To assess the prevalence of renal disorders and renal dysfunction in patients with Stage I-III primary arterial hypertension, AH (n=1846; 837 men and 1009 women aged from 16 to 72 years), a clinical, biochemical, and instrumental examination was performed. It included urine assay, Nechiporenko and Zimnitsky urine tests, assessment of glomerular filtration rate (GFR) by endogenous creatinine clearance, measurement of microalbuminuria, blood levels of urea, creatinine and uric acid, renal and pelvic ultrasound, colour Doppler ultrasound of renal vessels, dynamic renal scintigraphy, static renal scintigraphy, excretory urography, and, if necessary, X-ray contrast angiography of renal vessels. Even in the patients from the youngest age group (16-39 years), there were signs of structural renal disorders and renal dysfunction (over 50% of the participants), congenital and acquired renal vessel or abdominal aorta pathology (20%), and disturbed nitrogen excretion rate (33%). In the patients aged 40-72 years, the prevalence of these disturbances was even higher. The nature of renal, uro-renal, and renovascular pathology was different across age groups of AH patients. In younger participants, congenital pathology and nephroptosis were much more prevalent than in patients aged over 40 years. On the other hand, older patients were characterised by high prevalence of pyelonephritis, renal cysts, hydronephrosis, abdominal and thoracic aorta deformation, atherosclerotic stenosis of additional renal arteries, nephroptosis (without co-existing obesity), nephrosclerosis and reduction in functioning renal parenchyma.

To assess prognostic value of chronic heart failure (CHF) severity markers in patients aged over 74 years, and to optimise the risk stratification accordingly. This prospective study included 104 CHF patients aged 75 years or older, who were followed up for 2,5 years after hospital discharge. The effects of 150 clinical, instrumental, and laboratory parameters on survival were investigated. The survival over 2,5 years reached 30%. The main risk factors (RFs) of adverse outcome included age and levels of brain natriuretic peptide (BNUP). A prognostic model – BNUP-agE surVivAl model (NEVA-75) – was created. The main RFs of adverse outcome over 2,5 years of the follow-up were age and plasma BNUP levels. The model NEVA-75 could be used for assessing the prognosis and selecting the optimal therapeutic strategy in CHF patients aged over 74 years, who are discharged from hospital after CHF clinical stabilisation and are followed at a non-specialised polyclinic.

In 72 patients (32 athletes at recovering stage of training and 35 patients with patello-femoral arthrosis), femoral quadriceps muscle was stimulated (Kotz current), to assess the effects on electrocardiographic parameters of vegetative disbalance. After 10 electro-stimulation procedures, there was a significant decrease in the number of supraventricular and ventricular extrasystoles, a reduction in QT interval dispersion (within the range of baseline and dynamic normal values), and an increase in circadian index. No significant change in time and spectral parameters of heart rate variability was observed; however, there was a tendency towards a greater reduction in vegetative disbalance among athletes.

Aim: To study vascular stiffness and elasticity, microcirculation (MC) parameters, and mildronate effects in patients with arterial hypertension (AH). Material and methods. The study included 99 patients with Stage I-II AH (mean age 63,2+2,6 years). Pulse wave velocity was assessed by volume sphygmography (Poly-Spectre system, Neuro-Soft). MC parameters were assessed with a computerised Doppler ultrasound device (Minimax-Doppler-K). After a wash-out period, the participants were randomised into 2 groups. Group I received enalapril (Renipril, Pharmstandard; 10 mg/d) and mildronate (0,25 g twice a day). Group II was administered Renipril (10 mg/d) only. Results. After 12 weeks of the treatment, blood pressure (BP) levels were significantly reduced. In Group I, a significant increase in mean linear blood flow velocity after occlusion test, as well as in volume blood flow velocity, was observed, compared to the baseline. In 66% of the patients, blood flow velocity after occlusion test was increased by at least 20%. Conclusion. Adding mildronate to the standard antihypertensive therapy with ACE inhibitors facilitates faster normalisation of vascular function.

Lercanidipine, a calcium channel antagonist, is currently employed in the treatment of essential hypertension and angina pectoris. The purpose of this study was to elucidate the anti-proliferative effect of lercanidipine and to investigate the molecular role of this agent. Both in vitro studies and in a balloon injury rat carotid artery model were employed to study the effect of lercanidipine on smooth muscle cell proliferation. Lercanidipine-inhibited rat vascular smooth muscle cell (VSMC) proliferation and migration in a dose-dependent manner following stimulation of VSMC cultures with 10% fetal bovine serum (FBS) and 20 ng/ml platelet-derived growth factor (PDGF)-BB. FBS- and PDGF-BB-stimulated intracellular Ras, MEK1/2, ERK1/2, proliferative cell nuclear antigen (PCNA), and Akt activations were significantly inhibited by lercanidipine; however, lercanidipine did not affect FBS- and PDGF-BB-induced STAT3 phosphorylation. Lercanidipine also inhibited PDGF-receptor b chain phosphorylation and reactive oxygen species (ROS) production induced by PDGF-BB. Lercanidipine blocked the FBS-inducible progression through the G0/G1 to the S-phase of the cell cycle in synchronized cells. In vivo, 14 days after balloon injury, treatment with 3 and 10 mg/kg lercanidipine resulted in significant inhibition of the neointima/media ratio. Suppression of neointima formation by lercanidipine was dependent on its influence on ERK1/2 phosphorylation. These results demonstrate that lercanidipine can suppress the proliferation of VSMCs via inhibiting cellular ROS, Ras-MEK1/2- ERK1/2, and PI3K-Akt pathways, and suggesting that it may have therapeutic relevance in the prevention of human restenosis.

Treatment compliance and quality of life (QoL) in long-term monotherapy with various beta-adrenoblockers, BAB (propranolol, metoprolol, nadolol, atenolol, bisoprolol, and nebivolol) were compared in 130 men with arterial hypertension (AH), aged 30-59 years. Treatment compliance was assessed using the Morisky-Green test, and QoL – the General Well Being Questionnaire (GWBQ). Together with good antihypertensive effectiveness, tolerability, and low incidence of adverse effects, nebivolol demonstrated the best treatment compliance and QoL improvement, compared to the other BAB. The lowest treatment compliance and minimal QoL improvement were observed in patients receiving propranolol. Therefore, in long-term BAB monotherapy among AH patients, nebivolol is a medication of choice, due to high treatment compliance and positive effects on QoL (in particular, on sexual function in men).

The study investigated effectiveness and safety of a cytoprotector mexicor in patients with chronic cor pulmonale (CCP). All participants (n=56; age 38-80 years) were divided into four groups. Group I (n=16) received a standard pulmonary therapy, while Group II (n=20) also received mexicor (300 mg/d intravenously, for 10 days), Group III (n=10) received a standard therapy plus verapamil (80-240 mg/d for 10 days), and Group IV (n=11) was administered intravenous mexicor (300 mg/d) plus verapamil (80-240 mg/d) for 10 days. All participants underwent daily measurement of blood pressure and heart rate, 6-minute walk test, spirography, Holter ECG monitoring, echocardiography, and colour Doppler ultrasound of common and internal carotid arteries. Adding mexicor to the standard therapy of CCP patients increased treatment effectiveness for the leading pathology, as well as for co-morbidities (heart failure, cardiac arrhythmias). Additionally, in these patients, mexicor improved effectiveness and safety of verapamil treatment, increasing its antihypertensive and antiarrythmic activity and reducing its negative effects on intracardiac hemodynamics.

The study aimed to assess the effectiveness and safety of a fixed-dose combination of an ACE inhibitor (losartan) and a diuretic (hydrochlorothiazide) in patients with arterial hypertension (AH) and high or very high cardiovascular risk. The study included 30 patients with Stage I-III AH (13 men and 17 women; mean age 51,9±1,9 years). For 12 weeks, the participants were administered a combination of losartan (50 mg) and hydrochlorothiazide (12,5 mg; once a day, in the morning). Echocardiography and 24-hour blood pressure monitoring (BPM) were performed. In 2 and 4 weeks, a reduction in office systolic BP (SBP) and office diastolic BP (DBP), respectively, was observed. In 12 weeks, BP reduction was even more pronounced, with a reduction in 24-hour SBP (from 141,9±1,9 to 128,6±0,8 mm Hg; p<0,001), daytime SBP (from 146,8±2,6 to 135,8±1,0 mm Hg; p><0,01), and nighttime SBP (from 131,5±1,9 to 118,8±1,9 mm Hg; p><0,001). A reduction was also observed for 24-hour DBP (from 91,7±1,8 to 78,7±1,6 mm Hg; p><0,05), daytime DBP (from 94,3±1,3 to 85,0±1,2 mm Hg; p><0,05), and nighttime DBP (from 83,5±2,0 to 71,2±1,7 mm Hg; p><0,01). Circadian BP variability, time BP index, and morning BP surge were also decreased (from 37,6±2,0 to 23,9±1,9 mm Hg; p><0,001). After 12 weeks of the combined therapy with losartan and hydrochlorothiazide, circadian BP profile was normalized in most participants. There was a reduction in the percentage of the patients with myocardial hypertrophy (from 50% to 30%; p><0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p><0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,001), daytime SBP (from 146,8±2,6 to 135,8±1,0 mm Hg; p<0,01), and nighttime SBP (from 131,5±1,9 to 118,8±1,9 mm Hg; p><0,001). A reduction was also observed for 24-hour DBP (from 91,7±1,8 to 78,7±1,6 mm Hg; p><0,05), daytime DBP (from 94,3±1,3 to 85,0±1,2 mm Hg; p><0,05), and nighttime DBP (from 83,5±2,0 to 71,2±1,7 mm Hg; p><0,01). Circadian BP variability, time BP index, and morning BP surge were also decreased (from 37,6±2,0 to 23,9±1,9 mm Hg; p><0,001). After 12 weeks of the combined therapy with losartan and hydrochlorothiazide, circadian BP profile was normalized in most participants. There was a reduction in the percentage of the patients with myocardial hypertrophy (from 50% to 30%; p><0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p><0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,01), and nighttime SBP (from 131,5±1,9 to 118,8±1,9 mm Hg; p<0,001). A reduction was also observed for 24-hour DBP (from 91,7±1,8 to 78,7±1,6 mm Hg; p><0,05), daytime DBP (from 94,3±1,3 to 85,0±1,2 mm Hg; p><0,05), and nighttime DBP (from 83,5±2,0 to 71,2±1,7 mm Hg; p><0,01). Circadian BP variability, time BP index, and morning BP surge were also decreased (from 37,6±2,0 to 23,9±1,9 mm Hg; p><0,001). After 12 weeks of the combined therapy with losartan and hydrochlorothiazide, circadian BP profile was normalized in most participants. There was a reduction in the percentage of the patients with myocardial hypertrophy (from 50% to 30%; p><0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p><0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,001). A reduction was also observed for 24-hour DBP (from 91,7±1,8 to 78,7±1,6 mm Hg; p<0,05), daytime DBP (from 94,3±1,3 to 85,0±1,2 mm Hg; p><0,05), and nighttime DBP (from 83,5±2,0 to 71,2±1,7 mm Hg; p><0,01). Circadian BP variability, time BP index, and morning BP surge were also decreased (from 37,6±2,0 to 23,9±1,9 mm Hg; p><0,001). After 12 weeks of the combined therapy with losartan and hydrochlorothiazide, circadian BP profile was normalized in most participants. There was a reduction in the percentage of the patients with myocardial hypertrophy (from 50% to 30%; p><0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p><0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,05), daytime DBP (from 94,3±1,3 to 85,0±1,2 mm Hg; p<0,05), and nighttime DBP (from 83,5±2,0 to 71,2±1,7 mm Hg; p><0,01). Circadian BP variability, time BP index, and morning BP surge were also decreased (from 37,6±2,0 to 23,9±1,9 mm Hg; p><0,001). After 12 weeks of the combined therapy with losartan and hydrochlorothiazide, circadian BP profile was normalized in most participants. There was a reduction in the percentage of the patients with myocardial hypertrophy (from 50% to 30%; p><0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p><0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,05), and nighttime DBP (from 83,5±2,0 to 71,2±1,7 mm Hg; p<0,01). Circadian BP variability, time BP index, and morning BP surge were also decreased (from 37,6±2,0 to 23,9±1,9 mm Hg; p><0,001). After 12 weeks of the combined therapy with losartan and hydrochlorothiazide, circadian BP profile was normalized in most participants. There was a reduction in the percentage of the patients with myocardial hypertrophy (from 50% to 30%; p><0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p><0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,01). Circadian BP variability, time BP index, and morning BP surge were also decreased (from 37,6±2,0 to 23,9±1,9 mm Hg; p<0,001). After 12 weeks of the combined therapy with losartan and hydrochlorothiazide, circadian BP profile was normalized in most participants. There was a reduction in the percentage of the patients with myocardial hypertrophy (from 50% to 30%; p><0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p><0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,001). After 12 weeks of the combined therapy with losartan and hydrochlorothiazide, circadian BP profile was normalized in most participants. There was a reduction in the percentage of the patients with myocardial hypertrophy (from 50% to 30%; p<0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p><0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,01) or left ventricular diastolic dysfunction (from 43,3% to 30%; p<0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.>< 0,05). Therefore, a fixed-dose combination of losartan and hydrochlorothiazide (50 mg + 12,5 mg) demonstrated good antihypertensive and cardioprotective effectiveness.

 

The justification of this study is the need for new methods (potentially, immuno-correcting therapy) of increasing nitrate effectiveness in complex angina treatment, reducing nitrate adverse effect incidence, and minimizing nitrate contraindications. It was suggested that angina-related endothelial dysfunction is related to impaired metabolism of NO, as one of the principal immune mediators. Nitrate therapy, acting via NO release, is aimed at endothelial function improvement. The study included 580 patients, in whom immune and cardiovascular status was assessed, together with nitrate tolerability and adverse effects. In 64% of the angina patients, clinical manifestations of immune insufficiency were observed, with monocyte-macrophage dysfunction as the major symptom. According to the results of ultrasound assessment of vaso-regulating endothelial function, more advanced endothelial dysfunction was registered in patients with reduced nitrate effectiveness. Immuno-correcting therapy was administered to 33 patients. After the treatment course, improved nitrate effectiveness was observed in all 33 individuals, in contrast to the control group (n=33).

The VIOS (Vascular Improvement with Olmesartan medoxomil Study) study is a randomized, parallel study to determine the relative effects of suppressing the renin-angiotensin system (RAS) with the angiotensin receptor antagonist olmesartan medoxomil versus suppressing sympathetic drive with the beta-adrenoceptor antagonist atenolol on remodeling of the subcutaneous small resistance vessel. Remodeling of small resistance vessels may be the earliest pathologic finding associated with hypertension. It may predate the onset of clinically apparent hypertension. Methods: In this study, 100 patients with stage I hypertension are characterized at baseline before being treated for 1 year to obtain a goal BP of less than 140/90 mm Hg, as defined by Joint National Committee (JNC)-7. Resistance vessel remodeling is determined using the gluteal fat biopsy technique in the hypertensive patients and a group of normotensive healthy volunteers. Additionally, efforts will be made to define whether noninvasive hemodynamic parameters, retinal vessel measurement changes, or biologic markers may predict and track the underlying vascular morphologic and physiologic changes induced by either regimen during the 12-month treatment period. Results: The primary endpoint will be the degree of vascular remodeling as obtained from percutaneous biopsy of gluteal subcutaneous resistance vessels in each of two treatment arms compared with the healthy volunteers. The design of the study and the pertinent baseline characteristics of these patients with uncomplicated essential hypertension are presented. Conclusion: The suppression of the RAS by the blockade of angiotensin II type 1 (AT (1)) receptors may demonstrate remodeling effects on the ubiquitous small resistance vessels similar to that seen in the myocardium and renal glomeruli, thus affording more complete end-organ protection.

Pharmaceutical treatment of coronary heart disease (CHD) should be able to solve the key task – reduction of myocardial oxygen demand, or improvement of oxygen supply via vasodilatation. Currently, metabolic therapy of CHD is of particular interest, since it can reduce myocardial oxygen demand and substantially increase the effectiveness of oxygen utilisation in myocardial ischemia settings. The study was aimed at investigating the effectiveness of pre-hospital therapy with a cytoprotector mexicor, with subsequent intracoronary mexicor administration in the first hours of acute myocardial infarction (AMI). In total, 112 AMI patients, hospitalised no later than 4 hours after AMI onset, were included in the study. Successful angioplasty of infarct-related coronary artery (IRCA) and intracoronary administration of a cardio-protector mexicor were associated with a substantial improvement in clinical effectiveness of coronary blood flow normalisation and prevention of myocardial reperfusion injury.

The review discusses various reperfusion strategies in patients with acute myocardial infarction with ST segment elevation (STEMI), based on the evidence from international clinical trials. The modern views on real-world invasive and conservative strategies of STEMI management in European countries are presented. The key factor for patients’ survival is the timing, not the method of reperfusion. The strategy of primary percutaneous coronary intervention (PCI) may fail to reduce mortality, if the door-to-balloon time is over 60 minutes, compared to immediate thrombolytic therapy (TLT). PCI is more effective than TLT only if the time difference (door-to-balloon vs. door-to-needle) is under 2 hours. The choice of reperfusion method should be based on the patient’s risk level. Primary PCI has limitations, since this method is not widely accessible, requires specially trained staff and special equipment. Early TLT is an acceptable standard method in STEMI management, highly applicable for the Russian clinical practice. However, in patients already treated with TLT, pharmaco-invasive strategy could be the method of choice. The description of thrombolytic drugs is focussed on the agents of II and III generations – alteplase (Actilyse®) and tenecteplase (Metalyse®), respectively. Before the introduction of Metalyse®, continuous infusion of Actilyse® was regarded as the gold standard of pharmacological reperfusion therapy. Recently, it has been shown that single-bolus Metalyse® therapy is as effective as continuous Actilyse® infusion, but with better safety profile. Pre-hospital TLT with single-bolus Metalyse® therapy (5-10 seconds) provides a unique clinical opportunity for early STEMI management and maximal myocardial rescue.

The paper reviews the currently available evidence on cardiac arrhythmia treatment, in particular, on allapinine therapy. The original data on allapinine effectiveness, obtained in 24 patients with different variants of cardiac arrhythmias, are presented.