[Cardiovascular effects of omega-3 polyunsaturated fatty acids: position of omega-3 polyunsaturated fatty acids in Russian and international guidelines. Council of Experts].

This Expert Council focuses on the meta-analysis of studies on the risk of atrial fibrillation (AF) in patients taking omega-3 polyunsaturated fatty acids (PUFA) and of data on the omega-3 PUFA treatment in patients with cardiovascular and kidney diseases.The major statements of the Expert Council: the meta-analysis of AF risk in patients taking omega-3 PUFA showed an increased risk of this arrhythmia. However, it should be taken into account that the risk of complications was low, and there was no significant increase in the risk of AF when omega-3 PUFA was used at a dose of ≤1 g and a standard dose of the only omega-3 PUFA drug registered in the Russian Federation, considering all AF episodes in the ASCEND study.At the present time, according to Russian and international clinical guidelines, the use of omega-3 PUFA can be considered in the following cases: • for patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction as a supplement to the basic therapy (2B class of recommendations according to the 2020 Russian Society of Cardiology guidelines (RSC) and the 2022 AHA / ACC / HFSA guidelines); • for patients with hypertriglyceridemia (>1.5 mmol/l) as a part of combination therapy (IIb class of recommendations and B level of evidence according to the 2021 European guidelines on cardiovascular disease prevention, etc.); • for adult patients with stage 3-4 chronic kidney disease (CKD), long-chain omega-3 PUFA 2 g/day is recommended for reducing the level of triglycerides (2C class of recommendations). Data on the use of omega-3 PUFA for other indications are heterogenous, which can be partially explained by using different form and doses of the drugs.

[Inclisiran - a new era in lipid-lowering therapy].

Inclisiran is a novel hypolipidemic drug that inhibits synthesis of the PCSK9 protein through the process called RNA interference. Inclisiran is a double-stranded, modified RNA bound to the N-acetylgalactosamine (GalNAc) carbohydrate molecule, a ligand of the acialoglycoprotein receptor, that is expressed by hepatocytes. After entering hepatocytes, inclisiran cleaves matrix RNA and, thereby, reduces the PCSK9 protein synthesis. This, in turn, enhances the uptake of circulating low-density lipoproteins (LDL) by specific receptors on hepatocytes, thereby lowering LDL levels in circulation. Efficacy and safety of inclisiran for lowering LDL cholesterol (C) in blood and its effect on the risk of clinical complications of atherosclerosis have been studied in the ORION program that includes multiple clinical trials. According to results of this program, inclisiran effectively reduces both LDL-C levels and the incidence of cardiovascular complications in the absence of clinically significant adverse reactions. An important advantage of inclisiran compared with other lipid-lowering drugs is the administration schedule (twice a year), which allows a considerable improvement of patients' compliance with the treatment and also of the effectiveness of the hypolipidemic treatment.

[Possibilities of clinical use of ezetimibe Otrio (JSC "AKRIKHIN", Russia) in patients with high and very high cardiovascular risk who have not reached the target values of lipid metabolism. Conclusion of the Board of experts].

This Conclusion of the Board of experts is devoted to the analysis of the evidence base, the position in modern clinical guidelines, the efficacy and safety analysis as well as the options of combined therapy with statins and ezetimibe (Otrio, JSC "AKRIKHIN") in various categories of patients in routine clinical practice in theRussian Federation. Cardiovascular diseases (CVD) continue to lead in the structure of morbidity and mortality inRussia. Hypercholesterolemia is one of the main modifiable risk factors for CVD. Administration of HMGCo-A-reductase inhibitors (statins) remains the basis for the prevention and treatment of the main complications of atherosclerosis, but the achievement of target levels of LDL-C on of statin monotherapy in Russian practice among different categories of risk does not exceed 50%. Proportion of patients (up to 12%) does not tolerate statin therapy, which requires the search for alternative therapies. To optimize the control of the level of LDL-C, combination therapy with statins and ezetimibe is used. Ezetimibe is an effective lipid-lowering drug, an inhibitor of intestinal absorption of cholesterol, which was investigated in many international and Russian studies, the results of which have demonstrated good tolerability, safety and efficacy (reduction of LDL-C levels by 18% in monotherapy). It was noted that the combined therapy with low/medium doses of statins and ezetimibe effectively reduces the level of LDL-C by 44-53%, which is comparable to the effect of high doses of statins and reduces CV risk in patients with CKD and ACS. Otrio (INN Ezetimib) tablets 10 mg ( JSC "AKRIKHIN",Russia) has demonstrated bioequivalence to the original drug Ezetrol tablets 10 mg (Schering-plough Labo N. V,Belgium). Broad use of a new generic product Otrio in combination with different statins will significantly increase the frequency of achievement of target lipid levels in patients with high and very high CV risk, including patients with chronic renal failure, type 2 diabetes and in patients with high hypercholesterolemia (LDL-C > 5 mmol/l) and, ultimately, reduce the burden of CV disease and mortality in Russia.

[Improvement of outcomes in patients with recent acute coronary syndrome: the place of PCSK9 inhibitors. The Resolution of National Advisory Board].

On April 9, 2018, the national advisory board "Improvement of outcomes in patients with recent ACS: the place of PCSK9 inhibitors" was held in Moscow. Leading Russian experts in the field of atherosclerosis and lipid-lowering treatment attended the board. The purpose of the Board was to determine the place of PCSK9 inhibitors in the improvement of outcomes in patients with recent (less than 1 year) acute coronary syndrome (ACS). During the Board, three major aspects of lipid-lowering treatment were discussed: 1) issues in reaching the target levels of LDL cholesterol in real clinical practice among patients with recent ACS; 2) the results of ODYSSEY OUTCOMES study and their role in the improvement of outcomes in patients with recent ACS; 3) treatment with PCSK9 inhibitors in the management of patients with recent (less than 1 year) ACS in everyday clinical practice, the role of lipid centers.

[The extent of coronary stenosis and the level of antibodies to atherogenic lipoproteins in patients with coronary heart disease].

AIM: To study association between the level of antibodies to oxidized low-density lipoproteins (anti-OLDL) and the extent of coronary stenosis (CS) in patients with coronary heart disease (CHD). MATERIAL AND METHODS: Sixty CHD patients were examined for titer of anti-OLDL, levels of total cholesterol (TC), LDLP cholesterol, HDLP cholesterol, triglycerides. Selective coronarography (SC) was made on demand. RESULTS: Elevated titer of anti-OLDL was found only in 12 examinees. It was significantly lower in CHD women than in men. No significant differences by anti-OLDL were found in CHD patients with and without significant risk factors. SC registered in all CHD examinees local stenosis of different severity. Stenosis in 3 coronary arteries was detected in 31 cases, in 2 coronary arteries--in 14, in 1 coronary artery--in 15 patients, most frequently the affection was located in the diagonal branch of the left coronary artery. Stenosis of the left coronary artery trunk was diagnosed in one case. The correlation analysis revealed a strongly significant positive correlation between content of anti-OLDL and the degree of CS. CONCLUSION: The level of anti-OLDL in CHD patients directly correlates with the degree of CS and is a marker of coronary atherosclerosis severity.

[Optimization of lipid-lowering therapy in patients after ischemic stroke. Resolution of the Council of Experts]. / Optimizatsiya gipolipidemicheskoi terapii u patsientov, perenesshikh ishemicheskii insul't. Rezolyutsiya Soveta ekspertov.

Hyperlipidemia is the main risk factor for diseases caused by atherosclerosis including ischemic stroke. This publication provides practical recommendations and an algorithm for prescribing lipid-lowering therapy to post-ischemic stroke patients. The algorithm presents the steps for sequential administration of statins, ezetimibe, and PCSK9 inhibitors to achieve target levels of low-density lipoprotein cholesterol.

Antioxidative activity of high density lipoproteins in vivo.

The present study consists of experimental and clinical investigations. It was shown that a single intravenous injection of a large dose of human HDL3 (200 mg protein) to rabbits with induced hypercholesterolemia (plasma cholesterol 500-700 mg/dl) was accompanied by a significant elevation of plasma HDL and led to a decrease (P < 0.05) of conjugated dienes and trienes by 20-30% after 6 h. Conjugated dienes remained stable for 24 h after HDL administration. In the clinical investigations a weak but statistically significant negative correlation (r = 0.262; P = 0.006) between HDL cholesterol and the content of conjugated dienes in the plasma of a total group of healthy subjects and patients with coronary heart disease (CHD) was found. The data allowed us to conclude that, in addition to other antioxidative systems, HDL also take part in the protection of plasma lipids from peroxidation.

Platelet activation during provocation of coronary artery spasm by ergonovine and cold pressor testing in patients with angina pectoris.

The role of coronary spasm in variant angina is well established. We have studied the time course of platelet activation during Ergonivine provocation to determine one significance of platelet indices for spasm testing. The results showed that spontaneous platelet aggregates and beta-thromboglobulin levels in patients with coronary vasospasm were increased during provocation and that platelet activation during a positive Ergonivine test precede ECG changes and chest pain.

Influence of taurine on the electrically regulated ionic channels of the somatic membrane of neurons of the pond snail.

The influence of taurine (in concentrations of 10(-8) to 10(-2) mole/liter) on the fast sodium, calcium, and potassium, the slow potassium, and the leakage currents of the somatic membrane of the neurons of the pond snail was investigated. A monotonic decrease was demonstrated in the calcium and the slow potassium currents with an increase in the concentration of taurine. The sodium currents increased at taurine concentrations of 10(-8)-10(-4) mole/liter, while at concentrations of 10(-3)-10(-2) mole/liter they decreased. The fast potassium currents remained essentially unchanged at all concentrations of taurine. The leakage currents of the membrane at small concentrations of taurine decreased somewhat, and increased insignificantly at higher concentrations of it. All of the effects of taurine were reversible. It is hypothesized that the mechanism of the neuromodulatory, anticonvulsant, antihypoxic effects of taurine is at its base associated with changes in the electrically regulated ionic channels of the cell membrane.

Evidence of combined therapy of dyslipoproteinemia by HMG-CoA reductase inhibitors and "essential" phospholipids.

Platelets are involved in the initiation of atheromas and arterial thrombosis and thus may play a cardinal role in the pathogenesis of myocardial and cerebral infarction. In 18 patients with coronary artery disease and hypercholesterolemia resistant to low-lipid diet a 12 week treatment with lovastatin (HMG-CoA reductase inhibitor) leads to the reduction of total cholesterol, LDL-cholesterol and triglycerides but also to a marked increase of platelet activity. Lovastatin is an inactive lacton prodrug which must be enzymatically or chemically transformed to the active form. In in-vitro experiments, it was discovered that both chemically hydrolysed lovastatin and plasma containing lovastatin metabolites stimulate induced platelet aggregation in whole blood samples. "Essential" phospholipids (Lipostabil) added to the blood samples in concentrations according to those which are used clinically prevent this stimulation. This corresponds to data obtained earlier from Lipostabil-treated ischemic heart disease patients. Besides a lipid-lowering effect Lipostabil showed a 50% reduction of spontaneous aggregates in plasma, an increase of the susceptibility threshold to aggregation inducers and a decrease of the platelet aggregation amplitude in whole blood samples. Therefore, it would be promising to combine the therapy by lovastatin with "essential" phospholipids possessing a remarkable improving effect on the platelet function based on a molecular action independent of their moderate lipid-reducing action.

[The regulation of protein kinase C activity in normal, immortalized and transformed rat fibroblasts]. / Reguliatsiia aktivnosti proteinkinazy C v normal'nykh, immortalizovannykh i transformirovannykh fibroblastakh krysy.

In view of recent studies showing that cell proliferation of E1Aad5+c-Ha-ras-transformed fibroblasts cannot be regulated by growth factors and phorbol eaters in contrast to normal and E1Aad5-immortalized cell lines, the present work was undertaken to examine the role of protein kinase C (PKC) in the mitogenic signal transduction machinery in rat embryonal fibroblasts. It is shown that PKC is activated by acidic growth factor and phorbol esters in all the three cell lines. These findings suggest the existence of an additional, not associated with PKC-, growth-signaling pathway in E1Aad5-Ha-ras-transformed rat embryonal fibroblasts.

[Influenza viruses and atherosclerosis: the role of atherosclerotic plaques in prolonging the persistent form of influenza infection]. / Virusy grippa i ateroskleroz: rol' ateroskleroticheskikh bliashek v podderzhanii persistentnoi formy grippoznoi infektsii.

It was established that viral particles, like low-density lipoproteins (LDLP), when subjected to some modification changes, lost their ability to be internalized by tissue somatic cells and acquired tropism to macrophage cells. The data, obtained by us by using the polymerase chain reaction (PCR) method, made it possible to assert that atherosclerotic plaques, isolated from vessels of patients with ischemic heart disease (IHD) who underwent coronary bypass, contained RNA of the A(HINI) and AH3N3) influenza viruses. Whereas, the vessel portions, undamaged by atherosclerosis, did not contain any genetic substances of influenza viruses. It was for the first time that an experimentally supported understanding was expressed on that the atherosclerotic plaques serve as a "reservoir" for influenza viruses. It is also suggested that the mentioned plaques can be the carriers of influenza viruses for a long time, thus, prolonging the persistent form of influenza infection in the human body.

[The thrombocyte function of subjects with atherogenic hyperlipidemias during lovastatin treatment]. / Funktsional'naia aktivnost' trombotsitov u lits s aterogennymi giperlipidemiiami v protsesse lecheniia lovastatinom.

The effects of lovastatin on in vivo spontaneous and in vitro ADP-induced platelet aggregability were studied in the blood of 36 persons with primary hyperlipidemias (HLP) of Types IIIa and IIb. In addition to decreases in blood cholesterol levels by an average of 33% and the atherogenicity coefficient to the normal levels, there was an increase in spontaneous and/or ADP-induced platelet aggregability in the first 2-3 months of lovastatin therapy. Lovastatin-induced in anti- and proaggregatory potential in the platelet-vascular wall system towards of the latter and spontaneous intravascular platelet formation suggest that there is a higher risk for thromboembolic events in the examined patients with Type II HLP, especially if they have coronary heart disease, during early stages of the drug administration. Therefore, there are reasons for recommending that lovastatin should be given under the control of the platelet hemostatic system.

[Alterations in the functional activity of platelets in patients with angina pectoris during the cold test]. / Izmenenie funktsional'noi aktivnosti trombotsitov pri provedenii kholodovoi proby u bol'nykh so stenokardiei.

The functional activity of platelets was examined in patients with coronary heart disease and healthy individuals during cold test (CT). Patients prone to vasospastic responses to CT exhibited platelet activation along with beta-thromboglobulin release and formation of spontaneous platelet aggregates. Comparison of functional changes in platelet functional activity which occurred during cold test and intravenous ergometrine test suggest that the response to CT may be substantially higher if platelet aggregability is concurrently determined. The unidirectional changes in platelet aggregability during cold and ergometrine tests in patients with signs of dynamic coronary occlusion may indicate a relation of platelets with coronary vasoconstriction.

[Various indicators of vascular-thrombocytic hemostasis and blood rheology in ergometrine tests]. / Dinamika nekotorykh pokazatelei sosudisto-trombotsitarnogo gemostaza i reologii krovi pri érgometrinovykh probakh.

The function of platelets and erythrocytes and content of Willebrand's factor in the plasma from 45 patients with exercise-induced or spontaneous angina pectoris were examined before and after ergometrine, 0.1 mg. The patients with a negative ergometrine response showed a lower platelet sensitivity to all the aggregation inductors used in vitro, spontaneous platelet aggregation being absent. The function of erythrocytes and plasma levels of Willebrand's factor remained unchanged. The patients with a significant ischemic response to ergometrine exhibited platelet activation attended by the release of granule contents and formation of blood circulating platelet microaggregates. Concurrently, there was a decrease in erythrocyte deformability, as well as spontaneous blood red cell aggregation, the plasma levels of Willebrand's factor were increased 1.5-2-fold.

[Effects of ubinon-9, a synthetic antioxidant, on intensity of lipid peroxidation in blood platelets and plasma of patients with ischemic heart disease]. / Vliianie sinteticheskogo antioksidanta ubinona-9 na intensivenost' perekisnogo okisleniia lipidov v thrombotsitakh i plazme krovi bol'nykh ishemicheskoi bolezn'iu serdtsa.

The antioxidant ubinon-9 was tested for its effects on platelet and plasma lipid peroxidation parameters in patients with acute ischemic heart diseases. The use of ubinon-9 in the multimodality therapy of patients with ischemic heart disease was shown to result in a significant decrease in lipid peroxidation intensity by enhancing superoxide dismutase activity in the platelets and plasma from the patients. Ubinon-9 equally prevented lipid peroxidation activation during enzymatic and nonenzymatic induction in the platelets of patients with unstable angina or acute myocardial infarction. Unlike a daily dose of 30 mg, 90 mg a day is a more effective dose in reducing platelet and plasma lipid peroxidation parameters. One may suggest that addition of ubinon-9 into the routine treatment regimen allows the therapy for acute ischemic heart disease to be optimize.

[Influenza virus infection in progressing atherosclerosis]. / Infektsiia virusami grippa pri progressiruiushchem ateroskleroze.

AIM: To study relationship between influenza virus infection and activity of clinical presentations of atherosclerosis. METHODS AND RESULTS: Average blood level of IgG to influenza A virus was significantly higher in patients with progressing forms of ischemic heart disease then in patients without objective signs of exacerbation of atherosclerotic process. Mean titles of antibodies to parainfluenza virus and adenoviruses were similar in both groups of patients. Direct detection of viral DNA by polymerase chain reaction was carried out in samples of aortic wall taken during coronary artery bypass surgery with the use of primers for hemagglutinin of H1N1, H3N2 viruses. RNA of influenza virus was found in these samples. CONCLUSION: The presence of viral RNA in vascular atherosclerotic lesions could be indicative of possible pathogenetic role of influenza infection in progression of clinical course of atherosclerosis.

[Taurine and the function of excitable tissues]. / Taurin i funktsiia vozbudimykh tkanei.

Integration of electrophysiological and neurochemical studies secured considerable success in analysis of inhibitory and activating effects of some aminoacids on the c. n. s. Taurine, in particular, was shown to participate in some important physiological and pathophysiological phenomena. In this review, the literature data as well as the author's own data on participation of taurine in some physiological reactions, are presented. Main hypotheses of the molecular mechanisms of the taurine effect upon excitable structures, are discussed.

[The effect of taurine on the electrically controlled ion channels of the somatic membrane of pond snail neurons]. / Vliianie taurina na élektroupravliaemye ionnye kanaly somaticheskoi membrany neironov prudovika.

Isolated and internally dialysed neurons from the molluscs Lymnaea stagnalis were investigated under voltage-clamp conditions. The increasing of taurin concentration (from 1.10(-8) to 1.10(-2) mol/l) reduced the calcium inward--and delayed potassium outward currents, and exerted no effect on the fast potassium outward current. Sodium inward current was increased by taurin concentrations 1.10(-8)-1.10(-4) mol/l, and reduced by 1.10(-3)-1.10(-2) mol/l. Membrane leakage currents were reduced by small taurin concentrations and increased by large concentrations.

[Various indices of lipid peroxidation in thrombocytes of patients with ischemic heart disease]. / Nekotorye pokazateli perekisnogo okisleniia lipidov trombotsitov u bol'nykh ishemicheskoi bolezn'iu serdtsa.

Interaction between lipid peroxidation activation and the antioxidant system was studied in thrombocytes of patients with cardiovascular pathology. Positive correlation between superoxide dismutase activity and malonic dialdehyde content was found in healthy persons, while in patients with unstable stenocardia and acute myocardial infarction an inversion of the correlation parameters occurred. The data obtained may be used for prognosis of heart ischemic disease development.