Spotty Carotid Plaques Are Associated with Inflammation and the Occurrence of Cerebrovascular Symptoms (original) (raw)
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European Journal of Vascular and Endovascular Surgery, 2001
Objectives: to investigate the inflammatory response within intact carotid plaques from carotid eversion endarterectomy (CEE) to determine the relationship between immunohistological plaque morphology and ischaemic cerebrovascular symptoms. Material and methods: intact CEE plaques from 71 patients with high-grade (>70%) stenosis undergoing CEE (group I, symptomatic, n=42; group II, asymptomatic, n=29) and 12 normal postmortem arteries (control group) were analysed with ). Both groups were matched for gender, age, risk factors, degree of carotid artery stenosis. Plaques were measured using a semiquantitative score system in a blinded fashion by two observers. Statistical analysis of the group differences were performed by using the Kruskal-Wallis test and the Multitest Procedure with Permutation-Testing. Significance was taken as a p<0.05. Results: there were significantly more inflammatory cells, an overexpression of P-selectin and the procoagulatory markers thrombomodulin and tissue factor in symptomatic compared to both asymptomatic plaques and the ones of the control group. In both groups there was no significance for ICAM-1, VCAM-1, macrophages and co-stimulatory molecule CD40. There was also no significance for any factor between the asymptomatic and the control group. However, the differences between the symptomatic and the asymptomatic group were highly significant for all factors. Conclusion: these data suggest that structural changes and inflammatory damage within the individual plaque seems to be a critical step in promoting plaque rupture with embolic sequelae.
Annals of Vascular Surgery, 2020
Background: The aim of this study is to investigate the correlation of clinical and ultrasound parameters with characters of vulnerable atherosclerotic carotid plaque, as evaluated at preoperative magnetic resonance angiography (MRA), in patients submitted to carotid endarterectomy (CEA), in order to develop a clinical risk score for plaque vulnerability. Methods: Preoperative data of patients submitted to CEA for significant carotid stenosis from January 1, 2012 to December 31, 2016 were retrospectively collected. The available case series was randomly divided into 2 groups, including a training (60%) and a validation series (40%). Data of plaque vulnerability were assessed at preoperative MRA scans. Univariate analysis was used on the training series to correlate the preoperative covariates available to the features of plaque vulnerability. Therefore, a backward selection procedure was performed again on the training series and on the validation series to assess if the same variables were associated to data of plaque vulnerability, in order to obtain a prediction model for the risk of plaque vulnerability. Odds ratios (ORs) with 95% confidence intervals were reported. P values <0.05 were considered statistically significant. Results: The training case series consisted of 352 patients, while the validation case series of 248 patients. After univariate analysis and logistic regression, on the training and the validation series respectively, 6 variables were significantly associated to features of vulnerable plaque at preoperative MRA. These included male sex (OR 2.05), diabetes mellitus (OR 3.06), coronary artery disease (OR 1.95), neutrophil/lymphocyte ratio (OR 17.99), platelet counts (OR 1.03), and gray-scale median value (OR 0.84). A nomogram was then obtained from the final logistic model, in order to predict the probability of the presence of vulnerable carotid plaque, using a weighted points system. This risk score was then applied to the validation series. The validation data were found to have a C-index of 0.934.
Degree of carotid plaque calcification in relation to symptomatic outcome and plaque inflammation
Journal of Vascular Surgery, 2004
Objective: We undertook this study to quantitate differences in the degree of calcification between symptomatic and asymptomatic plaques removed at carotid endarterectomy (CEA) and to determine associated extent of plaque macrophage infiltration, a histopathologic feature of plaque instability. Methods: CEA plaques (n ؍ 48) were imaged at 1.25-mm intervals with spiral computed tomography (CT; 10-15 images per plaque). Indications for CEA were transient ischemic attack (n ؍ 16), stroke (n ؍ 5), amaurosis (n ؍ 4), and critical asymptomatic stenosis (n ؍ 23). The percent area calcification for each plaque was determined in spiral CT serial sections and averaged for each plaque. In 31 of 48 plaques macrophage infiltration was quantitated in corresponding histologic sections with immunohistochemical techniques. Results: The mean (؎ SD) age of patients with symptomatic and asymptomatic plaques was 66 ؎ 7 years vs 71 ؎ 7 years, respectively, and degree of stenosis was 76% versus 82%, respectively (P ؍ .05). Atherosclerosis risk factors were similar between groups. Percent plaque area calcification was twofold greater in asymptomatic versus symptomatic plaques (48% ؎ 19% vs 24% ؎ 20%, respectively; P < .05). At receiver operating characteristic curve analysis, 80% of symptomatic plaques were below and 87% of asymptomatic plaques were above a cutoff point of 30% plaque area calcification. Macrophage burden was greater in the symptomatic plaques than in the asymptomatic plaques (52% vs 23%; P < .03). A strong inverse relationship between the degree of plaque calcification and macrophage infiltration was found in critical carotid stenoses (r ؍ ؊0.87; P < .001). Conclusions: Symptomatic plaques are less calcified and more inflamed than asymptomatic plaques. Regardless of clinical outcome, a strong inverse correlation was found between the extent of carotid plaque calcification and the intensity of plaque fibrous cap inflammation as determined by the degree of macrophage infiltration. Carotid plaque calcification is associated with plaque stability, and is a potential spiral CT in vivo quantitative marker for cerebrovascular ischemic event risk. (J Vasc Surg 2004;40:262-9.)
Circulation: Cardiovascular Imaging, 2012
Background-Several high-risk morphological features (HRM) of plaques, especially in combination, are associated with an increased risk of a clinical event. Although plaque inflammation is also associated with atherothrombosis, the relationship between inflammation and number of HRM is not well understood. Methods and Results-Thirty-four patients underwent 18 flurodeoxyglucose positron emission tomography (FDG-PET) imaging, and carotid atherosclerotic inflammation was assessed (target-to-background ratio). Additionally, in a subset of 10 subjects with carotid stenosis who underwent carotid endarterectomy, inflammation was histologically assessed (CD68 staining). Vessel wall morphology was examined using computed tomography for the presence of visible plaque and presence of 3 HRM: positive remodeling, luminal irregularity, and low attenuation. A total of 100 vascular segments were analyzed, of which 69 contained visible plaque (26 plaques with Ն1 HRM). Inflammation, by FDG uptake (target-to-background ratio), was higher in plaques with (versus without) HRM (meanϮSEM: 2.21Ϯ0.20 versus 1.66Ϯ0.07, Pϭ0.0003) and increased with the number of HRM observed (PϽ0.001 for trend). Similarly, inflammation within atherosclerotic specimens (% CD68 staining) was higher in plaques with (versus without) HRM (median [interquartile range]: 10 [0, 19.85] versus 0 [0, 1.55], Pϭ0.01) and increased with the number of HRM observed (PϽ0.001 for trend). Conclusions-Inflammation, as assessed by both FDG uptake and histology, is increased in plaques containing HRM and increases with increasing number of HRM. These data support the concept that inflammation accumulates relative to the burden of morphological abnormalities.
Ultrasonographic Risk Score of Carotid Plaques
European Journal of Vascular and Endovascular Surgery, 2002
Objective: to determine the relative significance of ultrasonographic parameters of carotid plaques to develop an Activity Index (AI) which could correlate with clinical findings. Method: two hundred and fifteen plaques in 141 patients underwent ultrasonography and computer-assisted structural analysis. In half the patients (group 1), plaques were classified as either homogeneous and heterogeneous and ultrasonographic appearances related symptomatic (SP) or asymptomatic (AP) station. The probability of SP for each ultrasound parameter was used to define an Activity Index (AI). The AI was then applied the second half of patients (Group 2) to assess the value of AI in determining symptomatic station. Results: the parameters with highest morbility were surface disruption, severe stenosis and low grey scale median and, additionally in heterogenous plaques heterogeneity and the presence of a juxta-luminal echolucent area. The power in group 2 of AI to identify symptomatic plaques was determined. Mean AI was for SP-75 (41±100) and for AP-43 (22±100); 78% of SP have AI 4 60 and 70% of AP have AI 5 50. The cut-off point between the two groups was 52. ROC curve analysis of the AI were obtained to determine its diagnostic accuracy. Conclusion: Activity Index is an objective parameter of plaque echostructure that positively correlates with symptoms. AI may contribute to better selection for treatment of patients with carotid artery disease.
Determinants of Carotid Plaque Occurrence
Cerebrovascular Diseases, 2006
Background: Increased carotid intima media thickness (CIMT) is frequently associated with established modifiable and non-modifiable cardiovascular risk factors, and is thought to be an independent predictor of ischemic cerebrovascular and cardiac events. The presence of carotid plaque is considered an established feature of atherosclerosis. There exist few longitudinal data on the predictive role of CIMT in the occurrence of carotid plaque. Methods: We restudied the survivors of a cohort of the San Daniele Project, a large randomized general population study, investigated in 1990 regarding the prevalence and determinants of carotid atherosclerosis. Using ultrasonography, we determined in 1,193 subjects (548 men and 645 women), the common carotid IMT and the presence of non-stenotic and stenotic plaque. Results: In 795 subjects without plaques or previous ischemic events at baseline, we found in multivariate analysis that CIMT ≧1 mm, age, hypertension and history of smoking are signi...
European Journal of Vascular and Endovascular Surgery, 2011
Introduction: Indication to carotid revascularisation is commonly determined by percent of stenosis as well as neurological symptoms and clinical conditions. High plaque embolic potential is defined as 'vulnerability'; however, its characterisation is not universally used for carotid revascularisation. We investigated the role of contrast-enhanced ultrasonography (CEUS) to identify carotid vulnerable plaque. Methods: Patients undergoing carotid endarterectomy were preoperatively evaluated by cerebral computed tomography (CT) scan and CEUS. Contrast microbubbles detected within the plaque indicated neovascularisation and were quantified by decibel enhancement (dB-E). Plaques were histologically evaluated for five features: (microvessel density, fibrous cap thickness, extension of calcification, inflammatory infiltrate and lipid core) and blindly scored 1e5 to assess plaque vulnerability. Analysis of variance (ANOVA), Fisher's and Student's t-test were used to correlate patients' characteristics, histological features and dB-E. Results: In 22 patients, dB-E (range 2e7.8, mean 4.85 AE 1.9 SD) was significantly greater in symptomatic (7.40 AE 0.5) vs. asymptomatic (3.5 AE 1.4) patients (p Z 0.002). A higher dB-E was significantly associated with thinner fibrous cap (<200 mm, 5.96 AE 1.5 vs. 3 AE 1, p Z 0.01) and greater inflammatory infiltrate (3.2 AE 0.9 vs. 6.4 AE 1.2, p Z 0.03). Plaques with vulnerability score of 5 had significantly higher dB-E compared with those with vulnerability score of 1 (7.6 AE 0.2 vs. 2.5 AE 0.6, respectively, p Z 0.001). Preoperative ipsilateral embolic lesions at CT were correlated with higher dB-E (5.96 AE 1.5 vs. 3.0 AE 1.0, p Z 0.01). Conclusion: CEUS with dB-E is indicative of the extent of plaque neovascularisation. It can be used therefore as a marker for vulnerable plaque. ª