Aim. To identify the criteria of early left ventricular (LV) remodelling; to assess the baseline structure and function of left and right cardiac chambers, as well as their dynamics during adequate antihypertensive therapy (AHT), in patients with Stage 2 arterial hypertension (AH).
Material and methods. In total, the study included 79 individuals: 35 patients with Stage 2 AH and 44 healthy volunteers. All participants underwent echocardiography (EchoCG), with the assessment of standard structural and functional remodelling parameters, as well as the original linear parameters “a”, “b”, and “c”, proposed by the authors. Twenty five AH patients were re-examined 1,5 years after the start of adequate AHT.
Results. Even early stages of AH are characterised by left and right ventricular dysfunction, as a manifestation of complex heart reaction to pressure overload. Simple, accessible EchoCG criteria, specifically, linear parameters of LV geometry “a”, “b”, and “c”, have been proposed to assess LV remodelling at earlier stages, compared to traditional parameters and spherical index. Adequate AHT resulted in improvement of left and right heart structure and function, with geometric parameters “a” and “b” being the most sensitive criteria.

Conclusion. In AH patients, the proposed linear parameters could be used as diagnostic criteria for earlyLV remodelling, as well as indicators of AHT effectiveness, considering their higher sensitivity, compared to traditional EchoCG parameters.

Aim. To compare the effects of ACE inhibitors zofenopril and perindopril on endothelial function and oxidative stress (OS) in patients with stable CHD and AH.
Material and methods. In total, 40 patients with stable CHD (Functional Class II-III effort angina) and Stage 1-2 AH received zofenopril (7,5-30 mg/d; mean dose 18,6±8,8 mg/d; n=17) or perindopril (2-8 mg/d; mean dose 4,1±2,1 mg/d; n=23) for 12 weeks. At baseline and in the end of the study, all patients underwent reactive hyperemia test (RHT), to assess flow-dependent vasodilatation of brachial artery, and the measurement of OS parameters (malone dialdehyde, MDA, in low-density lipoproteins, MDALDL) and antioxidant parameters (superoxide dismutase (SOD) and glutathione peroxidase (GPO) activity in erythrocytes).

Results. In both groups, a similar reduction in systolic and diastolic blood pressure levels was observed. In the zofenopril group, a significant elevation in brachial artery diameter increase during RHT, a significant increase in GPO activity, and some reduction in MDALDL levels were observed, which points to antioxidant system (AOS) activation and OS reduction. No similar changes of these parameters were observed in the perindopril group.
Conclusion. In patients with stable CHD and AH, zofenopril, but not perindopril, reduced OS severity and increased AOS system activity, which was associated with improved endothelial-dependent vasodilatation.

Background. For patients with hypertension, effective 24-hour blood pressure (BP) control is vital to ensure protection against the early morning surge in BP and the associated increased risk of cardiovascular events. The aim of this analysis was to assess the 24-hour antihypertensive efficacy of olmesartan medoxomil (20 mg once daily) compared with candesartan cilexetil (8 mg once daily), with particular emphasis on BP control during the early morning period.
Methods. This is an additional analysis of a previously reported randomised, double-blind study in which 635 patients with mainly mild to moderate hypertension were randomised to 8 weeks of treatment with either olmesartan medoxomil 20 mg/day or candesartan cilexetil 8 mg/day. Changes from baseline during the last 4 and 2 hours of ambulatory BP measurement (ABPM) after 1, 2 and 8 weeks of treatment were compared between the two groups. In addition, the proportions of patients who achieved various ABPM goals, including those suggested by the European Society of Hypertension/European Society of Cardiology (ESH/ESC) [<125/80 mm Hg] and the Japanese Society of Hypertension (JSH) [<135/80 mm Hg], over 24 hours, during the daytime and at the last 4 and 2 hours of ABPM measurement were also compared.
Results. After 8 weeks, significantly greater proportions of patients treated with olmesartan medoxomil 20 mg achieved 24-hour and daytime ABPM goals recommended by the guidelines of the ESH/ESC (25,6 % and 18,3 %, respectively) and JSH (37,5 % and 26,6 %, respectively) compared with candesartan cilexetil 8 mg (24-hour ESH/ESC goal 14,9 %, p<0,001; 24-hour JSH goal 26,6 %, p=0,003; daytime ESH/ESC goal 9,6 %, p=0,002; daytime JSH goal 16,4 %, p=0,002). During the last 4 hours of 24-hour ABPM, the proportions of patients who achieved the ESH/ESC and JSH ABPM goals were significantly greater with olmesartan medoxomil (33,3 % and 39,1 %, respectively) than with candesartan cilexetil (22,9 %, p<0,001 and 31,6 %, p=0,047, respectively). Similarly, during the last 2 hours of 24-hour ABPM, the proportions of patients who achieved these BP goals were either significantly greater (JSH) or approached statistical significance (ESH/ESC) with olmesartan medoxomil (26,9 % and 19,9 %, respectively), compared with candesartan cilexetil (19,6 %, p=0,028 and 14,3 %, p=0,061, respectively).
Conclusion. Compared with candesartan cilexetil 8 mg, greater proportions of olmesartan medoxomil-treated patients (20 mg) achieved ESH/ESC and JSH ABPM goals over 24 hours. The superior BP control of olmesartan medoxomil was also reflected in the larger proportions of olmesartan medoxomil-treated patients who achieved the ESH/ESC and JSH ABPM goals during the early morning surge period. This not only demonstrates that olmesartan medoxomil 20 mg provides superior 24-hour BP reduction, but also suggests that olmesartan medoxomil may provide greater protection against the increased risk of cardiovascular events associated with the early morning BP surge period.

Aim. To assess the potential of adding perindopril and indapamide CR (controlled release) to standard therapy, as a method for additional correction of cardiovascular risk factors (RFs) among patients with Stage 1-3 arterial hypertension (AH) of very high risk and coronary heart disease (CHD).
Material and methods. In total, 44 patients (29 men, 15 women; age 45-80 years, mean age 56±10,7 years) with Stage 1-3 AH of very high risk and CHD were examined. At baseline and after 2, 4, and 16 weeks of the treatment, all participants underwent physical examination, office blood pressure (BP) measurement, standard laboratory tests, electrocardiography (ECG), Holter ECG monitoring, 24-hour BP monitoring, echocardiography (EchoCG), and arterial stiffness assessment.
Results. All participants completed the study protocol, with no adverse effects during the treatment phase. In all patients with Stage 1-3 AH, target BP levels and improved 24-hour BP profile were achieved. In CHD patients, a reduction in the incidence of ischemic episodes and their duration was observed. There was a positive dynamics of arterial stiffness parameters.
Conclusion. Perindopril and indapamide CR demonstrated good antihypertensive effectiveness, as well as cardioand vasoprotective activity in patients with very high-risk AH and CHD.

Aim. To assess effectiveness, tolerability, and safety of combined antihypertensive therapy (AHT) with an ACE inhibitor (perindopril) and thiazide-like diuretic (indapamide) in postmenopausal women with arterial hypertension (AH).
Material and methods. This open, one-centre study included 43 postmenopausal women with AH. For 3 months, the patients in the main group (MG; n=22) received indapamide MR (modified release) (1,5 mg/d) and perindopril. The comparison group (CG; n=21) was administered non-MR indapamide (2,5 mg/d) and perindopril. The dynamics of office blood pressure (BP) levels, 24-hour BP monitoring parameters, laboratory parameters, quality of life (QoL), as well as therapy safety and tolerability, was assessed.
Results. In both groups, the treatment was clinically effective, safe, and QoL-improving. Target BP levels were achieved in the majority of the patients: 85,3 % and 72,4 % in the MG and CG, respectively. The combination therapy including indapamide MR provided greater improvement of circadian BP rhythm, larger reduction in both morning BP surge and increased BP variability, as well as target BP achievement in higher proportion of the patients.
Conclusion. In postmenopausal women with AH, combined therapy with perindopril and indapamide MR provided more benefits, compared to the treatment with perindopril and non-MR indapamide.

Aim. To assess the long-term effectiveness and safety of moxonidine (Physiotens®), as antihypertensive treatment in patients with metabolic syndrome (MS), including women with menopausal MS.
Material and methods. The study included 274 patients: 203 women (74 %) and 70 men (26 %). Postmenopausal women comprised a separate study subgroup. At baseline and after 24 weeks of moxonidine treatment, all participants underwent anthropometry and the measurement of systolic and diastolic blood pressure (SBP, DBP), lipid and carbohydrate metabolism parameters.
Results. Moxonidine therapy was associated with a reduction in SBP and DBP levels. A positive dynamics in the levels of fasting glucose, total cholesterol, low and high-density lipoproteins (LDL, HDL), and triglycerides was observed. The changes in these parameters were similar among postmenopausal women and all study participants.
Conclusion. In MS patients, moxonidine improved circadian BP profile, and also demonstrated beneficial effects on carbohydrate and lipid metabolism parameters in women with menopausal MS.

Aim. To study the specific clinical features in patients with coronary heart disease, CHD (stable effort angina, SEA) and chronic obstructive pulmonary disease (COPD), in order to improve early diagnostics of this combined pathology.
Material and methods. The study was a retrospective analysis of 958 medical histories. Co-existing COPD was registered in 251 patients (26,3 %). Therefore, Group I included 251 patients with SEA and COPD (26,3 %), while Group II included 707 SEA patients without COPD (73,7 %).
Results. In Group I, there were more men than women, by 5,7 % (р<0,05). No significant differences in age and angina functional class were observed between Groups I and II. In patients with SEA and COPD, the prevalence of arterial hypertension and myocardial infarction was higher than in Group II (р<0,05). In addition, Group I was characterised by higher prevalence of dyspnoea, palpitation, C-reactive protein elevation, and lipid metabolism disturbances.
Conclusion. Among chronic CHD patients hospitalized to the cardiology unit, co-existing COPD was registered in 26,3 %. The combination with COPD aggravated the clinical course of CHD. The study results support the use of lung function assessment in smoking CHD patients, to diagnose co-existing COPD.

Aim. To investigate the correlation between clinical and morphological characteristics of coronary heart disease (CHD) and high-definition electrocardiography (HD-ECG) parameters.
Material and methods. In total, 85 patients with unstable angina and ST segment depression (ST-UA) underwent HD-ECG during the angina attack, with late ventricular potential (LVP) analysis. One-year survival data were also analysed. Post-mortem histological examination of cardiac tissue was performed in 6 patients with ST-UA.
Results. The important morphologic features of ST-UA included cardiomyocyte (CMC) dystrophy, due to acute and chronic myocardial ischemia, and acute injury in the cardiac conduction areas. LVPs were registered in 27 % of the ST-UA patients, mostly among people with transient myocardial ischemia (69,57 %). In patients who previ-ously underwent myocardial infarction, LVP prevalence was lower (28,57 %). At the early stages of hospitalization, LVP were registered in 14 patients (60,87 %), while pharmacotherapy and clinical course stabilization were associated with decreased LVP prevalence (21,74 %). The study results suggest that in patients with acute coronary syndrome, LVP registration predicts not an adverse outcome, but a better prognosis.
Conclusion. ST-UA is characterised by typical changes of CMC and myocardial stroma in posterior septal area, which result in metabolic, energetic, and electrical myocardial instability. LVPs could be used as a marker of functional (ischemic) myocardial heterogeneity in patients with ST-UA. LVP registration could be associated with a better prognosis in this clinical group.

Aim. To study the prevalence and features of cardiac arrhythmias (CA) in postmenopausal women, as well as to investigate the CA association with carbohydrate metabolism disturbances.
Material and methods. This cross-sectional study included 210 postmenopausal women (median age 57 years; age range 54,0-61,0 years). Median menopause duration was 7,9 years (3,0-12,0 years). The examination included Holter ECG monitoring, clinical evaluation, measurement of blood pressure, body mass index, waist and hips circumference the levels of glucose, insulin, lipids, Mg, Ca, uric acid, brain natriuretic peptide, and thyrotropin.
Results. CA were registered in 99,5% of the participants, including ischemia (17,1%), supraventricular extrasystolia (88,1%), ventricular extrasystolia (VE; 53,8%), high-grade VE (HGVE; 21,5%), SV tachycardia paroxysms (19%), atrial fibrillation (2,3%), V tachycardia paroxysms (1,4%), asystolic periods (0,9%), sino-atrial and atrioventricular blocks (9,1%), bundle branch blocks (3,3%), sinus tachycardia (50,9%), and sinus bradycardia (23,8%). In postmenopausal women with disturbed carbohydrate metabolism, CA prevalence was higher for VE (1,9 times), HGVE (2,4 times), and polytopic VE (2,5 times). VE prevalence was higher in women with abdominal obesity and chronic pancreatitis. In addition, CA odds were higher in postmenopausal women with coronary heart disease (CHD; 2,75 times), chronic heart failure (CHF; 2,6 times), and acute cardiovascular events such as myocardial infarction or stroke (3,3 times).
Conclusion. CA and ischemia prevalence was high in postmenopausal women, 21,5% of whom had high potential risk of sudden death. Increased odds of ventricular arrhythmias among postmenopausal women were associated with carbohydrate metabolism disturbances, CHD, CHF.

Aim. To assess hemostasis effects of various glucose-lowering medications (GLM), such as sulphanilamides, biguanides, and insulin, in regard to micro- and microangiopathy progression over 5 years in patients with Type 2 diabetes mellitus (DM-2).
Material and methods. The study included 72 patients with DM-2 (47 women, 25 men; median age 54,0 years (49,0-59,0 years); mean DM-2 duration 4,0 years (0,5-8,0 years)), receiving one of the following GLMs for 5 years: glibenclamide, gliclazide, metformin, insulin, or the combination of glibenclamide and metformin.
Results. Various GLMs had different effects on platelet activity. In the gliclazide group, aggregant activity was decreased, compared to the glibenclamide and insulin groups. In the metformin group, aggregant activity and platelet disaggregation were similar to that in the gliclazide group. The microangiopathy progression over 5 years was related to GLM therapy, being minimal in the DM-2 patients receiving metformin, and maximal among participants administered glibenclamide. The microangiopathy progression was minimal in the metformin and gliclazide groups, and maximal — in the glibenclamide group.
Conclusion. Carbohydrate and lipid metabolism compensation is not the only condition of angiopathy prevention. The latter should be based on the complex intervention, aimed at the complete metabolic compensation and hemostasis balance. The need for taking pleiotropic activity of specific agents into consideration when choosing GLM therapy is emphasized by protective effects of metformin (micro- and microangiopathy prevention) and gliclazide (microangiopathy prevention), but not glibenclamide.

The paper presents modern views on cardiovascular aspects of menopause and metabolic therapy of menopausal disturbances with meldonium (Mildronate®). The role of estrogen deficiency in climacteric disturbance development, key pathogenetic mechanisms of menopausal metabolic syndrome (MS), and relevant features of arterial hypertension and endothelial dysfunction development are discussed. The data on Mildronate® clinical use for cardiovascular prevention are summarized. The wide prevalence and multiple clinical manifestations of menopausal disturbances point to the need for their complex therapy. Mildronate® therapy is a new approach for systemic correction of metabolic disturbances in women with climacteric symptoms and menopausal MS.

The authors discuss the action mechanisms of β-adrenoblockers (β-AB), as well as pharmacokinetics, pharmacodynamics, and drug interaction of a highly selective β-AB bisoprolol. The paper presents the data on bisoprolol effectiveness and safety in arterial hypertension, coronary heart disease, chronic heart failure, and their combination with other diseases.

Aim. Most calcium antagonists do not seem to reduce microalbuminuria or proteinuria. We have tried to assess the antiproteinuric effect of a calcium channel blocker, lercanidipine, in patients previously treated with ACE inhibitors or angiotensin receptor blockers.
Design and methods. The study included 68 proteinuric (>500 mg/day) patients (age 63,1±12,9 years, 69,1 % males and 30,9 % females). All patients were receiving ACE inhibitors (51,4 %) or angiotensin II receptor blockers (48,6 %) therapy but had higher blood pressure (BP) than recommended for proteinuric patients (<130/80 mm Hg). Patients were clinically evaluated one, three, and six months after starting treatment with lercanidipine (20 mg/day). Samples for urine and blood examination were taken during the examination. When needed, a third drug was added to treatment. Creatinine clearance was measured using 24 h urine collection.
Results. BP significantly decreased from 152±15/86±11 mm Hg to 135±12/77±10 mm Hg at six months of follow-up (p<0,001). After six months of treatment, the percentage of normalized patients (BP <130/80 mm Hg) was 42,5 %, and the proportion of patients whose BP was below 140/90 mm Hg was 58,8 %. Plasmatic creatinine did not change nor did creatinine clearance. Plasmatic cholesterol also decreased from 210±48 to 192±34 mg/dL (p<0,001), as did plasma triglycerides (from 151±77 to 134±72 mg/dL, p=0,022). Basal proteinuria was 1,63±1,34 g/day; it was significantly (p<0,001) reduced by 23 % at the first month, 37 % at three months, and 33 % at the last visit.

Conclusion. Lercanidipine at 20 mg dose, associated with renin-angiotensin axis-blocking drugs, showed a high antihypertensive and antiproteinuric effect. This antiproteinuric effect seems to be dose-dependent as compared with previous reports and proportionally higher than blood pressure reduction.

The paper summarizes the specific features of post-marketing studies, which are performed after the medication registration, in the settings close to the real-world clinical practice. In particular, the authors discuss the design and results of the Russian post-marketing study of nifedipine CR (controlled release) — ORIENTIR Study. The aim of the study was to assess antihypertensive effectiveness and tolerability of nifedipine CR in patients with arterial hypertension (AH).
Results. The study included 38 doctors from 24 clinical centres in 16 Russian cities, as well as 3179 patients with AH. Mean blood pressure (BP) reduction reached 22,9±6,75/16,56±8,74 mm Hg. Target BP levels were achieved in 94,9 % of AH patients without diabetes mellitus (DM), and in 72,1 % patients with a combination of AH and DM. At the last visit, 98 % of the participants continued taking the study medication. Adverse effects were registered in 1,5 % of the participants. Doctor-assessed effectiveness, tolerability, and therapy compliance for nifedipine CR were “excellent” or “good” in 95,8 %, 96,4 %, and 97,7 % of the patients, respectively.
Conclusion. The results of this study are consistent with the data from other post-marketing studies of nifedipine CR, confirming its antihypertensive effectiveness and good tolerability.

β-blockers have played a key role in the management of hypertension-related cardiovascular disease for decades, and continue to be recommended as a mainstay of therapy in national guidelines statements. Recent data have shown less optimal reductions in total mortality, CVD mortality, and CVD events with β-blockers compared with renin-angiotensin system-blocking agents or calcium channel blockers. The β-blocker class, however, spans a wide range of agents, and the growing concern about the risk-benefit profile of β-blockers should not be generalized to later-generation vasodilating β-blockers such as carvedilol and nebivolol. A growing database from hypertension studies confirms the clinical efficacy and safety of vasodilating β-blockers, and outcome studies indicate that these agents can play an important role in global CVD reduction in patients with hypertensive or ischemic heart failure.

HMG-CoA inhibitors have been widely used in primary and secondary prevention of atherosclerosis for more than 30 years. The evidence base for statins includes dozens of randomized clinical trials (RCT), involving hundreds of thousands patients. According to the results of the latest meta-analyses, reducing low-density lipoprotein cholesterol (LDL-CH) level by 1 mmol/l in statin-treated patients could decrease cardiovascular risk by 0,8 %. Atorvastatin (Liprimar®) is a modern synthetic statin, which has been thoroughly studied in several RCTs over the last 15 years. These trials demonstrated its effectiveness and tolerability in patients with chronic coronary heart disease, acute coronary syndrome (ACS), Type 2 diabetes mellitus, and arterial hypertension. In the studies comparing atorvastatin (10-80 mg/d) to other statins, baseline LDL-CH levels were reduced by 53 % in atorvastatintreated patients. Atorvastatin therapy was also well tolerated. Compared to placebo, atorvastatin therapy in the dose of 10 and 80 mg/d was associated with the incidence of hepatic transaminase elevation of 0,1 % and 0,6 %, respectively. This evidence base (in particular, the results of the trials on 80 mg/d atorvastatin therapy in ACS patients) has been a cornerstone of modern clinical guidelines, recommending target LDL-CH levels of 2 mmol/l. Currently, atorvastatin is the most widely prescribed statin in the majority of both developed and developing countries. Increasing initial dose and prescribing high-dose atorvastatin therapy (40-80 mg/d) could facilitate an improvement in treatment quality and a reduction in high levels of cardiovascular mortality inRussia.

Familial hypercholesterolemia (FHCH) is characterised by early atherosclerosis development and its fast progression. The prevalence of FHCH inRussiahas been increasing, therefore, it is important to evaluate the potential of various methods for atherosclerosis diagnostics. Arterial ultrasound is an informative, accessible, and safe method for evaluating atherosclerotic vascular changes. The modern ultrasound methods allow describing vascular wall status in detail, including qualitative and quantitative characteristics of its structure and function. At the same time, most ultrasound characteristics of arterial wall are used in research settings or are under development, and not implemented into clinical practice. The most promising parameters, applicable for clinical use in FHCH patients, simultaneously describe atherosclerosis severity and its localization, such as total plaque height, ankle-brachial index, and plaque number.

The adverse consequences of estrogen deficiency in postmenopause include cardiovascular disease (CVD), which affects not only women’s quality of life, but also their life expectancy. Before premenopause, women have significantly lower risk of arterial hypertension than men of the same age. However, in people aged over 50, AH is more prevalent among women. Currently, most experts regard hormone replacement therapy (HRT) in peri- and postmenopausal women as pathogenetic, since it facilitates the adaptation of the female organism to the new metabolic state, with reduced ovarian function. Drospirenone, as a part of HRT, reduces CVD risk in postmenopausal women with climacteric disturbances.