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Issue. Articles

¹2(53) // 2017




1. Original researches


The polymorphism of the gene of angiotensin converting enzyme in the pathogenesis of myocardial hypertrophy in patients with arterial hypertension and type 2 diabetes mellitus

O.M. Bilovol, L. R. Bobronnikova

Kharkiv National Medical University

Objective — to study the relationship between the 2350 G/A polymorphic marker of the angiotensin converting enzyme (ACE) gene with the development and progression of left ventricular myocardial hypertrophy (LVH) in patients with combined course of arterial hypertension (AH) and type 2 diabetes mellitus (DM 2).
Materials and methods. A total of 54 patients with arterial hypertension (AH) of Stage II, 2nd degree and 58 patients with AH and DM 2 were examined. The mean age of the patients was (51.2 ± 5.4) years. Patients of both groups, depending on the presence of LVH, were divided into subgroups. The control group (n = 30) consisted from age- and sex-matching subjects.
Results and discussion. The LVH was revealed in 87.5 % of patients in the 2nd group and in 55.6 % of patients in the 1st group (p < 0.05). The GG genotype was 3.3 times more common in patients in LVH subgroups. Allele G was 1.4 times more often in patients with LVH. The genotype of AA was found in subgroups with LVH 2 times less frequently than in subgroups without LVH. Also reliable relationships of 2350A/G polymorphism of the AEC gene with mean values of LVMI were established. A direct relationship between the increase in LVMI, depending on the number of alleles G (p < 0.05) in patients of the 1st and 2nd group was established.
Conclusions. The A/G and G/G genotypes of the 2350A/G polymorphic marker of the ACE gene were found to be associated with LVH, both in patients with AH and in patients with concomitant AH and DM 2. The determination of the polymorphic marker 2350 A / G of the AEC gene will contribute to the improvement of early diagnosis and prognosis of cardiovascular risk in both patients with AH and in patients with combined course of AH and DM 2.

Keywords: arterial hypertension, type 2 diabetes mellitus, myocardial hypertrophy, angiotensin converting enzyme, genetic polymorphism.

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Original language: Russian

2. Original researches


The comparative efficacy of «nitrate-centric» and «diuretic-centric» treatment strategies of acute decompensated heart failure in patients with chronic kidney disease as regards decongestion and severe cardiovascular complications

K. M. Amosova1, I. I. Gorda1, A. B. Bezrodnyi1, G. V. Mostbauer1, Yu. V. Rudenko1, A. V. Sablin2, N. V. Melnychenko2, Yu. O. Sychenko1, I.V. Prudkyi1, K. I

1 Î. Î. Bogomolets National Medical University, Kyiv
2 Oleksandrivska Clinical Hospital, Kyiv

Objective — to perform a comparative evaluation of the efficacy of different treatment strategies for «wet and warm» patients with acute decompensated heart failure (ADHF) with a reduced glomerular filtration rate (GFR).
Materials and methods. A prospective study involved 141 patients with ADHF aged 38 to 85 years (mean age 66.4 ± 2.2) who were hospitalized sequentially in the cardiology departments of the Oleksandrivska Clinical Hospital in Kyiv during the years 2012—2014. Among all patients with CKD, the GFR levels  < 60 at admission were in 95 patients (67.3 %), including 57 patients in the group of DC and 38 subjects in the NC group. They were included in the study population.
Results and discussion. Hospital mortality in the NC group was 2 patients (5.3 %), and in the DC group 4 subjects (7.0 %) (p < 0.05). The duration of the hospital treatment period was significantly higher in the DC group ((16.4 ± 1.2) days vs. (13.2 ± 0.9) days, p < 0.05). The E/E index was significantly lower in the NC group than in the DC, at D3
(p < 0.05) and Ddsc (p < 0.01). A significant increase in daily diuresis in both groups compared with D1 occurred with D2 (p < 0.01), and at the 3rd and 5th days of treatment in the NC group was more pronounced than in the DC group
(p < 0,01).
Conclusions. In patients with ADHF with GFR < 60 without signs of systemic hypotension, the «nitrate-­centric» strategy, compared with «diuretics­-centric», is associated with more pronounced clinical decongestion and decrease in the serum level of NT-pro­BNP.

Keywords: chronic kidney disease, acute decompensated heart failure, NT-pro­BNP, decongestion and glomerular filtration rate.

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Original language: Ukrainian

3. Original researches


The personalized antiplatelet therapy in patients with stable ischemic heart disease

O.M. Bilovol1, O.Ye. Zaprovalna2

1 Kharkiv National Medical University
2 SI «National Institute of Therapy named after L.T. Mala of NAMS of Ukraine», Kharkiv

Objective — to develop a concept for predicting the risk of thrombotic and hemorrhagic complications for selecting the optimal and effective antiplatelet therapy regimen for ischemic heart disease (IHD) based on the study of clinical, metabolic and pharmacogenetic peculiarities of the antiplatelet agents’ effects.
Materials and methods. Examinations involved 382 patients with stable forms of ischemic heart disease who were on prolonged  (12—60 months) antiplatelet therapy with acetylsalicylic acid. Methods of research included anthropometry, bioelectrical impedance measurement, study of the endothelial function, morphological and aggregation characteristics of platelets, determination of carbohydrate metabolism and lipid profile, determination of autoimmune indices and indicators of oxidative stress Determination of genetic polymorphism of cyclooxygenase­1 genes and glycoprotein receptors of platelets (GP IIIa, GPI, TBXA2R-­924T). The effects of the studied factors on the course of IHD were assessed using the stepwise regression analysis on their relationship with the development of adverse cardiovascular events (ACVE).
Results and discussion. The results of the analysis showed that the development of ACVE was significantly associated with the acute cardiovascular event in anamnesis, the diabetes mellitus, with an increased body mass index
(> 30), with age over 65, with an increased aggregation activity and the presence of a minor allele of the platelet thromboxane receptor’s gene RTxA2.
Conclusions. Based on the study of clinical and anamnestic, metabolic, pharmacogenetic factors and activity of platelet hemostasis, the criteria for unfavorable course of IHD were identified and a personified approach to the appointment of antiplatelet therapy was proposed.

Keywords: ischemic heart disease, acetylsalicylic acid, personalized antiplatelet therapy.

List of references:
1.    Beitelshees AL, Voora D, Lewis JP. Personalized antiplatelet and anticoagulation therapy: applications and significance of pharmacogenomics. Pharmgenomics Pers Med. 2015;8:43-61. doi:10.2147/PGPM.S52900.
2.    Bell GC, Crews KR, Wilkinson MR et al. Development and use of active clinical decision support for preemptive pharmaco­genomics. J Am Med Inform Assoc. 2013. doi:10.1136/amiajnl‑2013-001993.
3.    Bondar’ TN, Kravchenko NA. Polymorphism of the cyclo­oxigenase‑1 gene and aspirin resistance. Cytol Genet. 2012;46(4):246-250. doi: 10.3103/ S 009545271 2040044.
4.    Bots SH, van der Graaf Y, Nathoe HM et al. The influence of baseline risk on the relation between HbA1c and risk for new cardiovascular events and mortality in patients with type 2 diabetes and symptomatic cardiovascular disease. Cardiovasc Diabetol. 2016;15(1):101. doi: 10.1186/s12933-016-0418-1.
5.    Coccheri S. Antiplatelet therapy: controversial aspects. Thromb Res. 2012;129:225-229. doi: 10.1016/j.thromres. 2011.10.036.
6.    Communication From The Commission To The European Parliament, The Council, The European Economic And Social Committee And The Committee Of The Regions eHealth Action Plan 2012-2020 — ​Innovative healthcare for the 21st century /* COM/2012/0736 final */ http://eur-lex.europa.eu/legal-content/EN/ALL/?uri=CELEX:52012DC 0736.
7.    Cui H, Lin S, Chen X et al. Correlation Between SNPs in Candidate Genes and VerifyNow-Detected Platelet Respon­siveness to Aspirin and Clopidogrel Treatment. Cardiovasc Drugs Ther. 2015;29(2):137-146.
8.    De Servi S, Crimi G, Calabrò P et al. Relationship between diabetes, platelet reactivity, and the SYNTAX score to one-year clinical outcome in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention. EuroIntervention. 2016;12(3):312-318.
9.    Fabre J.E, Gurney ME. Limitations of current therapies to prevent thrombosis: a need for novel strategies. Mol Biosyst. 2010;6 (2):305-315.
10.    Farrugia G, Weinshilboum RM. Challenges in implementing genomic medicine: the Mayo Clinic Center for Individualized Medicine. Clin Pharmacol Ther. 2013;94:204-206.
11.    Fisch AS, Perry CG, Stephens SH et al. Pharmacogenomics of anti-platelet and anti-coagulation therapy. Curr Cardio Rep. 2013;15:381.
12.    Frelinger AL, Li Y, Linden MD et al. Association of cyclooxygenase‑1-dependent and -independent platelet function assays with adverse clinical outcomes in aspirin-treated patients presenting for cardiac catheterization. Circulation. 2009;120(25):2586-2596.
13.    Goodman T, Ferro A, Sharma P. Pharmacogenetics of aspirin resistance: a comprehensive systematic review. Br J Clin  Pharmacol. 2008;66 (2):222-232.
14.    Gurbel PA, Myat A, Kubica J, Tantry US. State of the art: Oral antiplatelet therapy. JRSM Cardiovasc Dis. 2016;5, 2048004016652514, doi: 10.1177/2048004016652514.
15.    Johnson JA, Cavallari LH. Pharmacogenetics and cardiovascular disease - ​implications for personalized medicine. Pharmacol Rev. 2013;65(3):987-1009.
16.    Êrasopoulos G, Brister SJ, Beattie WS et al. Aspirin resistance and risk of cardiovascular morbidity: systematic review and meta-analysis. Brit Med J. 10:1136.
17.    Lordkipanidzå M, So D, Tanguay JF. Platelet function testing as a biomarker for efficacy of antiplatelet drugs. Biomark Med. 2016;8:903-918. doi: 10.2217/bmm‑2016-0070.
18.    McCarthy JJ, McLeod HL, Ginsburg GS. Genomic medicine: a decade of successes, challenges, and opportunities. Sci Transl Med. 2013;5:184-189.
19.    Naimo PhS, McGiffinD, Konstantinov IE. Aspirin resistance in the era of personalized medicine: Should we not take it personally? J Thorac Cardiovasc Surg. 2015;150:e99-100. doi.org/10.1016/j.jtcvs.2015.09.049.
20.    Siller-Matula M, Trenk D, Schrr K et al. How to improve the concept of individualised antiplatelet therapy with P2Y12 receptor inhibitors — ​is an algorithm the answer?. Thrombosis and Haemostasis. 2015;113/1(Jan):1-220. http://dx.doi.org/10.1160/TH14-03-0238.
21.    Spence JD. Rational Medical Therapy Is the Key to Effective Cardiovascular Disease Prevention. Can J Cardiol. 2017;33(5):626-634. doi: 10.1016/j.cjca.2017.01.003.
22.    Tahir U, Yeh RW. Duration of dual antiplatelet therapy (DAPT): a call for personalized medicine. J Thorac Dis. 2016;10:E1226-E 1229.
23.    Zhang JH, Wang J, Tang XF et al. Effect of platelet receptor gene polymorphisms on outcomes in ST-elevation myocardial infarction patients after percutaneous coronary intervention. Platelets. 2015;19:1-5.

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Original language: Russian

4. Original researches


The nutrigenetic peculiarities and eating behavior as the significant components of the modern personalized medicine

G. D. Fadieienko, Ya.V. Nikiforov, M. M. Vovchenko, O. O. Buryakovska

SI «National Institute of Therapy named after L.T. Mala of NAMS of Ukraine», Kharkiv

Objective — to examine the association between nutrigenetic characteristics and eating behavior (EB) in patients with nonalcoholic fatty liver disease (NAFLD) in combination with essential hypertension (EH) against the background of visceral obesity (VO).
Materials and methods. The study involved 26 patients with NAFLD in combination with EH against VO background, the mean age (51.0 ± 2.4) years. All patients were surveyed with the use of DEBQ questionnaire to define the EB peculiarities, and with the special questionnaire, designed for the purposes of this investigation, to study the specific features of the actual nutrition (AN). The nutrigenetic test was performed to define the nucleotide polymorphisms of the PPARG2 and ADRB3 genes by polymerase chain reaction using the metabolic test kit «Liteh» (OOO NPF).
Results and discussion. In the NAFLD patients with EH, three types of EB violation have been established with a significant prevalence of EB externalities such emotiogenic and restrictive (61.5 % (n = 16), 26.9 % (n = 7) and 11.5 % (n = 3) respectively). All patients (n = 26) were the carriers of Pro12Ala and Trp64Arg polymorphism. From them, homozygotes Pro/Pro (allele carriers SS) 73 % (n = 19), heterozygotes Pro/Ala (native alelyuSG) (n = 7) and homozygotes Trp/Trp (TT allele carriers) 88,5 % (n = 23), heterozygotes Trp/Arg (allele carriers TS) — 11,5 % (n = 3). The maximal severity of EB violations were the carriers of alleles CC, CG and TC (for externalities — 4.5 (4.0, 5.0) points, 3.8 (3.2, 4.0) and 3.2 points (3.0; 3.8) points, respectively) (p < 0.05), for emotiogenic — 4.2 (4.4, 4.8) points, 3.6 (3.2, 4.0) and 2 scores 8 points (2.2, 3.2), respectively (p < 0.05)). The AN violations were reveled in all patients: the abuse with «light» carbohydrates, saturated fats (including fast-food), red meat, deficiency of polyunsaturated fatty acids, fresh fruit and vegetables, malnutrition (intervals between eating more than 4 hours, the late high calorie dinner).
Conclusions. The result of investigation showed that the maximal violations of EB were observed in the patients homozygotes Pro/Pro and heterozygotes Trp/Arg, indicating the presence of other than genetic predisposition to an increased risk of development and progression of metabolic disorder. The malnutrition was defined as an important factor, requiring timely individual correction on the basis of identified polymorphism and types of EB.

Keywords: nutrigenetic characteristics, eating behavior, personalized medicine, nonalcoholic fatty liver disease, hypertension, visceral obesity.

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Original language: Ukrainian

5. Original researches


The clinical and pathogenetic peculiarities of angiopathy at the systematic autoimmune rheumatic diseases

O. V. Syniachenko1, E. D. Iegudina2, Î. Î. Khanyukov2, M. V. Yermolaeva1, M. F. Gulmamedova1, Yu. Î. Potapov1

1 M. Gorky’s Donetsk National Medical University, Lyman
2 SE «Dnipropetrovsk Medical Academy», Dnipro

Objective — to improve the quality of diagnostics, to establish the new links in pathogenesis and to identify prognostic criteria for the course of vascular lesion at the systemic autoimmune rheumatic diseases.
Materials and methods. The observations involved 379 patients, among whom 112 patients suffered from systemic lupus erythematosus (SLE), 57 from systemic scleroderma (SSD), 131 subject had rheumatoid arthritis (RA), and
79 patients with ankylosing spondylitis (AS). The examinations included echocardiography, sonography and ultrasound dopplerography of vessels, conjunctival biomicroscopy, integral indices of clinical and instrumental vascular pathology.
Results and discussion. The nature of angiopathy in patients with SLE associated with the general severity of the disease and the state of the autonomic nervous system. It was determined by the degree of pathological process activity, levels of the antinuclear factor in blood and antibodies to cardiolipin; the character of vascular changes revealed at conjunctival biomicroscopy may serve as the integral criterion for diagnosis. The manifestation lesions of blood vessels in patients with SSD was closely related to the degree of activity, duration of the disease, the nature of the «vegetative passport» (vagotonic or sympathotonic type), seropositivity of the disease according to anti-topoisomerase antibodies which are involved in pathogenetic constructions of angiopathy. In turn, it was accompanied by the changes in vasodilation, increase pulmonary pressure and vascular resistance, while the integral parameters of angiopathy affect the severity of scleroderma pneumonia and nephropathy. The systemic angiopathy in RA patients occurred more often in cases of high disease activity with osteoporosis and reflects the increase pressure in the lesser circulation. At the same time, development of vasculitis of the skin and peripheral vasoneuropathy closely correlated with the serum levels of cyclic citrulline peptide antibodies, and the appearance of digital arteritis is determined by the activity of the joint syndrome. The angiopathy development at AS directly correlated with the degree of the pathological process activity and seropositivity for the rheumatoid factor, and the vascular lesion proceeds with an increase in pulmonary pressure and vascular resistance, in the genesis of which the C-reactive protein participates.
Conclusions. Systemic angiopathy develops in 88 % of patients with SSD, in 85 % of cases at AS, 84 % with SLE and 61 % with RA. The results of laboratory and instrumental methods of investigation of patients with different nosological forms of systemic autoimmune rheumatic diseases revealed peculiarities of vascular damage that served as a basis for definition of the informative prognostic criteria.
Further clarification of clinical, laboratory and instrumental peculiarities of vascular damage at SLE, SSS, RA and AS will help to improve the quality of early diagnosis of the pathological process, and to develop criteria for predicting the course of the disease.

Keywords: systemic rheumatic diseases, angiopathy, clinic, pathogenesis.

List of references:
1.    Anic B. New classification of vasculitis. Lijec Vjesn 2014; 136 (7-8): 226-8.
2.    Dessertenne G, Canaud L, Marty-Ané C, Alric P. Saccular thoracoabdominal aneurysms in systemic lupus erythematosus. Ann Vasc Surg. 2015;29(7):14481-3. doi: 10.1016/j.avsg.2015.03.056.
3.    Giannakakis S, Galyfos G, StefanidisI, Kastrisios G, Maltezos C. Hybrid treatment of lower limb critical ischemia in a patient with systemic lupus erythematosus. Ann Vasc Surg. 2015;29(3):5961-5. doi: 10.1016/j.avsg.2014.10.040.
4.    Heijnen T, Wilmer A, Blockmans D, Henckaerts L. Outcome of patients with systemic diseases admitted to the medical intensive care unit of a tertiary referral hospital: a single-centre retrospective study. Scand J Rheumatol. 2016;45(2):146-50. doi: 10.3109/03009742.2015.1067329.
5.    Maldonado A, Blanzari JN, Asbert P, Albiero JA, Gobbi C, Albiero E, Alba P. Medium vessel vasculitis in systemic lupus erythematosus. Rev Fac Cien Med Univ Nac Cordoba. 2016;73(1):50-2.
6.    Ramos-Casals M, Brito-Zerón P, Kostov B, Sisó-Almirall A, Bosch X, Buss D, Trilla A, Stone JH, Khamashta MA, Shoenfeld Y. Google-driven search for big data in autoimmune geoepidemiology: analysis of 394,827 patients with systemic autoimmune diseases. Autoimmun Rev. 2015;14(8):670-9. doi: 10.1016/j.autrev.2015.03.008.
7.    Sharma A, Dhooria A, Aggarwal A, Rathi M, Chandran V. Connective tissue disorder-associated vasculitis. Curr Rheumatol Rep. 2016;18(6):31-41. doi: 10.1007/s11926-016-0584-x.
8.    Ungprasert P, Srivali N, Kittanamongkolchai W. Ankylosing spondylitis and risk of venous thromboembolism: A systematic review and meta-analysis. Lung India. 2016;33(6):642-5. doi: 10.3978/j.issn.2305-5839.
9.    Wong U, Yfantis H, Xie G. Urticarial vasculitis-associated intestinal ischemia. Case Rep Gastrointest Med. 2016;20(16):8603679. doi: 10.1155/2016/8603679.
10.    Yang Z, Ren Y, Liu D, Lin F, Liang Y. Prevalence of systemic autoimmune rheumatic diseases and clinical significance of ANA profile: data from a tertiary hospital in Shanghai, China. APMIS 2016;124(9): 05-11. doi: 10.1111/apm.12564.

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Original language: Russian

6. Original researches


The hormonal­metabolic peculiarities in patients with nonalcoholic fatty liver disease and the role of subclinical hypothyreosis in their development

Î. V. Kolesnikova, A. V. Potapenko

SI «National Institute of Therapy named after L. T. Mala of NAMS of Ukraine», Kharkiv

Objective — to study the hormonal-metabolic indexes and cardiovascular risk factors depending on the state of vascular endothelium and level of insulin resistance in the patients with nonalcoholic fatty liver disease (NAFLD) in combination with a subclinical hypothyreosis (SH).
Materials and methods. The examinations involved 87 patients with the mean age (48.6 ± 4.52) years, who passed the medical check­up in the Consulting Clinic of the National Institute of Therapy named after L. T. Mala of NAMS of Ukraine, from them 27 men (31 %) and 60 women (69 %), 19 men (70.3 %), 43 women (71.6 %) were over 50 years old. All patients were divided into 2 groups: the 1st  group (n = 35) included patients with NAFLD, 27 patients (77 %) with the mean age (52.3 ± 9.72). The  2nd (n = 52) consisted of patients with NAFLD in combination with SH, and in the process of the study they were divided into two sub-groups, depending on the TSH levels: subjects of sub-group À had values of 5 to 10; sub-group B TSH values >10. The mean age of 35 patients (67 %) in the 2 group was (52.3 ± 9.72) years. The control group consisted of 30 age-matched healthy male and female persons. The analysis was performed for the indexes of carbohydrate and lipid exchange, as well as level of thyroid hormones and circulating desquamated endothelial cells (CDEC).
Results and discussion. During the study, patients of the 2nd group (NAFLD in combination with a SH) demonstrated more significant pro-atherogenic changes (ğ < 0.05) and manifestations of insulin resistance, the number of women was in twofold higher than that of men. The patients of this group had the expressed manifestations of endothelial dysfunction (the higher CDEC levels), that was associated  with the considerable signs of dyslipidemia and insulin resistance. These changes confirm the higher risk of the cardiovascular complications development in a comorbide patient with NAFLD in combination with SH.
Conclusions. Thus, in NAFLD patients, presence of SH strengthens the changes of hormonal-metabolic indexes. The significant changes in a lipid profile in the patients with NAFLD in combination with a SH carry rather a pro-athero­genic character, and alteration of carbohydrate profile directly specify on the formation of considerable insulin resistance in comparison with NAFLD patients. With the increase of hypothyreosis degree, indices of vascular endothelium of NAFLD patients demonstrate significant changes.

Keywords: nonalcoholic fatty liver disease, subclinical hypothyreosis, cardiometabolic risk.

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Original language: Russian

7. Original researches


Immune dysregulation as a factor in the progression of the metabolic syndrome in young people

L. M. Pasiyeshvili

Kharkiv National Medical University

Objective — to optimize the diagnosis of endotoxemia at the metabolic syndrome (MS) among young people, and to assess the predictability of the pathological process.
Materials and methods. The study involved 23 patients aged 19 to 34 years with established diagnosis of «metabolic syndrome». The level of endogenous intoxication was determined by leucolysis method with defining of the cytolytic activity of autologous serum in relation to its own white blood cells. Lymphocyte proliferative activity was determined using lymphocyte cultures, with phytohemagglutinin (PHA), lipopolysaccharide (LPS) and monocultures without mitogen. Activity autoimmune processes defined in the reaction autologous lymphocyte rosette with its own red blood cells.
Results and discussion. The formation of endotoxemia syndrome has been established, that manifested by an increase in the average molecular weight due to hydrophobic fraction; changes in the phagocytic activity of neutrophil granulocytes and monocytes; and deficit and changes in functional activity of T-lymphocytes. This leads to dysregulation of cellular and humoral immune responses, and thus to uncontrolled activation of autoimmune reactions.
Conclusions. In the young people with metabolic syndrome, the formation of endotoxemia syndrome, the violations in the antigenic homeostasis, immune cell reactivity with stimulation of phagocytosis extension have been established, which stipulates the prolonged and therapy resistant course of the acute disease phase. At the same time, the deficiency of T-lymphocytes with a reduction in their functional activity has been reveled, that resulted in the disruption of the mechanisms of regulation of cellular and humoral responses. This process disrupts the control of the B-lymphocytes and ensures the activation of autoimmune processes.

Keywords: metabolic syndrome, pathogenesis, immune disorders, endotoxemia syndrome.

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Original language: Russian

8. Original researches


Efficiency of control of cardiovascular risk factors at the ambulator stage

G.S. Isayeva, L.A. Reznik, M.M. Vovchenko, Î.Î. Buryakovska

SI «National Institute of Therapy named after L.T. Mala of NAMS of Ukraine», Kharkiv

Objective — to determine the effectiveness of blood pressure monitoring and lipid metabolism indicators at the outpatient stage in patients with high and very high cardiovascular risk who were previously treated in the hospital for in-patients of the SI «National Institute of Therapy named after L.T. Mala of NAMS of Ukraine».
Materials and methods. 43 patients were examined. The middle age was 63,3 years.
Results and discussion. The overwhelming majority of patients had an overweight or obesity of I—III degree. It was established. It was found that in 53 % of cases target blood pressure levels were not achieved against the background of long-term outpatient therapy. The cholesterol levels of low-density lipoproteins were not optimal in 51 % of patients.
Conclusions. The overwhelming majority of patients on outpatient treatment do not achieve the targets of blood pressure and low-density lipoprotein cholesterol.

Keywords: blood pressure, cholesterol, effectiveness of treatment.

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Original language: Ukrainian

9. Original researches


The study of quality of life of the liquidators of the accident at the Chernobyl NNP with essential hypertension

Î. A. Oparin, V. P. Sinelnik

Kharkiv Medical Academy of Postgraduate Education

Objective — to assess MOS SF-­36 questionnaire for the study and evaluation of quality of life (QOL) and the factors, determining the level of the basic QoL indicators in the liquidators of the Chernobyl accident with essential hypertension (EH) before and after the treatment.
Materials and method. The study involved 53 patients with EH aged 48 to 71 years, the mean age (58.5 ± 0.8 years), who were surveyed with the use of the MOS SF-­36 questionnaire. All patients were investigated and treated in the hospital, the Therapeutic departments of the Kharkiv Regional Clinical Specialized dispensary of radiation protection of the population from January 2016 to December 2016. The investigated group included 45 men (84.9 %), and 8 women (15.1 %). All patients were divided into 2 groups. Patients of group I received standard therapy, patients of group II received the drug «Àctovegin®» (Takeda Austria GmbH) in addition to standard therapy. All indicators of quality of life were evaluated before and after the treatment.
Results and discussion. It has been established that in the first group of patients, only the indicator (ğ ≤ 0.05) of physical functioning (PF) c 48.5 (35—65) scores to 58.3 (55—80) significantly improved. The limitations of patients in this sphere of life activity decreased. After the treatment in the II group, the indices (p ≤ 0.05) significantly improved, and consequently the limitations in the role functioning due to the physical condition (RP) c 61.1 (0—100) scores to 71.3 (0—100); Improved overall health (GH) score from 42.7 (35—47) to 52.1 (47—60); in role functioning, conditioned by emotional state (RE) from 67.9 (0—100) points to 76.5 (0—100).
Conclusions. The result of investigation showed that MOS SF­36 questionnaire could serve as a reliable method for assessment of the QoL of patients with essential hypertension before and after treatment.

Keywords: Chernobyl accident liquidators, essential hypertension, quality of life, MOS SF-­36.

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Original language: Russian

10. Original researches


Dismetabolic disorders in patients with arterial hypertension and diabetes mellitus type 2

O. Al-Trawneh

Kharkiv National Medical University

​Objective — to study the peculiarities of dysmetabolic disorders in patients with arterial hypertension (AH) and type 2 diabetes mellitus (DM 2).
Materials and methods. 61 patients with stage II second degree AH without carbohydrate metabolism disorders were observed; 64 patients with combined course of AH and DM 2. The control group (n = 20) was the most comparable with observed patients in age and gender.
Results and discussion. Patients with combined course of AH and DM 2 had exceeding levels of LDL and triglycerides in the serum compared with the parameters of the 1st group and control group (p < 0.05). Decreased high-density lipoprotein cholesterol (HDL) in patients with AH and DM 2 observed significantly more frequent than in the comparison group (55.4 and 22.4 % respectively, p < 0.05). The combi­nation of AH and DM 2 contributed to an increase in atherogenicity coefficient
by 2.3 ti­­mes against the control and by 1.2 times the comparison group. Analysis of insulin resistance in patients of both groups indicated that the maximum values ​​of HOMA-IR, insulin and C-peptide index occurred in patients of the group 2 compared to the group 1 and control parameters. In both groups there was a significant increase in serum TNF-α level against the control group (p < 0.05). The greatest increase in the index by 2.5 times (p < 0.001) was observed in both AH and DM 2.
Conclusions. The mechanisms of metabolic disorders formation are analyzed in patients with both AH and DM 2. They are characterized by the progression of insulin resistance, the development of atherogenic dyslipidemia, increased markers of systemic inflammation, which most pronounced in patients with overweight and obesity, thus significantly increases the level of cardiovascular risk in patients with both AH and DM 2.

Keywords: arterial hypertension, diabetes mellitus type 2, carbohydrate disorders, insulin resistance, dyslipidemia.

List of references:  
1.    Arror AR. Insulin resistance and heart failure: molecular mechanisms. Heart Fail Clin. 2012;8(4):3133-3140.
2.    Biesma R, Aagaard-Hansen J, Hanson MA, Norris SA. A complex behavioural change intervention to reduce the risk 2 diabetes and prediabetes in the pre-conception period in Malaysia: study protocol for a randomised controlled trial. Trials. 2016;7(1):215.
3.    Horr S, Nissen S. Managing hypertension in type 2 diabetes mellitus. Best Pract Res Clin Endocrinol Metab. 2016;30(3):445-454.
4.    Hackam DG. The 2010 Canadian Hypertension Education Program recommendations for the management of hypertension. Can J Cardiol. 2010;26:249-258.
5.    Kim DI, Yang HI, Park JH et al. The association between resting heart rate and type 2 diabetes and hypertension in Korean adults. Heart. 2016(9):10-15.
6.    Large V, Peroni O, Letexier D. Metabolism of lipids in human white Adipocyte. Diabetes Metab. 2004;30:294-309.
7.    Montecucco F, Pende A, Quercioli A et al. Inflammation in the pathophysiology of essential hypertension. J Nephrol. 2011;24:23-34.
8.    Pereira M, Lunet N, Azevedo A, Barros H. Differences in prevalence, awareness, treatment and control of hypertension between developing and developed countries. J Hypertens. 2009;27:963-975.
9.    Schneider AL, Kalyani RR, Golden S et al. Diabetes and Prediabetes and Risk of Hospitalization: The Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care. 2016;39(5):772-779.
10.    Shimamoto K. Metabolic syndrome. Nippon Rinso. 2009;67(4):771-776.

Original language: English

11. Original researches


The state of oxidative and antioxidant systems in patients with the concomitant course of arterial hypertension, type 2 diabetes and hypothyroidism

V. D. Nemtsova

Kharkiv National Medical University

Objective — to investigate the state of oxidative and antioxidant systems in the comorbid course of arterial hypertension (AH), type 2 diabetes mellitus (DM 2) and subclinical hypothyroidism (SH).
Materials and methods. 233 patients (92 males and 141 females) aged 40 to 75 years were divided into groups. The 1st group of isolated AH stage II (comparison group) included 50 patients, the 2nd group consisted of 67 patients with AH II stage in combination with DM 2, the 3rd group involved 64 subjects with AH II stage and SH, the 4th group included 52 subjects with AH II stage, DM 2 and SH. The lipid, carbohydrate and thyroid metabolism, oxidative (malonic dialdehyde (MDA)) and antioxidant (glutathione peroxidase (GPO), SH-­groups) systems were studied.
Results and discussion. Hypercholesterolemia, dyslipidemia, signs of insulin resistance were observed in all groups. In the 1st group, MDA levels were the lowest, and the levels of GPO and SH-­groups were the highest (p < 0.05). In the 4th group, the MDA level of was significantly higher (p < 0.05), and the levels of GPO and SH­groups were significantly lower (p < 0.05) than in other groups. There were no significant differences between the levels of MDA, GPO, SH­groups between patients of the 2nd and 3rd groups (p > 0.05).
Conclusions. In the blood of patients with cardio­endocrine comorbidity, the disturbances of oxidative metabolism occur to a greater extent than at the isolated AH. This became apparent as the intensification of lipid peroxidation processes against the background reduction of antioxidant protection; simultaneous presence of AH, SH and DM 2 is accompanied by more intensive oxidative stress than combination of AH with DM 2 or SH.

Keywords: arterial hypertension, diabetes mellitus, hypothyroidism, oxidative stress.

List of references:
1.    Ageev F.T, Svirida ON, Blankova ZN i dr. Gipotireoz i serdechno-sosudistyie zabolevaniya (Rus). RMJ. 2014;13:980-5.
2.    Arutyunov AV, Dubinina EE, Zyibina NN. Metodyi otsenki svo­bodnoradikalnogo okisleniya i antioksidantnoy sistemyi organizma: metodicheskie rekomendatsii. SPb.: IKF «Foliant»;2000:104-9
3.    Blankova ZN, Ageev FT, Seredenina EM i dr. Gipotireoz i serdechno-sosudistyie zabolevaniya (Rus). RMJ. 2014;13:980-11.
4.    Bobrik MI. Vzaimnoe vliyanie tireoidnogo i uglevodnogo obmena. Paradigmyi i paradoksyi (Rus). Int J Endocrinol. 2015;3:127-132-15.
5.    Budnevskiy AV, Kravchenko AYa, Feskova AA, Drobyisheva ES. Dislipidemiya pri subklinicheskoy gipofunktsii schitovidnoy zhelezyi i effektivnost eYo korrektsii zamestitelnoy terapiey L-tiroksinom (Rus). Young Scientist. 2014;17:138-141.
6.    Horodyns’ka OYu. Rehional’ni osoblyvosti hipotyreozu v Poltavs’kiy oblasti (Ukr) Semeynaya meditsina. 2015;3 (59):186-188-3.
7.    Nakaz ¹ 356 MOZ Ukrayiny vid 22.05.2009 «Pro zatverdzhennya protokoliv nadannya medychnoyi dopomohy patsiyentam z endokrynnymy zakhvoryuvannyamy (Ukr). Available from: http://www.moz.gov.ua/ua/portal/dn_20090805_574.html -7
8.    Pankiv VI. Sindrom gipotireozu (Ukr). Int Neurolog J. 2013;5(59):174-191.
9.    Rasprostranennost saharnogo diabeta v Ukraine uvelichilas v poltora raza (Rus). Available from: http://socportal.info/2015/12/05/v-ukrayini-majzhe‑3-naselennya-hvoriye-na-tsukrovij-diabet.html‑2.
10.    Tsukrovyy diabet: vyznachennya, klasyfikatsiya, epidemiolohiya, faktory ryzyku: sympozyum N 156 (Ukr). Available from: http://www.mif-ua.com/education/symposium/cukrovij-diabet-viznachennya-klasifikaciya-epidemiologiya-faktori-riziku‑1.
11.    Catapano AL, Graham I, Backer G et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J. 2016;37(39):2999-3058. doi:10.1093/eurheartj/ehw272-12.
12.    Asvold BO, Vatten LJ, Nilsen TI et al. The association between TSH within the reference range and serum lipid concentrations in a population-based study. The HUNT Study. Eur J Endocrinol 2007;156(2):181-186.
13.    Brenta G. Diabetes and thyroid disorders. Br J Diabet Vasc Dis. 2010;10(4):172-177. doi: 10.1177/1474651410371321-16.
14.    Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hyperten. 2013;31(7):1281-1357. doi: 10.1097/01.hjh.0000431740.32696.cc‑6.
15.    Marwaha RK, Tandon N, Garg MK et al. Dyslipidemia in subclinical hypothyroidism in an Indian population. Clin Biochem. 2011; 44(14-15):1214-1217. doi: 10.1016/j.clinbiochem.2011.07.003-13.
16.    Pearce HS, Brabant G, Duntas LH et al. 2013 ETA Guideline: Management of Subclinical Hypothyroidism. Eur Thyroid J. 2013;2(4):215-228. doi: 10.1159/000356507-8.
17.    Roberto Testa, Anna Rita Bon fi gli, Francesco Prattichizzo, Lucia La Sala, Valeria De Nigris, Antonio Ceriello. The «Metabolic Memory» Theory and the Early Treatment of Hyperglycemia in Prevention of Diabetic Complications. Nutrients. 2017;9:437-45. doi:10.3390/nu9050437-17.

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12. Original researches


The peculiarities of portal hemodynamics in patients with non­alcoholic steatohepatitis and essential hypertension

K.À. Lapshyna

Kharkiv National Medical University

Objective — to evaluate the parameters of portal hemodynamics and intrahepatic blood flow in patients with non­alcoholic steatohepatitis (NASH) and essential hypertension (EH).
Materials and methods. Examinations involved 60 patients with NASH, aged 30 to 60 years (mean age (46.36 ± 5.1) years) with hypertension (EH) and 30 NASH patients without EH, included in the group of comparison. The control group consisted of 20 practically healthy volunteers. The clinical and laboratory parameters of blood, urine and biochemical blood parameters, echosonographic examination of the abdominal cavity organs have been performed to all patients.
Results and discussion. The increase in the diameter and volumetric flow velocity of the portal vein has been established in all patients with NASH. The maximal, minimal and maximal linear time-averaged velocity of blood flow in the portal vein in patients with NASH were lower than in practically healthy volunteers. For the splenic vein, the maximal blood flow velocity, the minimal blood flow velocity and the maximal linear blood flow velocity averaged over time were significantly higher in NASH patients vs the control group by 16, 24 and 7 %, respectively (< 0.001). The parameters of aortic hemodynamics, in patients with NASH and ET significantly differed from the indices of obtained from the common hepatic artery in comparison with the control group.
Conclusions. In NASH patients with ET, indices of the portal hemodynamics were mainly higher and significantly differed from those in the group of NASH patients without ET. The NASH and ET comorbidity resulted more intensive pathological alterations in the portal blood flow took place, than at the isolated disease course.

Keywords: portal hemodynamics, non-alcoholic steatohepatitis, blood indices.

List of references:  
1.    Balasubramanian P et al. Assessment of Portal Venous and Hepatic Artery Haemodynamic Variation in Non-Alcoholic Fatty Liver Disease (NAFLD) Patients. J Clin Diagn Res. 2016;10(8):TC07–TC10.
2.    Erdogmus B et al. Portal vein hemodynamics in patients with non-alcoholic fatty liver disease. Tohoku J Exp Med. 2008;215(1):89-93.
3.    Hano H, Takasaki S, Kobayashi H, Koyama T et al. In the non-cirrhotic stage of nonalcoholic steatohepatitis, angioarchitecture of portal veins and lobular architecture are maintained. Virchows Arch. 2013;462(5):533-540.
4.    Hirooka M et al. Nonalcoholic fatty liver disease: portal hypertension due to outflow block in patients without cirrhosis. Radiology. 2014;274(2):597-604.
5.    Mendes FD, Suzuki A, Sanderson SO et al. Prevalence and indicators of portal hypertension in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2012;10(9):1028-1033.
6.    Ochi H, Hirooka M, Koizumi Y et al. Real-time tissue elastography for evaluation of hepatic fibrosis and portal hypertension in nonalcoholic fatty liver diseases. Hepatology. 2012;56(4):1271-1278.
7.    Shigefuku R et al. Correlations of hepatic hemodynamics, liver function, and fibrosis markers in nonalcoholic fatty liver disease: Comparison with chronic hepatitis related to hepatitis C virus / Int J Molecular Sci. 2016;17(9):1545.
8.    Soresi M et al. Effects of steatosis on hepatic hemodynamics in patients with metabolic syndrome // Ultrasound Med Biol. 2015;41(6):1545-1552.
9.    Tana C et al. Hepatic artery resistive index (HARI) and non-alcoholic fatty liver disease (NAFLD) fibrosis score in NAFLD patients: cut-off suggestive of non-alcoholic steatohepatitis (NASH) evolution. J Ultrasound. 2016;19(3):183-189.

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13. Original researches


Lung function features and response to bronchodilator in patients with bronchial asthma, COPD and combined pathology of bronchial asthma and COPD

K.V. Nazarenko

SI «National Institute of Phthisiology and Pulmonology named after F.G. Yanovskyi of NAMS of Ukraine», Kyiv

Objective — to determine the lung function features and response to bronchodilator in patients with the asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) and to compare them with those in patients with bronchial asthma (BA) and COPD.
Materials and methods. The investigation involved patients with ACOS signs, aged above 30 years (n = 140), and
34 BA patients and 17 COPD patients. All patients underwent spirography with the analysis of the forced expiration «flow-volume» curve with the kit for the study of the respiratory system.  General body plethysmography, MasterScreenPneumo (CardinalHealth, Germany) was performed to determine the total bronchial resistance and the main respiratory capacity.
Results and discussion. Before the bronchodilator probe, the investigated patients with COPD and ACOS had the signs of pulmonary hyperinflation of different severity, as indicated by a significantly increased total bronchial resistance (Rtot), a nearly 50 % increased residual volume (RV), an enlarged intrathoracic gas volume (ITGV), reduced inspiratory capacity (IC) and expiratory reserve volume (ERV). In patients with asthma, the total bronchial resistance (149.54 ± 10.7) % was increased, while the other indicators were within the normal range.
In patients with asthma at the time of the initial examination in the whole group, the bronchial patency rates were within the normal range. Patients with COPD and ACOS had signs of moderate bronchial obstruction, significantly expressed in comparison with patients with asthma, but there was no significant difference between COPD and ACOS. MEF75 in patients with COPD was reduced to (38.66 ± 6.58) %, in patients with ACOS — to (33.78 ± 1.36) %, MEF50 was reduced to (24.54 ± 4.22) % in patients with COPD and up to (22.42 ± 0.85) % in patients with ACOS, MEF25 — to (21.66 ± 3.28) % in patients with COPD and up to (17.81 ± 0.71) % in patients with ACOS. PEF was also reduced in patients with COPD — up to (66.78 ± 5.13) %, in patients with ACOS — to (61.03 ± 1.76) %.
After 400 µg of salbutamol, the total bronchial resistance in patients with asthma and ACOS decreased (p < 0.05) relative to the baseline data, and in patients with ACOS — by more than 80 % — from (224.22 ± 8.56) to (143.42 ± 5.98) %. Significant (p < 0.05) dynamics was observed in patients with ACOS — RV decreased from (152.86 ± 3.63) to
(135.44 ± 3.62) %. FEV1 and FVC significantly (p < 0.05) increased only in patients with ACOS (from (59.02 ± 1.39) to (70.79 ± 1.63) % and from (89.94 ± 1.62)) to (100.74 ± 1.76) % respectively.
In patients with ACOS bronchial patency at the level of medium and small bronchi significantly (p < 0.05) increased (MEF75, 50, 25).In patients with asthma, MEF25 significantly increased. PEF also significantly increased in patients with ACOS (from (61.03 ± 1.76) to (73.07 ± 1.96) %.
Conclusions. The study revealed significant negative changes in the form of direct and indirect signs of pulmonary hyperinflation, the presence of fixed bronchial obstruction and a decrease in bronchial patency in patients with combined pathology of asthma and COPD.
In view of the revealed clear signs of pulmonary hyperinflation and impaired bronchial patency against the background of the fixed bronchial obstruction at the ACOS, the early detection and timely correction of the combined pathology proved to be rational.

Keywords: bronchial asthma, COPD, combined pathology of bronchial asthma and COPD, spirometry, body plethysmography.

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14. Reviews


Strategy for Harm Reduction in health care of Ukraine: challenges and prospects

V.V. Korolenko

O.O. Bogomolets National Medical University, Kyiv

The concept of harm reduction is a strategy for public policy, which includes a set of measures against harmful behavioral patterns (excessive alcohol consumption, smoking, poor nutrition, lack of physical activity, dependence on psychoactive substances, other variants of deviant behavior) through the introduction of mechanisms and instruments for stimulating consumption as less harmful products and services. In addition to the known practices in combating the dangerous consequences of drug use and paid sex services, there are many examples of effective use of harm reduction approaches in other areas of life: the creation of protective clothing for athletes and travelers, monitoring drivers sobriety, regulation of harmful emissions. All of this are pragmatic solutions to prevent disease, disability and mortality, as a practical implementation of European principles «Health in all policies». The primary step in implementation of harm reduction approach in the Ukrainian health care should be urgent development and regulatory approval of the appropriate concept of a unified conceptual apparatus in accordance with international law to answer the current global challenges and further involvement of harm reduction principles to solve health issues in all life areas.

Keywords: epidemiology, public health, WHO, Ukraine, harm reduction.

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15. Reviews


Endothelial dysfunction and its role in the pathogenesis of chronic obstructive pulmonary disease (Chapter I)

O. I. Lemko, N. V. Vantyukh

GI «The Scientific-practical Medical Center “Rehabilitation” Health Ministry of Ukraine», Uzhhorod

The article presents generalized data about peculiarities of endothelial dysfunction’s development in patients with chronic obstructive pulmonary disease (COPD). The relevance of the problem is formulated, the role of vascular endothelium in the regulatory activity of the organism is underlined and the main causes of its disturbances are presented. In particular, the significance of tobacco smoking as a major factor damaging the endothelium at COPD has been considered. The role of lipids peroxidation intensifying with the development of oxidative and nitrozolic stress in condition of hypoxia, which leads to the vascular wall remodeling and secondary chronic vasoconstriction, has been analyzed. The high prevalence of insulin resistance and metabolic disorders, which are accompanied by comorbid cardiovascular diseases negatively effect on the clinical picture of the dominating disease, is discussed.

Keywords: chronic obstructive pulmonary disease, endothelial dysfunction, lipids peroxidation, metabolic syndrome.

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50.    Yang L, Cheriyan J, Gutterman D. Mechanisms of Vascular Dysfunction in COPD and Effects of a Novel Soluble Epoxide Hydrolase Inhibitor in Smokers. Chest. 2017;151(3):555-563. doi:10.1016/j.chest.2016.10.058.

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