Vol 86, No 9 (2014)

Pulmonary hypertension (PH) is a group of diseases characterized by progressive increases in pulmonary vascular resistance and pulmonary artery pressure, which results in right ventricular heart failure and sudden death. Based on the current version of the guidelines for PH diagnosis and treatment, adopted by the experts of the European Society of Cardiology and the European Respiratory Society in 2009, and on the data of Russian and foreign clinical trials, the Russian experts elaborated clinical guidelines for PH in 2013. The latter consider the current classifications of PH, the specific features of its pathogenesis, and its diagnostic algorithm. The section dealing with drugs for maintenance therapy discusses data on the use of oral anticoagulants, diuretics, cardiac glycosides, and oxygen therapy. PH-specific therapy includes calcium antagonists, prostanoids, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. Surgical procedures for PH involve atrial septostomy, thromboendartectomy, and lung or heart-lung transplantation. A treatment algorithm is proposed for PH patients. The current medicinal approaches using specific therapy agents and their combinations offer new promises for the effective treatment of patients with PH and improve its prognosis.

AIM. To study the association between cystatin C levels and preclinical lesions in the target organs (heart, kidney, vessels) of patients with hypertensive disease (HD) at moderate and high risks for cardiovascular events (CVE). MATERIALS AND METHODS. The investigation enrolled 47 patents (30 men and 17 women) with Stages I-II HD at moderate (n=23) and high (n=24) risks for CVE. The patients' mean age was 46.0±1.8 years; the duration of HD was 4.1±0.2 years. The blood level of cystatin C was estimated by photometry using a biochemical autoanalyzer. Glomerular filtration rate (GFR) was calculated by the MDRD formula. Microalbuminuria (MAU) was determined by turbidimetry employing a biochemical autoanalyzer. RESULTS. No association between cystatin C level and 24-hour blood pressure (BP) monitoring readings was found in the patients except the men in whom it was correlated with 24-hour diastolic BP (DBP) (r=0.36; p<0.05). The hypertensive patients showed a positive correlation of cystatin C with their age (r=0.51; p<0.001). There were higher cystatin C levels in smoking patients with HD (n=19) and no statistically significant differences in the level of MAU, urine uric acid, and GFR between them. There was a statistically highly significant negative correlation between cystatin C concentration and GFR by the MDRD formula (r=-0.59; p<0.001), at the same time, no correlation was found between creatinine clearance (by the Cockroft-Gault formula). There were no statistically significant differences in cystatin C levels in relation to the presence or absence of carotid atherosclerosis (1.01±0.03 and 0.93±0.02 mg/l, respectively; p=0.08). Overall, there was a positive correlation of cystatin C levels with left ventricular mass index (r=0.58; p<0.001) and relative myocardial thickness index (r=0.40; p<0.05). CONCLUSION. The findings of the association of cystatin C and 24-hour DBP, preclinical lesions in the heart, vessels, and kidney seem to argue for the concept of cardiorenal syndrome in patients with HD just at its early stages.

AIM. To estimate the spread and distribution of genotypes and alleles of thrombosis predisposition gene polymorphisms in adolescents with essential hypertension (EH). MATERIALS AND METHODS. One hundred and thirty-seven 14- to 17-year-old adolescents were examined. There were 3 examined groups: 1) 37 EH patients with prothrombotic changes (PTC); 2) 60 EH patients without PTC; 3) 40 healthy adolescents. Prothrombin time, activated partial thromboplastin time, and the levels of fibrinogen and soluble fibrin monomer complexes were determined. The adolescents were assigned to a PTC group if they had changes by one or several above indicators. Polymerase chain reaction assay was used to type coagulation factor II (FII) and factor V (FV), plasminogen activator inhibitor type 1 (PAI-1), 5,10-methylenetetrahydrofolate reductase (MTHFR), and methionine syntase reductase (MTRR) gene polymorphisms. Group differences were determined by qualitative signs, by using the χ2 test and Yates' correction for continuity and Fisher's exact test if one of the groups had at least 5 individuals. All differences were considered statistically significant at p<0.05. RESULTS. FV R506Q, FII G20210A, PAI1 -675 4G/5G, MTHFR A1298C, and MTRR A66G polymorphisms have not been found to affect the hemostatic system in adolescents with EH. MTHFR С677Т may act as a risk factor of PTC in adolescents with EH, by increasing the risk of thrombotic events at an old age. CONCLUSION. It is recommended that the determination of molecular genetic markers for predisposition to thrombosis be actively used in adolescents with EA to form a risk group for thrombotic events and to implement preventive measures.

AIM. To investigate the demographic and clinical characteristics of patients with pulmonary hypertension (PH) and chronic thromboembolic pulmonary hypertension (CTEPH), regions of their residence, the specific features of diagnosis and drug therapy, and the patients' survival within the framework of a multicenter open-label prospective study. MATERIALS AND METHODS. The study enrolled patients over 18 years of age with PH classified as Group 1 (PH) and Group 4 (CTEPH). The follow-up was made in 9 expert centers of Russia on January 1 to February 28, 2014. The data of patients with PH and CTEPH were electronically entered at the register website: www.pul-hyp.medibase.ru. RESULTS. The study included 242 patients (183 women and 59 men) from 44 regions of the Russian Federation. PH of different etiologies was present in 79.3%, including 43.8% with idiopathic PH, 28.5% with congenital heart disease-associated PH, 6.2% with diffuse connective tissue-associated PH, 0.8% with hereditary PH; 20.7% were diagnosed with CTEPH. The patients' mean age at the inclusion in the register was 43.2±15.8 years; the median PH duration was 4.4 years (1.4 to 10.6%). The distance covered during a 6-minute walk test was 395.2±111.1 m; the Borg dyspnea index was 3.4±1.4 scores and the functional class was 2.5±0.8. After right cardiac catheterization, the mean pulmonary artery pressure was 53.1±19.5 mm Hg; cardiac output, 3.8±1.2 l/min; cardiac index, 2.1±0.6 l/min/m2; pulmonary vascular resistance, 1105±677.6 dyn·sec/cm5. A positive acute pharmacological test was seen in 16.3% of the patients. The most common comorbidity was erosive ulcerative lesion of the gastrointestinal tract (23.5%), hypertension (16.9%), and obesity (16.5%). 66% of the patients received PH-specific therapy: sildenafil (51.6%), bosentan (20.9%), or iloprost (7%); 7.4% of the patients were observed within the framework of clinical trials, 17.7% received combined therapy for PH: 16.3 and 1.4% had dual- or triple-component therapy, respectively; 55.8% of the patients took calcium antagonists, 61.4% had diuretics, 85.6% had antithrombotic drugs. The survival rates were 98% in the first year of the follow-up and 90.1% by the end of 2013. CONCLUSION. The formation of a national register of patients with PH and CTEPH makes it possible to introduce current approaches to diagnosing and treating the patients of this category and to evaluate the efficiency and quality of rendered medical care and will contribute to the estimation of required health care volumes and the expenditure of public health resources.

AIM. To evaluate the efficacy and safety of a fixed-dose combination of the angiotensin-converting enzyme inhibitor lisinopril 10 mg and the calcium antagonist amlodipine 5 mg (ekvator) in conjunction with rosuvastatin (mertenil). MATERIALS AND METHODS. The investigation enrolled 50 patients (mean age 57.9 years) with essential hypertension. All the patients received the fixed-dose antihypertensive combination. Stable Functional Class I or II exertional angina was in 46% of the patients. The remaining 54% were found to have brachiocephalic atherosclerosis. All the patients had dyslipidemia and were given rosuvastatin. RESULTS. The mean systolic blood pressure (SBP) initially reached 164.26 mm Hg. During the whole follow-up, the reduction in mean SBP generally accounted for 22.6% (p=0.000). At the study inclusion, the mean diastolic blood pressure (DBP) reached 99.38 mm Hg. The total decline in mean DBP was 19.3% (p=0.000). The mean level of total cholesterol (TC) decreased significantly by 32.1% (p=0.000); that of triglycerides (TG) also fell significantly by 31.8% (p=0.04); that of high-density lipoproteins increased insignificantly by 11.1% (p=0.599); that of low-density lipoproteins (LDL) dropped significantly by 47.5% (p=0.000). CONCLUSION. Being safe, the fixed-dose lisinopril and amlodipine combination is effective in lowering blood pressure in patients with hypertensive disease (HD) concurrent with coronary heart disease (CHD) or atherosclerotic changes in the carotid artery. The use of rosuvastatin in patients with HD concurrent with CHD during 2 months causes positive changes in the blood lipid composition as a significant reduction in the levels of (TC), LDL, and TG.

AIM. To study factors influencing platelet aggregation in patients with acute coronary syndrome (ACS). MATERIALS AND METHODS. The investigation enrolled 147 patients with ACS. Their blood was sampled on days 1, 3-5, and 8-12 days after the onset of ACS. All the patients received acetylsalicylic acid (ASA) 300 mg on day 1, then 100 mg/day and clopidogrel 300-600 mg on day 1, then 75-150 mg/day. Platelet aggregation was analyzed in 65 patients on day 1 after ASA intake, but prior to clopidogrel therapy. The aggregation was induced by 5 and 20 µmol of ADP. RESULTS. With the use of clopidogrel 75 mg/day on day 3-5, platelet aggregation was reduced by 2.1 and 1.7 times for 5 and 20 µmol of ADP, respectively, as compared to day 1 (ASA without clopidogrel) and remained unchanged on days 8-12. Increasing the dose of clopidogrel up to 150 mg/day potentiated its antiaggregatory effect. On day 1 (ASA without clopidogrel), there was a direct correlation between platelet aggregation levels and mean platelet volume (MPV) (correlation coefficients (r), 0.526 (p<0.001) and 0.368 (p=0.015) for 5 and 20 µmol of ADP, and between platelet aggregation levels and glycoprotein (GP) IIb-IIIa (r=0.387; p=0.002 and r=0.411 (p<0.001) for 5 and 20 µmol of ADP. No similar correlations were found on days 3-5 and 8-12 of administration of ASA and clopidogrel. The genetic polymorphism of GP IIb-IIIa (GP IIIa Leu33Pro) was not noted to affect platelet aggregation. Examining the effects of genetic variations in cytochrome P450 isoform CYP2C19 (a clopidogrel metabolizer) revealed the enhanced aggregation stimulated with 20 µmol of ADP in the carriers of slowly clopidogrel-metabolizing haplotype of CYP2C19 (differences were found on days 3-5 as compared to rapidly and routinely metabolizing haplotypes). CONCLUSION. In the patients with ACS, platelet aggregation is influenced by MPV, GP IIb-IIIa levels, and CYP2C19 polymorphism and is not by GP IIb-IIIa polymorphism.

AIM. To estimate the value of the dosing Valsalva-Weber test (VWT) in the diagnosis of autonomic disorders in patients with vasovagal syncope (VVS). MATERIALS AND METHODS. The dosing VWT using a specialized Task Force Monitor unit ("CNSystem", Austria) with synchronous noninvasive ECG and blood pressure (BP) monitoring was carried out in 30 patients (mean age 32±14 years) with VVS and 12 healthy individuals (31±7 years). The analysis of the test results encompassed the visual assessment of BP change curves and heart rate in different test phases and the calculation of pressure indices, Valsalva coefficient, arterial baroreflex sensitivity, and other parameters (a total of 26). RESULTS. The abnormally changed form of the mean BP curve, which was characterized by that BP by the end of Phase II test failed to achieve the baseline level, was recorded in 10 (33%) patients with VVS and in none of the healthy individuals (p=0.04). An individual analysis of the gender- and age-adjusted Valsalva coefficient revealed its reduction in 9 (30%) patients while this indicator was within the normal range in all the healthy individuals (p=0.04). CONCLUSION. During the dosing VWT, the signs of sympathetic insufficiency (impaired adrenergic regulation of BP) are found in 33% of the patients with VVS and those of parasympathetic insufficiency (impaired vagus regulation of cardiochronotropic function) are in 30%.

Pulmonary thromboembolism (PTE) is a nosological entity that complicates the course of many diseases. This circumstance determines difficulties in the diagnosis and determination of further patient management tactics. Bolus-enhanced computed tomography of pulmonary arteries, a method having high resolution and high accuracy, is presently accepted to be the gold standard to verify the diagnosis. At the same time this radiocontrast study cannot be used as a screening tool by economic and other reasoning, which determines the importance of the clinical diagnosis of the disease. This review considers different approaches to diagnosing PTE and a base of elaborated clinical algorithms and comparatively assesses empirical and scoring systems for the diagnosis and prediction of a disease course characterized by the rapidness and unpredictability of an outcome even in correctly made diagnosis.

Chronic heart failure (CHF) is a serious health problem today. Despite all advances in modern medicine, the high morbidity and mortality rates of CHF force physicians to search for new more effective methods for its control. At the same time, the fact that the designing of new effective medicaments is complex and expensive and that patients show low compliance with drug therapy increases the value of non-drug treatments for heart failure, such as patient education, higher treatment compliance, which make it possible to significantly enhance the efficiency of current combined drug therapy, to improve quality of life, and, possibly, to reduce future heart failure death rates.