Symptomatic Carotid Occlusive Disease Research Articles

Abstract 290: Ccr2 Expression Is Increased In Patients With Symptomatic Carotid Arterial Occlusive Disease

Objectives: Chemokines and their receptors play critical roles in the progression of atherosclerosis. The chemokine receptor, C-C chemokine receptor type 2 (CCR2), mediates an essential role in the differentiation of pro-inflammatory monocytes into macrophages. Recent studies suggest that proinflamatory macrophages in plaques predict plaque progression. While there is no clinical consensus on which patient with asymptomatic carotid artery stenosis would benefit from carotid endarterectomy (CEA), we hypothesized that CCR2 plaque content may predict plaque progression. Methods: Carotid plaque of ten patients undergoing elective CEA were harvested from the operating room, paraffin-embedded, sectioned into 5μm segments, immuno-stained for CCR2 and CD68, and imaged. Three 200х500μm regions-of-interest (ROIs) were randomly selected within 200μm of the lumen (superficial intima), outside 200μm of the lumen (deep intima), and the arterial media. Two independent observers evaluated the number of CCR2 and/or CD68 positive cells. Counts in each ROI were averaged and analyzed with Student’s t-test. Results: Patients with symptomatic carotid artery stenosis (6/10) demonstrated higher CCR2 and CCR2-CD68 double positive cells within the superficial intima of carotid artery plaques (A, p<0.05, n=10). Similarly, patients with symptomatic disease also showed increased CCR2 in the plaque media (B, p<0.05, n=10). Interestingly, we also observed a higher number of CCR2 positive cells in the media layer of smokers (6/10) compared to non-smokers (C, p<0.05, n=10). Conclusions: Our study demonstrates the close association between CCR2 cellular content and the incidence of symptomatic carotid artery disease. Additionally, CCR2 plaque content appears to correlate with risk-factors such as smoking. These studies have important implications regarding the impact of immune modulation on carotid plaque vulnerability in patients with asymptomatic carotid artery stenosis.

Factors Influencing Long-Term Blood Flow in Extracranial-to-Intracranial Bypass for Symptomatic Internal Carotid Artery Occlusive Disease: A Quantitative Study.

Maintaining the patency of extracranial-to-intracranial (EC-IC) bypass is critical for long-term stroke prevention. However, reports on the factors influencing long-term bypass patency and quantitative assessments of bypass patency are limited. To quantitatively evaluate blood flow in EC-IC bypass using four-dimensional (4D) flow magnetic resonance imaging (MRI) and investigate factors influencing the long-term patency of EC-IC bypass. Thirty-six adult Japanese patients who underwent EC-IC bypass for symptomatic internal carotid or middle cerebral artery occlusive disease were included. We examined the relationships between decreased superficial temporal artery (STA) blood flow volume and perioperative complications, long-term ischemic complications, patient background, and postoperative antithrombotic medications in patients for whom STA flow could be quantitatively assessed for at least 5 months using 4D flow MRI. The mean follow-up time was 54.7 ± 6.1 months. One patient presented with a stroke during the acute postoperative period that affected postoperative outcomes. No recurrent strokes were recorded during long-term follow-up. Two patients died of malignant disease. Seven cases of reduced flow occurred in the STA, which were correlated with single bypass (P = .0294) and nonuse of cilostazol (P = .0294). STA occlusion was observed in 1 patient during the follow-up period. Hypertension, age, smoking, dyslipidemia, and diabetes mellitus were not correlated with reduced blood flow in the STA. Double anastomoses and cilostazol resulted in long-term STA blood flow preservation. No recurrence of cerebral infarction was noted in either STA hypoperfusion or occlusion cases.

Ccr2 Expression Is Increased in Patients with Symptomatic Carotid Arterial Occlusive Disease

Ccr2 Expression Is Increased in Patients with Symptomatic Carotid Arterial Occlusive Disease

P3714Cerebral blood flow and cognitive functioning in the heart-brain axis

Abstract Background Recent studies suggest that cardiovascular disease and dementia are closely related, which led to the concept of a “heart-brain axis”. Dysfunction in any component of the heart-brain axis could be a risk factor for the development of brain damage and consequently to the development of cognitive impairment. In the Heart-Brain study, we focus on vascular cognitive impairment (VCI), symptomatic carotid occlusive disease (COD) and heart failure (HF) as three extreme phenotypes of haemodynamic dysfunction in different components of the heart-brain axis (i.e. heart – carotids – brain). We compared values of cerebral blood flow (CBF), measured with arterial spin labeling (ASL) between patients with HF, COD and VCI and investigated the association between CBF and cognitive functioning. Methods We included 442 participants (129 VCI; 75 COD; 124 HF; and 114 controls) from the Heart-Brain Study (67±9 yrs; 38% F; MMSE 28±2). We used 3T pseudo-continuous ASL to estimate whole-brain and regional partial volume-corrected CBF. Using a standardized neuropsychological assessment, we measured global cognitive functioning and four cognitive domains. Compound z-scores were constructed for each cognitive domain. We investigated associations using linear regression analyses, adjusted for age, sex, education, center and diagnosis. Subsequently, we stratified for diagnosis. Results Whole-brain and regional CBF values were lowest in patients with COD, followed by VCI and HF, compared to controls. Global cognitive functioning was lowest in patients with VCI, followed by COD and HF, compared to controls. Overall, we found hardly any association between whole-brain or regional CBF values and cognitive functioning (standardized beta [stb] = 0.00–0.10, p>0.05). Subsequent stratification for diagnosis showed no association between whole-brain or regional CBF and cognitive functioning in any participant group. Conclusions Our results suggest that reduced CBF is not the major explanatory factor underlying impaired cognitive functioning in patients with disorders along the heart-brain axis. The predisposition of cognitive impairment in these patients is likely to be driven by other (haemodynamic) mechanisms than CBF. Acknowledgement/Funding We acknowledge the support of the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation (CVON 2012-06 Heart Brain Connection), Du

Local Cerebral Hemodynamics after Superficial Temporal Artery-Middle Cerebral Artery Bypass in Patients with Symptomatic Carotid Occlusions.

Context:Physiological insights into blood flow alterations in cortical vessels after superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery are important for the prognosis of bypass sustainability and hemodynamic patency.Aims:This study aims to assess the impact of STA-MCA bypass on local hemodynamics for patients with symptomatic carotid occlusions and Moyamoya disease.Settings and Design:This article presents a prospective nonrandomized study of intraoperative blood flow measurements in cortical branches of MCA and donor vessel before and after cerebral revascularization.Materials and Methods:Evaluation of local hemodynamic parameters was established for 112 patients with symptomatic carotid occlusive disease and cerebrovascular insufficiency during STA-MCA bypass surgery. We used intraoperative Doppler ultrasonography (89 patients – 72%), flowmetry (56 cases – 50%), and in 33 cases both methods. For physical justification of observed facts, we performed computational simulation with OpenFOAM CFD framework using Navier-Stokes nonstationary hemodynamic model.Statistical Analysis Used:All calculations were performed with IBM SPSS Statistics version 10.0 software. We used parametric (Z-test and Student's t-test) and nonparametric models (Wilcoxon, Mann–Whitney). For categorical values, we used Fisher's exact test.Results:Local cerebral hemodynamics after revascularization surgery significantly depended on initial perfusion deficit and the ability of bypass to reverse the blood flow in proximal parts of cortical artery (86 cases, 77%). Mechanism of cortical blood flow alteration was related to donor vessel cut flow value and potential consumption threshold of acceptor artery.Conclusions:Knowledge of hemodynamic principles of flow redistribution after STA-MCA bypass is important to improve bypass stainability and leads to better revascularization results.

A Modified Encephalo-Duro-Synangiosis Technique Induced Neovascularization in Symptomatic Atherosclerotic Carotid Artery Occlusion: A Phase I trial

To the best of our knowledge, the present study is the first to assess the safety and feasibility of a modified encephalo-galeo-duro-synangiosis operation in patients with atherosclerotic carotid artery occlusion. Eight patients who had experienced new ipsilateral cerebrovascular events after the diagnosis of carotid artery occlusion were recruited. To facilitate extracranial-to-intracranial collateralization, 5 or 6 burr holes were made, and the dura mater and arachnoid were opened. The patients were closely monitored for complications and underwent conventional angiography, magnetic resonance imaging, and perfusion-weighted magnetic resonance imaging at baseline and 1 year of follow-up. After 10 years, the patients who were still alive were interviewed and assessed for functional outcomes and neurological status. No surgery-related adverse events were observed, apart from temporary headache and subcutaneous effusion. Four of six patients had developed an extracranial-to-intracranial collateral blood vessels on angiography, and these patients had no incident ischemic events during the follow-up period. During the long-term follow-up period (10 years), 3 patients had died. Of those living, 4 of the 5 patients reported total resolution of the symptoms, with no incident ischemic events. One patient still experienced disability from an ischemic stroke that occurred as a result of the 1-year follow-up angiography. Encephalo-duro-galeo-synangiosis for symptomatic carotid occlusion seems to be safe and feasible and might be able to induce extracranial-to-intracranial collaterals in patients with carotid artery occlusion. Further studies are needed to define the optimal therapeutic window and yield of burr hole surgery in the treatment of symptomatic carotid occlusive disease as an adjuvant to extracranial-intracranial bypass.

Abstract 509: Screening for Carotid Occlusive Disease in Patients With Mild Peripheral Vascular Disease

Objectives: Peripheral vascular disease (PVD) is a systemic disorder, which can affect all territories of arteries. In order to maximize screening survey yield: we aimed to describe the association between positive lower extremity (LE) non-invasive flow studies in symptomatic patients and occult carotid occlusive disease (COD). Methods: A retrospective chart review was performed on 420 patients who underwent carotid duplex ultrasound and non-invasive flow studies (NIFS; aka Pulse volume recordings) for evaluation of COD and LE PVD respectively. Additional clinical variables collected included age, gender, and indication for NIFS and indication for carotid duplex. The respective studies were performed within a year of each other. Statistical analysis was performed using SPSSv20 software and SAS statistical software. Univariate analysis was performed using Mann-Whitney, student t-test and receiver operating curve (ROC). Results: 66% (266/420) of the patients were male and 43% (181/420) of patients had documented history of bruit. Patients with mild PVD (ABI between 0.81 and 1) were more likely to have clinically significant COD than patients with moderate to severe PVD (ABI < 0.8) (25% vs 16.19%, P=0.03). Therefore, severity of peripheral vascular disease did not correlate with likelihood of clinically significant COD (p>0.05). ROC analysis was performed (AUC=0.602, p=0.05). Low ABI 0.50 was found to be 92% sensitive (Se) but only 14% specific (Sp). The optimal ABI cutoff point for predicting COD was 0.95 (Se=40%,Sp 60%, Youden’s index 0.194) Conclusion: Therefore, routine screening for COD in patients with lower extremity peripheral vascular disease is unlikely to uncover clinically significant carotid stenosis. These findings do not indicate a population of patients for which a combined prospective screening is warranted.

Management of Bilateral Carotid Occlusive Disease

Background: Symptomatic bilateral internal carotid occlusive disease is a rare but potentially devastating entity. Medical therapy alone is associated with high rates of mortality and recurrent stroke. The optimal management of this disease remains poorly understood. Methods: A retrospective review of a prospectively maintained database was conducted for patients who presented with an acute stroke in the setting of bilateral carotid occlusive disease between May and October 2013. Results: We identified 3 patients. The admission National Institutes of Health Stroke Scale score ranged from 4 to 7. All patients had small- to moderate-sized infarcts in the anterior circulation on presentation. Angiography confirmed bilateral internal carotid occlusions with collateral filling via the posterior communicating artery and retrograde filling via external carotid artery supply to the ophthalmic artery. All patients were initially managed with permissive hypertension and anticoagulation followed by carotid angioplasty and stenting. At 1-year follow-up, all patients demonstrated a modified Rankin scale score of 0-1. Conclusions: Carotid stenting may be a safe and effective therapy for patients presenting with symptomatic bilateral carotid occlusions.

慢性期脳虚血性病変に対して安全確実にSTA-MCAバイパス術を完遂するための外科的治療戦略

Extracranial-intracranial (EC-IC) bypass is one of the most fundamental techniques for cerebrovascular surgery. We describe our surgical results and strategy for performing the EC-IC bypass safely and precisely in patients with chronic stage ischemia. Surgical indications were decided for symptomatic internal carotid or middle cerebral artery occlusive disease with misery perfusion detected using quantitative single-photon emission computed tomography. Antiplatelet medications were continued, and intravenous hyperosmotic colloid infusion was started 1 week before operation. Target recipient M4 arteries were superimposed on the superficial temporal artery and cranial bone. Preparation of the superficial temporal artery was performed by using an ultrasound instrument (Harmonic Scalpel®). The craniotomy site was located under the supratemporal line. Various anastomotic techniques were adopted, including continuous, running, and intermittent suturing methods. The second target recipient artery was confirmed using intra-arterial indocyanine green videoangiography. Hyperbaric oxygen therapy was performed for wound problems. Forty patients (43 sides) underwent EC-IC bypass between September 2010 and March 2015 (mean age, 64.5 years; 28 men and 12 women; double bypass in 35 patients and single bypass in eight). Postoperative complications were chronic subdural hematomas and skin problems in five patients each. None of the patients had permanent deficit. Well-drained operative field and steady hand movements are necessary to perform safe and secure bypass procedures. The various technical tips and surgical strategies that we have suggested can contribute to improving surgical results.

Altered Low Frequency Oscillations of Cortical Vessels in Patients with Cerebrovascular Occlusive Disease – A NIRS Study

Analysis of cerebral autoregulation by measuring spontaneous oscillations in the low frequency spectrum of cerebral cortical vessels might be a useful tool for assessing risk and investigating different treatment strategies in carotid artery disease and stroke. Near infrared spectroscopy (NIRS) is a non-invasive optical method to investigate regional changes in oxygenated (oxyHb) and deoxygenated hemoglobin (deoxyHb) in the outermost layers of the cerebral cortex. In the present study we examined oxyHb low frequency oscillations, believed to reflect cortical cerebral autoregulation, in 16 patients with both symptomatic carotid occlusive disease and cerebral hypoperfusion in comparison to healthy controls. Each hemisphere was examined with two NIRS channels using a 3 cm source detector distance. Arterial blood pressure (ABP) was measured via a finger plethysmograph. Using transfer function analysis ABP-oxyHb phase shift and gain as well as inter-hemispheric phase shift and amplitude ratio were assessed. We found that inter-hemispheric amplitude ratio was significantly altered in hypoperfusion patients compared to healthy controls (P = 0.010), because of relatively lower amplitude on the hypoperfusion side. The inter-hemispheric phase shift showed a trend (P = 0.061) toward increased phase shift in hypoperfusion patients compared to controls. We found no statistical difference between hemispheres in hypoperfusion patients for phase shift or gain values. There were no differences between the hypoperfusion side and controls for phase shift or gain values. These preliminary results suggest an impairment of autoregulation in hypoperfusion patients at the cortical level detected by NIRS.

Neovascular endothelial-cell activation: The link between angiogenesis, intimal leukocyte content, and development of symptomatic carotid occlusive disease

New blood vessels in atherosclerotic lesions are postulated to be responsible for plaque instability by acting as conduits for inflammatory cells. This study assessed the association between macrophage content of plaque caps of carotid atherosclerotic lesions, plaque vascularity, and endothelial-cell activation within these blood vessels. Carotid endarterectomy specimens from patients who underwent endarterectomy for carotid occlusive disease (ten symptomatic, six asymptomatic) were examined. Sequential transverse sections were obtained and were stained conventionally and immunohistochemically with CD 34 (an endothelial-cell marker) and CD 68 (a macrophage marker), as well as VCAM-1 and ICAM-1 (markers of endothelial-cell activation). Microvessel and macrophage counts were performed for the whole plaque and the plaque cap respectively. The differences in microvessel density, macrophage content, and ICAM-1 and VCAM-1 expression, between symptomatic and asymptomatic patients and in different plaque types were examined, as was the association between microvessel density and microvessel content of atherosclerotic lesions. Higher microvessel counts were observed in patients with symptomatic carotid occlusive disease (p < 0.01). Higher ICAM-1 and VCAM-1 expression was noted in new blood vessels in plaques obtained from patients with symptomatic carotid occlusive disease, compared with asymptomatic patients (p < 0.001 and p < 0.01 respectively). A close association was observed between macrophage content of the plaque cap and microvessel counts in atherosclerotic lesions (p < 0.0001), as well as ICAM-1 (p < 0.001) and VCAM-1 (p < 0.001) expression, in these microvessels. This study highlights the significance of neovascularity and endothelial-cell activation in the evolution of symptomatic carotid occlusive disease. Furthermore, it points to a relationship between the inflammatory process and angiogenesis within the plaque, which may be mediated through endothelial-cell activation.

Management of Stenosis of the Extracranial Internal Carotid Artery: Endarterectomy Versus Angioplasty and Stenting

Recent randomized clinical trial data support the safety and efficacy of carotid artery stenting and carotid endarterectomy for treatment of symptomatic and asymptomatic carotid occlusive disease. Endarterectomy is more effective in preventing stroke, but this may be countered by a higher risk of perioperative myocardial infarction. Age is an important determinant in selecting patients for either carotid endarterectomy or stenting. Patients older than 70years achieve better outcomes with endarterectomy, and younger patients achieve better outcomes with stenting. Comparative clinical and anatomic durability of endarterectomy and stenting will require additional follow-up from recently completed trials. The efficacy of carotid revascularization compared with modern medical therapy in asymptomatic patients remains an important and unanswered clinical question.

Problematik höhergradiger Karotisstenosen vor kardiochirurgischen Eingriffen – Konservative, katheterinterventionelle oder chirurgische Versorgung

There is a definitely increased risk of stroke during or after coronary bypass surgery in patients suffering simultaneously from carotid occlusive disease. In approximately 50 % of such cases the stroke is considered to be potentially due to the stenosis of the carotid artery. Some clinical centers have achieved good results with combined revascularization in cases of symptomatic carotid occlusive disease and in more than 80 % of non-symptomatic stenoses. However, the total rate of complications in such patients is relatively high, namely, approximately on a ten per cent level. An alternative could be an endovascular treatment with stent implantation before cardiac surgery. However, this demands specific pre-planning- due to the fact that it involves the need for inhibiting platelet aggregation. No definite recommendations can be given on the basis of available data. It would be desirable to have a randomized comparison of conservative and surgical (surgery or stenting) procedures, but this is hardly likely in view of the relatively few combined interventions. Hence, optimal treatment will continue to be determined by a multi-disciplinary team of internal medicine experts/cardiologists, surgeons, and interventional experts, individually for each patient and depending on local expertise.

Autoregulation in the Vertebrobasilar System Using Transcranial Doppler and Co2 Inhalation

Loss of cerebral hemodynamic autoregulation plays an important pathophysiological role in brain injury such as stroke.1 It has been shown that the magnitude of vasodilation in the anterior circulation serves as an indirect measure of cerebral autoregulation and that degree of vasoreactivity loss correlates with subsequent risk of stroke in symptomatic and asymptomatic carotid occlusive disease. 2–6 Similar data for the posterior circulation have not been consistent. Some evidence suggests that vertebrobasilar circulation may harbor significantly different autoregulative characteristics which could explain its susceptibility to the posterior reversible leukoencephalopathies, hypertensive encephalopathy, immunosuppressive vasculopathy, and pre-/eclampsia. 7 Our goal was to better characterize the autoregulatory profile of the vertebrobasilar circulation in healthy controls. By simultaneously assessing vasodilatory capacity (CVC) in anterior and posterior circulation, we aimed to establish normative data for the vertebrobasilar system, to compare the two circulations, and to assess for differential contributions of age, gender or blood pressure.

Randomized Clinical Trials: Impact on Clinical Practice for Symptomatic and Asymptomatic Extracranial Carotid Occlusive Disease

Carotid artery stenting (CAS) has emerged as a useful and potentially less invasive alternative to carotid endarterectomy (CEA) for the treatment of extracranial carotid stenoses. In this regard, it has been suggested that specific patient subgroups who may benefit from CAS including those with significant medical comorbidities, recurrent stenosis, anatomically inaccessible lesions, and a hostile neck. However, the purpose of this report is to evaluate whether or not CAS should replace CEA in the treatment of symptomatic and asymptomatic disease in better risk patients, also. This report contains results from recently published randomized clinical trials.

Commentary on "Randomized Clinical Trials: Impact on Clinical Practice for Symptomatic and Asymptomatic Extracranial Carotid Occlusive Disease"

Commentary on "Randomized Clinical Trials: Impact on Clinical Practice for Symptomatic and Asymptomatic Extracranial Carotid Occlusive Disease"

Randomized clinical trials: How will results influence clinical practice in the management of symptomatic and asymptomatic extracranial carotid occlusive disease?

Evaluation of the efficacy of carotid endarterectomy and stenting requires careful consideration of clinical trial methodology as applied to the primary clinical end points of the specific trial. Although publication of observational data including registries is helpful in selecting options for further study, these reports are not considered replacements for the randomized clinical trial. This article reviews methodology and results of registries and randomized clinical trials. Pending publication of larger clinical trials on the management of symptomatic and asymptomatic carotid stenosis within the next 1 to 3 years, carotid endarterectomy remains the preferred technique for cerebral revascularization. The only exceptions to this recommendation come from higher risk categories of patients; however, their identification is frequently difficult and controversial.

Cerebral Vasoreactivity: A Comparison of Color Velocity Imaging Quantification and Stable Xenon-Enhanced CT

Compromised cerebral vasoreactivity increases the risk of stroke. In this study, we sought to determine whether extracranial arterial blood flow volume measured on color velocity imaging quantification could be predictive of cerebral vasoreactivity after the administration of acetazolamide. Cerebral blood flow and extracranial arterial blood flow volume of 35 patients with symptomatic carotid occlusive disease were measured before and after the administration of acetazolamide on stable xenon CT and color velocity imaging quantification, respectively. The changes in unilateral extracranial arterial blood flow volume and respective hemispheric cerebral blood flow were compared. The mean difference in the percentage of change in flow volume, the 95% limit of agreement, and Cohen's kappa coefficient were calculated. A total of 64 unilateral extracranial arterial blood flow volume changes were successfully compared with the changes in the ipsilateral hemispheric cerebral blood flow. The mean difference in percentage of change in flow volume between the two techniques was 4.7%, with the 95% limit of agreement ranging from -90.2% to 99.7%. Cohen's kappa coefficient was 0.41 (95% confidence interval, 0.13-0.68; p = 0.001). The performance of color velocity imaging quantification for evaluating cerebral vasoreactivity is comparable to that of transcranial Doppler sonography. Because color velocity imaging quantification is not as limited as transcranial Doppler sonography, it could be an ideal complementary tool to transcranial Doppler sonography. More studies are required to define its clinical value.

Vascular Endothelial Growth Factor and Matrix Metalloproteinase 9 Expression in Human Carotid Atherosclerotic Plaques: Relationship with Plaque Destabilization via Neovascularization

Background: The aim of this study was to evaluate the potential impact of vascular endothelial growth factor (VEGF) on carotid plaque destabilization in association with matrix metalloproteinase 9 (MMP-9) production. Methods: Expression of VEGF and MMP-9 were determined immunohistochemically in 53 human endarterectomized atherosclerotic carotid plaques. The relationship to carotid plaque characteristics, clinical data and histological morphology was investigated. Results: VEGF and MMP-9 had parallel overexpression in the inflammatory cells, especially in the neovascularized plaque lesions and around the cholesterol crystals. Strong expression of VEGF was evident in symptomatic patients (p < 0.057), in high-degree stenosis (p = 0.005), and in patients with ischemic infarct in brain scan (p = 0.021). No relation was proved between molecule expression and plaque ultrasonic characteristics. Conclusions: An intense expression of VEGF and MMP-9 in carotid plaques is related to plaque instability, high degree of stenosis and presence of symptomatic carotid occlusive disease.

Neovascular endothelial-cell activation: The link between angiogenesis, intimal leukocyte content, and development of symptomatic carotid occlusive disease

New blood vessels in atherosclerotic lesions are postulated to be responsible for plaque instability by acting as conduits for inflammatory cells. This study assessed the association between macrophage content of plaque caps of carotid atherosclerotic lesions, plaque vascularity, and endothelial-cell activation within these blood vessels. Carotid endarterectomy specimens from patients who underwent endarterectomy for carotid occlusive disease (ten symptomatic, six asymptomatic) were examined. Sequential transverse sections were obtained and were stained conventionally and immunohistochemically with CD 34 (an endothelial-cell marker) and CD 68 (a macrophage marker), as well as VCAM-1 and ICAM-1 (markers of endothelial-cell activation). Microvessel and macrophage counts were performed for the whole plaque and the plaque cap respectively. The differences in microvessel density, macrophage content, and ICAM-1 and VCAM-1 expression, between symptomatic and asymptomatic patients and in different plaque types were examined, as was the association between microvessel density and microvessel content of atherosclerotic lesions. Higher microvessel counts were observed in patients with symptomatic carotid occlusive disease (p < 0.01). Higher ICAM-1 and VCAM-1 expression was noted in new blood vessels in plaques obtained from patients with symptomatic carotid occlusive disease, compared with asymptomatic patients (p < 0.001 and p < 0.01 respectively). A close association was observed between macrophage content of the plaque cap and microvessel counts in atherosclerotic lesions (p < 0.0001), as well as ICAM-1 (p < 0.001) and VCAM-1 (p < 0.001) expression, in these microvessels. This study highlights the significance of neovascularity and endothelial-cell activation in the evolution of symptomatic carotid occlusive disease. Furthermore, it points to a relationship between the inflammatory process and angiogenesis within the plaque, which may be mediated through endothelial-cell activation.