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Aim    To study specific features of administering platelet P2Y12 receptor inhibitors to patients with myocardial infarction (MI) in real-life clinical practice; to reveal a possible inconsistency of the therapy with clinical guidelines; to evaluate the patients' compliance with the medication at the outpatient stage; and to outline major direction for improving quality of the antiplatelet treatment.Material and methods    REGION-MI is a multicenter prospective, observational study. The observational period is divided into 3 stages: during the stay in the hospital and at 3 and 12 months following the inclusion into the registry. Information about the drug therapy (used at the time of hospitalization, administered before the hospitalization, received in the hospital, and prescribed at discharge from the hospital) was recorded in the patient's individual registration card. Information about the antiplatelet treatment at 6 months following enrollment into the study was obtain by phone.Results    The study included 4 553 patients. Dual antiplatelet therapy was administered after MI to 94.4 % patients: clopidogrel was administered to 52 %, ticagrelor to 42.2 %, and prasugrel to 11 patients (0.2 %). Ticagrelor was administered significantly more frequently in ST segment elevation myocardial infarction (STEMI) than in NSTEMI, 45 % and 33 %, respectively (p<0.001); clopidogrel was also administered more frequently to patients with STEMI than with NSTEMI, 59 % and 50 %, respectively. According to ARC-HBR criteria, in MI and a high risk of bleeding, clopidogrel was administered more frequently than ticagrelor (p <0.001). Ticagrelor was significantly more frequently administered to patients with MI and a low risk of bleeding than to patients with a high risk (p<0.001). In STEMI and a low risk of bleeding, ticagrelor was administered somewhat more frequently than clopidogrel, 56 % and 44 %, respectively (р<0.05). In NSTEMI and a low risk of bleeding, clopidogrel was administered more frequently than ticagrelor, 53 % and 47 %, respectively (p<0.05). At 6 months post-MI, 94 % of patients continued taking one of the P2Y12 inhibitors.Conclusion    According to data of the REGION-MI registry, the frequency of administering P2Y12 inhibitors to patients with acute MI was high, and the patients' compliance with this therapy was high at 6 months following MI. Although ticagrelor (the most available drug of all powerful platelet P2Y12 receptor inhibitors) has been prescribed more frequently in the recent years, a definite reserve exists for increasing the frequency of its administration. This is particularly important with a low risk of bleeding and the absence of requirement for anticoagulants. Thus, the prognosis for MI patients can be considerably improved.

Aim      To study the prevalence of hyperlipidemia in patients with myocardial infarction (MI) in the Russian Federation; to assess the compliance with clinical practice guidelines of the lipid-lowering therapy prescribed upon discharge from the hospital; and to determine the number of patients who are indicated for the combination lipid-lowering therapy to achieve the low-density lipoprotein cholesterol (LDL-C) goal.Material and methods  REGION-MI is Russian rEGIstry Of acute myocardial iNfarction, a multicenter, retrospective and prospective observational study. The observation period was divided into 3 stages: observation during the stay in the hospital and at 6 and 12 months after the inclusion in the registry. Plasma total cholesterol (TC) and LDL-C were measured in all patients on admission. Evaluation of the prescribed lipid-lowering therapy included the intensity of the treatment.Results The study included 3 620 patients; 62.4 of them had hyperlipidemia on admission. Mean TC on admission was 5.29 mmol/l and LDl-C level was 3.35 mmol/l. Upon discharge, 95.4% of patients after myocardial infarction continued on or were prescribed statin therapy; ezetimibe was prescribed to 1.22% of patients. Patients with an extremely high level of LDL-C >5 mmol/l accounted for 10.7% of patients with hyperlipidemia. The target level of LDL-C ≤1.4 mmol/l cannot be achieved with the statin and ezetimibe combination therapy in these patients; drugs from the group of PCSK9 inhibitors are indicated for them.Conclusion      According to the data of the Russian registry of acute myocardial infarction, REGION-MI, a high incidence of hyperlipidemia is observed in patients with acute MI. Despite multiple studies that have proven the importance of achieving a low LDL-C level and good tolerance and safety of ezetimibe and PCSK9 inhibitors, the prescription frequency of combination therapy remains unreasonably low. Results of a simulation study that was conducted in Sweden and the data of the REGION-MI registry showed that PCSK9 inhibitors as a part of the combination therapy are indicated for many patients. The combination therapy is presently the most powerful type of lipid-lowering treatment that allows, in most cases, achievement of the LDL-C goal.

Aim      To study features of diagnosis and treatment of acute myocardial infarction (AMI) in Russian hospitals, results of the treatment, and early and late outcomes (6 and 12 months after AMI diagnosis); to evaluate the consistence of the treatment with clinical guidelines; and to evaluate patients' compliance with the treatment.Material and methods  The program was designed for 3 years, including 24 months for recruitment of patients to the study. The study will include 10, 000 patients hospitalized with a confirmed diagnosis (I21 according to ICD-10) of ST segment elevation acute myocardial infarction (MI) (STEMI) or non-ST segment elevation MI (NSTEMI) based on criteria of the European Society of Cardiology Guidelines on Forth Universal Definition of Myocardial Infarction (2018). The follow-up period was divided into three stages: observation during the stay in the hospital and at 6 and 12 months following inclusion into the registry. The primary endpoint included cardiac death, nonfatal MI during the hospitalization and after one-year follow-up. Secondary endpoints were 6-months and one-year incidence of repeated MI, heart failure, ischemic stroke, clinically significant hemorrhage, unscheduled revascularization after discharge from the hospital, and the proportion of patients who continue on statins, antiplatelet drugs, and drugs of other groups for 6 months and 1 year.Results The inclusion of patients into the registry started in 2020 and will continue for 24 months. By the time of the article publication (June, 2021), more than 2,000 patients will be included.Conclusion      REGION-MI (Russian rEGIstry Of acute myocardial iNfarction) is a multicenter, retrospective and prospective observational cohort study that excludes any interference with the clinical practice. Results of the registry will help to analyze a real picture of medical care provided to patients with myocardial infarction and to schedule ways to improve the situation.

Coronary artery disease is the most clinically significant manifestation of atherosclerosis and the main cause of morbidity and mortality around the world. Atherogenesis is a complex process, involving various types of cells and regulatory molecules. MicroRNA molecules were discovered at the end of the 20th century, and nowadays are the important regulators of several pathophysiological processes of atherogenesis. The review examines data on the participation of various microRNAs in the development of atherosclerosis and its main clinical manifestations and discusses the possibility of using microRNAs as diagnostic markers for these diseases.

Atherosclerotic coronary artery disease (CAD) and myocardial infarction (MI) as its most severe clinical complication remain the leading causes of mortality in the majority of countries. Despite the progress in the treatment of MI, quite often the patients, after the first-time MI, develop subsequently a variety of adverse cardiovascular events. In this retrospective study we evaluated the contribution of allelic variations in 9p21.3 locus and in 21 atherogenesis-related genes to the development of hard cardiac events in a cohort of patients of Russian ethnicity after the first acute MI during long-term follow-up (7-10 years). Death from cardiac causes and recurrent nonfatal MI were considered as key clinical outcomes. We have shown the association of rs1333049 and rs10757278 in 9p21.3 and MTHFR rs1801133 with recurrent unfavorable events, the latter was observed in time-dependent manner. Multilocus analysis additionally suggested the influence of carriage of the CRP and ENOS genes variants at the development of subsequent adverse events after MI. The composite model built for prediction of the individual genetic risk of postinfarction hard cardiac events included 9p21.3 rs1333049*GG and MTHFR*TT and was characterized by area under the curve (AUC) = 0.65. Our data show that 9p21.3 locus and MTHFR gene polymorphisms could influence long-term prognosis of recurrent hard cardiac events in patients who underwent the first MI. It is possible that addition of genotyping at such loci to existing clinical scores could improve their predictability., (Copyright © 2018. Published by Elsevier B.V.)

In search of genetic markers of myocardial infarction (MI) risk, which have prognostic significance for Russians, we performed a replication study of MI association with genetic variants of PCSK9 (rs562556), APOE (epsilon polymorphism, rs7412 and rs429358), LPL (rs320), MTHFR (rs1801133), eNOS (rs2070744), and the 9p21 region (rs1333049) in 405 patients with MI and 198 controls. Significant MI association was observed with variants of the lipid metabolism genes ( PCSK9 , APOE and LPL ), and of eNOS . The SNPs in the MTHFR gene and the 9p21 region were not significantly associated with MI one by one but were included in several different MI-associated allelic combinations identified by multilocus analysis. Since we have not revealed nonlinear epistatic interactions between the components of the identified combinations, we postulate that the cumulative effect of genes that form a combination arises from the summation of their small independent contributions. The prognostic significance of the additive composite model built from the PCSK9 , APOE , LPL, and eNOS genes as genetic markers was assessed using ROC analysis. After we included these markers in the previously published composite model of individual genetic risk of MI, the prognostic efficacy in our sample reached AUC = 0.676. However, the results obtained in this study certainly need to be replicated in an independent sample of Russians.

Epidemiological genetics established that heritability in determining the risk of myocardial infarction (MI) is substantially greater when MI occurs early in life. However, the genetic architecture of early-onset and late-onset MI was not compared. We analyzed genotype frequencies of SNPs in/near 20 genes whose protein products are involved in the pathogenesis of atherosclerosis in two groups of Russian patients with MI: the first group included patients with age of first MI onset <60 years (N = 230) and the second group with onset ≥60 years (N = 174). The control group of corresponding ethnicity consisted of 193 unrelated volunteers without cardiovascular diseases (93 individuals were over 60 years). We found that in the group of patients with age of onset <60 years, SNPs FGB rs1800788*T, TGFB1 rs1982073*T/T, ENOS rs2070744*C and CRP rs1130864*T/T were associated with risk of MI, whereas in patients with age of onset ≥60 years, only TGFB1 rs1982073*T/T was associated with risk of MI. Using APSampler software, we found composite markers associated with MI only in patients with early onset: FGB rs1800788*T + TGFB1 rs1982073*T; FGB rs1800788*T + LPL rs328*C + IL4 rs2243250*C; FGB rs1800788*T + ENOS rs2070744*C (Fisher p values of 1.4 × 10 -6 to 2.2 × 10 -5 ; the permutation p values of 1.1 × 10 -5 to 3.0 × 10 -4 ; ORs = 2.67-2.54). Alleles included in the combinations were associated with MI less significantly and with lower ORs than the combinations themselves. The result showed a substantially greater contribution of the genetic component in the development of MI if it occurs early in life, and demonstrated the usefulness of genetic testing for young people.

Objective: to elaborate a complex model for myocardial infarction (MI) risk assessment considering the combined effect of genetic predisposition, age and smoking., Materials and Methods: The study included two independent samples of ethnic Russians: 325 patients with MI and 185 individuals without history of cardiovascular diseases (controls) from the Moscow region, and 220 patients and 197 controls from the Republic of Bashkortostan. Genotyping of polymorphic loci of genes CRP (rs1130864), IFNG (rs2430561), TGFB1 (rs1982073), FGB (rs1800788) and PTGS1 (rs3842787) was performed. To construct the predictive models, we used logistic regression with stepwise inclusion of variables. The predictive value was evaluated by the area under the curve (AUC) in a ROC-analysis. The factor was considered as a marker at pAUC <0.05 calculated by the method of DeLong. The marker was considered effective at AUC >0.60., Results: Three separate genetic variants FGB rs1800788*T, TGFB1 rs1982073*TT, CRP rs1130864*TT, and biallelic combination IFNG rs2430561*A + PTGS1 rs3842787*T whose association with MI we described earlier, were used to construct the composite genetic marker (AUC=0.66 in the training and test samples) by the logistic regression method. Adding to the obtained composite genetic marker such parameters as age and smoking allowed to create a complex MI risk marker, which was characterized by the predictive value stability (AUC=0.77 in the training sample and 0.82 in the test sample)., Conclusion: The obtained complex model for MI risk assessment was reproduced in two independent samples of Russian ethnicity individuals from different regions of Russia with different gender identities, and allowed to have a reasonable chance (about 80%) of distinguishing patients and healthy individuals.

Background: In spite of progress in cardiovascular genetics, data on genetic background of myocardial infarction are still limited and contradictory. This applies as well to the genes involved in inflammation and coagulation processes, which play a crucial role in the disease etiopathogenesis., Methods and Results: In this study we found genetic variants of TGFB1, FGB and CRP genes associated with myocardial infarction in discovery and replication groups of Russian descent from the Moscow region and the Republic of Bashkortostan (325/185 and 220/197 samples, correspondingly). We also found and replicated biallelic combinations of TGFB1 with FGB, TGFB1 with CRP and IFNG with PTGS1 genetic variants associated with myocardial infarction providing a detectable cumulative effect. We proposed an original two-component procedure for the analysis of nonlinear (epistatic) interactions between the genes in biallelic combinations and confirmed the epistasis hypothesis for the set of alleles of IFNG with PTGS. The procedure is applicable to any pair of logical variables, e.g. carriage of two sets of alleles. The composite model that included three single gene variants and the epistatic pair has AUC of 0.66 both in discovery and replication groups., Conclusions: The genetic impact of TGFB1, FGB, CRP, IFNG, and PTGS and/or their biallelic combinations on myocardial infarction was found and replicated in Russians. Evidence of epistatic interactions between IFNG with PTGS genes was obtained both in discovery and replication groups.