Atherosclerotic Plaques In Carotid Arteries Research Articles

Echogenicity of atherosclerotic plaque - a criterion for assessing the dynamics and prognosis of cardiovascular diseases

Aim: to measure the echogenicity of atherosclerotic plaques (AP) of carotid arteries to assess the dynamics of atherosclerosis and risk of cardiovascular outcomes (CVO) in patients with different CVD risk.Materials and methods. The study included 223 patients: 80 patients (47 males) with moderate CVD risk (mean age: 53 years, range: 39-66) (Group 1) and 143 patients (123 males) with acute coronary syndrome (ACS) and high CVD risk (mean age: 57, range: 32-83) years (Group 2). All patients were examined at the Chazov National Medical Research Center of Cardiology. Patients underwent a standard clinical examination, biochemical blood test with lipid profile determination, and ultrasound duplex scanning. Patients with ACS were re-examined after 1-1.5 years and patients with moderate CVD risk were re-examined after 1 and 7 years.Results. We analyzed 181 APs in Group 1 and 378 APs in Group 2. Analysis of gray-scale median (GSM) at the first and second visit showed a significant increase in GSM in both groups: from 67.02 [54.13; 82.85] to 73.5 [59.5; 88.7] (p<0.0001) in Group 1, and from 49.3 [39.73;63.64] to 50.7 [40.04;66.54] (p<0.05) in Group 2. An increase in GSM was observed in 79% of patients in Group 1, in 53% of patients in Group 2. Unfavorable CVO (CVO+) developed after 7 years in 7 (8.8%) patients in Group 1, and after 1 year in 23 (23%) patients in Group 2. In Group 1, an increase in GSM was observed only in patients with favorable prognosis (CVO-): from 67.7[52.13; 79.0] to 77.5[64.12; 91.0] (n=148 AP, p<0.05), in patients with CVO+, GSM increased non-significantly from 60.1[53.5; 66.5] to 66.5[55.0; 71.6] (n=18 AP, p=NS). In Group 2, a significant increase in GSM was observed in patients with CVO-: from 48.7[39.0; 63.4] to 51.3[40.0; 67.4] (n=141 AP, p<0.01), in patients with CVO+, GSM decreased from 51.6[42.9; 72.5] to 50.2[40.4; 65.0] (n=43 AP, p=NS). In Group 2, GSM significantly increased by 2.75 (6.05%) from the initial value (p<0.05) in patients with CVO-, while patients with CVO+ showed a significant decrease in the average GSM of AP by 3.33 (7.8%) (p<0.05). Using ROC analysis, a Δ% GSM value of 6.96% was found (area under the curve 0.628 ± 0.0465 [95% CI 0.556 - 0.696], p = 0.0058). According to Cox regression analysis, the risk of CVO increased by 2.16 times with a decrease in GSM AP in the carotid arteries over time by ≥ 6.96% (НR=2.16; 95% CI=1.331 – 3.507); p=0.009.Conclusion. The ultrasound method of measuring the echogenicity of an atherosclerotic plaque of the carotid artery using GSM parameter can be effective for assessing the dynamics of atherosclerosis and prognosis of adverse cardiovascular events in patients with high and moderate CVD risk

Extracranial carotid artery atherosclerotic plaque and APOE polymorphisms: a systematic review and meta-analysis.

Carotid atherosclerotic plaque is an important independent risk factor for stroke. Apolipoprotein E (APOE) influences cholesterol levels and certain isoforms are associated with increased carotid atherosclerosis, though the exact association between APOE and carotid plaque is uncertain. The study aimed to evaluate the association between APOE and carotid plaque. A systematic review was performed to retrieve all studies which examined the association between carotid plaque and APOE. This study was conducted in accordance with the PRISMA guidelines. Independent readers extracted the relevant data from each study including the type of imaging assessment, plaque definition, frequency of APOE E4 carrier status and type of genotyping. Meta-analyses with an assessment of study heterogeneity and publication bias were performed. Results were presented in a forest plot and summarized using a random-effects model. After screening 838 studies, 17 studies were included for systematic review. A meta-analysis of 5 published studies showed a significant association between ε4 homozygosity and carotid plaque [odds ratio (OR), 1.53; 95% CI, 1.16, 2.02; p = .003]. Additionally, there was a significant association between patients possessing at least one ε4 allele, heterozygotes or homozygotes, and carotid plaque (OR, 1.25; 95% CI, 1.03, 1.52; p = .03). Lastly, there was no association between ε4 heterozygosity and carotid plaque (OR, 1.08; 95% CI, 0.93, 1.26; p = .30). APOE ε4 allele is significantly associated with extracranial carotid atherosclerotic plaque, especially for homozygous individuals.

The FCGR2A Is Associated with the Presence of Atherosclerotic Plaques in the Carotid Arteries-A Case-Control Study.

Atherosclerotic plaques in carotid arteries (APCA) are a prevalent condition with severe potential complications. Studies continuously search for innovative biomarkers for APCA, including those participating in cellular metabolic processes, cell adhesion, immune response, and complement activation. This study aimed to assess the relationship between APCA presence and a broad range of cardiometabolic biomarkers in the general population. The study group consisted of consecutive participants of the population study Bialystok PLUS. The proximity extension assay (PEA) technique from the Olink Laboratory (Uppsala, Sweden) was used to measure the levels of 92 cardiometabolic biomarkers. The study comprised 693 participants (mean age 48.78 ± 15.27 years, 43.4% males, N = 301). APCA was identified in 46.2% of the participants (N = 320). Of the 92 biomarkers that were investigated, 54 were found to be significantly linked to the diagnosis of APCA. After adjusting for the traditional risk factors for atherosclerosis in multivariate analysis, the only biomarker that remained significantly associated with APCA was FCGR2A. In the general population, the prevalence of APCA is very high. A range of biomarkers are linked with APCA. Nonetheless, the majority of these associations are explained by traditional risk factors for atherosclerosis. The only biomarker that was independently associated with APCA was the FCGR2A.

Ишемический инсульт с наличием и отсутствием диссекций брахиоцефальных артерий: результаты комплексного обследования пациентов

Currently, there are no clearly defined optimal diagnostic strategies of detection of dissections. This study aimed to analyze and compare the results of comprehensive examinations of people who suffered an ischemic stroke (IS) with and without brachiocephalic artery (BCA) dissections. Dissections group, formed based on the results of multispiral computed tomography angiography that confirmed dissections, included 53 patients, and control group — patients without BCA dissections — comprised 1451 people; examination of all patients involved duplex scanning (DS) of BCA and transcranial part, transthoracic echocadiography (TTE), multispiral computed tomography angiography (msCTA) and/or magnetic resonance imaging (MRI). Patients with dissection were younger (p < 0.0005) and had a lower body mass index (p < 0.0005) than participants from the control group; according to echocadiography, they were less likely to have left (p = 0.014) and right (p = 0.018) atrial dilation and aortic stenosis (p = 0.017). Also, dissections were significantly less often associated with atherosclerotic plaques in the common carotid artery (CCA) (p < 0.002), and BCA deformations (p < 0.05). Duplex scanning of BCA revealed that in patients with dissections, differentiation of the intima-media complex in CCA was compromised significantly less often, and signs of thrombosis of the internal carotid artery were registered significantly more often (p = 0.021 and p = 0.004); according to MRI, such patients had less pronounced changes in the periventricular and deep white matter of the brain (p < 0.0005 and p = 0.001) and never suffered strategic infarcts affecting the thalamus area (p < 0.0005). Comparison of the results of examinations of IS patients with and without BCA dissections revealed differences that are probably conditioned by the younger age of those who had said dissections.

Fluid-structure interaction study of hemodynamics and its biomechanical influence on carotid artery atherosclerotic plaque deposits

Atherosclerotic plaque deposits are common causes of blood flow disruption in the carotid artery bifurcation and the associated fluid mechanics has been extensively studied using Computational Fluid Dynamics (CFD) and Fluid Structure Interaction (FSI). However, the elastic responses of plaques to hemodynamics in the carotid artery bifurcation has not been deeply studied using either of the above-mentioned numerical techniques. In this study, a two-way FSI study was coupled with CFD technique, using Arbitrary-Lagrangian-Eulerian method, to study the biomechanics of blood flow on nonlinear and hyperelastic calcified plaque deposits in a realistic geometry of the carotid sinus. FSI parameters such as total mesh displacement and von Misses stress on the plaque, as well as flow velocity and blood pressure around the plaques, were analyzed and compared to variables such as velocity streamline, pressure and wall shear stress obtained from CFD simulation in a healthy model. The blood flow simulations reveal complete reversed blood flow behavior in the internal carotid artery, ICAs and external carotid artery, ECAs for both cases. In particular, this study suggests that plaques, irrespective of the masses, possess a high yielding response to hemodynamic forces at the attaching edges, while the surfaces are vulnerable to rupture.

Characteristics of the carotid intima-media thickness and atherosclerotic plaques of carotid arteries in elderly people with rheumatoid arthritis at University Medical Center Ho Chi Minh City

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease that has been strongly associated with atherosclerosis. Comprehensive cardiovascular disease (CVD) assessment is advised, which entails screening for asymptomatic atherosclerotic plaques using carotid ultrasound. The objective of this study is to examine the features of carotid ultrasound, including carotid intima-media thickness (cIMT) and carotid plaques (CP), and to compare these characteristics between individuals with RA and control subjects. Materials and Methods: A cross-sectional study involved 66 participants, including 40 RA patients and 26 controls. Medical history and physical examination were conducted by a rheumatologist, while cIMT and CP were recorded via carotid ultrasound. Results: cIMT was significantly higher in the RA group compared to the control group (0.94 (0.83 - 1.25) mm vs 0.84 (0.80 - 0.92) mm, p = 0.030) and the prevalence of increased cIMT was found significantly higher in RA-patients than non-RA patients (70.00% vs 38.46%, p = 0.011). Compared to non-RA patients, carotid plaques in the RA group were statistically more prevalent on either side of the carotid artery (left 57.50% vs. 26.92%, p = 0.015; right 67.50% vs 26.92%, p = 0.001) and bilateral CP was over three times more common in RA than controls (55.00% vs 15.38%, p = 0.001). cIMT was correlated with age and body mass index. Conclusion: The occurrence of subclinical atherosclerosis is higher among patients with RA than in the control participants without RA. Measuring cIMT and CP may be a useful guide to better assess CVD risk in patients with RA and enable clinicians to take interventions promptly. Key words: rheumatoid arthritis, cardiovascular diseases, carotid intima-media thickness, carotid plaques, carotid ultrasound.

Image and Laboratory Aspects of Carotid Atherosclerosis

Abstract Carotid atherosclerosis is a main risk factor for ischemic stroke. Plaque instability is determined by the morphological characteristics of the plaque and can be characterized by immunological biomarkers. The study aimed to examine the connection between serum levels of hs-CRP, fibrinogen, ICAM-1, VCAM-1 and carotid atherosclerosis and the different types of atherosclerotic plaques imaged by ultrasound and magnetic resonance. The study involved 120 patients with carotid atherosclerosis and 33 patients without carotid atherosclerosis. Blood samples were collected to analyze the serum level of hs-CRP, fibrinogen, ICAM-1 and VCAM-1. The ultrasound analysis included detection of atherosclerotic plaques in the internal carotid arteries, measurement of artery stenosis in percentage and determination of plaque types by the classification of Gray-Weales/Gerolacus. A small subset of 30 patients with carotid atherosclerosis performed 3T magnetic resonance imaging. Atherosclerotic plaques were classified into 8 types based on the modified MR classification of the American Heart Association. Significantly higher serum levels of hs-CRP (p <0.001) and fibrinogen (p = 0.018) were observed in patients with carotid atherosclerosis compared to patients without atherosclerosis. Criterion values for hs-CRP > 4.13mg/l and for fibrinogen > 3.6 g/l were associated with the presence of carotid plaques with accuracy of 70%. No relation was observed between the investigated biomarkers, the artery stenosis and the types of atherosclerotic plaques determined by ultrasound and magnetic resonance diagnostic methods. Hs-CRP and fibrinogen are reliable serum markers whose increased serum concentrations are connected with the presence of carotid atherosclerosis.

Carotid atherosclerotic plaque segmentation in multi-weighted MRI using a two-stage neural network: advantages of training with high-resolution imaging and histology.

A reliable and automated method to segment and classify carotid artery atherosclerotic plaque components is needed to efficiently analyze multi-weighted magnetic resonance (MR) images to allow their integration into patient risk assessment for ischemic stroke. Certain plaque components such as lipid-rich necrotic core (LRNC) with hemorrhage suggest a greater likelihood of plaque rupture and stroke event. Assessment for presence and extent of LRNC could assist in directing treatment with impact upon patient outcomes. To address the need to accurately determine the presence and extent of plaque components on carotid plaque MRI, we proposed a two-staged deep-learning-based approach that consists of a convolutional neural network (CNN), followed by a Bayesian neural network (BNN). The rationale for the two-stage network approach is to account for the class imbalance of vessel wall and background by providing an attention mask to the BNN. A unique feature of the network training was to use ground truth defined by both high-resolution ex vivo MRI data and histopathology. More specifically, standard resolution 1.5 T in vivo MR image sets with corresponding high resolution 3.0 T ex vivo MR image sets and histopathology image sets were used to define ground-truth segmentations. Of these, data from 7 patients was used for training and from the remaining two was used for testing the proposed method. Next, to evaluate the generalizability of the method, we tested the method with an additional standard resolution 3.0 T in vivo data set of 23 patients obtained from a different scanner. Our results show that the proposed method yielded accurate segmentation of carotid atherosclerotic plaque and outperforms not only manual segmentation by trained readers, who did not have access to the ex vivo or histopathology data, but also three state-of-the-art deep-learning-based segmentation methods. Further, the proposed approach outperformed a strategy where the ground truth was generated without access to the high resolution ex vivo MRI and histopathology. The accurate performance of this method was also observed in the additional 23-patient dataset from a different scanner. In conclusion, the proposed method provides a mechanism to perform accurate segmentation of the carotid atherosclerotic plaque in multi-weighted MRI. Further, our study shows the advantages of using high-resolution imaging and histology to define ground truth for training deep-learning-based segmentation methods.

Heterozygosity for ADP-ribosylation factor 6 suppresses the burden and severity of atherosclerosis.

Atherosclerosis is the root cause of major cardiovascular diseases (CVD) such as myocardial infarction and stroke. ADP-ribosylation factor 6 (Arf6) is a ubiquitously expressed GTPase known to be involved in inflammation, vascular permeability and is sensitive to changes in shear stress. Here, using atheroprone, ApoE-/- mice, with a single allele deletion of Arf6 (HET) or wildtype Arf6 (WT), we demonstrate that reduction in Arf6 attenuates atherosclerotic plaque burden and severity. We found that plaque burden in the descending aorta was lower in HET compared to WT mice (p˂0.001) after the consumption of an atherogenic Paigen diet for 5 weeks. Likewise, luminal occlusion, necrotic core size, plaque grade, elastic lamina breaks, and matrix deposition were lower in the aortic root atheromas of HET compared to WT mice (all p≤0.05). We also induced advanced human-like complex atherosclerotic plaque in the left carotid artery using partial carotid ligation surgery and found that atheroma area, plaque grade, intimal necrosis, intraplaque hemorrhage, thrombosis, and calcification were lower in HET compared to WT mice (all p≤0.04). Our findings suggest that the atheroprotection afforded by Arf6 heterozygosity may result from reduced immune cell migration (all p≤0.005) as well as endothelial and vascular smooth muscle cell proliferation (both p≤0.001) but independent of changes in circulating lipids (all p≥0.40). These findings demonstrate a critical role for Arf6 in the development and severity of atherosclerosis and suggest that Arf6 inhibition can be explored as a novel therapeutic strategy for the treatment of atherosclerotic CVD.

Disparities in the Prevalence and Risk Factors for Carotid and Lower Extremities Atherosclerosis in a General Population—Bialystok PLUS Study

This study was conducted in a representative sample of area residents aged 20-80 years old. The aim of the study was to assess the prevalence of classic risk factors of atherosclerosis in the studied population and to search for new risk factors in these patient subpopulations. A total of 795 people (mean age 48.64 ± 15.24 years, 45.5% male) were included in the study group. Two independent data analyses were performed. In the first analysis, the study group was divided into two subgroups depending on the presence or absence of atherosclerotic plaques in carotid arteries (APCA). APCA were observed in 49.7% of the study group: in the population aged between 41 and 60 years in 49.3%, and those between 61 and 70 years in 86.3%. Patients with APCA were more often diagnosed with arterial hypertension, diabetes, and hypercholesterolemia. In the second analysis, the study group was divided into two subgroups depending on the presence of lower extremities atherosclerotic disease (LEAD). Patients with an ABI (ankle-brachial index) ≤ 0.9 constituted 8.5% of the study group, and they were significantly older, and more often diagnosed with diabetes and APCA. To identify the factors most strongly associated with APCA and an ABI ≤ 0.9, logistic regression was used, with stepwise elimination of variables. The strongest factors associated with APCA were current smoking and diastolic central pressure. We did not note such an association and did not find additional parameters to facilitate the diagnosis of LEAD in asymptomatic patients. The most important observation in our study was the high prevalence of APCA in the study population, especially in the group of young people under the age of 60.

Transcription factor 21 accelerates vascular calcification in mice by activating the IL-6/STAT3 signaling pathway and the interplay between VSMCs and ECs.

Vascular calcification is caused by the deposition of calcium salts in the intimal or tunica media layer of the aorta, which increases the risk of cardiovascular events and all-cause mortality. However, the mechanisms underlying vascular calcification are not fully clarified. Recently it has been shown that transcription factor 21 (TCF21) is highly expressed in human and mouse atherosclerotic plaques. In this study we investigated the role of TCF21 in vascular calcification and the underlying mechanisms. In carotid artery atherosclerotic plaques collected from 6 patients, we found that TCF21 expression was upregulatedin calcific areas. We further demonstrated TCF21 expression wasincreased in an in vitro vascular smooth muscle cell (VSMC) osteogenesis model. TCF21 overexpression promoted osteogenic differentiation of VSMC, whereas TCF21 knockdown in VSMC attenuated the calcification. Similar results were observed in ex vivo mouse thoracic aorta rings. Previous reports showed that TCF21 bound to myocardin (MYOCD) to inhibit the transcriptional activity of serum response factor (SRF)-MYOCD complex. We found that SRF overexpression significantly attenuated TCF21-induced VSMC and aortic ring calcification. Overexpression of SRF, but not MYOCD, reversed TCF21-inhibited expression of contractile genes SMA and SM22. More importantly, under high inorganic phosphate (3 mM) condition, SRF overexpression reduced TCF21-induced expression of calcification-related genes (BMP2 and RUNX2) as well as vascular calcification. Moreover, TCF21 overexpression enhanced IL-6 expression and downstream STAT3 activation to facilitate vascular calcification. Both LPS and STAT3 could induce TCF21 expression, suggesting that the inflammation and TCF21 might form a positive feedback loop to amplify the activation of IL-6/STAT3 signaling pathway. On the other hand, TCF21 induced production of inflammatory cytokines IL-1β and IL-6 in endothelial cells (ECs) to promote VSMC osteogenesis. In EC-specific TCF21 knockout (TCF21ECKO) mice, VD3 and nicotine-induced vascular calcification was significantly reduced. Our results suggest that TCF21 aggravates vascular calcification by activating IL-6/STAT3 signaling and interplay between VSMC and EC, which provides new insights into the pathogenesis of vascular calcification. TCF21 enhances vascular calcification by activating the IL-6-STAT3 signaling pathway. TCF21 inhibition may be a new potential therapeutic strategy for the prevention and treatment of vascular calcification.

Assesmen of atherosclerotic lesions of the carotid artery and risk factors for rheumatoi arthritis patients

Aim . To study and evaluate risk factors and analyze carotid artery intima-media thickness parameters as an early predictor of atherosclerosis in patients with rheumatoid arthritis. Materials and methods . The study involved 86 patients (women - 67, men - 19) observed in the State Institution “City Medical Center №2”, Dushanbe, aged from 37 to 67 years (mean age - 56.5±2.9 years). The diagnosis of rheumatoid arthritis was established according to the American College of Rheumatologists/EULAR 2010 criteria. The examination program included general clinical and instrumental methods (examination of common and accessible parts of internal and external carotid arteries), estimation of lumen size, the thickness of intima-media complex (TCIM), straightness of its course, atherosclerotic plaques of carotid arteries (ABS), echocardiography (ECHO-KG). Results and discussion . Thus, in the absence of significant gender differences in the frequency of arterial hypertension and increased intima-media thickness (the earliest manifestation of atherosclerotic vascular lesions), hypercholesterolemia and long-term glucocorticoid intake were more frequently recorded in women. Undoubtedly, each of the considered risk factors makes a definite contribution to the development of vascular atherosclerosis and the instability of their organic changes. However, the significance of these risk factors in the thickening of the intima-media complex of vessels may differ. Conclusion . Data correlated with intima-media thickness show sex differences, the significance of risk factors, and an increase in intima-media thickness despite the duration of glucocorticoid therapy. The factors mentioned are more significant in men, while in women, intima-media thickness is closely related to the duration of rheumatoid arthritis, total cholesterol levels, and blood pressure.

Sleep apnea-COPD overlap syndrome is associated with larger left carotid atherosclerotic plaques.

Little is known about whether the overlap syndrome (OS) combining features of chronic obstructive pulmonary disease (COPD) and sleep apnea-hypopnea syndrome increases the risk of stroke associated with COPD itself. We prospectively studied 74 COPD patients and 32 subjects without lung disease. Spirometry and cardiorespiratory polygraphy were used to assess the pulmonary function of the study population and ultrasound measurements of intima media thickness (IMT) as well as the volume of plaques in both carotid arteries were also evaluated. Polygraphic criteria of OS were met in 51% of COPD patients. We found that 79% of patients with OS and 50% of COPD patients without OS had atherosclerotic plaques in the left carotid artery (p = 0.0509). Interestingly, the mean volume of atherosclerotic plaques was significantly higher in the left carotid artery of COPD patients with OS (0.07 ± 0.02 ml) than in those without OS (0.04 ± 0.02 ml, p = 0.0305). However, regardless of the presence of OS, no significant differences were observed in both presence and volume of atherosclerotic plaques in the right carotid artery of COPD patients. Adjusted-multivariate linear regression revealed age, current smoking and the apnea/hypopnea index (OR = 4.54, p = 0.012) as independent predictors of left carotid atherosclerotic plaques in COPD patients. This study suggests that the presence of OS in COPD patients is associated with larger left carotid atherosclerotic plaques, indicating that OS might be screened in all COPD patients to identify those with higher risk of stroke.

Subclinical Carotid Atherosclerosis in Patients with Rheumatoid Arthritis at Low Cardiovascular Risk.

To evaluate the rate of subclinical carotid atherosclerosis and clinical significance of immunoinflammatory markers in patients with rheumatoid arthritis (RA) at low cardiovascular risk. The study included 275 RA patients and a control group of 100 participants without autoimmune diseases. All study participants were at low cardiovascular risk, calculated by the QRISK3 scale (<20%), and free of cardiovascular disease. Ultrasound examination of carotid arteries was performed to measure cIMT and to detect atherosclerotic plaques (ASP) in carotid arteries. sIСАМ-1, sVСАМ, and sCD40L levels were determined by enzyme immunoassay. Carotid ASP was observed more frequently in RA patients (27%) than in the control group (17%), p = 0.03. The frequency of ASP in RA patients did not depend on the disease's stage or activity. There was a significant correlation between cIMT and age, cardiovascular risk determined by QRISK3, level of total cholesterol, LDL, and blood pressure in RA patients, p < 0.05 in all cases. No correlation between cIMT and blood levels of sCD40L, sVCAM, and sICAM was found. In RA patients, a higher concentration of sVCAM was detected in the carotid ASP group compared to the non-atherosclerotic group. sCD40L was associated with cIMT and total cholesterol in the ASP group and with total cholesterol and blood pressure in non-atherosclerotic patients. Subclinical atherosclerotic lesions of the carotid arteries were observed significantly more frequently in RA patients with low cardiovascular risk than in the control group. The results of the study demonstrate the association between cIMT, traditional cardiovascular risk factors, and immunoinflammatory markers in RA patients.

Soluble low-density lipoprotein receptor-related protein 1 as a surrogate marker of carotid plaque inflammation assessed by 18F-FDG PET in patients with a recent ischemic stroke

Background18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) identifies carotid plaque inflammation and predicts stroke recurrence.AimOur aim was to evaluate the performance of soluble low-density lipoprotein receptor-related protein 1 (sLRP1) as an indicator of carotid plaque inflammation.MethodsA prospective study was conducted among adult patients with recent (< 7 days) anterior circulation ischemic stroke and at least one atherosclerotic plaque in the ipsilateral internal carotid artery. Patients underwent an early (< 15 days from inclusion) 18F-FDG PET, and the maximum standardized uptake value (SUVmax) within the plaque was measured. sLRP1 levels were measured in plasma samples by ELISA. The association of sLRP1 with SUVmax was assessed using bivariate and multivariable linear regression analyses. Hazard ratios (HR) were estimated with Cox regression to evaluate the association between circulating sLRP1 and stroke recurrence.ResultsThe study was conducted with 64 participants, of which 57.8% had ≥ 50% carotid stenosis. The multivariable linear and logistic regression analyses showed that sLRP1 was independently associated with (i) SUVmax within the plaque (β = 0.159, 95% CI 0.062–0.257, p = 0.002) and (ii) a probability of presenting SUVmax ≥ 2.85 g/mL (OR = 1.31, 95% CI 1.00–1.01, p = 0.046), respectively. Participants with stroke recurrence showed higher sLRP1 levels at baseline [6447 ng/mL (4897–11163) vs. 3713 ng/mL (2793–4730); p = 0.018].ConclusionssLRP1 was independently associated with carotid plaque inflammation as measured by 18F-FDG PET in patients with recent ischemic stroke and carotid atherosclerosis.

Metformin Directly Binds to MMP-9 to Improve Plaque Stability

Vulnerable atherosclerotic plaque rupture is the principal mechanism that accounts for myocardial infarction and stroke. High matrix metalloproteinase-9 (MMP-9) expression and activity have been proven to lead to plaque instability. Metformin, a first-line treatment for type 2 diabetes, is beneficial to plaque vulnerability. However, the mechanism underlying its anti-atherogenic effect remains unclear. Molecular docking and surface plasmon resonance experiments showed that metformin directly interacts with MMP-9, and incubated MMP-9 overexpressing HEK293A cells with metformin (1 μmol·L-1) significantly attenuates MMP-9's activity using zymography and MMP activity assays. Moreover, metformin treatment drives MMP-9 degradation. Next, we constructed a carotid artery atherosclerotic plaque model and administered consecutive 14-day metformin (200 mg·kg-1·d-1) treatment by intragastric gavage. Immunofluorescence staining of the right carotid common artery and serum MMP activity assay results showed that metformin treatment decreased local plaque MMP-9 protein level and circulating MMP-9 activity, respectively. Histochemical staining revealed that after metformin treatment, the collagen content in plaque was significantly preserved, and the plaque vulnerability index decreased. These findings suggested that metformin improved atherosclerotic plaque stability by directly binding to MMP-9 and driving its degradation.

Carotid atherosclerosis in people of European, South Asian and African Caribbean ethnicity in the Southall and Brent revisited study (SABRE).

Atherosclerotic cardiovascular disease (ASCVD) risk differs by ethnicity. In comparison with Europeans (EA) South Asian (SA) people in UK experience higher risk of coronary heart disease (CHD) and stroke, while African Caribbean people have a lower risk of CHD but a higher risk of stroke. To compare carotid atherosclerosis in EA, SA, and AC participants in the Southall and Brent Revisited (SABRE) study and establish if any differences were explained by ASCVD risk factors. Cardiovascular risk factors were measured, and carotid ultrasound was performed in 985 individuals (438 EA, 325 SA, 228 AC). Carotid artery plaques and intima-media thickness (cIMT) were measured. Associations of carotid atherosclerosis with ethnicity were investigated using generalised linear models (GLMs), with and without adjustment for non-modifiable (age, sex) and modifiable risk factors (education, diabetes, hypertension, total cholesterol, HDL-C, alcohol consumption, current smoking). Prevalence of any plaque was similar in EA and SA, but lower in AC (16, 16, and 6%, respectively; p < 0.001). In those with plaque, total plaque area, numbers of plaques, plaque class, or greyscale median did not differ by ethnicity; adjustment for risk factors had minimal effects. cIMT was higher in AC than the other ethnic groups after adjustment for age and sex, adjustment for risk factors attenuated this difference. Prevalence of carotid artery atherosclerotic plaques varies by ethnicity, independent of risk factors. Lower plaque prevalence in in AC is consistent with their lower risk of CHD but not their higher risk of stroke. Higher cIMT in AC may be explained by risk factors. The similarity of plaque burden in SA and EA despite established differences in ASCVD risk casts some doubt on the utility of carotid ultrasound as a means of assessing risk across these ethnic groups.

Phenotyping of embolic cryptogenic stroke based on ultrasound diagnosis and determination of serum concentration NT-proBNP

Determining the potential mechanisms underlying cryptogenic ischemic stroke is essential to guide diagnostic discovery and personalize secondary prevention.Purpose is to study the phenotypes of embolic stroke of undetermined source (ESUS) based on ultrasound diagnosis and determination of the serum concentration of pro-natriuretic N-terminal peptide B-type (N-Terminal Pro-brain Natriuretic Peptide, NT-proBNP).Materials and methods. 141 patients with ESUS were examined. In addition to the standard examination aimed at fi nding the cause of stroke, the functional characteristics of the left atrium were assessed using the emptying fraction (left atrial emptying fraction, LAEF) and the functional index (left atrial function index, LAFI), and the concentration of NT-proBNP in blood serum was also measured.Results. The most common potential sources of embolism were atherosclerotic plaques in the stroke-associated carotid artery with stenosis in 30–49% (31.9% of patients) and atrial cardiopathy with a decrease in LAEF &lt; 51.8% (24.8% of patients). An analysis of combinations of potential sources showed that 46.1% of patients had a negative phenotype, 21.3% of patients had a cardiac phenotype, 19.1% of patients had an atherosclerotic phenotype, and 13.5% of the examined patients had a mixed phenotype. Patients with a cardio-atherosclerotic phenotype diff ered from patients with a negative phenotype by higher disability on the Rankin scale at discharge from the hospital.Conclusion. The main potential embolic sources in patients with ESUS are non-stenosing carotid atherosclerosis and atrial cardiopathy with decreased LAEF. Cardiac and atherosclerotic phenotypes are determined in a quarter of patients, a mixed phenotype is found in every seventh patient, while in almost half of the patients no sources of embolism are found.

ROLE OF NON-CONTRAST MAGNETIC RESONANCE ANGIOGRAPHY IN THE DIAGNOSIS OF THE ATHEROSCLEROTIC LESIONS OF THE EXTRACRANIAL CAROTID ARTERIES

Formation of atherosclerotic plaque in the carotid arteries is the leading factor of hemodynamic disturbance in the cere-bral arteries. Visualization and characteristic of these plaques are most important factors from the viewpoint of preven-tive treatment- surgical or conservative. The goal of this study was to assess sensitivity and specificity of non-contrast MRA in evaluation and characteristics of atherosclerotic plaques in the extracranial carotid arteries. Our data was ob-tained from 130 patients: 38 were female (29.2%) and 92-male (70.8%). The middle age is 54.8 years (range 17-78 years). Patients were subjected to 3 diagnosis procedures, namely 85 patients were investigated by Doppler USG &amp; 45 patients by MRA method. All patients underwent selective cerebral arterial angiography by DSA as a gold standard method. From 130 patients 27 patients had no atherosclerotic disease; 57 had bilateral atherosclerotic changes; 46 pa-tients had monolateral carotid atherosclerotic process. From 260 investigated carotid arteries 51 arteries were detected with complete occlusion (22 right and 21 left occlusion), in 4 patients (8 carotid arteries) bilateral occlusion was seen. 54 carotid arteries had severe degree of stenosis. From this stenosis 27 arteries were more than 90%.32 carotid arteries had moderate degree of stenosis. In 23 carotid arteries mild degree was seen, but in a 100 carotid arteries had complete pa-tency. We concluded that complex noninvasive methods- colored Doppler USG and non-contrast MRA distinguished good accuracy (90%) and may be used as an alternative to DSA.

Assessment of the prevalence of target organ damage at various stages of the cardiometabolic continuum. According to the ESSE RF study

Objective: to assess the prevalence of target organ damage (TOD) at various stages of the cardiometabolic continuum, including abdominal obesity (AO) without metabolic syndrome (MS), MS, and type 2 diabetes mellitus (DM).Materials and methods: this study presents an analysis of data from a sample of residents of Tomsk (1,104 examined from an unorganized adult population of 25-64 years), performed within the framework of the ESSAY RF-2012 project (Epidemiology of Cardiovascular Diseases in the Regions of the Russian Federation). The analysis included the presence of LV hypertrophy (LVH), a decrease in glomerular filtration rate (GFR), an increase in the thickness of the intima-media complex (TIM), the presence of atherosclerotic plaques (ASP) in the common carotid arteries (CCA).Results: TODs were already reported among individuals with isolated AO (without MS), whose prevalence was statistically significantly higher compared to those with normal body weight. Atherosclerosis of CCA turned out to be the most frequent TOD phenotype, ASP was detected in 22% of individuals with isolated AO, in 33% patients with MS and 35% patients with type 2 DM, the second most common was LVH, which was detected in 0.8%, 4,7% and 17,5% of cases, respectively, the least common was a decrease in GFR – in 1,37%, 3,7% and 6,7% of patients, respectively. Differences in the frequency of TOD in all groups were statistically significant (p &lt; 0,01).Conclusions: Thus, the prevalence of TODs detected already at the stage of isolated AO progressively increased from group to group, as they moved along the cardiometabolic continuum.