Aim. To analyze the social and economic burden of cardiovascular disease (CVD) in the Russian Federation for the period of 2006-2009.
Material and methods. The analysis of the economic CVD burden included direct spending and economic loss related to CVD. Direct spending included hospitalization, ambulance service use, out-patient visits, high medical technologies, and out-patient pharmaceutical treatment. Economic loss included the loss in gross domestic product (GDP) due to death or disability in working-age people, as well as the disability benefits.
Results. Total economic burden of CVD for 2008-2009 exceeded 1 trillion RUB, or 3 % of GDP for the respective period. Only one-fifth (21,3 %) of total economic burden of CVD in 2009 was represented by direct costs of the healthcare system. As much as 78,7 % of the total economic burden of CVD was represented by such indirect costs as economic loss, mostly due to premature mortality in working-age men.
Conclusion. Substantial economic burden of CVD in theRussian Federation requires increased funding of preventive programs, aimed at CVD risk reduction, and healthcare optimization programs. This increased funding should facilitate mortality risk reduction in the working-age population.

Aim. To investigate the prognostic role of cigarette smoking in the end-point development during the 25-year prospective follow-up of 40-59-year-old men.
Material and methods. The baseline examination of a representative sample of Tashkent City men took place in 1979-80. During the 25-year follow-up (up to 2005), the death certificate data were collected for the deceased participants of the initial study — men aged 40-59 years at baseline. All-cause mortality, cardiovascular disease (CVD) mortality, cancer mortality, and their association with smoking were analyzed.
Results. Out of 862 participants who smoked at baseline, 56,7 % died during 25 years of the prospective follow-up. Among smokers, 25-year all-cause mortality was 34,4 per 1000 person-years, while CVD and cancer mortality was 18,7 and 7,0 per 1000 person-years, respectively. Smoking was a strong predictor of 25-year all-cause mortality: compared to never-smokers, all-cause, CVD, and cancer mortality in smokers was 1,8, 1,6, and 3,5-4,6 times higher.
Conclusion. Among all deceased participants, the prevalence of baseline smoking was 61,2 %, while among people who died from CVD or cancer, it was 58,9 % and 71 %, respectively. Among men who were regular smokers at baseline, the levels of all-cause, CVD, and cancer mortality were 1,5, 1,6, and 3,3 times higher than among neversmokers. There was a direct linear association between the contribution of smoking in the end-point development and the follow-up length.

Aim. To assess the degree of cardiovascular (CV) risk adjustment in patients with low and intermediate risk by the SCORE scale, who were further examined in accordance with the European Society of Hypertension/European Society of Cardiology Guidelines (2003, 2007, 2009), and also underwent carotid artery (CA) ultrasound, as an extension of the ambulatory examination protocol.
Material and methods. The study included 600 individuals aged 30-65 years (445 women, 155 men), with low to intermediate SCORE-assessed risk, and without diagnosed atherosclerosis or diabetes mellitus. The algorithm of CV risk stratification included SCORE scale, the ESH/ESC Guidelines (2003, 2007, 2009) and duplex CA ultrasound, with intima-media thickness (IMT) and atherosclerotic plaque (AP) assessment.
Results. At the first stage of CV risk classification, which included routine examinations only, 73,8 % of the patients remained in the “low-risk” group, 14,5 % remained in the “intermediate-risk” group, and 11,7 % were moved to the “high-risk” group. After taking into account the duplex CA ultrasound results, the “low-risk”, “intermediaterisk”, and “high-risk” groups included 35,7 %, 33,5 %, and 30,8 % of the patients, respectively. In the “low-risk” and “intermediate-risk” groups, most patients had normal blood pressure levels (72,8 % and 83,5 %, respectively), while most patients in the “high-risk” group had arterial hypertension (56,7 %). The reason for moving the patients to the “high-risk” group was visualization of AP in CA (100 %). The percentage of subjects with one AP in this group was 22,7 %. In total, AP were visualized in 358 out of 600 participants (59,6 %). Out of these 358 patients, 26 (7,2 %) had IMT value >0,9 mm. Out of 242 patients without AP in CA, 2 (0,8 %) had IMT value >0,9 mm.
Conclusion. At both risk stratification stages, the most prevalent causes of moving the patients to the groups of higher CV risk were dyslipidemia (81,3 % and 92,5 %, respectively), smoking (26,7 % and 22,2 %), abdominal obesity (77,7 %), and metabolic syndrome (98,5 %). The level of CV risk was affected by AP presence to a substantially greater extent than by IMT.

Aim. To investigate the specific features of stress reactivity and diagnostic potential of psycho-emotional tests for identification of the patients with workplace arterial hypertension (WPAH).
Material ad methods. The study included 197 patients with WPAH and 132 subjects with essential AH (EAH). All participants underwent blood pressure monitoring (BPM) during work and leisure hours and stress reactivity assessment (count test).
Results. In WPAH and EAH patients, the count test resulted in increased systolic (SBP), diastolic (DBP) BP, and heart rate (HR) (р<0,001), which was an evidence of stress-related functional cardiovascular reaction. In subjects with new-onset WPAH, compared to EAH patients, the SBP and HR increases were greater by 7,9 mm Hg (р<0,005) and 4,3 bpm (р<0,001), respectively. In patients with long-term EAH, SBP increase was greater by 3,4 mm Hg (p=0,03), with a halved HR increase (p<0,001). In healthy controls and AH patients, the differences between baseline levels of SBP and DBP, peak levels during the count test, and BMP levels for work hours were comparable.
Conclusion. The patients at early WPAH stages were characterized by increased cardiovascular reaction to acute induced psycho-emotional stress. At the later WPAH stages, BP reactivity was reduced. The cont test could be used as a screening tool in patients with undiagnosed WPAH.

Aim. To study antihypertensive and metabolic effects of combined antihypertensive therapy with fixed doses of ACE inhibitor and thiazide-like diuretic (Noliprel®), in comparison with ACE inhibitor monotherapy (ramipril).
Material and methods. The study included 44 men, aged 30-65 years, with Stage I-II arterial hypertension (AH) and at least one manifestation of metabolic disturbances (dyslipidemia, pre-diabetes, or hyperuricemia). All participants were divided into two groups: Group I received ramipril, and Group II was administered a combination of ACE inhibitor and thiazide-like diuretic (Noliprel®/ forte).
Results. Medication doses were increased in patients who failed to achieve target blood pressure (BP) levels. At baseline and after 6 months of the treatment, all patients underwent BP and heart rate (HR) measurement, electrocardiography (ECG) at rest, and the assessment of lipid profile, fasting and post-load (2 hours) glucose, insulin resistance (IR) index, uric acid (UA) and potassium (К+), as well as total coronary risk level.
Conclusion. In men with AH and metabolic disturbances, combined antihypertensive therapy with fixed doses of ACE inhibitor and thiazide-like diuretic, as well as ACE inhibitor monotherapy, demonstrated good antihyperten-sive effectiveness and no deterioration in metabolic parameters. Combined antihypertensive therapy was associated with a reduction in coronary risk by 30 %.

Aim. To study the effectiveness of a direct renin inhibitor, aliskiren, in patients with menopausal metabolic syndrome (MMS), and to assess aliskiren effects on blood pressure (BP), carbohydrate and lipid metabolism parameters, microalbuminuria, and arterial stiffness.
Material and methods. The study included 23 women with MMS, to whom aliskiren monotherapy (150-300 mg/d) was administered. At baseline and in the end of the study, anthropometry, carbohydrate and lipid metabolism parameters assessment, 24-hour BP monitoring, and arterial stiffness assessment by volume sphygmography were performed.
Results. By the end of the study, most parameters of circadian BP profile significantly decreased. Target levels of systolic and diastolic BP were achieved in 80 % of the patients. There was a significant reduction in postprandial glucose levels. According to the volume sphygmography results, a decrease in arterial stiffness was accompanied by a significant reduction in pulse wave velocity and augmentation index, with normalization of the former parameter.
Conclusion. Aliskiren therapy demonstrated not only high antihypertensive effectiveness in MMS patients, but also a reduction in postprandial glucose levels and arterial stiffness.

Aim. To compare the antihypertensive effectiveness, cardio- and nephroprotection, and metabolic effects of the combinations “enalapril + indapamide” vs. “enalapril + nifedipine slow release (SR)” in patients with arterial hypertension (AH) and secondary chronic pyelonephritis (CPN).
Material and methods. In total, 60 patients with AH and secondary CPN, aged 45-65 years, were divided into two groups: Group I (n=30) receiving combined therapy with enalapril (mean dose 15,9±2,3 mg/d) and indapamide (2,5 mg/d); and Group II (n=30) receiving the combination of enalapril (16,1±2,4 mg/d) and nifedipine SR (40 mg/d). The complex examination included 24-hour blood pressure monitoring (BPM), echocardiography, measurement of morning urine specific gravity, microalbuminuria (MAU), urine levels of ß2-microglobulines, blood creatinine and glomerular filtration rate (GFR) calculation by MDRD formula, fasting glucose, potassium, uric acid, total cholesterol, and triglycerides. The follow-up time was 12 weeks.
Results. The combinations “enalapril + indapamide” and “enalapril + nifedipine SR” had similar effects in terms of BP lowering, MAU reduction, and improvement of proximal renal tubular function. In both groups, there was a decrease in the number of patients with circadian BP rhythm disturbances, adverse left ventricular remodelling types, or diastolic dysfunction. The combination of enalapril and indapamide was significantly more effective in terms of restoring renal concentrating function, compared to the combination “enalapril + nifedipine SR”. Both antihypertensive therapies were metabolically neutral, not affecting carbohydrate, purine, lipid, or electrolyte metabolism parameters.

Conclusion. The combinations “enalapril + indapamide” and “enalapril + nifedipine SR” demonstrated high antihypertensive effectiveness, cardio- and nephroprotection, and metabolic neutrality.

Aim. To analyze the association between quality of life (QoL) and recurrent coronary insufficiency (CI) within 12 months after primary, uncomplicated myocardial infarction (MI) in working-age men, who underwent various types of coronary reperfusion.
Material and methods. In total, 114 men aged <60 years — patients with primary, uncomplicated MI, were examined. CI recurrence was assessed clinically, based on typical angina (A) attacks. To diagnose silent CI, all patients underwent an exercise test (veloergometry) before the discharge, as well as 3, 6, and 12 months after MI. QoL was assessed with a Russian version of SF-36 questionnaire.
Results. In CI-free men from the percutaneous coronary intervention (PCI) group, some QoL scales demonstrated a significant improvement at 3, 6, and 12 months. In the thrombolytic therapy (TLT) group, all QoL scales were significantly improved. The maximal QoL score was observed at 12 months in both groups. Patients with angina had decreased QoL, with the minimal score observed for role functioning domains (median score 0 and 12,5 in PCI and TLT groups, respectively) and emotional status (33 and 16,7, respectively).
Conclusion. Regardless of the coronary reperfusion method in acute MI phase, CI-free patients demonstrated improved QoL, with the highest scores registered 12 months after MI. Angina recurrence affected physical and emotional role functioning in MI patients, restricting their daily life activities. However, recurrent CI did not affect social activity levels or the need for social interaction.

Aim. To assess the interrelations in the dynamics of immune, clinical, and functional parameters among patients with myocardial infarction (MI) and early fluvastatin administration.
Material and methods. The study included 129 men, aged from 42 to 67 years (mean age 57 years): 99 MI patients and 30 healthy controls. In all participants, clinical, biochemical, functional, and immune parameters were assessed, with comparisons between healthy individuals vs. MI patients, as well as between MI patients taking fluvastatin (80 mg/d) vs. MI patients not receiving this medication.
Results. In men with MI, chronic systemic inflammation was manifested in elevated levels of C-reactive protein, interleukin (IL) 1β, IL8, tumor necrosis factor α, immunoglobulin A and G, and complement components, as well as in decreased levels of IL1 receptor antagonist, CD 3, CD 4, CD 16, and CD 4/CD 8, compared to healthy controls. Early fluvastatin administration (first post-MI hours) was associated with reduced severity of immune disturbances and systemic inflammation.
Conclusion. In MI patients, early fluvastatin administration is associated with a significant reduction in systolic and diastolic blood pressure levels, compared to controls, as well as with a substantial increase in exercise capacity at 2 months.

Aim. To assess the impact of renal risk factors (RFs) and local vascular factors on cardiovascular survival in patients with disturbed intracoronary hemodynamics after myocardial revascularization.
Material and methods. In total, 99 patients with indications for myocardial revascularization (mean age 56,5±0,8 years) were examined. All participants were divided into two groups: Group I — with 3 or less RFs, and Group II — with 4 or more RFs. The renal RFs included microalbuminuria (MAU) and glomerular filtration rate (GFR). The area of atherosclerotic plaque (SAP) and the rate of its intra-luminal growth (VAP) were calculated.
Results. Group II demonstrated higher MAU levels than Group I: 171,2±23,9 vs. 112,9±11,99, respectively (р=0,03). In addition, SAP values were higher in Group II (8,02±0,22 vs. 6,94±0,29 in Group I; р=0,004), as well as VAP values (6,62±1,26 vs. 1,44±0,18 in Group I; р<0,001).
Conclusion. Increased number of traditional RFs could be associated with increased MAU, hemodynamically significant coronary stenosis, and higher rate of atherosclerotic plaque growth.

Aim. In a non-randomised study, to assess middle-term (9 months) effectiveness and safety of percutaneous coronary intervention (PCI) with “Ephesos II” stent implantation.
Material and methods. The study included 41 patients, treated at the Sani Konukoglu Medical Centre, Gaziantep, Turkey.
Results. Immediate angiography-confirmed PCI success was achieved in 100 % of the participants. Nine months after the intervention, the percentage of survived patients without restenosis and repeat revascularization was 77,6 %. Control angiography at 9 months was performed in 95,1 % of the patients. The mean in-stent late loss was 0,32±0,25. Restenosis was observed in 22,4 % of the subjects. In all cases of in-stent restenosis, successful repeat PCI was performed. At 9 months, the proportion of the survived patients without moderate to severe cardiac complications and events reached 70,3 %.
Conclusion. This non-randomised study demonstrated good short and middle-term results of PCI with standard metallic stent “Ephesos II” implantation.

Aim. This subanalysis of the Study of the Effects of Nebivolol Intervention on Outcomes and Hospitalisation in Seniors with Heart Failure (SENIORS) investigates whether treatment with nebivolol, a β-blocker with nitric oxide-releasing properties, can provide additional benefits besides its effects on heart failure (HF), by reducing cardiac ischaemic events in patients with HF of ischaemic aetiology.
Material and methods. A double-blind, randomised, placebo-controlled, multicentre trial of nebivolol in 2128 elderly patients. For this analysis, data were extracted for 2128 elderly (≥70 years) HF patients in whom coronary artery disease (CAD) was the underlying aetiology (68,2 %; 717 placebo-treated patients and 735 assigned to nebivolol). The main endpoint was the composite of cardiac ischaemic events at 2 year follow-up: death/hospitalisation for myocardial infarction, unstable angina or sudden death, as originally identified in the case report form.
Results. At follow-up, nebivolol treatment was associated with a one-third reduction in the risk of ischaemic events, the composite endpoint occurring in 15,9 % of placebo and 10,7 % of nebivolol-treated patients (HR 0,68; 95 % CI 0,51 to 0,90; p=0,008). This effect was independent of age, gender and ejection fraction. No difference in this composite endpoint was observed in the subgroup of patients of non-ischaemic aetiology.
Conclusion. Nebivolol was effective in reducing cardiac ischaemic events in patients with HF of ischaemic aetiology. The prevention of ischaemic events can be an additional beneficial effect of β-blockade in HF patients with underlying CAD.

Aim. To assess the effectiveness of vildagliptin, its effects on visceral obesity (VO), carbohydrate and lipid metabolism parameters, and circadian profile (CP) of blood pressure (BP) in patients with metabolic syndrome (MS), Stage I arterial hypertension (AH), and impaired glucose tolerance (IGT).
Material and methods. The study included 30 patients, aged 18-60 years (16 men and 14 women). All patients had IGT, VO, and Stage I AH. Previously prescribed antihypertensive therapy (AHT) was not modified after the start of the study. In all participants, carbohydrate and lipid metabolism parameters, BP CP, and body weight were measured at baseline and after 24 weeks of vildagliptin treatment.
Results. Vildagliptin therapy was associated with a significant reduction in body weight, waist circumference, postprandial and fasting glucose levels, the levels of total cholesterol and low-density lipoprotein cholesterol, as well as with a sustained reduction in systolic and diastolic BP levels.
Conclusion. Vildagliptin therapy resulted in weight reduction, improved carbohydrate and lipid profiles, and target BP achievement, without inducing hypoglycemia episodes.

Aim. To assess the tolerability and the impact of various glucose-lowering medications on carbohydrate and lipid profile and anthropometric parameters in women with menopausal metabolic syndrome (MMS).
Material and methods. The baseline examination included 122 women in early postmenopause. Thirty three patients with MS, carbohydrate metabolism disturbances, and/or insulin resistance (IR) were included in the 12-week open comparative study. Group I (n=15) received acarbose (150 mg/d) for 12 weeks, while Group II (n=18) was administered metformin (850 mg/d) for 12 weeks. At baseline and 12 weeks later, anthropometry, oral glucose tolerance test with insulin and C-peptide level measurement, and lipid profile assessment were performed.
Results. Acarbose therapy was associated with a reduction in body weight (BW), body mass index (BMI), waist circumference (WC), fasting insulin, post-load insulin, post-load C-peptide, and HOMA-IR index. However, no significant improvement in lipid metabolism parameters was observed in the acarbose group. Metformin treatment was linked to a significant reduction in BW, WC, glycated hemoglobin, post-load glucose, C-peptide, and insulin, as well as to an increase in post-load Caro index.
Conclusion. Women with MMS, carbohydrate metabolism disturbances, and/or IR, require not only non-pharmaceutical lifestyle modification, but also glucose-lowering pharmaceutical therapy with acarbose or metformin. In particular, it should be considered that metformin, but not acarbose, reduces the levels of total cholesterol and triglycerides.

Aim. To study the associations between polymorphic variants of hemostasis protein-coding genes, hemostasis system functioning, and atherothrombosis development in patients with cardiovascular disease (CVD).
Material and methods. The study included 76 patients. Polymorphic gene marker alleles were analyzed by PCRPDRF method.
Results. The genotype prevalence was assessed for the polymorphic variants of F V, F II, Gp Iα, Gp IIIα, Gp Iβα, PAI-1, and FBG genes. In CVD patients, a polymorphic variant 4G (-675)5G of PAI-1 gene was associated with peripheral hemostasis disturbances.
Conclusion. 5G allele of PAI-1 gene was associated with higher plasminogen concentration and lower PAI-1 levels, which resulted in reduced plasma thrombogenicity.

Aim. To assess the clinical benefits of the original trimetazidine medication (Preductal® MR) in patients with stable coronary heart disease and angina attacks resistant to trimetazidine generics.
Material and methods. The study included 112 patients with stable coronary heart disease (CHD), who experienced angina attacks, despite the treatment with trimetazidine generics added to the standard CHD therapy (antiaggregants, statins, β-аadrenoblockers, ACE inhibitors). All participants received Preductal® MR (35 mg twice a day) instead of trimetazidine generics. The follow-up duration was 3 months. Treatment effectiveness was assessed by the changes in angina attack incidence, short-acting nitrate consumption, and general status, using a visual analogue scale (VAS). In addition, pharmaco-economic analysis of the treatment effectiveness was performed.
Results. The replacement of trimetazidine generics with Preductal® MR was associated with a reduction in angina attack incidence by 63 % and in the number of nitroglycerine tablets/doses by 65 % (p<0,01). VAS score increased from 45,3±13,8 to 71,6±11,9 (р<0,0001). Preductal® MR therapy is the best pharmaco-economic option, since the ratio between weekly treatment costs (RUB) and the weekly number of prevented angina attacks is minimal for this original medication.
Conclusion. In patients with stable CHD and angina attacks, resistant to trimetazidine generics, Preductal® МR therapy is associated with a significant reduction in angina attack incidence and consumption of short-acting nitrates. Preductal® MR is the most cost-effective medication, providing optimal effectiveness with minimal costs.

This review is focussed on the problem of venous thromboembolism in patients with heart failure (HF). The results of the major clinical trials of antithrombotic therapy in HF patients are presented. The authors discuss comparative effectiveness, safety, and tolerability of unfractionated heparins, low molecular weight heparins, and fondaparinux. The results of the two trials, MAGELLAN and ADOPT, are expected to clarify the clinical potential of such oral anticoagulants as rivaroxaban and apixaban (Factor Xa inhibitors). The problem of low rates e of preventive antithrombotic administration is emphasized.

This review summarizes the literature evidence on humoral disturbances in arterial hypertension (AH), as well as on AH interrelationship with individual components of metabolic syndrome (MS). Based on the results of multi-centre randomised trials, the rationale for the use of antihypertensive agents with favourable metabolic profile is demonstrated, in particular, for antagonists of slow calcium channels, angiotensin-converting enzyme inhibitors, and selective imidazoline receptor agonists.

The review presents the latest evidence on the calcium antagonist amlodipine, summarizing its mechanisms of action, its pleiotropic, endothelial function-related effects, and its anti-atherogenic activity. Amlodipine suppresses the proliferation of vascular smooth myocytes and extracellular matrix and improves endothelial vasodilatation, despite the absence of L-type calcium channels in these cells. This mechanism is related to an increase in endothelial nitric oxide (NO) release. The results of experimental studies on the role of S and R amlodipine isomers in its hemodynamic and pleiotropic activity are presented. While S-amlodipine is a pharmacologically active blocker of L-type calcium channels, R-amlodipine increases endothelial NO release. New medications have been developed, based on S-amlodipine. It has been shown that S-amlodipine 5 mg/d is bioequivalent to amlodipine 10 mg/d. The pharmacodynamics analysis demonstrated that S-amlodipine 5 mg/d and amlodipine 10 mg/d did not differ significantly in terms of mean levels of systolic and diastolic blood pressure, or mean heart rate. S-amlodipine was better tolerated and characterised by a lower incidence of peripheral edema than amlodipine. However, the effects of S-amlodipine on hard end-points should be investigated in the long-term prospective studies.

The treatment of recurrent, refractory post-infarction myocardial ischemia remains an unresolved clinical problem. Aggressive pharmaceutical therapy has limited effectiveness, while percutaneous coronary intervention or coronary artery bypass graft surgery are not possible in these patients, due to various reasons. Currently, alternative methods for refractory angina treatment are being developed for patients with chronic stable angina. The potential of these methods in patients with acute coronary syndrome should be investigated in the future studies.

Despite certain success in the recent years, the problem of cardiovascular disease (CVD) in women remains one of the greatest challenges of the 21st century. Its social and economic burden will continue to increase, due to increasing proportion of older women in the population. Recently, cardiologists have been focusing on menopause as a specific CVD risk factor in women. At the same time, other conditions, also increasing CVD risk, such as certain pregnancy complications and premature menopause, have not received enough attention. Hormone replacement therapy (HRT) remains the first-line treatment and the most effective strategy in young women with estrogen deficiency and postmenopausal women with menopausal symptoms. HRT effectiveness and safety is based on its timely start, low dose, and individually appropriate combination of estrogens and progestins. Interdisciplinary approach is essential for early identification of high-risk women, since lifestyle modification recommendations, diagnostic procedures, and, if needed, an active therapeutic intervention could reduce future CVD incidence in these women.