From the second half of the XX century, cardiovascular disease (CVD) remains one of the main problems of the modern medicine. Over the last two decades, developed countries demonstrated a marked decrease in all-cause mortality and CVD mortality, in particular. InRussia, since the mid-1960s, all-cause mortality gradually increased, with the proportion of CVD deaths being over 50 %, which led to unparalleled high levels of national mortality. In 2009, the absolute number of CVD deaths was 1136661, or 1 case out of 1,8. In other words, 3114 Russian people die from CVD every day. From 2004, all-cause mortality, including CVD mortality, started to decline, and this tendency has continued until at least 2009, as demonstrated by the mortality rate of 801 per 100,000. However, the mortality levels are still higher than in the late 1980s. The authors analysed the CVD dynamics between 2003 (the highest levels) and 2009 inclusive, using the official national statistics data. The last few years demonstrated a positive tendency of declining mortality. In particular, the all-cause mortality (deaths per 100,000) decreased from1644,2 in2003 to1416,8 in2009 (by 13,8 %). CVD mortality decreased by 13,6 %, and more markedly mostly in working-age people (by 18,9 %). Therefore, in 2009, the number of lives saved due to the decreasing CVD mortality was 260741. Further studies will explain the recent mortality trends inRussia.

Aim. To assess the prevalence of masked inefficacy of arterial hypertension treatment (AH MTI) and its predictors in various clinical groups and for various blood pressure (BP) control strategies, in order to evaluate the true effectiveness of antihypertensive therapy (AHT).
Material and methods. AHT effectiveness was assessed in two groups of the patients with Stage I-II AH (n=219 and n=39), by comparing the ratios of clinical (cl) to ambulatory (a) BP parameters. AH MTI was defined as elevated aBP and target clBP levels during AHT. The potential predictors of AH MTI included gender, age, body mass index (BMI), anamnestic data, frequency of the clinical visits to measure BP, quality of life (QoL) parameters (GWBQ questionnaire), circadian BP profile, orthostatic BP, and ECG signs of left ventricular hypertrophy (LVH).
Results. AH MTI prevalence in Groups I and II was 11,0-15,7 % and 22,6-58,1 %, respectively, depending on the definition used. The groups were significantly different in terms of age, BMI, and QoL questionnaire III and VI domains. According to the regression analysis results, in Group I AH MTI was associated with QoL questionnaire II, V, and VI domains, baseline parameters of 24-hour BP monitoring, 24-hour systolic BP (SBP) variability, minimal daytime levels of mean BP, and metoprolol and atenolol therapy. In Group II, AH MTI was predicted by age, BMI, previously administered AHT, alcohol consumption, orthostatic SBP levels, Sokolow-Lyon index, Cornell voltage and Cornell product, Gubner index, and QoL questionnaire I, IV, and VI domains.
Conclusion. AH MTI prevalence is associated with some baseline characteristics of the patients and the character of AHT. Due to regression to the mean, AH MTI prevalence could increase substantially when clBP parameters are measured more often.

Aim. To compare the effectiveness of different antihypertensive medications in the management of hypertensive crise (HC) in the early post-surgery period after carotid endarterectomy (CEE).
Material and methods. The study included 39 patients (14 women, 25 men; mean age 65,6±6,6 years) hospitalised to the Cardiovascular Surgery Department of a major Moscow City hospital. All patients underwent CEE, with a HC developed in the early post-surgery period. All participants were divided into three groups: in Group I, HC was treated with nimodipine, while Groups II and III received enalaprilat and uradipil, respectively.
Results. Intravenous administration of all three medications resulted in an antihypertensive effect. A significant reduction in blood pressure (BP) levels was observed after the administration of nimodipine and uradipil. However, nimodipine caused reflectory tachycardia, which was not observed in patients treated with uradipil.
Conclusion. The results obtained are consistent that out of the three studied medications, uradipil appeared the most appropriate for the HC management in the early post-CEE period. It reduced BP levels without causing reflectory tachycardia or clinical hypotension, which confirms clinical effectiveness and safety of uradipil as a medication of choice for the urgent HC management.

Aim. To assess the potential of the angiotensin II receptor antagonist losartan for the correction of hyperuricemia (HU) in patients with arterial hypertension (AH) and metabolic syndrome (MS).
Material and methods. This open, randomised, controlled comparative study in parallel groups included 60 AH patients with MS and HU. The patients received losartan or standard therapy for 12 weeks.
Results. Throughout the follow-up period, no significant difference in antihypertensive effect was observed between the losartan and standard therapy groups. Losartan group patients demonstrated a more pronounced decrease in uric acid levels (-34,7 % vs. -7,8 % in the standard therapy group; p<0,05). In addition, losartan therapy, compared to the standard treatment, was associated with improved vascular elasticity, as manifested by the pulse wave velocity decrease (-27,8 % vs. -8,1 % for carotid-femoral index, and -30,2 % vs. -12,6 % for carotidradial index, respectively; both p<0,05).

Aim. To compare the dynamics of various parameters of circadian blood pressure profile (BP CP) and to assess the selection criteria for two combinations of the first-choice antihypertensive agents (AHA): angiotensin-converting enzyme (ACE) inhibitor plus thiazide diuretic (TD) or angiotensin II receptor antagonist (ARA) and calcium antagonist (CA) in patients with moderate to severe arterial hypertension (AH).
Material and methods. This randomised study included 66 men aged 35-60 years with Stage 2-3 AH. Group I (n=37) received the combination of enalapril and hydrochlorothiazide (ENP + HCT; 20/12,5 mg/d), while Group II (n=29) was administered the combination of valsartan and S-amlodipine (VAL + S-AMD; 160/5 mg/d). All medications were taken daily, once a day. At baseline and after 12 weeks of the treatment, all participants underwent 24-hour blood pressure monitoring (BPM). The analysed parameters included: mean values and variability of systolic and diastolic BP (SBP, DBP), time index and pressure load index for SBP and DBP over 24 hours, dayand night-time, magnitude and velocity of SBP and DBP morning surge (MS), and diurnal/nocturnal BP ratio.
Results. Twelve-week therapy with combinations significantly reduced mean SBP and DBP levels in patients with moderate to severe AH, regardless of the time of the day/night. It was also associated with reduced BP variability, mostly during the day-time. The ENP+HCT combination was more effective in terms of SBP MS reduction, while the VAL+S-AMD combination effect was more pronounced for DBP MS prevention. The VAL+S-AMD combination significantly improved diurnal/nocturnal BP ratio.
Conclusion. The results obtained should be considered in the design of the antihypertensive combination therapy for Stage 2-3 AH patients with “non-dipper”, “night-peaker”, and “over-dipper” types of the two-phase BP CP.

The extent to which the clinical effects of angiotensin receptor blockers (ARB) are related to ambient renin system activity remains poorly defined. Therefore, we measured blood pressure (BP), large (C1) and small (C2) arterial compliance, systemic vascular resistance (SVR), plasma renin activity (PRA), and the 24-h urinary excretion of sodium (UNaV) and aldosterone before and 1, 2, 4, and 24 h after administration of single doses of placebo, and 5, 20, and 40 mg of the ARB olmesartan medoxomil to 12 unmedicated normotensive subjects. In the basal state, SVR was inversely related to UNaV (r=-0,3, p=0,04); the greater the UNaV, the more vasodilated the subject. Indices of arterial compliance, both C1 (r=-0,32, p=0,03) and C2 (r=-0,35, p=0,02) were inversely related to the basal PRA. Renin also predicted olmesartan-induced changes in C1 (r=0,43, p=0,004) and C2 r=0,33, p=0,04). The greater the basal PRA, the less the arterial compliance, and the more compliance improved after olmesartan. Both systolic (p=0,003) and diastolic (p<0,0001) BP fell significantly on olmesartan compared with placebo (MANOVA with time), and relations were observed between the basal PRA and olmesartan-induced changes in pressure (systolic BP: r=-0,414, p=0,012; diastolic BP: r=-0.561, p<0,0001) — the greater the initial PRA, the more olmesartan lowered BP. Furthermore, the more pressure fell, the more PRA rose reciprocally (r=-0,44, p=0,007). Finally, aldosterone excretion fell (sig=0,05) on each dose of olmesartan compared with placebo. We conclude that 1) the inverse relation of UNaV and SVR illustrates the reciprocal role of volume versus constrictor factors in maintaining normal BP; and 2) PRA is a physiologic determinant of arterial compliance in normal individuals and of the response to the ARB olmesartan. Measurement of PRA may help to predict clinical ARB responses in individual subjects.

Aim. To study the effects of the fixed-dose combination antihypertensive therapy (noliprel A forte, valsaforce, and indapamide) and the renal function dynamics in patients with Type 2 diabetes mellitus (DM-2) and arterial hypertension (AH).
Material and methods. In total, 40 patients with DM-2 and AH were randomised into two groups: Group I received noliprel A forte, and Group II received valsaforce and indapamide for two months. The clinical effectiveness of the fixed-dose combination antihypertensive therapy was assessed by 24-hour blood pressure monitoring (BPM), blood biochemistry, and renal function parameters measured at baseline and 8 weeks after the start of the treatment.
Results. The treatment was associated with a substantial reduction in BP levels, improved circadian BP profiles, and metabolic neutrality. The therapy with noliprel A forte resulted in markedly improved circadian BP profiles and renal function, as demonstrated by the microalbuminuria dynamics (Rehberg-Tareev test: by 11±0,56 ml/min; Cockgroft-Gault formula: by 12±0,36 ml/min; MDRD formula: by 10±0,16 ml/min/1,73 m2).
Conclusion. In patients with DM-2 and AH, the therapy with noliprel A forte significantly improved renal function parameters.

Aim. To study the effectiveness of the fixed-dose combination therapy with perindopril and amlodipine (Prestance 5/5 mg/d) in coronary heart disease (CHD) patients after coronary artery bypass graft (CABG) surgery.
Material and methods. The clinical trial included 65 patients (37 men, 28 women aged 45-68 years; mean age 56,3±3,5 years) after CABG. All patients were randomised into two groups: the control group (CG; n=35) and the main group (MG; n=30). Both groups received antiplatelet agents and statins, while the MG patients additionally received Prestance (5/5 mg/d). Prestance therapy started three-four weeks after CABG and lasted for four months. All participants underwent 24-hour monitoring of ECG and blood pressure (BP), Doppler echocardiography, and Doppler ultrasound of brachial and common carotid arteries.
Results. Compared to the CG, the MG demonstrated decreased incidence of pain and painless ischemia episodes, reduced maximal ST segment depression and its total duration, and increased rate threshold of myocardial ischemia. In addition, Prestance therapy was associated with improved systolic and diastolic heart function and significantly improved endothelium-dependent vasodilatation. In patients with normal BP, Prestance (5/5 mg/d) did not cause hypotension, but reduced excessive BP variability. In the MG, acute coronary syndrome (ACS) was registered in 1 individual (3,3 %), while in the CG, it was registered in 4 patients (11.4 %), and in 3 cases, coronary artery stenting was performed.
Conclusion. In patients with normal BP, Prestance (5/5 mg/d) therapy in the early post-CABG period had a pronounced anti-ischemic, cardio- and vasoprotective effects, and also prevented excessive BP variability.

Aim. To study the signal-averaged ECG (SA-ECG) parameters of atrial complex and supraventricular arrhythmias (SVA) in patients with coronary heart disease (CHD) and chronic heart failure (CHF), treated with diuretics (D) torasemide and furosemide.
Material and methods. The study included 107 patients with CHD and CHF. All participants underwent 24-hour ECG monitoring and the registration of SA-ECG atrial complex parameters. In total, 52 patients received furosemide, and 55 were administered torasemide.
Results. In both groups, D therapy was associated with some increase in the duration of filtered P and LAS5, as well as a decrease in RMS20. These changes were more pronounced in the furosemide-treated patients. Torasemide demonstrated better effects on the SVA dynamics, which manifested in the decreased numbers of single, paired, and grouped SV extrasystoles.
Conclusion. In CHD and CHF patients, the disturbed atrial depolarisation was manifested in negative dynamics of SA-ECG atrial complex parameters. Torasemide therapy did not affect the atrial complex parameters and also reduced SVA incidence, which made torasemide a medication of choice for patients with CHD and CHF.

Aim. To assess the clinical effectiveness of thrombolytic therapy (TLT) with alteplase in patients with acute myocardial infarction (AMI).
Material and methods. The study included 54 AMI patients, divided into two groups: Group I (n=26), which underwent TLT, and Group II (n=28), which had contraindications to TLT. The TLT method was an accelerated alteplase infusion. Both groups were comparable by age and sex. In all patients, AMI biomarker levels and echocardiography (EchoCG) parameters were measured.
Results. Successful thrombolysis was performed in 19 patients (73 %). The mean “symptom-to-needle” time was 3,7±0,6 hours. In Groups I and II, the 50 % reduction in the ST segment deviation from isoelectric line at 180 minutes was observed in 34,6 % and 0 % of the patients, respectively. In addition, in Group I, there was a reduction in the number of patients complaining of general weakness, dyspnoea, and recurrent angina attacks. The levels of cardio-specific AMI biomarkers were higher in Group II. According to the EchoCG results at 10 days after admission, the Group I patients demonstrated higher minute volume (by 28,8 %), higher ejection fraction (by 30 %), and higher end-diastolic dimension (by 23,8 %).
Conclusion. The results obtained confirm high effectiveness of the in-hospital TLT with accelerated alteplase infusion. Alteplase therapy was associated with clinical and morphological myocardial salvage in AMI patients.

Aim. High-sensitive C-reactive protein (hsCRP) is currently regarded as an important marker of cardiovascular disease (CVD). The aim of the study was to assess the population characteristics of hsCRP in the sample of Moscow residents aged 55 years and older.
Material and methods. The analysis included 1851 people (response rate 65 %), who participated in the SAHR (Stress, Aging, and Health in Russia) study.
Results. The hsCRP levels were similar in men and women, with the right-skewed distribution. The hsCRP values ranged from 0,5 to 69,5 mg/dl in men (median 1,5 mg/l), and from 0,5 to 75 mg/l in women (median 1,5 mg/l). The mean hsCRP levels were slightly higher in men than in women (3,4±0,19 vs. 3,1±0,15, respectively; р=0,36). Overall, there was no marked age-related dynamics of hsCRP levels in men or women. The prevalence of high hsCRP levels (>3 mg/l) non-significantly increased from 31,2 % in the youngest age group to 36,2 % in those aged 75 years and older. Acute inflammation (hsCRP levels >10 mg/l) was registered in 85 participants (4,5 %), including 42 men and 43 women. After adjustment for age and gender, the lower education level remained a significant predictor of hsCRP elevation.
Conclusion. No clear associations between hsCRP and age or gender were observed. However, participants with university and secondary education had significantly lower hsCRP concentrations, compared to their peers with education level lower than secondary.

Aim. As a clinical part of the Russian multi-centre randomised study, to assess the clinical benefits and safety of adding Trimetazidine MB to the standard treatment scheme in patients with stable angina (SA), in order to optimise their ambulatory therapy and improve their compliance.
Material and methods. The study included 981 patients with Functional Class (FC) II-III SA and various concomitant diseases and syndromes, such as chronic heart failure (CHF), Type 2 diabetes mellitus (DM-2), or chronic obstructive pulmonary disease (COPD) in smokers. All participants were divided into two groups: Group I (n=838) received standard therapy plus trimetazidine MB (70 mg/d, twice a day), while Group II (n=143) received standard therapy only. The treatment and follow-up phases lasted for 12 months.
Results. In Group I, the weekly number of angina attacks decreased by 42 % from the baseline at one month (р<0,0001), and by 70 % at 12 months (р<0,0001). The number of nitroglycerin (NTG) tablets taken decreased, respectively, by 41 % (р<0,0001) and 68 % (р<0,0001). In Group II, the decrease in angina attack number and NTG tablet number was significant only at 6 months and was less pronounced than in Group I. Therefore, in Group I, the number of patients with FC I increased by 7 times, while the number of FC III patients decreased by 1,8 times. No marked FC dynamics was observed in Group II. In Group I, left ventricular ejection fraction (LVEF) increased by 2,4 % (р<0,001), while interventricular septum and LV posterior wall thickness decreased, respectively, by 4,2 % (р<0,01) and 3,5 % (р<0,01). These parameters, however, did not change substantially in Group II patients. At 12 months, the number of patients hospitalised due to clinical decompensation, or becoming disable, was twice as high in Group II as in Group I.
Conclusion. The Russian “PERSPECTIVE” Study results demonstrated high clinical effectiveness and safety ofTrimetazidineMB therapy, combined with standard treatment, in SA patients with CHF, DM-2, and COPD. Therefore, metabolic therapy could be more widely used in the real-world clinical settings.

Aim. To assess the effects of original statins as monotherapy or in combination with ezetimibe on the levels of proinflammatory cytokines and high-sensitive C-reactive protein (hsCRP) in patients with coronary heart disease (CHD) and hyperlipidemia (HLP).
Material and methods. The study included 60 male and female patients with CHD, primary polygenic HLP, and the levels of low-density lipoprotein cholesterol (LDL-CH) of 2,9-4,9 mmol/l. Monotherapy with original statins or ezetimibe lasted for 6 months, while the combination therapy lasted for 3 months. In all randomised patients, the levels of hsCRP, interleukin 6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) were measured at baseline, 12 and 24 weeks after the therapy started.
Results. At baseline, median hsCRP levels in the groups of Ezetrol, Zocor, Liprimar, and Crestor monotherapy were 0,5-0,88 mg/l, with no significant dynamics after 3 months of the treatment. Baseline IL-6 levels across the monotherapy groups were 1,94-2,54 pg/ml; at 3 months, there was a non-significant reduction by 7-32 %. After 3 months of the therapy, the decrease in MCP-1 levels was not statistically significant (-1,3-7,7 %). The combined therapy did not result in a significant dynamics of hsCRP concentrations, with the exception of the group receiving Ezetrol and Liprimar. Although the combined therapy further reduced MCP-1 levels (by 30-78 pg/ml), these changes were not statistically significant. No significant difference was observed across statin and Ezetrol groups in terms of their effects on IL-6 and MCP-1 levels.
Conclusion. The comparison of the three treatment schemes demonstrated similar, but not statistically significant reduction on the levels of hsCRP, IL-6, and MCP-1. No marked benefits were observed for either monotherapy or combination therapy over 12-24 weeks of the follow-up.

Aim. As a part of the LIS Study (Lyubertsy Study of mortality in patients after acute myocardial infarction), to assess the patients’ demographic characteristics, specifics of the clinical course and treatment of coronary heart disease (CHD) and other cardiovascular pathology, as well as the risk factor (RF) prevalence before acute myocardial infarction (AMI).
Material and methods. The study included all patients (n=1133) who, within the three-year study period, developed AMI and were admitted to Lyubertsy clinics (Moscow Region).
Results. The study population included 54,5 % men and 45,5 % women. Mean age of male and female AMI patients was, respectively, 60,1±0,5 and 71,4±0,4 yeas. Approximately 35 % of all participants were working-age men. The majority of the patients had several RFs, among which arterial hypertension (AH) was the most prevalent (76 %). Over 30 % of the patients did not have pre-existing CHD before AMI. Prior to AMI, pharmaceutical treatment was rare; antiplatelet agents and statins were administered to 16 % and 2 %, respectively.
Conclusion: AMI often developed in people without pre-existing CHD, being, therefore, the first CHD manifestation. Cardiovascular risk assessment in people with RFs should be an important part of the everyday clinical practice.

Despite their proven mortality and morbidity outcomes benefits, β-blockers remain substantially underused in patients with cardiac conditions. Reluctance to prescribe β-blockers may be owing to concerns about tolerability with the traditional drugs in this class. β-blockers with vasodilatory properties, such as carvedilol and nebivolol, may overcome the tolerability and metabolic issues associated with traditional β-blockers. Because endothelial dysfunction, the pathophysiologic hallmark of hypertension, may be heightened in populations with difficult-totreat hypertension (e.g., elderly patients, African American patients), a vasodilating β-blocker may be a particularly appropriate choice for these patient groups.

In the 1970s, pharmacological therapy interrupting the renin-angiotensin system was considered beneficial for patients with high-renin hypertension. Angiotensin-converting enzyme (ACE) inhibitors proved to be effective not only in patients with high renin and elevated blood pressure, but also in many hypertensive patients with normal levels of plasma renin activity. ACE inhibitors are used in a wide range of chronic illnesses such as atherosclerosis, hypertension, myocardial infarction, heart failure, diabetic complications, and stroke. To date, more than ninety controlled clinical trials evaluating the beneficial effects of 14 different ACE inhibitors were conducted. Moreover, data from experimental studies showed that ACE inhibitors can attenuate the development of atherosclerosis, oxidative stress, and vascular inflammation in a wide range of species indicating that ACE inhibition also favourably affects the vasculature. More than fifteen years ago, the bi-sulfydryl ACE-inhibitor zofenopril has shown an excellent clinical safety and efficacy in patients with hypertension and in those with myocardial infarction. More recently, this compound exhibited a potent antioxidant and antiatherosclerotic effect indicating a clinical useful vasoprotective action.

The assessment and correction of the traditional parameters of atherogenic dyslipidemia are important, but not exclusive methods in the management of atherosclerosis, including coronary artery atherosclerosis. More accurate diagnostic and therapeutic assessment requires the measurement of apolipoprotein (Apo) A, ApoB, and their ratio.Lower ApoB/ApoAI ratio values denote lower levels of cardiovascular risk.

The review analyses the specifics of enoxaparin therapy in the most prevalent cardiovascular diseases, such as acute coronary syndrome, venous thromboembolism, and atrial fibrillation. The decision strategy is presented for difficult and non-standard clinical situations (renal dysfunction, elderly age, heparin medication change, or abnormal body weight), when the optimal balance between effectiveness and safety requires modifying the standard treatment protocols.

The review is focussed on the mechanisms of action, lipid-lowering activity, structural characteristics, and safety of plant sterins and stanols. Phytosterins and phytostanols inhibit intestinal cholesterol (CH) absorption, therefore decreasing plasma CH levels. The emphasis is put on prospective epidemiological studies of representative samples, which demonstrated that plasma concentrations of phytosterins and phytostanols in patients with coronary heart disease (CHD) are substantially lower than in CHD-free participants. A two-fold increase in serum sytosterin concentration was associated with a reduction in relative risk of CHD by 22 %. Plant sterin and sterol esters could be regarded as effective and safe dietary ingredients decreasing blood levels of CH — one of the major cardiovascular disease risk factors.