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The journal "Ateroskleroz"

2019 year, number 1

1.
SERUM LIPOPROTEIN(a) LEVEL IN SUBJECTS FREE OF CLINICAL MANIFESTATIONS OF ATHEROSCLEROSIS-RELATED DISEASES: THE RELATIONSHIP WITH LIPID AND GLUCOSE METABOLISM PARAMETERS AND ARTERIAL STIFFNESS

O.V. Alexandrovich, N.V. Perova, A.D. Deev, N.V. Gomyranova, V.A. Metelskaya
National Research Centre for Preventive Medicine of Minzdrav of Russia101990, Moscow, Petroverigskiy ln., 10, bldg. 3
Keywords: lipoprotein(a), apolipoprotein AII, pulse wave velocity.

Abstract >>
Aim of the study – in subjects without any signs of atherosclerosis to study the associations between blood serum level of lipoprotein(a) (Lp(a)) from one hand, and lipoprotein profile, insulin-mediated glucose utilization parameters and pulse wave velocity (PWV), from the other. Material and methods. Totally 202 subjects (68 men, 134 women) aged 25–75 years without clinical manifestations of atherosclerosis-related diseases but with cardiovascular disease risk factors were included into the study. Blood lipid and carbohydrate parameters were measured by standard methods, serum concentration of Lp(a), apolipoproteins (apo) AI, AII, and B – immunoturbidimetrically. PWV was used as a measure of arterial stiffness. Results. Serum level of Lp(a) positively correlated with apo B concentration (R=0,143; p=0,043) and negatively with apo ÀII content (R=–0,286; p<0,0001). No associations between Lp(a) level and glucose metabolism parameters were found. At the same time, the comparison in groups differed by Lp(a) level according to the highest quintile of its distribution, showed that in subjects with elevated Lp(a) (≥ 50 mg/dl), PWV, apo AII concentration, and postprandial glycemia were lower, while apo B concentration and apo B/apo AI ratio were higher, than in those with Lp(a) < 50 mg/dl. Subjects with high Lp(a) level have upward trend to increased frequency of atherosclerotic plaques presence in carotid arteries. Conclusions. The relationship between elevated Lp(a) level with the initial stages of atherosclerosis was found; however, this association wasn’t coupled with increased arterial stiffness. Higher Lp(a) level positively correlated with apo B concentration and negatively with apo AII content. The relationship between Lp(a) and glucose level was observed only after glucose load in glucose tolerance test and might be explained by more favorable glycemic control in subjects with increased Lp(a) level.



2.
ASSOCIATION OF LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 (LP-PLA2) WITH PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9) IN FAMILIAL HYPERCHOLESTEROLEMIA

K.S. Benimetskaya1,2, V.S. Shramko1, E.M. Stakhneva1, K.V. Makarenkova1, L.V. Shcherbakova1, Yu.I. Ragino1, M.I. Voevoda1


1 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
2 Novosibirsk National Research State University, 630090, Novosibirsk, Pirogov str., 1
Keywords: lipoprotein-associated phospholipase A2, Lp-PLA2, proprotein convertase subtilisin/kexin type 9, PCSK9, familial hypercholesterolemia.
Pages: 15-23
Abstract >>
Objective was to study the levels and the relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) and proprotein convertase subtilisin/kexin type 9 (PCSK9), their relationship with other lipid parameters in patients with familial hypercholesterolemia (FH) in Russia. Material and methods. The study involved 47 patients (11 males) observed in the Scientific-clinical center of lipidology of Research Institute of Internal and Preventive Medicine - Branch of the Institute of Cytology and Genetics of SB RAS with diagnosis of «possible» or «definite» FH according to the criteria of The Simon Broome Register Group and «probable» or «definite» FH according to the Dutch Lipid Clinic Network Criteria. Patient age was 49.13 ± 12.67 years (mean ± SD); 50.00 [40.00; 59.00] years (median [lower quartile; upper quartile]). Lp-PLA2 and PCSK9 content was determined by enzyme-linked immunosorbent assay using a test systems «Human Proprotein Convertase 9/PCSK9 Immunoassay» («R&D Systems», USA) and «ELISA Kit for Phospholipase A2 Group VII (LpPLA2)» («Cloud-Clone Corp.», USA). Results. Lp-PLA2 level was 73,69 [64,99; 106,53] ng/ml, PCSK9 – 352,16 [272,94; 416,79] ng/ml. There was a trend to moderate positive correlation between Lp-PLA2 and PCSK9 content (r = 0.614; p = 0.059), the statistical significance value was borderline due to the small number surveyed. Males showed a strong positive correlation of LP-FLA2 concentration with age (r = 0.746; p = 0.008), partial – with triglyceride (TG) content (r = 0.793; p = 0.019). A strong positive correlation of PCSK9 level with apolipoprotein B / apolipoprotein A ratio (r = 0.702; p = 0.007) and a weak positive correlation with TG concentration (r = 0.330; p = 0.033) were shown in the general group. Moderate positive correlation of PCSK9 content with age (r = 0.660; p = 0.038), a strong negative correlation with total cholesterol (r = –0.815; p = 0.004), low-density lipoprotein cholesterol (r = –0.828; p = 0.006) and non-high-density lipoprotein cholesterol (r = –0.851, p = 0.002) concentration were shown. Women with TG level <1.7 mmol/l had lower PCSK9 level then women with TG level ≥1.7 mmol/l (328.45 [231.02; 387.82 and 397.12 [348.45; 531.62] ng/ml, respectively (p = 0.013)). Conclusion. The correlation of PCSK9, the perspective marker of cardiovascular diseases, with the avowed marker Lp-PLA2 confirms the importance of PCSK9 in lipid metabolism and cardiovascular homeostasis and is the basis for its further research as a biological marker of cardiovascular diseases.



3.
FACTORS ASSOCIATED WITH THE SEVERITY OF CHRONIC CEREBRAL ISCHEMIA IN PATIENTS WITH MYOCARDIAL INFARCTION COMPLICATED BY LEFT VENTRICULAR FAILURE

L.Yu. Chesnokova1,3, N.B. Lebedeva1,2, N.I. Tarasov2

1Scientific Research Institute for Complex Issues of Cardiovascular Diseases, 650002, Kemerovo, Sosnovy boul., 6

2Kemerovo Regional Clinical Cardiology Dispensary named after academician L.S. Barbarash, 650002, Kemerovo, Sosnovy boul., 6

3Kemerovo State Medical University of Minzdrav of Russia, 650056, Kemerovo, Voroshilov str., 22 a 
Keywords: myocardial infarction, chronic cerebral ischemia.
Pages: 24-29
Abstract >>
We aimed to analyze the factors determining a severity degree of cerebral pathology in patients with myocardial infarction complicated with left ventricular failure and associated with chronic cerebral ischemia. Material and methods. The study included 182 patients with Q-wave myocardial infarction and concomitant chronic cerebral ischemia (CCI), complicated with left ventricular failure, 149 (81.9 %) men and 33 (18.1 %) women. The mean age was 60.5 (53.0; 69.0) years. The following procedures were performed: clinical and anamnestic examination, selective coronary angiography, echocardiography and duplex scanning of the arteries. Results. The signs of CCI grade II were revealed in 67.6 % of the patients, CCI grade I – in 20.9 % of the patients, 11.5 % of the patients had cerebrovascular accident and transient ischemic attack. All the patients had intima-media thickness more than 0.1 cm. No patients with hemodynamically significant stenoses of extracranial arteries were revealed; in 37.4 % of the patients less than 50 % carotid stenoses were detected. The patients with multivessel coronary bed lesions prevailed. The severity of CCI was associated with the multifocality of the atherosclerosis, history of arterial hypertension, hypercholesterolemia, angina pectoris, previous MI and chronic heart failure. Conclusion. The factors which determine the severity of the clinical course of CCI in this group are not the presence of hemodynamically significant extracranial stenoses, but the previous coronary history and multifocality of the atherosclerotic process.



4.
ASSOCIATION OF MINERAL ELEMENTS IN THE ATHEROSCLEROTIC PLAQUE IN CORONARY ATHEROSCLEROSIS

E.Ya. Zhuravskaya1, T.I. Savchenko2, O.V. Chankina2, Ya.V. Polonskaya1, E.V. Sadowski1, E.M. Stakhneva1, Yu.I. Ragino1, A.M. Chernyavskii3

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

2Voevodsky Institute of Chemical Kinetics and Combustion of SB RAS, 630090, Novosibirsk, Institutskaya str., 3

3National Medical Research Center named academician E.N. Meshalkin of Minzdrav of Russia, 630055, Novosibirsk, Rechkunovskaya str., 15


Keywords: coronary atherosclerosis, atherosclerotic plaque, mineral elements, calcium, zinc.
Pages: 30-34
Abstract >>
Purpose: to determine the content of mineral elements in the homogenates of atherosclerotic plaques of human coronary arteries. Methods: research material – homogenates of samples of atherosclerotic plaques of coronary arteries obtained during coronary bypass surgery. The concentration of chemical elements Ca, Pb, Fe, Cu, Zn, Br, Sr, Zr in the homogenates of atherosclerotic plaques was determined by x-ray fluorescence analysis using synchrotron radiation (SRXRF). Results: in all the studied samples the predominant presence of Ca was observed, in stable plaques 1791.93±3042.25 µg/ml, in unstable atherosclerotic plaques 2024.33±1267.13 µg/ml.Association of Ca with Fe (r = 0.798; p < 0.01), Zn (r = 0.963; p < 0.01) and Sr (r = 0.981; p < 0.01) in the atherosclerotic focus was revealed. No significant difference between the measured elements in stable and unstable plaques was found. Conclusion: the method x-ray fluorescence analysis using synchrotron radiation revealed some patterns of the mineral composition of an atherosclerotic plaque of a human. The main mineral component of the atherosclerotic plaque is calcium, with a tendency to increase the concentration of the element in the unstable focus. Minor components-iron, zinc, strontium are associated with calcium. In this case, iron tends to reduce the concentration in an unstable atherosclerotic focus, and the concentration of strontium and zinc does not change significantly.



5.
BIOLOGICAL RISK FACTORS FOR CHRONIC NON-COMMUNICABLE DISEASES IN MEN WITH VARIOUS CLINICAL AND CORONARY ANGIOGRAPHIC VARIANTS OF ACUTE CORONARY SYNDROME

M.V. Strelnikova1,2, A.V. Sineglazova2


1Chelyabinsk Regional Clinical Hospital, 454000, Chelyabinsk, Vorovskogo str., 70

2South-Ural State Medical University of Minzdrav of Russia, 454092, Chelyabinsk, Vorovskogo str., 64


Keywords: acute coronary syndrome, coronary artery stenosis, occlusion, biological risk factors for chronic non-communicable diseases.
Pages: 35-40
Abstract >>
Purpose of the study was to evaluate the features of biological risk factors for chronic non-infectious diseases in various clinical forms and coronary angiography manifestations of acute coronary syndrome in men. Material and methods. 77 men with acute coronary syndrome (62 patients with myocardial infarction (MI) and 15 with unstable angina (UA)) were examined. The biological risk factors of chronic non-communicable diseases (RF CNÑD) have been investigated: abdominal obesity, dyslipidemia, arterial hypertension, hyperglycemia. All patients underwent emergency coronary angiography. Results. It has been established that in patients with MI with stenosis of the coronary arteries (CA) ≥75 %, the level of low-density lipoproteins is higher than in UA with CA stenosis <75 %, and the concentration of high-density lipoproteins is lower than in UA with stenosis ≥75 %. In MI with stenosis of CA ≥75 %, the frequency of occurrence of atherogenic index > 3 is higher than with MI with stenosis of CA <75 % and UA with stenosis of CA <75 %. When analyzing the carbohydrate metabolism, it was found that in patients with MI with stenosis ≥75 %, the fasting plasma glucose level has higher than in infarction with narrowing of the CA <75 %, moreover, a direct correlation is shown between the presence of hyperglycemia and the occurrence of CA occlusion. The level of diastolic blood pressure in patients with stenosis ≥75 % and myocardial infarction with stenosis ≥75 % is higher than in patients with congenital stenosis with CA <75 %. With a combination of three or more risk factors, a more significant percentage of stenosis and an increase in the frequency of occlusion of spacecraft is established than with one or two risk factors. Conclusion. Heavier clinical and coronary angiographic variants of acute coronary syndrome were diagnosed in men with risk factors such as hypercholesterolemia, increased low-density lipoprotein content and atherogenic index, decreased high-density lipoprotein concentration, fasting hyperglycemia and increased diastolic blood pressure. The chance of CA occlusion significantly increased when combining three or more biological RF CNCD.



6.
ASSOCIATIONS OF METABOLIC RISK FACTORS OF THERAPEUTIC DISEASES WITH DIFFERENT LEVELS OF SIMPLE CARBOHYDRATES CONSUMPTION

S.V. Mustafina, G.I. Simonova, V.I. Oblaukhova, A.K. Kuntsevich, Yu.I. Ragino, L.V. Shcherbakova, 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: metabolic syndrome, non-alcoholic sugar-sweetened beverages, simple sugars, body mass index.
Abstract >>
Aim of the study was to assess the chance of metabolic syndrome development in individuals aged 45-69 years consuming simple carbohydrates and non-alcoholic sugar-sweetened beverages. Material and methods. Data of the epidemiological survey of Novosibirsk residents aged 45–69 years conducted in 2003–2005 are analyzed. The population of the Oktyabrsky and Kirovsky districts of Novosibirsk was examined – 9.360 people, including 4.266 men and 5.094 women. Data was processed for 8096 respondents: 3.699 men and 4.397 women, without diabetes mellitus. The average age of the examined is 57.6 years. Results. In cross-sectional epidemiological study of actual nutrition, data were obtained on the high level of consumption of simple sugars, with a low consumption of total carbohydrates. When comparing the levels of consumption of basic nutrients (g/day) in diets between men and women with the standardization of calories, it is noted that men have higher content of fat, protein components of the diet, total carbohydrates, while women have higher content of simple sugars. In the Siberian population 67.9 % of persons aged 45–69 years drink sugar-sweetened beverages in a volume of 200 ml more than once a 3 month. An assessment of the metabolic status of individuals in our study showed that in the group of more frequent intake of sugar-sweetened beverages (both sexes), there are more individuals with elevated levels of low-density lipoprotein cholesterol and a frequency of abdominal obesity. The high level of consumption of simple carbohydrates and sugary soft drinks against the background of low consumption of common and complex carbohydrates is a marker of an unhealthy diet. Recommendations to increase the consumption of complex carbohydrates while simultaneously reducing simple sugars, including sugar-sweetened beverages, are a necessary measure to reduce the risk of metabolic disorders in the Siberian population.



7.
INSULIN AND LEPTIN: DISPUTABLE AND UNSOLVED QUESTIONS OF THEIR INTERACTION

E.V. Belik1, O.V. Gruzdeva1,2, E.I. Palicheva1,2


1Scientific Research Institute for Complex Issues of Cardiovascular Diseases, 650002, Kemerovo, Sosnovy blvd., 6

2Kemerovo State Medical University of Minzdrav of Russia, 650056, Kemerovo, Voroshilov str., 22à


Keywords: leptin, insulin, adipocytes, obesity, insulin resistance.
Abstract >>
Leptin and its receptor are widely distributed mainly in white adipose tissue. Serum leptin concentration correlates with body mass index, and its levels decrease with fasting. Insulin appears to increase leptin mRNA and protein expression, as well as release by adipocytes, synthesized both in advance and de novo, and reduces the levels of adiponectin and its receptors. According to the literature, chronic hyperinsulinemia increases leptin levels. This review summarizes the latest knowledge on the effect of insulin on leptin synthesis and secretion; cellular mechanisms that control the synthesis and release of white adipose tissue are presented.



8.
CLINICAL GUIDELINES FOR FAMILIAL HYPERCHOLESTEROLEMIA

M.V. Ezhov1, S.S. Bazhan2, A.I. Ershova3, A.N. Meshkov3, A.A. Sokolov4, V.V. Kukharchuk1, V.S. Gurevich5,6, M.I. Voevoda2, I.V. Sergienko1, E.V. Shakhtshneider2, S.N. Pokrovsky1, G.A. Konovalov7, I.V. Leontyeva8, V.O. Konstantinov6, M.Yu. Shcherbakova9, I.N. Zakharova10, T.V. Balakhonova1, A.E. Filippov5, N.M. Akhmedzhanov3, O.Yu. Aleksandrova11, B.M. Lipovetsky12


1 Federal State Budgetary Institution «National Medical Research Center of Cardiology» of the Ministry of Health of the Russian Federation, Moscow, Russia

2 Institute of Internal and Preventive Medicine – Branch of Fedaral Research Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia

3 Federal State Budgetary Institution “National Medical Research Center for Preventive Medicine” of the Ministry of Health of the Russian Federation, Moscow, Russia

4 Military Medical Academy n.a. S.M. Kirov, St. Petersburg, Russia

5 Federal State Budgetary Educational Institution of Higher Professional Education “St. Petersburg State University”, St. Petersburg, Russia

6 North-Western State Medical University n.a. I.I.Mechnikov, Ministry of Health of the Russian Federation, St. Petersburg, Russia

7 Center for Diagnostics and Innovative Medical Technologies of the CDC Medsi in Belorusskaya, Moscow, Russia

8 SBEI of HE «NI Pirogov Russian National Research Medical University» of the Ministry of Health of the Russian Federation, Moscow, Russia

9 FSAEI of HE «Peoples’ Friendship University of Russia», Moscow, Russia

10 FGBOU DPO «Russian Medical Academy of Continuing Professional Education» Ministry of Health of the Russian Federation, Moscow, Russia

11 Moscow Regional Research Clinical Institute n.a. M.F. Vladimirsky, Russia

12 Institute of Human Brain n.a. N.P. Bekhtereva of the Russian Academy of Sciences, St. Petersburg, Russia


Keywords: familial hypercholesterolemia, atherosclerosis, coronary heart disease, low density lipoprotein cholesterol, xanthomas.
Pages: 58-98
Abstract >>
These guidelines represent all current aspects of etiology, diagnosis, and treatment of the clinical and statistical group of familial hypercholesterolemia in both adults and children in accordance with the requirements of the Ministry of Health of Russia.