Monomeric form of C-reactive protein in the assessment of the residual inflammatory cardiovascular risk in patients with subclinical carotid atherosclerosis.

Aim      To study the relationship between monomeric C-reactive protein (mCRP) and the progression of asymptomatic carotid atherosclerosis in patients with a moderate risk for cardiovascular diseases (CVD) as assessed with the SCORE model.Material and methods  The study included 80 men and women aged 53.1±5.8 years assigned to the category of a moderate risk for CVDs by the SCORE model with a low-density lipoprotein cholesterol (LDL-C) level of 2.7-4.8 mmol/l and asymptomatic, hemodynamically insignificant (<50% luminal narrowing) carotid atherosclerosis according to ultrasonic data. All patients were prescribed atorvastatin to achieve a LDL-C level <2.6 mmol/l. After 7 years of follow-up, ultrasonic examination of carotid arteries was performed, and concentrations of high-sensitivity C-reactive protein (hsCRP) and mCRP were measured.Results A concentration of LDL-C <2.6 mmol/l was achieved in all patients. The progression of atherosclerosis as determined by an increased number of atherosclerotic plaques (ASPs), was observed in 45 (56 %) patients. At 7 months of follow-up, concentrations of cCRP were higher in the group of patients with progressive carotid atherosclerosis, while the levels of hsCRP did not differ between the groups. Increased mCRP concentrations were associated with changes in variables of the "atherosclerotic load", including the number of ASPs, total ASP height, and the intima-media thickness (IMT). In patients with a median mCRP concentration of 5.2 [3.3; 7.1] µg/l and more, the increases in mean ACP number and total ASP height were considerably higher than in patients with mCRP concentrations lower than the median (3.9 and 2.7 times, respectively), whereas the odds ratio for the progression of asymptomatic carotid atherosclerosis was 5.5 (95 % confidence interval, CI: 2.1-14.6; p=0.001). ROC analysis showed that the concentration of hsCRP had no predictive value for prognosis of asymptomatic carotid atherosclerosis (p=0.16), while the area under the ROC curve (AUC) for mCRP was 0.75±0.056 (95 % CI: 0.64-0.86; p=0.001).Conclusion      According to the results of 7-year follow-up, the plasma concentration of mCRP was significantly higher in patients with an increased number of ASPs than in patients without this increase. An increased level of mCRP may indicate a higher inflammatory risk of CVD.

Endovascular repair of the aorti arch. / Éndovaskuliarnoe protezirovanie dugi aorty.

AIM: The study was aimed at assessing the in-hospital results of aortic arch endoprosthetic repair using different variants of endovascular supraaortic debranching. PATIENTS AND METHODS: The analysis included 27 patients subjected within the framework of aortic arch endoprosthetic repair to various types of supraaortic endobranching, including the technique of parallel prostheses and implantation of fenestrated stent grafts. We analysed the clinical and morphological status of patients prior to operation, peculiarities of the intervention (type of debranching and Ishimaru's classification zones in which the reconstruction was performed) and in-hospital results of treatment. RESULTS: The patients' mean age amounted to 66 years. The main nosology (70%) was an aortic aneurysm. Nearly in 30% of cases, the operation was performed emergently for acute aortic syndrome. The main causes of refusal from the traditional prosthetic repair included chronic kidney disease (22.5%), chronic obstructive pulmonary disease (11%), acute cerebral ischaemia within the previous 6 months (15%). The technical success rate of the operation was achieved in 100% of cases. The average duration of the intervention amounted to 226 min, with the mean blood loss equalling 355 ml. The majority of reconstructions were performed in zones 1 and 2 according to Ishimaru (59 and 33%, respectively), in 2 (7%) patients prosthetic repair was performed in zone 0. The total number of the aortic branches involved into reconstruction amounted to 45. Intervention-related complications included 3 (11%) cases of acute cerebral circulation impairment, 2 (7.4%) aortic branch occlusions, and 1 (3.7%) type II endoleak. The in-hospital and 30-day mortality rates amounted to 3.7 and 7.4%, respectively. CONCLUSION: Aortic arch endoprosthetic repair using supraaortic endobranching is considered to be an effective alternative method of treatment for patients with various pathology of the aortic arch and contraindications to traditional prosthetic repair involving artificial blood circulation.

Factors of Progression and Occurrence of Atherosclerosis in Rheumatoid Arthritis.

Aim      To determine in a prospective study factors of progressive atherosclerotic lesion of blood vessels in patients with rheumatoid arthritis (RA).Material and methods  This prospective study included 124 patients with RA and suspected ischemic heart disease (IHD) and 30 patients with IHD (comparison group) aged 58 [52; 63] years. On enrollment to the study and at 3 years of follow-up, all patients underwent clinical and instrumental examination according to European and Russian guidelines for diagnosis and treatment of stable IHD (2013), including coronography as indicated. For all RA patients of the comparison group, risk factors (RF) were evaluated, including arterial hypertension, smoking, excessive body weight, family history of cardiovascular diseases (CVD), diabetes mellitus, and dyslipidemia. The following laboratory data were evaluated: blood count; biochemistry, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), rheumatoid factor (RhF), cyclic citrullinated peptide antibodies, and high-sensitivity C-reactive protein (hsCRP). Proinflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF- α), were measured in RA patients once, at 3 years of follow-up.Results Incidence of FRs for CVD was similar in RA patients and in the comparison group. Median RA duration before inclusion into the study was 11 years, and median DAS28 index score was 3.8. Incidence of dyslipidemia due to increased TC, LDL-C, and HDL-C was higher for RA patients at baseline. The LDL-C goal (<1.8 mmol/l) was achieved only in 3 (10 %) patients of the comparison group and 10 (8 %) RA patients. RA patients had higher levels of the inflammation indexes, hsCRP (0.75 mg/dl vs. 0.16 mg/dl; p<0.05) and erythrocyte sedimentation rate (ESR) (15 mm/h vs. 11.5 mm/h; p<0.05). In the RA group at baseline, atherosclerotic plaques with carotid artery (CTA) stenosis of 20% or more were found in 94 (77 %) patients; in 3 of them, CA stenosis was >50%. Patients with RA frequently had unchanged or slightly changed coronary arteries (CA) (47% of patients), and less frequently they had hemodynamically significant multi-arterial coronary atherosclerotic lesions (7 % vs. 57 % of patients in comparison group). At 37.5 months, 21 (23 %) of 94 RA patients had progressive atherosclerosis in CA and/or CTA; 12 (13 %) RA patients had only progressive CA atherosclerosis; 7 (8 %) had only progressive CTA atherosclerosis; and 2 (2 %) had simultaneous progression of CA and CTA atherosclerosis. Two groups of RA patients were formed, with the progression of atherosclerosis (n=21) and without the progression of atherosclerosis (n=69). RFs for the development/progression of atherosclerosis in RA patients included smoking, family history of CVD, and duration of the disease. Levels of lipids did not differ. Levels of proinflammatory cytokines (IL-1ß, IL-6, TNF-α) were higher in RA patients with progressive atherosclerosis. No effects of the anti-rheumatic therapy on the progression of atherosclerosis were observed.Conclusion      Progression of atherosclerosis in RA remains in disease with low and moderate activity during the anti-rheumatic and hypolipidemic treatment. The development of atherosclerosis in RA is determined by lipid, inflammatory, and immune disorders.

The severity of internal carotid artery stenosis is associated with the circulating Th17 level.

AIM: Immune and inflammatory reactions contribute to the progression of atherosclerosis. The walls of the different arteries and segments of the arteries have heterogeneous haemodynamic and histological features. We aimed to explore the relationship between the circulating T-cell subsets and the abundance of carotid atherosclerosis in different segments of carotid arteries. METHODS: 70 patients underwent ultrasound duplex scanning to determine the degree of stenosis of the common carotid artery (CCA), the CCA bifurcation or the internal carotid artery (ICA). The blood frequencies of T-, B-, NK-cells, regulatory T cells (Treg), activated T-helpers (Th), IL10-producing Th, Th1 and Th17, as well as blood levels of hsCRP, sCD25, IL10 and IL17a were assessed. RESULTS: The frequencies of Th17 were increased in patients with ICA stenosis >35% and >50% vs. patients with ICA stenosis <35%. Th17 blood level ≥0.55 % of lymphocytes was associated with more severe stenosis of ICA (OR 4.3 (1.0-17.6), p < 0.05 for ICA stenosis of 35-50% and 6.8 (1.3-35.0), p < 0.05 for ICA stenosis >50%). BMI positively correlated with the CCA bifurcation stenosis degree (r = 0.33, p < 0.05). CONCLUSION: The severity of ICA stenosis can be associated with the circulating Th17 level.

[Association of lipoprotein (a) with ischemic stroke and stenotic carotid atherosclerosis]. / Sviaz' lipoproteida(a) s ishemicheskim insul'tom i stenoziruiushchim aterosklerozom sonnykh arterii.

INTRODUCTION: Lipoprotein(a) [Lp(a)] is a genetically determined risk factor of coronary heart disease and its complications. Meanwhile data about the role of Lp(a) in development of ischemic stroke are controversial. AIM: To investigate the association of Lp(a) with atherothrombotic ischemic stroke and stenotic (≥50%) atherosclerosis of carotid arteries. MATERIAL AND METHODS: The study included 490 patients (mean age 60 years, 53% male). The first group comprised 157 patients with ischemic stroke, the second group 68 patients with isolated stenotic atherosclerosis of carotid arteries, but without significant lesion of coronary and low limbs arteries. The control group included 265 patients without stroke, myocardial infarction, stenotic atherosclerosis of coronary, carotid and low limbs arteries according to instrumental examinations. The levels of Lp(a) and lipids were measured in blood serum of all patients. RESULTS: Lp(a) concentration was significantly higher in patients of the first and second groups in comparison with the control group (median [interquartile range]): 24 [9; 48], 20 [8; 55] vs 13 [5; 27] mg/dl, respectively (p<0,05 in both cases). Hyperlipoproteinemia(a) (Lp(a) ≥30 mg/dl) was more frequent in the group with stroke, stenotic atherosclerosis of carotid arteries, than in the control group: 43%, 40% vs 22% (p<0.01 in all cases). In patients with hyperlipoproteinemia(a), odds ratio (OR) for ischemic stroke was 2.7 (95% confidence interval (CI) 1.7-4.1), and OR for stenotic atherosclerosis of carotid arteries was 2.3 (95% CI 1.3-4.0) compared to the patients with Lp(a) level <30 mg/dl (p<0.01 in both cases). In logistic regression analysis adjusted for age, sex, hypertension, type 2 diabetes, smoking and Lp(a) concentration, the hyperlipoproteinemia(a) was associated with ischemic stroke and isolated stenotic carotid atherosclerosis. In the group with severe carotid atherosclerosis, 16 patients (24%) had ischemic stroke. Lp(a) concentration in these patients was higher 36 [20; 59] mg/dl, than in the patients with isolated carotid atherosclerosis without stroke 15 [7; 54] mg/dl (p=0.04). Other risk factors of atherosclerosis did not differ in patients with or without ischemic stroke. CONCLUSION: The study shows the association of elevated level of Lp(a) with ischemic stroke and isolated stenotic atherosclerosis of carotid arteries. In the presence of isolated stenotic carotid atherosclerosis, the median of Lp(a) concentration was significantly higher in patients with ischemic stroke than in patients without stroke.

[Lipoprotein(а) Level, Apolipoprotein(а) Polymorphism аnd Autoаntibodies Against Lipoprotein(а) in Patients with Stenotic Cаrotid Atherosclerosis].

Аim. Comparative assessment of respiratory indicators according to multifunctional monitoring (PFM) with the recommended standard for a complete polysomnographic study and an assessment of the effect of blood pressure (BP) measurements in PFM on sleep quality. Triаls on the аssociаtion of Lp(а) and cаrotid аtherosclerosis аre limited. The аim of the study wаs to investigаte the аssociаtion of Lp(а), аpolipoprotein(а) [apo(а)] polymorphism аnd аutoаntibodies to Lp(а) with stenotic (≥50%) cаrotid аtherosclerosis in dependence on CHD presence. Materials and methods. The study included 785 pаtients аt the аge from 21 to 92 with dаtа of instrumentаl exаmination of coronаry, cаrotid аnd lower limbs аrteries. Stenotic cаrotid аtherosclerosis wаs diаgnosed in 447 pаtients who were divided into two groups depending on presence (n=344) or аbsence (n=103) of CHD. The control group comprised of 338 pаtients without stenotic аtherosclerosis of coronаry, cаrotid аnd lower limbs аrteries. In the blood serum of pаtients levels of Lp(а), аutoаntibodies to Lp(а) were determined аnd аlso аpo(а) phenotyping wаs conducted. Results. There were more mаles, higher аverаge аge аnd frequency of hypertension, type 2 diаbetes mellitus, smoking, Lp(а) concentrаtion (mediаn [interquаrtile rаnge]): 30 [11; 63] vs. 14 [5; 30] mg/dl, p<0.01) in the group with stenotic cаrotid аtherosclerosis in compаrison with control group. Besides, Lp(а) level wаs higher in CHD subgroup thаn in pаtients with stenotic cаrotid аtherosclerosis without CHD: 32 [12; 72] vs. 24 [8; 50] mg/dl, respectively, p=0.01. Elevаted (≥30 mg/dl) Lp(а) level, low moleculаr weight аpolipoprotein(а) [(LMW аpo(а)] phenotype were аssociаted with stenotic cаrotid аtherosclerosis (odds rаtio (OR) 2.9; 95% confidence intervаl (CI) 2.1-4.0, p<0.01 аnd OR 2.3; 95% CI 1.6-3.4, p<0.01, respectively). Logistic regression аnаlysis showed independent аssociаtion of elevаted Lp(а) level аnd LMW аpo(а) phenotype with stenotic cаrotid аtherosclerosis both in the presence аnd absence of CHD. The level of IgM аutoаntibodies to Lp(а) wаs higher in control group thаn in pаtients with stenotic cаrotid аtherosclerosis, p=0.02. Conclusion The level of Lp(a) ≥30 mg/dl and low molecular weight phenotype of aprotein(a) are predictors of stenotic atherosclerosis CA, regardless of the presence of coronary heart disease and other risk factors, while a reverse relationship was found between the level of autoantibodies of the IgM class against Lp(a) and the severity of atherosclerosis CA.

Rate of Complications at Early Removal of Compression Bandage After Transradial Coronary Angiography.

PURPOSE: to compare rates of access site complications at early (after 4 hours) and traditional (after 24 hours) removal of a compression bandage after diagnostic transradial (TR) coronary angiography (CA) in patients not receiving anticoagulants. MATERIALS AND METHODS: We included into this study 392 patients (mean age 63±8.7 years, 62.8% men) who underwent transradial coronary angiography. Patients were divided into 2 groups. In group 1 patients (n=221) compression bandage was removed from puncture site in 4 hours after procedure with subsequent control of radial artery patency using presence of pulse metric curve during ulnar artery compression (the reverse Barbeau test with pulse oximeter). In patients of group 2 (n=171) compression band was removed after 24 hours. In both groups control of radial artery patency was carried out after 24 hours using the reverse Barbeau test. Upon detection of radial artery occlusion (RAO) ultrasound imaging of the forearm arteries was performed. RESULTS: No RAO was detected in group 1 while in group 2 number of detected RAO was 15 (8.8%) (р<0.05). Rates of hematomas at puncture site were not significantly different. Puncture site bleeding after band removal requiring repeated banding occurred in 1 patient of group one (0.6%); no such cases were registered in group 2 (p>0.05). CONCLUSION: Compared with traditional method early removal of compression bandage after TR CA was associated with lower rate of RAO.

[Comparative efficacy and safety of enoxaparin followed by warfarin and rivaroxaban monotherapy in the treatment of venous thrombosis in patients after intracardiac catheter interventions].

AIM: to compare two anticoagulant therapy (ACT) regimens in the treatment of venous thrombosis (VT) in patients after catheter interventions - electrophysiological studies (EFIs) and ablations: enoxaparin followed by warfarin, and rivaroxaban monotherapy. MATERIALS AND METHODS: The study included patients from 18 years and older with heart rhythm disorders and planned catheter ablation. When parietal venous thrombosis (VT) were detected at the femoral vein puncture site, all patients were randomly assigned to two treatment groups. In group I enoxaparin 1 mg/kg was prescribed every 12 hours with switching to warfarin after 7 days with maintenance of the target INR values (2.0-3.0). In group II rivaroxaban therapy was started at a dose of 15 mg twise/day for 21 days with a further transition to a dose of 20 mg/day. The total period of observation and treatment of patients was at least 3 months. RESULTS: 408 patients were observed, 42 (10.3%) patients with parietal VT were divided into two treatment groups. In group I (n=16) complete lysis of VT was noted by the 7th day of treatment in 7 (58.3%) patients, however this scheme was associated with a greater risk of complications (р=0.003) at the puncture site in the form of arteriovenous fistulae (n=1; 8.3%) and intermuscular hematomas (n=4; 25%). In group II (n=26), no complications were noted, the lysis time of VT was on average 21 days (n=18; 69.2%). Complete lysis of VT was noted in both groups at the time of the control observation point (3rd month). CONCLUSION: The efficiency of the two VT treatment regimens was comparable. Enoxaparin therapy is associated with a high risk of local complications, namely intermuscular hematomas (n=4; 25%) and arteriovenous fistulas (n=1; 8.3%). Rivaroxaban monotherapy is safer (p=0.003); in Group II none of the patients had any complications.

[Dynamics of asymptomatic atherosclerosis of carotid arteries depending on the achieved level of cholesterol in moderate-risk patients]. / Dinamika bessimptomnogo ateroskleroza sonnykh arterii v zavisimosti ot dostignutogo urovnia kholesterina u patsientov s umerennym riskom.

The study was aimed at assessing the dynamics of asymptomatic atherosclerosis of carotid arteries (CA) depending upon the achieved level of low-density lipoprotein cholesterol (LDLC) in patients with moderate total risk by the SCORE scale. We followed up a total of eighty-two 40-to-65-year-old patients with the LDLC level above 2.6 mmol/l, being at moderate total risk by the SCORE scale and having symptom-free atherosclerosis of the extracranial portion of brachiocephalic arteries (up to 50% narrowing of their lumen) as diagnosed by duplex scanning. The patients were randomly divided into two groups. Group One patients (n=41) received therapy with atorvastatin in order to achieve the LDLC level less than 1.8 mmol/l. Group Two patients (n=41) were treated in order to achieve the LDLC level below 2.6 mmol/l. At 12 months of follow up we compared the dynamics of carotid atherosclerosis (change in the number, total height, structure, echogenicity, as well as the state of the surface of atherosclerotic plaques, alteration of the thickness of the CA intima-media complex). Group Two patients were found to have an increase in the number and average sum of the heights of atherosclerotic plaques. An increase of the maximum thickness of the intima-media complex of the wall of the right and left CA was more pronounced as compared with that in Group One patients. Aggressive hypolipidemic therapy aimed at achieving the LDLC level below 1.8 mmol/l turned out to be more effective in slowing down the progression of asymptomatic carotid atherosclerosis in patients with moderate cardiovascular risk than therapy targeted at achieving the LDLC level below 2.6 mmol/l.

Specific Lp(a) apheresis: A tool to prove lipoprotein(a) atherogenicity.

BACKGROUND: An elevated lipoprotein(a) (Lp(a)) level is observed in more than 30% of patients with stable ischemic heart disease (SIHD). We conducted an investigation of the effects of specific Lp(a) apheresis on the progression of atherosclerosis in SIHD patients with Lp(a) levels greater than 50 mg/dL. METHODS: We prospectively enrolled 15 patients diagnosed with SIHD based on symptom-driven coronary angiography findings, with Lp(a) ≥50 mg/dL and a low density lipoprotein cholesterol (LDL-C) ≤2.5 mmol/L, who were on long-term statin therapy. They underwent weekly Lp(a) apheresis using Lp(a) Lipopak® adsorption columns which contain monospecific sheep polyclonal antibodies against human Lp(a). Fifteen age and gender matched SIHD patients receiving atorvastatin monotherapy served as controls. At baseline and 18 months post-treatment, quantitative coronary angiography, intracoronary ultrasound with virtual histology and carotid ultrasound were performed. Lipid profile, including Lp(a), was measured at the scheduled visits, and before and after each apheresis procedure. Levels of high-sensitivity C-reactive protein (hsCRP), matrix metalloproteinases (MMP)-7 and 9, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 and 2 were determined at baseline and at the end of the study period. RESULTS: Each specific Lp(a) apheresis procedure was carried out with two adsorption columns resulting in an average acute decrease in Lp(a) levels of 75% (from 110 ± 22 to 29 ± 16 mg/dL) without significant changes in other plasma components. Lp(a) reduction over the course of 18 months was associated with a decrease in the mean percent diameter stenosis of 5.05% and an increase in minimal lumen diameter of 14%; the mean total atheroma volume was reduced by 4.60 mm3 (p < 0.05 for all). There was a decrease in absolute common carotid intima-media thickness in the Lp(a) apheresis group of 0.07 ± 0.15 mm both from baseline and compared with the control group (p = 0.01). Levels of hsCRP were reduced by 40% in patients on Lp(a) apheresis without significant changes in the levels of other biomarkers at the end of the study. CONCLUSION: Reduction of the atherosclerotic burden in coronary and carotid arteries was observed in patients treated with specific Lp(a) apheresis and statin over 18 months compared with statin therapy alone. These findings support the atherogenic role of Lp(a) and reinforce the need to assess the effects of Lp(a)-lowering on cardiovascular events and mortality. Trial Registration Clinicaltrials.gov (NCT02133807).

[Subpopulation Composition of CD4+ T-lymphocytes as Factor Contributing to the Progression of Atherosclerosis of Carotid Arteries].

AIM: to assess prognostic significance of blood content of regulatory and effector T-lymphocytes for progression of atherosclerosis (AS) of carotid arteries. MATERIAL AND METHODS: We enrolled in this study 33 men with various severity of carotid AS. Carotid artery duplex scan was done at admission and in 1 year after enrollment. AS progression was defined as appearance of novel stenosis in common or internal carotid artery or more or equal 5% increase of preexisting stenosis. Peripheral blood lymphocyte phenotyping was performed by direct immunofluorescence and flow cytometry at the enrollment. T-helpers (Th) 1 were identified as CD4+IFNgamma+ cells, Th2 - CD4+IL4+, activated T-cells (T-act) - D4+CD25lowCD127high, regulatory T-cells (T-reg) - D4+CD25highCD127 low and CD4+FoxP3+, Th17 - CD4+IL17a+ cells. RESULTS: Progression of carotid AS was observed in 18 patients. Basal values of Th17 were higher while ratio T-reg/Th17 was lower in patients with compared with those without AS progression. ROC-analysis showed high sensitivity and specificity of blood levels of Th17, T-act and T-reg/Th17 ratio for carotid AS progression during one year in patients with low density lipoprotein cholesterol (LDLCH) level below 3.5 mmol/l. CONCLUSION: The imbalance between circulating levels of regulatory T-cells and T-helpers 17 with the prevalence of proinflammatory T-helpers 17 may reflect a predisposition for carotid AS progression, what also refers to patients with relatively low LDLCH.

[Carotid Plaque Instability in Patients With Acute Coronary Syndrome as Assessed by Ultrasound Duplex Scanning].

AIM: to study carotid plaques structure in patients with acute coronary syndrome by ultrasound duplex scanning. MATERIALS AND METHODS: We included in this study143 patients with acute coronary syndrome (ACS) aged 32-83 years and 28 patients with documented coronary heart disease (CHD) aged 46-83 years. Duplex scanning of carotid arteries was carried out with Philips iU22 ultrasound system and L9-3 linear array transducer. Atherosclerotic plaques in CCA, CCA bifurcation, and ICA from right and left side were investigated. Off-line analysis of B-mode images and plaque gray scale median (GSM) was performed with computer semiautomated workstation MultiVox. RESULTS: 378 plaques of ACS and 59 plaques of CHD patients were studied. We assessed traditional (heterogenous structure, hypoechogenic component, irregular plaque surface) as well as additional (positive remodeling, "layered" structure of plaque, local calcification) criteria of plaque instability. In ACS compared with CHD group there were more plaques with hypoechogenic component (43.4 and 28.8%, p=0.0459), heterogenous structure (77.8 and 64.4%, p=0.0327), irregular surface including irregularities more than 2.0 mm (22.5 and 6.8%, p=0.0048, respectively). There was significant difference in "layered" structure (55.7 and 35.8%, p=0.0011) and insignificant difference in positive remodeling (16.3 and 7.5%, p=0.06, respectively). There were no differences of GSM value (53.1 and 57.2, p=0.24) and local calcification (23.2 and 24.5%, p=0.23, respectively). CONCLUSION: In our study ultrasound duplex scanning revealed that signs of plaque instability in carotid arteries in patients with ACS were more frequent than in patients with stable CHD. The newly introduced parameter "layered" structure of atherosclerotic plaque was found to be most significant.

Specific Lipoprotein(a) apheresis attenuates progression of carotid intima-media thickness in coronary heart disease patients with high lipoprotein(a) levels.

BACKGROUND: To date, there have been no studies evaluating the effect of isolated lipoprotein(a) (Lp(a)) lowering therapy on carotid atherosclerosis progression. METHODS: We enrolled 30 patients who had coronary heart disease (CHD) verified by angiography, Lp(a) level ≥50 mg/dL, and low density lipoprotein cholesterol (LDL-C) level ≤2.6 mmol/L (100 mg/dL) on chronic statin therapy. Subjects were allocated in a 1:1 ratio to receive apheresis treatment on a weekly basis with immunoadsorption columns ("Lp(a) Lipopak"(®), POCARD Ltd., Russia) added to atorvastatin, or atorvastatin monotherapy. The primary efficacy end-point was the change from baseline in the mean intima-media thickness (IMT) of the common carotid arteries. RESULTS: After one month run-in period with stable atorvastatin dose, LDL-C level was 2.3 ± 0.3 mmol/L and Lp(a) - 105 ± 37 mg/dL. As a result of acute effect of specific Lp(a) apheresis procedures, Lp(a) level decreased by an average of 73 ± 12% to a mean of 29 ± 16 mg/dL, and mean LDL-C decreased by 17 ± 3% to a mean of 1.8 ± 0.2 mmol/L. In the apheresis group, changes in carotid IMT at 9 and 18 months from baseline were -0.03 ± 0.09 mm (p = 0.05) and -0.07 ± 0.15 mm (p = 0.01), respectively. In the atorvastatin group no significant changes in lipid and lipoprotein parameters as well as in carotid IMT were received over 18-month period. Two years after study termination carotid IMT increased by an average of 0.02 ± 0.08 mm in apheresis group and by 0.06 ± 0.10 mm in the control group (p = 0.033). CONCLUSION: Isolated extracorporeal Lp(a) elimination over an 18 months period produced regression of carotid intima-media thickness in stable CHD patients with high Lp(a) levels. This effect was maintained for two years after the end of study. TRIAL REGISTRATION: Clinicaltrials.gov (NCT02133807).

[Lipoprotein-associated phospholipase A2 serum levels in patients from different categories of cardiovascular risk].

AIM: To compare levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) in blood serum of patients from different cardiovascular risk categories. MATERIAL AND METHODS: Patients from Moscow prospective study database (n = 519) were divided into 4 cardiovascular risk categories according to present clinical recommendations (low, moderate, high, very high). Measurement of Lp-PLA2 concentration (mass) was performed using PLAC Test ELISA Kit. Measurement of Lp-PLA2 activity was made using PLAC Test for Lp-PLA2 Activity. Blood serum levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), lipoprotein (a) (Lp(a)), high sensitive C-reactive protein (hsCRP) and uric acid were also determined. RESULT: Preliminary analysis showed that associations between Lp-PLA2 mass and activity became more obvious in patients not treated with statins and patients without diabetes mellitus. So patients receiving statins and diabetics were excluded from final analysis. Lp-PLA2 mass and activity were lower in low cardiovascular risk category patients. There were no significant differences in Lp-PLA2 mass and activity between patients from moderate, high and very high risk categories. There was moderate correlation between Lp-PLA2 mass and Lp-PLA2 activity (r = 0.38, p < 0.00001). We did not find any correlation between Lp-PLA2 and hsCRP, Lp(a) levels, but detected moderate correlation between Lp-PLA2 mass and activity and TC, LDL-C. We also found a mild positive correlation between Lp-PLA2 mass and HDL-C levels. There was a positive correlation between Lp-PLA2 activity and TG, uric acid and negative correlation between Lp-PLA2 activity and HDL-C levels. CONCLUSION: In this group of nondiabetic patients not treated with statins both Lp-PLA2 activity and mass were similarly related to categories of cardiovascular risk.

[Possibilities of instrumental methods of diagnosis of unstable atherosclerotic plaques of carotid arteries].

Today there exists a wide variety of laboratory and instrumental methods aimed at diagnosing an unstable carotid aortosclerotic plaque. Assessment of the laboratory indices is not sufficiently effective since it does not allow of revealing the fact of the formation of an unstable plague at early stages and to determine its localization. The instrumental methods employed (ultrasonographic study, magnetic resonance imaging, multiplanar computed tomography, positron emission tomography) were focussed on detecting pathomorphological markers of instability - thickness of the fibrous coating, structural plaques, the presence of erosions, ulcerations, haemorrhages, calcifications, lipid nucleus, activity of the cellular processes inside the plaque. The revealed signs promote early diagnosis of unstable atherosclerotic plaque with the determination of its localization. Nevertheless, they do not provide evidence about the danger of its rupture, whereas the overwhelming majority of acute vascular catastrophes including acute impairments of cerebral circulation is directly associated with arterial thrombosis resulting from rupture of the atherosclerotic plaque. Therefore, search for new methods aimed at prediction of complications of the atherosclerotic plaque which would be employed in routine clinical practice still remain urgently important today. The most promising is the study of the state of the atherosclerotic plaques of carotid arteries for prediction of acute impairment of cerebral circulation.

[Arterial stiffness and blood levels of glycation end-products in patients with arterial hypertension and carotid atherosclerosis].

Combination of arterial hypertension (AH) and carotid atherosclerosis significantly increases the risk of cardiovascular complications. Arterial stiffness is believed to be a key risk factor of the development of such complications. This paper described peculiarities of this condition, methods for its assessment in patients with AH and carotid atherosclerosis, and importance of characteristics of regional and local stiffness for estimation of cardiovascular risks. The role of glycation end-products in damaging arterial walls and triggering pathogenetic mechanisms of atherosclerosis is discussed.

[Comparison of morphological features of carotid arteries atherosclerotic plaques with clinical-instrumental data in symptomatic and asymptomatic patients with severe carotid atherosclerosis].

A complex histomorphometric and clinical-instrumental analysis of atherosclerotic lesions of the carotid arteries obtained during carotid endarterectomies (CEE) of patients with hemodynamically significant stenoses was conducted. Two groups of patients were compared: symptomatic, which earlier underwent cerebral vascular accident (CVA) or transitory ischemic attacks (TIA), and asymptomatic ones with no complications of the disease. Statistical analysis of clinical and laboratory data showed no significant differences between two groups except for the level of lipoprotein(a) [Lp(a)] in the blood plasma, which was higher (p<0.05) in asymptomatic patients compared with symptomatic ones. Statistical analysis of carotid arteries ultrasound duplex scanning (USDS) in the preoperative period did not reveal significant differences in the degree of maximum vessels stenosis between the compared groups of patients. Surface defects of atherosclerotic plaques (ASP) were shown to be significantly more common (p<0.05) in the group of symptomatic patients compared with asymptomatic ones. According to histological analysis 88% of extracted ASP was unstable in symptomatic patients and 77% of ASP - in asymptomatic patients. This may indicate high risk of CVA/TIA in both groups of patients. Statistical evaluation of magnetic resonance tomography (MRT) and USDS techniques in comparison with abilities of the most reliable histological analysis showed that both non-invasive diagnostic methods are highly sensitive in detecting unstable ASP, though MRT showed higher level of specificity compared with USDS.

[Structural and functional status of arteries in young and middle-aged men with ischemic heart disease].

Aim of the study was to determine whether structural and functional status of arteries differ between young and middle-aged men with ischemic heart disease (IHD). A total of 78 men aged 28 to 50 years were recruited in this study: 49 with angiographically proven obstructive atherosclerosis of coronary arteries, 29 without clinical manifestations of IHD (control group). Those with arterial hypertension, diabetes mellitus or marked hypercholesterolemia (LDL cholesterol more or equal 4.5 mmol/l) were excluded from the study. All patients underwent carotid ultrasound, endothelial function, and arterial stiffness measurements. Patients with IHD more often had multiple carotid plaques (86.7% vs 13.7%, p<0.001), and increased aortic pulse wave velocity (PWV) assessed by ultrasound duplex scanning (53.1% vs. 24.1%, p=0.02). Aortic PWV was related to the severity of coronary atherosclerosis. Presence of a carotid intima-media thickness more or equal 0.9 mm and abnormal flow-mediated dilatation (FMD) of the brachial artery was not significantly different between the groups.

[Comparative characteristics of the possibilities of imaging techniques (magnetic resonance imaging and 3D ultrasound study) in the qualitative estimation of atherosclerotic plaque volume].

OBJECTIVE: To estimate the possibilities of using three-dimensional ultrasound study (3D USS) in the diagnosis of the sizes and structure of an atherosclerotic plaque (ASP). MATERIAL AND METHODS: The data obtained by examination of 20 heterogeneous ASPs in the carotid artery wall, by applying 3D USS and magnetic resonance imaging (MRI), were compared. Intra- and interoperator reproducibilities were assessed by the Bland-Altman method; the volume of each plague was measured by two (contour and ellipse) methods. The contour method was used to estimate all plagues; the ellipse method was applied to 13 of the 20 plagues, which was due to the shape of ASPs that rarely had an ellipsoid shape. RESULTS: Intra- and interoperator reproducibilities in ASP volume estimation by 3D USS was as follows: with the use of contour and ellipse algorithms, the coefficient of variation was 7.72 and 3.77%, respectively; with these algorithms, the interoperator reproducibility was 8.18 and 6.21%, respectively; the derived values were not greater than those allowed for medical studies (10%). The coefficients of variations for MRI in the estimation of ASP sizes were significantly higher for inter- and intrareproducibilities (68.82 and 43.4%, respectively). CONCLUSIONS: The results of this investigation agree with thedata available in the literature and support that 3D USS is an effective diagnostic me-hod in evaluating the magnitude of an ather-sclerotic process.

[The biological reaction of inflammation, methylglyoxal of blood plasma, functional and structural alterations in elastic type arteries at the early stage of hypertension disease].

The article deals with studying of the relationship between biologic reaction of inflammation with glycosylation reaction and content of methylglyoxal in blood serum. The positive correlation between pulse wave velocity and content of methylglyoxal, C-reactive protein in intercellular medium and malleolar brachial index value was established. This data matches the experimental results concerning involvement of biological reaction of inflammation into structural changes of elastic type arteries under hypertension disease, formation of arteries' rigidity and increase of pulse wave velocity. The arterial blood pressure is a biological reaction of hydrodynamic pressure which is used in vivo by several biological functions: biological function of homeostasis, function of endoecology, biological function of adaptation and function of locomotion. The biological reaction of hydrodynamic (hydraulic) pressure is a mode of compensation of derangement of several biological functions which results in the very high rate of hypertension disease in population. As a matter of fact, hypertension disease is a syndrome of lingering pathological compensation by higher arterial blood pressure of the biological functions derangements occurring in the distal section at the level of paracrine cenoses of cells. The arterial blood pressure is a kind of in vivo integral indicator of deranged metabolism. The essential hypertension disease pathogenically is a result of the derangement of three biological functions: biological function of homeostasis, biological function of trophology - nutrition (biological reaction of external feeding - exotrophia) and biological function of endoecology. In case of "littering" of intercellular medium in vivo with nonspecific endogenic flogogens a phylogenetically earlier activation of biological reactions of excretion, inflammation and hydrodynamic arterial blood pressure occur. In case of derangement of biological function of homeostasis, decreasing of perfusion even in single paracrine cenoses and derangement of biological function of endoecology ("purity" of intercellular medium) the only response always will be the increase of arterial blood pressure.