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The journal "Ateroskleroz"

2015 year, number 4

1.
CASCADE GENETIC SCREENING FOR FAMILIAL HYPERCHOLESTEROLEMIA

M.I. Voevoda, E.V. Shakhtshneider, K.V. Makarenkova, D.E. Ivanoshchuk, P.S. Orlov, Yu.I. Ragino
FSBSI «Institute of Internal and Preventive Medicine, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: cascade genetic screening, familial hypercholesterolemia, low density lipoprotein receptor gene, proprotein convertase subtilisin/kexin 9 gene, apolipoprotein B gene, mutations

Abstract >>
Familial hypercholesterolemia (FH) is one of the most common congenital metabolic disorders. Cascade genetic screening used for diagnostic of patients with FH. Aim of study is to explore the awareness of FH patients of the problem of familial hypercholesterolemia and conduct a pilot study of patients with FH using the principle of a cascade genetic screening. The study was performed in patients with a clinical diagnosis of definite FH. The study was approved ethics committee. Target was selected for high-throughput sequencing (GS Junior, Roche). Participation in the survey was voluntary and anonymous. An analysis of the responses to the questions provided data on the lack of awareness of patients with the FH about the problem. Certain mutations in this study and LDLR gene polymorphisms confirmed genetic heterogeneity of the spectrum of structural modifications of LDL receptor gene in patients with FH.



2.
THE RELATIONSHIP OF GENE POLYMORPHISMS OF C-REACTIVE PROTEIN WITH THE DEVELOPMENT OF MYOCARDIAL INFARCTION AND FORMATION OF MULTIFOCAL ATHEROSCLEROSIS IN CHD PATIENTS

O.L. Barbarash, Yu.V. Bayrakova, A.V. Ponasenko, M.V. Khutornaya, A.A. Kuzmina, Ya.V. Kazachek, L.S. Barbarash
FSBSI «Institute for Complex Issues of Cardiovascular Diseases, 650002, Kemerovo, Sosnovy bulvar, 6
olb61@mail.ru
Keywords: myocardial infarction, multivessel disease, C-reactive protein, CRP gene polymorphic sites (rs3093077, rs1130864, rs1205)

Abstract >>
Purpose. To assess the contribution of the CRP gene polymorphisms rs3093077, rs1130864 and rs1205 in the development of myocardial infarction (MI) and multivessel disease (MVD) in CAD patients based on gender and age. Material and methods. 303 patients with stable coronary artery disease were included in the study. C-reactive protein ( CRP ) levels were measured by high sensitive immunoturbidimetric assay. The genotyping studies were performed in 96-well plates using the TaqMan assay. Results. Male gender and older age are proven to be among independent clinical predictors of myocardial infarction and the development of MVD in patients with coronary artery disease. The rs1205 C/C CRP homozygous carriers have a significantly higher risk of multivessel coronary lesions at age > 65, regardless of gender (OR = 4.72, 95 % CI = 1.27-17.56; p = 0.045). The C/C genotype of rs3093077, A/G of rs1130864 and P/T of rs1205 in female patients reduce the risk of myocardial infarction (OR = 0.53, 95 % CI = 0.30-0.95; p = 0.0079, OR = 0.37, 95 % CI = 0.16 - 0.82; p = 0.0027 and OR = 0.35, 95 % CI = 0.14-0.84; p = 0.0097, respectively). The groups with and without myocardial infarction were comparable by the allele frequencies and genotype distribution combinations of the CRP polymorphisms (rs3093077, rs1130864 and rs1205). Regardless of a positive history of MVD and myocardial infarction, serum levels of CRP over 3 mg/L indicates a high risk of cardiovascular events in patients with stable coronary artery disease. However, there is no relationship between protein levels and the polymorphisms of the genes encoding them ( p = 0.56). Conclusion: The prediction of myocardial infarction and MVD requires not only assessing clinical and demographic data of patients, but also measuring CRP levels and studying its gene polymorphisms.



3.
THE CARDIOTONIC PROPERTIES OF HUMAN APOLIPOPROTEIN A-I

A.R. Kolpakov1,2, R.A. Knyazev1, N.V. Trifonova1, L.M. Polyakov1
1Institute of Biochemistry, 630117, Novosibirsk, Timakov str., 2
kolpakov2@yandex.ru
2Novosibirsk State Medical University, 63091, Novosibirsk, Krasny av., 52
Keywords: high density lipoproteins, apolipoprotein A-I, isolated rat heart, endogenous cardiotonics

Abstract >>
The aim of this study was to determine the action of apoliporotein A-I (apoA-I) - the main protein of plasma high density lipoproteins on the work capacity of isolated rat heart and the influence on its effects of classic cardiotoinc drugs (adrenaline, digoxin) and nonselective β-blocker propranolol. Results. By the regime of the recirculation the physiological concentration of apoA-I (20 g/ml) has stably elevated the intraventricular pressure but the coronary flow was changed insignificantly. Adrenaline has induced two-stage effect: initially it increased the frequency and the force of heart contractions but the induced left ventricular pressure decreased significantly. In the experiments with the simultaneous common perfusion of adrenaline and apoA-I the increased working capacity of isolated heart was recorded during the whole time of observation (30 min). ApoA-I has eliminated the cardiotonc activity of digoxin, and digoxin has removed cardiotonc effect of apoA-I too, and indicators of cardiac activity turned to control parameters but coronary flow was decreased. ApoA-I didnt abolish the negative chronotropic effect of propranolol but substantially (more 2 fold) increased the left ventricular pressure.



4.
ROLE OF GENETIC POLYMORPHISMS ASSOCIATED WITH LIPID DISORDERS AND ARTERIAL HYPERTENSION IN THE ASSESSMENT OF CLINICAL SEVERITY AND IN-HOSPITAL PROGNOSIS IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION

A.A. Inozemtseva1, V.V. Kashtalap1, L.A. Gordeeva2, E.N. Usoltseva1, O.V. Gruzdeva1, N.A. Terenteva3, O.L. Barbarash4,5
1FSBI «Research Institute for Complex Issues of Cardiovascular Diseases
nastya060988@yandex.ru
2FSBI «Institute of Human Ecology SB RAS, 650029, Kemerovo, Leningradski av., 10
gorsib@rambler.ru
3Kemerovo State Medical Academy, 650029, Kemerovo, Voroshilov str., 22A
queentna@gmail.ru
4FSBI «Research Institute for Complex Issues of Cardiovascular Diseases, 650029, Kemerovo, Voroshilov str., 22A
olb61@mail.ru
5Kemerovo State Medical Academy
Keywords: myocardial infarction, genetic polymorphism, prognosis, lipid metabolism, prognosis

Abstract >>
Objective: To study the clinical and prognostic significance of gene polymorphisms APOA1 rs670, APOA5 rs662799 and ACE rs4341 in patients with ST-segment elevation myocardial infarction. Materials and Methods: 358 patients admitted with STEMI and undergoing diagnosis and treatment at the Kemerovo Cardiology Clinic were included in the study. Blood samples were collected at days 2-14 for genotyping. Clinical and demographic data, laboratory and instrumental findings were assessed. Data analysis was performed using the STATISTICA program (version 8.0; StatSoft, Tulsa, Oklahoma) and the genetic calculators (GeneXpert) with the construction of different inheritance models. Results: The carriers of the CC genotype of gene APOA5 demonstrated significantly higher triglyceride levels, whereas the level of high density lipoprotein cholesterol was lower in the carriers of the CC-genotype. The carriers of the GG genotype had a 3-fold increased risk of recurrent myocardial infarction (OR = 2.99, 95 % CI = 1.33-6.73, p = 0.006), and a 2.12-fold increased risk of early post-infarction angina, pulmonary edema and in-hospital death (OR = 2.12, 95 % CI = 1.14-3.94, p = 0.02). Allele D of gene ACE was associated with thickening intima-media complex of carotid arteries (OR = 1,65, 95 % CI = 1,04-2,61, p = 0,03). Conclusion: The polymorphic variants of genes associated with lipid metabolism disorders ( APOA1, APOA5 ) and arterial hypertension ( ACE ) may be used to assess the clinical severity and in-hospital prognosis in patients with myocardial infarction.



5.
EFFECTS OF LUDARTIN AND GROSSHEMIN ON EXPERIMENTAL HYPERLIPIDEMIA INDUCED BY TRITON WR 1339

A.V. Ratkin1, O.A. Kaidash1, V.V. Ivanov1, V.S. Chuchalin1, S.M. Adekenov2, A.I. Vengerovskiy1
1Siberian State Medical University, 634050, Tomsk, Moskovsky trakt, 2
ratkin@ssmu.ru
2JSC «International scientific-industrial holding Phytochemistry, Karaganda, Kazakhstan, M. Gazaliyev str., 4
phyto_pio@mail.ru
Keywords: ludartin, grosshemin, triton WR 1339, gemfibrozil, sesquiterpene γ-lactones, experimental hyperlipidemia, lipid-lowering effect

Abstract >>
The hypolipidemic action of sesquiterpene γ-lactones ludartin and grosshemin was studied in vivo experiments on the model of acute hyperlipidemia induced by Triton WR 1339. Hyperlipemia model induced by Triton WR 1339, characterized by a sharp increase in the content in the serum of triacylglycerides and total cholesterol, mainly due to the increase of cholesterol in proatherogenic fractions of lipoproteins (low density). Hypolipidemic action of ludartin and grosshemin on the background of triton WR 1339 induced hyperlipemia, and drug comparison of phenofibrate, evident decrease in the content of triacylglycerides and pro-atherogenic cholesterol in low density lipoproteins in the blood serum, as well as reducing the amount of triacylglycerides and cholesterol in the liver of rats.



6.
LIPID METABOLISM IN WOMEN WITH CORONARY HEART DISEASE OF DIFFERENT AGES DUE TO LEVELS OF SEX HORMONES

O.V. Tsygankova1, L.D. Latyntseva2, Yu.I. Ragino2, Z.G. Bondareva1, K.Yu. Nikolaev2, V.N. Maksimov2, M.G. Pustovetova1
1Novosibirsk State Medical University, 630091, Novosibirsk, Krasny av., 52
oksana_c.nsk@mail.ru
2FSBSI «Institute of Internal and Preventive Medicine, 630089, Novosibirsk, Boris Bogatkov str., 175/1
ludmilanov2010@mail.ru
Keywords: FSH, testosterone, women, coronary heart disease, lipids

Abstract >>
Objective: To analyze the basic components of the lipid profile of blood serum in patients with coronary artery disease based on the levels of follicle stimulating hormone (FSH), testosterone and age, to explore their association with anthropometric parameters and indices of insulin-glucose homeostasis. The study involved 285 women aged 35-65 years who have had myocardial infarction at least 30 days before the survey. The median age was 54.4 years (25 and 75 % percentile: 43.2 and 61.3 years). Patients were divided into age groups: 35-55 years and 56-65 years (first and second groups of age, respectively), as well as groups on levels of sex hormones FSH and ≥ <30 mIU / ml and ≥ testosterone and <3 nm / l. Using analysis of covariance it is determined that in women 35-55 years with coronary heart disease significant factor determining the back high density lipoprotein (HDL) cholesterol is FSH ≥30 mIU / ml ( p = 0.001) for low density lipoprotein (LDL) cholesterol directly affects T ≥ 3 nmol / l ( p = 0.002), and triglyceride (TG) levels is mediated by the direct influence of FSH ≥ 30 mIU / ml ( p = 0.001). In the category of patients 56-65 years of multivariate analysis indicator back to determining the level of HDL cholesterol, the index was the HOMA-R ( p = 0.015), TG directly dependent on blood glucose ( p = 0.001), T ≥ 3 nmol / l ( p = 0.007), the index of HOMA-R ( p = 0.035) and FSH ( p = 0.042). Thus, in women 35-55 years a fundamental factor in the development of hypertriglyceridemia and gipoalfaholesterinemia is a high level of follikulotropin; hyperandrogenism in this age group was accompanied by an increase LDL cholesterol. In patients 56-65 years raising of TG and lowering of HDL cholesterol is mediated primarily indices of insulin-glucose-axis, as well as smaller but independent influence of hyperandrogenism and FSH ≥ 30 mIU / ml.



7.
THE ASSOCIATION OF THE MARKER OF CARDIOVASCULAR RISK - QTc interval with 64V/64I CCR2 GENE POLYMORPHISM AND METABOLIC SYNDROME COMPONENTS IN THE GENERAL MALE POPULATION OF NOVOSIBIRSK

A.A. Kuznetsov, M.I. Voevoda, V.N. Maksimov, I.V. Kulikov, T.I. Batluk, A.A. Kuznetsova, N.I. Tereshchenko, S.K. Malyutina, Yu.P. Nikitin
FSBSI «Institute of Internal and Preventive Medicine, 630089, Novosibirsk, Boris Bogatkov str., 175/1
kuznetsoviimed@gmail.com
Keywords: QTc interval, 64V/64I polymorphism, CC chemokine receptor 2 gene, metabolic syndrome components, general population

Abstract >>
Myocardial electric instability, apparently , has a multigenic and multifactorial basis. It is interesting to examine of the association of the QTc interval with CC chemokine receptor 2 gene polymorphism ( CCR2 ) and metabolic syndrome components. Survey data from a representative sample 831 men aged 25-64 out of a general population of Novosibirsk («MONICA WHO project) were used. For genetic research by randomly were selected 393 people. The components of the metabolic syndrome (obesity, hypertension, hypertriglyceridemia and hypo-alpha-lipoproteinemia) were determined according to the WHO criteria. To calculate the corrected QTc interval Bazett formula has been used. The analysis in the multivariate linear regression model showed that the QTc interval was independently associated with 64V/64I(rs1799864) CCR2 gene polymorphism ( p = 0.04) and hypertension ( p = 0.0003).



8.
GALECTIN-3 - PROSPECTIVE BIOMARKER OF RISK STRATIFICATION IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION

N.V. Fedorova1, V.V. Kashtalap1,2, O.N. Khryachkova1, O.L. Barbarash1
1FSBSI «Research Institute for Complex Issues of Cardiovascular Diseases, 650002, Kemerovo, Sosnovy bulvar, 6
BNatalia88@mail.ru
2Kemerovo State Medical Academy, 650029, Kemerovo, Voroshilov str., 22a
v_kash@mail.ru
Keywords: galectin-3, myocardial infarction, risk stratification

Abstract >>
Galectin-3, being one of the most recent studied biomarkers, may be used as a laboratory marker of neoplastic transformation and a biomarker of chronic heart failure. Purpose: To evaluate the clinical and prognostic significance of galectin-3 in patients with ST- segment elevation myocardial infarction (MI). Material and Methods: 87 patients with ST-segment elevation myocardial infarction admitted to the hospital were included in the study. Galectin-3 levels were measured with ELISA on days1-2 in all patients. The serial measurement was performed in 81 patients on days 10-14. Results: Galectin-3 level was 9.5 [3.3; 11.9] ng / ml on days 1-2, and increased to 15.6 [9.9; 37.4] ng / ml after MI on days 10-14 ( p = 0.003). Higher levels of galectin-3 ( p = 0.04) were found in patients with a positive history of acute cerebrovascular accidents (ACVA), compared to patients without prior ACVA (42.5 [25.4; 57.1] ng / ml vs. 15.5 [9.9; 35.9] ng / ml). Galectin-3 levels in patients who had a history of hypercholesterolaemia on days 10-14 after MI increased by 47 % ( p <0.01) compared to patients without it. Similar results were observed in patients with hereditary coronary artery disease ( p = 0.02). Patients with arterial hypertension demonstrated elevated galectin-3 levels on days 10-14 after MI, compared to patients without it (20.1 [10.4; 38.9] ng / ml vs. 9.9 [9.1; 33.8] ng / ml, respectively, p = 0.04). Patients with type 2 diabetes mellitus also reported higher values of the analyzed markers on days 10-14 after MI ( p = 0.01). Patients with LV dilatation and reduced left ventricular ejection fraction < 40 % reported significantly higher galectin-3 levels measured on days 10-14 ( p = 0.02) compared to patients with normal LV size and preserved ejection fraction. A positive correlation has been determined between galectin-3 levels and LV EDD and LV ESD ( r = 0.39 and r = 0.40, respectively, p < 0.01), and an inverse correlation - between galectin-3 and left ventricular ejection fraction ( r = -0.26, p = 0.02 ). CAD patients with three-vessel disease had higher levels of galectin-3 on days 10-14 after MI days ( p = 0.02), 35.8 [13.2; 43.0] ng / ml, than patients with one-vessel disease - 11.1 [9.5, 31.5] ng / ml. The serial management of galectin-3 in groups with two and three-vessel disease reported its increase by days 10-14 (10.2 [5.1; 13.3] ng / ml vs. 18.5 [10.4; 35.9] ng / ml, p <0.01; 3.4 [2.9, 4.6] ng / ml vs. 35.8 [13.2; 43.0] ng / ml, p < 0.01, respectively). A direct correlation has been determined between the levels of this biomarker on days 10-14 and door-to-balloon time (min) ( r = 0.27; p = 0.02). Conclusion. The results of the current study have shown the possibility to use galectin-3 level for risk stratification of MI patients. Despite the large number of experimental and clinical studies of this biomarker, some matters of concern require further investigation.



9.
PREVALENCE OF METABOLIC SYNDROME COMPONENTS IN YOUNG ADULTS

M.I. Voevoda, N.A. Kovalkova, Yu.I. Ragino, N.Yu. Travnikova, D.V. Denisova
FSBSI «Institute of Internal and Preventive Medicine, 630089, Novosibirsk, Boris Bogatkov str., 175/1
mvoevoda@ya.ru
Keywords: metabolic syndrome, prevalence, epidemiology, population

Abstract >>
Objective: To study the prevalence of metabolic syndrome and its components in the population aged 25-45 in Novosibirsk. Materials and Methods: During the years 2013-2015 conducted a cross-sectional population-based survey of the population of one of the typical areas of Novosibirsk. The study included 346 men and 408 women. To identify the criteria used Russian Society of Cardiology (RSC, 2009). According to the criteria RSC recorded in the MetS by waist circumference (WC) > 80 cm in women and >94 cm men, plus two of the following criteria: blood pressure (BP) ≥ 130/85 mm Hg, triglycerides (TG) ≥ 1.7 mmol/l, high-density lipoprotein cholesterol (HDL-C) < 1.2 mmol/l (women) and <1,0 mmol/l (men); low-density lipoprotein cholesterol (LDL-C) > 3.0 mmol/l, plasma glucose ≥ 6.1 mmol/l. Results: According to the definition RSC (2009), the prevalence of WC was 42.6 % (41 % in men, 44 % in women; = 0.433), arterial hypertension - 33.5 % (53 % in men, 21 % in women; < 0,0001), TG ≥ 1.7 mmol/l - 17.5 % (26.3 % in men, 9.6 % in women; < 0,0001), decreased HDL-C - 24.3 % (27.7 % in women, 20.5 % in men; = 0.023), increased LDL - 64.8 % (66.8 % in men, 63.7 % in women; = 0.383), increased plasma glucose - 29 % (39.3 % in men, 20.1 % in women). Thus, the high prevalence of metabolic syndrome components in young adults of Novosibirsk identified.



10.
The role of Central arterial pressure in cardiovascular remodeling in patients with prehypertension

O.N. Antropova, I.V. Osipova, V.D. Kondakov
Altai State Medical University, 656049, Barnaul, Lenin av., 40
vladislav.kondakov@gmail.com
Keywords: prehypertension, central blood pressure, arterial stiffness

Abstract >>
Aim. To study the features of vascular remodeling in patients with prehypertension, taking into account the level of the peripheral and central blood pressure compared to the patients with hypertension. Material and methods. Inclusion criteria: men 40-55 years. The first group - 92 men with prehypertension, the second - 89 men diagnosed with hypertension, the third - 30 volunteers with normal blood pressure numbers. The estimation of anthropometric indices, blood pressure, heart rate, blood lipid research was performed. We measured ankle-brachial index (ABI), the thickness of the brachiocephalic intima-media, vascular stiffness and central blood pressure parameters. Results. Central BP in the first group was 129.0 2.5 mm Hg, in the second group - 130.0 3.5 mm Hg ( p < 0,05), in the third - 108.0 2.5 mm Hg. Correlation analysis showed the of links with the central BP and smoking ( r = 0.8; p < 0.001), IMT ( r = 0.7; p < 0.001) and the presence of dyslipidemia ( r = 0.4; p < 0.01). For peripheral blood pressure links with smoking were identified ( r = 0.5; p < 0.05). Stiffness index (SI) of large arteries in the 1st group was 7.20 1.99 m / s in the second - 8.90 1.85 m / s in the 3rd - 5.5 1.85. The average value of the reflection index the small resistance arteries (RI) - 36.59 15.43 %, 35.469 14.50 % and 30.39 13.43 in the groups, respectively. Augmentation index in the groups were comparable. PWV>10 m / s was found in 3 % and 4 % in the first and second groups, respectively, in the third group, the value of PWV> 10 m / s have not been diagnosed. The differences between the groups did not reach statistical significance. In patients with PH in the test with mental and emotional stress the growth of SBP and heart rate appeared greater compared with the 2nd and 3rd groups ( p < 0.05), increase in diastolic blood pressure more than in the third group ( p < 0.05) .Conclusions. People with prehypertension have a comparable rate of endothelial dysfunction, arteriosclerosis and brachiocephalic atheroma, but a lower incidence of atherosclerosis of the lower extremities compared to the hypertension. Patients with prehypertension in 40 % have high normal BP, a greater incidence of brachiocephalic atherosclerosis and lower extremities vessels compared to normal central BP. Central blood pressure correlated with risk factors for CVD, ABI and brachiocephalic intima-media thickness.



11.
INTERRELATION OF LEPTIN LEVELS IN BLOOD AND THE MAIN COMPONENTS OF METABOLIC SYNDROME AMONG OILMEN WORKING IN THE OIL INDUSTRY IN WESTERN SIBERIA

I.I. Logvinenko, Ya.S. Koleda, Yu.I. Ragino, M.I. Voevoda
FSBSI «Institution of Internal and Preventive Medicine, 630089, Novosibirsk, Boris Bogatkov str., 175/1
111157@mail.ru
Keywords: the main components of metabolic syndrome, leptin, C-peptid, abdominal obesity, hypertension, general risk of development of cardiovascular diseases, workers of the oil industry

Abstract >>
The purpose of this research is to examine leptin levels in blood serum and frequency of the main components of metabolic syndrome among oilmen working in shifts in Western Siberia. Materials and methods : The research design is solid and cross-sectional. The research object is 125 men working in the oil industry in Western Siberia at the age of 30.2-45.7 (mean age is 35.33.5). Examination methods are anthropometry, measurement of blood pressure, electrocardiogram and determination of total cholesterol, glucose, leptin and C-peptid in blood plasma. Statistical data processing was performed using the Statistica 8.0 software package. Results : 73.60 % of the examined had certain components of metabolic syndrome: abdominal obesity (32.8 %), hypertension (23.2 %), hypercholesterolemia (59.2 %). The combination of these features was observed in 52.17 % of cases. 43.2 % of oilmen had overweight, 36.0 % - high normal blood pressure. Leptin concentrations in plasma fluctuated within 0.22-140.06 ng/ml (mean value is 16.9321.19 ng/ml). C-peptid concentrations in plasma fluctuated within 0.01-6.19 mmol/l (mean value is 0.460.71 mmol/l). Conclusion: There were revealed essential differences between the leptin levels in the oilmen groups working in shifts with a normal BMI and obesity; with hypercholesterolemia and total cholesterol level below 5.1 mmol/L; with hyper-C-peptidemia and normal basal concentration of C-peptide ( p ≤ 0.01). While estimating the binding force according to the scale Cheddoka, there was established a statistically significant p < 0.05 dependence between the concentration of leptin and C-peptide in plasma: it is reverse and noticeable.



12.
Myocardial revascularization in multivessel coronary lesions in conjunction with chronic occlusion. Choosing tactics

L.S. Kalugina, I.A. Urvantseva
BI District Cardiological Dispensary - Centre for Diagnostics and Cardiovascular surgery, 628400, Surgut, Lenin str., 69/1
disonto@mail.ru
Keywords: coronary heart disease, multivessel coronary disease, chronic coronary artery occlusion, myocardial revascularization

Abstract >>
The review presents the current scientific literature on the status of the problem of myocardial revascularization in multivessel coronary lesions channel.Shows the results of studies conducted in the past 15 years, including a systematic review and meta-analysis. Describes the main indications, complications of percutaneous coronary intervention in patients with chronic total occlusion.Presents outcomes and long-term effects of different types of revascularization. Shows the results of the analytical and comparative research published papers on the issue.