patients with MS were conditionally divided according to the level of HbA1c into 2 groups (group 1 – HbA1c from 6.6 to 7.8%, group 2 – more than 7.8%). In MS patients with hyperglycemia, the SCEM values were significantly lower than in the group of patients without hyperglycemia (1.58±0.05×107 and 1.64±0.03×107, respectively; p=0.001)., Significant negative correlations between SCEM and the fasting blood glucose level, hyperglycemia duration, HbA1c level were found in patients with MS.
Conclusion. SCEM indices reliably depended on the presence, severity and duration of hyperglycemia, which indicated the effect of impaired carbohydrate metabolism on the state of electric charge of erythrocyte membranes and, therefore, on the mechanisms of microvascular blood flow, thereby contributing to the development of vascular changes in patients with MS.

328-334 37
Abstract

Aim. To study some vascular remodeling markers in hypertensive patients depending on the presence of type 2 diabetes mellitus.
Material and methods. The study included patients with essential hypertension 1-2 degrees of increase in blood pressure with/without type 2 diabetes (30 and 32 patients respectively). Using photoplethysmography in combination with reactive hyperemia test structural and functional markers of vascular remodeling were determined: in large vessels – stiffness index and phase shift; in microvessels – reflection index and the occlusion index. Using the computer video capillaroscopy of the nail bed the density of the capillary network at rest, after venous occlusion and after the test with reactive hyperemia was determined. ELISA was used for determining the level of humoral markers of endothelium dysfunction and vascular bed remodeling: metalloproteinase 9, metalloproteinase 9 inhibitor, E-selectin, endothelin, transforming growth factor (TGF-β1), endothelial growth
factor A.
Results. In compare with hypertensive patients in hypertensive patients with type 2 diabetes significantly higher stiffness index values (11.15 [10.05; 12.35] vs 10.15 [8.83; 11.83] m/s; p=0.04) were found as well as significantly lower (p=0.00) capillary network density at rest (26.4 [24.2; 27.6] vs 35.1 [33.0; 45.0] cap/mm2; p=0.00) after the tests with reactive hyperemia (29 [24; 33.3] vs 40.0 [35.0;43.3] cap/mm2; p=0.00) and venous occlusion (32.5 [27.8; 34.5] vs 40.0 [33.0; 45.0] cap/mm2). In hypertensive patients with type 2 diabetes significantly higher levels of TFG-β1 (11648 [4117.8; 37933.8] vs 3938.5 [1808.8; 7694] pg/ml; p=0.00) and significantly lower levels of endothelin-1 (0,46 [0,29;1,3] vs 1.73 [0.63; 2.30] ng/ml; p=0.01) was detected in compare with hypertensive patients without type 2 diabetes.
Conclusion. In both groups some signs of vascular remodeling were found at the level of both large arteries and microvessels (arterioles and capillaries). However, the group of hypertension + type 2 diabetes mellitus had statistically significantly more pronounced changes in arterial stiffness, capillary network density, as well as humoral markers levels of fibrosis and endothelial dysfunction. 

335-342 35
Abstract

Aim. To assess the influence of addition of nicorandil on long-term cardiovascular complications in patients with chronic coronary artery disease (CAD) in the framework of a prospective observational study.
Material and methods. Prospective observational multicenter NIKEA study included 590 patients with stable CAD. All patients were recommended to add nicorandil to their baseline therapy. After 21 months, 547 telephone contacts were made, the life status of 524 people was specified, 23 patients were lost to follow-up. The following complications were registered: death from any cause; non-fatal myocardial infarction (MI); non-fatal stroke; urgent myocardial revascularization; hospitalization due to deterioration of CAD, chronic heart failure (CHF) or atrial fibrillation (AF). In 479 patients, a telephone survey was performed to identify adherence (persistence) to nicorandil– i.e. to verify the continuing the treatment for the prescribed duration.
Results. During the follow-up period, 15 deaths were recorded, the causes of which were as follows: 3 CAD (2 MI, 1 left ventricular aneurysm), 1 pulmonary embolism, 2 CHF; 1 stroke, 1 oncology, 1 bilateral pneumonia. In the remaining 6 cases, the causes of death were not known. Cardiovascular (CV) complications were MI (8 cases in 7 patients, 1 patient had 2 MI in the follow-up period, 3 patients from this group died), stroke in 6 patients (7 cases, 1 patient had 2 strokes, 1 patient died). Urgent percutaneous coronary intervention was performed in 3 patients (in 2 patients due to acute MI, in 1 patient due to unstable angina). During the observation period, 21 people were urgently hospitalized due to deterioration of clinical condition. According to the results of a medical survey, by the end of the follow-up period, 237 people were not adherent to prescribed nicorandil, and 242 patients took the recommended medication (adherent patients). The main cardiovascular complications and death from any cause (р<0.001) as well as the number of urgent hospitalizations (р=0.017) were significantly more common in non-adherent to nicorandil patients in comparison with adherent patients.

Conclusion. The overall rate of CAD complications in NIKEA study was typical for patients with stable CAD receiving contemporary medical therapy. Addition of nicorandil significantly reduced the rate of CV complications in adherent patients in comparison with non-adherent patients. 

343-348 42
Abstract

Aim. To study the association of V640L (rs6133) polymorphism in the P-selectin gene with acetylsalicylic acid (ASA) resistance in patients with coronary heart disease after coronary bypass surgery (CABG).
Material and methods. The study included 104 patients aged 36-78 years (mean age 61.6±6.9 years) with stable angina pectoris: 61 (58.7%) patients had functional class II (according to Canadian Cardiovascular Society), 41 (39.4%) – class III and 2 (1.9%) – class IV. Atherosclerotic lesions of the coronary arteries were confirmed by coronary angiography. The antiplatelet therapy was stopped for at least 5 days before CABG. In the postoperative period, from the first day, all patients received 100 mg of ASA in enteric form, 61 patients received alone ASA therapy, 43 patients – combined antiplatelet therapy: ASA+clopidogrel (75 mg/day). The aggregation study was performed with an optical aggregometer, using 5 μM adenosinediphosphate (ADP) and 1 mM arachidonic acid inductors before CABG, on 1-3 day and on 8-10 day after surgical treatment. DNA samples were examined for the V640L (rs6133) polymorphism in the P-selectin gene by real-time polymerase chain reaction (PCR) using the allele-specific primers.

Results. The frequency of the homozygous GG genotype of the rs6133 polymorphism was 84.6%; heterozygous GT genotype – 15.4%. The amplitude of aggregation with ADP before CABG, on 1-3 day and on 8-10 day after CABG for carriers of homozygotes of allele G vs carriers of the allele T were: 47.9±19.3%, 44.5±17.8%, 30.1±13.2% vs 47.9±17.1%, 46.3±16.5%, 39.6±22.0%, respectively (p=0.497, 0.441 and 0.687, respectively). The amplitude of aggregation with arachidonic acid before CABG, on 1-3 day and on 8-10 day after CABG for carriers of homozygotes
of allele G vs carriers of the allele T, were: 47.9±23.2%, 24.5±21.7%, 12.3±16.3% vs 54.3±17.8%, 29.7±23.7%,  11±10.9%, respectively (p=0.416, 0.825 and 0.872, respectively). In the first 10 days of the postoperative period, 6 thrombotic events (5.7%) were observed in the study group: 2 strokes and 4 perioperative myocardial infarctions. Five events occurred in the group of patients with the GG genotype, 1 event in the group of patients with the GT genotype.
Conclusion. V640L (rs6133) polymorphism in the P-selectin gene is not associated with ASA resistance in patients with coronary artery disease after CABG. The T allele of the rs6133 polymorphism is not associated with increased platelet aggregation activity after CABG and does not increase the risk of adverse events in the first 10 days after CABG.

ASSOCIATED PROBLEMS OF CARDIOLOGY

349-358 37
Abstract

The article presents the case report of a rare hereditary form of systemic ATTR-amyloidosis in Russian patient with a discussion of approaches to the diagnosis and treatment of this form, also based on the own experience in the management of such patients. Modern ideas about the pathogenesis of the disease as well as detailed information about the clinical manifestations of amyloid cardiopathy and of other organs are presented. The nature of structural and hemodynamic changes in the heart is discussed on the basis of experience, including own, ultrasound examination of the heart in patients with amyloidosis, especially the article focuses the reader's attention on the true infiltrative nature of transtiretin amyloid cardiopathy in contrast to AL-amyloidosis, in which there is a significant inflammatory component that determines a more unfavorable natural course of AL-amyloidosis of the heart. The article discusses the differential diagnosis of different types of amyloidosis, the diagnostic difficulties associated with weak congophilia of transtiretin amyloidosis and at the same time substantiates the need for morphological verification of the diagnosis. Modern methods of treatment of ATTR-amyloidosis are discussed.

359-367 32
Abstract

In the second part of the literature review, data are presented on the possible effect of anti-osteoporosis therapy on the vascular wall and the development of calcification. The discovery of common biological substances involved in the development of atherosclerosis, calcification of the vascular wall and osteoporosis attracts the attention of scientists in terms of targets for assessing the effects of already known drugs or developing new drugs that can simultaneously prevent or slow the progression of both atherosclerosis and osteoporosis. Currently, various groups of drugs for the treatment of osteoporosis have been studied to prevent or reduce the progression of subclinical atherosclerosis and calcification. Both antiresorptive drugs (bisphosphonates, monoclonal antibodies to RANKL, selective estrogen receptor modulators), and bone-anabolic therapy, which includes teriparatide, were studied. However, there are a few such studies and the most promising drugs that have a preventive effect in the early stages of atherosclerotic damage are bisphosphonates. Other classes of antiosteoporotic drugs did not reveal a positive effect on the vascular wall, and some of them increased the cardiovascular risk. Divergences in the results of experimental and clinical studies attract attention. If in the experiment almost all drugs for the treatment of osteoporosis had an atheroprotective effect and suppressed vascular calcification, then in clinical conditions only bisphosphonates confirmed the positive effect on the vascular wall.

368-373 27
Abstract

Aim. To study the features of the progression of atrial fibrillation (AF) in patients with arterial hypertension (HT) and comorbid extracardiac diseases.
Material and methods. In the observational cohort study 308 men 45-65 years old with AF and HT were observed Most patients also had the following comorbid extracardiac diseases: diabetes mellitus (DM; n=40), diffuse toxic goiter (DTG; n=42); hypothyroidism (HTH; n=59), abdominal obesity (AO; n=64), and chronic obstructive pulmonary disease (COPD; n=47). The comparison group consisted of 56 patients with AF and HT only. Clinical, anthropometric, laboratory parameters, levels of NT-proBNP and galectin-3, results of ECG, daily monitoring of ECG and blood pressure were
assessed initially and after 12 months.
Results. Persistent AF (29.6-65.2%) and long-term persistent AF (16-31.3%) were more common in groups with extracardiac diseases compared with the AF+HT group (20.4% and 14.2%, respectively). Permanent form of AF was statistically significantly more common in the DM (11.1%), AO (14.8%) and HTH (6.2%) groups compared with the AF+HT group (0.6%). A comparative assessment of risk factors (smoking and alcohol) did not show significant differences in prevalence in the groups (22-44%). An assessment of the levels of fibrosis and remodeling markers found a statistically significant increase in the level of galectin-3 in groups of patients with concomitant extracardiac diseases and an increase in the NT-proBNP level, relative to reference values in all groups except DTG.
Conclusion. Patients with AF in combination with HT and comorbid extracardiac diseases have a more rapid AF progression.

374-378 25
Abstract

Aim. To study some structural and functional parameters of the heart and the parameters of hepato-lienal blood flow in patients with chronic viral hepatitis (CVH).
Material and methods. 74 patients with CVH were examined, the average age was 41 years, the disease duration – 3.6 years. The patients were divided into 2 groups: group 1 – patients with minimal biochemical activity of hepatitis (n=39); group 2 – patients with moderate hepatitis activity (n=35). The control group included 22 healthy patients. Parameters of tissue doppler echocardiography, hepato-lienal blood flow were evaluated depending on the laboratory activity of CVH.
Results. The systolic velocity of the fibrous ring displacement of the tricuspid valve in patients of groups 1 and 2 was lower than in the control by 15% and 17%, respectively (p<0.001). Em decreased in groups 1 and 2 in comparison with healthy individuals in the basal segment of the left ventricle lateral wall, on the mitral valve fibrous ring, in the basal segment of the interventricular septum (p<0.001). The Em/Am ratio decreased in patients of groups 1 and 2 compared with healthy patients in the basal segment of the left ventricle lateral wall, in the medial segment of the interventricular septum, on fibrous ring of the tricuspid valve, in the basal and medial segments of the right ventricular lateral wall (p<0.001). Isovolumic contraction and relaxation time as well as the volume index of the left atrium were increased in patients of the 1st and 2nd groups in comparison with control; more severe violations were observed in patients of the 2nd group (p<0.001). In patients of both groups, acceleration of blood flow and dilation of arteries and veins in the hepato-lienal circulation system (p<0.001) were found. Besides, in patients with moderate hepatitis activity there was an acceleration of blood flow in the hepatic artery in comparison with the control (p<0.001).
Conclusion. In patients with CVH the follow disorders were observed: decrease in the global longitudinal systolic function of the right ventricle, violation of diastolic relaxation of the ventricles, increase in the volume index of the left atrium, as well as expansion of the arteries and veins of the hepato-lienal circulation system. These violations were more pronounced in patients with a moderate laboratory activity of CVH. Correlations between cardiohemodynamic parameters, indicators of hepato-lienal blood flow and viral load were revealed. 

PREVENTIVE CARDIOLOGY AND PUBLIC HEALTH

379-385 22
Abstract

With the development of atrial fibrillation (AF), patients with acute coronary syndrome (ACS) are characterized by a twofold increase in the 30-day mortality compared with patients with sinus rhythm. In this regard, there is great interest in developing models of risk stratification to identify adverse outcomes in these patients with a view to more careful monitoring of patients in this group.
Material and methods. For the construction of predictive models, a statistical method was used for the classification trees and, the procedure for neural networks implemented in the STATISTICA package. For the construction of prognostic models, a sample was used, consisting of 201 patients with and without fatal outcome; condition of each patient was described by 42 quantitative and qualitative clinical indices. Each patient belonged to one of 3 groups according to the type of AF: new-onset AF in ACS patient, paroxysmal AF, documented in an anamnesis before the episode of ACS and the constant or persistent form of AF.
Results. To determine predictors of models predicting the possible fatal outcome of a patient, the Spearman correlation coefficient was used. Examination of the correlations for each of the 3 groups separately allowed to reveal clinical indicators for each group – predictors of predictive models with predominantly moderate correlations to the categorical variable “lethal outcome”. After analyzing the prognostic ability of the developed models, a software module was created in the Microsoft Visual C # 2015 programming environment to determine lethal outcome possibility in patients with ACS in the presence of AF using classification trees and neural networks.
Conclusion. It is shown that for patients with ACS in the presence of AF, it is possible to construct mathematically based prognostic models that can reliably predict the lethal outcome possibility in patients based on actual values of clinical indices. In this case, clinical indicators can be both quantitative and qualitative (categorical), breaking patients into certain categories. Similar applications, unlike risk scales, are mathematically justified and can form the basis of systems for supporting decision-making.

PAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPY

386-392 57
Abstract

The article focuses on the problem of low adherence to treatment among patients, in general, and provides data on the high adherence among patients in randomized controlled trials. Low adherence remains one of the most debated and difficult problems to solve nowadays. Poor medication adherence of the patient can significantly worsen the effectiveness of treatment and leads to increased health care costs. And although the factors that improve adherence are varied, and include the skills of the doctor, the patient’s personal characteristics, the external environment, an individual approach to each patient and etc., the absence of a “gold standard” for assessing adherence in clinical practice makes it difficult to predict and significantly improve it among patients. Nevertheless, the article discusses the existing doctor-patient interaction model, which strictly regulates the algorithms and technical means to achieve the best medication adherence. Randomized clinical trials (RCT) are the basis of evidence-based medicine, the results obtained in RCT form the basis of existing clinical guidelines. While participating in RCT patients can receive comprehensive information about the disease, the effectiveness of drug therapy, possible side effects of the therapy being conducted, the research objectives and prognosis from their attending physician; patients are trained to be disciplined and adhere to the recommendations of the doctor. The RCT, for a number of objective reasons, uses a variety of methods for assessing adherence and ways to improve it, which leads to higher patient adherence then among patients in general.

INNOVATIVE CARDIOLOGY

393-406 48
Abstract

Aim. To summarize Russian studies using pharmacogenetic testing as applied to cardiology.
Material and methods. The authors conducted an online search for articles in December 2018 using the following databases: PubMed, Google Scholar, eLIBRARY. The search was carried out by keywords: "Russia", "Russian", "cardiology" together with the terms associated with the polymorphic marker, including: «P450», «CYP2C19», «CYP2D6», «CYP2B1», «CYP2B6», «CYP2Е1», «CYP2C8», «CYP2C9», «CYP3A4», «CYP3A5», «CYP1A1», «CYP1A2», «CYP4F2», «CYP4F1», «ABCB1», «SLCO1B1», «VKORC1», «GGCX», «SULT1A1», «CULT1», «CES1», «gene», «genes», «pharmacogenetics», «pharmacogenomics», «ethnic group».
Results. Generalization of information allowed to identify obscure genes that need to be investigated in pharmacogenetic studies. This information can be used for the development of dosing algorithms and the priority choice of drugs, considering the results of pharmacogenetic testing and planning future research.
Conclusion. The results of the literature review indicate the importance of studying the most clinically valid and clinically useful pharmacogenetic markers (CYP2C19, CYP2C9, VKORC1, SLCO1B1) among various ethnic groups in the Russian Federation. With the accumulation of evidence of clinical validity and clinical utility of other pharmacogenetic markers (CES1, CYP2D6*4, etc.), the problem of interethnic differences in the carriage of clinically significant polymorphisms of these genes identified in previous studies in the Russian Federation increasingly requires attention. The most promising for the introduction into the clinical practice in the Russian Federation in the near future are polymorphic markers of the CYP2C19, CYP2C9, VKORC1 and SLCO1B1 genes.

407-415 26
Abstract

Atrial fibrillation (AF) is one of the most common arrhythmia that occurs in patients with cardiovascular diseases. Congenital forms of AF are quite rare. Many studies have shown that genetic, epigenetic and transcription factors may play an important role in the development and the progression of AF. In our review, studies have been conducted on the identification of mutations in ionic and non-ionic channels, possibly associated with AF. These mutations were found only in isolated groups of patients with AF, and in general, monogenic forms of AF are a rare subtype of the disease. Genomic association studies have helped to identify potential links between single nucleotide polymorphisms and AF. The risk of AF in the general population is likely to be determined by the interaction between environmental factors and many alleles. In recent years, the emergence of a genome-wide associative studies has significantly expanded the understanding of the genetic basis for the inheritance of AF and has led to the emergence of new evidence of the important role of genetic factors in the development of AF, in the risk stratification of AF and the recurrence of AF. Epigenetic factors are also important in AF. Epigenetic therapy aimed at treating a disease through exposure to epigenome is currently under development. A newly emerged area of ablatogenomics includes the use of genetic profiles that allow assessing the likelihood of recurrence of AF after catheter ablation. The results of genetic studies in AF show that, in addition to their role in the appearance of congenital heart pathologies, transcription factors play an important role in the pathogenesis of AF.

POINT OF VIEW

416-423 59
Abstract

Headache is considered to be one of the main symptoms of arterial hypertension (HT). Complaints of headache are presented by many patients with HT: from 44% to 87%. It is obvious that the majority of complaints of headache in patients with HT is not due to headaches due to increased blood pressure (BP), but multimorbidity (polymorbidity) – the presence of coexisting primary headaches, most often, as in the population as a whole, chronic tension headache (57-85%) and migraine (15-30%). On the other hand, the frequency of HT in patients with migraine ranges from 32% to 44%. The relationship between migraine and HT may be due to common exogenous (external) and endogenous (genetic) factors, as well as common pathophysiological mechanisms. External risk factors, which can be associated with both migraine and HT, include the nature of the diet (excessive consumption of table salt with food), low physical activity, chronic stress; both diseases are also associated with the presence of a connection with the metabolic syndrome. The role of hyperactivation of the renin-angiotensin-aldosterone and adrenergic system and endothelial dysfunction are actively discussed. Angiotensin-converting enzyme takes an active part in the BP control and vascular tone; it is known that some angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) have demonstrated efficacy in preventing migraine attacks. The presence of HT can contribute to the chronic course of primary headache, and effective treatment of HT with antihypertensive drugs, on the contrary, can have a positive effect on the course of primary headaches. Antihypertensive drugs reduce the frequency of headaches compared to placebo, but heterogeneity between different classes was revealed. There was a statistically significant decrease in the frequency of headaches compared to placebo during treatment with beta-blockers, ACEI, ARB, diuretics, while calcium antagonists did not reduce the frequency of headaches. According to a number of studies, the frequency of headaches during the treatment with ARB (candesartan) is comparable to that in the placebo group. Some antihypertensive drugs are used to prevent migraine attacks.

424-430 25
Abstract

Prospects for the use of mammographic detection of breast arterial calcification (BAC) to improve the stratification of cardiovascular risk in the female population are of increasing interest. The purpose of the 2 part of the review is the analysis of modern literature on the relationship of the BAC with the prevalence and mortality from cardiovascular diseases (CVD). The presence of BAC on mammograms is associated with a higher likelihood of myocardial infarction, death from coronary heart disease (CHD) and CVD, as well as a 3.5-fold increase in the risk of CHD and a 5-year coronary incident (p=0.003). Women with BAC have a higher likelihood of coronary artery disease detected during angiography than women without BAC (p<0.001). Severe BAC has a stronger association with CVD than mild calcification. The association of BAC with cerebrovascular diseases and a 1.4-fold increase in the risk of ischemic stroke (p=0.004), atheromatosis of the carotid arteries and an increase in the thickness of the intima-media complex is shown. BAC is associated with atherosclerotic lesions of peripheral arteries and a decrease in the ankle-brachial index <0.9 (p=0.048). In women with chronic kidney disease, the presence of BAC indicates a 4.5-fold increase in the risk of complications associated with impaired blood flow in peripheral arteries. It is shown that the addition of BAC to the generally accepted (standard) vascular risk assessment algorithms Framingham Risk Score and Pooled Cohort Equation significantly increases the accuracy of prediction of CHD (p=0.02 and p=0.010, respectively). The detection of BAC on mammographic screening is a new promising direction for cardiovascular prophylaxis in women and opens up new opportunities for identifying groups of people with subclinical forms of CVD and high cardiovascular risk.

431-438 25
Abstract

Fibromuscular dysplasia of the coronary arteries is a rare non-atherosclerotic and non-inflammatory vascular lesion that is asymptomatic until serious complications develop: stenosis, dissection, rupture, sudden cardiac death. Since there are no long-term numerous clinical observations of patients with fibromuscular dysplasia of the coronary arteries, recommendations have not been developed for diagnosing and treating the disease, which often manifests with acute coronary syndrome. In 2014, the European Consensus was published, and in 2019, the first international consensus document on the diagnosis and treatment of fibromuscular dysplasia with lesions of vessels from different regions (renal, cerebrovascular, coronary, and others). The documents state that the development of fibromuscular dysplasia of the coronary arteries considers the participation of the PHACTR1 gene mutation and the transcriptional activity of the EDN1 gene, smoking, prolonged exertion of the vascular wall, and possibly female sex hormones. In the case of acute coronary syndrome, the most informative diagnostic method is computed tomography with angiography, which reveals a smooth narrowing of the lumen in the middle or distal section in the epicardial artery, often due to intramural hematoma, and also finds dissection, spasm, and tortuous vessel. Additional diagnostic methods ‒ intravascular ultrasound and optical coherence tomography allow differentiation of fibromuscular dysplasia with atherosclerosis of the coronary artery, vasculitis, and other diseases. The choice of treatment tactics for fibromuscular dysplasia of the coronary arteries depends on the severity of the clinical manifestations ‒ conservative medical treatment and interventional methods are used.

THERAPY GUIDELINES

439-441 18
Abstract

Conclusion of the Expert Panel (November 24, 2018)*
Novosibirsk, 11/24/2018
*The Composition of the Board of Experts: Novosibirsk: Lifshits G.I., Ekaterinburg: Burleva E.P., Grachev V.G., Lipchenko A.A., Khabarovsk: Davidovich I.M., Barnaul: Efremushkina A.A., Korennova O.Yu., Moscow: Karpov Y.A.** (Chairman), Vladivostok: Nevzorova V.А., Kemerovo: Barbarash OL, Krasnoyarsk: Petrova MM, Irkutsk: Protasov K.V., Tyumen: Shalaev S.V.

 The publication of the opinion was prepared with the support of the medical advisor of JSC BAYER Elovoy-Vronskiy A.A.. 

The resolution discusses the issues of diagnosis and management of patients with coronary artery disease depending on regional particularities, the role of the new approach to antithrombotic therapy of stable patients with atherosclerotic diseases and its pathogenetic basis (inhibition of both coagulation and platelet). Experts noted that combination of rivaroxaban 2.5 mg BID and acetylsalicylic acid can be recommended after registration of the indication for almost all patients with atherosclerotic diseases. Nevertheless, first of all this therapy, at any stage of patient management, should be considered for patients with high cardiovascular risk, namely, patients with multiple atherosclerotic lesions, patients with history of myocardial infarction after the termination of the period of double antiplatelet therapy and patients with concomitant diabetes mellitus, chronic kidney disease and other risk factors that worsen the prognosis. The experts expressed hope that soon the combined antithrombotic therapy will not only be registered for use in Russia but will also be included in the national guidelines for the management of patients with coronary artery disease or peripheral arterial disease.

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