Aim. To analyse the pre-hospital treatment of uncomplicated hypertensive crises (HC), using complex pharmacoeconomic approach. Material and methods. A retrospective study based on the data from ambulance visits to the Kirov City patients with uncomplicated HC. Pharmacological anamnesis analysis, frequency analysis, ABC/VEN analysis. Results. The study included 482 patients with essential arterial hypertension (AH). No preceding antihypertensive treatment (AHT) was received by 20,9%, and irregular AHT was documented for 19,3%. Ambulance doctors prescribed 1-7 medications on average; the complete list included 51 medications. Total expenses (n=482) on medications and syringes were 7372,93 roubles; expenses per patient were 16,0±18,2 and 15,0±10,7 roubles for specialised and general ambulance teams (SAT, GAT), respectively. According to the ABC analysis results, the costs were mostly presented by NaCl (as a basis for intravenous injections), followed by phenazepam and magnesium sulphate. According to the VEN analysis, group V included 24,4-31,4% of all medications, while groups E and N included 20-21,6% and 47,1-55,6%, respectively. Conclusion. High HC rates in AH patients were linked to inadequate AHT at the out-patient level. AHT medication costs comprised, on average, one-fifth of the total expenses on medications prescribed by ambulance doctors. According to the frequency analysis results, SAT mostly used parenteral AHT for HC treatment, while GAT preferred oral AHT and non-recommended magnesium sulphate and dibazol. In the ABC analysis, medication distribution agreed with recommended one. The VEN analysis demonstrated over-prescription of second-line medications.

Aim. To study the changing activity of renin-angiotensin-aldosterone system (RAAS) and sympatho-adrenal system (SAS) in progressing arterial hypertension (AH). Material and methods. The study included 480 AH patients with high cardiovascular risk, aged 18-65 years (mean age 52±12 years); 102 men and 378 women. The participants were randomized by the levels of Reberg-estimated glomerular filtration rate (GFR) and the results of radio-isotope renography (RRG) with 123 I-hippuran. Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were assessed by the radio-immune method, and circadian excretion of adrenaline and noradrenaline (CAE, CNAE) – by the fluorometric method. Results. In patients with GFR 115-135 ml/min, mean PAC was 0,53±0,06 nmol/l, in those with GFR 80-115 ml/ min - 0,76±0,08 nmol/l (43,4% increase; р<0,05), and in those with GFR <60 ml/min - 0,84±0,06 nmol/l (58,5% increase; р<0,01). The maximal increase in PRA (+47,6%; р<0,05), CAE (+36,6%; р<0,05), and CNAE (+92,4%; р<0,01) was observed in patients with chronic heart failure (CHF). Conclusion. At the early stages of renal dysfunction, noradrenaline synthesis was decreased. Progressing renal dysfunction, with increased secretion phase of RRG and GFR<80 ml/min, adrenaline and noradrenaline synthesis significantly increased, while PRA tended to increase. In Functional Class III CHD, SAS and RAAS activation were even more pronounced.

Aim. To compare left ventricular (LV) remodelling and LV myocardial mass indices (MMI) in overweight and nonoverweight women with arterial hypertension (AH). Material and methods. The study included 89 women (mean age 48,3±8,7 years) with AH, but no regular antihypertensive treatment at the study enrolment. By the levels of body mass index (BMI), all women were divided into two groups: 47 women with BMI 18-25 kg/m2 (Group I) and 42 women with BMI 26-29 kg/m2 (Group II). All participants underwent two-dimensional transthoracic echocardiography (EchoCG), with the calculation of LVMM, LVMMI adjusted to body surface area (BSA) or height to the power of 2,7, and remodeling indices. Results. Overweight, even without obesity, was linked to a statistically significant increase of LV wall thickness, LVMM and height-adjusted LVMMI (р=0,002), while BSA-adjusted LVMMI demonstrated only a tendency towards increase (р=0,06). The latter finding demonstrates that the traditional, BSA-adjusted LVMMI could result in under-diagnostics of LV hypertrophy (LVH) among overweight patients. Conclusion. To diagnose LVH early in overweight patients, LVMMI should be adjusted to height to the power of 2,7.

Aim. To study the effects of the fixed combination trandolapril 2 mg + verapamil 120 mg medication on endothelial function in patents with Stage II-III essential arterial hypertension (AH). Material and methods. In total, 39 AH patients were examined (mean age 66,7±6,9 years; Stage II and III AH – in 41,0% and 59,0%, respectively). At baseline and during the treatment phase, blood pressure (BP) measurement, 24-hour BP monitoring (BPM), and endothelium-dependent vasodilatation (EDVD) assessment were performed. All patients received the fixed combination trandolapril 2 mg + verapamil 120 mg in the dose of 1 tablet once a day, in the morning; if after four weeks, routinely measured BP did not achieve target levels (<140/90 mm Hg), the dose was increased up to 2 tablets once a day. The follow-up period lasted for 24 weeks. Results. A significant reduction (p<0,05) in “office” systolic and diastolic BP (SBP, DBP) levels – by 36,3 and 24,4 mm Hg, respectively – was observed. At baseline, endothelial dysfunction was registered in 15 individuals. After 24 weeks of the therapy, EDVD normalized in 9 out of 15 patients (60,0%), and improved in other 6 (40,0%). Conclusion. The fixed-dose combined medication, the fixed combination trandolapril 2 mg + verapamil 120 mg, administered to patients with Stage II-III AH for 24 weeks, significantly reduced SBP and DBP levels and improved endothelial function.

Aim. To study right ventricular (RV) structure and function, assessed by standard echocardiography (EchoCG), tissue myocardial Doppler (TMD) EchoCG, and natriuretic peptide (NUP) levels, in patients with pulmonary hypertension (PH) of various aetiology. Material and methods. The study included 102 PH patients: 29 with idiopathic PH (IPH), 15 – with PH and pulmonary thromboembolia (PTE), 18 – with PH and systemic scleroderma (SS), 13 – with PH and chronic obstructive pulmonary disease (COPD), 12 – with residual PH. The control group included 21 healthy volunteers. In all participants, standard EchoCG, TMD, measurement of brain and atrial NUP levels were performed. Results. According to the standard EchoCG results, the maximal and minimal heart and pulmonary artery remodelling was observed, respectively, in IPH and COPD. NUP levels correlated with remodelling severity in PH patients. The extent of RV ejection fraction (EF) reduction correlated with the decrease in systolic velocity of tricuspid valve motion. Maximal and minimal systolic RV dysfunction was observed in patients with IPH and COPD, respectively. Although at standard EchoCG, there was no clear evidence of diastolic RV dysfunction, TMD revealed diastolic RB dysfunction in all PH patients. According to TMD results, diastolic RV dysfunction (RVDD) was maximal in IPH individuals. Additionally, TMD demonstrated substantial RVDD, combined with high NUP levels, in patients with PTE and SS. In contrast with standard EchoCG, TMD revealed RVDD in all PH patients. Conclusion. TMD is more effective than standard EchoCG in diagnosing RVDD, associated with elevated NUP levels, in PH patients.

Aim. To study the effectiveness of generic simvastatin in hyperlipidaemia (HLP) correction (isolated hypercholesterolemia, HCH, or HCH combined with hypertriglyceridemia, HTG) in patients with confirmed diagnosis of coronary heart disease (CHD), in regard to their smoking status. Material and methods. In total, 43 CHD patients with HLP (22 men and 21 women) were divided into two groups: never-smokers (n=22) and smokers (n=21). All patients received generic simvastatin (40 mg/d) for 12 weeks. Results. The dynamics of lipid-lowering effect of simvastatin was more manifested in the first 6 weeks of the therapy, regardless of smoking status of CHD patients with HLP. However, in non-smoking individuals, this effect was stronger. Smoking restricted lipid-lowering activity of generic simvastatin, which was manifested in smaller reduction in total cholesterol (TCH) levels, lower percentage of patients achieving target TCH concentration, and unchanged TG levels in the first 6 weeks among smokers, in contrast to a significant triglyceride-lowering effect in non-smokers. According to veloergometry results, generic simvastatin therapy was associated with increased physical stress tolerability in both groups, with a tendency towards increased peak oxygen uptake in smokers. Conclusion. Generic simvastatin (40 mg/d) was as effective in HLP correction as original statins, being less expensive than the latter. Generic simvastatin therapy could neutralise adverse effects of smoking on blood lipids. Therefore, generic statins could be used in many CHD patients who cannot afford buying original statins.

Aim. To investigate indapamide retard effects on clinico-laboratory parameters and clinical course in patients with Functional Class (FC) II-IV chronic heart failure (CHF) and arterial hypertension (AH). Material and methods. The study included 60 patients (33 men and 27 women) with FC II-IV CHF and AH; mean age 65,9±1,7 years. All participants were divided into two groups: Group I (n=30) received standard CHF therapy only, Group II (n=30) received standard CHF therapy plus indapamide retard (1,5 mg/d) for 6 months. The dynamics of CHF FC, blood pressure (BP), laboratory parameters, and adverse effect (AE) prevalence were assessed. Results. Indapamide retard therapy was associated with a significant reduction in CHF FC and improved left ventricular ejection fraction. In controls, the results of the 6-minute walk test increased from 299,4±18,8 to 338,4±32,5 m (р>0,05), while in patients receiving indapamide retard, they increased from 288,7±19,2 to 354,6±22,7 m (р=0,031). Positive dynamics of 24-hour BP monitoring parameters was more manifested in the indapamide retard group. After 6 months, NT-pro-BNP level significantly decreased in Group II, but not in Group I. Indapamide retard therapy was not associated with AE, and renal function or glycemia parameters were not affected. Conclusion. Adding indapamide retard to standard treatment of the patients with CHF and AH demonstrated good antihypertensive effects, improved CHF course, and minimal risk of AE.

Aim. To evaluate the effects of insulin and other glucose-lowering medications on platelet function and coagulation haemostasis in patients with Type 2 diabetes mellitus (DM-2). Material and methods. The study included 147 patients with DM-2, aged 49—60 years (mean age 54 years), not receiving any glucose-lowering therapy, or regularly taking various glucose-lowering medications (glibenclamide, gliclazide, metformin, insulin, and glibenclamide + metformin combination). Results. Platelet function activation and increased pro-coagulation activity are typical for DM-2 patients, including individuals at early DM stages, without angiopathy, and not receiving pharmaceutical treatment. Various groups of glucose-lowering medications have different effects on hemostasis parameters. Specifically, insulin, glibenclamide, metformin and glibenclamide + metformin combination do not have any anti-aggregant activity. At the same time, insulin and glibenclamide activate the internal coagulation pathway. Anti-platelet activity of glibenclamide is similar to that of acetylsalicylic acid. Conclusion. Different haemostasiologic effects of glucose-lowering medications should be considered while choosing individual treatment strategy in DM-2 patients.

Aim. To evaluate the effectiveness and safety of zopiclone in apnoea-free sleep disorders among patients with metabolic syndrome (MS). Material and methods. The study included 60 patients with chronic cerebrovascular disease (CerVD) and MS (mean age 53,3±11,2 years). Zopiclone was administered in the dose of 7,5 mg once a day, 30 minutes before going to bed, for 21 days. Therapy effectiveness was evaluated by various subjective and objective sleep assessment methods. Results. After a zopiclone treatment course, all patients reported substantial improvement of sleep quality. These beneficial effects were explained by changing sleep architecture — the duration of sleep phases and stages (%). In particular, Stage 1 of slow sleep phase, the most affected at the pre-treatment level, was significantly reduced by 20 %, while Stage 2 of slow sleep phase increased by 14 % (p<0,05). Conclusion. Zopiclone therapy in CerVD patients with MS and apnoea-free sleep disorders substantially improved subjective and objective sleep parameters. Zopiclone could be recommended as a first-choice medication in MS patients with apnoea-free sleep disorders.

This analytic paper reviews the evidence on effectiveness, benefits and limitations of one of the best-studied antiplatelet agents – acetylsalicylic acid (ASA). The results of clinical trials, together with so called “gastro-toxicity” of ASA, or Aspirin, and a need for long-term anti-platelet therapy, were the basis for development of various Aspirin forms – soluble, with controlled release, enteric-coated, local (cutaneous), buffer, and combined (Aspirin plus antacids). Currently, the minimal gastro-toxicity has been demonstrated for enteric-coated forms. Specifics of bio-availability, laboratory effects, gastro-intestinal tolerability, and safety could not be the main criteria for choosing a medication form. The choice of an ASA form is defined by the evidence on risk reduction by this form. The extensive evidence on Aspirin as an anti-platelet agent has been obtained in clinical trials using standard ASA. For enteric-coated ASA forms, the evidence on end-point reduction, including mortality reduction, is also available. For other “improved” Aspirin forms, such as buffer, soluble and combined, this evidence is lacking; therefore, their choice could be based only on similarity of laboratory effects and expected lower gastro-toxicity.

The review presents the results of some large-scale clinical trials on the prognostic value of endothelial dysfunction, as a predictor of cardiovascular events. Coronary endothelial function, assessed invasively, is an independent predictor of spontaneous cardiovascular events, such as sudden cardiac death, myocardial infarction and cerebrovascular events, even after adjustment for pre-existing coronary heart disease (CHD) and other cardiovascular risk factors. Other studies demonstrated that coronary endothelial dysfunction is the strongest predictor of cerebrovascular events. Preoperative non-invasive assessment of endothelial function could independently predict postoperative cardiovascular and cerebrovascular events.

Aim. To study velocity and volume parameters of hemodynamics, as well as their relation to larger artery remodelling, in elderly patients with arterial hypertension (AH). Material and methods. In total, 46 elderly AH patients, aged 61-90 years (mean age 75,6±0,7 years), were examined; 62,2% were aged over 80 years. Mean AH duration was 16,0±1,0 years. The examination included duplex scanning of common carotid artery (CCA), brachial artery (BA), and femoral artery (FA). Intima-media thickness (IMT), artery diameter (AD), peak (V_max), minimal (V_min) and mean maximal (Vta_max) blood flow velocity, blood volume per vessel section per 1 second (Q cm3/s), and specific blood kinetic energy (hv cm²/s²) were measured. Endothelium-dependent and endothelium-independent vasodilatation (EDVD, EIVD), as well as pulse rate velocity (PRV), were also assessed. Results. In elderly AH patients, all large arteries demonstrated increased IMT (by 12,5%, compared to healthy controls; p<0,001), while AD for CCA and BA was increased by 29,8% and 15,4%, respectively (р><0,001). For FA, there was a tendency towards reduction in all velocity parameters. For CCA and BA, velocity parameters were ><0,001), while AD for CCA and BA was increased by 29,8% and 15,4%, respectively (р<0,001). For FA, there was a tendency towards reduction in all velocity parameters. For CCA and BA, velocity parameters were independent from minimal and maximal systolic blood pressure, SBP (SBP_max, SBPmin). For FA, BP_max negatively correlated with V_max and Vta_max. For CCA and BA, Q parameter was significantly higher than in controls in all hemodynamic phases, while for FA, it was the same as in controls. Compared to healthy controls, FA blood volume in Vta_max phase was reduced by 40%, with increased blood flow in CCA and BA and a 20% reduction in low extremities blood flow. PWV was similar in elderly AH patients and controls for CCA, while for BA and FA, it was increased in those with AH. There was no association between PWV and BP. Conclusion. In elderly AH patients, CCA and BA remodelling was characterised by increased IMT and AD parameters. Blood flow was increased in CCA and BA and decreased in FA, which resulted in lower extremities blood flow reduction by 20%, compared to healthy controls.

Recently, more and more attention has been paid to metabolic risk factors (RFs), due to their prognostic importance in the development of cardiovascular disease (CVD) and Type 2 diabetes mellitus. The metabolic effects of antihypertensive medications are actively discussed in the literature. It has been demonstrated that ACE inhibitors, calcium antagonists, and I1-imidasoline receptor agonists (IRA) do not affect metabolic RFs, while diuretics (D) and beta-adrenoblockers could worsen the prognosis. In the new European guidelines, alpha-adrenoblockers and IRA are not regarded as first-choice medications, due to the lacking evidence of their effects on end-points. The paper analyses in detail the results of large-scale international trials on D. In particular, the authors discuss the potential of low-dose thiazide D, as a part of combined therapy, in patients with metabolic disturbances and high cardiovascular risk.

Pulmonary arterial hypertension (PAH) is one of the most severe cardiovascular disorders. It is characterised by progressing clinical course, right ventricular failure development, and very poor prognosis. In September 2009, the European Society of Cardiology and the European Respiratory Society released a new revision of clinical recommendations on pulmonary hypertension (PH) diagnostics and treatment. The recommendations review the evidence for supportive therapy (oral anticoagulants, diuretics, digitalis medications, and oxygen), specific therapy (calcium antagonists, prostanoids, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors), and surgery. Modern pharmaceutical approaches, including specific therapy medications and their combinations, could increase the effectiveness of PH treatment and improve PH prognosis. The meta-analysis of 23 randomised trials demonstrated that in PAH patients, specific therapy (mean duration 14,3 weeks) decreased mortality and hospitalisation rates by 43% and 61%, respectively. In other countries, specific therapy medications are included into targeted treatment programs. In Russia, only bosentan is officially recommended for PAH treatment, while the registration of inhaled iloprost and sildenafil citrate is expected in the nearest future.

This review discusses statin treatment in patients with coronary heart disease (CHD), including acute coronary syndrome (ACS), based on the results of the latest clinical trials. The modern views on statin mechanisms of action are presented, including their pleiotropic effects, important for CHD and ACS treatment. Currently, the most effective and safe statin is atorvastatin.

Diabetes mellitus (DM) is a serious medico-social problem, due to high risk of its complications and, as a result, high prevalence of disability in DM patients. DM substantially increases the risk of heart failure (HF), mostly because of diabetic cardiomyopathy (DCMP). The development of the latter is influenced by many factors, sharing the main pathophysiological mechanism – insulin resistance. The paper discusses in detail the mechanisms of DCMP development and the principal relevant factors.

Chronic activation of renin-angiotensin-aldosterone system (RAAS) is characterised by vasoconstriction, increased total peripheral vascular resistance, organ and tissue hypoperfusion, fluid detention, increased circulatory volume, increased myocardial sensitivity to toxic effects of catecholamines, myocardial and vascular remodelling, myocardial and perivascular fibrosis. RAAS activity could be reduced by suppressed angiotensin II synthesis, or AT-1 receptor blockage. ACE inhibitors are highly effective in the treatment of such cardiovascular pathology as arterial hypertension, chronic heart failure, or coronary heart disease. Their main pharmacological effects include hemodynamic, neuro-humoral, anti-proliferatory, cardio- and nephroprotective action, as well as endothelial function improvement. AT-1 receptor antagonists are characterised by high antihypertensive effectiveness, perfect tolerability, organ protection, administration simplicity, and no significant interactions with other medications, which makes them essential in daily clinical practice.