ORIGINAL STUDIES 
Background. Dyslipidemia is one of the most serious modifiable risk factors for acute coronary syndrome which is the most leading cause of mortality and morbidity worldwide.
Aim. To assess the short-term safety and efficacy of full dose rosuvastatin and atorvastatin in patients with acute coronary syndrome.
Material and methods. Single center, prospective, randomized study included 100 patients who were randomized from first 24-hour of admission to either atorvastatin 80 mg daily (group 1) or rosuvastatin 40 mg daily (group 2). Primary outcomes included levels of inflammatory markers (erythrocyte sedimentation rate [ESR], high-sensitive C-reactive protein [hs-CRP] and total leukocyte count [TLC]) after 4 weeks of treatment and lipid profile after 3 months. Secondary outcomes included recurrent myocardial infarction, recurrent angina, stroke and side effects.
Results. At admission, both groups were comparable in age, without statistically significant difference regarding risk factors (diabetes, hypertension, smoking and obesity), echocardiography (end-diastolic volume, end-systolic volume and ejection fraction), laboratory parameters of inflammation and lipid profile. After 1 month, there was insignificant difference between rosuvastatin and atorvastatin in the reduction of ESR, Hs-CRP or TLC. After 3 months rosuvastatin showed statistically significant reduction in the level of low-density lipoprotein cholesterol, triglyceride (p<0.001) and significant increase in high-density lipoprotein cholesterol (p<0.001) when compared to atorvastatin and at the same time the rosuvastatin group was safer regarding liver enzymes elevation, p<0.001 for alanine and p<0.01 for aspartate aminotransferases, respectively.
Conclusions. Our findings demonstrated that rosuvastatin 40 mg/day is safer and more effective than the atorvastatin 80 mg/day in the terms of lipid parameters and inflammatory biomarkers.
Aim. To investigate arterial stiffness parameters in middle-aged patients with stage II grade 1-2 essential arterial hypertension (HT) and evaluate their changes after treatment with single pill combinations (SPC) of antihypertensive drugs.
Methods. At the first phase of the study, according to the medical records data, a group of untreated patients with stage II grade 1-2 HT (n=100, 47 men, mean age 51.9±6.5 years), and a group of healthy controls with normal blood pressure (BP) (n=86; 28 men; mean age 48.8±5.8 years) were formed. The analysis of arterial stiffness was performed by the volumetric sphygmography technique using VaSera VS-1500N device (Fukuda Denshi Co., Ltd, Japan). All the subjects underwent ambulatory BP monitoring (BPLab, BP2005-01.04.00.2540, Petr Telegin, Russia) as well as a routine BP measurement by the Korotkov method. At the second stage of the study, a group of HT patients (n=90) was formed according to the medical history data. These patients thanks to antihypertensive treatment with SPC (perindopril arginine/indapamide or valsartan/amlodipine) achieved the target BP level (<140/90 mm Hg) according to routine measurements and they were assessed in terms of therapy efficacy (general clinical data, SMAD, volume sphygmography) 12 weeks after the target BP level was reached.
Results. At the first phase of the study, in HT patients cardio-ankle vascular index (CAVI), both on the left (7.9±1.3) and right side (8.1±1.3), as well as the right-side augmentation index (1.22±0.31%) were significantly higher (p=0.006, p=0.003, p=0.047, respectively) compared to the controls (7.5±0.9, 7.6±0.9, 1.13±0.28%, respectively). At the second phase of the study, after SPC treatment the CAVI significantly decreased both on the left- (up to 7.36±1.37, p=0.02) and right-side (up to 7.46±1.44, p=0.02).
Conclusions. In untreated 40-65 years-old patients with stage II grade 1-2 HT arterial stiffness assessed by volumetric sphygmography is significantly higher compared with sex-matched healthy individuals. 12-week therapy with SPCs improves the elastic properties of the major arteries, reducing the CAVI value.
Aim. To assess the relationship between pre-diabetes/type 2 diabetes mellitus (type 2 DM) and long-term adverse prognosis in patients with coronary artery disease (CAD) who underwent coronary artery bypass grafting (CABG).
Material and methods. 347 CAD patients who underwent CABG in the period from 2006 to 2009 were enrolled into the study. All patients were divided into 3 groups: 148 patients with type 2 DM (the median age – 58 years, the median follow-up – 1.8 years), 23 patients with pre-diabetes, i.e. impaired fasting glycemia and/or impaired glucose tolerance (the median age – 58 years, the median follow-up – 1.7 years); and 176 patients without diabetes and other carbohydrate metabolism disorders (CMD) (the median age – 58 years, the median follow-up – 1.7 years). The prognosis was considered as unfavorable in case of any major adverse cardiovascular events (MACEs) defined as myocardial infarction, stroke, cardiovascular death. Logistic regression was used to identify the predictors of the unfavorable prognosis.
Results. All patients in the study groups were comparable in age (p=0.345) and the median of the follow-up (p=0.134). The comparative assessment of the long-term prognosis showed the similar rate of major adverse cardiovascular events in the groups with CMD (the diabetes group – 14.2% vs the pre-diabetes group – 13.0%), compared to 6.3% in patients without any CMD (p=0.028 for the groups with DM and without CMD). The regression analysis reported that type 2 DM appeared to be a significant factor associated with the development of the long-term MACEs (odds ratio [OR] 3.307, 95% confidence interval [95%CI] 1.372-7.968, p=0.007). The addition of pre-diabetes as a potential predictor of the unfavorable prognosis increased 3.6-fold the risk of long-term MACEs (OR 3.617; 95%CI 1.557-8.403, p=0.001).
Conclusion. Pre-diabetes significantly affects the prognosis of patients after CABG, similarly to type 2 DM. The diagnosis of CMD in patients undergoing CABG is of significant clinical relevance.
Aim. We aimed to compare effectiveness of new class III antiarrhythmic drug Refralon with direct current cardioversion (DCC) in patients with persistent atrial fibrillation (AF).
Material and methods. 60 patients with persistent AF were randomized to groups of DCC (n=30) and pharmacologic conversion (PCV; n=30). There were no differences in age, sex, AF duration, concomitant cardiovascular diseases, CHA2DS2-VASc score and echocardiographic parameters between the groups compared. Initial assessment excluded contraindications to restore sinus rhythm (SR). In DCC group two attempts using biphasic synchronized shocks of 150 J and 170 J were performed. In PCV group patients received up to three subsequent intravenous injections of Refralon 10 μg/kg (maximal dose 30 μg/kg).
Results. SR was restored in 27 of 30 patients (90%) in DCC group and in 28 of 30 patients (93.3%) in PCV group. 95% confidence interval (CI) for primary effectiveness criterion was [-0.1 – 0.16]. AF recurred in 1 patient after successful DCC. There were no AF recurrences in PCV group. 26 of 30 patients (86.7%) in DCC group and 28 of 30 patients (93.3%) in PCV group remained in SR 24 hours after cardioversion. 95%CI for secondary effectiveness criterion was [-0.07 – 0.19].
Conclusion. Effectiveness of Refralon is noninferior to DCC in patients with persistent AF.
Aim. Comparison of different treatment tactics – medicated antiarrhythmic therapy (AAT) and radiofrequency ablation (RFA) of elderly and senile pa- tients with relapsing atrial fibrillation (AF) as more severe patients with a burdened comorbid background.
Material and methods. The study included 108 patients with paroxysmal and persistent AF who were in hospital and then under outpatient observation for 2 years. Depending on the method of treatment, patients were divided into 2 groups: the group receiving medicated AAT (n=45) and the group treated with RFA (63 patients). Most patients of the 2nd group (n=60) after the RFA received AAT, i.e. so-called hybrid therapy. These groups were comparable in age (mean age 64.9 and 64.7 years, respectively), sex and underlying pathology, comorbid diseases.
Results. In patients who received "hybrid" therapy after 2 years of observation, it was more often possible to preserve the sinus rhythm and achieve a reduction in arrhythmia episodes in comparison with the drug group (95.2% and 86.6%, respectively). Quality of life and the frequency of complications of AAT in these groups of patients were comparable.
Conclusion: In elderly and senile patients with paroxysmal and persistent atrial fibrillation, RFA and hybrid therapy was more effective for maintaining sinus rhythm compared to drug therapy. After RFA in this category of patients, in most cases, medicated AAT was used. When choosing the tactics of rational AAT in elderly patients, preference should be given to tactics in which it is possible to achieve an improvement in the quality of life.
Aim. To study the combined effect of cardiovascular risk factors and genetic markers that encode the proteins of the main components of neurophysiological systems (renin-angiotensin-aldosterone, sympathetic-adrenal systems, endothelial dysfunction) on the development of arterial hypertension among the indigenous and non-indigenous population of Mountain Shoriya.
Material and methods. We performed a clinical and epidemiological study of the compactly settled population in the remote areas of Mountain Shoriya. This region of middle mountains is situated in the south of Western Siberia. We examined 1409 subjects (901 subjects – the representatives of indigenous nationality [the Shors], 508 subjects – representatives of non-indigenous nationality [90% among them were the representatives of the European ethnicity]). Hypertension was diagnosed according to the National Guidelines of the Russian Society of Cardiology/the Russian Medical Society on Arterial Hypertension (2010). All patients underwent clinical, laboratory and instrumental investigation. Polymorphisms of genes ACE (I/D, rs 4340), АGT (c.803T>C, rs699), AGTR1 (А1166С, rs5186), ADRB1 (с.145A>G, Ser49Gly, rs1801252), ADRA2B (I/D, rs 28365031), MTHFR (c.677С>Т, Ala222Val, rs1801133) and NOS3 (VNTR, 4b/4a) were tested using polymerase chain reaction.
Results. Cardiovascular risk factors associated with hypertension in cohort of Shorians: hypercholesterolemia [Odds Ratio (OR) 1.54, low density lipoproteinemia (OR 1.48), violation of carbohydrate metabolism (OR 1.53), obesity (OR 2.25), including its abdominal type (OR 1.53), the family anamnesis of early cardiovascular diseases (OR 1.88)] and rs4340 polymorphisms of the ACE gene (OR 4.39), rs5186 of the AGTR1 gene (OR 10.02); in the cohort of the non-indigenous ethnos – hypercholesterolemia (OR 1.87), hypertriglyceridemia (OR 1.87), obesity (OR 2.75), abdominal obesity (OR 2.73), family anamnesis of early cardiovascular diseases (OR 2.48), the polymorphism rs5186 of the AGTR1 gene (OR 26.77). Genotype G/G ADRB1 gene was characterized by protective effect against hypertension in the Shorians.
Conclusion. Evaluation of the complex influence of clinical and genetic factors on the development of hypertension in the population of Mountain Shoriya showed their comparable importance among the indigenous population and the predominance of non-genetic factors among the non-indigenous population.
NOTES FROM PRACTICE 
The purpose of this article is to demonstrate a new approach to polypharmacy management in ambulatory practice using as example a case report of adverse drug event (ADE) in patient with atrial fibrillation and comorbidity. The patient had excessive polypharmacy level (11 drugs). Minor bleeding developed when using these drugs (INR – 6.70). The analysis of drug interactions was performed at patient’s home by online database "Multi-Drug Interaction Checker" and "Time-effect-drug administration" graphic. As a result of analysis, it was described two drug interactions led to minor bleeding: warfarin+rosuvastatin, warfarin+amiodarone. It was found that the patient had not taken rosuvastatin before and it was first-time administration of rosuvastatin. Therapy was corrected, the causes and effects of ADE are eliminated. The drugs without proven benefit and known drug interactions were cancelled. There were no clinical signs of bleeding after correction and the last INR was 2.54.
Combined using of "Multi-Drug Interaction Checker" and "Time-effect-drug administration" graphic allowed to detect causal relationship between ADE and drugs initiating it and then to make a rational decision right at the patient’s home in a short time.
Pericarditis is not enough researched and described in literature despite the emergence of a large quantity of up-to-date laboratory and instrumental methods of verification. The main problem is that pericarditis might be a sign of many infectious and non-infectious diseases. It is quite difficult to define the etiopathogenetic reason of process. The article presents a clinical observation of a 53 years old mail patient with paroxysms of atrial flutter, non-symptomatic febrile fever, arthralgia and signs of exudative pericarditis, which were manifested after the acute viral infection. The symptoms have been lasting for 8 months before the patient’s hospitalization. In lab tests anemia, leucopenia, increase level of platelets and increase antinuclear antibody level were found. Several conceptions were considered: cancer with paraneoplastic syndrome, systemic disease, infectious process, myeloma, which were subsequently excluded. Due to the fact that pericardial effusion may often be associated with tuberculosis Diaskin test and T-SPOT were performed and they appeared to be positive. After several months of antituberculous treatment temperature normalized, atrial flutter episodes and arthralgia diminished. So empirically and laboratory tuberculous pericarditis with atypical manifestation was confirmed. The particularity of this observation is a nontypical clinical picture and the absence of a primary focus of infection. That is why the clinicians could not define the diagnosis rapidly.
The considered clinical case of combination of multifocal atherosclerotic vascular lesion with type 2 diabetes mellitus and liver fibrosis demonstrates a combination of polyvalent risk factors for resistance to antiplatelet therapy with clopidogrel. The decrease in the effectiveness of prolonged therapy with P2Y12 inhibitor was clinically manifested by repeated thrombotic events and was confirmed by laboratorial VerifyNow P2Y12 Assay test system as a low percentage of inhibition of ADP-induced platelet aggregation. We established probable genetic predictors of the decrease in the effectiveness of antiplatelet therapy in this patient, namely, the carriage of polymorphic markers of the ABCB1 CT, CES1 CA and CYP3A4*22 CT genes that determine the decrease in absorption, excessive hydrolysis of the drug and reduced activity of isoenzymes and transporters, that leads to disorders of active clopidogrel metabolite formation. A potential contribution of hepatic dysfunction to reduction in antiaggregant effect of P2Y12 inhibitor was demonstrated. Variant of drug interaction of clopidogrel and an inhibitor/substrate of P450 CYP2C19 – omeprazole, accompanied by a decrease in the effectiveness of antiplatelet therapy, was also considered.
ASSOCIATED PROBLEMS OF CARDIOLOGY 
Rheumatoid arthritis (RA) is a disease with a high cardiovascular risk, which is caused, in particular, by an increased incidence of chronic heart failure (CHF). Analysis of the results of the main studies on the prevalence of CHF, the features of the etiology and pathogenesis of myocardial dysfunction in RA was the purpose of the review. According to the registers, population and epidemiological studies, the risk of CHF and CHF-associated mortality in RA patients is 1.5-2.5 times higher than in the general population. In most of the studies only clinically manifested congestive heart failure (HF) was considered, so the actual prevalence of CHF may be significantly underestimated. An increase in the risk of CHF was noted immediately after the debut of RA, with the prevalence of HF with preserved systolic function of the left ventricle, which indicates the important role of diastole disturbance in the pathogenesis of myocardial dysfunction. Chronic systemic autoimmune inflammation contributes to the development of CHF in RA patients, in addition to coronary heart disease, traditional risk factors (TRFs) of cardiovascular diseases (CVD). Inflammation plays a leading role in the development of CHF through various mechanisms including direct damage to the myocardium and coronary arteries (myocarditis, coronary vasculitis, microcirculatory disorders), aggravation of the severity of TRFs of CVD, accelerated progression of ischemic heart disease, endothelial dysfunction, increased vascular wall stiffness, cardiac and vascular remodeling. Early diagnosis of CHF and timely measures that can slow its progression is needed due to the high risk of CHF and CHF-associated mortality in RA patients, especially in patients with risk factors for CHF.
Background. Patients with psoriatic arthritis (PsA) have increased risk of cardiovascular diseases (CVD). Anti-tumor necrosis factor (TNF) therapy is an effective in PsA but its cardiovascular effects are poorly understood.
Aim. To study the changes in carotid intima-media thickness (c-IMT), parameters of arterial stiffness (AS), ambulatory blood pressure monitoring (AMBP) in early PsA (EPsA) patients during the anti-TNF therapy with adalimumab (ADA).
Material and methods. Patients with EPsA (n=16; 11 females, 5 males; median age 45.5 years, EPsA duration – 7.7 months) were included into the study. All patients were treated with ADA 40 mg every other week up to 3 months. At baseline and after 3 months of therapy all patients were assessed for conventional cardiovascular risk factors, DAS (Disease Activity Score) and HAQ (Health Assessment Questionnaire) indices, C-reactive protein (CRP), c-IMT, ABPM. At baseline the 4 patients had arterial hypertension, and all patients received effective antihypertensive therapy. All patients were assessed for AS parameters: carotid-femoral pulse wave velocity (PWVcf) and index of wave reflection (rigidity index; RI, %). c-IMT was measured using a high-resolution B-mode ultrasound machine. The results are presented in the form of a median – Me (25; 75 percentiles).
Results. By the end of the 3rd month of therapy, a decrease in the activity of early PsA was observed as compared to baseline values: DAS decreased from 4.6 (2.9; 1.9) to 1.6 (1.3; 1.9), p=0,001; HAQ from 0.93 (0.81; 1.31) to 0.25 (0; 0.56), p=0,001; CRP from 27.2 (9.7; 33.7) to 1.8 (0.8; 3.1) mg/l, p=0.001. EPsA remission (DAS<1.6) was achieved in 94% of patients. By the end of therapy c-IMT decreased from 0.8 (0.74; 0.85) to 0.73 (0.58; 0.77) mm, p=0,01; as well as AS parameters: PWVcf from 9.9 (7.7; 17.7) to 9.2 (7.4; 10.6) m/s, p<0.05; RI from 69.5 (58; 74) to 49.5 (44; 64)%, p<0.05. AMBPs parameters didn't change significantly. We found significant (p=0.03) decrease in the frequency of the increase in 24-hour diastolic blood pressure.
Conclusions. Anti-TNF treatment with ADA improves arterial wall state by decreasing inflammation. These data confirm the idea that inflammation involves in acceleration of atherosclerosis in EPsA patients.
PREVENTIVE CARDIOLOGY AND PUBLIC HEALTH 
Aim. To assess the economic burden associated with the absence of lipid-lowering therapy (LLT) in patients with cardiovascular diseases (CVD) and hypercholesterolemia (HCS) in the Russian population in 2016, including direct costs of the health care system and indirect economic losses due to premature death, absenteeism and disability.
Material and methods. The calculation includes data from local population-based studies (prevalence of HCS, treatment coverage and efficiency), as well as Russian statistics on CVD for 2016. Population attributive risk (PAR) was determined, which reflected the incidence of excessive morbidity associated with the lack of HCS therapy in developing CVD for the Russian population, based on LDL cholesterol level. Direct and indirect components of economic burden associated with the absence of LLT have been calculated, as well as the number of deaths with the calculation of "lost years of potential life" lacking to reach the age of 72 years, and losses associated with premature mortality in the economically active age. Indirect costs (economic losses) included non-received gross domestic product (GDP) due to premature mortality and disability in economically active age and loss of earnings due to temporary disability (TD). To estimate the indirect costs, the number of people of the working age with permanent disability in each of the disability groups has been calculated. The indirect costs due to temporary disability were calculated as payments of salary including for days of incapacity for work multiplied by the number of days of TD according the Russian statistics data.
Results. The absence of LLT in people with HCS increases the risk of CVD related mortality by one third, death due to cerebrovascular diseases, including stroke, by more than a half. PAR was estimated to be 17% for CVD mortality in general, 26% for cerebrovascular diseases. Contribution of HCS and the lack of LLT to morbidity is 29% for ischemic heart disease (IHD), 20% for myocardial infarction. Outpatient calls take the first place among all out-patient care statistics, and those associated with IHD are in the leading position among them. Hospitalization takes the second place. The absence of LLT caused the loss of more than 400,000 years of life in economically active age. The direct costs are determined by expenses for hospitalizations in the presence of IHD. The share of direct costs for hospitalizations is 86%, while in the presence of cerebrovascular diseases it is 76.8%. Payments for disability allowance, which refers to direct non-medical costs, exceed 154 million Russian rubles (RUR) for IHD and 104 million RUR for cerebrovascular diseases. The biggest share of economic burden associated with the lack of LLT in individuals with this risk factor is accounted for indirect economic losses: about 507 billion RUR in IHD, of which more than 90 billion RUR are associated with myocardial infarction. The costs associated with cerebrovascular diseases make up over 305 billion RUR, the vast majority of which is due to stroke: over 248 billion RUR. Due to the low LLT coverage in the Russian Federation, the economic burden associated with its absence is over 80% of the calculated HCS related losses in total.
Conclusion. Economic burden of the lack of LLT in HCS patients is calculated as 530 billion RUR, which is about 0.6% of GDP in 2016, and the largest part of expenditures is related to IHD. The increased awareness of HCS and its improved control with increasing treatment coverage will make possible to lower cholesterol values at the population level, which will also reduce the economic burden of this risk factor for CVD.
Obesity is one of the main risk factors for type 2 diabetes developing. The question of the advantages and disadvantages of using various anthropometric indices [body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHR), lipid accumulation product index (LAPI), visceral obesity index (VOI)] has been under discussion lately.
Aim. To perform an analysis of anthropometric obesity indicators (BMI, WC, WHR, VOI, LAPI) depending on the presence of type 2 diabetes in the adult population of the Russian Federation.
Material and methods. The results of the study "Epidemiology of Cardiovascular diseases and their risk factors in the regions of the Russian Federation" (ESSE-RF) performed in 2012-2014 in 13 regions of the Russian Federation are included into the analysis. People aged 25-64 years (n=20878; 8058 men and 12820 women) were examined. The following indicators in people with/without type 2 diabetes were analyzed: age; sex; anthropometric indicators: height, weight, WC; smoking status (“never smoked”, “smoked”, “smokes now”); alcohol consumption, which was ranked for “never in the last year” and “a lot” (≥168 g of ethanol per week for men and ≥84 g of ethanol per week for women); the level of systolic (SBP) and diastolic (DBP) blood pressure; heart rate (HR); levels of glucose, total cholesterol (TC), high density lipoproteins cholesterol (HDL-C), triglycerides (TG); WHR; VOI; LAPI, BMI.
Results. Levels of TC and glucose, excessive alcohol consumption, BMI were selected in a multifactor regression model in men after adjusting for age, region of residence and IVO. The same factors (SBP instead of alcohol and BMI instead of WHR were included in the model) were selected in women. VOI showed the greatest degree of association with type 2 diabetes regardless of gender after adjusting for age and region of residence (in men odds ratio 1,085; p=0.0001; in women odds ratio 1,136; p=0.0001). Thus, VOI (predictor of type 2 diabetes in population of working age) was common to both sexes.
Conclusion. VOI has statistically significant associations with type 2 diabetes. VOI is the best surrogate marker for measuring the degree of abdominal obesity in the Russian population and can be used to determine the presence of type 2 diabetes in clinical practice. Screening for elevated VOI values in healthy individuals and patients with pre-diabetes can serve as a guide for targeted aggressive preventive interventions.
Participants of the ESSE-RF Study: Vladivostok: Kulakova N.V., Nevzorova V.A., Shestakova N.V., Mokshina M.V., Rodionova L.V.; Vladikavkaz: Tolparov G.V.; Vologda: Shabunova A.A., Kalashnikov K.N., Kalachikova O.N., Popov A.V.; Volgograd: Nedogoda S.V., Chumachek E.V., Lediaeva A.A.; Voronezh: Chernyih T.M., Furmenko G.I., Ovsyannikova V.V., Bondarcov L.V.; Ivanovo: Belova O.A., Romanchuk S.V., Nazarova O.A., Shutemova O.A.; Kemerovo: Barbarash O.L., Artamonova G.V., Indukaeva E.V., Mulerova T.A., Maksimov S.A., Skripchemko A.E., Cherkass N.V., Tabakaev M.V., Danilchenko Ia.V.; Krasnoyarsk: Grinshtein Yu.I., Petrova M.M., Danilova L.K., Evsiukov A.A., Shabalin V.V., Ruph R.R., Kosinova A.A., Filonenko I.V., Baykova O.A.; Moscow: Gomyranova N.V., Oganov R.G., Oshepkova E.V.; Orenburg: Libis R.A., Basyrova I.R., Lopina E.A.; Samara: Dupliakov D.V., Gudkova S.A., Cherepanova N.A.; St. Petersburg: Konradi A.O., Baranova E.I.; Tomsk: Trubacheva I.A., Kaveshnikov V.S., Karpov R.S., Serebriakova V.N.; Tyumen: Efanov A. Yu., Medvedeva I.V., Storozhok M.A., Shalaev S.V.
Aim. In the framework of the database of patients with atrial fibrillation established in the Kursk region, to study the clinical and anamnestic indicators, the structure of the combined and concomitant diseases in the patients under study, and also to evaluate the usefulness of the diagnostic methods of the study and drug therapy of this pathology.
Material and methods. The regional study (REKUR-AF) included patients with atrial fibrillation (AF) from 18 years of age and older living in the city of Kursk and seven districts of the Kursk region. Recruitment of patients to the study was conducted from September 2015 to August 2016. When analyzing the outpatient charts of the studied patients, demographic data, the type and duration of AF, cardiovascular diseases (CVD), concomitant noncardiac pathology, laboratory and instrumental examination data, information about hospitalizations for the last year, pharmacotherapy were recorded.
Results. The research included 896 patients with AF. Mean age of patients was 69 (62-77) years, women were significantly older than men (p<0.001). When analyzing the most common CVD in patients with AF (chronic heart failure, stable exertional angina, arterial hypertension), it was found that comorbid pathology was found in 99.3% of patients. 22.7% of patients had myocardial infarction (MI) in the past, 12.3% – acute cerebrovascular accident. From concomitant noncardiac diseases, patients with AF most often suffered from chronic kidney disease, obesity, type 2 diabetes, diseases of the gastrointestinal tract. On the average, one patient had 4 (3-4) diagnoses of CVD, and together with concomitant pathology – 5 (4-6). The medical examination was not in line with required level in the existing diseases. The high risk according to CHA2DS2-VASc scale was revealed in 96.3% of patients and according to HAS-BLED scale – in 52.8%. Patients with AF most often received antiplatelet agents, angiotensinconverting enzyme inhibitors, β-blockers, statins and diuretics. Anticoagulants were only used in 18.3% of patients. The average number of prescriptions of drugs in all patients with AF was 5 (4-6) and was significantly (p<0.001) higher in the group of patients with MI in the past (6 [4-6]) compared with the cohort of patients without MI (5 [4-6]).
Conclusion. Patients included into the REKUR-AF study were characterized by a high incidence of combined cardiovascular pathology, a high risk of thromboembolic complications. In most patients, anti-platelet drugs were used as antithrombotic therapy, although they are significantly inferior to anticoagulants in their ability to prevent thromboembolic complications. Anticoagulants were used only in every fifth patient, warfarin was a significant part (52.6%) among all anticoagulants. Patients with AF also had an insufficient frequency of laboratory and instrumental examinations, that is required according to current guidelines.
PAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPY 
Aim. Within the framework of the outpatient registry of patients with acute myocardial infarction (AMI), to assess the influence of factors in medical history, especially cardiovascular diseases (CVD) preceding AMI, on the long-term results of the underlying disease.
Material and methods. 160 patients who sought medical care to the outpatient clinic from March 01, 2014 to June 30, 2015 after AMI were included into the registry. Patients were observed for at least 1 year (maximum 2.5 years). The primary end point (PEP) of the study were death from any cause, recurrent cardiovascular complications (non-fatal AMI, cerebral stroke), and urgent hospitalization due to the worsening of the current CVD.
Results. After 1 year of follow-up, 9 (6%) patients died (8 from CVD). A recurrent myocardial infarction occurred in 8 patients, and cerebral stroke in 1 patient. 20 patients were hospitalized due to CVD exacerbation. In total PEP was registered in a fifth part of patients (36 people). Factors that had a negative impact on the endpoint were age (relative risk [RR] 1,05; 95% confidence interval [CI] 1.01-1.09, p=0.016), the presence of cardiovascular diseases or conditions reflecting the severity of the underlying disease before the reference event: ischemic heart disease (RR 2.37; 95%CI 1.05-5.34, p=0.038), previously AMI (RR=5.93; 95%CI 2.28-15.4, p<0.001), percutaneous coronary intervention (RR 9.84; 95%CI 2.02-48.06, p<0.005), disability (RR 4.37; 95%CI 1.82-10.46, p<0.001).
Conclusion. The long-term life and disease prognosis in patients with AMI remains quite severe. Adverse long-term outcomes of the disease are largely determined by anamnestic factors, primarily the presence of ischemic heart disease before the reference event, previous AMI. The study indirectly demonstrated that percutaneous coronary intervention in patients with stable ischemic heart disease, at least, does not improve the prognosis of the disease.
POINT OF VIEW 
The urgency of the problem of orthostatic hypotension (OH) has increased in recent years. It was due to the high prevalence and its adverse effect on the prognosis and quality of life of patients, especially the elderly and oldest old. The purpose of this review was to summarize the contemporary domestic and foreign literature data about disease. The article presents an updated definition of OH, modern classification, pathophysiology, feature of the course of OH in the elderly, recommendations for diagnosis and treatment. Particular attention is paid to reviewing the results of scientific research on the influence of OH on the risk of developing coronary and cerebrovascular events and overall mortality. OH is one of the forms of orthostatic tolerance and diagnostic criteria were determined by the 2011 Consensus as a sustained fall of systolic blood pressure by at least 20 mm Hg and/or a diastolic blood pressure by 10 mm Hg within 3 min of standing. The prevalence of OH ranges depending on the age of the patients and the presence of a number of concomitant diseases: from 6% in healthy people without arterial hypertension up to 50% or more in people older than 75 years with a comorbid pathology. OH is an independent predictor of overall mortality and adverse cardiovascular events. OH is associated with an increased risk of serious adverse cerebrovascular and coronary events, and may also contribute to cognitive impairment and the development of dementia. For today, we have three clinical options OH: classical, early and delayed OH. In addition, OH is classified based on etiology – primary and secondary; and pathophysiological principle – neurogenic OH and not a neurogenic OH (or functional). The algorithm for identifying patients with a high risk of development of OH and diagnostic methods are also presented. Non-medicamentous and medicamentous methods of OH treatment are considered.
Obesity is one of the leading and the most serious risk factors of cardiovascular diseases. Overweight provokes many metabolic and hemodynamic disorders. About 30% of inhabitants of the planet have overweight and prevalence of obesity increases by 10% every 10 years according to the WHO data. The probability of arterial hypertension in obese patients is 50% higher than in people with normal body mass. Framingham study showed that obesity is an independent, significant risk factor of ischemic heart disease, myocardial infarction, cerebral stroke and diabetes mellitus. The most dangerous is the central obesity with the preferential fat deposition in the abdomen. Combination of visceral obesity, violation of carbohydrate and lipid metabolism, arterial hypertension, and close pathogenic relationship between these factors underlie the isolated symptom complex known as metabolic syndrome. J. Vague was the first to describe relationship between abdominal obesity with cardiovascular disease and mortality in 1947. In our country G.F. Lang noticed common combination of arterial hypertension with obesity, lipid and carbohydrate metabolism disorders. Thus, metabolic syndrome significantly increases risk and severity of cardiovascular disease. Within last decades criteria of metabolic syndrome stays constant. The factors of insulin resistance and endothelial dysfunction as stages of the pathogenesis of the metabolic syndrome have been studied in detail. The mechanisms of insulin resistance and endothelial dysfunction are discussed in detail in this article as well as inflammatory markers and the significance of highly sensitive C-reactive protein.
The new term «MINOCA» (myocardial infarction with nonobstructive coronary arteries) emerged in the literature about 5 years ago and characterizes the syndrome with heterogeneous etiology and pathogenesis, which reflects the development of myocardial infarction with non-obstructive lesions of the coronary arteries, occurring in both cardiological and noncardiac diseases. The article gives detail focus on origin, definition, pathological bases of MINOCA. It also examines the role of coronary (non-obstructive atherosclerosis, microvascular dysfunction, coronary spasm, "myocardial bridge", coronary arteries dissection) and non-coronary reasons, caused by cardiac (cardiomyopathy, myocarditis) and non-cardiac (pulmonary embolism, thrombophilia) diseases.
In analyses of publications much attention is given to the discussion of diagnosis and differential diagnosis, prognosis and treatment of MINOCA. Recommended methods of examination are given depending on the alleged cause of the occurrence of MINOCA. Two clinical cases demonstrated difficulty in diagnosis of this condition and the importance of an individual approach. Attention is also given to the absence of currently clinical guidelines for the management of patients with MINOCA and to the significant differences in the use of different classes of cardiotropic drugs according to different author’s mind.
Author gives the opinion that MINOCA has a certain practical significance as a preliminary "diagnosis" before final establishing the disease. In conclusion, it is emphasized that the MINOCA syndrome terminology and characteristic is controversial now. This mind confirmed by a new definition of this condition in the Forth Universal Definition of Myocardial Infarction (European Society of Cardiology, 2018).
The tendency of aging of the population and, together with it, the increase in the prevalence of arterial hypertension (HT) determines the need to study the peculiarities of treatment of HT in patients of elderly and senile age. In this regard, in the new Guidelines of the European Society of Cardiology for diagnosis and treatment of HT (2018), the authors identified groups of elderly patients (aged 65-79 years) and very elderly patients (aged ≥80 years), blood pressure (BP) levels for the initiation of antihypertensive therapy and target BP levels, and recommended the main principles of antihypertensive therapy. The new recommendations of the ESH/ESC in 2018 also presented the characteristics of HT management in elderly patients. The necessity of mandatory detection of senile asthenia in elderly patients and determination of the degree of their independence from outside help is emphasized. In all elderly patients, especially in very elderly or "fragile" patients, it is recommended to evaluate the presence or development of orthostatic hypotension during treatment, as well as actively to detect episodes of hypotension using the 24-hour BP monitoring. For antihypertensive therapy in elderly patients, the same five classes of antihypertensive drugs and their combination are recommended. It is emphasized that if it is not required for the treatment of concomitant diseases, loop diuretics and alpha-blockers should be avoided because their use is associated with an increased risk of falls. It is recommended to investigate the level of serum creatinine more often to evaluate the kidney function and to detect a possible decrease in the glomerular filtration rate because of a decrease in BP and perfusion of the kidneys. The target BP levels indicated in the Guidelines are: systolic BP values 130-139 mm Hg and diastolic BP 70-80 mm Hg. In the Guidelines it is emphasized that elderly patients need careful monitoring of any adverse side effects of antihypertensive drugs.
CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY 
This article affects the problems of using NOAC in the most defenseless groups of patients with atrial fibrillation: those who have high bleeding and high thromboembolic risk and elderly. The focus is on comparison of effectiveness and safety of NOACs based on randomized clinical trials (RCT) and real-world data (RWD). The possible reasons for the different interpretation of the data of the RCT and the RWD are shown. Use of NOAC in reduced doses prescribing according to RCT and RWD are shown. Our own 13-month observation of patients 75 years and older with very high thromboembolic risk (CHA2DS2-VASc – 4,5 points) on rivaroxaban therapy are presented. Good efficacy and safety of full and reduced doses of rivaroxaban were demonstrated: only 2 episodes of small bleedings and no large bleedings (ISTH criteria) were detected as well as no thromboembolic events. Thus, even difficult patients with AF and comorbidity may be safely and effectively treated with NOACs taking into consideration integrated approach and correction of modifiable risk factors.
FORUMS 
The article is devoted to the discussion of the main news from the annual congress of the European Society of Cardiology (Munich, August 25-29, 2018). The results of just completed randomized clinical trials (RCTs) are reviewed. The RCTs presented at the congress were mainly devoted not to new drugs, but to the features of the use of already known drugs, which was important for clinical practice.
JUBILEE 
INFORMATION 
OBITUARY 
ISSN 2225-3653 (Online)