Plaques Of Symptomatic Patients Research Articles

Ultrasound diagnostic potential of carotid plaques in symptomatic and asymptomatic patients: Insights from quantitative gray-scale analysis

ObjectivesTo determine the ability of ultrasound gray-scale analysis to differentiate between carotid plaques in symptomatic and asymptomatic patients and to assess the reproducibility of carotid plaque gray-scale analysis. MethodsUltrasound B-mode images from patients with carotid plaques were retrospectively evaluated. Gray-scale mean and median values of carotid plaque echogenicity were determined via computer-assisted quantification using the histogram feature in Adobe Photoshop. Gray-scale values of the entire plaque obtained by the two observers were used to measure echogenicity. Receiver operating characteristic and independent t-test were used to determine potential cut-off for normalized gray-scale values, and whether there was a significant difference between the normalized gray-scale values of carotid plaques in symptomatic and asymptomatic patients, respectively. Inter-observer reproducibility of gray-scale values was assessed using intraclass correlation coefficient (ICC). ResultsEighty-seven carotid plaques (59 symptomatic and 28 asymptomatic) from 54 patients with carotid plaques were evaluated on ultrasound B-mode. Gray-scale mean and median cut-off values of 25 and 22 showed sensitivity of 75% (95% CI 56.6–87.3%) and specificity of 23.7% (95% CI 14.6–35.9%). Carotid plaques in symptomatic patients had significantly lower gray-scale mean (p = 0.03) and median (p = 0.04) values compared with asymptomatic patients. Inter-observer agreement for gray-scale mean and median was excellent, with ICC values of 0.998 and 0.997, respectively. ConclusionUltrasound gray-scale analysis is reproducible and represents a promising diagnostic additive tool to differentiate between carotid plaques in symptomatic and asymptomatic patients. Further research is needed to establish the clinical utility of ultrasound gray-scale analysis for carotid artery disease management.

B-mode ultrasound characteristics of carotid plaques in symptomatic and asymptomatic patients with low-grade stenosis.

Carotid plaque features assessed using B-mode ultrasound can be useful for the prediction of cerebrovascular symptoms. Therefore, the aim of this retrospective study was to determine the ability of ultrasound B-mode imaging to differentiate between carotid plaques causing less than 50% stenosis in symptomatic and asymptomatic patients. A dataset of 1,593 patients with carotid disease who underwent carotid ultrasound between 2016 and 2021 was evaluated retrospectively between January and April of 2022. A total of 107 carotid plaques from 35 symptomatic and 52 asymptomatic patients causing low-grade stenosis on B-mode images were included in the analysis. Chi-square, independent t-test and Mann-Whitney U test were used to compare the variables. There was a significant association between hypertension and the presence of cerebrovascular symptoms (p = 0.01). Predominantly hypoechoic and hyperechoic carotid plaque were significantly associated with the presence and absence of cerebrovascular symptoms, respectively (predominantly hypoechoic: p = 0.01; predominantly hyperechoic: p = 0.02). Surface irregularity was significantly associated with the presence of cerebrovascular symptoms (p = 0.02). There is was a significant difference in the carotid plaque length and area between the symptomatic and asymptomatic patients (plaque length: symptomatic median 9 mm, interquartile range [IQR] 6 mm; asymptomatic median 6 mm, IQR 4.5 mm, p = 0.01; plaque area: symptomatic median 24 mm, IQR 30 mm; asymptomatic median 14 mm, IQR 17 mm, p = 0.01); however, this difference was not significant for plaque thickness (p = 0.55), or common carotid artery intima-media thickness (p = 0.7). Our findings indicate that hypertension patients with predominantly hypoechoic carotid plaques and plaques with an irregular surface are associated with the presence of cerebrovascular symptoms. In addition, the carotid plaques in symptomatic patients were longer and larger compared to asymptomatic patients.

Abstract 347: Using Deep Convolutional Neural Networks To Automate Classification Of Carotid Plaques From Ultrasound Imaging

Background: Stroke is a devastating consequence of plaque rupture from the carotid arteries. Current management of carotid plaques involves waiting for symptoms (e.g., stroke or mini-stroke), as intervention itself has risk of stroke and not all plaques are vulnerable to rupture. There is a need to better risk-stratify plaque that causes stroke. Carotid ultrasound (US) is a non-invasive and inexpensive visualization of plaques but is limited by human interpretation. We hypothesize that convolutional neural networks (CNNs) will identify unique features of carotid plaques for automated risk stratification. Methods: Our workflow is illustrated in Fig. a. A total of 141 B-mode US images of carotid arteries were included; 64 high-risk with symptomatic carotid plaques and 75 low-risk with no significant plaque. Data was cropped and divided into training (70%) and holdout test (30%) subsets. During model training, an ensemble of ResNet-18 CNNs learned classification of low-risk and high-risk cases using five-fold stratified cross validation and was used to predict on the holdout test set. The model was evaluated using ROC-AUC and sensitivity. Saliency maps were used for model interpretability to highlight relevant pixels for model decisions. Results: The cross-validation AUC was 0.995 ± 0.010. The testing AUC was 0.909 and class-wise sensitivities were 0.88 (low-risk) and 0.79 (high-risk). The density plot (Fig. b) shows that the classifier correctly identifies both classes with confidence. Model interpretability using saliency maps (Fig. c) shows pixels corresponding to carotid artery vessel edges and in high-risk cases, carotid plaques. Conclusions: Using this proof-of-concept model, carotid US long axis images are sufficient to identify high-risk plaques in symptomatic patients - we now need to determine whether we can identify high-risk plaques before symptoms to prevent devastating stroke caused by carotid disease.

Comparison of symptomatic vertebrobasilar plaques between patients with and without Diabetes Mellitus using computed tomographic angiography and vessel wall magnetic resonance imaging.

ObjectivesDiabetes mellitus is significantly associated with posterior circulation ischemic stroke. We aimed to compare the characteristics of vertebrobasilar plaques in symptomatic patients with and without diabetes using high-resolution vessel wall magnetic resonance imaging and computed tomographic angiography.MethodsFrom April 2017 to May 2021, cases from patients with transient ischemic attack or stroke in the posterior circulation territory who underwent high-resolution vessel wall magnetic resonance imaging and computed tomographic angiography were reviewed. Characteristics of culprit vertebrobasilar plaques were compared between patients with and without diabetes. Multivariate regression analysis was performed to assess the correlation between culprit plaque characteristics and diabetes.ResultsA total of 148 patients were included and 75 patients were diagnosed with diabetes mellitus. Patients with diabetes had more intraplaque hemorrhage, calcification, spotty calcification presence, and higher calcification volume (all p < 0.05) compared with those without diabetes. Multivariate analysis demonstrated differences in the presence of intraplaque hemorrhage (p = 0.045) and number of spotty calcifications (p = 0.047) were statistically significant after adjusting for baseline characteristics.ConclusionsSymptomatic patients with diabetes have a higher incidence of intraplaque hemorrhage and larger calcification burden than those without diabetes, indicating the association of diabetes with more advanced plaque features in the posterior circulation.

Association between carotid artery plaque inflammation and brain MRI

PurposeTo explore the association between presence of inflammatory cells in the carotid plaques surgically treated and brain MRI findings. Material and methodsForty consecutive patients were prospectively analyzed. Brain MRI was performed with a 1.5 Tesla scanner and infacts (lacuna and non-lacunar) pertinence of the anterior circulation were recorded. All patients underwent carotid endarterectomy “en bloc”; carotid plaques histological sections were prepared and immuno-cytochemical analysis was performed to characterize and quantify the presence of inflammatory cells. ROC curve analysis, Pearson Rho correlation and Mann–Whitney test were applied. ResultsThe immuno-cytochemical analysis demonstrated that plaques of symptomatic patients (stroke\\TIA; n = 25) had more inflammatory cells, mainly macrophages (CD68) compared with plaques of patients without symptoms (Mann–Whitney = P < 0.001, ROC curve area = 0.901). Correlation analysis showed a statistically significant association between the number of brain non-lacunar infarcts and the entity of macrophages (P < 0.001); whereas no association with lacunar infarcts (P = 0.1934) was found. ConclusionResults of this preliminary study suggest that the presence and amount of inflammatory cells within carotid artery plaque is associated with cerebrovascular events and with the number of MRI brain detectable infarct.

Sodium-fluoride PET-CT for the non-invasive evaluation of coronary plaques in symptomatic patients with coronary artery disease: a cross-correlation study with intravascular ultrasound

ObjectivesThe aim of this study was to evaluate the 18F-sodium fluoride (18F-NaF) coronary uptake compared to coronary intravascular ultrasound (IVUS) in patients with symptomatic coronary artery disease.Background18F-NaF PET enables the assessment of vascular osteogenesis by interaction with surface hydroxyapatite, while IVUS enables both identification and quantification of intra-plaque components.MethodsForty-four patients with symptomatic coronary artery disease were included in this prospective controlled trial, 32 of them (30 patients with unstable angina and 2 patients with stable angina), representing the final study cohort, got additional IVUS. All patients underwent cardiac 18F-NaF PET/CT and IVUS within 2 days. 18F-NaF maximum tissue-to-blood ratios (TBRmax) were calculated for 69 coronary plaques and correlated with IVUS plaque classification.ResultsSignificantly increased 18F-NaF uptake ratios were observed in fibrocalcific lesions (meanTBRmax = 1.42 ± 0.28), thin-cap atheroma with spotty calcifications (meanTBRmax = 1.32 ± 0.23), and thick-cap mixed atheroma (meanTBRmax = 1.28 ± 0.38), while fibrotic plaques showed no increased uptake (meanTBRmax = 0.96 ± 0.18). The 18F-NaF uptake ratio was consistently higher in atherosclerotic lesions with severe calcification (meanTBRmax = 1.34 ± 0.22). The regional 18F-NaF uptake was most likely localized in the border region of intensive calcification. Coronary lesions with positive 18F-NaF uptake showed some increased high-risk anatomical features on IVUS in comparison to 18F-NaF negative plaques. It included a significant severe plaque burden (70.1 ± 13.8 vs. 61.0 ± 13.8, p = 0.01) and positive remodeling index (1.03 ± 0.08 vs. 0.99 ± 0.07, p = 0.05), as well as a higher percentage of necrotic tissue (37.6 ± 13.3 vs. 29.3 ± 15.7, p = 0.02) in positive 18F-NaF lesions.Conclusions18F-NaF coronary uptake may provide a molecular insight for the characterization of coronary atherosclerotic lesions. Specific regional uptake is needed to be determined by histology.

Abstract 233: CHI3L1 and Its Role in Vascular Smooth Muscle Cell Proliferation and Migration in Advanced Atherosclerosis

Objectives: Stroke is one of the leading causes for death and disability worldwide. The underlying pathomechanism is most likely a thrombotic event caused by acute rupture or erosion of an unstable plaque in the carotid artery. Vascular smooth muscle cells (VSMCs) play an important role in both, development and rupture of atherosclerotic plaques. Thus, efforts have been devoted determining the characteristics of VSMCs in atherosclerotic plaques to develop novel diagnostic and therapeutic strategies to prevent unstable plaque rupture. Methods: Laser capture microdissections of the fibrous cap of ruptured plaques in symptomatic patients (n=20) and stable plaques in asymptomatic patients (n=20) were used to perform a GeneChip 2.0 Human Transcriptome Array. CHI3L1 could be detected as the most significantly upregulated transcript in ruptured plaques. Following, immunohistochemistry was performed to compare distribution of CHI3L1-positive cells, VSMCs and macrophages in ruptured and stable plaques. In-vitro MTT-assay, Boyden Chamber assay and TUNEL assay were performed to investigate the role of this gene in human VSMC proliferation, migration and apoptosis. Results: The MTT-assay revealed that silencing of CHI3L1 lead to a decreased proliferation of human VSMCs. Further, migration was reduced in absence of CHI3L1. Immunohistochemistry of human carotid plaques indicated that in stable plaques mainly macrophages were CHI3L1-postive, whereas in unstable plaques both macrophages and VSMCs were CHI3L1-positive. In-vitro knockdown of CHI3L1 in cultured human VSMCs significantly increased CD68 expression, suggesting a potential role in transformation of VSMCs to macrophages. CHI3L1/CD68-positive cells (putative macrophages) in unstable plaques appeared hyperproliferative (Ki-67 positive). Conclusion: In summary, CHI3L1 plays a role in VSMC-regulation in atherosclerotic plaques. Expression levels in unstable plaques are increased. Further, it seems to induce proliferation as well as migration in VSMCs. Results of CHI3L1-induced CD68 expression indicate a potential role in VSMC-macrophage transformation. &lt;!--EndFragment--&gt;

Plaque distribution of low-grade basilar artery atherosclerosis and its clinical relevance

BackgroundThe underlying pathophysiology of BA distribution is unclear and intriguing. Using high-resolution magnetic resonance imaging (HR-MRI), we sought to explore the plaque distribution of low-grade basilar artery (BA) atherosclerosis and its clinical relevance.MethodsWe retrospectively analyzed the imaging and clinical data of 61 patients with low-grade atherosclerotic BA stenosis (<50%). On HR-MRI, the plaques were categorized based on the involvement of the ventral, dorsal, or lateral sides of BA wall. A culprit plaque was defined if it was on the same slice or neighboring slices of symptomatic pontine infarcts and played a probable causal role (dorsal plaques with median pontine infarcts or lateral plaques with ipsilateral pontine infarcts). The relationships between plaque distribution and clinical presentations were analyzed.ResultsTwenty-five symptomatic and thirty-six asymptomatic BAs with 752 HR-MRI image slices were studied. The average length of BA atherosclerosis plaques was 12.16 ± 5.61mm (10.30 ± 6.44mm in symptomatic and 13.46 ± 7.03mm in asymptomatic patients, p = 0.079). The plaque distribution was similar at ventral (29.0%), dorsal (37.6%) and lateral walls (33.1%). The BA plaques in symptomatic patients were more frequently located at the dorsal (42.5%) and lateral (41.2%) walls than at the ventral walls (16.1%; P < 0.05). Compared with symptomatic patients, asymptomatic patients more likely had their plaques distributed at the ventral walls (P = 0.022). Culprit plaques were observed in 85.0% (17/20) pontine infarcts in symptomatic patients and only 14.3% (2/14) silent pontine infarcts in asymptomatic patients (p < 0.001).ConclusionsLow-grade BA atherosclerosis has a long distribution and evenly involves ventral, dorsal and lateral walls. The plaques at dorsal and lateral walls are associated with symptomatic pontine infarcts but not with silent infarcts.

Quantifying Intracranial Plaque Permeability with Dynamic Contrast-Enhanced MRI: A Pilot Study.

Intracranial atherosclerotic disease plaque hyperintensity and/or gadolinium contrast enhancement have been studied as imaging biomarkers of acutely symptomatic ischemic presentations using single static MR imaging measurements. However, the value in modeling the dynamics of intracranial plaque permeability has yet to be evaluated. The purpose of this study was to use dynamic contrast-enhanced MR imaging to quantify the contrast permeability of intracranial atherosclerotic disease plaques in symptomatic patients and to compare these parameters against existing markers of plaque volatility using black-blood MR imaging pulse sequences. We performed a prospective study of contrast uptake dynamics in the major intracranial vessels proximal and immediately distal to the circle of Willis using dynamic contrast-enhanced MR imaging, specifically in patients with symptomatic intracranial atherosclerotic disease. Using the Modified Tofts model, we extracted the volume transfer constant (Ktrans) and fractional plasma volume (Vp) parameters from plaque-enhancement curves. Using regression analyses, we compared these parameters against time from symptom onset as well as intraplaque hyperintensity and postcontrast enhancement derived from T1 SPACE, a black-blood MR vessel wall imaging sequence. We completed analysis in 10 patients presenting with symptomatic intracranial atherosclerotic disease. Ktrans and Vp measurements were higher in plaques versus healthy white matter and similar or less than values in the choroid plexus. Only Ktrans correlated significantly with time from symptom onset (P = .02). Dynamic contrast-enhanced MR imaging parameters were not found to correlate significantly with intraplaque enhancement or intraplaque hyperintensity (P = .4 and P = .17, respectively). Elevated Ktrans and Vp values found in intracranial atherosclerotic disease plaques versus healthy white matter suggest that dynamic contrast-enhanced MR imaging is a feasible technique for studying vessel wall and plaque characteristics in the proximal intracranial vasculature. Significant correlations between Ktrans and symptom onset, which were not observed on T1 SPACE-derived metrics, suggest that Ktrans may be an independent imaging biomarker of acute and symptom-associated pathologic changes in intracranial atherosclerotic disease plaques.

NLRP3 Inflammasome Expression and Activation in Human Atherosclerosis.

BackgroundThe NLR family, pyrin domain containing 3 (NLRP3) inflammasome is an interleukin (IL)‐1β and IL‐18 cytokine processing complex that is activated in inflammatory conditions. The role of the NLRP3 inflammasome in the pathogenesis of atherosclerosis and myocardial infarction is not fully understood.Methods and ResultsAtherosclerotic plaques were analyzed for transcripts of the NLRP3 inflammasome, and for IL‐1β release. The Swedish First‐ever myocardial Infarction study in Ac‐county (FIA) cohort consisting of DNA from 555 myocardial infarction patients and 1016 healthy individuals was used to determine the frequency of 4 single nucleotide polymorphisms (SNPs) from the downstream regulatory region of NLRP3. Expression of NLRP3, Apoptosis‐associated speck‐like protein containing a CARD (ASC), caspase‐1 (CASP1), IL1B, and IL18 mRNA was significantly increased in atherosclerotic plaques compared to normal arteries. The expression of NLRP3 mRNA was significantly higher in plaques of symptomatic patients when compared to asymptomatic ones. CD68‐positive macrophages were observed in the same areas of atherosclerotic lesions as NLRP3 and ASC expression. Occasionally, expression of NLRP3 and ASC was also present in smooth muscle cells. Cholesterol crystals and ATP induced IL‐1β release from lipopolysaccharide‐primed human atherosclerotic lesion plaques. The minor alleles of the variants rs4266924, rs6672995, and rs10733113 were associated with NLRP3 mRNA levels in peripheral blood mononuclear cells but not with the risk of myocardial infarction.ConclusionsOur results indicate a possible role of the NLRP3 inflammasome and its genetic variants in the pathogenesis of atherosclerosis.

Distribution and features of middle cerebral artery atherosclerotic plaques in symptomatic patients: a 3.0 T high-resolution MRI study

Objectives:To investigate the distribution and features of middle cerebral artery (MCA) atherosclerotic plaques in patients with acute ischaemic strokes using high-resolution magnetic resonance (MR) imaging.Methods:Forty-six plaques from 44 MCAs (18 right and 26 left) in patients with acute symptomatic ischaemic strokes were studied. High-resolution MR imaging including tb1 weighted imaging (T1WI), tb2 weighted imaging (T2WI), PD weighted imaging (PDWI) and three-dimensional magnetization-prepared rapid acquisition gradient-echo (MPRAGE) sequences were used to visualise the plaques. The locations of plaques were classified into ventral, distal, superior and inferior wall of the MCA on oblique sagittal images. The thickness, area and signal intensities of plaques were recorded. The stenosis degree of MCA was calculated.Results:Among all 46 plaques, 26 plaques were located at the ventral wall (56.5%), 6 at the dorsal wall (13.0%), 9 at the superior wall (19.6%), and five at the inferior wall (10.9%). The average thickness and area of plaques were 1.37 ± 0.53 mm (range: 0.61–3.20 mm) and 3.80 ± 2.13 mm2 (range: 1.01–12.2 mm2), respectively. No significant differences in plaque thickness (P = 0.464), plaque area (P = 0.107) or stenosis degree (P = 0.563) were noted between different locations. Most of the plaques (44/46) showed iso-intensity on tbl1WI. On tbl2WI and PDWI, 24 plaques showed iso-intensity, 12 plaques showed a slightly high signal intensity (SI), and eight plaques showed a slightly low SI. Intraplaque haemorrhage was found in two plaques, with high SI on tbl1WI and MP-RAGE and high or mixed SI on tbl2WI and PDWI.Discussion:Middle cerebral artery plaques in patients with acute infarction have certain tendency to locate at ventral and superior walls. Distribution and features of plaques revealed some plaque formation characteristics and would help to understand underlying mechanisms of ischaemic events.

094 The prevalence of non-calcified plaques in symptomatic patients with zero calcium score

IntroductionAtheromatous plaque rupture is the most common cause of coronary artery thrombosis. Non-calcified plaques, with thin fibrous cap and large thrombogenic lipid core, are predominantly the most susceptible to rupture.AimsTo...

Abstract 426: Epidermal Growth Factor Receptor Increases MMP-9 Expression in Carotid Plaques of Symptomatic Patients with Carotid Stenosis

Unstable carotid atherosclerotic plaques are characterized by rupture of their fibrous cap, leading to thromboembolism and stroke. The role of MMPs in plaque disruption is not well understood. The control of MMP transcription is complex but recently, EGFR expression has been implicated in the up-regulation of MMP-9. The aim of this study was to determine the MMP-9 mRNA expression as well as other MMPs (MMP-3, -7, and -14/MT1-MMP) expression in carotid plaques as well as in isolated SMCs from asymptomatic and symptomatic patients with carotid stenosis. The MMP-2 and MMP-9 activities were determined by gelatin zymography. The mRNA transcripts of MMP-9, -3, -7, -14 and EGFR were quantified by qPCR. The activity of MMP-9 on gelatin zymograms and the MMP-9 mRNA transcripts were significantly increased in symptomatic carotid plaques and isolated SMCs compared to those from plaques of asymptomatic patients. There was a parallel increase in the mRNA transcripts of MMP-7, -3 and -14. The mRNA transcripts for EGFR were also up-regulated. These results suggest that MMP-9 may be activated by MMP-7 and -3 and thus destabilizes the symptomatic plaques of patients compared to those from asymptomatic plaques and this effect may be mediated by EGFR.

Enhanced Expression of Lp-PLA 2 and Lysophosphatidylcholine in Symptomatic Carotid Atherosclerotic Plaques

Circulating lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has emerged as a novel biomarker for cardiovascular diseases. However, the correlation between the plaque expression of Lp-PLA(2) and plaque oxidative stress, inflammation, and stability as well as the clinical presentation remains poorly defined, especially for cerebrovascular disease. Therefore, this study was performed to test the hypothesis that Lp-PLA(2) expression is higher in symptomatic than in asymptomatic carotid plaques of patients undergoing carotid endarterectomy. The expression of Lp-PLA(2) in 167 carotid artery plaques was determined by immunoblotting and immunostaining. Plaque oxidative stress, inflammation, and stability were quantified by NAD(P)H oxidase p67phox and MMP-2 immunoblotting, oxidized LDL (oxLDL) immunoreactivity, macrophage and Sirius red collagen staining. Lysophosphatidylcholine 16:0 (lysoPC) concentration was measured in 55 plaques using liquid chromatography tandem mass spectrometry. Lp-PLA(2) expression was significantly higher in plaques of symptomatic patients than asymptomatic patients (1.66+/-0.19 versus 1.14+/-0.10, P<0.05) and localized mainly to shoulder and necrotic lipid core areas in colocalization with oxLDL and macrophage content. Similarly, Lp-PLA(2) expression was related to collagen content, which was lower in plaques from symptomatic patients than in plaques from asymptomatic patients (9.1+/-2.2 versus 18.5+/-1.7% of staining/field, P<0.001). LysoPC plaque concentration was significantly higher in plaques of symptomatic than asymptomatic patients (437.0+/-57.91 versus 228.84+/-37.00 mmol/L, P<0.05). Symptomatic carotid artery plaques are characterized by increased levels of Lp-PLA(2) and its product lysoPC in correlation with markers of tissue oxidative stress, inflammation, and instability. These findings strongly support a role for Lp-PLA2 in the pathophysiology and clinical presentation of cerebrovascular disease.

Assessment of Carotid Plaque Vulnerability Using Structural and Geometrical Determinants

Because many acute cerebral ischemic events are caused by rupture of vulnerable carotid atheroma and subsequent thrombosis, the present study used both idealized and patient-specific carotid atheromatous plaque models to evaluate the effect of structural determinants on stress distributions within plaque. Using a finite element method, structural analysis was performed using models derived from in vivo high-resolution magnetic resonance imaging (MRI) of carotid atheroma in 40 non-consecutive patients (20 symptomatic, 20 asymptomatic). Plaque components were modeled as hyper-elastic materials. The effects of varying fibrous cap thickness, lipid core size and lumen curvature on plaque stress distributions were examined. Lumen curvature and fibrous cap thickness were found to be major determinants of plaque stress. The size of the lipid core did not alter plaque stress significantly when the fibrous cap was relatively thick. The correlation between plaque stress and lumen curvature was significant for both symptomatic (p=0.01; correlation coefficient: 0.689) and asymptomatic patients (p=0.01; correlation coefficient: 0.862). Lumen curvature in plaques of symptomatic patients was significantly larger than those of asymptomatic patients (1.50+/-1.0 mm(-1) vs 1.25+/-0.75 mm(-1); p=0.01). Specific plaque morphology (large lumen curvature and thin fibrous cap) is closely related to plaque vulnerability. Structural analysis using high-resolution MRI of carotid atheroma may help in detecting vulnerable atheromatous plaque and aid the risk stratification of patients with carotid disease.

D-dimer local expression is increased in symptomatic patients undergoing carotid endarterectomy

Background Although atherosclerosis is a silent widespread disease, the focal character of the lesions triggering the clinical manifestations is unquestionable. We hypothesized that symptomatic patients with advanced, unstable carotid plaques have increased local intraplaque and circulating levels of fibrin–fibrinogen related products. Methods Plaque tissue and plasma samples were studied in 106 patients undergoing endarterectomy for symptomatic and asymptomatic carotid disease. Fibrin–fibrinogen related products were evaluated by ELISA, Western-blotting, and histology. All tested parameters were compared with patient carotid symptomatology, multiple vascular risk factors (VRF), bilateral carotid pathology, ultrasound examination, and previous therapies with statins and/or antiplatelet drugs. Results In symptomatic patients, plasma D-dimer was elevated in patients with unstable carotid plaques (UNS) compared with stable (STA) ones (857 ± 121 vs. 692 ± 156 ng/ml, p = 0. 026). Furthermore, plasma D-dimer was significantly increased in patients with a coexistence of carotid and coronary artery disease, compared to others (976 ± 325 vs. 714 ± 197 ng/ml; p < 0.001). Intra-plaque D-dimer content was increased in ulcerated-complicated (UC) plaques compared with fibrous non-complicated (F) plaques in symptomatic patients (5.9 ± 1 vs. 1.8 ± 1, p < 0.001), and in patients with hypercholesterolaemia, compared with those with normal cholesterol levels (6.1 ± 1 vs. 2.9 ± 0.7; p = 0.027). However, there was no correlation between D-dimer content in the carotid plaque and plasma D-dimer levels. Conclusions Hypercholesterolemia and UC plaques appear to be associated with high fibrin intraplaque turnover as demonstrated by higher intraplaque D-dimer. Plasma markers of fibrin turnover were increased in UNS plaques, and in patients with coexisting carotid and coronary artery disease. Although, both plasma and plaque D-dimers were associated with unstable carotid disease, the usefulness of the measurement of plasma D-dimer in these patients should be confirmed by prospective studies.

Characterization of symptomatic and asymptomatic carotid plaques using high-resolution real-time ultrasonography.

High-resolution ultrasonography was used to classify carotid plaques into five different types in 72 patients with symptoms and in 49 without, and with stenosis of the origin of the internal carotid artery > 70 per cent. There were 72 plaques in the symptomatic group and 75 in the asymptomatic group. Type 1 plaques were uniformly echolucent, type 2 predominantly echolucent, type 3 predominantly echogenic, type 4 uniformly echogenic and type 5 consisted of plaques that could not be classified owing to heavy calcification and acoustic shadows. Type 1 plaque was found in 90 per cent of patients with symptoms and in 10 per cent of those without, type 2 plaque was found in 53 and 47 per cent, type 3 in 34 and 66 per cent, and type 4 in 5 and 95 per cent, respectively. The preponderance of echolucent plaques in symptomatic patients with stenosis > 70 per cent supports the hypothesis that this type of plaque is unstable and tends to embolize. In contrast, in patients without symptoms there is preponderance of echogenic plaques.

Unstable carotid plaques exhibit raised matrix metalloproteinase-8 activity.

The fibrous cap of atherosclerotic plaques is composed predominantly of type I and III collagen. Unstable carotid plaques are characterized by rupture of their cap, leading to thromboembolism and stroke. The proteolytic mechanisms causing plaque disruption are undefined, but the collagenolytic matrix metalloproteinase (MMP) -1, -8, and -13 may be implicated. The aim of this study was to quantify the concentrations of these collagenases in carotid plaques and to determine their relationship to markers of plaque instability. Atherosclerotic plaques were collected from 159 patients undergoing carotid endarterectomy. The presence and timing of carotid territory symptoms were ascertained. Preoperative embolization was recorded by transcranial Doppler. Each plaque was assessed for histological features of instability. Plaque MMP concentrations were quantified with ELISA. Significantly higher concentrations of active MMP-8 were observed in the plaques of symptomatic patients (20.5 versus 11.4 ng/g; P=0.0002), in plaques of emboli-positive patients (22.7 versus 13.5 ng/g; P=0.0037), and in those plaques showing histological evidence of rupture (20.8 versus 14.7 ng/g; P=0.0036). No differences were seen in the levels of MMP-1 and MMP-13. Immunohistochemistry, in situ hybridization, and colocalization studies confirmed the presence of MMP-8 protein and mRNA within the plaque, which colocalized with macrophages. These data suggest that the active form of MMP-8 may be partly responsible for degradation of the collagen cap of atherosclerotic plaques. This enzyme represents an attractive target for drug therapy aimed at stabilizing vulnerable plaques.

Carotid plaque spaces relate to symptoms and ultrasound scattering

We have previously found that spectral analysis of ultrasound (US) can discriminate in vitro plaques from asymptomatic and symptomatic (transient ischemic attack within previous 4 weeks) patients. That study found no differences in percentages of lipid or thrombus between the two groups by optical microscopy/planimetry. The present study was to find out if another feature from the microscopy could show a difference. The number and size of spaces resulting from cell death or new blood vessels were measured to see if they related to symptoms or could help explain US differentiation. Twelve plaques from each group were examined by optical microscopy. The sizes and concentrations of two kinds of spaces, endothelial lined (vessel spaces) and unlined (tissue spaces), were correlated both with symptoms and also with the US tissue characterization scores from the previous study. Symptomatic vs. asymptomatic plaques showed a higher concentration and a larger size: 0.87 vs. 0.21 per mm 2 ( p < 0.005) and 154 vs. 110 μm ( p < 0.02). A discriminant function of spaces with symptoms as dependent variables correctly identified 91.7% of the plaques ( p < 0.001). The concentration in plaques previously designated by US as true positive plaques or true negative was 1.21 vs. 0.22 per mm 2 ( p < 0.005). spaces were increased in plaques of symptomatic patients and were related to UTC scores. Both the lined and unlined spaces were useful as predictors. ( Jeffrey.Justin@Drexel.edu)

What's new in vascular surgery.

This article covers the period from October 2000 through September 2001 and focuses primarily on clinical advances in vascular and endovascular surgery. Surgical, medical, and radiologic journals were surveyed during this period and peer-reviewed publications form the bulk of this article. Although aortic stent graft treatment of aortic aneurysm (AAA) continues to dominate the vascular surgical literature, initial enthusiasm for this technique is now being moderated with caution and concerns centering on durability and longterm complications. Carotid angioplasty and stenting continue to enjoy enthusiastic reports as this technology advances with the introduction of cerebral protection devices, but durability again is emerging as an important issue that may limit the application of this approach. In addition to higher rates of significant restenosis on longterm followup, carotid angioplasty and stenting, to date, have failed to produce better or equivalent outcomes in comparison to wellperformed carotid endarterectomy (CEA). There have been many advances in the field of venous disease, particularly with the introduction of new antithrombotic agents and refinements in conventional antithrombotic therapy to tailor length of therapy according to risk factors and effectively prevent recurrent venous thromboembolism. Although there have been few seminal reports in the area of lower extremity arterial disease, there have been many publications that have more sharply delineated the relative benefits of surgical, interventional radiologic, and medical treatments. Outcomes analyses and epidemiologic studies are becoming increasingly important in the field of vascular disease, with many recent reports documenting that trained vascular surgeons “do it better.” CEREBROVASCULAR DISEASE Plaque morphology and noninvasive testing Tegos and colleagues characterized the echomorphology of 50% to 99% stenotic plaques in symptomatic patients and correlated computer-generated gray scale images with emboli detected by transcranial Doppler and brain CT infarction patterns. Emboli and CT scan evidence of discrete cortical infarcts were statistically more frequent in the presence of low plaque echodensity. Low plaque echodensity was more predictive of emboli and infarction than severity of carotid stenosis. In a followup study, these investigators documented that symptomatic plaques were associated with hypoechoic and predominately homogeneous echo patterns; asymptomatic ones were associated with hyperechoic and less predominant homogeneous patterns. In a corroborative study, Mathiesen and colleagues noted that echolucent carotid plaques have increased risk of ischemic cerebrovascular events independent of degree of stenosis and cardiovascular risk factors. Patients at high risk for cerebrovascular ischemic events may be identified by ultrasonographic assessment of plaque morphology. Events and factors leading to plaque instability that causes an asymptomatic plaque to become symptomatic are of considerable interest. Loftus and colleagues measured blood levels of matrix metalloproteinases (MMPs) and their inhibitors, and correlated these with the embolic potential of plaques in patients undergoing CEA. They noted that MMP-9 levels were elevated in patients with spontaneous plaque embolization. Numerous studies have reported the detection of Chlamydia pneumoniae in atherosclerotic plaques. In an interesting study, Nadareishvili and colleagues showed a preferential increase of CD8 T cells in symptomatic carotid artery plaques positive for C pneumoniae. They postulated that the presence of C pneumoniae in plaques may recruit these T cells, and that immune inflammatory responses may predispose to plaque rupture and ischemic complications. How C pneumoniae becomes incorporated in carotid plaques is anybody’s guess. But the implications of Received October 30, 2001; Accepted October 30, 2001. From the Division of Vascular Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Correspondence address: G Patrick Clagett, MD, Division of Vascular Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9157.