Aim. To assess the effects of combined lisinopril and betahistine dihydrochloride (Betaserc®) therapy on quality of life (QoL) and neurological status in patients with stable, mild to moderate arterial hypertension (AH) and vertigo. Material and methods. This randomized, cross-over, placebo-controlled study included 67 patients with stable, mild to moderate AH, Stage I-II, Risk 2-3 (20% of males, 80% of females). After two-week medication-free period, all participants were randomized into lisinopril or lisinopril plus Betaserc® groups. After one-month therapy and two-week washout period, patients moved to another group. Twenty-four-hour blood pressure monitoring (BPM), and QoL assessment were performed before and after each therapy course, neurological status was assessed after first course only Results. Both therapy schemes had similar antihypertensive effects on 24-hour BPM main parameters. Lisinopril monotherapy and combined treatment were both associated with neurological status improvement. But only in patients taking lisinopril and Betaserc®, the results of most remote point test increased significantly. During lisinopril therapy, QoL parameters improved for scales on physical health self-esteem, workability, and positive psychological health self-esteem. Combined therapy was associated with improvement in scales on physical health self-esteem, workability, positive and negative psychological health self-esteem, social contact openness. Conclusion. Lisinopril monotherapy and combined Betaserc® and lisinopril therapy had similar antihypertensive effect. Сombined therapy improved QoL better than lisinopril monotherapy. In Stable AH patients, vertigo was typically caused by chronic bilateral pathology of vestibular system.

Aim. To investigate vascular wall stiffness in young patients, for examining early vascular remodeling role in arterial hypertension (AH) pathogenesis in young age. Material and methods. The study included 291 individuals: 169 normotensives and 122 AH patients aged 16-34 years. All participants underwent volume sphygmography (VaSera-1000, «Fukuda Denshi», Japan), blood pressure (BP) measurement in upper and lower extremity basins, elastic and muscular vessel elasticity assessment. Results. In young age, high elastic vessel stiffness was observed in 13.6% of normotensives, and in 50% of AH patients. For muscular vessels, this parameter was 11.2% and 35%, respectively. In systolo-diastolic AH, muscular vessel stiffness increased, in isolated systolic AH (ISAH) – elastic or elastic and muscular vessel stiffness is increased. About 50% of young ISAH individuals had increased BP on upper extremities only – «pseudo-hypertension». Conclusion. Early vascular remodeling plays an important role in AH pathogenesis among young people.

Aim. To study metoprolol retard antihypertensive effects and its influence on circadian blood pressure (BP) profile, according to BP circadian rhythm type. Material and methods. The study included 20 patients with Stage I-II essential arterial hypertension (EAH). At baseline and after one-month metoprolol retard therapy (100 mg/d), 24-hour BP monitoring (BPM) was performed. According to BPM results, all patients were divided into two groups: Group D («dippers»), and Group ND («non-dippers»). Both groups were comparable by mean age, EAH duration, and BP levels. Results. By the end of the study, BP normalized in 45% (n=5) of Group D participants, and in 78% (n=7) of Group ND subjects. In both groups, mean 24-hour BP, daytime and nighttime BP, BP load, and BP variability decreased. BP decrease in Group ND was significantly greater than in Group D. The difference was statistically significant for mean 24-hour BP, daytime and nighttime systolic BP. Metoprolol retard did not affect circadian index (CI) and proportion of different circadian rhythm types. Nevertheless, during the therapy, «night-peakers» (CI<0) and «over-dippers» (CI>20%) were absent, «non-dippers» were rare, and, as a result, «dippers» number increased. Metoprolol retard (100 mg/d) tolerability was satisfactory in both groups. Аdverse effects – sleepiness, headache, nose stuffiness – did not result in medication withdrawal. Conclusion. Metoprolol had especially high antihypertensive effectiveness in patients with inadequate nighttime BP decrease.

Aim. To assess blood pressure (BP) increase type and circadian BP profile in young hypertensive men aged under 35 years. To describe the association between renal function and 24-hour BP monitoring (BPM) parameters. Material and methods. Twenty-four-hour BPM was performed in 58 patients by «SpaceLabs»device (USA), during 24 hours, with 15-minute intervals in daytime (7 AM - 11 PM), and 30-minute intervals in nighttime (11 PM - 7 AM). Dynamic angionephroscintigraphy with DTPA 99mTc was performed in all participants. Most young patients had Stage I arterial hypertension (AH) (n=51; 43%), or Stage II AH (n=49; 42%). Stage III AH was diagnosed in 18 individuals (15%). Results. Transitory AH was diagnosed by temporal index (TI) in 36 patients (72%). Stable AH with AH TI>50% was observed in 14 participants (28%). Glomerular hyperfiltration was more manifested in stable AH, comparing to transitory AH: 132.0±33.5 ml/min vs 165.57±38.5 ml/min (р=0.04). Significant difference in mean glomerular filtration rates (GFR) was observed in patients with isolated inadequate systolic BP (SBP) decrease, or simultaneous inadequate SBP and diastolic BP (DBP) decrease. In patients with disturbed SBP rhythm, hyperfiltration was observed. Circadian BP profile disturbances were associated with lower mean GFR. Conclusion. In stable AH, hyperfiltration is significantly more pronounced, that is a symptom of kidney pathology as target organ damage. Twenty-four-hour BPM helped to identify a substantial group of patients non-dippers among young males: in 60% of participants, for SBP, in 24% - for SBP and DBP. Circadian BP rhythm disturbances resulted in hyperfiltration development, and inadequate DBP decrease – in reduced GFR.

Aim. To study risk factor (RF) structure and relative prevalence of pathological alterations (RPPA) in arterial hypertension (AH) patients from various age groups. Material and methods. Main group included 70 AH patients, control group – 47 individuals with normal blood pressure (BP). Mean age was 55.2±13.67 years and 53.7±13.45, respectively. In all participants, anamnestic, hemodynamic, anthropometric, and biochemical parameters were assessed. Both groups were divided into three age intervals: <35 years; 35-55 years; >55 years. At first, the parameters assessed were compared in each age interval. Then RPPA of these parameters was assessed in main and control groups. Results. Under age of 35, AH development was significantly influenced by family predisposition (FP) and abdominal obesity (AO); in 35-55 years, it was influenced by FP, AO and high level of total cholesterol (TCH); over 55 years, it was influenced by AO and high TCH level. All anthropometric, morphological, functional, and biochemical parameters studied had greater RPPA in main group than in control group, in patients under 35; in 35-55 year-olds, the tendency was similar, with insulin resistance index as an exception; after 55 years, the exceptions were pulse Conclusion. Among traditional cardiovascular event RF, only AO was a universal AH development RF for all age groups. At the same time, the study results should be regarded as preliminary.

Aim. To assess microcirculation (MC) dynamics during rosuvastatin therapy in patients with dyslipidemia (DL) and mild to moderate arterial hypertension (AH). Material and methods. The study included 25 patients with total cholesterol (TCH) level >5,0 mmol/l, low-density lipoprotein CH (LDL-CH) level > 3,0 mmol/l, systolic blood pressure (SBP) 140-179 mm Hg, and diastolic BP (DBP) 90-109 mm Hg. For 12 weeks, all participants received rosuvastatin, in constant dose of 10 mg/d. MC was assessed by laser Doppler flowmetry. Results. Rosuvastatin beneficially influenced MC, in various pathological MC types – spastic and hyperemic, according to main MC parameters – MC and capillary blood flow reserve. Regulatory mechanisms’ changes (myogenic amplitude increase) pointed to a decrease in peripheral vascular resistance. Another positive vascular effect of rosuvastatin manifested in significant SBP and DBP reduction, by 8 and 6 mm Hg, respectively. Rosuvastain also demonstrated a substantial lipid-lowering effect. Conclusion. A new statin, rosuvastatin, demonstrated not only substantial lipid-lowering effect, but also beneficial vascular action: it improved MC and reduced BP in patients with DL and mild to moderate AH.

Aim. To compare effectiveness and tolerability of first- and second-generation dihydropyridine calcium antagonists (CA): instant-release nifedipine (Nifedipine IR) and slow-release nifedipine (Nifecard XL), in patients with arterial hypertension (AH). Material and methods. This 8-week randomized, open, comparative trail included 73 men and 74 women with Stage I-II AH; mean age was 53.4±12.9 and 55.3±9.3 years, AH duration - 13.8±9.3 and 16.3±9.7 years, respectively. All participants received either Nifecard XL (initial dose 30 mg/d, 1 tablet), or Nifedipine IR (30 mg/d, 3 tablets). Antihypertensive effect was assessed by office blood pressure (BP) measurement and 24-hour BP monitoring (BMP). Results. After 8 weeks of treatment, systolic and diastolic BP (SBP, DBP) reduced significantly in males and females, especially in Nifecard XL group. Daytime SBP variability also decreased. SBP variability tended to increase in females receiving Nifedipine IR. Women were more compliant to Nifecard XL therapy than to Nifedipine IR treatment: 99.8±7.9% vs 96.4±6.3%, respectively. Adverse effect rate was similar in males and females receiving Nifecard XL. Conclusion. High compliance, relatively low effective dose, low adverse effect rate, and better tolerability allow to recommend Nifecard XL for AH treatment in men and women.

Aim. To study moxonidine and calcium antagonist (amlodipine) effectiveness in essential arterial hypertension (EAH) treatment among patients with chronic obstructive pulmonary disease (COPD), and therapy effects on concomitant dyslipidemia. Material and methods. In total, 30 patients with EAH and Stage 2-3 COPD, aged 39-70 years, were examined. Antihypertensive therapy was started by amlodipine, in the dose of 5 mg/d, increasing up to 10 mg/d 7-10 days later, if target blood pressure (BP) level wasn’t achieved. If target BP figures were not achieved after three-week treatment, moxonidine (0.2-0.4 mg/d) was added. Treatment effectiveness was assessed by spirometry, 24-hour peak flowmetry, 24-hour BP monitoring, lipid profile (LP), glucose and uric acids level assessment. Results. In 16 COPD and EAH patients, BP was normalized in amlodipine monotherapy (5-10 mg/d); in 14 patients – after adding moxonidine (0.4 mg/d). At Week 6 of the combined therapy, LP improved substantially, with blood glucose, uric acid levels and bronchial conductivity remaining the same. Conclusion. To achieve target BP levels in COPD and EAH patients, the combination of amlodipine (10 mg/d) and moxonidine (0.2-0.4 mg/d) can be recommended. It provides effective BP control, as well as improves heart rate variability and BP improvement, without affecting lung function, or blood levels of uric acid and glucose.

Aim. To study effects of adding isosorbide dinitrate (ID) and trimetazidine MB 35 mg (Tr) to beta-adrenoblocker therapy in stable angina (SA) patients. Material and methods. In total, 40 patients with Functional Class II-III SA were examined. Combined therapy effectiveness was studied in a three-month randomized, open, comparative, parallel trial. Physical stress tolerance (PST) in treadmill test, angina attack incidence, nitrate dose, and health self-assessment dynamics (visual analogue scale) were assessed. Results. In both groups, PST increase by Month 1 was similar: 17% and 19%, respectively. Then PST stayed the same in ID group, and further increased in Tr group. By Month 3, PST in Tr group was twice as high as that in ID group: 15% and 34%, respectively. In Tr group, ST depression reduction, comparing to the baseline, was greater than in ID group: 49% vs 27%, respectively. It was associated with reduced angina attack incidence and need in short-acting nitrates. General health self-assessment improved by 20% (Month 1) and 35% (Month 3), comparing to 13% and 18% in ID group, respectively. Two participants dropped out of ID group, due to low medication tolerability (n=2), and myocardial infarction development (n=1). Conclusion. Comparing to ID, Tr demonstrated better tolerability profile, and long-run tolerance effect absence.

Aim. To investigate correlations of gastro-esophageal reflux (GER), Helicobacter pylori (HP) infection, and myocardial electric instability markers in patients with coronary heart disease (CHD) and GER disease (GERD). Material and methods. In total, 225 patients were examined: 67 individuals with CHD and GERD (main group), and two comparison groups: 72 CHD patients, and 86 GERD subjects. Markers of myocardial electric instability included: duration and asynchrony of repolarization. To assess GER influence on heart function, Bernstein test was used, combined with 24-hour electrocardiogram (ECG) monitoring. GERD was diagnosed by endoscopy data. GERD with catarrhal or erosive reflux-esophagitis (CRE, ERE) were registered. HP infection was diagnosed by polymerase chain reaction (PCR) and histobacterioscopy of gastric mucosa bioptates. Results. In CHD and GERD patients, ST segment ischemic changes, ventricular extrasystolia (VE) were registered more often. With associated ERE, these heart function disturbances were more frequent than in CRE. In patients with combined pathology, high HP invasion of gastric mucosa was significantly associated with greater duration and asynchrony of repolarization. Myocardial repolarization duration was independently linked to CHD exacerbation, red blood cell sedimentation rate, and HP dissemination of gastric mucosa. Inhomogeneity of myocardial repolarization was linked to myocardial infarction in anamnesis and RE severity. Factors affecting heart function during Bernstein test, HP infection, increased level of C-reactive protein, and instable CHD were independent predictors of RE development in imitated GER. Conclusion. In patients with CHD and GERD, myocardial electric instability was linked to RE severity and HP status.

Aim. To study hypocoagulation effectiveness and mechanisms of electro-magnetic radiation, terahertz range, NO molecular specter frequencies (EMR THF-NO), in patients with various angina forms. Material and methods. The authors examined 80 patients with unstable angina, Class IIA and IIB (E. Braunwald classification), or effort angina, Functional Class II-IV (Canadian Cardiovascular Society). Twenty patients received standard medication therapy plus EMR THF-NO. Noteworthy, EMR THF-NO effects in unstable angina (UA) were studied in the absence of heparin therapy. The effects on main hemostatic parameters were studied: activated partial thromboplastin time (APTT), activated recalcification time (ART), prothrombin time, euglobulin fibrinolysis, fibrinogen (F) levels, antithrombin-III (At-III) activity, complex parameter of protein C system disturbances, Va factor resistance to activated C-protein. Results. EMR THF-NO demonstrated hypocoagulation effect in patients with stable angina (SA) and UA. In SA, hypocoagulation mechanism is explained by procoagulation potential reduction, by affecting the first (APTT and ART increase) and the third (F level decrease) coagulation phases. In US, it’s explained by increase in anticoagulant potential, due to At-III and modulation of initially disturbed fibrinolysis. Conclusion. EMR THF-NO should be included into complex therapy of angina patients, for greater hypocoagulation effect. EMR THF-NO could be used as an alternative method in patients with hypercoagulation and contraindications to special pharmaceutical hypocoagulation, or intolerance to these medications.

Aim. During prospective 6-month follow-up, to compare spirapril and enalapril effectiveness in patients with coronary heart disease (CHD)-caused chronic heart failure (CHF). Material and methods. In total, 61 patients with CHD-caused CHF, according to inclusion/exclusion criteria, were divided into spirapril group (n=29; mean dose 5±1.3 mg/d) and enalapril group (n=32, mean dose 18.3±9.0 mg/ d). At baseline and after 6-month follow-up, all patients underwent general clinical examination, 6-minute walking test, echocardiography (EchoCG), and quantitative measurement of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level. Data analysis was performed with STATISTICA package (Version 6.0). Results. Both agents had similar clinical effects: during follow-up, left ventricular ejection fraction (LVEF) increased by 9.6% in spirapril group (р=0.00013), and by 7.0% in enalapril group (р=0.01). In 6-minute walking test, the distance walked increased by 25.1% (р=0.00016) and 14.8% (р=0.01), respectively. NT-proBNP levels significantly correlated with patients’ functional status, assessed in 6-minute walking test (r=-0.43, p=0.002), and EchoCG-assessed LF systolic dysfunction (r=-0.46, p=0.001). In both groups, NT-proBNP levels had raised: non-significantly, up to 25 pmol/l (р=0.66) in spirapril group, and significantly, up to 150 pmol/l (р=0.045), in enalapril group. Conclusion. In patients with CHD-caused CHF, spirapril was as clinically effective as a traditionally administered ACE inhibitor. Spirapril was more effective in delaying NT-proBNP level increase.

In spite of recent achievements in Q-wave myocardial infarction (Q-IM) management, prevention of reperfusion syndrome, developing due to coronary artery opening in thrombolytic therapy (TLT), is still an unsolved problem. Aim. To assess the incidence of reperfusion syndrome and its manifestations, cardiac arrhythmias and recurrent pain syndrome attacks, in Q-IM patients treated with perftoran. Material and methods. In total, 166 Q-IM patients were examined and treated. All participants received TLT; 46 individuals also received perftoran. The incidence of cardiac arrhythmias and recurrent pain syndrome attacks was assessed. Results. In Q-IM patients, perftoran and TLT reduced reperfusion syndrome incidence by 26.8%, ventricular extrasystolia incidence – by 24.2%, and sinus bradycardia – by 17.3%; no ventricular fibrillation cases were registered. Moreover, perftoran decreased recurrent pain syndrome attack incidence. Conclusion. Perftoran beneficially influenced clinical course of reperfusion syndrome in Q-IM. Perftoran could be included into Q-IM complex therapy.

Aim. To study prognostic value of high-resolution electrocardiography (HR-ECG), heart rate variability (HRV), QT interval dispersion and duration parameters, for assessing the risk of chronic heart failure (CHF) decompensation, atrial fibrillation (AF), and sudden cardiac death (SCD) in coronary heart disease (CHD) patients. Material and methods. In total, 70 patients with various CHD forms, Functional Class II-III CHF (NYHA), and documented AF paroxysms in anamnesis, were examined. Instrumental examination included 24-hour ECG monitoring, echocardiography, ECG, HR-ECG, HRV assessment. Results. During prognostic follow-up, the participants were divided into groups, according to disease course and clinical outcome. End-points included: CHF decompensation, resulted in hospitalization; arrhythmic complications - prolonged AF paroxysms; SCD. Assessing prognostic value of HR-ECG, HRV and QT interval duration in predicting CHF decompensation, ECG predictors with maximal positive prognostic value were filtered QRS complex duration and corrected maximal QT interval. In predicting AF paroxysms, HR-ECG parameter, filtered P wave duration, had maximal prognostic value. Conclusion. Non-invasive ECG-diagnostics methods: HR-ECG, HRV and QT interval duration assessment, could be used in predicting arrhythmic complication and decompensation risk among CHD patients with CHF.

Aim. To study ACE inhibitor fosinopril effects on remodeling, diastolic filling of left and right ventricles (LV, RV), ectopic myocardial activity, heart rate variability, endothelial function, and microcirculation in patients with arterial hypertension (AH) and LV diastolic dysfunction (LVDD). To study fosinopril effects on clinical status, central hemodynamics, remodeling, LV and RV diastolic filling in patients with chronic heart failure (CHF) and LV systolic dysfunction (LVSD). Material and methods. In total, 40 patients with Functional Class II-IV CHF (NYHA), and LV ejection fraction below 40%, as well as 72 patients with AH and LVDD, were examined. Echocardiography, 24-hour ECG monitoring, duplex ultrasonography, laser Doppler flowmetry were performed. Results. In patients with CHF and LVSD, fosinopril treatment improved clinical status, central hemodynamics, remodeling parameters, normalized LV and RV diastolic filling. In patients with AH and LVDD, the drug beneficially influenced heart remodeling, LV and RV diastolic filling, endothelial function, microcirculation, as well as reduced sympathetic tonus and ectopic myocardial activity, decreasing sudden arrhythmic death risk. Conclusion. Fosinopril is a drug of choice in CHF and LVSD treatment, as well as for CHF prevention in patients with AH and LVDD.

Aim. To study simvastatin effects on lipid metabolism in elderly patients with Type 2 diabetes mellitus (DM-2) and isolated hypercholesterolemia (HCH) or combined hyperlipidemia (CHL). Material and methods. The study included compensated or subcompensated DM-2 patients (n=41) with isolated HCH or CHL, after 3 months of lipid-lowering diet. All participants received Vasilip (10 mg/d) for the first 6 weeks. In patients with less than 10% reduction in total and low-density lipoprotein cholesterol (TCH, LDL-CH) levels, simvastatin dose was increased up to 20 mg/d. This treatment regimen lasted for another 6 weeks. Results. Simvastin (10-20 mg/d) was effective for achieving target TCH and LDL-CH levels in 58.5% of the patients. After 6-week simvastatin treatment (10 mg/d), mean levels of TCH reduced by 13.8%, LDL-CH – by 16.7%, triglycerides (TG) – by 18.4%, atherogenic index (AI) – by 25,5%; the dynamics was statistically insignificant. Medication dose was increased up to 20 mg/d in 24 cases; after 6 weeks of this therapy regimen, levels of TCH decreased by 26.2%, LDL-CH – by 22.8%, and AI – by 39.6%, comparing to the baseline. Vasilip was welltolerated; gastro-intestinal adverse effects did not result in medication withdrawal. Conclusion. In elderly DM-2 patients, 6-week vasilip therapy (10-20 mg/d) demonstrated significant lipid-lowering effect. Optimal TCH and LDL-CH levels were achieved in 60% of the patients. Vasilip was an effective and welltolerated medication.

Principal results of the Russian Research and Clinical Program ARGUS. In this patient group, arterial hypertension (AH) control is very low, as well as diuretic prescription rate. High AH-related hospitalization rate is an evidence of a need for studying AH in-patient management problem, clinical and psychological profiles of hospitalized patients. Blood pressure (BP) control improvement is possible only with complex efforts of health professionals and patients. Theory-practice gap in AH management could not be eliminated by traditional educating programs, focused on doctor and patient awareness increase only. BP control problem might be a result of doctors’ psychological barriers, in respect to BP target level achievement, ad well as of patients’ low motivation and unsatisfactory therapy compliance. There is a need for a program studying psychological problems of health professionals and patients, obstacles for adequate AH management and demonstrating perspectives of rational diuretic use in patients with uncontrolled AH. To solve these tasks, the project «Improving arterial hypertension control in patients with high cardiovascular event risk» (ARGUS-2) was developed.

Background. Pregnancy-associated plasma protein (PAPP-A) is Zn-containing proteinase, activating insulin-like growth factor. PAPP-A level increase is observed in acute coronary syndrome (ACS) and other inflammatory and destructive pathology. Aim. To investigate PAPP-A blood levels in patients with various forms of coronary heart disease (CHD), and their link to two-year prognosis. Material and methods. The study included 75 patients aged 62.3±10.1 years: 17 individuals with myocardial infarction (MI), 23 participants with unstable angina (UA), 24 patients with effort angina, and 11 healthy volunteers. The follow-up lasted for two years. End-points (EP) included death, MI, UA, and heart failure (HF) progression. Besides routine clinical tests, the levels of PAPP-A, interleukin-6 (IL-6), and C-reactive protein (CRP) were measured by highly sensitive immuno-enzyme methods. Results. PAPP-A levels significantly correlated with CRP (r=0.361; р=0.043) and IL-6 concentration (r=0.387; р=0.035). PAPP-A, IL-6, and CRP blood levels were similar in healthy volunteers and SA patients. Comparing to SA patients, UA participants had increased levels of PAPP-A (8.6±6.7 vs 14.4±9.5 mIU/l; p<0.05) and CRP (4.5±4.0 vs 7.3±5.5 mg/l; p<0.05). In CHD patients with PAPP-A level <10 mIU/l (n=32), EP were registered in 4 cases. Among patients with PAPP-A levels >10 mIU/l (n=32), EP were registered in 11 participants. Mean time till EP registration was 1030±52 and 656±51 days, respectively (p<0.05). Comparing EP-free survival (logrange method), it was demonstrated that prognosis was better in subjects with PAPP-A levels <10 mIU/l, than in participants with PAPP-A levels >10 mIU/l (p=0.047). Conclusion. PAPP-A is a marker participating in CHD pathogenesis. Its blood levels correlated with systemic inflammation severity, being elevated in ACS patients. Patients with higher PAPP-A levels had poorer prognosis.

Arterial hypertension (AH) is reviewed as the leading cause of cardiovascular disease mortality. The authors stress target blood pressure level achievement as the crucial factor in effective prevention of AH complications. Typically, the latter is possible only with combined pharmaceutical therapy. Information on generic quality is very important for practitioners.