Aim. To assess middle-size vessel wall status, by volume compression oscillometry method, in patients with arterial hypertension (AH) and various variants of left ventricular (LV) remodeling. Material and methods. The study included 112 patients (44 males; mean age 53.5±11.1 years) with AH and reproducible LV myocardial mass index (LVMMI) >100 g/m2 at echocardiography. Brachial artery (BA) wall status was assessed by volume compressive oscillometry method. Results. LVMMI significantly correlated with levels of systolic and pulse blood pressure (BP) (r=0.28 and r=0.29, р<0.01). LV hypertrophy (LVH) was associated with minimal BA lumen diameter (BAD). Compared to eccentric LVH, concentric LVH was characterized by lower BAD and vascular wall deformation coefficient, as well as by increased linear blood flow velocity, volume elasticity module, total peripheral vascular resistance. Conclusion. LV remodeling variant could be linked to middle-size vessel viscosity and elasticity parameters.

Aim. To investigate risk factors (RF) and target organ damage (TOD) prevalence in working-age men with stressinduced arterial hypertension (AH). Material and methods. The study included 100 males, working as machinists and machinist assistants, with blood pressure (BP) above 140/90 mm Hg. Control group included males working as railway assemblers (n=40). General physical, laboratory, and instrumental examinations were performed, including psycho-mental test (PMT). Results. TOD was quite prevalent among normotensive males. Twenty-four hour BP monitoring (BPM) demonstrated the difference in mean BP levels at workplace and during weekend, that confirmed stress-induced AH diagnosis. Psychoemotional stress tests are highly sensitive in stress reactivity assessment among individuals with high professional stress levels. These tests can help in identifying AH risk groups. Conclusion. For early diagnostics and adequate therapy choice in patients with high psychoemotional stress levels, not only RF and TOD control, but also 24-hour BPM at workplace and during weekend, and PMT, are necessary.

Aim. To study orthogonal electrocardiography (ECG) parameters among arterial hypertension (AH) patients, in regard to renin-angiotensin-aldosterone system (RAAS) functional status. Material and methods. The study included 41 AH patients, mean age 45±2.8 years, and control group of 41 healthy individuals, mean age 41±7 years. Plasma aldosterone concentration (PAC) and plasma rennin activity (PRA) were measured at rest and after 4-hour walking. In all participants, 12-lead ECG and orthogonal ECG were registered, assessing left ventricular hypertrophy (LVH) criteria: Sokolow-Lyon criterion, Cornell index, Rx+Sz summary index, and repolarization acceleration vector module (G). Results were compared with echocardiography (EchCG) signs of LVH. Results. All patients had low-renin AH with various PAC levels. Three groups were identified: Group I (n=16), with adrenal cortex aldosteroma; Group II (n=12), with adrenal cortex hyperplasia; Group III (n=13), with normal PAC and no adrenal pathology. Comparing to Groups II and III, Group I had higher levels of systolic and diastolic blood pressure (BP), as well as more pronounced hyperaldosteronemia and hypokaliemia (p<0.05). Mean Cornell index in Group III was significantly lower than in Group I: 1.6±0.2 vs 2.5±0.2 mV, respectively. G index in Group III (71±9 ms) was significantly greater than in Groups I (35±5 ms) or II (47±6 ms). Inter-group differences for other parameters were not observed. Conclusion. Patients with adrenal cortex aldosteroma had significantly higher BP levels, more pronounced hyperaldosteronemia, hypokaliemia, and ECG signs of LVH, comparing to Groups II or III.

Aim. To study antihypertensive effects of AT1-receptor blocker eprosartan and ACE inhibitor enalapril, in regard to leading pathway of angiotensin II (AT II) synthesis among arterial hypertension (AH) patients with various functional status of renin-angiotensin-aldosterone system (RAAS). Material and methods. In total, 54 AH patients were examined. RAAS parameters and chymase activity were measured at rest and after orthostatic and captopril tests. Thirty-eight out of 54 patients were included into an open comparative cross-over two-group study, being administered eprosartan or enalapril. Antihypertensive effect was assessed after 8 weeks of treatment, by office blood pressure (BP) levels and 24-hour BP monitoring (BMP) results. Results. Basic criteria for identifying leading AT II synthesis pathway were proposed: antihypertensive reaction type in captopril test and baseline level of plasma chymase activity. Assessing eprosartan and enalapril treatment efficacy, it turned out that both agents had significant, similar antihypertensive effects, with eprosartan’s dominating influence on pulse BP. Eprosartan therapy was more effective in low-renin AH patients. Enalapril was less effective than eprosartan in patients with alternative, chymase-dependent pathway of AT II synthesis. Conclusion. Leading pathways of AT II synthesis in AH patients might be BP reduction in captopril test and baseline level of plasma chymase activity. Eprosartan therapy was more effective in low-renin and severe AH, that might be linked to its effects on alternative pathway of AT II synthesis.

Aim. To assess effectiveness of ACE inhibitor moexipril (Moex®) in postmenopausal women with arterial hypertension (AH). Material and methods. In total, 50 women were examined; mean age 64.1±0.9 years, mean AH duration – 10.1±2.5 years. Moexipril treatment in daily dose 7.5-15 mg lasted for 12 weeks. Office blood pressure (BP), autonomous dysbalance symptoms (questionnaire on autonomous disturbances and hyperventilation syndrome), night sleep disturbances (questionnaire on subjective sleep disturbances), reactive and personal anxiety (RA, PA; Spielberger scale), depression (Zung test), quality of life (QoL; WHO questionnaire QoL-100) were assessed. Results. By the end of moexipril treatment, target BP levels were achieved for 76.5% of the patients. Vegetative symptoms, sleep quality, RA and depression parameters significantly improved (р<0.5). Moexipril therapy was associated with QoL improvement by 5.2%. Conclusion. Moexipril demonstrated antihypertensive effects as well as autonomous balance and QoL improvement in postmenopausal women with AH.

Aim. To study effects of therapy with bisoprolol (Concor®) and deproteinized hemoderivate (Actovegin®) on circadian blood pressure profile (CBPP), carbohydrate, lipid metabolism, and cerebral perfusion in patients with metabolic syndrome (MS) and mild arterial hypertension (AH). Material and methods. The study included 30 patients with mild AH and MS: 15 participants received Concor®, 15 - Concor® and Actovegin®, for 12 weeks. All individuals underwent clinical and laboratory examination, as well as cerebral perfusion assessment by single-photon emission computer tomography. Results. In both groups, therapy was associated with significant BP decrease and CBPP normalization, together with neutral metabolic effect. At baseline, cerebral perfusion was reduced in all patients. Actovegin® treatment substantially improved cerebral perfusion. Conclusion. In MS patients, Actovegin® facilitated cerebral perfusion improvement, with neutral metabolic effect.

Aim. To assess perspectives of pulse wave velocity (PWV) correction during acarbose treatment in patients with impaired glucose tolerance (IGT) and arterial hypertension (AH). Material and methods. An open clinical trial included 45 patients (18 males and 27 females) aged 18-60 years, with body mass index (BMI) > 25 kg/m2, IGT, and elevated blood pressure (BP). After envelope method randomization, all patients were divided into three groups: active acarbose treatment groups (maximal dose 150 mg/d or 300 mg/d) and previous therapy group. In all groups, non-pharmaceutical lifestyle modification and weight control measures were performed (diet, increased physical activity). Treatment phase lasted for 24 weeks. Dynamics of BP, carbohydrate and lipid metabolism, PWV for vessels of various diameters, by Complior protocol and with Colson device, were registered. Results. Acarbose treatment resulted not only in carbohydrate and lipid metabolism improvement, but also in artery elasticity improvement among overweight patients with IGT. Conclusion. In patients with IGT and excess body weight, acarbose in doses of 150-300 mg/d, added to nonpharmaceutical intervention, was associated with PWV normalization, and could be regarded as a sign of beneficial acarbose influence on large vessel elasticity.

Aim. To study ahtihypertensive therapy effects on carbohydrate metabolism in patients with arterial hypertension (AH) and Type 2 diabetes mellitus (DM-2). Material and methods. In total, 84 AH and DM-2 patients were examined: males and females aged 45-78 years (mean age 62.56±15.44 years). General physical examination, anthropometry, body mass index (BMI) calculation, blood pressure (BP), heart rate measurement, electrocardiography, general blood and urine assays, glucose tolerance test were performed; lipid profile, glycemia, fasting insulin, creatinine levels were measured. Results. In all participants, systolic and diastolic BP (SBP, DBP) levels decreased (p=0.001; p=0.001, respectively). Six months later, in Group I (BMI<30) mean SBP decreased from 160.9 to 145 mm Hg; mean DBP – from 94.8 to 86.8 mm Hg. In Group II (BMI 30-35) these figures were 160.8 to 144.5 mm Hg, and 97.3 to 88 mm Hg, respectively. In Group III (BMI>35), they were 167.9 to 148.9 mm Hg, and 99.8 to 87.6 mm Hg, respectively. In all three groups, glucose and cholesterol dynamics was not significant. Conclusion. In DM-2 patients receiving hypoglycemic agents, antihypertensive therapy did not affect carbohydrate metabolism. Significant cholesterol level decrease was observed in patients on strict fat-free and low-carbohydrate diet.

Aim. To study hemostasis and blood rheology in patients with chronic obstructive pulmonary disease (COPD), during chronic pulmonary heart (CPH) development and heart failure (HF) progression. Material and methods. In total, 54 COPD patients (mean age 56.3±8.2 years) were examined: Group I – 17 COPD patients without CPH; Group II - 17 COPD patients with compensated CPH; Group III – 20 COPD patients with CHD and chronic HF (CHF). Control group consisted of 16 healthy volunteers. Vascular-platelet hemostasis parameters: platelet number, spontaneous platelet aggregation, induced aggregation activity and disaggregation potential; plasma hemostasis: coagulation, anticoagulation, and fibrinolysis components; blood rheology: hematocrit, free red cell sedimentation, red cell aggregation - were measured. Results. In COPD patients, moderately decompensated chronic syndrome of disseminated intravascular coagulation (DIC syndrome), leading to microcirculation pathology, was observed. In CPH pathogenesis, microthrombogenesis progression, pulmonary microcirculation abnormalities, pulmonary hypertension progression play an important role. In patients with COPD and CPH, hemostasis was characterized by decompensated DIC syndrome. Compensatory potential of secondary fibrinolysis was substantially decreased at local, organ level. Conclusion. The study demonstrated a leading role of hemostasis in CPH pathogenesis and CHF progression among COPD patients. Disbalance between microthrombosis and secondary organ fibrinolysis could be regarded as CHF marker in COPD individuals.

Aim. To evaluate local contractility of left and right ventricular (LV, RV) myocardium, as well as its dynamics in acute drug test (AMT) with nitroglycerin (NG) in patients with recurrent atrial fibrillation (AF), during sinus rhythm maintenance period. Material and methods. The study included 120 patients aged 39-82 years (mean age 61.3±8.9 years): 20 patients with recurrent AF and arterial hypertension (AH) (Group IA); 50 patients with coronary heart disease (CHD) and recurrent AF (Group IB); 50 individuals from control group (Group II). To assess inotropic myocardial function, balanced radionuclide ventriculography was performed in all participants. Local LV and RV contractility was studied in unified 16-segment ventricular model. After registering baseline hemodynamic parameters, local contractility was assessed again in ADT with NG – 30 minutes after sublingual NG administration (0.5-1.0 mg). Results. In Groups IA and IB, local hypo- and akinesis were observed. In ADT with NG, patients from Groups IA and IB demonstrated improved local contractility: akinetic segment number significantly reduced, normokinetic LV and RV zone number substantially increased. In Group II, during ADT with NG, local contractility increased due to hypokinetic segments. Conclusion. Local contractility disturbances in patients with recurrent AF during sinus rhythm maintenance were manifested as hypo- and akinetic zones. In ADT with NG, patients demonstrated significant improvement of local contractility, due to decreased number of akinetic segments. In control group, number of hypokinetic segments significantly decreased.

Aim. To investigate cardiohemodynamic parameters and serum cytokine levels in patients with severe alcohol intoxication (AI). Material and methods. In total, 100 patients with severe AI were examined. All participants underwent 24-hour electrocardiogram (ECG) monitoring, echocardiography (EchoCG), and measurement of serum pro-inflammatory cytokine levels . Results. In patients with severe AI, acute alcohol heart damage (AAHD) was diagnosed relatively often (31.4%). Among these individuals, EchoCG disturbances and increase in serum cytokine levels were maximal. Conclusion. In patients with AAHD, complicated by fatal arrhythmias, pro-inflammatory cytokine synthesis was increased, comparing to arrhythmia-free patients. Maximal cytokine concentration was registered in patients with systolic and/or diastolic left ventricular dysfunction.

In CLIP-ACCORD study, 6000 patients from 21 cities of Russia, Ukraine, and Belorussia are participating. Aim. To study antihypertensive efficacy and safety of fixed-dose combination of enalapril and thiazide diuretic hydrochlorthiazide (Co-Renitec ®) among patients with arterial hypertension (AH) and high or very high risk of cardiovascular complications (CVC), in real-world clinical practice settings. Material and methods. CLIP-ACCORD is a multi-center, international, open prospective program. At present, 4224 AH patients (37% of males, 63% of females, aged 20-85 years; mean AH duration 8.4±7.6 (0-50) years) completed study protocol. The program included AH patients with high or very high CVD risk; antihypertensive therapy, if any, was ineffective. Co-Renitec® was administered once per day, at 8-10 AM. If target blood pressure (BP) level was achieved 4 weeks later, therapy in the same dose continued for another 8 weeks. Otherwise, Co-Renitec® dose was increased, and/or other antihypertensive agent was added. Full data were available for 4203 participants. Results. At baseline, BP was at Stage I AH level (National Cardiology Society classification, 2004) in 3% of patients; at Stage II level – in 67%; and at Stage III level – in 30%. After four-week Co-Renitec® treatment, complete BP normalization was achieved in 41% of participants, Stage I BP was registered in 40% of patients, Stage II – in 18%, and Stage III – in 1%. Co-Renitec® dose was increased in 26% of patients; other antihypertensive medications were added in 15%. After 12 weeks of Co-Renitec® treatment, target BP levels were achieved in 82% of patients. AH clinical symptoms improved in 98% of participants. After program end, 98% of participants continued CoRenitec® intake. Conclusion. Co-Renitec® antihypertensive therapy in AH patients with high and very high CVC risk was effective in full-dose combination, and facilitated target BP level achievement in 82% of patients.

Aim. To study association of arterial hypertension (AH) and coronary heart disease (CHD) in real-world cardiology practice. This was the aim of the national PREMIERE Study. Material and methods. The study involved cardiologists from 14 cities of the Russian Federation. During 5 days, every doctor included all consecutive AH and/or CHD male and female patients, aged 18-65 years. During epidemiology phase, 14 075 patients were recruited in the study. For the analysis, 8578 patients were randomly selected, including 3615 (42.1%) males and 4963 (57.9%) females. In all participants, socio-demographic characteristics were measured; complaints, main risk factors (RF), already prescribed therapy, intake regularity and causes of irregular medication intake were registered. Blood pressure and heart rate were measured; electrocardiogram at rest was analyzed. Results. Various CHD forms, including myocardial infarction, effort angina, painless CHD, cardiac arrhythmias, were observed in 72.4% of AH males and 61.2% of AH females. Analyzing RF, associated with AH and CHD, it turned out that 88.5% of AH patients and 95.6% of AH and CHD patients had at least one RF. Education level was a significant determinant for Russian population health, defining awareness, behavioral RF and, therefore, morbidity and treatment attitudes. Persons with higher education more often had cardiovascular disease in family history, lipid profile disturbances, and chronic stress exposure. On the contrary, patients with lower than secondary education level significantly more often smoked, drank alcohol, and had cardiovascular symptoms. Conclusion. Therefore, REMIERE Study results give a chance to assess present cardiology practice, to characterize patients with isolated AH or AH combined with CHD, including complaints and treatment compliance, according to social status and other parameters.

Aim. To assess indapamide (Arifon retard) effects on blood pressure (BP), carbohydrate, lipid, purine and electrolyte metabolism in patients with mild arterial hypertension (AH) and metabolic syndrome (MS). Material and methods. In total, 573 patients with mild AH and MS participated in MINOTAUROS Study (Patients with MetabolIc SyNdrOme - effecTiveness And ToleRability of ArifOn Retard in Arterial HypertenSion Treatment). All participants were randomized into two groups: 459 were administered Arifon retard and non-pharmaceutical treatment (Group I); 114 patients received only non-pharmaceutical treatment, without pharmaceutical antihypertensive therapy (control Group II). At baseline and after 12 weeks of therapy, BP, body mass (BM), waist circumference (WC), parameters of carbohydrate, lipid, purine, and electrolyte metabolism were measured.. Results. BM and WC decreased in both groups. Arifon retard therapy resulted in greater BP decrease, substantial improvement in carbohydrate and lipid metabolism, with unchanged purine and electrolyte metabolism parameters. Conclusion. Additional beneficial metabolic effects of Arifon retard, as well as its antihypertensive effectiveness, make it a diuretic of choice in treating MS and AH patients.

Aim. To assess antihypretensive effect quality and duration for ACE inhibitor spirapril (Quadropril®; daily dose 6 mg) among arterial hypertension (AH) patients, in real-world out-patient clinical settings. Material and methods. The trial involved 11 Russian cities. This Russian multi-center, non-comparative, open study QUADRIGA (QUADRoprIl and AH) involved 235 AH patients with Stage I-II of blood pressure (BP) elevation; systolic BP (SBP) 140-179 mm Hg and/or diastolic BP (DBP) 90-109 mm Hg; age 25-75 years (mean age 51.1 years); <60 years – 74.8%, and 60 years – 25.2%; females – 54.5%; 17 patients with coronary heart disease, 32 patients with diabetes mellitus. Effectiveness criteria for Quadrorpil® antihypertensive action: normalization of SBP and/or DBP (<140/90 mm Hg); beneficial antihypertensive effect: DBP decrease 10 mm Hg; SBP decrease 20 mm Hg, in regard to baseline BP level. Results. During Quadropril® treatment, as monotherapy or in combination with a diuretic - hydrochlorthiazide was additionally administered to 122 patients (51.9%) - daily dose increase up to 25 mg was necessary in 78 participants; significant SBP and DBP reduction was observed. On average, SBP decreased from 159.8 to 132.8 mm Hg – by 25.7 mm Hg (16.1%), and DBP decreased from 98.7 to 83.3 mm Hg – by 15.1 mm Hg (15.3%). Target BP was achieved in 83.56% of the patients. Conclusion. According to Russian QADRIGA Study results, a new ACE inhibitor Quadropril® demonstrated good antihypertensive effect. Quadropril® in daily dose 6 mg, once per day, combined with hydrochlorthiazide 12.5-25 mg if needed, can be recommended for AH patients’ treatment.

The article is devoted to treatment of psychoemotional disturbances, typical for cardiovascular disease patients: asthenic syndrome, anxiety and depression. Basic principles of their pharmacotherapy in general and cardiology practice are presented.

The review focuses on clinical practice perspectives for angiotensin II receptor blockers (ARB). The authors discuss the results of the trials on biotransformation genes (CYP2C9) polymorphism and renin-angiotensin-aldosterone system influence on ARB pharmacokinetics and pharmacodynamics. Pharmacogenetic studies have been performed not only in healthy volunteers, but also in patients with arterial hypertension or chronic heart failure.

The results of randomized clinical trials comprising SMILE (The Survival of Myocardial Infarction Long term Evaluation) Project were analyzed. Six-week therapy with an ACE inhibitor zofenopril in acute myocardial infarction (AMI) patients resulted in one-year mortality reduction by 29%. Xofenopril was safe and well-tolerated in AMI patients. Ongoing zofenopril trials are also reviewed.

The review contains original data and international studies’ results demonstrating that selective I1 imidazoline receptor agonists, and, in particular, Albarel®, a new sympatholytic agent, provide not only adequate and longterm blood pressure control, but also other beneficial metabolic and vascular effects. Most important ones are insulin resistance reduction, improvement of endothelial function and elasticity in middle-sized and large vessels. In Russian guidelines on arterial hypertension diagnostics and treatment, this medication class is recommended in patients with metabolic disturbances. Nevertheless, in real-world clinical practice, the indications might be widened, including sympathetic hyperactivity in post-menopause women, patients with insulin resistance, chronic obstructive pulmonary disease, and bronchial asthma.