ORIGINAL STUDIES 
Aim. To evaluate drug therapy received by patients who had survived acute myocardial infarction (AMI) in the framework of the AMI register (the “LIS” study) and estimate this therapy influence on long-term outcomes of the disease. Material and methods. The total of 961 patients of 1133 enrolled in the “LIS” study , were discharged from hospital. 191 patients had died during follow-up. 632 patients (who had survived and consented to visit out-patient clinic) underwent repeated examination (median of follow-up 1.6 [1.0; 2.4] years). Data about treatment before and during AMI were received from patient’s charts; data about treatment after AMI were obtained from out-patient medical records. Results. Before reference AMI only a small number of the patients received the main drug groups (antiplatelet agents, β-blockers, ACE inhibitors, statins), at that ACE inhibitors were prescribed more often than the others. Use of β-blockers and ACE inhibitors before reference AMI significantly improved long-term life prognosis [relative risk (RR) 0.70 and 0.66, respectively]. Rate of the main drug groups prescribed in hospital was rather high with the exception of thrombolytics (less than 10%). Thrombolytics, β-blockers and antiplatelet agents prescribed in hospital significantly improved long-term life prognosis of patients (RR 0.42, 0.65 and 0.58 respectively). At the second visit (according to data of out-patient medical records) rate of antiplatelet agents, ACE inhibitors, β-blockers and statins prescription exceeded 60%. Conclusion. Very low prevalence of adequate drug therapy preceding AMI determines high mortality rate among survived acute stage of myocardial infarction patients in long-term period.
Aim. To study the sex characteristics of microcirculation in healthy volunteers and in patients with degree 1 arterial hypertension (HT). Material and methods. Patients (n=71; 34 men and 37 women) with degree 1 HT participated in the study. Besides 28 normotensive men and 41 women were included. The microcirculation study was performed with LAKK-02 analyzer on the palmar surface of the third finger of the right hand. The average values of the microcirculation index, the standard deviation of perfusion fluctuations (σ), the variation coefficient of tissue blood flow (Kv) were evaluated. Results. The microcirculation index in HT men 26.64 (21.00–32.45) perfusion units (p.u.) was significantly higher than this in HT women 20.91 (16.98–24.30) p.u., p=0.031. The variability of microcirculation index was significantly higher in HT patients than this in healthy subjects. Capillary blood flow reserve in healthy women was higher than this in healthy men. Amplitude, reflexing myogenic factor of blood flow regulation was significantly lower in HT men than this in HT women: 13.37 (10.51–16.43) vs 14.69 (11.35–19.13), respectively , p=0.023. Amplitudes, reflecting respiration effects on peripheral blood flow in HT men were significantly higher than these in HT women. Amplitudes, reflecting pulse effect on the tissue perfusion in HT women were significantly higher than these in HT men. Influence of sympathetic adrenergic innervation on the blood flow was higher in healthy men than this in healthy women. Conclusion. Received data suggests the intensification of microcirculation regulation mechanisms in men with HT degree 1. It was found that sympathetic adrenergic effect on the microcirculation regulation was significantly less in healthy women than this in healthy men.
Aim. To study the dynamics of physical performance in young people with mitral valve prolapse (MVP) while taking magnesium orotate. Material and methods. Patients with MVP and phenotypic characteristics of undifferentiated connective tissue dysplasia (n=54, aged 19.2±0.3 years) were included into the study. Hemodynamic parameters of physical performance were evaluated before and after taking magnesium orotate for 8 weeks. Results. Improvement of physical performance was found after magnesium orotate taking: threshold double product elevated from 1.86±0.05 to 2.06±0.05 units (p<0.001); threshold power increased - relative physical performance raised from 1.35±0.04 W/kg to 1.44±0.04 W/kg (p<0.05) and specific work from 12.3±0.65 W/kg to 14.2±0.71 W/kg (p<0.001); recovery time decreased. Conclusion. Improvement of hemodynamic maintenance of exercise load was found in adolescents with MVP during magnesium orotate taking. It was accompanied with physical performance and threshold power elevation and recovery time reduction.
Aim. To study the relationship of arterial stiffness (determined by contour analysis of peripheral pulse wave) with cardiovascular risk factors in women with rheumatoid arthritis (RA). Material and methods. Women with high activity of RA (n=130) were examined. Women without rheumatic diseases (n=25) were included into control group. Assessment of the major traditional risk factors (TRF) of cardiovascular disease (CVD), duplex scanning of the common carotid arteries, transthoracic echocardiography (Echo-CG), and determination of serum inflammation marker levels were performed, in addition to evaluation of clinical symptoms, RA activity and severity. Indicators of digital pulse volume were determined by photoplethysmography. Results. Young and middle aged patients with RA after adjusting for the major TRF of CVD compared with women without RA have higher stiffness index (SI), reflecting increased stiffness of large arteries, and reflection index (RI), that shows raised tone of small arteries. The value SI>9.6 m/s or RI>70% is associated with a higher rate of diastolic dysfunction (DD), and left ventricular hypertrophy (LVH), while the more severe RA [high frequency III/IV radiographic stage, high levels of IgM rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP)] and the history of inefficacy of tumor necrosis factor-α (TNF-α) inhibitors in the absence of significant differences in TRF of CVD. SI and RI values in patients treated with methotrexate were significantly lower than in patients receiving other basic anti-inflammatory drugs or not treated patients. Conclusion. Increased arterial stiffness that is associated with the development of DD and LVH, irreversible joint damages, higher IgM RF and anti-CCP levels may be one of the possible mechanisms of the relationship of RA severity and increased risk of cardiovascular complications. RI determination can be used for screening of LVH in women with RA of high activity.
Aim. To assess the risk of diabetes mellitus type 2 (DM2) in patients with various cardiovascular (CV) risk, and to identify the relationship between a high risk of DM2 and the major CV risk factors. Material and methods. Men (n=378) with one or more CV risk factors (hypertension of stage 1–3, smoking, hypercholesterolemia) and various CV risk (SCORE) were included in the one- stage clinical trial. All patients were interviewed with standard questionnaire and FINDRISC questionnaire, as well as glucose tolerance test was performed. Results. The patients were split into three groups based on the total CV risk (SCORE): 33.6% had low-to-moderate CV risk, 38.9% — high CV risk and 27.5% — very high CV risk. Most of the men were in the 50–59 and 60–69 years age groups. Most of the patients aged 40–49 years had the high CV risk, while 59% of men aged 50–59 had moderate CV risk. Every second older male had a very high CV risk. According to the FINDRISC questionnaire low risk of DM2 in the next 10 years was detected in 40.2% of patients, intermediate risk — in 35.2%, moderate risk — in 10.3%, high risk — in 11.1%, a very high risk — in 3.2% of patients. Conclusion. Men with very high CV risk (SCORE) have also high and very high risk of DM2 (according to FINDRISC questionnaire). Detection of early markers of glucose metabolism disturbances as well as DM2 risk assessment should be performed in patients with one or more of the above mentioned CV risk factors. This strategy is able to contribute to proper DM2 risk assessment and development of methods of DM2 prevention.
ANALYSIS OF CLINICAL PRACTICE 
Aim. To study the coronary atherosclerosis progression in patients with 5-year history of myocardial infarction (MI) depending on the statin therapy compliance. Material and methods. Patients (n=31) with a five year history of MI were involved into the study. Patients were divided into two groups depending on the statin therapy compliance during 5 years after MI: group 1 — patients with high compliance, group 2 — patients with low compliance. Assessment of the coronary angiography and lipid profile was performed first time in 2005–2006 during hospital treatment for MI and after 5 years again. Results. Increase in the proportion of patients with two and three coronary vessel disease was found after 5 years of observation, despite the high rate of percutaneous coronary intervention (77.4%) and hypolipidemic therapy. Hemodynamically significant restenosis was found in 11.8% (group 1) and 21.4% (group 2) of patients. Target total cholesterol level was reached only in 42.9% and 11.8% of patients in group 1 and 2, respectively. The target level of low density cholesterol was achieved in no one patient. Conclusion. The findings suggest that in patients with 5-year history of MI coronary atherosclerosis progresses regardless of the statin therapy compliance.
NOTES FROM PRACTICE 
Rational pharmacotherapy in Takotsubo cardiomyopathy is based on clinical picture and data of functional and laboratory investigations of concrete patient. In patients with hypotension and moderate-to-severe left ventricle outflow tract obstruction inotropic agents must not to be used because they can worsen the degree of obstruction. In these patients beta blockers can improve hemodynamics by causing resolution of the obstruction. If intraventricular thrombus is detected, anticoagulation for at least 3 months is recommended. The duration of anticoagulant therapy may be modified depending on the extent of cardiac function recovery and thrombus resolution. For patients without thrombus but with severe left ventricular dysfunction, anticoagulation is recommended until the akinesis or dyskinesis has resolved but not more than 3 months.
Tissue Doppler imaging is evolving as a useful echocardiographic tool for quantitative assessment of left ventricular systolic and diastolic function. Over the last 10 years, myocardial deformation imaging has become possible initially with tissue Doppler , and more recently with myocardial speckle-tracking using 2D echocardiography. Unlike simple tissue velocity measurements, deformation measurements are specific for the region of interest. Strain rate or strain measurements have been used as sensitive indicators for subclinical diseases, and it is the most widely used tool to assess mechanical dyssynchrony. Left bundle branch block is a frequent, etiologically heterogeneous, clinically hostile and diagnostically challenging entity. About 2% of patients underwent cardiac stress testing show stable or intermittent left bundle branch block. Presence of left bundle branch block is associated with a lower and slower diastolic coronary flow velocity especially during hyperemia. Stress echocardiography is the best option for the diagnosis of ischemic heart disease, albeit specificity and sensitivity reduce in patients with left bundle branch block in the territory of left anterior descending artery in presence of initial septum dyskinesia.
POINT OF VIEW 
The most pressing issues of the secondary drug prevention of the most common cardiovascular diseases are focused. These are arterial hypertension, stable ischemic heart disease, chronic
heart failure.
Advantages of metoprolol succinate in patients with chronic heart failure (CHF) are covered. Results of MERIT-HF study are taken as the main evidences. Patterns of the metoprolol succinate use in the treatment of different categories of patients with CHF (women, the elderly , severe CHF forms, CHF with concomitant hypertension or diabetes) are considered.
Published data demonstrating genetic determination of sick sinus syndrome is presented. The definition of this pathology is presented; the main symptoms are described, as well as genes that influence the development of idiopathic sick sinus syndrome, their polymorphisms and role in disorders of the cardiovascular system.
Nowadays conception of blood pressure (BP) variability (BPV) includes a number of indicators related to various physiological factors. All the indexes are calculated with the standard deviation (SD) or more complex formulas, including SD. BPV main varieties are considered a 24-hour BPV (measured by ambulatory BP monitoring – ABPM), midterm BPV (BP self-control or home BP – HBP), and long-term, visit-to-visit, BPV (traditional BP measurement or office BP – OBP). The 24-hour BPV was the main subject of study for many years. Recently significant attention has been paid to the visit-to-visit BPV assessment. Retrospective meta-analysis showed that in a cohort of patients after stroke or transient ischemic attack, this index was a strong and independent (from the average BP level) predictor of stroke. In ASCOT-BPLA study visit-to-visit systolic BPV also was a strong predictor of stroke and coronary events. Long-term BPV in patients of amlodipine/perindopril treatment group was significantly lower than this in patients of atenolol/diuretic group during the follow-up that was associated with a lower risk of cardiovascular complications. However , the concept of visit-to-visit BPV use for risk stratification and monitoring of antihypertensive therapy efficacy is associated with significant limitations (basic data is obtained in the post hoc analysis, difficulties in objective evaluation of prognostic significance of indicators, their dependence on medication adherence, etc.). The HBP self-control is a promising approach to the BPV analysis; it may be the "happy medium" between ABPM and OPB. New-designed prospective comparative studies are needed to evaluate the clinical significance of the various BPV parameters.
Dabigatran is the new oral anticoagulant that directly inhibits thrombin (factor IIa). In RE-LY clinical trial dabigatran 150 mg b.i.d was more effective than warfarin in prevention of ischemic stroke and systemic embolic events in more than 18000 patients with nonvalvular atrial fibrillation. At that time dabigatran and warfarin showed similar safety. Practical issues of dabigatran treatment, e.g. therapeutic indications, choice of dosage etc. are discussed.
CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY 
Topical issues of cardiovascular disease pharmacotherapy influencing function of the renin-angiotensin-aldosterone system are discussed. Efficacy and safety of two major cardiovascular drug classes, angiotensin converting enzyme inhibitors and sartans, are compared. Data from evidence base of the both drug classes are presented.
JUBILEE 
ISSN 2225-3653 (Online)