Aim. To study the role of Glu298Asp and C242T point substitutions and their combinations in the development of essential arterial hypertension (AH). Material and methods. The study included 511 men aged 19—61 years (mean age 36,2±5,5 years): 409 patients with confirmed AH diagnosis (main group, MG), and 102 healthy men without cardiovascular disease (control group, CG). Alleles of interest were identified using polymerase chain reaction and restriction fragment length analysis. Results. Among AH patients, the prevalence of mutant allele 298Asp was 22,8 %, vs. 24,2 % in the CG (р>0,05). The prevalence of mutant allele 242Т was 31,8 % and 37,8 % in MG and CG, respectively (p>0,05). The combinations where mutant allele 298Asp outnumbered mutant allele 242Т were shown to increase AH risk. In the binary logistic regression model, AH odds ratio and confidence intervals were calculated. The p value of the model was assessed with maximal likelihood test. In people with “prevalent” NOS3 mutation, AH risk was higher (OR 1,55; 95 %CI 1,00—2,40; p=0,049). Adverse genotypes included 298Het/242Wt; 298Mut/242Het; 298Mut/242Wt и 298Wt/242Het. Conclusion. Point mutations of Glu298Asp and C242T did not increase AH risk in men substantially. However, other genotype combinations, associated with increased AH risk, were identified.

Aim. To study the sleep structure and sleep disturbances in obese (O) patients with arterial hypertension (AH). Material and methods. Group I included 62 patients (30 women and 32 men) with chronic cerebrovascular disease (CerVD) and arterial hypertension (AH), aged 53,4±7,4 years. Group II included 42 patients (27 women and 15 men) with increased body mass index (BMI), over 30 kg/m2 (mean BMI 33,5±2,6 kg/m2 ), aged 49,3±7,3 years. In all participants, Stage I-II discirculatory encephalopathy was diagnosed. The control group (CG) included 24 healthy volunteers (14 women and 10 men), aged 49,3±8,2 years. Sleep disturbances were evaluated with the questionnaire on subjective assessment of sleep disturbances, as well as with an objective method of polysomnography. Results. Subjective complaints of sleep disturbances were reported by 87% of AH patients. All elements of sleep structure were disturbed: comparing to the CG, falling-asleep time was significantly increased (31,5±9,8 minutes), as well as the prevalence of within-sleep wakefulness (21,1±7,9%; р<0,01). No sleep apnoea symptoms were registered in AH patients. Up to 695 of O patients were not satisfied with their night sleep. Total sleep duration (375±71 minutes) and sleep effectiveness index (80,7±19,2) were decreased. Apnoea index was significantly higher than in the CG: 17,1±9,8 vs. 5,3±1,4, respectively (р<0,001), while saturation parameters were lower than in controls: 84,2±1,4% vs. 96,4±1,1%, respectively (р<0,05). Conclusion. AH patients demonstrated a correlation between sleep disturbances (psycho-physiological insomnia type), psycho-vegetative syndrome severity, and AH severity. In O patients, sleep disturbances were secondary, with the leading role of sleep apnoea.

Aim. To study the dynamics of blood pressure (BP) and peripheral blood flow parameters during thyroid status compensation in patients with primary hypothyroidism (PHT) and arterial hypertension (AH). Material and methods. The main group (MG) included 70 patients with decompensated PHT and AH (64 women, 6 men; mean age 54,0±1,2 years). The control group (CG) included 40 women with essential AH (mean age 53,4±2,3 years). All participants underwent 24-hour BP monitoring (BPM), high-frequency Doppler ultrasound, with maximal systolic (Vs) and end diastolic (Vd) velocity assessment, as well as reactive hyperemia test (RHT). Results. MG and CG patients were comparable by day and night-time levels systolic and diastolic BP (SBP, DBP). Hormone replacement therapy in MG patients resulted in a significant SBP reduction during the day (-5,6 %; p<0,01) and the night (-4,3 %; p<0,05). At baseline and after RHT, Vs was 21 % higher in PHT patients than in the CG (p<0,01). Thyroid status compensation was associated with a 24 % Vs reduction (p<0,05), and no statistically significant Vs difference, comparing to the CG. Conclusion. In PHT and AH patients, thyroid status compensation resulted in a significant SBP decrease during the day and night, as well as in reduced Vs.

Aim. To study the effects of skeletal electromyostimulation (SEMS) on intracardiac hemodynamics and arrhythmia risk in elderly patients with myocardial infarction (MI). Material and methods. The study included 92 MI patients aged >60 years (mean age 71,4±0,6 years), divided into 4 groups: two SEMS groups of patients aged 60-69 years (n=18) and over 70 years (n=30), plus two control groups, aged 60-69 years (n=19) and over 70 years (n=25). In the main groups (MG), SEMS course was started from treatment day 4-5 (2 hours per day, 10 days; “Myorithm-040” device). Before hospital discharge, strength and endurance of leg skeletal muscles, general physical stress tolerability (PST), 24-hour electrocardiography (ECG) monitoring, and echocardiography (EchoCG) parameters were assessed. Results. In MI patients aged over 70 years, SEMS course increased power and endurance of leg muscles and PST, while these effects were absent among patients aged 60-69 years. In the MG, SEMS was associated with reduced mean circadian heart rate (HR), and no adverse changes in intracardiac hemodynamics, comparing to the CG. During veloergometry stress test, PST in elderly patients significantly and directly correlated with leg muscle strength and endurance, and moderately and inversely correlated with age and maximal HR at night. Conclusion. SEMS is a safe method of PST increase in MI patients aged over 70 years. This method should be studied further and implemented into clinical practice.

Aim. To measure the blood levels of pregnancy-associated plasma protein A (PAPP-A) and inflammatory markers in patients with various forms of coronary heart disease (CHD); to evaluate their diagnostic and prognostic role. Material and methods. The study included 75 patients with unstable angina (UA), acute myocardial infarction (AIM), and stable angina. The concentrations of PAPP-A, vascular adhesion molecule (sVCAM-1) and interleukin-6 (IL-6) were measured by immuno-enzyme method; the levels of C-reactive protein (CRP) and fibrinogen were measured by latex-enhanced micro-plate immuno-turbidimetry method. The follow-up period lasted for two years. Results. A significant elevation of PAPP-A, CRP, IL-6, and sVCAM1 levels was observed in UA and AMI patients. The level of PAPP-A was significantly higher in UA participants than in those with AMI, and demonstrated the highest sensitivity and specificity in UA diagnostics. Conclusion. PAPP-A could be used as a marker of acute coronary syndrome. Its elevated levels (>10mIU/l) predict adverse outcomes in CHD patients.

Aim. To study clinical and hemodynamic parameters, in association with thyroid status (TS) markers, in patients with dilated cardiomyopathy (DCMP); to assess the effectiveness of 12-week combination of basis therapy and levothyroxine natrium (LTN) treatment. Material and methods. The study included 53 DCMP patients (39 women and 14 men), aged 22—58 years (mean age 41±2,7 years). In addition to clinical examination and hemodynamics assessment, plasma levels of triiodthyronin, thyroxin, and thyrotropin were measured in all participants. According to biochemical data, 43 patients were divided into 2 groups: Group I (n=21) with hypothyrosis (HT), and Group II (n=22) with normal TS. Group I received standard heart failure (HF) therapy and LTN. Twelve months later, the number of deaths and hospital admissions due to HF decompensation were retrospectively assessed. Results. In 39,6 % of DCMP patients, HT was observed, despite the absence of primary thyroid disease. Decreased plasma levels of thyroid hormones were associated with reduced physical stress tolerability and reduced myocardial contractility. Conclusion. The 12-week combination of basis HF therapy and LTN treatment was linked to TS normalization, improvement in clinical status and selected parameters of intracardiac hemodynamics, as well as with a significant reduction in repeat hospital admissions. 

Warfarin effectiveness and safety is substantially affected by concurrent therapy. This paper reviews the main mechanisms of warfarin interactions with other agents, which underlie adverse effect development: platelet dysfunction, gastro-intestinal effects, suppressed intestinal synthesis of vitamin K, disturbed warfarin metabolism, or disrupted vitamin K cycle. The main medication groups, affecting warfarin effectiveness and safety, are presented. The effects of foods, supplements, and herbal medications on anticoagulant effect of warfarin are discussed.

Currently, the prevalence of diastolic chronic heart failure (DCHF) in the population of chronic heart failure (CHF) patients reaches 40—55 %, being as high as ≥73 % in Russia. The prevalence of DCHF is higher in older age groups and women. The CHF diagnosis is mostly based on clinical examination of the patient, since a standard assessment of E/A ratio is often not informative enough. Detailed assessment of diastolic function requires measurement of heart wall thickness and atrial sizes during four-chamber position echocardiography. According to the European clinical guidelines, the leading role in diastolic function assessment belongs to E/Em parameter, reflecting early diastolic mitral flow E and early diastolic myocardial relaxation. An increase in E/Em up to 8—15 is a sign of diastolic dysfunction. Despite substantial advances in the treatment of CHF with decreased ejection fraction, currently, there are no medications for the treatment of DCHF with effectiveness demonstrated in largescale randomised clinical trials. Therefore, the present approaches to DCHF treatment remain empirically based.

Aim. To evaluate the potential of dispersion ECG mapping (ECG-DM) in diagnosing cardiovascular disease (CVD) and general health problems (GHP) during the screening examination of various population groups. Material and methods. In total, ECG-DM was performed in 1000 Uryupinsk and Uryupinsk Region citizens (537 healthy people, 156 people with GHP, and 307 people with CVD). In 84 participants, ECG-DM was performed before and after a simple stress test (20 squats). Additional examination of 21 CVD patients was performed before Results. An optimal cut-off for separating “norm” and “pathology” was 15 % level of “myocardium” parameter (sensitivity 75,6 %, specificity 80,3 %). For differentiation between CVD and GHP, this parameter had specificity of 58,3 % and sensitivity of 68,4 %. Out of 537 “healthy” people, in 39 (7,3 %) “myocardium” parameter was elevated, and an additional examination revealed CVD. In all participants (n=1000), no correlation between “myocardium” parameter and age, gender, cholesterol, blood pressure, or heart rate levels was observed, which points to its independent value in CVD diagnostics. A combination of ECG-DM and stress test improved sensitivity. Negative changes in ECG-DM parameters after stress test reflect changes in myocardial electrophysiology, and should not be regarded as direct evidence of myocardial ischemia. During the treatment of CVD patients, an improvement in ECG-DM parameters was associated with subjective improvement in patients’ well-being. Conclusion. ECG-DM method could be recommended for various screening programs, to identify people in need for additional examination because of potential CVD and other pathology.

Aim. To compare the effectiveness of Health School (HS) initiative in male and female patients with chronic heart failure (CHF). Material and methods. The study included 239 CHF patients: 118 women and 119 men. For both genders, the patients were randomised into intervention groups, studying at HS (58 women and 59 men), and control groups, not receiving any educational intervention (60 women, 60 men). The follow-up period lasted for one year. The criteria of HS effectiveness included relative and absolute parameters of hospitalisation due to decompensated CHF; seeking for urgent medical care due to CHF decompensation; unplanned visits to the doctor; clinical CHF status dynamics by the scale modified by V.Yu. Mareev (2000); 6-minute walk test results; electrocardiography (ECG) and echocardiography (EchoCG) results. Results. HS effectiveness was significantly different in female and male intervention vs. control groups. In women, being educated at HS did not affect the incidence of hospitalizations and unplanned visits to the doctor due to decompensated CHF, while in men, the same parameters were substantially lower in those from the intervention group. Similarly, clinical CHF status, 6-minute walk test results, and ECG repolarization parameters were not changed by HS participation in women, but were improved in men attending HS. At the same time, the incidence of seeking for urgent medical help was significantly lower in both female and male HS groups. Conclusion. Planning the strategy of secondary CHF prevention should take into account the gender differences; otherwise, the effectiveness could be inadequate in female patients.

Aim. To assess the effects of the complex therapy, including trimetazidine MB, on the clinical course of chronic heart failure (CHF), cardiac hemodynamics, myocardial structure, function, and bio-electric activity in patients with coronary heart disease (CHD) complicated by CHF. Material and methods. In 82 patients (67 men, 15 women), mean age 62,2±7,3 years, with CHD and Functional Class (FC) II-III CHF, the effects of 16-week complex therapy including trimetazidine MB (70 mg/d; Group I) vs. trimetazidine-free therapy (Group II) on CHF FC dynamics, left ventricular (LV) remodelling, physical stress tolerance, and myocardial bio-electric activity were investigated. Results. After 16 weeks of the treatment, clinical improvement and CHF FC reduction were observed in 28 % and 26 % of the patients from Groups I and II, respectively. The percentage of the patients with FC III decreased to 27,2 % and 30,9 %, respectively, while for FC II, the respective percentages decreased to 67,5 % and 66,7 %. According to the Holter ECG monitoring results, the incidence of paired ventricular extrasystoles (VE) decreased by 57,6 % and 28,8 % in Groups I and II, respectively (р<0,05), the incidence of isolated VE — by 23,6 % (р>0,05) and 6,9 % (р>0,05), and the incidence of supraventricular extrasystoles (SVE) — by 26,4 % (р>0,05) and 10,8 % (р>0,05), respectively. The 24-hour number of ST depression episodes decreased by 55,5 % (р<0,05) and 23,3 % (р<0,05) in Groups I and II, while the total duration of these episodes was reduced, respectively, by 17,8 % (р<0,05) and 12,7 % (р<0,05). According to echocardiography results, LV ejection fraction increased by 13,7 % (р<0,05) and 10,4 % (р<0,05), respectively. In treadmill test, total load time increased by 16,8 % (р<0,05) in Group I and 8,2 % (р<0,05) in Group II. Conclusion. Trimetazidine MB, as a part of complex CHF therapy in CHD patients, significantly improved clinical symptoms and reduced CHF FC, which was also associated with improvement in cardiac structure, function, and bio-electric activity.

Aim. To assess the effectiveness of ivabradine therapy in heart rate (HR) reduction among patients with acute heart failure (AHF). Material and methods. ОIn total, 40 dopamine-treated patients with inferior myocardial infarction (MI) were examined. All participants were randomised into Groups A (n=21; ivabradine dose 10-20 mg/d) and B (n=19; controls). In all patients, HR was measured, and echocardiography was performed. Results. In Group A, HR decreased as early as 12 hours after the start of ivabradine therapy, from 106,4±2,7 to 98,5±2,8 bpm (p<0,05), while in Group B, no HR reduction was observed in the first 24 hours. By Day 14, HR was reduced in both groups. In Group A, however, it was significantly lower — 81,5±1,8 vs. 91,6±2,5 bpm (p<0,001), despite similar baseline HR levels. According to the echocardiography results, Group A demonstrated an increase in left ventricular ejection fraction (LV EF), from 29,4±1,7 to 34,9±1,8 % (р<0,05), without LV dilatation. In Group B, no LV EF increase was observed by Day 14, and LV size increased from 56,8±1,1 to 60,5±1,2 mm (p<0,005). Conclusion. Ivabradine reduced HR in AHF, which was associated with improved LV contractility and prevented further LV dilatation.

Aim. To investigate neuro-vegetative features of cardiovascular regulation in patients with metabolic syndrome (MS); to study the potential of nebivolol in correction of vegetative disbalance among MS patients. Material and methods. This prospective study included 28 untreated patients with MS. All participants received nebivolol (5—10 mg/d) for 6 months. At baseline and 6 months later, bifunctional 24-hour blood pressure (BP) and electrocardiography (ECG) monitoring was performed. Results. After 6 months of nebivolol treatment, a significant reduction in SDANN (p=0,031) was observed, associated with decreased low-frequency (LF) power (р=0,065) and sympatho-vagal LF/HF index (р=0,034). Left ventricular (LV) relative wall thickness also decreased (p=0,002), as well as the prevalence of concentric LV hypertrophy. All patients achieved target BP levels, without any disturbances of lipid and carbohydrate metabolism. Conclusion. In MS patients, nebivolol, as a cardioprotective and metabolically neutral agent, could be effectively used as a regulator of sympathetic influences on heart rate.

Aim. To investigate the early stages of cardiac neuropathy development in patients with metabolic syndrome (MS) and carbohydrate metabolism disturbances, based on the analyses of short segment rhythmogram variation (SSV) and average weighted rhythmogram variation (AWV). Material and methods. In total, 90 patients were divided into three groups: Group I (n=30) included MS patients with impaired glucose tolerance (IGT); Group II (n=30) included MS patients with Type 2 diabetes mellitus (DM-2), with DM-2 duration of 5—10 years; Group III (n=30) included healthy controls. All participants underwent general clinical examination, 24-hour ECG monitoring (Holter-DMS system), with subsequent heart rate variability (HRV) analysis of both traditional (RMSSD, pNN50) and new (SSV, AWV) parameters. Results. Impaired monotonous increase of SSV during HR deceleration was observed in Groups I and II. A substantial AWV reduction was observed in Group II during all monitoring periods. In Group I, circadian AWV values were decreased in the morning and normal in the night. In Group II, RMSSD and pNN50 values were significantly reduced during the 24 hours of the monitoring, while in Group I, these values were normal, with some reduction in the morning. Conclusion. HRV analysis identified early, completely reversible during the night, manifestations of cardiac neuropathy in patients with MS and IGT. A new parameter AWV was more effective than the traditional parameters (RMSSD, pNN50) in diagnosing cardiac neuropathy in MS and IGT patients.

Aim. To study the effectiveness of long-term low-dose atorvastatin therapy in elderly patients with Type 2 diabetes mellitus (DM-2) and dyslipidemia (DLP). Material and methods. In total, 135 elderly patients with DM-2 and DLP were included in the main group (MG), receiving atorvastatin (10—20 mg/d; mean dose 15,3 mg/d) for 5 years. The control group (CG) included 55 elderly patients with DM-2 and DLP, who received lipid-lowering diet only. Lipid profile and intima-media thickness (IMT) of brachio-cephalic and lower extremity arteries (Duplex scanning) were assessed at baseline and 5 years later. Results. During the five-year follow-up period, MG demonstrated improved lipid profiles, with target lipid levels achieved in 68 % of the patients receiving atorvastatin in the dose of 20 mg/d. Brachio-cephalic IMT was relatively stable (1,23±0,2 mm and 1,22±0,01 mm, respectively, at baseline and 5 years later). In CG, lipid levels remained high, brachio-cephalic IMT increased from 1,25±0,23 mm at baseline to 1,35±0,23 mm 5 years later (p<0,001), and lower extremity IMT increased from 1,21±0,14 mm to 1,45±0,12 mm, respectively (p<0,001). Conclusion. Long-term low-dose atorvastatin therapy improved lipid profile in elderly patients with DM-2 and DLP. Among those receiving atorvastatin in the dose of 20 mg/d, target lipid levels were achieved in 68 %. The therapy also prevented progressing of brachio-cephalic and lower extremity macroangiopathy, was safe and well tolerated.

Aim. To study the stages of metabolic disorder progression after hysterectomy (HE). Material and methods. In total, 104 women (mean age 44,0±2,1 years) after supravaginal hysterectomy with intact ovaries were examined. The participants were divided into three main subgroups, according to the time since HE (1 year, 3 years, and 5 years). The comparison group (CG) included 25 women (mean age 43,0±1,6 years). The levels of blood pressure (BP), blood lipid profile, immuno-reactive insulin (IRI) and C-peptide in plasma (fasting level and the level after oral glucose tolerance test) were measured. Results. Longer time since HE was associated with a significant increase in body mass index, systolic and diastolic BP, basal and stimulated C-peptide levels, basal and stimulated ITI levels, as well as in total cholesterol (CH) and low-density lipoprotein CH, comparing to the CG. There parameters were significantly and directly correlated with the time since HE. Conclusion. Metabolic disturbances were more pronounced in patients with longer time since HE. This allowed to specify the stages of post-HE metabolic syndrome and to justify the strategy for post-HE patients’ management.

Aim. To compare clinical manifestations of cerebrovascular disease (CerVD) with the results of modern instrumental examination methods, using the semi-quantitative approach. Material and methods. In total, 40 CerVD patients with ischemic stroke in anamnesis or discirculatory encephalopathy were examined. All participants underwent duplex scanning (DS) of neck and head vessels, magnetic resonance angiography (MRA) of cerebral vessels and positron emission tomography (PET) of the brain. The observed disturbances were coded as “mild” (+), “moderate” (++), or “severe” (+++). Results. Clinical manifestations of CerVD correlated with PET-diagnosed cerebral perfusion disturbances. In 50 % of the cases, cerebral atherosclerosis in CerVD patients was characterised by combined pathology of carotid and vertebro-basilar arteries (CA, VBA), while isolated VBA pathology was relatively rare (10 %). The first-affected segments were extracranial vessels (35 %) or extracranial and intracranial vessels (27 %). A strong correlation between clinical CerVD symptoms and morphological vascular changes at DS and MRA was observed in 45 %. Conclusion. Among CerVD patients, complex instrumental examination could help in assessment of the disease severity, prognosis and therapy choice.

Aim. To develop, test and evaluate the workplace (wp) programme of multifactorial prevention of cardiovascular disease (CVD). Material and methods. In a technical research institute, with 523 employees, a complex programme of CVD prevention was introduced, including preventive examination, preventive intervention, and clinical effectiveness monitoring. Preventive examination included complex assessment of CVD and CVD risk factors (RFs) (response rate 89,5 %). Preventive intervention, developed with consideration of CVD prevention demand, was performed in the intervention group (IG). The control group (CG) was formed according to “case-control” principle. In clinical effectiveness analysis, the dynamics of blood pressure (BP), total cholesterol (TC), psycho-emotional RFs, and SCORE-calculated CVD risk was assessed. Results. Preventive examination demonstrated high prevalence of arterial hypertension (AH), metabolic and psycho-emotional RFs at wp, together with high interest in RF correction. Preventive intervention resulted in a significant reduction in systolic BP (SBP) — by 9 mm Hg, in diastolic BP (DBP) — by 9,7 mm Hg, in TC — by 0,7 mmol/l, and also in SCORE-calculated CVD risk — from 3,8 % to 3,0 %. Conclusion. Complex CVD prevention at wp was associated with substantial beneficial effects within first 12 months.