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The journal "Ateroskleroz"

2018 year, number 3

1.
ATHEROGENIC NORMOLIPIDEMIA IN MEN WITH CORONARY ATHEROSCLEROSIS: SOME PECULIARITIES OF SUBFRACTIONAL DISTRIBUTION OF APO B-CONTAINING LIPOPROTEINS

I.N. Ozerova, V.A. Metelskaya, N.E. Gavrilova
National Medical Research Center for Preventive Medicine of Minzdrav of Russia, 101990, Moscow, Petroverigskiy lane, 10, str., 3
Keywords: коронарный атеросклероз, нормолипидемия, субфракционный спектр, ЛПНП Липопринт-система, coronary atherosclerosis, normolipidemia, subfractional profile, Lipoprint LDL system

Abstract >>
Background: Plasma apo B-containing lipoproteins of low densities represent a heterogeneous population of particles varying by physicochemical composition, functional activity, and atherogenicity. Aim: To study some peculiarities in low density lipoproteins subfractional distribution in men with coronary atherosclerosis at normolipidemia. Material and methods: Patients with angiographically documented coronary atherosclerosis were included into the study ( n = 177; mean age 62.5 ± 9.3 yrs). Lipoprotein subfractional distribution was analyzed using Lipoprint LDL System (Quantimetrix, USA). Results: Out the total cohort normolipidemic patients (total C < 5,0 mmol/l, TG < 1.7 mmol/l, LDL-C < 2.5 mmol/l) with coronary atherosclerosis were selected and thereafter were split into those without small dense LDL (sdLDL) - group 1, n = 16, and and group 2 with presence of sdLDL ( n = 22). Patients from group 2 had lower portion of IDLB: 7.0 ± 1.2 vs 8.5 ± 1.0 %, IDLА: 7.9 ± 1.7 vs 9.6 ± 2.5 %, and higher LDL2 portion: 7.0 ± 2.0 vs 4.3 ± 1.6 %. In group 2 C level in LDL2 was higher than in group 1 while in IDL B it appeared to be lower. Mean LDL particles size in group 2 was lower as well: 270.7 ± 1.3 и 273.8 ± 0.8 Е. Conclusion. In men with coronary atherosclerosis at normolipidemia two different patterns of subfractional distribution of apo B-containing lipoproteins were detected. Presence of sd LDL associated with decreased LDL size could be regarded as more atherogenic profile even at normal lipid levels.
																								



2.
A PANEL OF GENETIC MARKERS FOR ANALYZING THE RISK OF LONG-TERM ADVERSE PROGNOSIS OF CARDIOVASCULAR DISEASES

E.V. Shakhtshneider1, P.S. Orlov1,2, L.V. Shcherbakova1, D.E. Ivanoshchuk1,2, S.K. Malyutina1, V.N. Maksimov1,2, V.V. Gafarov1, M.I. Voevoda1,2
1Institute of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
2Federal Research Center Institute of Cytology and Genetics of SB RAS, 630090, Novosibirsk, Academician Koptyug av., 2
Keywords: генетический рискометр, неблагоприятные исходы, инфаркт миокарда, APOE, CETP, сердечно-сосудистые заболевания, model of genetic risk, unfavorable outcomes, myocardial infarction, APOE, CETP, cardiovascular diseases

Abstract >>
Aim: to form a panel of genetic markers for analyzing the risk of long-term adverse prognosis of cardiovascular diseases in Russia population. Material and methods. A sample of nine hundred individuals was formed within the framework of the HAPIEE project (age 45-69 years, middle age 53.9 ± 6.9, male/female - 50/50). Molecular genetic analysis was performed using PCR followed by restriction fragment length polymorphism analysis for the APOC3 gene rs5128 polymorphism, APOE gene rs429358 and rs7412, CETP gene rs708272, LPL gene rs320, SCARB1 gene rs5888, and SREBF2 gene rs2228314 . Results. 10 single nucleotide polymorphisms were analyzed for the inclusion in the risk model of adverse prognosis of cardiovascular diseases in Russia population. The APOE gene e4/e4 genotype (rs429358 and rs7412) was associated with the development of adverse cardiovascular outcomes for 7 years of observation. For the CETP gene rs708272, the association with the development of cases of fatal myocardial infarction for 7 years of observation was demonstrated for the genotypes carrying C allele. No statistically significant association with the risk of adverse prognosis of cardiovascular diseases was obtained for the APOC3 gene rs5128, LPL gene rs320, SCARB1 gene rs5888, and SREBF2 gene rs2228314 in this pilot study. Conclusions. Pilot data on the presence of statistically significant association with the risk of long-term adverse prognosis of cardiovascular diseases in Russia population were obtained for the APOE and CETP genes.
																								



3.
ASSESSMENT OF THE EFFECT OF RS2230806 ALLELIC VARIANT IN THE ABCA1 GENE ON THE LIPID-LOWERING EFFECTS OF ATORVASTATIN IN PATIENTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA

G.P. Smirnov1, T.A. Rozhkova1, M.Yu. Zubareva1, Yu.A. Shuvalova1, D.V. Rebrikov2,3, A.I. Kaminny1, V.N. Titov1, V.V. Kukharchuk1, P.P. Malyshev1
1National Medical Research Center of Cardiology of Minzdrav of Russia, 121552, Moscow, 3rd Cherepkovskaya str., 15A
2Pirogov Russian National Research Medical University of Minzdrav of Russia, 117997, Moscow, Ostrovityanova str., 1
3Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology of Minzdrav of Russia, 117997, Moscow, Academician Oparin str., 4
Keywords: аторвастатин, АТФ-связывающий кассетный транспортер А1, полиморфизм гена АВСА1, семейная гиперхолестеринемия, R219K, rs2230806, ABCA1 gene polymorphism, atorvastatin, ATP-binding cassette transporter A1, familial hypercholesterolemia, R219K, rs2230806

Abstract >>
Objective: to evaluate the effect of rs2230806 variant in the ABCA1 gene on lipid and apolipoprotein (apo)A-I and apoB levels after the atorvastatin treatment in patients with heterozygous familial hypercholesterolemia (FH). Material and methods. The study included 83 patients with FH according to the British clinical SBR-criteria of the disease, all patients received atorvastatin at a dose of 40 mg/day for 3 months.Genotypingthe rs2230806 polymorphism was determined by «real time» polymerase chain reaction (PCR) using adjacent samples and melting reaction products after PCR. Total cholesterol (TC) and triglycerides (TG) were determined by a unified enzymatic method, high - density lipoproteins (HDL) and low - density lipoproteins (LDL) - by a direct homogeneous method, apoproteins - by immunoturbidimetric method. Results. Carriers of allelic variant were 52.9 % of patients (with one allele in 31.4 %, with two in 21.4 %). We revealed a difference in the change from the initial values of TC (-40.2 % vs. -34.4 %; p = 0.041), LDL (-50.8 % vs. -44 %; p = 0.041) and apoB (-48 % vs. -38.3 %; p = 0.02) with greater response to atorvastatin in homozygous carriers (genotype A/A) compared with heterozygous (genotype G/A) ones. The selective analysis depending on the sex and genotype rs2230806 among male carriers of allelic variant revealed a significant increase in the levels of HDL and apoAI by 10.6 % and 15.5 %, respectively, while in patients without polymorphism these lipid parameters decreased (by 3.8 % and 3.9 %, respectively). Conclusion. The variant rs2230806 in the ABCA1 gene was associated with a significant lipid-lowering effect of atorvastatin, and also increased the levels of apoA-containing plasma lipoproteins in male patients with FH.
																								



4.
THE ASSOCIATION OF RISK FACTORS FOR ATHEROSCLEROSIS AND POLYMORPHISM OF THE ADRB1 GENE WITH PRO-ARRHYTHMIC ELECTROCARDIOGRAPHIC PATTERNS IN THE GENERAL POPULATION OF NOVOSIBIRSK

A.A. Kuznetsov, A.A. Kuznetsova, T.I. Batluk, V.N. Maksimov, M.I. Voevoda, S.K. Malyutina, Yu.P. Nikitin
Institute of Internal and Preventive Medicine - Branch of Feseral Research Institute of Cytology and Genetics of SB RAS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: факторы риска, полиморфизм гена ADRB1, Бругада-паттерн, ранняя реполяризация, фрагментация QRS, общая популяция, risk factors, ADRB1 gene polymorphism, Brugada-pattern, early repolarization, QRS fragmentation, general population

Abstract >>
The dangerous electrophysiological shifts in the myocardium, with the exception of rare congenital canalopathies, are overwhelmingly secondary, being a consequence of various pathological conditions. These processes, in turn, can also be genetically determined. Thus, the association of indices of ventricular repolarization with polymorphism of adrenoreceptor genes is shown. The electrical instability of the myocardium, apparently, has a multigenic and multifactorial basis. The aim of the study was to study the relationship between the risk factors and the polymorphism of the ADRB1 gene with pro-arrhythmic electrocardiographic patterns in the general population of Novosibirsk. Material and methods. Materials of epidemiological study of the general population of Novosibirsk under the WHO project «MONICA» (a sample of 831 men aged 25-64 years) were used. For genetic research 195 people were randomly selected. ECG-patterns were identified in a 30 % subsample - 261 people. The number of people with both genetic and electrocardiographic data was 105 people. According to the WHO criteria, components of the metabolic syndrome were identified. The A145G (rs1801252) polymorphism of the ADRB1 gene was determined. The Brugada, early repolarization, QRS fragmentation patterns were detected according to current criteria. The multivariate general linear model (GLM) were applied. Results. The QRS fragmentation was independently associated with obesity ( p = 0.014), increased TG level ( p = 0.040), decreased HDL cholesterol level ( p = 0.00079) and polymorphism of the ADRB1 gene (p = 0.00019). Conclusion. The integral approach is advisable in analyzing the genetic, metabolic and electrophysiological factors causing the electrical instability of the myocardium.
																								



5.
FEATURES OF LIPID AND CARBOHYDRATE METABOLISM IN THE INDIGENOUS POPULATION ОF YAKUTIA, DEPENDING ON ETHNICITY

S.I. Sofronova, A.N. Romanova, V.M. Nikolaev
Yakut Scientific Center of Complex Medical Poblems, 677010, Republic of Sakha (Yakutia), Yakutsk, Sergelyakhskoe shosse, 4
Keywords: гиперхолестеринемия, гипергликемия, коренное население, Якутия, hypercholesterolemia, hyperglycemia, indigenous people, Yakutia

Abstract >>
The features of lipid and carbohydrate metabolism in the indigenous population of the north of Yakutia are studied depending on ethnicity. The analysis of blood parameters found that the average values of atherogenic low-density lipoprotein cholesterol exceeded reference values in all ethnic groups. The high frequency of hypercholesterolemia due to the atherogenic fraction in all ethnic groups was shown, the highest was observed in Evenks and Yakuts. The frequency of hyperglycemia is significantly higher in the Dolgans, Evenks and Yakuts in comparison with other ethnic groups.
																								



6.
Lipid profile in young people with newly diagnosed type 2 diabetes mellitus

A.K. Ovsyannikova, L.V. Shcherbakova, S.V. Mustafina, Yu.I. Ragino, D.V. Denisova, A.K. Kuntsevich, O.D. Rymar
Institute of Internal and Preventive medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: сахарный диабет 2 типа, липидный профиль, молодые пациенты, type 2 diabetes mellitus, lipid profile, young patients

Abstract >>
Diabetes mellitus (DM) is one of the most important not only medical but also social problems. With the development of vascular complications in people with diabetes in all age groups associated with the presence of dyslipidemia which is why these patients need to determine the lipid spectrum. In 30 patients aged 45 years with newly diagnosed type 2 diabetes (DM2) and in a control group comparable in sex, age and body mass index (BMI), the lipid profile was studied. Statistically significant differences were not detected not by one indicator between persons with hyperglycemia and with normoglycemia but the average levels of total cholesterol and low-density lipoprotein cholesterol were higher than the target values in both groups. There are no gender differences either. Perhaps this is due to a small amount of DM at which metabolic changes have not yet developed.
																								



7.
THE KLOTHO PROTEIN CONTENT AND LIPID BLOOD PROFILE BY AGE IN MEN 20-65 YEARS

O.V. Timoshchenko, Yu.I. Ragino, E.M. Stakhneva, Yu.V. Shchepina, E.V. Kashtanova, L.D. Latyntseva
Institute of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: белок Клото, старение, липиды, ЛП(а), коэффициент атерогенности, Klotho protein, aging, lipids, Lp(a), atherogenic index

Abstract >>
Purpose of the study. To study the special of protein Klotho and lipid profile in blood in young men and middle-aged men. Material and methods. Men ( n = 71) at the age of 20-35 years old (I group) and 50-65 years old (II group) were examined.Patients underwent general clinical, anthropometric, biochemical and instrumental examinations. The concentration in the blood serum of the Klotho protein was measured by the immunoenzyme technique ELISA. The content of total cholesterol and its components was determined by enzymatic methods. Results. The mean serum of protein Klotho in men I group was 687.6 ± 222.8 pg/ml, in II -1051.6 ± 121.5 pg/ml. The differences are significant - 1.5 times, but statistically unconvincing ( p = 0.161). A positive correlation was obtained between the protein Klotho and lipid metabolism indices: TC, TG, VLDL,non-LDL cholesterol, atherogenic index and inverse correlation with HDL-cholesterol. Conclusion.There is a tendency to increase with age the content of lipid components in the blood - non-HDL cholesterol, LDL-cholesterol, VLDL and atherogenic index. It can be concluded that, at the age of 20-65 years, the level of protein Klotho remains a tendency to increase in parallel with an increase in lipid parameters, in particular, the atherogenic index.
																								



8.
THE STUDY OF THE ASSOCIATIONS OF BLOOD LIPID PROFILE WITH THE EXPRESSION OF ATHEROSCKLEROSIS AND STRUCTURAL CHANGES IN THE ACHILLES TENDON

A.V. Anikina1, M.E. Amelin2, Yu.P. Nikitin1
1Institute of Internal and Preventive medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
2Federal Center of Neurosurgery of Minzdrav of Russia, 630108, Novosibirsk, Nemirovich-Danchenko str., 130/1
Keywords: атеросклероз, гиперхолестеринемия, сухожилия трехглавой мышцы голени, atherosclerosis, hypercholesterolemia, triceps tendon

Abstract >>
Objective. To study the possible relationship between the level of different cholesterol fractions and the severity of atherosclerosis with the change in the Achilles tendon. Material and methods. A random selective group of patients of the vascular neurosurgery department of the Federal Center of Neurosurgery of the Ministry of Health of the Russian Federation (Novosibirsk) was examined for monolateral or bilateral atherosclerosis of the carotid arteries with varying degrees of stenosis. Our study included 25 people aged 42-65 years. All patients underwent a series of clinical and instrumental studies (ECG, computed tomography, angiography, collection of clinical data, biochemical studies of blood serum). Results. In the group with a high content of low cholesterol and low-density lipoprotein cholesterol, a direct correlation was observed between cholesterol level and severity of atherosclerosis with the size and density of the Achilles tendons. Conclusions. An increased level of blood cholesterol concentration, especially in individuals with carotid stenosis, may be involved in the processes of connective tissue degeneration. With an increase in the level of total cholesterol above 5 mmol / l, an increase in the volume of the Achilles tendon and an increase in its density is noted.
																								



9.
PROTEOMIC STUDIES IN ATHEROSCLEROSIS

Yu.I. Ragino, E.M. Stakhneva
Institute of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and genetics of SB RAS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: протеомика, атеросклероз, биомаркеры, масс-спектрометрия, proteomics, atherosclerosis, biomarkers, mass spectrometry

Abstract >>
The review is devoted to the analysis of literature data related to the role of proteomic technologies in the study of atherosclerotic cardiovascular diseases. The results of research on the search for new proteomic potential biomarkers of coronary atherosclerosis, coronaryc heart disease, acute coronary syndrome, myocardial infarction, carotid atherosclerosis, and proteomic markers of unstable atherosclerotic plaque are presented. It is discussed that proteomic analysis is a promising developing field of research.
																								



10.
NUMBER OF COPIES OF MITOCHONDRIAL DNA OF LEUKOCYTES AS A MARKER OF PREDISPOSITION TO CORONARY HEART DISEASE AND SUDDEN CARDIAC DEATH

V.N. Maksimov1,2, A.A. Gurazheva1, Yu.V. Maksimova1,3
1Institute of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
2Federal Research Institute of Cytology and Genetics of SB RAS, 630090, Novosibirsk, Academician Lavret’ev av., 10
3Novosibirsk State Medical University of Minzdrav of Russia, 630091, Novosibirsk, Krasny av., 52
Keywords: количество копий митохондриальной ДНК (мтДНК), фактор риска, атеросклероз, ишемическая болезнь сердца, инфаркт миокарда, внезапная сердечная смерть, популяция, 10.15372/ATER20180310, number of copies of mitochondrial DNA (mtDNA), risk factor, atherosclerosis, IHD, myocardial infarction, sudden cardiac death (SCD), population

Abstract >>
The review provides information on studies that have studied the relationship between the number of copies of mitochondrial DNA (mtDNA) in peripheral blood leukocytes with coronary heart disease and sudden cardiac death (SCD). Mitochondrial dysfunction is a major component of the aging process and can play a key role in the development of cardiovascular diseases of atherosclerotic origin, and the number of copies of mtDNA is an indirect biomarker of mitochondrial function. According to a number of studies, measuring the number of copies of mtDNA in peripheral blood leukocytes can improve the risk assessment of CVD to decide on the beginning of primary prevention of CVD. So far, relatively few such studies have been carried out. Nevertheless, the results obtained, according to the authors, allow us to hope that this indicator can be used in assessing the risk of individual CVD. Further studies carried out on large groups in a prospective design should provide the necessary additional information on the feasibility of including this indicator in the appropriate risk meters.
																								



11.
PCSK9: NEW VICTORY AND HORIZONS

M.O. Smolina, K.S. Benimetskaya, Yu.I. Ragino, M.I. Voevoda
Institutе of Internal and Preventive Medicine - Вranch of Federal Research Institute of Cytology and Genetics of SB RAS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
Keywords: ингибиторы пропротеинконвертаза субтилизин/кексин 9 типа, PCSK9, гиперхолестеринемия, семейная гиперхолестеринемия, гипертриглицеридемия, алирокумаб, эволокумаб, inhibitors ofproprotein convertase subtilisin/kexin type 9, PCSK9, Familial Hypercholesterolemia, hypertriglyceridemia, alirocumab, evolocumab

Abstract >>
The review presents the latest data from the world scientific literature of clinical studies of inhibitors protoprotein convertasesubtilisin/kexin 9 type (PCSK9). The results of the most important completed clinical trials and announcements of prospective clinical trials are presented, the completion of which is expected in the near future. The place of PCSK9 inhibitors in modern recommendations of the European and Russian Cardiological Society is highlighted.The results of studies on the efficacy and safety of PCSK9 inhibitors in selected patient groups (familial hypercholesterolemia, hypertriglyceridemia) are presented. A review of the research aimed at finding new inhibition mechanisms for PCSK9, opening new horizons in the treatment of patients with dyslipidemia.
																								



12.
PATHOPHYSIOLOGICAL AND CLINICAL ASPECTS OF HIGH-DOSE ATORVASTATIN CARDIOPROTECTION IN PATIENTS WITH ACUTE CORONARY SYNDROME

I.D. Astrakhantseva1, I.A. Urvantseva1, A.S. Vorob’yev1, K.Yu. Nikolaev2,3
1District Cardiology Clinic Center of Diagnostics and Cardiovascular Surgery, 628403, Surgut, Lenin av., 69/1
2Institute of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS, 630089, Novosibirsk, Boris Bogatkov str., 175/1
3Surgut State University, 628412, Surgut, Lenin av., 1
Keywords: аторвастатин, острый коронарный синдром, кардиопротекция, atorvastatin, acute coronary syndrome, cardioprotection

Abstract >>
According to modern guidelines, statins are an integral part of treatment of acute coronary heart disease. Cardioprotective effects of atorvastatin in patients with acute coronary syndrome (ACS) are multifaceted and maximally manifested in high doses. The purpose of this review is to analyze international medical literature on the use of high doses of atorvastatin in patients with ACS. The results of the analysis demonstrate significant reduction in post-infarction cardiovascular events, a positive impact on the key pathophysiological processes in ACS.