Aim. To assess the effects of the multiple-set resistance exercise on the functional status of patients with Stage II essential arterial hypertension (EAH).
Material and methods. In total, 40 patients with Stage II EAH, aged 45-55 years, took part in the physical rehabilitation programme, including exercise training on the resistance exercise machine. In the control group, weight lifting was followed by the complete relaxation of involved muscle groups and, therefore, a fast weight lowering. In the main group, the muscle relaxation after weight lifting was only partial, with a slower weight lowering, which resulted in increased lactate production and muscle ache. Ergospirometry, volumetric compression oscillometry, and resistance tests were used.
Results. Blood pressure normalization, myocardial contractility increase, and exercise capacity improvement were more pronounced in the main group (p<0,05), as a greater extent of neuromuscular strain stimulates the hormone production both during and after the exercise session.
Conclusion. The complex multiple-set resistance exercise programme demonstrated a marked beneficial effect in patients with Stage II EAH.

Aim. To investigate the parameters of pulse wave contour analysis (PWCA) and microcirculation (MC) in patients with arterial hypertension (AH), dyslipidemia (DLP), and high cardiovascular risk levels (SCORE >5%); to compare the dynamics of these parameters during the treatment with rosuvastatin or atorvastatin.
Material and methods. The study included 82 patients (mean age 53±10 years) with the high-risk AH (SCORE levels >5%), DLP, and no strict contraindications to statins. All patients were randomised into two comparable groups: Group I (n=40; mean age 51±10 years), receiving atorvastatin and standard AH treatment; and Group II (n=42; mean age 52±10 years), receiving rosuvastatin and standard AH treatment. At baseline and after 5 weeks, all patients underwent the MC assessment (conjunctival biomicroscopy) and PWCA (AngioScan-01). The following parameters were assessed: stiffness index (SI), reflection index (RI), augmentation index (AIx), and increased pulse wave amplitude (PWA).
Results. In the atorvastatin group, mean SI values were 5,87±2,05 m/s, RI values 35,64±19,98%, mean AIx values for heart rate of 75 beats per minute (AIx75) 41,21±14,56%, and mean central blood pressure (BP, Spa) levels 144,35±22,31 mm Hg. In the rosuvastatin group, the respective values were 5,01±2,56 m/s (SI), 37,01±14,56% (RI), 41,23±14,35% (AIx75), and 148,98±7,89 mm Hg (BP, Spa). All participants demonstrated PW Types A and B, as a marker of increased arterial stiffness, and positive AIx and AIx75 values. The treatment with atorvastatin and rosuvastatin was associated with a significant reduction in ∆SI (-0,87 and -0,89 m/s, respectively). Both groups demonstrated a non-significant reduction in ∆RI (-7,89 and -7,21%, respectively) and ∆AIx (-1,88 and -1,92%, respectively). PWA increased by 1,82±0,62 times in the atorvastatin group and by 1,95±0,81 times in the rosuvastatin group. At baseline, both groups demonstrated disturbed conjunctival MC (arterio-venular coefficient 1:3, stasis, and Stage III erythrocyte aggregation). Atorvastatin and rosuvastatin treatment was linked to a regression in the last two parameters, which could be explained by the improved vascular wall elasticity.
Conclusion. In high-risk patients with AH, the PWCA data suggested an increase in arterial stiffness, which was combined with conjunctival MC disturbances. Statin therapy improved not only blood lipid levels, but also MC, vascular stiffness, and endothelial function parameters, which was more pronounced in the rosuvastatin group.

Aim. To investigate the effects of simvastatin therapy on antioxidant enzyme activity and the correction of disturbed antioxidant status in patients with coronary heart disease (CHD) – post-infarction cardiosclerosis (PICS) – in combination with dyslipidemia (DLP).
Material and methods. The study included 132 CHD patients with PICS and 20 healthy controls. All participants underwent the measurement of plasma levels of lipids, lipid peroxidation (LP) products – diene conjugates (DC) and 2-thiobarbituric acid reagents (TBAR), antioxidant enzymes – glutathione peroxidase (GP) and superoxide dismutase (SOD) in red blood cells, plasma activity of the antioxidant ceruloplasmin/transferrin system (AOS CP/TF) (electron paramagnetic resonance method), and 24-hour Holter monitoring of electrocardiogram (ECG).
Results. The three-month simvastatin therapy (20 mg/day), as a component of the complex cardiac treatment, demonstrated its antioxidant effects and antiperoxidation activity in 60% of CHD patients. The subsequent therapy with 2-ethyl-6-methyl-3-hydroxypyridine sulphate (ES; 375 mg/day) and ubidecarenone (30 mg/ day) normalised the parameters of LP-antioxidant defence (AOD) and the levels of hepatic transaminases. Plasma AOS CP/TF activity inversely correlated with the duration of myocardial ischemia in CHD patients (r=-0,34; p=0,004).
Conclusion. To optimise the treatment of atherogenic DLP in simvastatin-treated CHD patients, ubidecarenone and ES could be used to improve the LP-AOD parameters.

Aim. To study the association between antiischemic effects (AIE) of metoprolol (MP), glucose tolerance, and insulin sensitivity in patients with stable angina (SA).
Material and methods. The study included 28 male patients, aged 46-68 years, with stable effort angina, Functional Class II-III, and positive exercise stress test (EST). The time of the ST segment depression by ≥1 mm defined the threshold exercise stress time. MP in a selected dose was administered twice a day, for one month. Its hemodynamic effects were assessed by the dynamics of heart rate (HR), blood pressure (BP), and double product (DP). Glucose tolerance test (GTT) was performed at baseline (before MP administration) and after one month of MP treatment. Tissue insulin sensitivity and insulin resistance (IR) were assessed by ISI0.120 and HOMA-IR parameters, respectively.
Results. AIE was registered in 57% of the patients, while 43% failed to demonstrate it. Both groups did not differ by the extent of MP impact on the levels of HR, BP, and DP. The presence or absence of AIE was linked to selected parameters of glucose metabolism. In patients with AIE, the pre-treatment levels of glucose and insulin 2 hours after glucose load were higher (p=0,028 and 0,043, respectively) and ISI1,120 values lower than in patients without AIE (p=0,023). Among participants with AIE, impaired glucose tolerance (IGT) was observed in 4 at baseline and in 8 one month later; among patients without AIE, IGT was not registered.
Conclusion. For the first time, the presence of AIE during MP therapy of SA patients was linked to the decreased insulin sensitivity of peripheral tissues (ISI0.120). Paired EST with a single MP dose at baseline provides an opportunity to identify the patients with a higher risk of metabolic disturbances during the longer-term MP treatment.

Aim. To study the prevalence of selected parameters of subclinical atherosclerosis and their association with muscle function and muscle volume in patients with different levels of cardiovascular risk (CVR).
Material and methods. The study included 20 patients (11 men and 9 women; mean age 54,5±8,5 years) with chronic coronary heart disease (CCHD; mean duration 6,4±2,3 years) in the main group (MG), as well as 20 CCHD-free people in the control group (CG). Arterial stiffness was assessed by pulse wave velocity (PWV) and calculated carotid-femoral index (CFI). Endothelial function was assessed by endothelium-dependent vasodilatation (EDVD) in the reactive hyperemia (RH) test. Common carotid artery (CCA) ultrasound was performed in order to assess intima-media thickness (IMT) of carotid arteries. All participants underwent veloergometry (VEM); exercise capacity (EC) was measured by calculated metabolic equivalents (MET). Muscle tissue volume was assessed using a bioelectrical impedance analyser. The percentage of active muscle mass (%AMM) and fat-free muscle mass (%FFM), out of the total body mass, was calculated.
Results. Increased CFI values >12 m/s, as a marker of adverse prognosis, were observed in 20% CCHD patients and in 10% of controls (z=0,17; p=0,87). Vasomotor endothelial dysfunction (EDVD <10%) was registered in 65% and 50%, respectively (z=0,74; p=0,46), while increased IMT values >0,9 mm were observed in 55% and 15%, respectively (z=2,3; p=0,02). Most patients with pathologically increased arterial stiffness and vasomotor endothelial dysfunction had low EC. In CCHD patients with low EC, CFI significantly correlated with %AMM and %FFM (r=-0,32; p<0,05; and r=-0,36; p<0,05, respectively). EDVD significantly correlated with both %AMM and %FFM (r=0,47; p<0,05; and r=0,5; p<0,05, respectively). There was a significant correlation between CFI and EDVD (r=-0,3; p<0,05). In CG participants with low EC, EDVD correlated with %AMM and %FFM (r=0723; p<0,05 and r=0,7; p<0,05, respectively). In both groups, %AMM and %FFM correlated with MET (r=0,49; p<0,05 and r=0,55; p<0,05, respectively; r=0,34; p<0,05 and r=0,31; p<0,05, respectively).
Conclusion. EDVD and PWV reflect the lower PA levels and functional disadaptation of CCHD patients, which can result in a faster progression of atherosclerosis.

Aim. To assess the short- and long-term angiographic and clinical effectiveness of endovascular bilateral recanalization of chronic coronary artery occlusion (CCAO), compared to conservative therapeutic strategy.
Material and methods. The study included 56 patients with coronary heart disease and CCAO. Angina Functional Class (FC) was assessed clinically and in electrocardiography tests. Local and global myocardial contractility was assessed using echocardiography. Group I (n=36) included CCAO patients who underwent an attempt of bilateral percutaneous coronary angioplasty; Group II (n=20) included CCAO patients who were treated conservatively. Clinical effectiveness of the treatment was assessed at 12 months.
Results. At baseline, 16 and 20 Group I patients had FC III and II, respectively. Out of 36 attempts of bilateral recanalization, 27 were successful, based on the angiography results. All these 27 cases were also clinically successful in the short term, and 20 in the long term. Global myocardial contractility increased from 54±3% to 56,9±4% (p=0,03). In Group II, 10 and 10 patients had baseline FC III and II, respectively. The long-term stabilisation of clinical status was observed in 15 patients, with the mean levels of left ventricular ejection fraction of 53,9±2,4% (p=0,9). Observed complications of coronary angioplasty did not result in clinically significant ischemic and haemorrhagic events, while the clinical improvement was substantially more pronounced, compared to Group II.
Conclusion. Bilateral CCAO recanalization is a technically demanding procedure, requiring an extensive surgical expertise and experience, and linked to a higher risk of complications. However, it could be used when the antegrade access is impossible; the anaesthesiological risk of coronary artery bypass graft surgery is high; and the patient refuses the cardiac surgery intervention.

Aim. To assess the prognostic performance of the GRACE scale extended by cystatin C levels in the prediction of ischemic and hemorrhagic in-hospital complications among patients with acute coronary syndrome (ACS).
Material and methods. In 160 ACS patients, admitted to the Moscow City Clinical Hospital No. 29 and included in the hospital register, blood levels of cystatin C were measured within the first 24 hours from admission. All patients were treated conservatively. The in-hospital risk of mortality and bleeding was assessed. The cut-off level of cystatin C was 1,53 mg/l.
Results. High levels of cystatin C, high GRACE scale risk, and their combination were associated with a significant increase in the in-hospital risk of hemorrhagic and ischemic complications. Independent mortality predictors included GRACE levels (odds ratio, OR, 1,05; 95% confidence interval (CI) 1,02-1,08; p=0,002) and cystatin C levels (OR 1,01; 95% CI 1,00-1,02: p=0,025). Major and moderate bleeding complications were independently predicted by fibrinolysis (OR 9,86; 95% CI 1,74-55,20; p=0,01), leukocyte levels (OR 1,34; 95% CI 1,11-1,62: p=0,002), and haemoglobin levels (OR 0,96; 95% CI 0,91-0,99; p=0,043), as well as the combination of high GRACE risk levels and elevated cystatin C levels (OR 11,78; 95% CI 1,95-71,06; p=0,007). Adding cystatin C to the high GRACE risk improved the prognostic specificity by approximately 20% and did not affect the prognostic sensitivity in the prediction of in-hospital risk of major and moderate bleeding complications.
Conclusion. The combination of high GRACE risk levels and elevated cystatin C levels was an independent predictor of major and moderate in-hospital bleeding complications, but not in-hospital death. Adding cystatin C to the GRACE scale by approximately 20% increased its specificity for the prediction of in-hospital risk of major and moderate bleeding complications.

The first paper of the series on the treatment of patients with vascular comorbidity (VC) is focused on the role and therapeutic potential of the correction of free radical processes (FRP) as pathogenetic factors of multifocal vascular pathology.
Aim. To analyse the effects of VC on the incidence and outcomes of cerebral stroke (S), in order to create therapeutic algorithms of FRP correction.
Material and methods. This prospective study included 634 S patients. The following factors were analysed: pre-stroke disability due to various VC variants; VC effects on the clinical course, as well as in-hospital and post-discharge outcomes; and FRP specifics in various VC variants.
Results. VC was registered in 97% of S patients; in 45,3%, it resulted in pre-stroke disability. FRP parameters, reflecting the progression of tissue energy deficiency, differed significantly in patients with coronary heart disease, myocardial infarction, atrial fibrillation, and diabetes mellitus. Based on these findings, the therapeutic algorithms for effective energy deficiency correction have been created.
Conclusion. The analysis of pre- and post-stroke disability and prevention of repeat events in cardiovascular patients has demonstrated the need for a more active implementation of modern multidisciplinary preventive programs.

Aim. To compare the effects of renin-angiotensin-aldosterone system (RAAS) modulators in patients with severe chronic heart failure (CHF).
Material and methods. In total, 148 patients (57,4±0,4 years), with severe systolic left ventricular (LV) dysfunction (ejection fraction (EF) <40%) were randomized into 4 groups: Group A (n=38), receiving only ACE inhibitors; Group B (n=37), receiving spironolactone (up to 50 mg); Group C (n=37), receiving valsartan (up to 320 mg); and Group D (n=36), receiving aliskiren (up to 300 mg), in addition to ACE inhibitors, diuretics, b-adrenoblockers, and digoxin. The follow-up phase was 37±0,7 months.
Results. There was a significant reduction in one-year mortality (relative risk (RR) reduction by 31,6% and 47,2%), two-year mortality (RR reduction by 38,6% and 50%), and three-year mortality (RR reduction 32% and 40,1%) in patients receiving ACE inhibitors in combination with spironolactone (p<0,05) or aliskiren (p<0,01), compared to Group A. Right heart functional parameters, as well as the levels of brain natriuretic peptide (BNP) and C-reactive protein (CRP) significantly improved after 12 months in Group A, compared to 6 months in Groups B and C, and to 3 months in Group D.
Conclusion. The combination therapy with ACE inhibitors and spironolactone or aliskiren significantly reduced the risk of mortality and hospitalisation, while the combination therapy with valsartan was associated only with reduced hospitalisation risk. Aliskiren therapy was linked to a significant improvement in right heart function, BNP and CRP levels, and a reduced risk of mortality and hospitalisation.

Aim. To prospectively study the prevalence and clinical manifestations of the risk factors (RFs) of adverse cardiovascular prognosis in patients with peripheral artery disease (PAD) of varied severity.
Material and methods. The study included 78 patients with Stage 2-4 PAD, aged 38-70 years. The following cardiovascular RFs were analysed, using standard clinical, laboratory, and instrumental methods: arterial hypertension (AH), smoking, family history of premature coronary heart disease (CHD), hypercholesterolemia (HCH), disturbed carbohydrate metabolism, low physical inactivity (LPA), heart rate (HR) >70 beats per minute (bpm), abdominal obesity (AO), metabolic syndrome (MS), blood hypercoagulation, and elevated levels of high-sensitivity C-reactive protein (hsCRP).
Results. In most PAD patients, atherosclerosis had multiple localization (75,0%). There was an association between duration of the disease, its severity, and disabled status. The prevalence of cardiovascular RFs was high: 94,0% for HCH, 90,0% for AH, 89,0% for smoking, 58,0% for premature CHD in family history, 81,0% for hyperfibrinogenemia, 73,0% for HR >70 bpm, 73,0% for MS, 73,0% for increased pulse blood pressure, 67,0% for overweight, 77,0% for LPA, and 53,0% for elevated hsCRP levels. The one-year follow-up data demonstrated a high incidence of cardiac (30,0%) and vascular (28,0%) complications. The three most important RFs of adverse cardiovascular prognosis included AH progression, CHD, and intermittent claudication.
Conclusion. The high prevalence of multifocal atherosclerosis (approximately 75%), AH, CHD, and MS in PAD patients warrants the need for early detection and effective control of modifiable RFs, in order to prevent the progression of the disease and the development of cardiovascular complications.

Aim. To study the physicians’ knowledge of the high blood pressure (BP) risk and to assess their attitude towards the prevention of arterial hypertension (AH).
Material and methods. In total, 118 internal disease specialists from three Russian regions participated in an anonymous questionnaire survey on the knowledge of high BP risk and the attitude towards the prevention of AH and its complications. The mean age of participants (13 men and 105 women) was 46,53±11,64 years. The respondents’ answers were compared to the information in the current clinical AH guidelines.
Results. More than one-half of the respondents demonstrated inadequate professional knowledge on prediction and prevention of AH complications. These physicians use the “traditional” disease model and do not consider elevated BP as a risk factor; predict the risk of AH complications using subjective complaints of their patients; do not realise the importance of the target organ damage (TOD) prevention; and limit their preventive strategy only to the prevention of hypertensive crises.
Conclusion. The demonstrated attitude towards AH management could be a serious barrier for effective AH prevention. This group of physicians needs extensive education and training, in order to modify their attitude and to increase their commitment to preventive strategies.

The paper discusses key aspects of the chronic heart failure (CHF) pathogenesis, which justify the use of β-adrenoblockers (β-AB) in the treatment of CHF. The authors present the clinical and experimental evidence confirming the effectiveness of these agents in CHF patients. Dose titration and the use of β-AB in various clinical groups are also discussed.

Coronary angioplasty is an important component of coronary heart disease (CHD) management. There is a substantial evidence of the need for dual antiaggregant therapy (clopidogrel and aspirin) in this clinical group, both before and after the intervention. The development of thrombotic complications during antiaggregant therapy suggests the antiplatelet drug resistance. The prevalence of this condition varies from 5% to 45% for aspirin, and from 20% to 45% for clopidogrel, depending on the assessment method and the specific clinical group. For dual antiplatelet therapy, the resistance prevalence is 6-8%. Presently, the gold standard method of the platelet functional activity assessment is optical aggregometry. To assess the resistance to aspirin, arachidonic acid is used as an aggregation inductor, with the calculation of absolute aggregation levels. To assess the resistance to clopidogrel, ADP is used as an aggregation inductor, and the relative aggregation parameters are calculated. The development of aspirin resistance is influenced by biological, clinical, and genetic factors. The clopidogrel resistance is associated with certain medications, hyperglycemia, atherosclerosis, and CYP2C19*2 gene polymorphism. Identification of the patients resistant to antiplatelet drugs enables the clinicians to adjust the antiplatelet treatment reasonably early and to reduce the risk of cardiovascular events. The possible methods of overcoming antiplatelet drug resistance are to double the loading and maintenance doses of clopidogrel and to use new agents.

The paper considers arterial hypertension and coronary heart disease as pathologies which share multiple pathogenetic mechanisms. The role of angiotensin II receptor antagonists (ARA) in the effective treatment of these diseases and in prevention of their complications is discussed. The modern views on ARA and their indications are presented.

Obese patients demonstrate the combination of dyslipidemia (DLP) and elevated transaminase levels, as a manifestation of non-alcohol fatty liver disease (NAFLD). Therefore, statins should be administered with care in this clinical group. In the real-world clinical practice, obese patients with high cardiovascular risk and concomitant NAFLD often receive low, inadequately effective doses of statins, due to the fear of their adverse effects on the hepatic function. An alternative method of DLP treatment is a combination of statins with ursodeoxycholic acid (UDCA). The need for a long-term combination treatment with statins and UDCA stresses the importance of the problem of drug interaction and the mechanisms of drug metabolism. Even high doses of atorvastatin are safe and well tolerated. The most severe adverse effects – myopathy and rhabdomyolysis – are very rare. Currently, there is no available evidence of adverse clinical effects of the combination of UDCA and atorvastatin. Presented results emphasise the need for a wider use of new therapeutic strategies in patients with DLP, obesity, and NAFLD. The combination of UDCA and statins is safe and effective. It facilitates not only the achievement of target lipid levels, but also the improvement in the hepatic function.

Patients with diabetes mellitus (DM) are at a high risk of cardiovascular events (CVE). Currently, the predominant clinical strategy of the CVE prevention in DM patients is aggressive lowering of low-density lipoprotein cholesterol and blood pressure levels. In this clinical group, statins are among the most widely used pharmacological agents. Recent clinical evidence suggests that statin therapy could be associated with an increased risk of DM. Both clinicians and researchers need to reevaluate the issue of statin safety in the patients at a higher CVE risk. This review focuses on the problem of DM development in statin-treated patients.

For many years, cardiovascular disease (CVD) remains the leading cause of death worldwide. According to the World Health Organization estimates, CVD accounts for 57% of all-cause mortality in Russia. Recently, research efforts have been concentrated on the search for new CVD markers which can improve the diagnostics and treatment of this large disease group, associated with poor prognosis. The markers of oxidative stress (OS) and antioxidant enzyme activity have been considered as potential pathogenetic mechanisms in the CVD development. The potential of statins, as medications with a wide range of pleiotropic – in particular, antioxidant – effects, for the effective management of chronic heart failure (CHF) has been extensively investigated. There is an ongoing discussion whether statins could be used for the treatment of nonischemic CHF.