Cardiovascular diseases are the most common cause of death both in Russia and throughout the world. Acute coronary syndrome (ACS) develops during the coronary heart disease and represents a serious medical and social problem. The effectiveness and safety of pharmaco­therapy for ACS can be influenced by the individual genetic characteristics of the patient, primarily single nucleotide polymorphisms (SNPs) of the primary DNA structure. The literature review contains information about the epidemiology of ACS, the nomenclature of SNPs, and the molecular basis of the influence of SNPs on physiological and pathological processes in the human body. The main groups of drugs used for ACS and the main functional groups of protein­coding genes, SNPs of which can modulate an individual’s response to pharmacother­apy, are listed in the review. SNPs of non­coding RNA genes have been characterized as promising objects of study. The review shows concept of multilevel regulation of the interaction between drug and human organism and the role of SNPs in that concept. Detection of SNPs is an important component of studying the pharmacokinetics and pharmacodynamics of drugs, since information about the patient’s genetic status is the basis for a personalized approach to pharmacotherapy.

The burden of heart failure (HF) has been increasing worldwide in recent decades. Early diagnosis of HF based on the outpatient measurement of natriuretic peptide (NP) concentration will allow timely initiation of the treatment and reducing the incidence of adverse outcomes in HF. Unfortunately, the frequency of NP testing remains low worldwide. At the online expert meeting held on March 15, 2024, the features of the N-terminal pro-brain natriuretic peptide (NT-proBNP) test (Elecsys proBNP by Roche) were discussed along with the interpretation of test results and presentation of results in laboratory reports. The experts addressed the features of the Elecsys proBNP test in patients with suspected HF in various clinical scenarios (chronic and acute HF). The limits of clinical decision for the NT-proBNP test were established depending on the clinical scenario. Changes in the Elecsys proBNP test results depending on the comorbidities were addressed. The experts suggested ways to optimize the format of the Elecsys proBNP test result reports in the Russian Federation, which will accelerate the implementation of the test in clinical practice and optimize the management of HF patients.

The Russian Society of Cardiology (RKO)With the participation of: Russian Scientific Medical Society of Internal Medicine (RSMSIM)Approved by the Research and Practical Council of the Ministry of Health of the Russian Federation (12.09.2024)

On March 15, 2024, in Moscow, the Russian Phlebological Association and the National Association of Specialists in Thrombosis, Clinical Hemostasiology and Hemorheology organized a meeting of the Council of Experts during the Russian Forum on Thrombosis and Hemostasis on the acute issues of venous thromboembolism (VTE) primary prevention using low molecular weight heparins (LMWH) in surgical patients with different body weight. The participants reviewed the relevance and prevalence of this problem in surgical practice, discussed risk factors and the frequency of VTE development, including bleeding in the postoperative period, and the Caprini risk score for complications. The discussion also focused on standard and personalized LMWH doses for primary prophylaxis of VTE in the perioperative period in surgical patients, depending on body weight, and the role of laboratory tests, including assessment of LMWH anti-Xa activity for monitoring the efficacy and safety of VTE primary prevention in clinical practice.

Training staff in personalized medicine implies modernisation of the traditional learning model that is to incorporate a curricular thread spanning all the stages (pre-university, undergraduate, post-graduate) of a doctor’s professional development.The article presents the experience of the Institute of Medical Education of The Almazov National Medical Research Centre in training personnel prepared to implement the principles of personalized medicine in domestic healthcare.

An erratum on « Insufficiency/deficiency of vitamin B12 in patients in the endocrinological practice» by Natalya G. Mokrysheva, Marina V. Shestakova, Alexander S. Ametov, Mikhail B. Antsiferov, Igor G. Bakulin, Tatiana V. Vavilova, Gagik R. Galstyan, Tatiana Y. Demidova, Fatima K. Dzgoeva, Tatiana L. Karonova, Elena A. Lukina, Ashot M. Mkrtumyan, Rodion V. Ponomaryov, Natalia A. Suponeva, Olga Y. Sukhareva, Minara S. Shamkhalova (2024). Diabetes mellitus. 27(3). doi: 10.14341/DM13181An error was made in the list of authors: Nina A. Petunina was not indicated as author of this article. The correct list of authors: Natalya G. Mokrysheva, Marina V. Shestakova, Alexander S. Ametov, Mikhail B. Antsiferov, Igor G. Bakulin, Tatiana V. Vavilova, Gagik R. Galstyan, Tatiana Y. Demidova, Fatima K. Dzgoeva, Tatiana L. Karonova, Elena A. Lukina, Ashot M. Mkrtumyan, Nina A. Petunina, Rodion V. Ponomaryov, Natalia A. Suponeva, Olga Y. Sukhareva, Minara S. Shamkhalova.The identifier in the ORCID system for F.K. Dzgoeva was also indicated incorrectly. The correct link is: https://orcid.org/0000-0002-0533-7652.The editorial board apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.

Background. Warfarin has a wide variability in response, depending on the pharmacogenetic profile and vitamin K intake. The aim of the study was to analyze the amount of vitamin K supplied with food, its effect on the efficacy and safety of warfarin therapy in patients with different pharmacogenetic profiles. Materials and methods: The study included 34 people taking warfarin and 70 healthy volunteers, residents of St. Petersburg and the Leningrad region. Vitamin K consumption was determined using food diaries, genetic variants of VKORC1, CYP2C9 and CYP4F2 were determined using DNA-Technology kits on a DT-96 detection amplifier of the same manufacturer. Results. Vitamin K consumption by healthy volunteers was 84.4 ± 5.4 mcg/day, while in patients taking warfarin it was 63.9 ± 7.4 mcg/day (p < 0.0001), and the higher the daily vitamin K consumption by patients, the more stable the response and the shorter the time the patient spends outside the therapeutic INR range. The carriage of the AA3730 VKORC1 and TT1347 CYP4F2 genotypes, which determine a reduced ability to metabolize vitamin K, which entails a higher level of vitamin K in the liver and requires increased doses of warfarin, was 16 % and 7 % of patients, respectively. The *2 and *3 alleles of the CYP2C9 gene were detected in 33.8 % of patients. These alleles significantly affected the stability of warfarin therapy, so in 91 % of cases of exceeding the therapeutic interval of INR in patients, variants of CYP2C9*2 or CYP2C9*3 were detected, and only in 56 % of cases of INR below the therapeutic interval in patients were these variants detected (p < 0.03). Conclusion. Vitamin K consumption by patients taking warfarin is significantly lower than that of healthy residents of the North-West region. Low vitamin K consumption reduces the stability of hypocoagulation in patients taking warfarin.

On March 20, 2024, an interdisciplinary meeting of the Expert Council on the current problem of B12 insufficiency/deficiency and the prevalence of this condition among endocrine patients was held at the Endocrinology Research Centre (Moscow). The purpose of the meeting was to assess the role of B12 deficiency in reducing the quality of life of patients of different groups and to outline a strategy for the management of patients with vitamin B12 insufficiency/deficiency by endocrinologists.The resolution of the expert council was developed by leading specialists in various specialties.

The system of personnel training for work in modern clinical diagnostic laboratories should meet the challenges that the development of personalized medicine sets for the medical community. Traditionally, departments and courses of clinical laboratory diagnostics in medical higher educational institutions as part of the training of highly qualified personnel — residency and postgraduate studies, carry out such work. The clinical orientation of laboratory diagnostics and its special role in providing personalized medicine urgently requires the close integration with clinical departments, which is implemented in the Almazov National Medical Research Centre within the framework of the University Clinic.

OBJECTIVE:To study serum quantities of neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP) and NR2-antibodies (NR2-ab) in various cerebrovascular pathology and assess their value as a panel used as a diagnostic and predictive tool for stroke.MATERIAL AND METHODS:NSE, GFAP and NR2-ab serum levels were measured twice for 84 patients with ischemic stroke (IS) and 8 patients with hemorrhagic stroke (HI), once for 8 patients with transient ischemic attack (TIA), 26 patients with chronic brain ischemia (CBI), 27 healthy volunteers (HV).RESULTS:NSE and GFAP levels were significantly higher in IS than in CBI and HV patients, and NR2-ab levels in IS were higher than in TIA and lower than in HV. In patients with more pronounced neurological deficiency and less favorable functional outcome by day 10-14 of IS, the levels of NSE, GFAP and NR2-ab were higher. Sensitivity and specificity of biomarker panel was higher than with their separate application.CONCLUSION:The NSE, GFAP and NR2-ab biomarkers have a diagnostic and predictive value for IS.

Background. Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease with a poor prognosis. The role of monocytic-macrophage inflammation in the incomplete recanalization of acute thromboembolic pulmonary artery disease and the formation of CTEPH was shown. The role of the coagulo-fibrinolytic system in the pathogenesis of CTEPH remains controversial. Objective. To assess the activity of the coagulo-fibrinolytic system and its relationship with the level of monocytic chemotactic factor 1 (MCP-1), as well as the severity of the disease in patients with long-term CTEPH. Design and methods. The study included 44 patients diagnosed with CTEPH: 21 men (mean age 57,0 ± 11,9 years) and 23 women (mean age 53,8 ± 14,7 years). The diagnosis of CTEPH was verified according to the clinical guidelines of the Ministry of Health of the Russian Federation for the diagnosis and management of patients with pulmonary hypertension from 2020. The control group consisted of healthy donors (n = 19, mean age 51,0 ± 11,9 years, 10 men, 9 women). All patients were on anticoagulant therapy with enoxaparin sodium at a therapeutic dose of 1 mg/kg subcutaneously twice a day. The study of markers of the fibrinolysis and inflammation system was carried out by enzyme immunoassay: thrombin-activated fibrinolysis inhibitor (TAFI), tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), monocytic chemotactic factor 1 (MCP-1). Results. In the CTEPH group, an increase in the level of t-PA was demonstrated — 6,06 [4,502; 8,03] vs 2,95 [2,75; 3,56] ng/ml in donors (p = 0,00001). The levels of PAI-1 and TAFI did not differ in patients (34,40 [22,47; 46,43] and 94,67 [90,03; 102,80] ng/mL, respectively) and donors (24,93 [21,41; 43,88] and 92,68 [87,99; 98,29] ng/ml, respectively) (p = 0,0970 and p = 0,233). A significant increase in the level of MCP-1 was found in patients with CTEPH compared to donors (34,95 [31,00; 42,08] vs 26,05 [20,40; 31,33] pg/ml, p = 0,016, respectively). A correlation was noted between MCP-1 and fibrinolysis indices t-PA (0,402, p = 0,046), PAI-1 (0,437, p = 0,029). Correlations of MCP-1 and fibrinolysis markers with hemodynamic and physical performance indicators are also shown: MCP-1 and SvO 2 (–0,574, p = 0,002), MCP-1 and cardiac index (CI) (–0,614, p = 0,001), distance in the six-minute walk test (6MWT) and t-PA (–0,435, p = 0,006). Conclusions. As a result of the study, the relationship between MCP-1 and the activity of the coagulo-fibrinolytic system and the severity of CTEPH was demonstrated. The data obtained can be used to further study the pathogenesis of postthromboembolic syndrome and develop criteria for assessing prognosis in patients with CTEPH.

Chronic thromboembolic disease (CTED) and chronic thromboembolic pulmonary hypertension (CTEPH) are the complications that comprise a serious problem for patients with history of pulmonary embolism (PE). Erythrocytes, extracellular microvesicles (EMVs) and miRNAs play a substantial role in the procoagulant states. The aim. To analyze the levels of miR-144-3р, miR-451a, and miR-451b in blood plasma-derived EMVs and erythrocytes in patients with history of PE and in the control group. Materials and Methods. 18 patients with history of PE (13 CTEPH, 5 CTED) and 8 controls were enrolled into the study. All the participants had undergone clinical and biochemical blood tests as well as the coagulogram. We used flow cytometry to assess plasma-derived EMVs (CD9, CD41, CD45, CD235a, CD105). We measured the expression of miR-144-3р, miR-451a, miR-451b by real-time PCR with endogenous control (miR-152-3p) and five exogenous quality controls. Results. The levels of miR-144-3р and miR-451a in patients were lower than in controls, both in EMVs (р = 0.030; р = 0.065) and in erythrocytes (р = 0.023;р = 0.086). In female patients, the levels of miR-144-3р and miR-451a in CTEPH were lower than in CTED (р = 0.087; р = 0.031). Mir-451b in EMVs has not been detected, while in erythrocytes its levels have not differed between the groups. In patients, the levels of miR-144-3р and miR-451a directly correlated with each other both in EMVs (р = 0.004) and in erythrocytes (р = 0.042). In all the participants, the levels of miR-144-3р and miR-451a in EMVs directly correlated with those in erythrocytes (р = 0.002; р = 0.078). The number of erythrocyte-derived EMVs correlated with miR-451a levels both in EMVs (R = 0.472; p = 0.065) and in erythrocytes (R = –0.829; p = 0.011). The level of miR-451a in EMVs correlated with blood plasma levels of factor VIII and fibrinogen (R = 0.584; p = 0.022 and R= –0.489; p = 0.047), and with the International Normalized Ratio (R = 0.894; p = 0.041). Conclusion. The microRNA-144/451 cluster may influence both the hemostasis system and the risk of post-thromboembolic complications development. In the present study, miR-144-3р and miR-451a showed themselves as protective factors in relation to both the development of PE and severity of post-thromboembolic complications.

The use of hormonal drugs for contraception and menopausal replacement therapy is widespread throughout the world. However, the use of these drugs is associated with an increased risk of thromboembolic complications (TEO). At present, it has been established that the most important cause of feasibility study is the initial, sometimes hidden, violations of the hemostasis system, predisposing to increased blood clotting and thrombosis. Their timely identification helps to personalize the use of the necessary hormonal therapy.

Currently, the routine assessment of rheumatoid arthritis (RA) disease activity includes the determination of joint syndrome indicators, such as tender and swollen joint counts, as well as a number of laboratory indicators. The most interesting are the latter, which include rheumatoid factor, cyclic citrullinated peptide antibodies, and some acute-phase indicators. However, these tests have low sensitivity and specificity, especially at early stages of the disease, when it is still possible to bring the indicators to their age-specific normal values and to achieve a stable disease remission. In addition, some of these medical tests are quite expensive and not covered by compulsory health insurance. Most importantly, there are still no reliable tools to assess the development of RA-associated inflammatory processes in joints depending on the degree of RA severity and the treatment strategy being applied. Here, we analyze the possibility of using the 14-3-3η protein as a promising biomarker for assessing RA immunoinflammatory process activity in joints. We demonstrate a higher informative value of this marker in terms of its accuracy, sensitivity and specificity as compared to conventional acute-phase indicators, such as the erythrocyte sedimentation rate and C-reactive protein level.

Genetic testing plays an increasing role in the diagnosis of various diseases every year. Special attention is paid to genes with an increased risk of cancer in case of mutation. Hereditary prostate cancer is usually more aggressive and is most often associated with mutations in DNA repair genes. These mutations carriers have an increased risk of metastasis and a shorter life expectancy. The study of mutations in the BRCA1/BRCA2 genes is most often used in clinical practice, while there are many other genes responsible for DNA repair processes that have not been sufficiently studied. In this paper, we report a review of literature sources studying the cellular mechanisms of functioning of DNA repair genes, the effect of such mutations on the disease state and oncological outcomes.

Background. Platelets play a key role in the pathogenesis of acute coronary syndrome (ACS). In recent years, the amount of data on the advisability of using the platelet function test (PFT) in the appointment of antithrombotic therapy has been growing. Objective. To access PFT in patients with unstable angina and various comorbidities. Design and methods. The study involved 74 patients with the diagnosis of unstable angina. All patients underwent standard clinical examination, PFT (impedance aggregometry with ADP and collagen), assessment of Charlson comorbidity index. Results. The most frequent comorbidities were: hypertension (95 %), type 2 diabetes mellitus (30 %), excessive body weight (35 %), multifocal atherosclerosis (22 %), smoking (24 %). Half of the patients (n = 36) had high level of comorbidity. Patients with a comorbidity index of 5 or more had high platelet aggregation on the 3rd day of hospitalization. Elderly patients, smokers, as well as patients with diabetes mellitus type 2 and multifocal atherosclerosis also had higher values of platelet activity, which may be associated with unfavorable prognosis and risk of recurrent events. Conclusion. We revealed association between PFT and comorbidities both with risk factors or diseases alone and in its integral assessment using the Charlson comorbidity index. Among the individual risk factors, smoking, diabetes mellitus and multifocal atherosclerosis were the most important, which confirms their direct role in the pathogenesis of thrombotic complications.

Expert Council: Drapkina O. M., Vavilova T. V., Karpov Yu. A., Kobalava Zh. D., Lomakin N. V., Martynov A. I., Roitman E. V., Sychev D. A.Scientific communities: the Russian Society for the Prevention of Non-Communicable Diseases (ROPNIZ), the Russian Scientific Medical Society of Therapists (RNMOT), the Russian Antithrombotic Forum (RAF), the National Association for Thrombosis and Hemostasis (NATH).

BACKGROUND: High platelet reactivity leads to the progression of atherosclerosis and its complications. Activated platelets adhere to the site of endothelium damage on the vessel wall and initiate the formation of an arterial thrombus, followed by acute ischemia of the organ. Biochemical and cellular marker such as platelet microvesicles and P-selectin can be analyzed using flow cytometry, which is based on a specific antigen-antibody interaction. Patients with peripheral arterial disease are at significantly greater risk of cardiovascular and cerebrovascular complications than individuals of the same age and sex. The use of antiplatelet agents is an important part of pathogenetic therapy and prevention of cardiovascular diseases and their complications. AIM: This study was to evaluate the level of platelet microparticles and P-selectin expression in patients with peripheral arterial disease receiving antiplatelet therapy. MATERIALS AND METHODS: The study included 49 people, which included three study groups: patients with obliterating disease of the arteries of the lower extremities (n = 14) on the background of long-term use (more than 14 days) of double (75 mg clopidogrel and 100 mg Acetylsalicylic acid) antiplatelet therapy, patients with COVID-19 (n = 15), who made up the positive control group in the determination of microparticles of platelet origin, and healthy volunteers (n = 20) without signs of acute respiratory disease, without a history of cardiovascular and thromboembolic episodes, not taking antiplatelet drugs. The functional activity of platelets was assessed by two methods: using light aggregometry and analysis of P-selectin expression on platelet surface by flow cytometry. The number of platelets microparticles in blood plasma was also determined using flow cytometry. RESULTS: A significant decrease in platelet aggregation was found in patients with peripheral arterial disease taking antiplatelet agents, compared with controls by used light aggregometry. Similar changes were obtained when analyzing the expression of P-selectin on platelets. A higher percentage of platelets microparticles with the CD9+CD41+ phenotype was found in patients with severe inflammation compared with peripheral arterial disease patients treated with antiplatelet agents and compared with the healthy controls. CONCLUSIONS: Thus, our study reflects the consistency of the results of three different laboratory tests in assessing the platelets reactivity in patients with the peripheral arterial diseases taking antiplatelet drugs.