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Carotid occlusive disease has been related to ischaemic strokes and cerebral hypoperfusion, thus affecting patients' quality of life, mainly because of cognitive decline and depressive symptoms. Carotid revascularization techniques [carotid endarterectomy (CEA) and carotid artery stenting (CAS)] may, postoperatively, have a positive impact on patients' quality of life and mental condition, though there have been also presented elusive findings and controversial results. The aim of the present study is to evaluate the effect of carotid revascularization (CEA, CAS) on patients' psychological condition and quality of life through a baseline and follow-up examination. We present data of a group of 35 patients (age range:60-80 years, ΜA=70,26-SD=9,05) with severe, left or right, carotid artery stenosis (>75%), presented with or without symptoms, who underwent surgical treatment with CEA or CAS. Baseline and follow-up (6 months post-surgery) evaluation was conducted in order to assess patients' depressive symptoms and quality of life, through completion of the Beck Depression Inventory and WHOQOL-BREF Inventory, respectively. No statistically significant (p < 0,05) effect of the revascularization process on mood or quality of life assessment could be documented for our patients, regardless of the applied technique (CAS or CEA). Our study supports existing evidence that all of the traditional vascular risk factors represent active participants in the inflammatory process, which has also been implicated in the pathophysiology of depression as well as in pathogenesis of atherosclerotic processes. Thus we have to illuminate new links between the two nosological entities, in the crossroads of psychiatry, neurology and angiology, through the pathways of inflammatory reactions and endothelium dysfunctions. Even though the effects of carotid revascularization on patient's mood and quality of life, are often characterized by opposing results, pathophysiological processes of "vascular depression" and "post stroke depression" remain a promising interdisciplinary medical domain, sharing both scientific and clinical interests between the fields of neurosciences and vascular medicine. Our results, regarding the bilateral connection of depression and carotid artery disease, advocate a most probable causality link between atherosclerotic process and depressive symptoms, rather than justifying a direct association between depressive disorders and carotid stenosis and inferred cerebral blood flow reduction per se.

Introduction: Two of the main reasons recent guidelines do not recommend routine population-wide screening programs for asymptomatic carotid artery stenosis (AsxCS) is that screening could lead to an increase of carotid revascularization procedures and that such mass screening programs may not be cost-effective. Nevertheless, selective screening for AsxCS could have several benefits. This article presents the rationale for such a program., Areas Covered: The benefits of selective screening for AsxCS include early recognition of AsxCS allowing timely initiation of preventive measures to reduce future myocardial infarction (MI), stroke, cardiac death and cardiovascular (CV) event rates., Expert Opinion: Mass screening programs for AsxCS are neither clinically effective nor cost-effective. Nevertheless, targeted screening of populations at high risk for AsxCS provides an opportunity to identify these individuals earlier rather than later and to initiate a number of lifestyle measures, risk factor modifications, and intensive medical therapy in order to prevent future strokes and CV events. For patients at 'higher risk of stroke' on best medical treatment, a prophylactic carotid intervention may be considered.

Objective: The optimal management of patients with asymptomatic carotid stenosis (AsxCS) is enduringly controversial. We updated our 2021 Expert Review and Position Statement, focusing on recent advances in the diagnosis and management of patients with AsxCS., Methods: A systematic review of the literature was performed up to August 1, 2023, using PubMed/PubMed Central, EMBASE and Scopus. The following keywords were used in various combinations: "asymptomatic carotid stenosis," "carotid endarterectomy" (CEA), "carotid artery stenting" (CAS), and "transcarotid artery revascularization" (TCAR). Areas covered included (i) improvements in best medical treatment (BMT) for patients with AsxCS and declining stroke risk, (ii) technological advances in surgical/endovascular skills/techniques and outcomes, (iii) risk factors, clinical/imaging characteristics and risk prediction models for the identification of high-risk AsxCS patient subgroups, and (iv) the association between cognitive dysfunction and AsxCS., Results: BMT is essential for all patients with AsxCS, regardless of whether they will eventually be offered CEA, CAS, or TCAR. Specific patient subgroups at high risk for stroke despite BMT should be considered for a carotid revascularization procedure. These patients include those with severe (≥80%) AsxCS, transcranial Doppler-detected microemboli, plaque echolucency on Duplex ultrasound examination, silent infarcts on brain computed tomography or magnetic resonance angiography scans, decreased cerebrovascular reserve, increased size of juxtaluminal hypoechoic area, AsxCS progression, carotid plaque ulceration, and intraplaque hemorrhage. Treatment of patients with AsxCS should be individualized, taking into consideration individual patient preferences and needs, clinical and imaging characteristics, and cultural, ethnic, and social factors. Solid evidence supporting or refuting an association between AsxCS and cognitive dysfunction is lacking., Conclusions: The optimal management of patients with AsxCS should include BMT for all individuals and a prophylactic carotid revascularization procedure (CEA, CAS, or TCAR) for some asymptomatic patient subgroups, additionally taking into consideration individual patient needs and preference, clinical and imaging characteristics, social and cultural factors, and the available stroke risk prediction models. Future studies should investigate the association between AsxCS with cognitive function and the role of carotid revascularization procedures in the progression or reversal of cognitive dysfunction., Competing Interests: Disclosures J.F.M. is co-Principal Investigator for the Clinical Coordinating Center of the CREST-2 multicenter randomized clinical trial (U01NS080168) and Principal Investigator of the Long-term Observational Extension of participants in the CREST-2 randomized clinical trial (C2LOE; U01NS119169). M.L.S. is the Principal Investigator of the ROADSTER-3 trial and is the Chair of the TCAR Surveillance Program in the Vascular Quality Initiative. L.H.B., P.J.N., and M.M.B. are co-Principal Investigators for the 2nd European Carotid Surgery Trial (ECST-2). P.S. is a consultant for Silk Road, Philips, Surmodics, Medtronic, Boston Scientific, Cagent, and LimFlow. E.A.S. has received research grants from the Food & Drug Administration (FDA), SCAI, BD, Boston Scientific, Cook, Laminate Medical, Medtronic, Philips, and NIH/NHLBIK23HL150290. He has received Consulting/Speaker fees from Abbott, Bayer, BD, Boston Scientific, Cook, Cordis, Heartflow, Inari, InfraRedx, Medtronic, Philips, RapidAI, Shockwave, and VentureMed. D.P.M. has given talks, acted as a consultant or attended conferences sponsored by Amgen and Novo Nordisk. B.K.L. is co-Principal Investigator of the CREST-2 multicenter randomized clinical trial (U01NS080168), Principal Investigator of the CREST-2 Registry (C2R; NCT02240862) and Principal Investigator for the Asymptomatic Carotid Stenosis and Cognitive Function Study (ACCOF; CX001621). The other authors have no conflicts of interest., (Copyright © 2023 Society for Vascular Surgery. All rights reserved.)

Objective: Despite the publication of various national/international guidelines, several questions concerning the management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis remain unanswered. The aim of this international, multi-specialty, expert-based Delphi Consensus document was to address these issues to help clinicians make decisions when guidelines are unclear., Methods: Fourteen controversial topics were identified. A three-round Delphi Consensus process was performed including 61 experts. The aim of Round 1 was to investigate the differing views and opinions regarding these unresolved topics. In Round 2, clarifications were asked from each participant. In Round 3, the questionnaire was resent to all participants for their final vote. Consensus was reached when ≥75% of experts agreed on a specific response., Results: Most experts agreed that: (1) the current periprocedural/in-hospital stroke/death thresholds for performing a carotid intervention should be lowered from 6% to 4% in patients with SxCS and from 3% to 2% in patients with AsxCS; (2) the time threshold for a patient being considered "recently symptomatic" should be reduced from the current definition of "6 months" to 3 months or less; (3) 80% to 99% AsxCS carries a higher risk of stroke compared with 60% to 79% AsxCS; (4) factors beyond the grade of stenosis and symptoms should be added to the indications for revascularization in AsxCS patients (eg, plaque features of vulnerability and silent infarctions on brain computed tomography scans); and (5) shunting should be used selectively, rather than always or never. Consensus could not be reached on the remaining topics due to conflicting, inadequate, or controversial evidence., Conclusions: The present international, multi-specialty expert-based Delphi Consensus document attempted to provide responses to several unanswered/unresolved issues. However, consensus could not be achieved on some topics, highlighting areas requiring future research., Competing Interests: Disclosures D.P.M. has given talks, acted as a consultant or attended conferences sponsored by Amgen and Novo Nordisk. J.F.M. receives funding from the United States National Institute of Neurologic Disorders and Stroke for work related to running the CREST-2 clinical trial (U01NS080168) and the CREST-2 Long-term Observational Extension study (U01NS119169). E.A.S. has received research grants from the United States Food and Drug Administration, BD, Boston Scientific, Cook, CSI, Laminate Medical, Medtronic and Philips; has received consulting/speaking fees from Abbott, Bayer, BD, Boston Scientific, Cook, Cordis, CSI, Inari, Infraredx, Medtronic, Philips, Shockwave and VentureMed. H.-H.E. is a local Principal Investigator for the ROADSTER 2 trial and a scientific committee member of SPACE-1, SPACE-2 and ACST-2. T.R. is funded by grants from the National Institutes of Health (R01 MD012467, R01 NS029993, R01NS040807, 1U24NS107267), and the National Center for Advancing Translational Sciences (UL1 TR002736, KL2 TR002737). J.S.M. has received institutional research grants from Abbott, Cook, Endologix, Gore and Medtronic., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Current guidelines do not recommend screening for asymptomatic carotid artery stenosis (AsxCS). The rationale behind this recommendation is that detection of AsxCS may lead to an unnecessary carotid intervention. In contrast, screening for abdominal aortic aneurysms is strongly recommended., Methods: A critical analysis of the literature was performed to evaluate the implications of detecting AsxCS., Results: Patients with AsxCS are at high risk for future stroke, myocardial infarction and vascular death. Population-wide screening for AsxCS should not be recommended. Additionally, screening of high-risk individuals for AsxCS with the purpose of identifying candidates for a carotid intervention is inappropriate. Instead, selective screening for AsxCS should be considered and should be viewed as an opportunity to identify individuals at high risk for atherosclerotic cardiovascular disease and future cardiovascular events for the timely initiation of intensive medical therapy and risk factor modification., Conclusions: Although mass screening should not be recommended, there are several arguments suggesting that selective screening for AsxCS should be considered. The rationale supporting such selective screening is to optimize risk factor control and to initiate intensive medical therapy for prevention of future cardiovascular events, rather than to identify candidates for an intervention., Competing Interests: Declaration of Competing Interest All authors are members of the Faculty Advocating Collaborative and Thoughtful Carotid Artery Treatments (FACTCATS; available at www.FACTCATS.org) with the shared goal of optimizing stroke prevention. The views of particular FACTCATS do not necessarily reflect the views of other FACTCATS., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Despite the publication of several national/international guidelines, the optimal management of patients with asymptomatic carotid stenosis (AsxCS) remains controversial. This article compares 3 recently released guidelines (the 2020 German-Austrian, the 2021 European Stroke Organization [ESO], and the 2021 Society for Vascular Surgery [SVS] guidelines) vs the 2017 European Society for Vascular Surgery (ESVS) guidelines regarding the optimal management of AsxCS patients.The 2017 ESVS guidelines defined specific imaging/clinical parameters that may identify patient subgroups at high future stroke risk and recommended that carotid endarterectomy (CEA) should or carotid artery stenting (CAS) may be considered for these individuals. The 2020 German-Austrian guidelines provided similar recommendations with the 2017 ESVS Guidelines. The 2021 ESO Guidelines also recommended CEA for AsxCS patients at high risk for stroke on best medical treatment (BMT), but recommended against routine use of CAS in these patients. Finally, the SVS guidelines provided a strong recommendation for CEA+BMT vs BMT alone for low-surgical risk patients with >70% AsxCS. Thus, the ESVS, German-Austrian, and ESO guidelines concurred that all AsxCS patients should receive risk factor modification and BMT, but CEA should or CAS may also be considered for certain AsxCS patient subgroups at high risk for future ipsilateral ischemic stroke.

Background: The optimal antithrombotic (antiplatelet or anticoagulant) treatment of patients undergoing extracranial carotid artery interventions is a subject of debate. The aim of this multidisciplinary document was to critically review the recommendations of current guidelines, taking into consideration the results of recently published studies., Methods: The various antithrombotic strategies reported were evaluated for asymptomatic and symptomatic patients undergoing extracranial carotid artery interventions (endarterectomy, transfemoral carotid artery stenting [CAS] or transcarotid artery revascularization [TCAR]). Based on a critical review, a series of recommendations were formulated by an international expert panel., Results: For asymptomatic patients, we recommend low-dose aspirin (75-100 mg/day) or clopidogrel (75 mg/day) with the primary goal to reduce the risk of myocardial infarction and cardiovascular event rates rather than to reduce the risk of stroke. For symptomatic patients, we recommend dual antiplatelet treatment (DAPT) initiated within 24 h of the index event to reduce the risk of recurrent events. We suggest that following transfemoral CAS or TCAR, patients continue DAPT for 1 month after which a single antiplatelet agent is used. High level of evidence to support anticoagulant treatment for patients with carotid artery disease is lacking., Conclusions: The antithrombotic treatment offered to carotid patients should be individualized, taking into account the presence of symptoms, the type of intervention and the goal of the treatment. The duration and type of DAPT (ticagrelor instead of clopidogrel) should be evaluated in future trials., Competing Interests: Declaration of Competing Interest Dr. Mikhailidis has given talks, acted as a consultant or attended conferences sponsored by Amgen and Novo Nordisk. Dr. Chaturvedi reports consulting for Astra Zeneca and BrainGate and serving as an Associate Editor for Stroke, and as an Editorial Board Member of Neurology and Journal of Stroke and Cerebrovascular Diseases. The other authors report no conflicts., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Arterial stiffness and its valid index, the cardio-ankle vascular index (CAVI), have emerged as predictors of adverse cardiovascular outcomes. We investigated the relationship of the CAVI with significant carotid stenosis (> 50%) and the related cerebrovascular symptoms or carotid plaque echogenicity, assessed by ultrasound gray-scale median (GSM) score, at baseline and after carotid artery stenting (CAS). We prospectively enrolled 113 patients with carotid stenosis (70-99% for asymptomatic and > 50% for symptomatic participants) eligible for CAS. Age- and sex-matched individuals (n = 38) served as controls (CON). Clinical data, CAVI, and biochemical profile were obtained at baseline. Clinical assessment and CAVI measurement were performed 6 months after CAS. Compared with the CON group, the CAS group had a higher incidence of co-morbidities (diabetes, hypertension, and hyperlipidemia), higher CAVI values (9.94 ± 2.14 vs 7.85 ± .97 m/sec, P < .001), but a better lipid profile due to increased prescription of statins. The symptomatic CAS subgroup showed higher CAVI ( P < .001), high-sensitivity C-reactive protein ( P = .048), and osteoprotegerin ( P = .002) levels than the asymptomatic one. In multivariate analysis, CAVI at baseline was independently associated with the presence of significant carotid atherosclerosis (β = .695, P < .001), cerebrovascular events (β = .474, P < .001), and GSM score (β = -.275, P = .042). Raised CAVI values were independently associated with significant carotid stenosis and plaque vulnerability.

The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement was to reconcile the conflicting views on the topic. A literature review was performed with a focus on data from recent studies. Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients <75 years and microembolic signals on transcranial Doppler. There is growing evidence that 80-99% ACS indicate a higher stroke risk than 50-79% stenoses. Although aggressive risk factor control and BMT should be implemented in all ACS patients, several high-risk features that may increase the risk of a future cerebrovascular event are now documented. Consequently, some guidelines recommend a prophylactic carotid intervention in high-risk patients to prevent future cerebrovascular events. Until the results of the much-anticipated randomized controlled trials emerge, the jury is still out regarding the optimal management of ACS patients.

The optimal management of patients with asymptomatic carotid stenosis (ACS) is the subject of extensive debate. According to the 2017 European Society for Vascular Surgery Guidelines, carotid endarterectomy should (Class IIa; Level of Evidence: B) or carotid artery stenting may be considered (Class IIb; Level of Evidence: B) in the presence of one or more clinical/imaging characteristics that may be associated with an increased risk of late ipsilateral stroke (e.g. silent embolic infarcts on brain computed tomography/magnetic resonance imaging, progression in the severity of ACS, a history of contralateral transient ischemic attack/stroke, microemboli detection on transcranial Doppler, etc.), provided documented perioperative stroke/death rates are <3% and the patient's life expectancy is >5 years. Besides these clinical/imaging characteristics, there are additional individual, ethnic/racial or social factors that should probably be evaluated in the decision process regarding the optimal management of these patients, such as individual patient needs/patient choice, patient compliance with best medical treatment, patient sex, culture, race/ethnicity, age and comorbidities, as well as improvements in imaging/operative techniques/outcomes. The present multispecialty position paper will present the rationale why the management of patients with ACS may need to be individualized.

Background: The purpose of the study was the comparative assessment of ticagrelor and clopidogrel effects on carotid post-balloon injury (PBI) and on post carotid artery stenting (CAS) rate of in-stent restenosis (ISR) and in-stent thrombosis in atherosclerotic rabbits., Methods: Forty-eight New Zealand white rabbits on high-fat diet were randomized into 4 groups: A1: PBI and clopidogrel (30 mg/kg/d), A2: PBI and ticagrelor (21 mg/kg twice daily), B1: PBI, CAS, and clopidogrel (30 mg/kg/d), B2: PBI, CAS, and ticagrelor (21 mg/kg twice daily). All rabbits received orally aspirin (10 mg/kg/d) and interventions were performed in their right carotid arteries (RCAs). Optical coherence tomography (OCT) and carotid angiography were performed at end point, while platelet aggregation and lipid profile were measured. After euthanasia both carotids were obtained for histological examination., Results: In B1 group, 3 rabbits presented thrombotic total occlusion of the stents, while none such episode was observed in B2 group. The neointimal areas in RCAs, calculated by OCT, did not differ between A1 and A2 groups, and between B1 and B2 groups ( P > .05). From the histological findings, the intima/(media + intima) percentage (%) in RCAs of balloon-injured rabbits did not present any difference between groups ( P = .812). Similarly, the immunohistochemically determined accumulation of endothelial cells and macrophages on vascular walls was equivalent between groups ( P > .05)., Conclusion: Following carotid balloon injury and stenting, clopidogrel and ticagrelor did not show any differential effects on the extent of neointimal formation and ISR in atherosclerotic rabbits receiving aspirin. Three thrombotic stent occlusions were noted in the clopidogrel treatment group, but this finding was not statistically significant.

Asynchronous movement of the carotid atheromatous plaque from B-mode ultrasound has been previously reported, and associated with higher risk of stroke, but not quantitatively estimated. Based on the hypothesis that asynchronous plaque motion is associated with vulnerable plaque, in this study, synchronisation patterns of different tissue areas were estimated using cross-correlations of displacement waveforms. In 135 plaques (77 subjects), plaque radial deformation was synchronised by approximately 50% with the arterial diameter, and the mean phase shift was 0.4 s. Within the plaque, the mean phase shifts between the displacements of the top and bottom surfaces were 0.2 s and 0.3 s, in the radial and longitudinal directions, respectively, and the synchronisation about 80% in both directions. Classification of phase-shift-based features using Random Forests yielded Area-Under-the-Curve scores of 0.81, 0.79, 0.89 and 0.90 for echogenicity, symptomaticity, stenosis degree and plaque risk, respectively. Statistical analysis showed that echolucent, high-stenosis and high-risk plaques exhibited higher phase shifts between the radial displacements of their top and bottom surfaces. These findings are useful in the study of plaque kinematics.

Background: S100-β protein has been introduced as a sensitive biomarker of silent cerebral injury. This study compares its serum levels before, during, and 24 hours after carotid artery stenting (CAS) and carotid endarterectomy (CEA)., Methods: We measured serum level of S100-β in arterial blood before (S100Ba), during (S100Bb), and 24 hours after (S100Bc) CAS and CEA. We assessed differences in S100-β levels using non-parametric tests. We analyzed the relationship between carotid plaque type (echolucency) and S100-β protein level. We also examined its relation to the oximetry results in the CEA group (ipsilateral and contralateral)., Results: Thirty patients were enrolled, including 15 CAS and 15 CEA patients, with no significant differences in baseline atherosclerotic characteristics. There was no significant difference in S100Ba or S100Bb levels between CAS and CEA patients. However, a significant difference was found in S100Bc: 331.3 pg/mL (IQ range 56.4-583.5) for CAS vs. 76.3 pg/mL (IQ range 29.7-117.4) for CEA (P=0.01). Type I and II plaques were associated with the higher S100Bc levels in CAS (P=0.048). S100Bc was higher in CEA patients when the contralateral cerebral hemisphere had oximetry values less than 60% (P=0.043)., Conclusions: Our study suggests that CAS might produce silent brain injury. Moreover, vulnerable plaques might be associated with higher levels of S100-β protein, especially in CAS. This pilot study demonstrates that S100-β is a useful biomarker for silent brain injury in carotid revascularization. Large scale studies are still needed to confirm these findings.

The identification/selection of appropriate patient subgroups with asymptomatic carotid artery stenosis and the performance of prophylactic carotid endarterectomy (CEA)/carotid artery stenting (CAS) exclusively on these asymptomatic patient subgroups is currently one of the "hottest" topics in vascular surgery. It is now clear that offering CEA/CAS to asymptomatic carotid patients based only on the degree of carotid stenosis is unjustified and scientifically flawed. On the other hand, offering only best medical therapy to every asymptomatic patient, irrespective of certain high-risk criteria (such as the detection of microemboli by transcranial Doppler, intraplaque hemorrhage, silent embolic infarcts on brain computed tomography/magnetic resonance imaging, elevated biomarkers, family history), is equally wrong. The validation of specific measures to identify those asymptomatic patients at high risk for developing symptoms is crucial to achieve optimal use of carotid interventions and avoid wasting stroke prevention resources.

Background: The decision for revascularization in patients with near-total internal carotid artery (ICA) occlusion still remains controversial. We undertook an extensive review of the literature and conducted a meta-analysis aiming to investigate the appropriate therapeutic approach for patients with near-total ICA occlusion., Methods: A multiple electronic health database search was performed on all articles published up to December 2014. All available data were analyzed giving emphasis on the applied therapeutic approach (best medical therapy [BMT], carotid endarterectomy [CEA], and carotid artery stenting [CAS]), whereas the main endpoints of the meta-analysis were transient ischemic attack (TIA), stroke, stroke-related death, myocardial infarction (MI), major adverse event (MAE), overall mortality, and restenosis., Results: Five articles on BMT and CEA, 8 articles on CEA, and 11 articles on CAS were deemed eligible. A statistically significant difference was recorded in pooled stroke incidence rates (IRs) per 100 patient-years (p-ys) of BMT (IR = 6.19) compared with CEA (IR = 2.24, P = 0.002) and CAS (IR = 1.64, P < 0.001) studies. No statistically significant differences were recorded in pooled IRs per 100 p-ys between CEA and CAS, concerning TIA (P = 0.96), stroke (P = 0.44), stroke-related death (P = 0.30), and MAE (P = 0.99), whereas a borderline significance was recorded concerning overall mortality (P = 0.08) and restenosis (P = 0.08). No nominally significant effects were demonstrated with respect to almost all the studied potential modifiers in meta-regression analysis among the eligible studies., Conclusions: An intervention is probably indicated for patients with near-total ICA occlusion. The results of our study underline the need for including patients with near-total ICA occlusion in future randomized controlled trials. Meanwhile, the treatment of these patients should be individualized., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The effect of carotid artery stenting (CAS) on cognitive function in patients with extracranial carotid artery stenosis is equivocal. The aim of this study was to examine the impact of CAS on various domains of cognitive function., Methods: We performed a meta-analysis of the studies evaluating various domains of cognitive function before and after CAS, namely, (1) global cognition using Mini-Mental State Examination (MMSE) and Rey Auditory Verbal Learning Test (RAVLT), (2) executive function using Trail Making Test (TMT) A or Color Trails Test (CTT) A and TMT B or CTT B, (3) language ability using Boston Naming Test (BNT), (4) memory, (5) attention/psychomotor speed, and (6) functional ability, using various cognitive tests. Pooled weighted mean differences (WMDs) and standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were appropriately calculated using fixed or random effects models after assessing between-study heterogeneity. Meta-regression analysis was performed with number of patients per study; mean age (years); follow-up (months); proportion of men; proportion of patients with hypertension, diabetes mellitus, hyperlipidemia, smoking, and coronary artery disease; proportion of symptomatic patients; and degree of ipsilateral and degree of contralateral carotid stenosis as covariates., Results: Sixteen studies were eligible, including a total of 626 CAS patients. A statistically significant improvement of global cognition was detected with MMSE (WMD = 0.67, 95% CI = 0.29-1.05, P < 0.001; follow-up = 5.6 months), but not with RAVLT (SMD = 0.45, 95% CI = -0.03 to 0.93, P = 0.07; follow-up = 2.4 months). Significant improvement of memory (SMD = 0.33, 95% CI = 0.11-0.55, P < 0.01; follow-up = 4.1 months) and attention/psychomotor speed (SMD = 0.21, 95% CI = 0.04-0.39, P = 0.02; follow-up = 4 months) was also detected. No statistically significant effect on executive function (TMT A/CTT A and TMT B/CTT B; SMD = 0.08, 95% CI = -0.10 to 0.26, P = 0.39; follow-up = 3.9 months and SMD = -0.02, 95% CI = -0.20 to 0.16, P = 0.82, respectively; follow-up = 3.9 months), language ability (BNT; SMD = 0.24, 95% CI = -0.05 to 0.54, P = 0.10; follow-up = 4 months), and functional ability (SMD = -0.05, 95% CI = -0.25 to 0.15, P = 0.63; follow-up = 3.8 months) was observed. No significant effects of the examined covariates were demonstrated in the meta-regression analyses., Conclusions: CAS may be associated with improvement in global cognition, memory, and attention/psychomotor speed. There was no positive effect on executive function, language, and functional ability, but CAS was not associated with a decline in any area of cognitive function. Future studies in larger groups of patients are probably needed to fully investigate the long-term effect of CAS on cognition in patients with carotid artery stenosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: We investigated the relationship of circulating novel adipokines, retinol-binding protein 4 (RBP4) and omentin-1, with advanced carotid atherosclerosis and ultrasound indexes of severity (total plaque area-TPA) and plaque echogenicity and vulnerability (Gray-Scale median - GSM score)., Methods: We enrolled 225 patients with high-grade carotid stenosis (HGCS) who underwent carotid revascularization (73 Symptomatic patients, 152 asymptomatic patients) and 75 age- and sex-matched, asymptomatic individuals with low-grade (<50%) carotid stenosis (LGCS). Seventy-three individuals without current manifestations of atherosclerotic disease served as control group (COG). All participants underwent carotid ultrasound with TPA and GSM score assessment. Moreover, clinical parameters, metabolic profile, and circulating levels of hsCRP and adipokines were assessed., Results: RBP4 was significantly elevated in HGCS (51.44 ± 16.23 mg/L) compared to LGCS (38.39 ± 8.85 mg/L), independent of symptoms existence, whereas RBP4 levels in COG were even lower (25.74 ± 10.72 mg/L, p < 0.001 compared to either HGCS or LGCS). Inversely, serum omentin-1 levels were significantly lower across HGCS (490.41 ± 172 ng/ml) and LGCS (603.20 ± 202.43 ng/ml) than COG (815.3 ± 185.32, p < 0.001). Moreover, the considerable difference between HGCS and LGCS (p < 0.001) was exclusively attributed to the excessive suppression of omentin-1 concentrations in symptomatic versus asymptomatic (p = 0.004) patients. HGCS and LGCS did not differ in the rest of clinical and biochemical parameters. In multiple regression analysis, RBP4 (beta = 0.232, p = 0.025) and hsCRP (beta = 0.300, p = 0.004) emerged as independent determinants of TPA in patients with carotid atherosclerosis. Low serum levels of omentin-1 correlated with GSM score and symptoms but that association was lost in multivariate analysis.., Conclusion: RBP4 serum levels were significantly elevated in patients with established carotid atherosclerosis and were positively associated with atherosclerosis severity. The association of low serum omentin-1 with carotid plaque echolucency requires further investigation.. ClinicalTrials.gov Identifier: NCT00636766., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: High-grade stenoses of both common (CCA) and the internal (ICA) carotid arteries are rare and represent a therapeutic dilemma for the treating physician. The aim of this article is to present our experience with fully endovascular repair of those lesions., Methods: Between January 2011 and December 2012, 5 patients (all male, age 73.6 years) with concomitant CCA and ICA stenoses were treated endovascularly. All patients were asymptomatic. The lesions involved the left carotid in 3 and the right carotid in 2 cases. Common carotid artery stenosis was located at the ostium (1 patient), the middle (3 patients) and the distal segment (1 patient) of the CCA. In 3 cases, CCA stenting was initially performed followed by ICA treatment, whereas in the remaining 2, ICA stenting preceded CCA stenting. A filter embolic protection device was used in 2 cases., Results: All procedures were successfully completed. Technical success rate was 100%. Mortality rate was 0%. One patient experienced transient neurologic complication. An 82-year-old who underwent left mid-CCA and ICA stenosis without embolic protection device suffered a transient ischemic attack with dysarthria lasting for a few minutes. A 73-year-old patient with left CCA and ICA stenosis and occlusion of the right ICA who underwent stenting under cerebral protection experienced symptoms consistent with cerebral hyperperfusion. Patients were followed up for a mean of 6 months. No neurologic complications or stent restenosis were detected., Conclusions: Angioplasty and stenting is a technically feasible method for the treatment of concomitant CCA and ICA stenosis with acceptable short- and mid-term results., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Internal carotid artery (ICA) occlusion is associated with acute stroke and carries significant morbidity and mortality. The aim of this study was to examine whether ultrasonographic carotid plaque type may be associated with ICA occlusion., Methods: Two hundred eleven patients (85% men, mean age 66.0±9.5 years, 28.9% asymptomatic) with ICA occlusion were included in this case-control study. Ultrasonographic Gray-Weale plaque type (I-IV, echolucent to echogenic) characterization was obtained in both the occluded and the contralateral ICA. Univariate and conditional logistic regression analyses with 1:1 pair matching per artery were undertaken. Each contralateral carotid artery with stenosis was treated as control to the ipsilateral-occluded ICA of the same patient., Results: A total of 261 ICAs (61.9%) were recorded with type I-II plaque, of which 165 (63.2%) were among the occluded and 96 (36.8%) were among the contralateral ICAs with stenosis (P<0.001). Mean contralateral ICA stenosis was 58.2%±20.4%. Regression analysis showed that carotid plaque type I-II was significantly associated with carotid artery occlusion compared with plaque type III-IV (crude odds ratio [OR]=4.29, 95% confidence intervals [CI]=2.81-6.57%, P<0.001, adjusted OR=5.60, 95% CI=3.23-9.70, P<0.001). Previous neurological events did not seem to be significantly associated with plaque echolucency (OR=0.62, 95% CI=0.29-1.35, P=0.23)., Conclusions: A significant association between echolucent plaque and ICA occlusion was observed. This observational hypothesis may prompt for further investigation of the causal mechanism between carotid plaque type and ICA occlusion by larger cohort studies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To present a systematic review and meta-analysis investigating the incidence of carotid artery stenting (CAS)-induced hemodynamic instability (HI) and to explore differences in periprocedural risk among patients with and without CAS-associated HI., Methods: Multiple electronic health databases were searched for all articles published between January 2000 and December 2011 describing CAS-associated hemodynamic instability. Twenty-seven studies with a total of 4204 patients were analyzed, placing emphasis on the HI incidence and its correlation with postprocedure morbidity and mortality. A meta-regression analysis was conducted to investigate the role of potential meaningful modifiers upon HI., Results: The meta-analysis for overall HI rate showed a pooled proportion of 39.4%. The pooled estimate for hypotension was 12.1%, 12.2% for bradycardia, and 12.5% for both hypotension and bradycardia. Persistent HI was found to occur in a pooled rate of 19.2%. No statistically significant differences were found between patients with and without HI after CAS with respect to death, stroke, transient ischemic attack (TIA), or major adverse events. The meta-regression analysis revealed statistically significant associations of mean age with HI, of ≤10-mm distance between the carotid bifurcation and the site of minimum lumen diameter with bradycardia, and of prior ipsilateral CEA with persistent HI., Conclusion: CAS-induced HI occurs in a considerable percentage of patients without increasing the perioperative risk. However, applying the appropriate prophylactic measures and strictly monitoring blood pressure and heart rate during the procedure and immediately after should be encouraged for early recognition and correction of these hemodynamic disturbances.

Herein, we present the European Society for Vascular Surgery Guidelines pertinent to the secondary prevention of cerebrovascular events in patients with carotid artery stenosis including lipid lowering therapy, antiplatelet therapy and other risk factor modification. These recommendations are based on current evidence from clinical trials. There is a need for aggressive prevention treatment in patients with carotid artery disease. We also discuss the diagnosis and grading of carotid artery stenosis.

Herein, we present the European Society for Vascular Surgery Guidelines pertinent to the secondary prevention of cerebrovascular events in patients with carotid artery stenosis including lipid lowering therapy, antiplatelet therapy and other risk factor modification. These recommendations are based on current evidence from clinical trials. There is a need for aggressive prevention treatment in patients with carotid artery disease. We also discuss the diagnosis and grading of carotid artery stenosis.

Most of the currently published randomized trials (RCTs) for carotid artery stenting (CAS) versus carotid endarterectomy (CEA) on symptomatic patients have concluded that CAS is associated with outcomes that are inferior to those of CEA. However, before final decision making on the future of CAS, there are some major issues of concern. Randomized controlled trials condemning CAS suffer from major study flaws, rendering comparison with CEA ineffective. These trials are challenged by methodological gaps, underpowered results, old-fashioned equipment and underuse of cerebral protection devices or even of stents. On the other hand, physicians' experience in CAS has not been that much appreciated, whereas CEA has been widely performed during the last 30 years by experienced and fully trained vascular surgeons. CAS is a recently emerged treatment that cannot yet be standardized. No matter the final verdict on CAS, the procedure will never be for low volume practitioners. It is required that CAS be performed exclusively in high volume centers with specific dedicated experience and adequate training. Yet, optimistic results on CAS have been constantly reported from single, highly specialized CAS centers around the world. Regarding restenosis rates, they should be evaluated on the true need for re-intervention, since its clinical significance is still debated; but even when decision is undertaken to operate a restenosis, a repeat endovascular procedure is safe with reported complication rates < 1%. Concluding, vascular surgeons should be thoughtful about rejecting it as an alternative to CEA, because with advancing technology, vascular surgeons electing to stay away, and not perform CAS, will stay out of the "race."

Objective: Atherosclerotic plaque stabilization is a promising strategy to prevent cerebrovascular events in patients with carotid atherosclerosis. Vascular calcification inhibitors, known osteopontin (OPN) and osteoprotegerin (OPG), have emerged as novel cardiovascular biomarkers. This open-label, prospective study aimed to examine whether aggressive lipid-lowering therapy with atorvastatin is more effective than moderate lipid-lowering in increasing carotid plaque echogenicity, assessed by Gray-Scale Median (GSM) score and suppressing serum OPN and OPG levels in patients with moderate carotid stenosis., Methods: One hundred forty patients (64 males, 76 females), aged 50 to 75 years, with carotid stenosis (North American Symptomatic Carotid Endarterectomy Trial [NASCET]: 30%-60% for symptomatic and 30%-70% for asymptomatic), but without indications for surgical intervention, were enrolled. Patients with coronary heart disease, renal failure, hypothyroidism, osteoporosis, and ongoing use of statins were excluded. Patients were randomly assigned to: Group A (N = 70): Moderate lipid-lowering therapy with low-dose of atorvastatin (10 mg-20 mg) to target LDL-C <100 mg/dL. Group B (N = 70): Aggressive lipid-lowering therapy with high-dose of atorvastatin (80 mg) to target LDL-C <70 mg/dL. Blood pressure, lipid and glycemic indexes, hsCRP, serum OPN, and OPG were measured at baseline and after 12 months as well as the GSM score. Independent samples t test, paired samples t test, Pearson correlation, and multiple regression analysis were used (P < .05)., Results: There were no significant differences between groups at baseline. Three patients in group A experienced either cerebrovascular or cardiac ischemic attacks, while two patients in group B underwent coronary angioplasty during follow-up. Group B showed a more pronounced improvement in total cholesterol and LDL-cholesterol compared with group A (P < .05). Moreover, atorvastatin treatment suppressed serum hsCRP, OPN, and OPG levels from baseline in both groups (P < .001). Notably, aggressive treatment decreased OPN (P = .012) and OPG (P = .025) levels to a greater degree compared with moderate treatment. Similarly, GSM score was remarkably increased in both groups, but that augmentation was greater in group B (from 66.39 +/- 23.66 to 100.4 +/- 25.31) than in group A (from 64.4 +/- 23.62 to 85.39 +/- 20.21) (P = .024). No change in the degree of carotid stenosis was noted in both treatment arms. Importantly, the aforementioned reduction in OPN (r = -0.517, P = .024) and OPG (r = -0.312, P = .008) levels was inversely associated with GSM score changes in univariate and standard multiple regression analysis (R(2) = 0.411, P = .021)., Conclusions: Among patients with moderate carotid stenosis, an aggressive atorvastatin regimen enhanced carotid plaque echogenicity and reduced serum OPN and OPG levels to a greater extent than respective moderate atorvastatin therapy. Most importantly, those atorvastatin-induced effects were associated with OPN and OPG suppression in a dose-dependent manner., (Copyright 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Osteopontin (OPN) and osteoprotegerin (OPG) are well-known vascular calcification inhibitors, which have been recently demonstrated to correlate with inflammation and cardiovascular events incidence. The aim of this cross-sectional study is to survey whether OPN and OPG are involved in carotid plaque vulnerability. For this reason, we assessed serum OPN and OPG levels in patients with carotid stenosis, and we explored their relationship with carotid plaque echogenicity and subsequent cerebrovascular ischemic events., Methods: A total of 164 Whites were selected from a large cohort of 297 subjects to participate. In particular, 114 patients (61 men, 53 women), aged 55 to 80, had recently-diagnosed ICA stenosis higher than 50%. A group of 50 age-, sex-, and body mass index (BMI)-matched healthy individuals served as healthy controls. Patients with renal failure, hypothyroidism, osteoporosis, and lipid-lowering therapy were excluded. Images of both carotids were obtained from all participants using a high-resolution color duplex ultrasound and the gray-scale median (GSM) score was calculated. Brain computed tomography (CT), and magnetic resonance imaging (MRI) scans when CT was questionable, were performed on all patients with carotid stenosis. Clinical parameters, lipid and glycemic indexes, hsCRP, fibrinogen, white blood cells (WBC) count, OPN, and OPG were measured. Independent t test, one-way ANOVA, Pearson correlation, and multiple regression analysis were used for statistical analysis., Results: Among patients with carotid stenosis, 60 had history of ipsilateral stroke or TIA and positive CT or MRI findings (group A), while 54 had no neurological symptoms and negative CT and MRI scan (group B). Overall, patients with carotid stenosis showed worse lipid profile and increased waist circumference, blood pressure, hsCRP, fibrinogen, WBC count, OPN, and OPG levels compared with healthy subjects (group C) (P <.05). Statistical analysis revealed that group A had significantly lower levels of GSM than group B (57.41 +/- 38.19 vs 76.32 +/- 36.72; P = .008) and higher levels of hsCRP, OPN, and OPG than groups B and C (P < .05). Concerning the latter, biochemical markers group B showed only elevated OPG levels compared with group C (P = .038). Notably, GSM was considerably associated with serum OPN and OPG and waist circumference in patients with carotid atherosclerosis in univariate (r = -0.333; P = .032, r = -0.575; P < .001, r = -0.590; P =.006, respectively) and multiple regression analysis (R(2) = 0.445; P =.006)., Conclusions: The present study demonstrated elevated serum OPN and OPG levels in patients with carotid stenosis and documented an independent association between these biochemical markers, GSM and carotid-induced symptomatology. Therefore bone-matrix proteins combined with GSM could be potential markers for vulnerable carotid plaques.

The aim of this article is to investigate the association between internal carotid artery occlusion (ICAO) and the presence of atherosclerotic disease and vascular risk factors. The clinical characteristics and risk factors of 120 patients presenting with ICAO were retrospectively reviewed. All patients (n = 120) had at least 1 of the 4 vascular risk factor (diabetes, smoking, hypercholesterolemia, and hypertension); 2, 3, or all 4 risk factors were present in 14 to 82 of the patients (11.7% to 68.3%), 10 to 39 of the patients (8.3% to 32.5%), and 9 of the patients (7.5%), respectively. A total of 84 patients (70%) with ICAO had disease in at least 1 additional vascular bed (aorta, coronary or lower limb arteries). In addition to ICAO, vascular disease was present in 2 and all 3 of these arterial beds in 42 (35%) and 9 (7.5%) patients, respectively. Furthermore, stenosis or occlusion of the ipsilateral or contralateral vertebral arteries was recorded in 19 of 120 patients (15.8%). Regarding the contralateral carotid artery, 1 patient had bilateral ICAO. One patient had contralateral common carotid artery occlusion, and 1 patient was excluded from the analysis because of surgery to the contralateral carotid artery. Of the remaining 117 patients, 34 (29.0%) had less than 50% contralateral carotid artery stenosis. Thirty-two patients (27.4%) had 50% to 69%, and 51 (43.6%) had 70% to 99% stenosis. Ultrasonographic imaging of the carotid plaque of the contralateral carotid artery revealed that 52 of the 120 arteries (43.3%) were uniformly or predominantly echolucent (types I and II, respectively). Fifty-nine (49.2%) were predominantly or uniformly echogenic (types III and IV), and 9 (7.5%) could not be classified. A similar distribution of echomorphology was observed on the occluded side. ICAO is associated with widespread atherosclerotic disease and a high prevalence of vascular risk factors. Detection of ICAO should prompt the investigation of other arterial beds and treatment of risk factors.

Objective: Metallothioneins (MTs) are antioxidant proteins expressed in response to injury. We evaluated MT immunoreactivity in carotid plaques obtained from asymptomatic and symptomatic patients. We also assessed the relationship between ultrasonic plaque echodensity, histological grading, computed tomography findings and MT expression., Methods and Results: In this ongoing prospective study, patients (n = 123, mean age (+/-SD) 68.4 +/- 7.7 years, 97 men) with high-grade carotid stenosis underwent carotid endarterectomy. Specimens were assessed histologically and immunohistochemically. Echolucent plaques (types 1+2) were more common in symptomatic patients (p < 0.0001) and had more advanced histological lesions (p < 0.0001). Echolucent plaques expressed MTs (in macrophages, fibroblasts and T-lymphocytes) significantly more than echogenic plaques (types 3+4) (all p < 0.0001). MT expression was mainly related to carotid plaque echolucency rather than the presence of symptoms. MT expression was significantly more common in advanced histological lesions. Plaques from asymptomatic or symptomatic patients with abnormal computed tomography findings also showed increased MT expression. There was a time-dependent fall in MT expression after cerebrovascular events (p < or = 0.011)., Conclusions: MT overexpression may be triggered in unstable plaques as a local protective factor. There is a need to identify both causative and protective predictors of the 'vulnerable plaque' in the 'vulnerable patient'. Further studies are needed to resolve these issues.

Objective: Inflammation and infection have been implicated in the pathogenesis of carotid artery atherosclerosis, but their role in cerebrovascular disease symptomatology is not so well defined. We hypothesized that carotid disease symptomatology was associated with specific serologic markers of inflammation and Chlamydia pneumoniae infection and the presence of the pathogen and concentration of tumor necrosis factor-alpha (TNF-alpha) on the atheroma., Methods: In 2004, 78 patients underwent carotid endarterectomy in our department, 46 of whom were symptomatic (group A) and 32 were asymptomatic (group B). A detailed medical history, the presence of atherosclerosis risk factors, ankle-brachial index and boxy mass index were recorded. We measured preoperatively the levels of C-reactive protein, fibrinogen, TNF-alpha, and the titers of immunoglobulin (Ig) A and IgG antibodies against C pneumoniae in the serum. Finally, the atherosclerotic plaques of all patients were immunohistochemically examined for the presence of C pneumoniae and their TNF-alpha concentration was determined., Results: Isolation of the pathogen on the atheromatous lesion was statistically correlated with several risk factors and some of the variables that were tested. After testing independence of association, using the multiple regression analysis, only male gender (P = .024), hypertension (P = .008), hypercholesterolemia (P = .001), and TNF-alpha plaque values (P = .008) remained significantly associated. Hypertension, serum levels of fibrinogen and anti-C pneumoniae immunoglobulin A, detection of C. pneumoniae on the plaque, and plaque TNF-alpha values were significantly correlated with carotid disease symptomatology. After multiple analyses, only the presence of the pathogen on the lesion (P = .008) and atheroma TNF-alpha levels (P = .025) remained significantly associated with cerebrovascular events., Conclusions: It seems that hypertensive hypercholesterolemic men are more likely to have C. pneumoniae infected carotid plaques and that these plaques have higher TNF-alpha concentrations. Cerebrovascular disease symptomatology is strongly correlated with both C. pneumoniae infection and TNF-alpha concentration of the atheroma.

Recurrent carotid stenosis is an ongoing process that may develop at or near the site of an operational or interventional procedure to treat an atheromatous stenosis. Although such a restenosis is most often initially without symptoms, as the disease progresses it may become symptomatic, and thus endanger the patient's life. Such patients are therefore candidates for revisional surgery. Extensive research investigation and numerous studies have incriminated several risk factors as predisposing conditions for recurrent carotid stenosis. The definite role of each predisposing factor, however, is still widely debated. Clarifying the extent of involvement of each factor in the pathogenesis of carotid restenosis is indeed demanding, as it would contribute enormously to the identification of the group of high-risk patients, and, therefore, determine the therapeutic approach in these patients.

Purpose: Several factors have been related to long-term survival after open abdominal aortic aneurysm (AAA) repair. The effect of carotid stenosis on outcome has not yet been examined. We performed an open prospective study to evaluate the prognostic significance of carotid stenosis on long-term survival of patients who had undergone elective operative repair of AAA., Methods: Two hundred eight patients who underwent elective open AAA repair in our department between March 1987 and December 2001 were included in the study. All patients were evaluated preoperatively with color duplex ultrasound (US) scanning of the carotid arteries, and were followed up with clinical examination and carotid duplex US scanning 1 month after the operation and every 6 months thereafter. Median duration of follow-up was 50 months (range, 5-181 months). Cardiovascular morbidity and mortality, as well as all causes of mortality, were recorded and analyzed with regard to traditional risk factors and carotid US findings., Results: Twenty-seven fatal and 46 nonfatal cardiovascular events were recorded. Both univariate and multivariate analysis showed that carotid stenosis 50% or greater and echolucent plaque were significantly associated with cardiovascular mortality and morbidity. Carotid stenosis was a stronger predictor of cardiovascular death than was ankle/brachial index. Age, hypercholesterolemia, coronary artery disease, and diabetes mellitus were also associated with higher mortality and morbidity from cardiovascular causes., Conclusion: Patients electively operated on for AAA repair and with stenosis 50% or greater and echolucent plaque at duplex US scanning are at significantly increased risk for cardiovascular mortality and morbidity. Carotid US can therefore be used to select a subgroup of patients with AAA who might benefit from medical intervention, including antiplatelet and lipid-lowering agents.

Background and purpose Accumulating evidence suggests that carotid plaque vulnerability can be used as a determinant of ischemic stroke risk stratification and carotid intervention. Novelmarkers of high-risk carotidplaquein patients areneeded. Summary of review Advances in cellular and molecular pathophysiology, the demand for accurately predicting carotid risk, and choosing the optimal prevention strategy are stimulating great interest in the development of novel surrogate markers. Biomarkers in cardiovascular disease are expected to predict the natural history, clinical outcomes, and the efficacy of disease-modifying interventions. We aimed to review the literature regarding clinical data on novel serum biomarkers related to ischemic cerebrovascular events associated with carotid artery disease. We provide background information on the biomarkers related to all aspects of carotid disease: natural history, carotid intervention strategies for symptomatic and asymptomatic patients, perioperative risk prediction, and their therapeutic implications. Conclusion At present, heterogeneous data support evidence that biological markers can help existing practices to more accurately assess patients at risk for stroke. Randomized- controlled trials for carotid artery disease and carotid intervention, incorporating biomarkers, are needed. [ABSTRACT FROM AUTHOR]

Carotid endarterectomy is a well-established procedure per formed throughout the world. Although its effectiveness and durability are established, many aspects of the operation are still controversial. These con troversies are depicted in daily medical practice in all countries and especial ly between vascular surgeons in the United States and the European Union. This paper describes and analyzes the main differences in opinions and prac tices on carotid endarterectomy that are emerging from the multicenter, ran domized studies performed in the two continents. Regarding symptomatic patients with high-grade internal carotid artery stenosis, there is a transat lantic agreement. Differences between the European Carotid Surgery Trial and the North American Symptomatic Carotid Endarterectomy Trial suggest that the degree of stenosis may only be a surrogate marker for outcome. Regarding asymptomatic patients, carotid endarterectomy is performed more frequently in the United States than in Europe. Until we can demonstrate a morbidity/mortality rate of less than 1%, carotid endarterectomy in asymp tomatic patients should be performed on a very selective basis. [ABSTRACT FROM PUBLISHER]