Artery Atherosclerosis Research Articles

Блеббинг плазматической мембраны лимфоцитов у пациентов с атеросклерозом магистральных артерий и ишемической формой синдрома диабетической стопы

Aim: to assess the blood flow state and the lymphocyte plasma membrane blebbing in atherosclerosis of the lower limb arteries and the ischemic diabetic foot (IDF).Patients and Methods: 75 patients (51 (68%) of them — women) underwent a prospective study with IDF and signs of chronic obliterating disease of lower limb arteries. In the majority of cases (92%), IDF occurred in the setting of type 2 diabetes mellitus. Blood circulation disorder corresponded to the stage II–III Fontaine–Pokrovsky classification, ulcerative defects — to the PEDIS grade 1–2 without signs of infection and with signs of local inflammation. The control group consisted of 25 healthy patients. Blood flow state (using Doppler ultrasound of the lower limb arteries) and diabetes mellitus compensation degree (by the level of glycated hemoglobin), as well as the lymphocyte membrane state were evaluated.Results: 72% of patients had a total occlusion of tibial and foot segments, 28% — stenosis. The level of glycated hemoglobin was 10.3 [8.5; 14.3]%, which indicated insufficient compensation of carbohydrate metabolism disorders. Total and terminal blebbing was 30.1 [25.4; 33.2]% and 15.8 [11.8; 18.4]%, which was 3 and 5 times higher than the control group, respectively. A high positive correlation was observed between the level of glycated hemoglobin and total (rS=0.72; p=0.001) and terminal (rS=0.78; p=0.001) lymphocyte membrane blebbing.Conclusion: given the presence of a high correlation between the indicator of glycated hemoglobin and lymphocyte plasma membrane blebbing, an increase in glycated hemoglobin can be used as a marker for the development of endothelial insufficiency in atherosclerosis of the lower limbs and IDF. At the same time, the level of total and terminal blebbing can be considered as a pathogenetic marker of macroangiopathy. KEYWORDS: diabetes mellitus, atherosclerosis, ischemia, hemodynamics, blebbing, glycated hemoglobin.FOR CITATION: Dunaevskaya S.S., Khachatryan A.T., Deulina V.V. Blebbing of plasma membrane of lymphocytes in patients with atherosclerosis of main arteries and ischemic form of diabetic foot syndrome. Russian Medical Inquiry. 2020;4(7):452–456. DOI: 10.32364/2587-6821-2020-4-7-452-456.

Робот-ассистированное подвздошно-глубокобедренное шунтирование у пациента с атеросклерозом артерий нижних конечностей (клиническое наблюдение)

Робот-ассистированное подвздошно-глубокобедренное шунтирование у пациента с атеросклерозом артерий нижних конечностей (клиническое наблюдение)

Levels of toll-like receptors 2 and 4 in serum of men with postinfarction cardiosclerosis and its relationship with antiphospholipid syndrome components

Annotation. There is a tendency for an increase of incidence of coronary heart disease (CHD) among young people, with the development of acute myocardial infarction (MI) in the absence of marked atherosclerosis and obstruction of the coronary arteries. Antiphospholipid syndrome (APS), cellular and humoral mediators of immunoinflammatory activation of endothelium are considered as factors of non-obstructive damage to the coronary vessels. New trigger factors for endothelial dysfunction, cardiac fibrosis, and myocardial hypertrophy include toll-like receptors (TLR2 and TLR4). Antiphospholipid antibodies may act as endogenous activators of toll-like receptors. The study of the association between APS components and expression of toll-like receptors in patients with CHD with postinfarction cardiosclerosis remains relevant. The aim is to study the levels of TLR2 and TLR4 and its relationship with APS components in men with postinfarction cardiosclerosis. 164 patients with stable CHD with postinfarction cardiosclerosis (100% of men, age 53.0±9.14 years) and 48 men of control group (without CHD) were examined. Levels of total antiphospholipid antibodies (aPL), antibodies to β2-glycoprotein 1 (anti-β2-GP 1) IgG and IgM, TLR2, TLR4 in serum were determined by ELISA. The studies were conducted in compliance with bioethical standards. Statistical processing of the results was performed in SPSS Statistics 22.0. Determined that men with postinfarction cardiosclerosis showed higher levels of TLR2 and TLR4 (in 1.8–2.2 times, p<0.001) in serum than control group. Higher (in 1.2–1.4 times) levels of TLR2 and TLR4 were found in patients who underwent Q-MI, recurrent MI and had clinical manifestations of APS (stroke, transient ischemic attacks, livedo reticularis). An increase TLR2 and TLR4 levels was closely associated with an increase of aPL and anti-β2-GP 1 of IgG (r = | 0.31 - 0.51 |, p<0.01). Thus, in men with postinfarction cardiosclerosis who had aPL and anti-β2-GP 1 IgG positivity had an unfavorable immunoinflammatory pattern, that characterized by increased expression of TLR2 and TLR4. The imbalance in TLR2 and TLR4 is more pronounced in young CHD patients and associated with Q-MI and recurrent MI.

Assessment methods and possibilities of instrumental diagnosis of subclinical atherosclerosis of coronary arteries

Subclinical coronary arteriosclerosis is a common cause of adverse cardiovascular events: myocardial infarction, stroke, sudden cardiac death. Currently, there is a large arsenal of methods for diagnosing coronary atherosclerosis. The article presents its main characteristics, advantages and disadvantages, the possibility of use in routine clinical practice.

Allelic variants of rs1800801 polymorphism in patients with stroke

Aim. To study the association of single nucleotide polymorphism (SNP) rs556621 (G>T) with the development of stroke in patients of the East Siberian population with cardiovascular pathology and risk factors. Material and methods. The study involved 260 patients with stroke (157 men and 103 women) and 272 patients of the control group (170 men and 102 women). The following cardiovascular pathology and risk factors were present in the patients of the main group: arterial hypertension, paroxysmal supraventricular tachycardias, dyslipidemia, atherosclerosis of the brachiocephalic arteries, disorders of the hemostatic system. All patients underwent clinical, instrumental and molecular genetic examination. Statistical processing of the material was carried out using the set of application programs Statistica for Windows 7.0, Excel and SPSS 22. Results. As a result of the study, no statistically significant associations of genotypes and alleles of the rs1800801 polymorphism (C>T) with stroke were found in any of the analyzed groups and subgroups. Conclusion. SNP rs1800801 (C>T) does not have a significant effect on the development of stroke in people of the East Siberian population, regardless of the preceding cardiovascular pathology and risk factors.

CHANGES IN THE HEMOSTATIC SYSTEM AGAINST THE BACKGROUND OF VARIOUS TREATMENT REGIMENS IN PATIENTS WITH ATHEROSCLEROSIS OF LOWER EXTREMITIES

About 2–3 % of the population and about 35–50 % of people over 65 years suffer from obliterating atherosclerosis of the main arteries of the lower extremities. There are many known factors that potentiate atherosclerosis. Some of them are referred to as leading, such as hyperlipoproteinemia or hypertension, others to concomitant contributing to the defeat of the arteries. According to J.S.A. Fuchs include hypertension, hypercholesterolemia and smoking as major risk factors for atherosclerosis. They are less affected by obesity, diabetes, hypertriglyceridemia, sedentary lifestyle, stress Objective of the study. The purpose of this study is to evaluate the functional status of the vascular – platelet, coagulation and fibrinolysis of the hemostasis system and their disorders using low – frequency piezoelectric thromboelastography (LPTEG) in patients with obliterating atherosclerosis of the lower extremities on the background of treatment. Materials and methods. The initial state of the hemostasis system was evaluated in 90 patients undergoing treatment for obliterating atherosclerosis of the lower extremities in the Odessa Regional Clinical Hospital and MD Odreks. All patients underwent surgery in the amount of femoral-popliteal autologous bypass grafting. Patients in the control (1st) group (45 patients) received analgesia during surgery and in the postoperative period based on epidural administration of bupivacaine, and their treatment regimen included enoxaparin 0.4 ml (40,000 anti-XA ME) 2 times a day subcutaneously into the anterolateral surface of the abdominal wall from the first postoperative day and pentoxifylline IV 200 mg twice a day for 7 days. Patients of the studied (2nd) group (45 patients) received analgesia during surgery and in the postoperative period on the basis of epidural administration of bupivacaine, also rivaroxaban 15 mg 2 times a day oraly on the first postoperative day was included in their treatment regimen. The dynamics of the state of the hemostatic system in both groups of patients with OA was evaluated using LPTEG in the first day before surgery and on the 3rd, 5th and 7th postoperative days. Results and conclusions. Before surgery and the start of treatment in patients with OA, against the background of activation of the vascular - platelet link of hemostasis, significant structural and chronometric hypercoagulation with increased thrombin generation and activation of blood fibrinolytic activity are noted. Against the background of treatment in the 1st group, platelet aggregation tends to normalize and there are significant differences compared with the indicators before treatment in the 1st group, the vascular-platelet and fibrinolytic systems did not reach normal values before 7 days, but showed a significant downward trend the degree of manifestation of their violations. Against the background of treatment of the 2nd group, significant changes were observed towards normalization in all components of the hemostatic system according to the LPTEG technique. The state of the coagulation unit of the hemostasis system in patients with OA on the 7th day of therapy does not significantly differ from the norm, it is possible to note significant shifts towards hypocoagulation within the normal range. The fibrinolytic system on the 7th day of treatment does not statistically differ from normal indicators, it has significant positive dynamics compared to 1 day. The second group revealed a statistically significant normalization of all indicators characterizing the blood coagulation potential of the blood and the aggregation ability of platelets, as well as the indicator that is responsible for changes in the fibrinolytic blood system.

Association of rs556621 Polymorphism with Development of Stroke in Patients with Cardiovascular Pathology

Aim. To study the association of single nucleotide polymorphism rs556621 (G> T) with development of stroke in patients of the East Siberian population with cardiovascular pathology and risk factors.Material and methods. The study involved 260 patients (157 men and 103 women) with stroke (mean age 57.0 [51.0-62.0]) and 272 patients (170 men and 102 women) of the control group (mean age 55.0 [51.0-62.0]). The examination of the main group included: collection of complaints, anamnesis, clinical examination, computed tomography of the brain, electrocardiography, echocardioscopy, ultrasound duplex scanning of extracranial brachiocephalic arteries, daily blood pressure and heart rate monitoring, analysis of the blood coagulation system. The patients of the main group have arterial hypertension, paroxysmal supraventricular tachycardias, dyslipidemia, atherosclerosis of the brachiocephalic arteries, disorders of the hemostatic system. The control group was studied in the framework of the HAPIEE international project. Molecular genetic research was performed by real-time polymerase chain reaction.Results. There were no statistically significant differences in the frequencies of genotypes and single nucleotide polymorphism rs556621 alleles (G>T) in the subgroup of patients with stroke and those in the control group. The frequency of the rare TT genotype among patients with stroke was 13.3%±4.16, among healthy individuals – 8.8±3.37% (p=0.1). Gender differences when comparing the frequencies of genotypes and alleles were also not detected (p>0.05). The frequencies of the TT genotype were approximately the same in the subgroup of patients with arterial hypertension (13.1%±4.22) and in the control group (7.4±5.25%; p>0.05). No significant differences were observed in the frequencies of the rare genotype of the studied polymorphism in the subgroup of patients with supraventricular tachycardias (20.0±14.37%), hypercoagulability (15.9±7.64%) and the control group (8.8±3.37%), p>0.05. A statistically significant relationship was found between the rare genotype TT of single nucleotide polymorphism rs556621 (G>T) and the development of stroke in patients with dyslipidemia and atherosclerotic lesions of the coronary arteries (p=0.041; odds ratio 1.86, 95% confidence interval 1.02-3.41).Conclusion. The genotype of TTs of single nucleotide polymorphism rs556621 (G> T) increases the risk of developing stroke in patients with dyslipidemia and atherosclerosis of the brachiocephalic arteries compared with carriers of the GG and GT genotypes. The obtained data are recommended to be considered when prescribing lipid-lowering and antithrombotic therapy.

The remote results of treatment of ischemic stroke conditioned by atherosclerotic affection of carotid arteries

The ischemic stroke is a disease that leads to dysfunctions in life of any individual. The mortality rate of cerebral infarcts reaches up to 39%. Besides, the most acute period of an ischemic stroke, which lasts up to 5-7 days, is especially problematic and is characterized by the highest mortality. The first day of disease results in 21.74% of deaths (out of the total annual number of deaths). The article presents the results of the analysis of treatment of the patients with ischemic stroke caused by the atherosclerosis of brachiocephalic arteries. The role of endovascular technologies in the treatment of the acute cerebrovascular cases has not been fully revealed. The retrospective analysis of treatment of 171 patients with atherosclerotic subtype of ischemic stroke was carried out. The patients were distributed in two groups: in the first group (83 patients) the applied conservative therapy was supplemented by endovascular intervention during the acute period of ischemic insult; in the second group (88 patients) the conservative therapy alone was applied. Both groups were comparable in terms of gender, age and associated diseases. The risk factors of ischemic insult were analyzed such as IHD that requires surgery; hypertensive disease; hypercholesterolemia; ischemic insult in medical history; heart dysrhythmia; diabetes mellitus. All patients had more than one risk factor. There mortality, incapacitation, degree of neurological impairment, frequency of symptoms of hemorrhagic suffusion and of hemorrhagic transformation were analyzed. The remote results were analyzed in sampling of 54 patients: 32 patients from the first group, 22 patients from the second group. The quality of life was measured using technique of non-specific survey SF-36 when its 36 items were grouped into eight scales: physical functioning, role activity, body pain, general health, vitality, social functioning, emotional state, psychological health. The degree of incapacitation was measured with the modified Rankin scale, the quality of life was examined with the SF-36 survey, the survival rate was measured with the Kaplan-Meier estimator. The statistical analysis was carried out with the help of the Statistica 6.0 software.

P1216Evaluation of alphavbeta3 integrin-targeted positron emission tomography and photoacoustic tracer for imaging of carotid plaque in apoE–/– mice

Abstract Background Cardiovascular disease is the leading cause of death in the world. The majority of cardiovascular events result from the rupture of vulnerable atherosclerotic plaques, which are characterized by high and active macrophage content. The integrin αVβ3 is expressed by activated macrophages and endothelial cells in atherosclerotic lesions and thus is a marker of high-risk plaques. Therefore, 89Zr-RGD-melanin nanoparticle (MNP) positron emission tomography (PET)/photoacoustic imaging (PAI) imaging of αVβ3 expression in plaques might provide a novel noninvasive biomarker of plaque vulnerability. Purpose In this study, the intrinsic photoacoustic signals and the native strong chelating properties with metal ions of MNP, positron-emitting metal ions 89Zr and αVβ3 integrins targeting ability of cyclic c (RGDfC) peptide was employed to construct an efficient nanoplatform. And we evaluated the feasibility of 89Zr-RGD-MNP PET/PAI of αVβ3 expression in vivo and in vitro. Methods We conjugated αVβ3 integrins, cyclic c (RGDfC) peptide, to MNP and chelated the long-lived positron-emitting nuclide 89Zr. The bio-stability and targeting action was detected in macrophages. And the PET/PAI imaging was performed in apoE−/− mice with partial carotid ligation leading to atherosclerosis. In PET imaging, tracer uptake was measured in the stenotic areas of the carotid arteries, as well as on the contralateral side at different time points in vivo. In PAI, photoacoustic signal was measured in the atherosclerosis of the carotid arteries in vivo. Melanin staining and immunohistochemistry of αVβ3 expression were detected in atherosclerosis of the carotid arteries. Results 89Zr-RGD-MNP showed excellent bio-stability and targeting action. PET imaging showed specific tracer accumulation at plaques in the left carotid artery, confirmed by competitive receptor blocking studies and the contrast in the right carotid artery. In the biodistribution studies, the left carotid (5.29%±0.78%) showed higher uptake than the right carotid (2.11%±1.55%). PAI showed the PA signal in the surgery group (452±85 a.u.) were stronger than the control (156±45 a.u.) and blocking group (254±66 a.u). The result was consistent with PET imaging and the presence of nanoparticles, as indicated by pathological examinations. These results presented good in vivo multimodality imaging (PET/PAI) properties. Conclusions We have developed 89Zr-labeled atherosclerotic plaques imaging agents based on the natural melanin nanoparticle. 89Zr-RGD-MNP demonstrates specific tracer accumulation in mice atherosclerotic carotid plaques. In this model, its uptake was associated with αVβ3 expression. 89Zr-RGD-MNP is a potential tracer for noninvasive imaging in atherosclerosis. Acknowledgement/Funding National Natural Science Foundation of China 81770452, 81470401

P2748Lipoprotein(a) and autotaxin in patients with stenotic atherosclerosis of coronary arteries and aortic valve stenosis

Abstract Background Lipoprotein(a) [Lp(a)] is an independent risk factor of coronary heart disease (CHD) and calcific aortic valve stenosis (CAVS). It has been recently shown that autotaxin (ATX), which breaks down lysophosphatidylcholine, derived from oxidized phospholipids, to lysophosphatidic acid, was strongly associated with CAVS. Purpose The aim of the study was to investigate the role of Lp(a) and ATX in CHD patients with and without CAVS. Methods The study included 438 patients (average age 66±11 years, men 310), 332 had CHD with ≥50% stenosis in at least one coronary artery according to angiography. CAVS was diagnosed with ultrasound. The control group consisted of 106 patients without CHD and CAVS. The concentrations of Lp(a), ATX, lipids and blood cells were measured for all the patients. Results CHD without CAVS (group I) was diagnosed in 287 patients, 45 patients had CHD and CAVS (group II). Patients in both groups were older than patients in the control group (75±8, 66±10 and 61±13 years respectively). ATX level was lower in group I (median [25; 75%]: 493 [406; 583] ng/ml) than in control group (544 [412; 655] ng/ml, p=0.02) or group II (553 [475; 609] ng/ml, p=0.003). Lp(a) was lower in control group (14.5 [5.5; 36.0] mg/dl) than in group I (25.6 [9.7; 58.5] mg/dl, p=0.0004) and group II (23.8 [9.9; 79.1] mg/dl, p=0.02). Elevated level of ATX was positively associated with CAVS in CHD patients, but negatively with CHD in patients without CAVS. We have shown that age, glucose level and neutrophil-lymphocytes index (NLI) could be predictors of CAVS in patients with CHD according to results of logistic regression analysis. Odds ratio of high (QIV) vs. low (QI) Odds ratio (95% confidence interval) Groups Autotaxin Lipoprotein(a) Neutrophil-lymphocytes index I vs. control 0.5 (0.3–0.9)* 2.7 (1.3–5.2)** 2.4 (1.3–4.6)* II vs. control 8.6 (1.1–70.1)* 3.4 (1.2–9.4)* 6.2 (2.2–16.9)** II vs. I 16.6 (2.1–131.1)** 1.3 (0.5–3.2) 2.5 (1.0–6.37)* *p<0.05, **p<0.005. Conclusion Elevated Lp(a) level is a predictor of CHD regardless of calcific aortic valve stenosis, whereas elevated concentration of autotoxin in CHD patients was associated with calcific aortic valve stenosis.

P4443Elevated levels of D-dimer are associated with inflammation and disease activity rather than risk of venous thromboembolism in patients with granulomatosis with polyangiitis

Abstract Background Granulomatosis with polyangiitis (GPA) is one of antineutrophil cytoplasmic autoantibody (ANCA) – associated vasculitis. The disease is characterized by necrotising inflammation of small vessels causing tissue ischemia in a variety of organs with a wide range of clinical presentations. It has been established that active GPA is associated with a very high risk of venous thromboembolic events (VTEs). Purpose The aim of the present study was an evaluation of inflammation, coagulation and fibrinolysis markers, and their association with various clinical and laboratory parameters in GPA patients. Methods The group of 100 consecutive patients with GPA was prospectively followed in the study. In all patients echocardiography and laboratory tests were performed. Results The patients were followed up for an average of 4.0±1.9 years. In this group, D-dimer was elevated in majority (56%) of patients. The circulating levels of D-dimer were significantly higher in GPA patients in active stage of disease compared with those in remission (652 vs. 405 ng/ml, p=0.0002). In 23 patients venous thromboembolism was diagnosed during observation. However, there was no difference in D-dimer concentration between patients with and without VTE either in active stage or in remission. Among the 100 GPA patients higher D-dimer levels were observed in patients with coronary artery disease (p=0.04), atherosclerosis (p=0.01), hypertension (p=0.0049), diabetes (p=0.0065) and hypercholesterolemia (p=0.03). Moreover, correlation analysis showed that the levels of D-dimer correlated with hs-CRP (r=0.42; p<0.0001) and creatinine (r=0.58; p<0.0001). In patients with VTE, D-dimer levels correlated positively with age (r=0.5, p=0.02), right ventricle diameter (r=0.63, p=0.0017), right ventricle systolic pressure (r=0.44, p=0.04), and negatively with pulmonary artery acceleration time (r=−0.43, p=0.05). D-dimer – normal D-dimer – elevated p Inclusion – active stage n=44 (44%) n=56 (56%) Elevated creatinine 1 (2.27%) 25 (44.6%) <0.0001 Elevated CRP 5 (11.3%) 22 (39.2%) 0.0015 Venous thromboembolism 7 (15.9%) 16 (28.6%) 0.0712 CRP: C-reactive proteine. Conclusion In patients with Granulomatosis with polyangiitis elevated levels of D-dimer are associated with disease activity and inflammation, rather than with risk of venous thromboembolism. D-dimer is not a useful marker of venous thromboembolism episodes in patients with small vessel vasculitis.

P6219Can too much exercise “burn” your endothelium?

Abstract Background/Introduction Regular aerobic exercise has beneficial effects on the cardiovascular system. Marathon running is an aerobic and extremely vigorous exercise. Endothelial function and carotid subclinical atherosclerosis are independent predictors of cardiovascular risk. Purpose We investigated the chronic alterations of these indices in marathon runners. Methods We studied 30 marathon runners and 20 age- and sex-matched recreationally active control subjects. Endothelial function was evaluated with flow-mediated dilatation of the brachial artery (FMD) and early atherosclerosis with carotid intima-media thickness (cIMT). All subjects completed analytical questionnaires about their medical history and training. Results Marathon runners had significantly higher systolic and pulse pressure compared to controls. They also had reduced body-mass index, waist to hip ratio and heart rate compared to controls (p<0.05, for all). Common cIMT was significantly lower in athletes than controls (0.56±0.11 vs. 0.63±0.07, p=0.029), while there was no difference in carotid bulb IMT between groups. FMD was higher in marathon runners compared to controls and nitrate-mediated dilatation (NMD) was similar in the two groups (9.0±3.7 vs. 6.4±1.7 and 12.6±5.7 vs. 12.3±3.4; p=0.002 and p=0.821, respectively). We also observed a reverse U-shaped curve between endothelial function and amount of exercise. (Figure) Effect of amount of exercise on FMD Conclusions Our study shows, that marathon runners have higher FMD compared to controls, indicating better vascular endothelial function, and also have lower cIMT compared to controls. Increased amount of exercise training seems to abolish the beneficial effect of exercise on endothelial function. These findings provide further insights in the effects of marathon running on endothelial function and carotid atherosclerosis.

Type 2 Diabetes and Cardiovascular Factors Contrasted with Fibrinolysis Disorders in the Blood of Patients with Peripheral Arterial Disease

Background and objectives: Both in the pathogenesis of type 2 diabetes (DM 2) and Peripheral Arterial Disease (PAD), a vital role is played by endothelial dysfunction. Metabolic disorders found in DM 2 (hyperglycemia, insulin resistance), endothelial dysfunction, and increased inflammation lead to intensified atherothrombosis. The fibrinolysis system comprises a natural compensatory mechanism in case of hypercoagulability. The aim of this study was to assess concentrations of selected fibrinolysis parameters in the blood of patients with symptomatic PAD, including in particular concurrent DM 2 and other cardiovascular factors. Materials and Methods: In the group of 80 patients with PAD (27 F/53 M) and 30 healthy volunteers (10 F/20 M), the following parameters were measured: Concentrations of fibrinogen, tissue-Plasminogen Activator (t-PA Ag), Plasminogen Activator Inhibitor-1 (PAI-1 Ag), D-dimer, and platelet (PLT) count. Results: In the blood of patients with PAD and concomitant DM 2 significantly higher concentrations of fibrinogen were found in comparison with patients with PAD and without diabetes (p = 0.044). No significant impact was observed in individuals with atherosclerotic complications (manifested by coronary artery disease, atherosclerosis of cerebral arteries) and selected cardiovascular risk factors (smoking, LDL and triglyceride concentrations, BP values) on the levels of t-PA, PAI-1, D-dimer, and PLT count. It was found that t-PA Ag and PAI-1 Ag values tended to rise along with a BMI increase in the subgroups of subjects (with normal body mass, overweight, and obesity), but no statistically significant differences were observed. However, two significant positive correlations were reported between t-PA Ag and BMI, as well as between PAI-1 Ag and BMI. Conclusions: Type 2 diabetes in peripheral arterial disease affects the concentration of fibrinogen causing its increase, which is connected with the inflammation and prothrombotic process in the course of both conditions. The concurrence of atherosclerosis of coronary or cerebral arteries, smoking, LDL and TG concentrations, and BP value do not have a significant impact on the levels of analyzed fibrinolysis parameters. A positive correlation between BMI and t-PA Ag and PAI-1 Ag concentrations needs to be supported in further studies on a larger number of overweight and obese patients.

Нарушения в системе протеина С и атеросклероз периферических артерий у пациентов высокого и очень высокого риска сердечно-сосудистых осложнений

Цель исследования: изучить частоту встречаемости нарушений в системе протеина С у пациентов высокого и очень высокого риска сердечнососудистых осложнений (ССО), а также выявить взаимосвязи данных нарушений и тяжести атеросклеротического поражения периферических артерий. Материалы и методы. В исследование были включены 165 пациентов высокого и очень высокого риска ССО. Скрининг нарушений в системе протеина С проводили с использованием набора реагентов Парустест (ООО ТехнологияСтандарт, Россия). Резистентность фактора Va к активированному протеину С определяли с использованием набора реагентов Фактор VPCтест (ООО ТехнологияСтандарт, Россия). По полученным данным рассчитывали нормализованное отношение (НО). Всем пациентам проводили ультразвуковое дуплексное сканирование артерий каротидного бассейна и артерий нижних конечностей (АНК). Результаты. Медиана НО протеина С составляла 1,20 0,801,60. Снижение НО менее 0,7 было выявлено у 16 (9,69 ) пациентов. Резистентность к АПС была установлена у 1 (0,61 ) больного. По результатам корреляционного анализа снижение НО протеина С ассоциировалось с увеличением степени стенозирования сонных артерий и АНК. По результатам полиномиального логистического регрессионного анализа снижение НО протеина С менее 0,7 с поправкой на такие факторы как пол, возраст, курение, артериальная гипертензия, сахарный диабет 2го типа, скорость клубочковой фильтрации и содержание липопротеинов низкой плотности ассоциировалось с увеличением относительного риска выявления тяжелого сочетанного поражения периферических артерий с их стенозированием более 50 в 10,8 раз (95 ДИ 1,8363,8 p 0,009). Заключение. У пациентов высокого и очень высокого риска ССО нарушения в системе протеина С выявлялись в 9,69 случаев. Снижение НО протеина С ассоциировалось с увеличением тяжести атеросклеротического поражения периферических артерий. Наличие у пациента нарушений в системе протеина С ассоциировалось с увеличением относительного риска выявления тяжелого сочетанного поражения периферических артерий в 10,8 раза. Aim: to study frequency of protein C system abnormalities in patients with a high and very high cardiovascular risk and to reveal the relationship of these disorders and the severity of atherosclerosis of peripheral arteries. Materials and methods. The study included 165 patients at high and very high cardiovascular risk. Screening of abnormalities in the protein C system was carried out using Parustest (OOO TechnologyStandard, Russia). Resistance factor Va to APS was determined using Factor VPCtest (OOO TechnologyStandard, Russia). The obtained data were used to calculate the normalized ratio (NO). All patients underwent ultrasound duplex scanning of carotid arteries and lower limb arteries. Results. The median NO of protein C was 1.20 0.801.60. A decrease in NO less than 0.7 was diagnosed in 16 (9.69 ) patients. Resistance to APC was established in 1 (0.61 ) patient. A decrease in the NO of protein C was associated with an increase in the degree of stenosis of carotid arteries and lower limb arteries. According to the results of the polynomial logistic regression analysis, the decrease in the NO protein C less than 0.7, adjusted for factors such as sex, age, smoking, hypertension, type 2 diabetes mellitus, glomerular filtration rate and low density lipoprotein content was associated with an increase in the relative risk of identifying severe combined atherosclerosis of peripheral arteries in 10.8 times (95 CI 1.8363.8 p 0.009). Conclusion. In patients with a high and very high cardiovascular risk abnormalities of the protein C system were detected in 9.69 of cases. Reduction of the normalized ratio of protein C was associated with an increase in the severity of peripheral arteries atherosclerosis. The presence of abnormalities in the protein C system was associated with a 10.8fold increase in the relative risk of detecting a severe combined atherosclerosis of peripheral arteries.

Skin microhemodynamics in patients with obliterating atherosclerosis of lower extremities arteries and diabetes mellitus type 2

Introduction. Chronic tissue ischemia appeared due to obliterating atherosclerosis of lower extremities arteries (OALEA) enhances diabetic microangiopathy making prognosis worse. Due to fundamental biological importance of microcirculation (MC), the study of tissue blood flow in case of this pathology receives huge theoretical value.Purpose of the study was to reveal features of skin MC in patients with diabetes mellitus type II (DM) with OALEA in comparison with the same group of patients without DM.Material and methods. The study involved 111 males with claudication IIB stage and ancle-brachial index (ABI) ≤0.85, which were randomized into two groups equal in age and main clinical and anamnesis data (Gr.1 –without DM (n=77) and Gr.2 – with DM (n=34)). Skin MC was examined using Laser Doppler Flowmetry.Results. Patients with DM had statistically important lowering of blood flow oscillatory amplitude in myogenic (34,5 %) and endothelial (27,8 %) frequency ranges in comparison with the alternative group. Together with the growth of myogenic tone (63,5 [38,6; 123,4] vs 43,6 [28,9; 75,0] u), it reflects depression of vasolytic features and constriction of precapillary segment of the bloodstream. The study revealed significant limitation (18,9 %) of nutritional blood flow and increase of the intensity of arterial and venous bypass grafting in patients of Gr.2 (2,6 [1,8; 4,0 vs 2,0 [1,2; 3,0] u) in Gr. 1.Conclusion. The studied patients had monotype MC alterations. However, they are more pronounced in patients with DM; it worsens the disease prognosis.

ACUTE CORONARY SYNDROME WITH NONOBSTRUCTIVE CORONARY ARTERIES: THE SEVERITY OF CORONARY ATHEROSCLEROSIS AND MYOCARDIAL PERFUSION DISORDERS (PILOT STUDY)

Aim. To study the structural and functional status of coronary blood flow in patients with acute coronary syndrome with nonobstructive coronary arteries using multispiral computed tomography (MSCT) and single photon emission tomography (SPECT) and to compare data of MSCT and invasive coronary angiography (ICA).Material and Methods. This study is a non-randomized, open-label, controlled clinical trial. The study is registered on ClinicalTrials.gov. The inclusion criteria are listed on the site. All patients underwent CT and SPECT.Results. The study included 14 patients with MINOCA; the group comprised predominantly women (n=11, 78.6%); the average age was 61.1±14 years. The risk according to GRACE (Global Registry of Acute Coronary Events) risk score was moderate in 8 patients (57%) and high in 5 patients (35.7%). 85.7% of patients were admitted to hospital within the first six hours from onset of diseases. Three patients (21.4%) received thrombolytic therapy and it was effective in two of them (14%). Risk factors included hypertension (64.2%), dyslipidemia (50%), and burdened history (71.4). According to the results of invasive coronary angiography, intact coronary arteries were detected in 9 patients (64.3%); 5 patients (35.7%) had stenosis up to 50%. Coronary slow-flow phenomenon (TIMI 2) was detected in 11 patients (78.6%) including 8 patients (57.1%) who had coronary slow-flow phenomenon and intact coronary arteries. Severe coronary spasm was registered in 1 patient (7.1%) in the group with ST segment elevation acute coronary syndrome (STE ACS). According to MSCT data, the proportion of patients with intact coronary arteries decreased from 7 (50%) to 5 patients (35.7%) whereas the proportion of patients with nonstenosing atherosclerosis increased from 7 (50%) to 9 patients (64.3%). Twenty six atherosclerotic plaques were detected including eccentric (76%), circular (11.5%), and semi-circular plaques (11.5%). In regard to morphological structure, the atherosclerotic plaques were calcified (59.5%), mostly calcified (7.7%), and soft (29%). Normal myocardial perfusion (Summed Stress Score (SSS) and Summed Rest Score (SRS) <4) was detected in two patients (14.3%); 12 patients (85%) had transitory perfusion defects. The median score values were 7.5 (4; 13) for SSS, 4.7 (1.0; 9.0) for SRS, and 4.7 (3.0; 8.0) for SDS.Conclusion.The introduction of MCTA and SPECT into the algorithm of the examination of patients with acute myocardial infarction and non-obstructive atherosclerosis of the coronary arteries was safe when additionally used during index hospitalization. These approaches provided new information about the structure and function of the coronary arteries. These data provide rationale for further study using a larger group of patients to determine a prognostic significance of detecting the atherosclerotic plaques with the signs of instability in this patient category.

Myocardial bridge and coronary artery fistulas in a patient with angina

Cardiovascular diseases (CVDs) are the leading cause of mortality among the population. At the core of the progression of the coronary heart disease is the atherosclerosis of the coronary arteries, which is found in majority of patients suffering from angina and in patients with myocardial infarction. However, in some cases, coronary angiography reveals, that patients with the mentioned clinical manifestations have their coronary arteries unchanged. This is treated as syndrome X or microvascular angina. Along with that, development or aggravation of the coronary heart disease may be based on the congenital peculiarities in the coronary arteries location and structure, such as muscular bridges and fistulas of the coronary artery. This is confirmed by a number of studies, which indicate the role of the above mentioned pathologies in the occurrence of angina and myocardial infarction. Nevertheless, there is also the opposite view, which is supported by a number of specialists. According to them, the presence of the mentioned peculiarities in the structure of the coronary channel is deemed as the patient-specific norm. Hence, the issue of the surgical treatment of the patients with the aforementioned coronary arteries anomalies remains controversial. The clinical case report of the patient with the symptoms of angina pectoris, in which the coronary angiography did not reveal the stenosis of the coronaries arteries, but located the myocardial bridge and the coronary fistula. The role of the congenital coronary vessels pathology in the angina pectoris is analyzed. The diagnosis guidelines and the tactics of the conservative and surgical treatment of patients with the above mentioned syndromes are discussed.

Nicorandil in the prevention of cardiac damage and type 4A myocardial infarction with planned percutaneous coronary intervention in patients with atherosclerosis of coronary arteries

Aim. To study the possibility of reducing the risk of intraoperative cardiac damage and 4a type myocardial infarction (MI) by administering the oral nicorandil in patients with a stable form of coronary artery disease (CAD) before planned percutaneous coronary intervention (PCI). Material and methods . The study included 182 patients with stable CAD who were randomized to the nicorandil treatment group (n=90) and the control group with a standard treatment (n=92). Nicorandil was prescribed 2 days before PCI (30 mg/day); on the day of PCI — 2 hours before surgery (20 mg orally), 6-12 hours after PCI — 10 mg, later — 30 mg/day within 30 days. The analysis of highly sensitive troponin I (hs-troponin) and creatine kinase-MB (CK-MB) was carried out before PCI and 24, 72 hours after the procedure, the type 4a diagnosis of MI was established according to fourth universal definition. Results . The rate of hs-troponin after 24 hours exceeded the 99th percentile from the upper limit of normal in 146 patients (80%). In the control group, there was a statistically significant more frequent increase in hs-troponin by more than 2000 ng/ml (10% of patients in the control group versus 1% of the patient in the nicorandil group, p=0,038). Type 4a MI was detected in 12% of patients in the control group, and it decreased to 3% of patients in the nicorandil group (p=0,05), and in women it was observed in 21% in the control group and in 3% in the nicorandil group. Among women (n=61), the increment of hs-troponin 24 hours after PCI was statistically significantly lower (287 versus 1135 pg/ml, p=0,04) in the nicorandil group compared to the control group. Conclusion. Reducing the risk of cardiac damage and 4a type MI by nicorandil using before PCI, compared with standard antianginal therapy, is an effective tool in cardioprotection of patients with stable CAD before planned PCI.

The prognostic value of various markers of lower limb atherosclerotic lesions in patients with high and very high cardiovascular risk

Aim. To study the prognostic significance of various markers of atherosclerosis of lower limb arteries (LLA) in patients at high and very high cardiovascular risk (CVR).Methods. The study included 108 patients at high and very high CVR, the median age of which was 62.0 (55.7; 67.0) years. All patients underwent duplex scanning of the LLA, as well as measurement of the ankle-brachial index (ABI) by the Doppler method. The combined end point was cardiovascular death, nonfatal myocardial infarction or unstable angina, requiring hospitalization, nonfatal stroke, coronary revascularization.Results. Atherosclerotic plaques in LLA were detected in 69.4% of cases, while a decrease in ABI was detected in 22.2% of patients, and LLA stenosis more than 50% in 36.1%. The follow-up duration was 25.0 (14.5; 35.5) months. The adverse cardiovascular events occurred in 41 (37.9%) patients. According to the Cox regression results, the following indicators had an independent predictive value in relation to the development of adverse cardiovascular events: a decrease in ABI ≤0.9 (RR 2.23; 95% CI 1.01-4.94; p=0.048), LLA stenosis ≥40% (RR 3.17; 95% CI 1.27–7.92; p=0.013) and the presence of plaque in the popliteal arteries (RR 2.49; 95% CI 1.27–7.92; p=0.013).Conclusion. In the group of patients at high and very high CVR, among ultrasonographic markers of lower limb arteriosclerosis, independent predictive value regarding the development of adverse cardiovascular events had a decrease in ABI ≤0.9, the presence of plaque in the popliteal arteries and LLA stenosis more than 40%.

Эффективность препарата Кавинтон® Комфорте (винпоцетина) у пациентов с артериальной гипертензией, атеросклерозом и церебральной венозной недостаточностью

Эффективность препарата Кавинтон® Комфорте (винпоцетина) у пациентов с артериальной гипертензией, атеросклерозом и церебральной венозной недостаточностью