Vol 89, No 12 (2017)


The new 2017 European society of cardiology (ESC) guidelines: important changes for introduction into clinical practice

Fomin V.V., Svistunov A.A., Napalkov D.A., Sokolova A.A., Skripka A.I., Morina N.A., Fedorova E.A.


The paper gives an overview of the European Society of Cardiology (ESC) guidelines updated in 2017. The revised and amended guidelines for areas, such as dual antiplatelet therapy (DAT), treatment of patients with ST-segment elevation myocardial infarction (STEMI), and management of patients with valvular heart disease and peripheral artery disease, were presented in late summer of this year. The authors of this paper present an independent analysis and discussion of new data on the key issues of diagnosis and treatment in patients in the above areas. The recommendations on DAT pay special attention to the timing of the therapy and to the choice of its drugs. The updated data on the treatment of patients with STEMI accurately determine the time to percutaneous coronary interventions, approaches to revascularization; the updates touch upon fibrinolytic therapy and new approaches to lipid-lowering therapy too. Recommendations for the management of patients with peripheral artery atherosclerosis propose for the first time a section devoted to the choice of antiplatelet therapy (an antiaggregant and/or an anticoagulant) depending on the clinical situation.
Terapevticheskii arkhiv. 2017;89(12):4-9
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Anticoagulant therapy in patients with atrial fibrillation and reduced kidney function of diabetic and non-diabetic etiologies

Sokolova A.A., Daabul I.S., Tsarev I.L., Napalkov D.A., Fomin V.V.


Aim. To evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and stages I-III chronic kidney disease (CKD). Subjects and methods. The cohort parallel-group study included 92 patients with AF and stages I-III diabetic and non-diabetic CKD, who were treated with DOACs (dabigatran, rivaroxaban, or apixaban) and vitamin K antagonists (warfarin). The follow-up duration was 12 months. Results. Thromboembolic events and bleeding, which required patient hospitalization or blood transfusions, were not recorded during 1-year follow-up. There was no clinically significant progression of CKD in the groups of therapy with vitamin K antagonists or DOACs. Just the same, a more intense decrease in glomerular filtration rate and a high rate of hemorrhagic complications were revealed in the subgroup of patients with diabetes mellitus (DM) versus those with non-diabetic CKD. Conclusion. In patients with non-valvular AF and diabetic and non-diabetic CKD, the use of DOACs effectively and safely prevents thromboembolic events, irrespective of the stage of CKD. At the same time, in patients taking anticoagulants, CKD progresses more rapidly in the presence of DM than in its absence, regardless of a specific anticoagulant. Hemorrhagic complications are more common in patients with AF, DM, and CKD, which requires more frequent monitoring of their kidney function.
Terapevticheskii arkhiv. 2017;89(12):10-14
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Multislice spiral computed tomography of the heart in dilated cardiomyopathy: possibilities in the verification of myocarditis (in comparison with myocardial biopsy) and in the evaluation of prognosis

Alieva I.N., Blagova O.V., Gagarina N.V., Nedostup A.V., Kogan E.A., Sedov V.P., Kadochnikova V.V., Donnikov A.E., Zaidenov V.A., Kupriyanova A.G., Ternovoy S.K.


Aim. To investigate whether intravenous contrast-enhanced multislice spiral computed tomography (computed tomography) (MSCT) versus myocardial morphological examination can diagnose myocarditis and the non-inflammatory causes of dilated cardiomyopathy (DCM) and evaluate prognosis in patients with the latter. Subjects and methods. A study group consisted of 130 patients, including 95 men (46.8±11.9 years), with DCM (mean left ventricular (LV) end-diastolic dimension (EDD), 6.6±0.8 cm; mean LV ejection fraction (EF), 29.8±9.3%; NYHA functional class (FC) III (II; III)). All the patients underwent intravenous contrast-enhanced 320-slice CT of the heart; myocardial morphological examination was made in 48 patients (endomyocardial biopsy in 29 patients, intraoperative biopsy in 7, and autopsy in 9, and study of the explanted heart in 3). In addition, cardiotropic viral DNA in the blood and myocardium and the level of anticardiolipin antibodies were determined; echocardiography (in all the patients), scintigraphy (n = 45), magnetic resonance imaging (MRI) (n = 21), and coronary angiography (CG) (n = 46), and a genetic consultation were performed. A comparison group comprised 20 patients, including 14 men (69.3±9.2 years), with coronary atherosclerosis (40% or more stenoses) according to MSCT findings in the absence of criteria for DCM (mean LV EDD, 4.8±0.5 cm; mean LV EF, 59.4±4.6%). Results. Morphological/comprehensive examination showed that myocarditis as a cause of DCM was diagnosed in 76 (65%) patients; its concurrence with genetic cardiomyopathies was in 17 more patients (17%). MSCT of the heart revealed lower accumulation areas in 2 (1.5%) patients (type 1 based on the proposed rating scale), delayed myocardial contrast agent accumulation (DMCAA) in 81 (62.3%): subendocardial accumulation (type 2) in 8, intramyocardial accumulation in 4 (type 3), subepicardial accumulation in 52 (type 4), and transmural accumulation in 15 (type 5); DMCAA was not noted in 49 patients. DMCAA was not found in the comparison group. As compared with biopsy, the sensitivity, specificity, predictive value of positive and negative results of the tests in detecting active myocarditis for all the types of DMCAA were 77.4, 47.1, 72.7, and 53.3%, respectively; those for types 3-5 of DMCAA were 77.4, 52.9, 75.0, and 56.3%; those in detecting all the morphological types of myocarditis were 68.3, 28.6, 84.8, and 13.3%, and those for types 3-5 were 65.9, 28.6, 84.4, and 12.5%, respectively. Comparison of the data of MSCT and those of comprehensive examination in all the patients with DCM, the diagnostic significance in detecting myocarditis for all the types of DMCAA was 70.6, 67.9, 88.9 and 38.8%, respectively; that for DMCAA types 3-5 was 60.8, 67.9, 87.3, and 32.3%. In the study group, MSCT also identified the non-compacted myocardium (n = 31 (23.8%)), coronary atherosclerosis (n = 31 (23%)), which is confirmed by CG findings in 15 patients. The patients with DMCAA significantly more frequently showed a relationship with previous infection, acute onset, significantly higher NYHA FCs, end-diastolic and end-systolic LV volumes, and insignificantly lower LV EF. During a mean follow-up periods of 12 (6; 37.25) months, the overall mortality rate was 17.7% (23 deaths); the death + transplantation index was 20% (n = 26). All the types of DMCAA were found to be significantly related to prognosis: in the DMCAA group, the mortality rate was 21.5% versus 7.8% in the non-DMCAA group (odds ratio 3.22; 95% confidence interval, 1.02 to 10.21; p < 0.05). Conclusion. MSCT with the assessment of delayed contrast enhancement (and simultaneous CT coronary angiography) can be used for the non-invasive diagnosis of myocarditis in patients with DCM, including that in the presence of contraindications to MRI. DMCAA correlates with the presence of myocarditis, its activity, the degree of functional disorders, and prognosis.
Terapevticheskii arkhiv. 2017;89(12):15-27
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Nocturnal pulse oximetry indicators in the evaluation of obstructive sleep apnea syndrome in outpatients with concomitant diseases of the upper respiratory tract and overweight

Glotov A.V., Fedorova T.N., Goltyapin V.V., Akhmedov V.A.


Aim. By using mathematical modeling, to evaluate the impact of upper respiratory tract diseases, retro- and micrognathia, and body mass index (BMI) on nocturnal pulse oximetry indicators (oxygen saturation level and oxygen desaturation index) in outpatients examined for suspected obstructive sleep apnea syndrome (OSAS). Subjects and methods. The study enrolled 260 subjects with a mean age of 47.8±12.0 years. All the examinees underwent outpatient pulse oximetry screening during nocturnal sleep because of suspected OSAS. Multislice spiral computed tomography was carried out to assess the paranasal sinuses and nasal septum. BMI was calculated. Variance factor analysis using an original programming application intended to create binary and ternary dispersion complexes was employed as a main mathematical tool. Results. There were statistically significantly sets of risk factors for OSAS: nasal septum deviation + increased BMI + male gender = 68.66%; chronic allergic rhinitis + increased BMI + male gender = 63.09%; retromicrognathia + increased BMI + male ganger = 59.48%; and chronic tonsillitis + increased BMI + male gander = 60.88%. Higher BMI and male gender are a most statistically significant set of risk factors. Conclusion. Pulse oximetry screening during nocturnal sleep in snoring patients with suspected OSAS in combination with an assessment of age, sex, BMI, ENT comorbidity, retro- and micrognathia can predict the severity of the disease and serve as a basis for elaborating an OSAS screening program.
Terapevticheskii arkhiv. 2017;89(12):28-33
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A retrospective historical study evaluating the safe use of current antidepressants in cardiology practice

Ivanov S.V., Volel B.A., Syrkina E.A., Ternovaya E.S., Troshina D.V., Grubova M.V., Tolkacheva I.A., Rozhkov A.N., Simonov A.N.


Aim. To confirm the data available in the literature on the cardiac safety of antidepressants. Subjects and methods. The archival data of 146 case histories were retrospectively analyzed. A study sample consisted of 96 cardiac inpatients regularly taking an antidepressant for more than 3 days during treatment for the underlying cardiovascular disease. The safe use of antidepressants was evaluated in terms of initial electrocardiogram (ECG) QTc interval changes, systolic and diastolic blood pressures (BP) (SBP and DBP), heart rate (HR), and hemorrhagic complications. The data obtained over periods of 3- and 6-8 days were analyzed. Results. The sample showed no clinically significant ECG QTc interval changes when taking regularly antidepressants within 8 days. Analysis of the dynamics of BP and HR in patients receiving antidepressants revealed no statistically significant differences in these indicators before and 3 and 6-8 days after drug administration. No case of hemorrhagic complications was seen in the study group taking antidepressants. Conclusion. The investigation generally confirms the high cardiac safety of new-generation antidepressants within at least the first week of therapy. Noteworthy are the low daily drug dosages (relatively specified in the instructions) that are sufficient for most cardiac patients with depressive disorders and an additional factor for minimizing adverse reactions.
Terapevticheskii arkhiv. 2017;89(12):34-42
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The clinical efficacy of allergen-specific immunotherapy with water-salt extracts and adjuvant allergens for atopic asthma with household sensitization

Ushakova D.V., Nikonov E.L.


Aim. To evaluate the clinical and economic efficiency of allergen-specific immunotherapy (ASIT); to comparatively analyze the efficiency of various therapy regimens for atopic asthma. Subjects and methods. The clinical and economic efficiency of asthma therapy using ASIT with water-salt allergen extracts or the adjuvant drug alustal “mite allergen” and only with medicines were comparatively analyzed. The investigation enrolled 156 patients with mild and moderate atopic asthma, household allergy. In Group 1 (n = 57), ASIT was performed using the classical scheme by subcutaneous injection of house dust mite allergen (JSC “I.I. Mechnikov Biomed”, Russia). In Group 2 (n = 43), ASIT was conducted using the alustal “mite allergen” (Stallergenes, France). Group 3 (n = 56) received only medical therapy. Results. ASIT with both water-salt allergen extracts and the adjuvant allergen alustal is an effective treatment for mild and moderate atopic asthma. ASIT greatly reduces the need for anti-inflammatory treatment and the use of symptomatic drugs and improves the physical and psychoemotional indicators of quality of life in patients. The economic benefit of ASIT is delayed, but its use significantly reduces financing costs. Conclusion. ASIT is a reasonable, highly effective and ultimately cost-effective treatment in patients with atopic asthma. A variety of drugs for ASIT can choose schemes that are convenient and acceptable for each patient, which allows wider use of this treatment.
Terapevticheskii arkhiv. 2017;89(12):43-50
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Enteral tube feeding in adult patients with cystic fibrosis and respiratory failure

Krylova N.A., Amelina E.L., Krasovsky S.A., Karchevskaya N.A., Tarabrin E.A., Gasanov A.M., Ibragimova D.F., Golovinsky S.V.


Aim. To evaluate the efficiency of nocturnal hyperalimentation in adult patients with cystic fibrosis (CF) and respiratory failure. Subjects and methods. The investigation enrolled 17 patients older than 18 years (mean age, 25.6±4.2 years) diagnosed with very severe CF (forced expiratory volume in one second (FEV), < 30%; body mass index (BMI), < 18.5 kg/m); all the patients were on the waiting list for lung transplantation. Nutritional status and pulmonary function parameters, such as body weight, height, BMI, and FEV, were measured at baseline, before and 6 and 9 months after tube feeding. Results. The study group showed a considerable increase in body weight and BMI after 6 and 9 months. The change in lung function was statistically insignificant. Lung transplantation was successfully conducted in 5 patients; 4 died while on the waiting list; the cause of death was respiratory failure. Conclusion. Supplemental PEG tube feeding improves the nutritional status (BMI, body weight) of patients with very severe CF.
Terapevticheskii arkhiv. 2017;89(12):51-55
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Annual blood pressure dynamics and weather sensitivity in women

Varlamova N.G., Zenchenko T.A., Boyko E.R.


Aim. To study the annual cycle of blood pressure (BP) and weather sensitivity in normotensive women aged 20-59 years. Subjects and methods. The same group of 25 non-smoking women who had been living in the European North of Russia (62° N, 51° E) almost since their birth and were engaged in moderate-intensity mental labor was daily examined. During a year, there were 11823 blood pressure measurements using the Korotkoff technique; heart rate was calculated by palpation. These meteorological parameters were taken at the websites: http://meteo.infospace.ru and ftp://ftp.ngdc.noaa.gov/stp/geomagnetic_data/indices/kp_ap. The statistical significance of differences in the indicators was determined using the Fisher’s test and the Newman-Keuls test. The study used a correlation analysis with the calculation of the Spearman’s rank correlation coefficient. Results. The maximum systolic and diastolic BP values were revealed in February and January, respectively. The minimum values of systolic BP were detected in July; those of diastolic BP were in August. An individual-based analysis of sensitivity to environmental variations showed that about 88% of the women responded to atmospheric temperature; nearly 44% did to geomagnetic activity; almost 24% were sensitive to relative air humidity, and about 16% of the women were to atmospheric pressure. Conclusion. The dynamics of systolic and diastolic BP in the annual cycle of women depends on meteorological factors and suggests that there is a change in the priorities of its control in different periods of a year.
Terapevticheskii arkhiv. 2017;89(12):56-63
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Association of FOXP3 gene -3279 C>A polymorphism with the risk of pulmonary sarcoidosis

Malysheva I.E., Topchieva L.V., Tikhonovich E.L., Kurbatova I.V., Balan O.V.


Aim. To investigate the association of the polymorphic marker -3279 C>A of the FOXP3 gene with the risk of pulmonary sarcoidosis (PS) and to estimate the transcription level of this gene in the carriers of different genotypes of this polymorphic marker. Subjects and methods. The investigation included 99 patients of Russian ethnicity (mean age, 45.41±1.31 years) living in the Republic of Karelia, who were diagnosed with persistent PS, and 116 healthy donors (mean age, 42.06±1.30 years) in the control group. The alleles and genotypes of the polymorphic marker -3279 C>A of the FOXP3 gene were identified using polymerase chain reaction (PCR)-restriction fragment length polymorphism. The number of transcripts of the studied gene in the peripheral blood leukocytes of healthy donors and PS patients was determined with real-time PCR. Results. The control group and the PS patient one had no statistically significant differences in the distribution of the frequencies of alleles and genotypes by the polymorphic marker –308G>A of the FOXP3 gene (p > 0.05). The number of FOXP3 gene transcripts was not statistically significantly different in the peripheral blood leukocytes of patients with PS and control individuals. No statistically significant differences were observed in the mRNA expression levels in the above-mentioned gene in the carriers of different genotypes by the polymorphic marker -3279 C>A of the FOXP3 gene in all examined groups. Conclusion. The polymorphic marker -3279 C>A of the FOXP3 gene is unassociated with the risk of PS.
Terapevticheskii arkhiv. 2017;89(12):64-67
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ACOS: Clinical and functional features The Russian formulation mesalazine (kansalazine) in the therapy of ulcerative colitis

Sobko E.A., Chubarova S.V., Demko I.V., Loktionova M.M., Ishchenko O.P., Solovyeva I.A., Kraposhina A.Y., Gordeeva N.V.


Aim. To investigate the clinical and functional parameters in patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) versus those with chronic obstructive pulmonary disease (COPD) and asthma. Subjects and methods. A total of 129 people were examined. 51 patients with ACOS were followed up in Group 1; Group 2 included 38 patients with severe asthma; Group 3 consisted of 40 patients with severe COPD. All the patients underwent clinical examination: history data collection, physical examination, evaluation of disease symptoms, and study of respiratory function (spirometry, body plethysmography). Results. ACOS is clinically characterized by considerable demands for emergency drugs and by more frequent asthmatic fits and exacerbations, which require hospitalization. The parameters of bronchial resistance in ACOS were established to be increased throughout the follow-up period and to be comparable with those in patients with COPD. In the patients with ACOS, the severity of pulmonary hyperinflation was associated with increased demands for emergency drugs (r=0.59; p=0.015). Fixed bronchial obstruction in ACOS can be caused by smoking intensity and duration associated with increased bronchial resistance in expiration (r=0.51; p=0.003) and intrathoracic volume (r=0.71; p=0.0001); as well as increased body mass index (p<0.001) and disease duration, which were interrelated with a reduction in the forced expiratory volume in one second/forced vital capacity ratio (r=–0.63; p=0.001 and r=–0.71; p=0.0034, respectively). Conclusion. Patients with ACOS show more severe clinical manifestations and a substantial increase in functional residual capacity and intrathoracic volume throughout the follow-up period, suggesting that the distal bronchi are impaired and pulmonary hyperinflation develops.
Terapevticheskii arkhiv. 2017;89(12):68-75
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Characteristics of the course of gastric and duodenal ulcer disease concurrent with duodenal insufficiency

Busygina M.S., Vakhrushev Y.M.


Aim. To comprehensively study the course of gastric ulcer disease (GUD) and duodenal ulcer disease (DUD) concurrent with chronic duodenal insufficiency (CDI). Materials and methods. Ulcer disease (UD) was verified on the basis of the results of clinical and fibrogastroduodenoscopic examinations. The data of contrast duodenography and cavitary manometry were used to identify CDI. Gastroduodenal motor activity was investigated using the peripheral electrogastrograph EGG-4M. The results of pH measurements were employed to assess the state of gastric acid secretion and duodenal pH values. Results. A comprehensive examination was made in 106 patients with UD concurrent with CDI (a study group) and 30 UD patients without CDI (a comparison group). Epigastric pain was noted in the patients with GUD in the study and comparison groups (91.5 and 84.6%, respectively), but the pain was mainly aching in the patients with concomitant CDI and more intense (77.8%) in those without this condition. In the study group, heartburn was more common in patients with GUD and DUD (75.3 and 71.4%, respectively) than in those with UD in the comparison group (28.5 and 37.5%, respectively). Helicobacter pylori tests were positive in 23.8% of the patients in the study group and in 57.2% in the comparison group. Electrogastrography indicated that the patients with GUD and CDI had bradygastria and hypokinesis on an empty stomach; the electrical activity was reduced after eating. In the comparison group, tachygastria and hyperkinesis were detected on an empty stomach; these postprandial indicators were elevated. H. pylori tests were positive in 34.7% of the patients with DUD and CDI and in 63.6% of those with DUD without CDI. The postprandial electrical activity increased in patients with DUD and decreased in the comparison group. The specific features of changes in gastric and duodenal pH values in GUD and DUD concurrent with CDI in comparison with the isolated course of UD. Conclusion. The immediate and long-term follow-ups show that GUD and DUD concurrent with CDI run a more persistent course; the time of ulcer healing increases and the periods of remission decrease.
Terapevticheskii arkhiv. 2017;89(12):76-80
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Evaluation of the efficacy of pregabalin in the therapy of chronic pain in patients with knee osteoarthritis

Filatova E.S., Turovskaya E.F., Alekseeva L.I.


Aim. To evaluate the efficacy of pregabalin in the therapy of chronic pain in patients with knee osteoarthritis (KOA). Subjects and methods. The study enrolled 60 patients with KOA and neuropathic pain component (NPC) (Douleur Neuropathique en 4 questions (DN4) questionnaire scores, >4) who were randomized into two groups to receive aceclofenac or aceclofenac + pregabalin for 5 weeks. All the patients underwent clinical and neurological examinations, assessment of the functional WOMAC index, pain intensity at rest and during movement, and diagnosis of neuropathic pain (NP) (DN4 and Pain DETECT questionnaires). Results. Both groups were observed to have positive changes in the studied parameters; however, combination therapy using an anticonvulsant drug (pregabalin) showed a more pronounced positive effect against not only NPC, but also the functional activity (WOMAC) and severity of pain (visual analogue scale). Conclusion. Combination therapy using pregabalin in KOA patients having the signs of NP is more effective than monotherapy with nonsteroidal anti-inflammatory drugs (aceclofenac).
Terapevticheskii arkhiv. 2017;89(12):81-85
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Results of following up patients with chronic myeloid leukemia and a deep molecular response without tyrosine kinase inhibitor therapy

Turkina A.G., Chelysheva E.Y., Shuvaev V.A., Gusarova G.A., Bykova A.V., Shukhov O.A., Petrova A.N., Vakhrusheva M.V., Goryacheva S.R., Kolosova L.Y., Krasikova P.S., Fominykh M.S., Martynkevich I.S., Abdullaev A.O., Sudarikov A.B., Savchenko V.G.


Aim. To assess the results of following up patients with chronic myeloid leukemia (CML) and a deep molecular response (MR) without tyrosine kinase inhibitor (TKI) therapy. Subjects and methods. The reasons for TKI discontinuation in 70 patients with CML and a deep MR of more than 1 year’s duration were adverse events, pregnancy, and patients’ decision. Information was collected retrospectively and prospectively in 2008-2016. Results. The median follow-up after TKI therapy discontinuation was 23 months (2 to 100 months). At 6, 12 and 24 months after TKI therapy discontinuation, the cumulative incidence of major MR (MMR) loss was 28, 41 and 48%, respectively; the survival rates without TKI therapy were 69, 50, and 39%, respectively. MMR loss was noted in 28 (88%) patients at 12 months; it was not seen without TKI therapy at 2-year follow-up. Deaths due to CML progression were absent. The Sokal risk group was a reliable factor influencing MMR loss (p ≤ 0.05). The cumulative recovery rate for deep MR after resumption of TKI use was 73 and 100% at 12 and 24 months, respectively, with a median follow-up of 24 months (1 to 116 months). Deep MR recovered at a later time when the therapy was resumed more than 30 days after MMR loss. Conclusion. Safe follow-up is possible in about 50% of the patients with CML and stable deep MRs without TKI therapy. The introduction of this approach into clinical practice requires regular molecular genetic monitoring and organizational activities. Biological factors in maintaining remission after TKI discontinuation need to be separately studied.
Terapevticheskii arkhiv. 2017;89(12):86-96
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Effect of an angiotensin-converting-enzyme inhibitor on the plasma concentration of cytokines and vasoactive molecules in patients with coronary heart disease and hypertension

Khadartsev A.A., Logatkina A.V., Terekhov I.V., Bondar S.S., Bondar N.V.


Aim. To investigate the plasma concentrations of cytokines and vasoactive molecules in patients with coronary heart disease (CHD) in the presence of hypertension in relation to the angiotensin-converting-enzyme (ACE) inhibitor level reflecting the degree of renin-angiotensin-aldosterone system (RAAS) inhibition. Subjects and methods. 72 patients with NYHA functional class (FC) II-III angina pectoris and 40 healthy persons at the age of 47-65 years were examined in a controlled cohort study. Enzyme immunoassay was employed to determine the serum concentrations of interleukins (IL) (IL-2, IL-12, IL-17A, and IL-24), the vasoactive molecules of bradykinin, serotonin, ACE, angiotensin-II (AT-II), NO, and endothelin-1 (ET-1), and plasma renin activity. In addition, the plasma level of the tetrapeptide N-acetyl-Ser-Asp-Lys-Pro was used as a marker for ACE inhibition. Results. The patients with CHD occurring in the presence of hypertension compared with the apparently healthy individuals displayed decreased ET-1 and NO production along with elevated levels of serotonin, AT-II, as well as IL-17A and IL-12. The found changes were accompanied by reduced renin activity. Thus, the individuals with low ACE inhibitor levels showed more pronounced production of the proinflammatory cytokine IL-17A, as well as high plasma concentrations of ACE and NO. The high ACE inhibitor level that reflects patient adherence to appropriate antihypertensive therapy is associated with the reduced production of IL-2 and with the minimum serum levels of ACE, AT-II, and NO, being characterized by the high production of IL-12 and serotonin at the same time. Conclusion. In patients with CHD and hypertension, the high plasma enzyme inhibitor concentration that reflects the activity of appropriate antihypertensive therapy, by contributing to the strengthening of the mechanisms of relaxation of blood vessels, is associated with the risk for proinflammatory activation of whole blood cells and platelets. The mean ACE inhibitor levels that reflect moderate RAAS suppression and are characterized by a relatively low proinflammatory activation of mononuclear cells may be more preferable than the maximum ones, from the point of view of slowing the progression of the subclinical inflammatory process of the vascular wall and preventing possible CHD exacerbations. This determines the feasibility of estimating the plasma level of an ACE inhibitor to control the depth of inhibition of RAAS activity.
Terapevticheskii arkhiv. 2017;89(12):97-102
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Implantable cardioverter defibrillators in the prevention of sudden cardiac death

Bockeria L.A., Neminushchiy N.M., Mikhaylichenko S.I., Novichkov S.A., Achkasov E.E.


The article highlights the role of implantable cardioverter defibrillators (ICDs) in the primary and secondary prevention of sudden cardiac death. It considers the results of multicenter studies comparing the efficacy of antiarrhythmic drugs and implantable devices in the primary and secondary prevention of sudden cardiac death, including that in patients with nonischemic cardiomyopathy and discusses quality of life in patients with ICDs.
Terapevticheskii arkhiv. 2017;89(12):103-109
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Role of neutrophil dysfunction in the pathogenesis of systemic lupus erythematosus

Smirnova E.V., Krasnova T.N., Proskurnina E.V., Mukhin N.A.


Neutrophil dysfunction plays a considerable role.in systemic lupus erythematosus (SLE) The protective function of neutrophils is carried out through various mechanisms: isolation of granular antimicrobial peptides (gAMP), microbial phagocytosis with subsequent degradation via reactive oxygen species inside the phagolysosomes; as well as bactericidal action due to the release of networks from chromatin and gAMP, also called neutrophil extracellular traps (NECTs). The development of neutropenia in SLE has multiple causes, including the formation of antibodies directly to leukocytes; that of neutralizing autoantibodies to the growth factors of neutrophils and cells - myeloid precursors; bone marrow suppression; involvement of neutrophils in the processes of apoptosis and NETosis. Neutrophils in SLE are characterized by reduced phagocytic ability and pathological oxidative activity. In SLE, there is a decrease in the ability to remove the products of neutrophil apoptosis, which is correlated with disease activity. SLE patients are noted to have a higher expression level of the genes specific for low-density granulocytes, an abnormal immature neutrophil population. The impaired processes of formation of NECTs and removal NETosis products play a substantial role in the pathogenesis of SLE. It is shown that the abnormal formation of NECTs also causes endothelial injury and increases the risk of thromboses. The design of novel drugs that act on the specific parts of the formation of NECTs or contribute to their removal from the extracellular environment can propel therapy for SLE and other autoimmune diseases to new heights. There is evidence for further investigations of neutrophil-mediated pathogenetic processes in SLE in order to identify potential therapeutic targets and to understand the mechanisms of action of drugs used in clinical practice.
Terapevticheskii arkhiv. 2017;89(12):110-113
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Alirocoumab: new perspectives of lipid-lowering therapy

Kobalava Z.D., Villevalde S.V., Vorobyeva M.A.


Alirocoumab (Praluent) is a fully human monoclonal antibody against proprotein covertase subtilisin/kexin type 9 (PCSK9). The data of ODYSSEY Phases II and III clinical trials demonstrate the high efficacy of alirocoumab in lowering the level of low-density lipoprotein (LDL) cholesterol in patients with primary hypercholesterolemia, with a considerable advantage over control groups (placebo, ezetimibe or modified statin therapy) in both monotherapy and combination therapy with statins and other lipid-lowering agents. Alirocoumab provides additional lipid-lowering effects against other atherogenic fractions of cholesterol, including non-high-density lipoprotein cholesterol, apolipoprotein B and lipoprotein (a). The agent show high safety and good tolerability and it can be considered as the drug of choice for patients who have not reached their target LDL cholesterol levels after statin therapy and have statin intolerance and familial heterozygous hypercholesterolemia. There are now the preliminary results of a secondary analysis of data from the ODYSSEY LONG TERM study, suggesting that alirocoumab therapy may be accompanied by a lower risk of cardiovascular events. The final results will be provided after the data of a study of cardiovascular outcomes after therapy with alirocoumab versus placebo (ODYSSEY OUTCOMES) are published.
Terapevticheskii arkhiv. 2017;89(12):114-121
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Melatonin and hypertension: a possible role in combination therapy

Budnevsky A.V., Ovsyannikov E.S., Rezova N.V., Shkatova Y.S.


This literature review gives the results of clinical trials studying the association of the level of endogenous melatonin and blood pressure (BP), the effects of exogenous melatonin on BP (particularly at night) in relation to the used rapid- or controlled-release formulation of melatonin.
Terapevticheskii arkhiv. 2017;89(12):122-126
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Diagnosis and treatment of pulmonary hypertension: from the point of view of 2017

Sarybaev A.S., Sydykov A.S., Sartmyrzaeva M.A., Mamazhakypov A.T., Maripov A.M., Dzhumagulova A.S.


Pulmonary hypertension (PH) is a group of diseases characterized by increased pulmonary vascular resistance (PVR). Regardless of its cause, PH leads to right ventricular failure and premature death. Recent advances in the diagnosis and treatment of PH have prompted the elaboration of new guidelines for the diagnosis and treatment of PH. This paper provides a brief overview of major achievements in diagnostic and treatment approaches in patients PH.
Terapevticheskii arkhiv. 2017;89(12):127-132
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A fixed-dose lisinopril+amlodipine+rosuvastatin combination: prospects for its use in patients with hypertension and concomitant dyslipidemia

Podzolkov V.I., Bragina A.E., Osadchiy K.K.


In Russia, target blood pressure (BP) levels are achieved in only 14.4% of men and in 30.9% of women. The need for combination therapy of hypertension is as high as 70.7%. There are well-known benefits of combined antihypertensive therapy allowing for higher efficiency and better tolerability. One of the current combinations is a combination of an angiotensin-converting enzyme inhibitor and a calcium antagonist, which have pronounced protective activity and metabolic neutrality. Fixed-dose combinations have substantial advantages over free ones, contributing to improving patient compliance with the used treatment regimen. Dyslipidemia is present in 60.7% of the hypertensive patients. Nonetheless, only 9.7% of Russian patients with coronary heart disease take statins and control of lipid levels remains very poor. The review discusses whether the use of the triple combination lisinopril + amlodipine + rosuvastatin is reasonable from the standpoint of evidence-based medicine. There are literature data suggesting the high value of this fixed-dose combination in the context of organ protection and the reduced risk of cardiovascular events.
Terapevticheskii arkhiv. 2017;89(12):133-140
pages 133-140 views

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