Atherosclerotic Lesions Of Carotid Arteries Research Articles

Adherence to Mediterranean Diet: A Population-Based Longitudinal Cohort Study.

Adherence to the Mediterranean diet (MedDiet) is recommended for cardiovascular disease prevention. However, recent epidemiological studies report a shift toward lower adherence to MedDiet. We have conducted a prospective cohort study to evaluate changes in individual determinants of MedDiet adherence over time. Clinical information and MedDiet adherence score (MEDAS) were collected in 711 subjects (mean age 68 ± 10 years; 42% males), enrolled in the PLIC study (Progression of Intimal Atherosclerotic Lesions in Carotid arteries), during two visits conducted, on average, 4.5 years apart. MEDAS score worsening and improvements (absolute change, ΔMEDAS) and the variation in the proportion of subjects reporting to meet each MEDAS criteria were assessed. Overall, 34% of the subjects improved their MedDiet adherence (ΔMEDAS: +1.87 ± 1.13), by consuming more olive oil, legumes and fish and use of dishes seasoned with sofrito and 48% subjects worsened their MedDiet adherence (ΔMEDAS: -2.02 ± 1.14) by consuming less fruit, legumes, fish and nuts, with higher rates of worsening in women and subjects aged 50-65 years. Subjects who improved the score were more obese, had higher plasma glucose levels, and metabolic syndrome at the basal visit. In summary, we report an overall decrease in MedDiet adherence, evaluated during a timeframe heavily affected by the COVID-19 pandemic, underlining the need for better dietary interventions.

Sonographic Intima-Media Thickness Evaluation of Common Carotid and Internal Carotid Arteries in Type-2 Diabetes Mellitus

Background: Intima-media thickness (IMT) is a useful marker in early detection of atherosclerotic lesions in carotid arteries in Type-2 Diabetes Mellitus (T2DM) patients. The study was conducted to determine the association of IMT with various physical and biochemical parameters in the Indian population. Objective: To compare IMT of common and internal carotid arteries in T2DM patients and healthy individuals and study the correlation of IMT with physical and biochemical parameters. Methods: Case group with T2DM (n=27) were matched with Control group consisting of healthy individuals (n=27) of similar age and sex were included. Physical parameters and routine biochemical data were collected and compared. Ultrasonographical imaging of the common and internal carotid arteries of both sides were performed presence of plaque was observed. Data was analyzed by software IBM® SPSS Statistics V20.0. For all analyses, P<0.05 was considered as statistically significant. Results: Mean IMT value obtained in case and control group are 0.711±0.14 mm and 0.601±0.16 mm respectively (P=0.005). Presence of plaque was noticed in 37.03% subjects in case group and in 14.81% subjects in control group. Mean IMT was significantly higher for smoker than non-smokers (P=0.004). Fasting blood sugar, postprandial blood sugar, Postprandial triglycerides and total cholesterol were significantly higher in case group (P<0.05). There was a strong family history of T2DM in case group (51.85%) compared to control group (14.81%) with a statistical significance between them (P=0.009). Conclusion: IMT of common and internal carotid arteries have a significant association in T2DM patients compared to healthy subjects and IMT is significantly associated with physical and biochemical parameters.

Stroke risk stratification in elderly patients with comorbid sarcopenia and atherosclerosis

The study was to investigate the features of carotid arteries atherosclerosis as the leading risk factor for atherothrombotic stroke in elderly patients depending on the presence of sarcopenia. 2 groups of patients above the working age were examined: 110 patients with normal muscle mass and 24 suffering sarcopenia. Ultrasound examination of carotid and vertebral arteries extracranial segments was performed with an assessment of atherosclerotic changes severity, atherosclerotic plaques instability, 10-year risk of stroke (according to Framingham risk score) and a 10-year risk of fatal cardiovascular disease (SCORE risk scale). 10-year risk of fatal cardiovascular disease was 3 [2; 5] points for patients without sarcopenia, 3 [2; 3] points for patients with sarcopenia (p=0.81). The 10-year risk of stroke was 16 [12; 18] for patients without sarcopenia, 18 [15; 22] points for patients with sarcopenia (p=0.1). Due to the ultrasound examination data the incidence of carotid arteries atherosclerotic lesions in patients without sarcopenia was 50 (46.3%), in patients with sarcopenia - 18 (75.0%) (p=0.01). Statistically significant (p<0.05) increase in the atherosclerotic plaques instability signs was revealed in patients suffering sarcopenia compared to those without it: heterogeneous echotexture - 66.7% cases versus 38.2% (p=0.01), presence of hypoechoic masses - 41.7% patients vs 12.7% (p=0.02). It is important to take into account not only traditional risk factors in the overall assessment of cardiovascular risk as well as therapeutic and preventive measures planning in elderly patients, but also pay attention to body composition since modern diagnostic systems may be not sensitive enough to identify high-risk patients with comorbid atherosclerosis and sarcopenia.

Automated deep learning-based paradigm for high-risk plaque detection in B-mode common carotid ultrasound scans: an asymptomatic Japanese cohort study.

The death due to stroke is caused by embolism of the arteries which is due to the rupture of the atherosclerotic lesions in carotid arteries. The lesion formation is over time, and thus, early screening is recommended for asymptomatic and moderate-risk patients. The previous techniques adopted conventional methods or semi-automated and, more recently, machine learning solutions. A handful of studies have emerged based on solo deep learning (SDL) models such as UNet architecture. The proposed research is the first to adopt hybrid deep learning (HDL) artificial intelligence models such as SegNet-UNet. This model is benchmarked against UNet and advanced conventional models using scale-space such as AtheroEdge 2.0 (AtheroPoint, CA, USA). All our resultant statistics of the three systems were in the order of UNet, SegNet-UNet, and AtheroEdge 2.0. Using the database of 379 ultrasound scans from a Japanese cohort of 190 patients having moderate risk and implementing the cross-validation deep learning framework, our system performance using area-under-the-curve (AUC) for UNet, SegNet-UNet, and AtheroEdge 2.0 were 0.93, 0.94, and 0.95 (P<0.001), respectively. The coefficient of correlation between the three systems and ground truth (GT) were: 0.82, 0.89, and 0.85 (P<0.001 for all three), respectively. The mean absolute area error for the three systems against manual GT was 4.07±4.70 mm2, 3.11±3.92 mm2, 3.72±4.76 mm2, respectively, proving the superior performance SegNet-UNet against UNet and AtheroEdge 2.0, respectively. Statistical tests were also conducted for their reliability and stability. The proposed study demonstrates a fast, accurate, and reliable solution for early detection and quantification of plaque lesions in common carotid artery ultrasound scans. The system runs on a test US image in <1 second, proving overall performance to be clinically reliable.

Long Noncoding RNA MIAT Controls Advanced Atherosclerotic Lesion Formation and Plaque Destabilization.

Long noncoding RNAs (lncRNAs) are important regulators of biological processes involved in vascular tissue homeostasis and disease development. The present study assessed the functional contribution of the lncRNA myocardial infarction-associated transcript (MIAT) to atherosclerosis and carotid artery disease. We profiled differences in RNA transcript expression in patients with advanced carotid artery atherosclerotic lesions from the Biobank of Karolinska Endarterectomies. The lncRNA MIAT was identified as the most upregulated noncoding RNA transcript in carotid plaques compared with nonatherosclerotic control arteries, which was confirmed by quantitative real-time polymerase chain reaction and in situ hybridization. Experimental knockdown of MIAT, using site-specific antisense oligonucleotides (LNA-GapmeRs) not only markedly decreased proliferation and migration rates of cultured human carotid artery smooth muscle cells (SMCs) but also increased their apoptosis. MIAT mechanistically regulated SMC proliferation through the EGR1 (Early Growth Response 1)-ELK1 (ETS Transcription Factor ELK1)-ERK (Extracellular Signal-Regulated Kinase) pathway. MIAT is further involved in SMC phenotypic transition to proinflammatory macrophage-like cells through binding to the promoter region of KLF4 and enhancing its transcription. Studies using Miat-/- and Miat-/-ApoE-/- mice, and Yucatan LDLR-/- mini-pigs, as well, confirmed the regulatory role of this lncRNA in SMC de- and transdifferentiation and advanced atherosclerotic lesion formation. The lncRNA MIAT is a novel regulator of cellular processes in advanced atherosclerosis that controls proliferation, apoptosis, and phenotypic transition of SMCs, and the proinflammatory properties of macrophages, as well.

Oxidation of Hemoglobin Drives a Proatherogenic Polarization of Macrophages in Human Atherosclerosis.

Aim: The aim of our study was to explore the pathophysiologic role of oxidation of hemoglobin (Hb) to ferrylHb in human atherosclerosis.Results: We observed a severe oxidation of Hb to ferrylHb in complicated atherosclerotic lesions of carotid arteries with oxidative changes of the globin moieties, detected previously described oxidation hotspots in Hb (β1Cys93; β1Cys112; β2Cys112) and identified a novel oxidation hotspot (α1Cys104). After producing a monoclonal anti-ferrylHb antibody, ferrylHb was revealed to be localized extracellularly and also internalized by macrophages in the human hemorrhagic complicated lesions. We demonstrated that ferrylHb is taken up via phagocytosis as well as CD163 receptor-mediated endocytosis and then transported to lysosomes involving actin polymerization. Internalization of ferrylHb was accompanied by upregulation of heme oxygenase-1 and H-ferritin and accumulation of iron within lysosomes as a result of heme/iron uptake. Importantly, macrophages exposed to ferrylHb in atherosclerotic plaques exhibited a proinflammatory phenotype, as reflected by elevated levels of IL-1β and TNF-α. To find further signatures of ferrylHb in complicated lesions, we performed RNA-seq analysis on biopsies from patients who underwent endarterectomies. RNA-seq analysis demonstrated that human complicated lesions had a unique transcriptomic profile different from arteries and atheromatous plaques. Pathways affected in complicated lesions included gene changes associated with phosphoinositide 3-kinase (PI3K) signaling, lipid transport, tissue remodeling, and vascularization. Targeted analysis of gene expression associated with calcification, apoptosis, and hemolytic-specific clusters indicated an increase in the severity of complicated lesions compared with atheroma. A 39% overlap in the differential gene expression profiles of human macrophages exposed to ferrylHb and the complicated lesion profiles was uncovered. Among these 547 genes, we found inflammatory, angiogenesis, and iron metabolism gene clusters regulated in macrophages.Innovation and Conclusion: We conclude that oxidation of Hb to ferrylHb contributes to the progression of atherosclerosis via polarizing macrophages into a proatherogenic phenotype. Antioxid. Redox Signal. 35, 917–950.

Abstract MP18: Mitochondrial Inducing Factor 1 Affects Stabilization Of Advanced Atherosclerotic Lesions In Carotid Artery Disease

Whereas cerebrovascular diseases, most and foremost ischemic events, being the second most deadliest disease as of today in the western world the process behind carotid artery plaque (CAP) vulnerability remains understood insufficiently. Through proteomic analysis of blood serum from patients treated for atherosclerotic lesions in carotid arteries we were able to determine proteins of potential relevance to CAP stability. One of the identified targets is mitochondrial apoptosis inducing factor 1 (AIFM1), which we found upregulated in serum profiles from patients with vulnerable atherosclerotic lesions. The study were conducted with human vascular tissue and blood samples from the 'Munich Vascular Biobank'. Proteomic profiling of serum was performed using the platform OLink (Uppsala, Sweden) taken from patients with either stable (n=53) or unstable (n=53) CAPs. Furthermore, gene expression of AIFM1 in stable (n=5) and unstable (n=3) CAPs was assessed via RT-qPCR .Via Immunostaining the regions showing higher expression of AIFM1 within the plaques (n=10) were determined and put in perspective with markers of cell types predominantly accumulated in those regions. In addition, blood monocyte-derived macrophages were stimulated with different factors and changes in expression of AIFM1 was assessed. With the proteomic sequencing of blood sera, higher levels of AIFM1 in patients with unstable versus stable CAP were determined. This trend was also seen assessing the gene expression of AIFM1 in the human vascular tissue. A significant enrichment of staining of AIFM1 positivity was observed in regions where apoptosis occured, such as the necrotic core and the shoulder regions of the advanced CAP. Furhtermore, AIFM1 enriched regions were identified as areas infiltrated by immune cells, especially macrophages. Monocytes of healthy donours showed an increased expression of AIFM1 when developed into macrophages. In conclusion AIFM1 was identified as a potential novel marker for advanced, unstable lesions in CAPs. Future studies (in vitro and in vivo) will reveal which role AIFM1 might play during processes that trigger CAP destabilization. Of further importance will be cell type expression patterns that we are also assessing in currently ongoing studies.

Application of cardiovascular risk scales to identify carotid atherosclerosis in patients with rheumatoid arthritis

To evaluate the cardiovascular risk (CVR) and analyze its relationship with detection of early carotid artery atherosclerotic lesion in patients with rheumatoid arthritis (RA). One hundred and nine RA patients aged 45 to 60 without established cardiovascular diseases (CVD) were included in the study. The median age was 52 [48; 54] years, duration of RA was 120 [36; 204] months, DAS28 was 4.7 [3.5; 5.6] points. CVD risk was calculated with mSCORE, Reynolds Risk Score (RRS), ASSIGN, QRISK3, ERS-RA scales and Carotid Artery Doppler Ultrasound Exam was performed for all patients. High risk was found in 5, 5, 14, 6, and 38% of patients according to mSCORE, RRS, ASSIGN, QRISK3, ERS-RA scales, respectively. Atherosclerotic plaques of carotid arteries were found in 30% of patients. It was found that carotid intima-media thickness is correlated to all CVR calculators, age, systolic and diastolic blood pressure, cholesterol, erythrocyte sedimentation rate, interleukin-6 levels. The sensitivity and specificity of the CVR algorithms in prognostication of atherosclerotic carotid artery lesions were 73 and 67% for mSCORE, 64 and 63% for RRS, 64 and 56% for ASSIGN, 73 and 49% for QRISK3, respectively, p0.05 in all cases, 67 and 50% for ERS-RA, p=0.06. RRS, mSCORE, ASSIGN, QRISK3 calculators equally predict atherosclerotic carotid artery damage in RA patients. The optimal ratio of specificity and sensitivity is shown for the mSCORE scale. Stratification of CVR in RA patients should include assessment of the carotid intima-media thickness. To identify CVR in RA patients, the most informative methods are mSCORE calculation and carotid intima-media thickness determination.

Domain adaptive and fully automated carotid artery atherosclerotic lesion detection using an artificial intelligence approach (LATTE) on 3D MRI.

To develop and evaluate a domain adaptive and fully automated review workflow (lesion assessment through tracklet evaluation, LATTE) for assessment of atherosclerotic disease in 3D carotid MR vessel wall imaging (MR VWI). VWI of 279 subjects with carotid atherosclerosis were used to develop LATTE, mainly convolutional neural network (CNN)-based domain adaptive lesion classification after image quality assessment and artery of interest localization. Heterogeneity in test sets from various sites usually causes inferior CNN performance. With our novel unsupervised domain adaptation (DA), LATTE was designed to accurately classify arteries into normal arteries and early and advanced lesions without additional annotations on new datasets. VWI of 271 subjects from four datasets (eight sites) with slightly different imaging parameters/signal patterns were collected to assess the effectiveness of DA of LATTE using the area under the receiver operating characteristic curve (AUC) on all lesions and advanced lesions before and after DA. LATTE had good performance with advanced/all lesion classification, with the AUC of >0.88/0.83, significant improvements from >0.82/0.80 if without DA. LATTE can locate target arteries and distinguish carotid atherosclerotic lesions with consistently improved performance with DA on new datasets. It may be useful for carotid atherosclerosis detection and assessment on various clinical sites.

Low shear stress-induced endothelial mesenchymal transformation via the down-regulation of TET2

Atherosclerotic cardiovascular disease is the major cause of death worldwide. Low shear stress plays key roles on the initiation and progression of atherosclerosis (As). However, its underlying mechanism remains unclear. In this study, the effect of low shear stress on endothelial mesenchymal transformation (EndMT) and its underlying mechanism were explored. Results showed that in cultured human umbilical vein endothelial cells, low shear stress down-regulated the expression of TET2 and promoted EndMT. Loss of TET2 promoted EndMT with the Wnt/β-catenin signaling pathway. The enhancement in EndMT induced by low shear stress was attenuated by TET2 overexpression. In apoE−/− mice subjected to carotid artery local ligation, the EndMT and atherosclerotic lesions induced by low shear stress was attenuated by TET2 overexpression. Taken together, low shear stress promoted EndMT through the down-regulation of TET2, indicating that intervention with EndMT or the up-regulation of TET2 might be an alternative strategy for preventing As.

Rehabilitation of patients after acute cerebrovascular accident followed by hemodynamically significant stenoses of the brachiocephalic arteries

The literature data is presented covering epidemiological significance of acute cerebrovascular accidents (CVA) in‑ cidence in patients with brachiocephalic arteries lesion. The role of atherosclerotic lesion of carotid arteries in the develop‑ ment of ischemic cerebral stroke is shown. The basic methods for diagnosis of carotid arteries lesion has been analyzed as well as their availability and informative value. A comparative analysis of modern methods for surgical treatment of athero‑ sclerotic lesion of carotid arteries such as carotid endarterectomy (classic and eversion), endovascular procedure has been done. The main advantages and disadvantages of these treatment methods, indications and contraindications for their use are described. The timing of cerebral revascularization in the acute and delayed periods of ischemic stroke was estimated. The role of bilateral lesion of the carotid territory is shown as well as approaches to the treatment strategy of such patients.

Honokiol inhibits carotid artery atherosclerotic plaque formation by suppressing inflammation and oxidative stress.

Honokiol is a natural active compound extracted from Chinese herbal medicine, Magnolia officinalis. In this study, the role of honokiol in the development of carotid artery atherosclerotic lesions was evaluated in an ApoE-/- mouse model fed with a normal diet (ND) or a Western-type diet (WD) for ten weeks. After first two weeks, a perivascular collar was surgically placed on the right common carotid arteries of the mice. Then, WD-fed mice were intraperitoneally injected with honokiol (10 or 20 mg/kg) or administrated with 10 mg/kg atorvastatin calcium by gavage once a day for eight weeks. After that, the right common carotid arteries were excised for further experiments. The result showed that honokiol substantially inhibited the development of atherosclerotic lesions. Furthermore, honokiol downregulated the expression of pro-inflammatory markers, like tumor necrosis factor-α, interleukin (IL)-6, and IL-1β. Additionally, honokiol treatment decreased reactive oxygen species level and enhanced superoxide dismutase activity. Nitric oxide level, inducible nitric oxide synthase (iNOS) expression, and aberrant activation of nuclear factor-κB pathway were also significantly inhibited by honokiol treatment. Together, these findings suggest that honokiol protects against atherosclerotic plaque formation in carotid artery, and may be an effective drug candidate for the treatment of carotid artery atherosclerotic stenosis.

Gradient of luminal narrowing of internal carotid artery on atherosclerotic plaque as risk factor for cerebral ischemic damage

Aim. To study the clinical significance of the gradient of narrowing of arterial lumen (GNL) for atherosclerotic stenosis of the internal carotid artery (ICA) as a risk factor for ischemic brain damage.Material and methods. We proposed a new parameter of hemodynamic severity of ICA atherosclerotic stenosis — GNL. It calculated as ratio of the difference in the ICA cross section areas on the stenotic lesion and the near non-stenotic region to the distance between them: Snorm — Sstenosis)/Dnorm — stenosis, mm2 /mm. We examined 25 patients with advanced atherosclerosis and with uni(n=22) or bilateral (n=3) ICA stenosis &gt;50% according to European Carotid Surgery Trial, and 11 individuals without ICA stenosis. Each participant underwent magnetic resonance angiography (MRA) of the carotid arteries with reconstruction of the arteries from C6-C7 level to the parietal bones, and the GNL was calculated. The thickness of the baseline slice was 0,8-1 mm. Each subject also underwent cerebral magnetic resonance imaging (MRI) in T1-, T2-, PD-, flair-weighted protocols. Results. Patients were divided into groups: group 1 (n=12) — without ischemic injury in the ICA system, and group 2 (n=13) — with MRI signs ischemic injury history. The groups did not differ in proportion of stenosis (74,9±4,25% and 77,8±3,8%, p&lt;0,05), ICA lumen area on the stenotic lesion (1,05±0,18 mm2 and 1,14±0,17 mm2 , p&lt;0,05) and the ICA diameter at the non-stenotic region (4,30±0,32 mm and 4,9±0,29 mm, p&lt;0,05). In control group, GNL was &lt;0,75 mm2 /mm. Groups 1 and 2 significantly differed (2,47±0,41 mm2 /mm and 4,60±0,51 mm2 /mm, p&lt;0,02). In group 2, 12 out of 13 patients had GNL &gt;3,35 mm2 /mm, and, in group 1, 9 out of 12 — less than 3,35 mm2 /mm. GNL did not correlate significantly with other parameters of ICA stenosis. Two patients with the highest GNL in each group (5,5 and 8,6 mm2 /mm) had a fatal ischemic stroke within six monthsConclusion. Firstly, proposed parameter of stenosis hemodynamic severity GNL is independent, informative and prognostically important indicator for carotid artery atherosclerotic lesion.

Gender Features of the Course of Atherosclerotic Lesion of Carotid Arteries

Gender Features of the Course of Atherosclerotic Lesion of Carotid Arteries

Screening test for extracranial carotid lesions' detection in patients of an outpatient vascular clinic.

Purpose The objective of the study was to evaluate the frequency and severity of atherosclerotic lesions in extracranial sections of carotid arteries and to determine the level of the correlation between these lesions and symptoms of cerebral ischemia. Secondly, to identify the most common risk factors of ischaemic stroke occurrence in population of patients of vascular outpatient clinic. Material and Methods Prospective study was conducted on a group of 1,000 people (217 women and 783 men), aged 50 to 86 years, the average age was 62 years (± 9.95). Results Atherosclerotic lesions of carotid arteries were observed in 670 examined people (67%). In 63 cases (6.3%) carotid artery occlusion was revealed. Patients with symptomatic carotid artery stenosis more frequently were addicted to cigarettes and suffered from hypertension in comparison to asymptomatic group. A statistically significant correlation between the TIA or ischemic stroke and smoking were noticed, as well as between TIA/ischemic stroke and hypertension Conclusions Among patients with atherosclerosis of peripheral arteries atherosclerotic lesions in the extracranial carotid sections occur with a high frequency. Statistically significant differences in the incidence and severity of atherosclerotic lesions in the carotid arteries were observed in this group. A statistically significant correlation was revealed between the prevalence and severity of atherosclerosis in the carotid arteries in symptomatic patients and smoking and hypertension. Performing screening in patients with atherosclerosis of the abdominal aorta and/or lower limb arteries may detect significant carotid artery stenosis, requiring surgical intervention.

IL-33/IL-33R in various types of carotid artery atherosclerotic lesions

ObjectiveInflammation plays a crucial role in the progression of atherosclerotic plaques. The aim of the study was to investigate serum levels and expression of Interleukin-33 (IL-33) and ST2 receptor in atherosclerotic plaques and to analyze correlation with the type of the carotid plaques in patients with carotid disease. MethodsThis study included 191 consecutive patients submitted for carotid endarterectomy (CEA). Preoperative serum levels of IL-33 and soluble ST2 (sST2) were measured. Atherosclerotic plaques obtained during surgery were initially histologically classified and immunohistochemical analyzes of IL-33, IL-33R, CD68 and alpha-SMA expression was performed. Ultrasound assessment of the level of carotid stenosis in each patient was performed prior to carotid surgery. Demographic and clinical data such as gender, age, smoking status, blood pressure, glycaemia, hemoglobin and creatinine levels, and comorbidities were collected and the comparisons between variables were statistically evaluated. ResultsSerum levels of IL-33 (35.86 ± 7.93 pg/ml vs.12.29 ± 1.8 pg/ml, p < 0.05) and sST2 (183 ± 8.03 pg/ml vs. 122.31 ± 15.89 pg/ml, p < 0.05) were significantly higher in the group of CEA patients vs. healthy subjects. We demonstrated abundant tissue expression of IL-33 and ST2 in atherosclerotic carotid artery lesions. The levels of IL-33 and IL-33R expression were significantly higher in vulnerable plaques and significantly correlated with the degree of inflammatory cells infiltration in these plaques (R = 0.579, p = 0.049). Immunohistochemical analysis also revealed that cells responsible for IL-33 expression are not only mononuclear cells confined to inflammatory atherosclerotic lesions, but also smooth muscle cells which gained phenotypic characteristics of foam cells and were loaded with lipid droplets. ConclusionThe obtained results confirm the importance of IL-33/ST2 axis in the process of atherosclerosis, and indicate its ambiguous function in immune response, whether as proinflammatory cytokine in advanced atherosclerotic lesions, or as profibrotic, in early lesions.

A monoclonal antibody to assess oxidized cholesteryl esters associated with apoAI and apoB-100 lipoproteins in human plasma

Atherosclerosis is associated with increased lipid peroxidation, leading to generation of multiple oxidation-specific epitopes (OSEs), contributing to the pathogenesis of atherosclerosis and its clinical manifestation. Oxidized cholesteryl esters (OxCEs) are a major class of OSEs found in human plasma and atherosclerotic tissue. To evaluate OxCEs as a candidate biomarker, we generated a novel mouse monoclonal Ab (mAb) specific to an OxCE modification of proteins. The mAb AG23 (IgG1) was raised in C57BL6 mice immunized with OxCE-modified keyhole limpet hemocyanin, and hybridomas were screened against OxCE-modified BSA. This method ensures mAb specificity to the OxCE modification, independent of a carrier protein. AG23 specifically stained human carotid artery atherosclerotic lesions. An ELISA method, with AG23 as a capture and either anti-apoAI or anti-apoB-100 as the detection Abs, was developed to assay apoAI and apoB-100 lipoproteins that have one or more OxCE epitopes. OxCE-apoA or OxCE-apoB did not correlate with the well-established oxidized phospholipid-apoB biomarker. In a cohort of subjects treated with atorvastatin, OxCE-apoA was significantly lower than in the placebo group, independent of the apoAI levels. These results suggest the potential diagnostic utility of a new biomarker assay to measure OxCE-modified lipoproteins in patients with CVD.

Surgical policy of managing patients with concomitant atherosclerotic lesions of the internal and common carotid arteries

The purpose of this study was to investigate the natural course of stenosis of the common carotid artery (CCA) after carotid endarterectomy, as well as the long-term outcomes of various methods of reconstruction of the internal carotid artery (ICA) in patients with extended atherosclerotic lesions. Presented herein are the remote retrospective and prospective results of carotid endarterectomy in a total of 78 patients with concomitant atherosclerotic lesions of carotid arteries. Depending on the degree of CCA stenosis, the patients were divided into 2 groups. Group One (n=25): stenosis of the internal carotid artery (ICA) of more than 70% and haemodynamically insignificant (30-35% stenosis) but extended (from 3.0 to 5.0 cm (Q1, Me, Q3); 3.5 cm, 4.0 cm, 5.0 cm) stenosis of the CCA. These patients underwent carotid endarterectomy (CEA) from the ostium of the ICA, during which an atherosclerotic plaque was not completely removed from the CCA because the stenosis was extended but haemodynamically insignificant. Group Two (n=53): stenosis of the ICA of more than 70% and haemodynamically significant, extended (from 7.0 to 10.0 cm (Q1, Me, Q3); 7.5 cm, 8.0 cm, 9.0 cm) stenosis of the CCA. The patients of this group were subjected to various methods of operative intervention on the ICA and CCA: carotid endarterectomy (ECA) combined with open endarterectomy from the CCA with plasty using the primary suture (n=23); carotid endarterectomy and alloreconstruction of the CCA (n=10); simultaneous eversion endarterectomy from the ICA and CCA (n=20). The remote period of follow up of patients ranged from 14 to 24 months ((Q1, Me, Q3; 19 months, 22 months, 24 months). The differences were statistically insignificant (Mann-Whitney U-test, p=0.881). In the remote postoperative period, 32% of Group One patients after previously performed carotid endarterectomy were found to have an increase in the degree of stenosis of the CCA up to a haemodynamically significant one (70% and more), thus suggesting progression of the atherosclerotic process. In Group Two patients, after plasty of the CCA with the primary suture, 21.7% of patients were diagnosed as having restenosis of the reconstruction zone up to 30%, with no neurological deficit. 20% of patients after carotid endarterectomy and alloreconstruction of the CCA were diagnosed as having restenosis of the reconstruction zone more than 70% and acute impairment of cerebral circulation with a lethal outcome. The patients after simultaneous eversion endarterectomy form the ICA and CCA in the intraoperative and postoperative periods had neither restenosis of the reconstruction zone nor neurological deficit. 32% of patients after previously performed carotid endarterectomy with the presence of extended, but haemodynamically insignificant stenosis of the CCA (30-35% stenosis) in the postoperative period were found to have progression of the atherosclerotic lesion in the form of an increased degree of stenosis up to haemodynamically significant (more than 70%), thus requiring repeat reconstructive operation. Therefore, in patients presenting with concomitant atherosclerotic lesions of the carotid arteries it is appropriate to carry out operative intervention simultaneously on the ICA and CCA, which would make it possible to considerably improve the remote postoperative results of reconstructive interventions on the carotid basin in this cohort of patients. A comparative study of the outcomes of various methods of reconstruction of carotid arteries in patients with concomitant atherosclerotic lesions of the ICA and CCA demonstrated that simultaneous eversion endarterectomy from the ICA and CCA resulted in good postoperative parameters: absence of restenosis and neurological deficit in the remote period of follow up.

Гендерные особенности течения атеросклеротического поражения сонных артерий

Гендерные особенности течения атеросклеротического поражения сонных артерий

Influence of multiple stents on periprocedural stroke after carotid artery stenting in the Carotid Revascularization Endarterectomy versus Stent Trial (CREST)

BackgroundIn the Carotid Revascularization Endarterectomy versus Stent Trial (CREST), carotid artery atherosclerotic lesion length and nature of the lesions were important factors that predicted the observed difference in stroke rates between carotid endarterectomy and carotid artery stenting (CAS). Additional patient-related factors influencing CAS outcomes in CREST included age and symptomatic status. The importance of the operator's proficiency and its influence on periprocedural complications have not been well defined. We evaluated data from CREST to determine the impact of use of multiple stents, which we speculate may be related to technical proficiency. MethodsCREST includes CAS performed for symptomatic ≥50% carotid stenosis and asymptomatic ≥70% stenosis. Both symptomatic and asymptomatic patients were enrolled in the trial and in the lead-in registry. Data from patients enrolled in the CREST registry and randomized trial from 2000 to 2008 were reviewed for patient- and lesion-related characteristics along with number of stents deployed. The occurrence of 30-day stroke and demographic and clinical features were recorded. Odds ratios for 30-day stroke associated with the use of multiple stents were calculated in univariate analysis and on multivariable analysis after adjustment for demographics (age, sex, symptomatic status), lesion characteristics (length, ulceration, eccentric, percentage stenosis), and risk factors (diabetes, hypertension, dyslipidemia, and smoking). ResultsThe registry (n = 1531) and trial (n = 1121) enrolled 2652 patients undergoing CAS. The mean age was 69 years; 36% were women, and 38% were symptomatic. The mean diameter stenosis was 78%, and the mean lesion length was 18 mm (±standard deviation, 8 mm). Risk factors included hypertension (85%), diabetes (32%), dyslipidemia (84%), and smoking (23%). All patients received Acculink stents (Abbott Vascular, Abbott Park, Ill) that were 20, 30, or 40 mm in length (straight or tapered) and Accunet (Abbot Vascular) embolic protection when possible. Most patients received one stent (n = 2545), whereas 98 patients received two stents and 9 patients received three stents (P < .001) to treat the lesion. Patients receiving more than one stent were older (P = .01) but did not differ in other demographic or risk factors. Strokes occurred in 118 (4.5%) of all CAS procedures, in 102 (4%) with the use of one stent, and in 16 (15%) with the use of two or three stents. After adjustment for demographics, lesion characteristics, and risk factors, the use of more than one stent resulted in 2.90 odds (95% confidence interval, 1.49-5.64) for a stroke. ConclusionsAlthough we know that lesion characteristics (length, ulceration) play an important role in CAS outcomes, in this early experience with carotid stenting, a significant and independent relationship existed between the number of stents used and procedural risk of CAS. We postulate that this was an indicator of the operator's inexperience with the procedure.