Aim. To investigate the role of lipoprotein(a) (Lp(a)) and apoprotein (a) (apo(a)) phenotype in pathogenesis of coronary artery (CorA) and carotid artery (CarA) atherosclerosis and its complications in women. Material and methods. The study included 200 women aged 55±10 years. All participants were divided into two groups, with (n=165) or without (n=35) diagnosed CorA and CarA atherosclerosis. In all patients, lipid profile parameters, Lp(a), and apo(a) phenotype were assessed. Results. Patients with atherosclerosis, compared to the controls, demonstrated higher prevalence of Lp(a) concentration ≥30 mg/dl (41,5% and 22,8%, respectively), low-molecular phenotype (LMP) of apo(a) (36,6% and 11,4%), and their combination (28,5% and 8,7%). Lp(a) concentration and LMP apo(a) prevalence were positively associated with the number of atherosclerotic CorA. Severe CorA atherosclerosis was 10 times more prevalent in women with LMP apo(a) and Lp(a) level ≥30 mg/dl than in women without LMP apo(a) and normal Lp(a) concentration. The combination of LMP apo(a) and Lp(a) ≥30 mg/dl significantly correlated with myocardial infarction in anamnesis, after adjustment for smoking status and lipid profile parameters (r=0,386, р<0,005). Increased intima-media thickness was stronger associated with LMP apo(a) than increased Lp(a) concentration. CarA atherosclerosis was 4 times more prevalent in patients with LMP apo(a) than in individuals with high-molecular apo(a) phenotype, and 5 times more prevalent in patients with the combination of LMP apo(a) and increased Lp(a) concentration than in subjects with high-molecular apo(a) phenotype and normal Lp(a) levels. Conclusion. Increased Lp(a) concentration, LMP apo(a), and their combination were independently associated with the presence and severity of CorA and CarA atherosclerosis in women.

Aim. May blockade of the angiotensin II type 1 receptor (AT1) with an angiotensin receptor blocker reverse vascular pathology independent of blood pressure (BP) lowering. Material and methods. Stage I hypertensive, nondiabetic patients (61% male; age 38 to 67 years) were randomized after a 4-week washout period to olmesartan medoxomil 20 to 40 mg or atenolol 50 to 100 mg plus additional agents (hydrochlorothiazide, amlodipine, or hydralazine) as needed for a goal BP <140/90 mm Hg. At baseline and after 1 year of treatment, subcutaneous gluteal resistance arteries were examined on a pressurized myograph to evaluate remodeling. Biopsies were available from 22 atenolol recipients, 27 olmesartan medoxomil recipients, and 11 normal volunteer controls. Results. BP was reduced to a comparable degree by olmesartan medoxomil (from 149±11/92±8 mm Hg to 120±9/77±6 mm Hg; p<0,05 [mean ± standard deviation]) and atenolol (from 147±10/90±6 mm Hg to 125±12/78±7 mm Hg; p<0,05 [mean ± standard deviation]) from baseline for each arm (p=0,08 for the 40-week treatment mean between arms). After one year’s treatment, the wall-to-lumen ratio in arteries from patients treated with olmesartan medoxomil was significantly reduced (from 14,9% to 11,1%; p<0,01), whereas no significant change was observed in arteries from atenolol-treated patients (from 16,0% to 15,5%; p=NS); the wall- to-lumen ratio in controls was 11,0%. Conclusion. Blockade of AT1 receptors showed a superior corrective effect on the altered structure of resistance arteries in essential hypertension that was independent of the magnitude of BP reduction, and resulted in values similar to those in normotensive controls.

Aim. To study losartan effectiveness and safety in postmenopausal women with essential arterial hypertension (EAH), and with or without hormone replacement therapy (HRT). Material and methods. In total, 58 postmenopausal women with EAH were followed up for 6 months after being administered antihypertensive therapy (AHT) with losartan, due to inadequate blood pressure (BP) control. Group I (n=30) did not receive HRT, while Group II (n=28) was administered HRT. Losartan effects on BP dynamics, endothelium-dependent vasodilatation (EDVD), intima-media thickness (IMT) of carotid arteries (CA), lipid and carbohydrate metabolism were assessed, as well as losartan tolerability. Results. Losartan therapy resulted in target BP level achievement in both groups. At the study end, EDVD increase was statistically significant in Group I (р<0,05) and highly significant in Group II (р<0,001). In both groups, a tendency towards CA IMT reduction was observed. In all participants, a positive dynamics of lipid profile was observed, but it reached statistical significance only for low-density lipoprotein cholesterol in Group II. After 6 months, insulin sensitivity was normalized in all patients. The tolerability of losartan was good throughout the study period. Conclusion. In postmenopausal women with AH, adding losartan to the AHT scheme demonstrated good antihypertensive effectiveness, insulin sensitivity normalization, endothelial function and lipid profile improvement. Among women receiving AHT and HRT, antihypertensive effect, as well as beneficial effects on endothelial function and lipid profile, was greater than in women receiving AHT only.

Aim. To evaluate the dynamics of cardiovascular risk factors (RFs) and quality of life (QoL) in young patients with Stage I-II arterial hypertension (AH) and overweight/obesity during pharmaceutical (carvedilol monotherapy) and non-pharmaceutical (School for AH Patient) intervention. Material and methods. This open, randomised, clinico-preventive study in parallel groups included 63 out-patients with Stage I-II AH and overweight/obesity. The patients aged 18-27 years were randomised into 2 groups. All participants were randomised into two groups and received carvedilol (25 mg/d). In patients with uncontrolled blood pressure (BP), carvedilol dose could be titrated up to 50 mg/d. In addition, the main group (MG; n=32) received non-pharmaceutical structured intervention “School for AH Patient”. At baseline and after 24 weeks of the therapy, the levels of BP, QoL, body mass index (BMI), biochemical parameters, and RFs were assessed. Results. In the MG, RF levels were reduced to a greater extent than in the comparison group (CG). The MG patients demonstrated a greater decline in BMI (from 32,5±0,4 to 26,4±0,7 kg/m2 ; p<0,01) than the CG individuals (from 31,8±0,8 to 28,9±1,18 kg/m2 ; p<0,05). In the MG, baseline systolic and diastolic BP levels decreased by 20,1% and 25,6%, respectively; the respective decrease in the CG was 18,9% and 26%. In contrast to the CG, the MG demonstrated a significant improvement in QoL scales for physical functioning (р=0,003) and pain (р=0,032), with subsequent improvement in summary score of physical health component (р=0,001). Conclusion. In young AH patients with overweight/obesity, pharmacotherapy (carvedilol) should be combined with educational programs.

Aim. To evaluate the prevalence of aspirin resistance, its clinical features, potential solutions, and prognostic role in patients with acute coronary syndrome (ACS). Material and methods. The study included 51 patients with ACS and ST segment elevation (STEACS) and 49 ACS patients without ST segment elevation (non-STEACS). All participants received aspirin in a standard dose of 100 mg/d. Platelet aggregation (PA) was measured with a laser assay method and arachidonic acid (0,5 mg/dl) as an inductor. Aspirin resistance was diagnosed if PA was at least 20% at Day 7 of aspirin treatment. Results. Aspirin resistance was observed in 11% of the patients receiving aspirin in a standard dose of 100 mg/d. The majority of aspirin-resistant patients had STEACS, therefore, the data for this group were analysed in detail. Major clinical characteristics of aspirin-resistant and aspirin-responding patients were similar. After the in vitro test with aspirin, to determine the pharmacokinetic type of aspirin resistance, the medication dose was increased to 300 mg/d. The comparison group included 10 patients with STEACS, receiving aspirin in the dose of 100 mg/d. Thirty days later, PA was significantly reduced in both aspirin-resistant groups, therefore, the aspirin dose increase did not affect PA dynamics. In aspirin-resistant patients, prognosis was slightly worse than in their aspirinresponding peers. Conclusion. Aspirin resistance was more prevalent in STEACS patients. By Day 30, PA was substantially reduced. Increasing aspirin dose to 300 mg/d did not affect PA dynamics.

Aim. In a clinical and epidemiological study PERSPECTIVE, to investigate the secondary prevention implementation among stable angina patients in real-world clinical practice, and to evaluate compliance to Russian and international clinical guidelines on stable angina management. Material and methods. The study involved general practitioners and cardiologists (n=277). In the first part of the PERSPECTIVE Study, the data from out-patient medical histories (2768 patients with verified diagnosis of stable angina, SA) were analysed. Results. In SA patients, the prevalence of coronary risk factors (RFs) was high. The mean levels of blood pressure, blood lipids and lipoproteins, body mass index, and heart rate were substantially higher than the recommended target levels. At the same time, some positive changes in the clinical course of SA were observed, such as reduced incidence of angina attacks, decreased number of administered nitroglycerine tablets, and increased prevalence of Functional Class I-II SA. The qualitative changes in prescribed medications, including antianginal, anti-aggregant, and lipid-lowering agents, were also observed. Conclusion. The results obtained point to the need for further improvement of SA management in real-world clinical practice and for optimization of pharmaceutical therapy, in accordance with modern Russian and international clinical guidelines.

Aim. To investigate the effects of a atorvastatin (Atoris, KRKA) on major clinical parameters in patients with high cardiovascular risk – the participants of the OSCAR Study (2006). Material and methods. The total number of high-risk patients was 930 (472 men). The mean age was 57,8 years. Coronary heart disease (CHD) was diagnosed in 80,1% of men and 70,0% of women. All participants were divided into three groups by their CHD status: no CHD; with uncomplicated CHD; with CHD complications (myocardial infarction, stroke, and revascularisation in anamnesis). In all patients, the levels of risk factors, lipid profile, anthropometric and hemodynamic parameters were assessed. A generic atorvastatin was administered in a fixed start dose of 10-20 mg/d. The duration of the study was approximately 1,5 months. Results. After 8 weeks of Atoris treatment, a significant improvement in hemodynamic and lipid parameters was observed. In patients with CHD complications, lipid profile dynamics was less manifested, but the prevalence of target lipid level achievement was higher, since these individuals started with higher doses of atorvastatin. The total risk of fatal cardiovascular events reduced significantly. Atorvastatin was well-tolerated. Conclusion. Atorvastatin (Atoris, KRKA) is effective and safe in real-world clinical practice. It reduces the risk of cardiovascular events and mortality, also improving quality of life in high-risk patients.

Background. Results from clinical studies suggest that the dihydropyridine calcium channel blocker (d-CCB) lercanidipine may be associated with a lower incidence of peripheral edema than are older d-CCBs. Aim. To conduct a meta-analysis of published data from randomized controlled trials (RCTs) to assess the relative risk (RR) of d-CCB-specific adverse events (AE) with lercanidipine versus the older d-CCBs (first generation: amlodipine, felodipine, and nifedipine), and versus the other lipophilic d-CCBs (second generation: lacidipine and manidipine). Material and methods. A systematic literature search (all years, through August 11 2008) of MEDLINE, EMBASE, and the Cochrane Library was conducted for English-language reports of single- or double-blind RCTs of ≥4 weeks’ duration that compared the tolerability of lercanidipine with other d-CCBs in participants with mild (140- 159/90-99 mm Hg) and moderate (160-179/100-109 mm Hg) hypertension. Results. Eight RCTs (6 used first-generation drugs, and 4 used second-generation drugs) met the criteria for inclusion. Efficacy outcomes for lowering blood pressure did not differ statistically between lercanidipine and either generation of d-CCBs. Compared with the first generation, lercanidipine was associated with a reduced risk of peripheral edema (52/742 with lercanidipine vs. 88/627 with first generation; RR=0,44 [95% CI 0,31-0,63]), but not flushing or headache. The frequency of peripheral edema, flushing, and headache did not differ statistically between lercanidipine and the second generation drugs. Study participants were less likely to withdraw from the RCTs because of peripheral edema (RR=0,24 [95% CI 0,12-0,47]) or any AE (RR=0,51 [95% CI 0,33-0,77]) when treated with lercanidipine rather than a drug from the first generation, but not when treated with lercanidipine rather than second-generation drugs. Conclusion. Lercanidipine was associated with a lower risk of peripheral edema and a lower risk of treatment withdrawal because of peripheral edema than were the first-generation, but not the second-generation, d-CCBs.

Aim. To study the lipid-lowering effectiveness, as well as the effects on inflammatory markers and vascular wall function, of ezetimibe as monotherapy and in combination with initial doses of original statins (simvastatin, atorvastatin, and rosuvastatin). Material and methods. The study included 60 male and female patients with coronary heart disease and hyperlipidemia. Mean age of the participants was 61,4 years; mean baseline level of low-density lipoprotein cholesterol (LDL-CH) was 4,1 mmol/l. The participants were randomised into four groups: ezetimibe monotherapy (10 mg/d) for 24 weeks, or statin monotherapy (simvastatin, atorvastatin, or rosuvastatin; 10 mg/d) for 12 weeks with following assessment of LDL-CH levels. If target levels were not achieved on statin monotherapy, a combination of ezetimibe and statins was administered for the next 12 weeks. The effects of monotherapy and combined therapy on lipid profile, C-reactive protein, pro-inflammatory cytokines, vascular elasticity and stiffness, as well as treatment tolerability, were assessed. Results. After 3 months of the treatment, LDL-CH levels in statin monotherapy groups decreased to 2,66-2,98 mmol/l. The decrease in LDL-CH concentration in ezetimibe group (-16,4 %) was significant. After 3 months, the percentage of the patients with achieved target LDL-CH levels was 17 % for ezetimibe, 42 % for simvastatin, 31 % for atorvastatin, and 58 % for rosuvastatin. After 6 months, the patients receiving combined therapy demonstrated LDL-CH reduction by 39,5-50,6 %. From Month 3 to Month 6, the additional lipid-lowering effect of ezetimibe, as a part of combined therapy, varied from 13 % to 25,9 %. Conclusion: Adding ezetimibe (10 mg/d) to any statins reduces LDL-CH levels by extra 20-30 %. Combined therapy was required in over 50 % of the patients. Therefore, the response to statin monotherapy is not universal and in one-third of the patients could be regarded as poor. In these individuals, the “double inhibition” approach (combining statins with ezetimibe 10 mg/d) could control LDL-CH levels more effectively.

An attempt has been made to systematize the data on Russian cardiological clinical trials, included in the first edition of the reference book “Russian clinical and epidemiological studies in cardiology”. Design, duration, sample size, study population and other characteristics are described for these studies (n=93). The majority of the Russian studies are relatively short (approximately 70% are under 1 year), and the sample size is relatively small (approximately 50% include <500 subjects). The limited duration and size do not allow assessing therapy effects on hard end-points, such as all-cause mortality, cardiovascular mortality, and incidence of major cardiovascular events as prognostic markers. Therefore, most of the studies use surrogate end-points with lower prognostic value. The results of the current analysis demonstrate that not all the Russian studies comply with the good clinical practice standards. Only 31% of the published studies were prospective, and 40% claimed to be randomised, however, in many publications, there was no detailed description of randomisation procedure or randomisation quality control. However, some studies were methodologically robust. As an example, a cohort, prospective, noncomparative study “PROGNOSIS of coronary heart disease (CHD)” is presented. The description of this study will be included in the next edition of the reference book.

The paper discusses the position of beta-blockers, nebivolol in particular, in the Reappraisal 2009 of ESH/ESC Guidelines on arterial hypertension (AH) management. Nebivolol is not only highly selective towards beta-1 angiotensin II receptors, but also metabolically neutral, and therefore, could be used in AH patients with metabolic disorders.

This review summarizes modern views on high-risk patients as atherosclerosis-free individuals. The importance of high-risk approach is explained by the fact that this group encompasses the majority of cardiac patients, as well as the majority of cardiovascular events. Therefore, early diagnostics and adequate management of high-risk patients could substantially reduce the incidence of cardiovascular events. The modern treatment strategy for high-risk patients requires pharmaceutical intervention, and has the same principles as the treatment of patients with diagnosed cardiovascular disease. Such components of pharmaceutical treatment as antihypertensive, lipidlowering, and anti-aggregant therapy are discussed in detail.

Antiarrythmic therapy is one of the most problematic areas of modern medicine, with a constant search for new, more effective and safe medications. One of these new agents is dronedarone — a Class III antiarrythmic drug, with a structure similar to that of amiodarone, but without iodine in its molecule. Dronedarone interacts with different types of ion channels, and is at least as effective as amiodarone. At the moment, the dronedarone dosage of 400 mg twice a day is the best-studied therapeutic regimen for this medication. The paper analyses the results of published clinical trials of dronedarone, with the focus on ANDROMEDA and ATHENA studies. The former demonstrated that in patients with severe chronic heart failure, dronedarone increased all-cause mortality. The latter showed that in the dronedarone group, the combined incidence of cardiovascular death and cardiovascular hospitalisation was significantly lower than in the placebo group — 31,9 % vs. 39,4 %, respectively. In addition, dronedarone significantly reduced the annual risk of stroke — by 34 %, from 1,8 % to 1,2 % (p=0,027). Dronedarone safety could be regarded as satisfactory, with the majority of withdrawal cases due to such adverse effects as nausea and diarrhoea.

The paper presents the studies of the Takotsubo syndrome – reversible local or diffuse myocardial hypokinesis, with clinical and electrocardiografical patterns of acute myocardial infarction, and elevated levels of cardio-specific enzymes without myocardial ischemia or reperfusion. Epidemiology, pathogenesis, clinical symptoms, diagnostics, and treatment of Takotsubo syndrome are described.

The paper presents a critical analysis of the guidelines on home blood pressure monitoring (HBPM) by the European Society of Hypertension (2008). Theoretical aspects, related to the clinical implementation of the method, are discussed in detail, including general HBPM description, prognostic value of its results, normal range of HBPM parameters, and indications for HBPM. In addition, problematic issues, not covered in the guidelines, are discussed, such as the “first measurement effect” and long-term HMPM informative value. Two major modern methods for blood pressure measurement are compared – HBPM and 24-hour ambulatory blood pressure monitoring (ABPM). HBPM is essential for routine assessment of long-term antihypertensive therapy effectiveness, while the focus of 24-hour ABPM is the baseline BP evaluation in hypertensive patients, including masked hypertension diagnostics, and additional BP assessment in the case of low response to antihypertensive therapy. Therefore, these two methods are complementary. Publication of the Russian translation of the guidelines will increase clinicians’ interest in HBPM, overcoming the current skeptical attitude towards this method, and, as a result, will help to improve the quality of arterial hypertension diagnostics and treatment in Russia.