What Is the Future of Asymptomatic Carotid Artery Disease?
Asymptomatic carotid artery stenosis is a significant health concern, as out of the 135,701 carotid revascularizations performed in the U.S. in 2005, 122,986 (92%) were for asymptomatic carotid artery stenosis.1 Current societal guidelines recommend revascularization in most patients with severe asymptomatic carotid artery stenosis.2 However, these guidelines are based on older studies that may not reflect the changing natural history of asymptomatic carotid artery stenosis with current optimal medical therapy (OMT). The old paradigms for deciding the timing of revascularization need to be revisited.3 Thus physicians today are faced with a dilemma regarding who to treat and when. This article addresses the evolving natural history of asymptomatic carotid artery stenosis, ongoing attempts to identify those more likely to become symptomatic, and advances in revascularization techniques that may decrease the risk from revascularization.
Conventional Management Paradigm for Asymptomatic Carotid Artery Stenosis
Current recommendations for revascularization for asymptomatic carotid artery stenosis2 are predominantly based on two seminal studies performed in the 1990s. The Asymptomatic Carotid Artery Study (ACAS) was a well-conducted study that assessed carotid endarterectomy (CEA) in asymptomatic carotid artery stenosis (>60%) for stroke prevention.4 A total of 1,662 patients were randomized to CEA or medical therapy. The study was halted at 2.7 years because of a projected 5.9% absolute risk reduction (ARR) at five years favoring CEA. The perioperative stroke rate was 2.3%. The five-year projected rate of ipsilateral stroke was 11% for the medical group versus 5.1% for the surgical group (a 47% relative risk reduction [RRR]). The Asymptomatic Carotid Surgery Trial (ACST) randomized 3,120 asymptomatic carotid artery stenosis patients into immediate CEA or delayed surgery for symptoms only. The 30-day risk of stroke or death was 3.1%. The five-year rates were 6.4% for CEA and 11.7% for medical therapy arm.5,6
However, medical therapy in these trials was not up to current standards, with only a minority of patients receiving lipid-lowering therapy and blood pressure (BP) was also significantly higher than today's standards.3,7
Evolving Natural History of Asymptomatic Carotid Artery Disease
The annual risk of stroke in ACAS and ACST was 2-3%.4,6 This relatively high risk with medical therapy would likely still make revascularization a reasonable choice today as the more recent Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) reported a four-year risk of stroke or death as 4.5% with carotid artery stenting (CAS) and 2.7% with CEA.8 However, recent evidence suggests that the natural history of asymptomatic carotid artery stenosis has improved remarkably, and the risk-benefit analysis of revascularization will need to be re-evaluated. Current OMT consists of high-dose statin drugs, optimal BP control, smoking cessation, antiplatelet therapy (generally aspirin alone), optimal diabetes control and other lifestyle changes.9 In ACST, in 2004, the five-year risk of any stroke in medically treated subjects was 11.8% (2.4% annually), while in 2010 the five-year risk was 7.2% (1.4% annually).3,10 Ipsilateral stroke risk was 5.3% (1.1% annual) and 3.6% (0.7% annually). In a sub-study of the Oxford Vascular Study, Marquardt et al. reported that in 101 patients with a mean follow-up of three years, the annual risk of any ipsilateral stroke was 0.34%.11 There are no large studies, but several meta-analysis have demonstrated a sustained trend towards a decline in the stroke.12-14 By most estimates, the annual risk of stroke with current OMT is likely <1%. Shah et al. recently showed that with OMT and risk factor control, the risk of progression of the degree of carotid stenosis is also significantly lower than in those with sub-optimal medical therapy.15
Current and Future Trials of Carotid Revascularization and OMT
There is an urgent need for studies that directly compare OMT with current revascularization techniques.
The Carotid Revascularization Endarterectomy Stenting Trial 2 (CREST 2) is currently recruiting subjects with asymptomatic carotid artery stenosis and ≥70% stenosis. The study will compare either OMT alone versus OMT plus CEA or OMT alone versus OMT plus CAS.16,17
The Stent-Protected Angioplasty in Asymptomatic Carotid Artery Stenosis versus Endarterectomy (SPACE-2) study aims to recruit about 3,500 patients and randomly assign them to OMT alone or CEA or CAS.18
Identifying the "High-Risk" Patient With Asymptomatic Carotid Artery Stenosis
Unarguably, the above-mentioned studies will help define the role of revascularization strategies in asymptomatic carotid artery stenosis patients. However, the reality is that the majority of patients with asymptomatic carotid artery stenosis will never become symptomatic and may undergo unnecessary procedures if these studies do show benefit of CEA or CAS. On the other hand, even if the studies show no benefit of OMT over CEA or CAS, there will still be patients who will become symptomatic. Thus, recognition of patients at higher risk would maximize the potential benefits of revascularization. However, there are several potential and promising tools that are being investigated.
There are few clinical predictors of increased stroke risk in asymptomatic carotid artery stenosis. Certain clinical characteristics, such as male sex, current smoking, poorly controlled hypertension, and history of contralateral transient ischemic attack (TIA)/stroke impart a higher risk of future stroke. However these are too non-specific to serve as useful guides for deciding about revascularization.19
In addition to identifying clinical factors, risk stratification attempts have focused on other indirect methods as discussed below.
Contrary to common belief, the stenosis severity in the 60-99% range has been an inadequate predictor of future events. The randomized ACAS and ACST trials did not show stenosis severity in this range as a predictor of future events.4,6 The ACSRS study did find that those with 50-69% stenosis had a lower risk compared to those with 70-89% and 90-99% stenosis (0.8% vs. 1.4% vs. 2.4%).20 However, stenosis severity alone is not a strong enough predictor to be used alone in decision making.
Progression of Stenosis
There is significantly stronger evidence in regard to the predictive value of progressively worsening stenosis. In a post-hoc analysis of the ACST data, incidence of ipsilateral neurologic events was four times higher for stenosis that had progressed by two categories.21 Kakkos et al. studied 1,121 patients with asymptomatic carotid artery stenosis and 50-99% stenosis (mean follow-up, four years).22 19.8% of patients showed stenosis progression of at least one grade and had twice the risk of ipsilateral stroke (21% vs. 12%). Balestrini et al. followed 535 patients with moderate asymptomatic carotid artery stenosis for a mean of 42 months.23 They found that 96.7% of subjects without progressive stenosis remained free from vascular events. Among those with progressive stenosis, 27.1% had an ipsilateral stroke. Thus, progressively increasing stenosis does identify patients with higher risk.
Using ultrasound, atherosclerotic plaques can be characterized based on their surface irregularity, ulcerations, echolucency and gray-scale values. The concept is to identify unstable plaque that is more likely to result in thromboembolic events. The ACSRS investigators have shown that those with predominantly echolucent, lipid-rich plaque had significantly higher stroke risk (3%) than those with mostly echodense, fibrotic plaque (0.8-0.4%).19,24,25 Ulceration on plaque surface detected by three-dimensional ultrasound has also been shown to identify high-risk subjects.26
Magnetic resonance imaging (MRI) has also been used to detect the presence of intraplaque hemorrhage as indicative of a high-risk plaque.27 In a retrospective study of 75 men with 98 asymptomatic carotid arteries of 50-70 % stenosis, intraplaque hemorrhage detected by MRI was present in 36 arteries (37 percent) and was associated with an increased risk of cerebrovascular events (hazard ration [HR] 3.59, 95% confidence interval [CI] 2.48-4.71).28
Looking for Silent Emboli
Since both progressive stenosis and high-risk imaging features identify unstable plaque more prone to atheroembolic events, another way to identify patients at risk is to assess for active silent emboli or evidence of prior asymptomatic cerebral emboli.
Silent Embolic Infarcts on Computed Tomography (CT) or MRI
Presence of ipsilateral silent embolic infarcts on neuroimaging may be predictive of increased risk of ipsilateral stroke.27 In the ACSRS study, among the 821 patients who had a baseline CT, the annual stroke rate was 3.6% when silent embolic infarcts were present at baseline and 1% when they were absent (log-rank P = 0.005).29
Microemboli on Transcranial Doppler (TCD)
Several observational studies demonstrate that detection of microemboli on TCD helps identify those at higher stroke risk.30,31 In the Asymptomatic Carotid Emboli Study (ACES),32 482 patients with asymptomatic carotid artery stenosis underwent six monthly TCDs. The annual risk of ipsilateral stroke was 3.62% in patients with embolic signals and 0.7% in those without them (HR 5.57). A meta-analysis of six reports involving 1,144 patients with asymptomatic carotid artery stenosis found that patients with embolic signals had a significantly higher risk of ipsilateral stroke (HR 6.6, 95% CI 2.9-15.4).33 However, most patients with these signals did remain stroke free at three years, and thus, this test lacks the specificity for stand-alone clinical use.30 Of note, consistently negative asymptomatic carotid artery stenosis patients are associated with an extremely low risk of subsequent stroke.31
Reduced Cerebrovascular Reserve
In patients with severe ipsilateral carotid stenosis, the presence of an incomplete circle of Willis or presence of intracranial or contralateral occlusive disease can reduce cerebral perfusion pressure. Cerebrovascular reserve in such patients can be assessed using TCD velocity measurements in response to acetazolamide or breathing 5% CO2.34-37 In a meta-analysis of 13 studies (991 patients, mean follow up 32.7 months), a strong association between impaired cerebrovascular reserve and ischemic events was seen (OR 3.86).38
Women were underrepresented in most randomized studies of CEA and CAS.4,5 However, a combined analysis of the ACAS and ACST trials found that men with asymptomatic carotid artery stenosis had a 51% relative risk reduction of stroke, whereas women did not have a reduction in stroke risk.39 This has been mostly attributable to the higher risk of perioperative events in women though not borne out in the recent CREST trial.8,40,41 Thus, there is a concern that women may benefit less from revascularization than men and future clinical trials focusing on women are needed to clarify the issue.42
The elderly (especially those over 80 years of age) is a group in which the benefit of revascularization for asymptomatic carotid artery stenosis is most controversial because in both the ACAS and ACST, the benefit from revascularization was seen after five-year follow-up.4,6 Further, ACAS did not enroll subjects greater than 75 years of age; in ACST, there was no benefit seen in those over 75 years (although this was not a pre-specified endpoint). However, age cannot be an absolute contraindication with increasing life expectancy of the overall population; certainly in carefully selected patients, excellent outcomes after both CEA and CAS have been demonstrated.43,44 In regards to the modality of revascularization, based on the CREST data, overall CEA had more favorable outcomes for those over 70 years of age and CAS for those under 70 years of age.8
Current State of Revascularization (Improving Outcomes)
In parallel with improved outcomes with OMT, there have been advances in revascularization techniques. The 30-day risk of stroke after CEA in the CREST study was 2.3 percent, which is lower than historical data.8
Similarly for CAS, most of the published randomized trials used the distal embolic protection devices (DEPD)8,45 and not the proximal embolic protection devices or flow reversal devices. These devices establish embolic protection before any wire/ hardware ever crosses the lesion and, thus, overcome one significant limitation of the DEPDs. Overall the proximal protection/flow reversal has been associated with less microemboli as detected by diffusion-weighted brain (DW-MRI).46-49 A recently published meta-analysis of seven studies with a total of 357 patients reported that following CAS, the incidence of new ischemic lesions/patient detected by DW-MRI was significantly lower in the proximal balloon occlusion group (effect size [ES]: 0.43; 95% CI: 0.84 to 0.02, I2 . 70.08,Q . 23.40).50
The ongoing ROADSTER trial involves an innovative technique with a limited proximal neck dissection to obtain direct carotid access and is paired with proximal reverse flow embolic protection.51,52 Direct carotid access is intended to minimize the risk of microemboli and stroke associated with arch navigation.
Conclusions and Recommendations for Clinical Practice
Both medical and surgical management arms of asymptomatic carotid artery stenosis are rapidly evolving and will continue to result in decreased stroke risk. Until results of CREST 2 and SPACE-2 trails are available, there will remain some uncertainty in regards to best management plan. We recommend that for asymptomatic carotid artery stenosis patients (even those with >80%) stenosis there is enough evidence for a more conservative approach and decisions regarding revascularization should be made after discussing the current available data on stroke risk with the patients. Serial ultrasounds should be performed and revascularization offered to those with >70% stenosis with evidence of progression of stenosis severity. All patients with asymptomatic carotid artery stenosis should be on OMT. For the very elderly (>80 years) and life expectancy less than five years, a conservative approach is most reasonable in most situations. Though more prospective data is needed (and not ready for "prime time" yet), it appears that in the future TCD and brain MRI will be part of the risk stratification process. Regarding optimal revascularization strategy, the authors of this Expert Analysis article believe that CREST is a well-conducted, contemporary trial done in multi-specialty collaboration and does represent current standards of care; based on its results, there is equipoise between the two modalities. Based on CREST results, younger patients (<70 years) may benefit more from CAS and older more from CEA. Individual patient and anatomic risks for CEA and CAS are different and should be considered and a multi-specialty approach should be followed.53
- McPhee JT, Schanzer A, Messina LM, Eslami MH. Carotid artery stenting has increased rates of postprocedure stroke, death, and resource utilization than does carotid endarterectomy in the United States, 2005. J Vasc Surg 2008;48: 1442-50, 1450 e1.
- Brott TG, Halperin JL, Abbara S, et al. 2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease: executive summary. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery. J Am Coll Cardiol 2011;57:1002-44.
- Naylor AR. Time to rethink management strategies in asymptomatic carotid artery disease. Nat Rev Cardiol 2012;9:116-24.
- Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 1995;273:1421-8.
- Halliday AW, Thomas D, Mansfield A. The Asymptomatic Carotid Surgery Trial (ACST). Rationale and design. Steering Committee. Eur J Vasc Surg 1994;8:703-10.
- Halliday A, Mansfield A, Marro J, et al. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet 2004;363:1491-502.
- Abbott AL. Current medical intervention alone is now the best solution for asymptomatic carotid stenosis. letter to the editors of Journal of Vascular Surgery and the European Journal of Vascular and Endovascular Surgery regarding trans-atlantic debate no. 1. Eur J Vasc Endovasc Surg 2010;40:678-9; author reply 679.
- Brott TG, Hobson RW, Howard G, et al., Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010;363:11-23.
- Constantinou, J, Jayia P, Hamilton G. Best evidence for medical therapy for carotid artery stenosis. J Vasc Surg 2013;58:1129-39.
- Halliday A, Harrison M, Hayter E, et al. 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial. Lancet 2010;376:1074-84.
- Marquardt L, Geraghty OC, Mehta Z, Rothwell PM. Low risk of ipsilateral stroke in patients with asymptomatic carotid stenosis on best medical treatment: a prospective, population-based study. Stroke 2010;41:e11-7.
- Abbott AL. Medical (nonsurgical) intervention alone is now best for prevention of stroke associated with asymptomatic severe carotid stenosis: results of a systematic review and analysis. Stroke 2009;40:e573-83.
- Hong KS, Yegiaian S, Lee M, Lee J, Saver JL. Declining stroke and vascular event recurrence rates in secondary prevention trials over the past 50 years and consequences for current trial design. Circulation 2011;123:2111-9.
- Naylor AR. What is the current status of invasive treatment of extracranial carotid artery disease? Stroke 2011;42:2080-5.
- Shah Z, Thapa R, Wani M. Effect of aggressive lipid therapy on progression of carotid stenosis: A longterm follow up study. J Am Coll Cardiol 2015;65:A1487.
- Pahigiannis K, Kaufmann P, Koroshetz W. Carotid intervention: is it warranted in asymptomatic individuals if risk factors are aggressively managed? Stroke 2014;45:e40-1.
- U.S. National Institutes of Health. Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) (ClinicalTrials.gov website). 2014-2015. Available at: https://clinicaltrials.gov/ct2/show/NCT02089217. Accessed 5/4/2015.
- Reiff T, Eckstein HH, Amiri H, Hacke W, Ringleb PA; SPACE-2 Study Group Modification of SPACE-2 study design. Int J Stroke 2014;9:E12-3.
- Nicolaides AN, Kakkos SK, Kyriacou E, et al. Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification. J Vasc Surg 2010;52:1486-1496.e1-5.
- Nicolaides AN, Kakkos SK, Griffin M, et al. Severity of asymptomatic carotid stenosis and risk of ipsilateral hemispheric ischaemic events: results from the ACSRS study. Eur J Vasc Endovasc Surg 2005;30:275-84.
- Hirt LS. Progression rate and ipsilateral neurological events in asymptomatic carotid stenosis. Stroke 2014;45:702-6.
- Kakkos SK, Nicolaides AN, Charalambous I, et al. Predictors and clinical significance of progression or regression of asymptomatic carotid stenosis. J Vasc Surg 2014;59:956-67.e1.
- Balestrini S, Lupidi F, Balucani C, et al. One-year progression of moderate asymptomatic carotid stenosis predicts the risk of vascular events. Stroke 2013;44:792-4.
- Griffin M, Nicolaides A, Kyriacou E. Normalisation of ultrasonic images of atherosclerotic plaques and reproducibility of grey scale median using dedicated software. Int Angiol 2007;26:372-7.
- Griffin MB, Kyriacou E, Pattichis C, et al. Juxtaluminal hypoechoic area in ultrasonic images of carotid plaques and hemispheric symptoms. J Vasc Surg 2010;52:69-76.
- Madani A, Beletsky V, Tamayo A, Munoz C, Spence JD, et al. High-risk asymptomatic carotid stenosis: ulceration on 3D ultrasound vs TCD microemboli. Neurology 2011;77:744-50.
- Paraskevas KI, Spence JD, Veith FJ, Nicolaides AN, et al. Identifying which patients with asymptomatic carotid stenosis could benefit from intervention. Stroke 2014;45:3720-4.
- Singh N, Moody AR, Gladstone DJ, et al. Moderate carotid artery stenosis: MR imaging-depicted intraplaque hemorrhage predicts risk of cerebrovascular ischemic events in asymptomatic men. Radiology 2009;252:502-8.
- Kakkos SK, Sabetai M, Tegos T, et al. Silent embolic infarcts on computed tomography brain scans and risk of ipsilateral hemispheric events in patients with asymptomatic internal carotid artery stenosis. J Vasc Surg 2009;49:902-9.
- Abbott AL, Chambers BR, Stork JL, Levi CR, Bladin CF, Donnan GA. Embolic signals and prediction of ipsilateral stroke or transient ischemic attack in asymptomatic carotid stenosis: a multicenter prospective cohort study. Stroke 2005;36:1128-33.
- Spence JD, Tamayo A, Lownie SP, Ng WP, Ferguson GG. Absence of microemboli on transcranial Doppler identifies low-risk patients with asymptomatic carotid stenosis. Stroke 2005;36:2373-8.
- Markus HS, King A, Shipley M et al. Asymptomatic embolisation for prediction of stroke in the Asymptomatic Carotid Emboli Study (ACES): a prospective observational study. Lancet Neurol 2010;9:663-71.
- Hopkins LN, Roubin GS, Chakhtoura EY, et al. The Carotid Revascularization Endarterectomy versus Stenting Trial: credentialing of interventionalists and final results of lead-in phase. J Stroke Cerebrovasc Dis 2010;19:153-62.
- Gur AY, Bova I, Bornstein NM. Is impaired cerebral vasomotor reactivity a predictive factor of stroke in asymptomatic patients? Stroke 1996;27:2188-90.
- Markus H, Cullinane M. Severely impaired cerebrovascular reactivity predicts stroke and TIA risk in patients with carotid artery stenosis and occlusion. Brain 2001;124:457-67.
- Silvestrini M, Vernieri F, Pasqualetti P, et al., Impaired cerebral vasoreactivity and risk of stroke in patients with asymptomatic carotid artery stenosis. JAMA 2000;283:2122-7.
- Yamamoto KK, Miyata T, Momose T, et al. Reduced vascular reserve measured by stressed single photon emission computed tomography carries a high risk for stroke in patients with carotid stenosis. Int Angiol 2006;25:385-8.
- Gupta A, Chazen JL, Hartman M, et al. Cerebrovascular reserve and stroke risk in patients with carotid stenosis or occlusion: a systematic review and meta-analysis. Stroke 2012;43:2884-91.
- Rothwell PM, Goldstein LB. Carotid endarterectomy for asymptomatic carotid stenosis: asymptomatic carotid surgery trial. Stroke 2004;35:2425-7.
- Goldstein LB, Bushnell CD, Adams RJ, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:517-84.
- Young B, Moore WS, Robertson JT, et al. An analysis of perioperative surgical mortality and morbidity in the asymptomatic carotid atherosclerosis study. ACAS Investigators. Asymptomatic Carotid Atherosclerosis Study. Stroke 1996;27:2216-24.
- De Rango P, Brown MM, Leys D, et al., Management of carotid stenosis in women: consensus document. Neurology 2013;80:2258-68.
- Ballotta E, Toniato A, Da Roit A, et al., Carotid endarterectomy for asymptomatic carotid stenosis in the very elderly. J Vasc Surg 2015;61:382-8.
- Chiam PT, Roubin GS, Panagopoulos, et al., One-year clinical outcomes, midterm survival, and predictors of mortality after carotid stenting in elderly patients. Circulation 2009;119:2343-8.
- SPACE Collaborative Group, Ringleb PA, Allenberg J, et al. 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial. Lancet 2006;368:1239-47.
- Cano MN, Kambara AM, de Cano SJ, et al. Randomized comparison of distal and proximal cerebral protection during carotid artery stenting. JACC Cardiovasc Interv 2013;6:1203-9.
- Castro-Afonso LH, Abud LG, Rolo JG, et al. Flow reversal versus filter protection: a pilot carotid artery stenting randomized trial. Circ Cardiovasc Interv 2013;6:552-9.
- Leal I, Orgaz A, Flores Á, et al. A diffusion-weighted magnetic resonance imaging-based study of transcervical carotid stenting with flow reversal versus transfemoral filter protection. J Vasc Surg 2012;56:1585-90.
- Taha MM, Maeda M, Sakaida H, et al. Cerebral ischemic lesions detected with diffusion-weighted magnetic resonance imaging after carotid artery stenting: Comparison of several anti-embolic protection devices. Neurol Med Chir (Tokyo) 2009;49:386-93.
- Stabile E, et al. Cerebral embolic lesions detected with diffusion-weighted magnetic resonance imaging following carotid artery stenting: a meta-analysis of 8 studies comparing filter cerebral protection and proximal balloon occlusion. JACC Cardiovasc Interv 2014;7:1177-83.
- U.S. National Institutes of Health. Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER) (ClinicalTrials.gov website). 2012-2015. Available at: https://clinicaltrials.gov/ct2/show/NCT01685567. Accessed 5/4/2015.
- Kwolek CJ, Ruedy RM. An Overview of the ROADSTER Trial (Endovascular Today website). 2013. Available at: http://evtoday.com/2013/09/an-overview-of-the-roadster-trial/. Accessed 5/4/15.
- Gupta K, Steffen KJ, Natarajan B, Biria M, Singh V, Cherian G. A multispecialty consensus-based approach to carotid artery revascularization is feasible in routine clinical practice and results in excellent clinical outcomes. J Invasive Cardiol 2014;26:123-7.
Keywords: Acetazolamide, Aged, Angioplasty, Aspirin, Balloon Occlusion, Blood Pressure, Brain, Carotid Arteries, Carotid Stenosis, Circle of Willis, Confidence Intervals, Constriction, Pathologic, Cooperative Behavior, Diabetes Mellitus, Embolic Protection Devices, Endarterectomy, Carotid, Follow-Up Studies, Hypertension, Incidence, Intracranial Embolism, Ischemic Attack, Transient, Life Expectancy, Life Style, Lipids, Magnetic Resonance Imaging, Neck Dissection, Neuroimaging, Plaque, Atherosclerotic, Prospective Studies, Research Personnel, Retrospective Studies, Risk, Risk Factors, Smoking, Smoking Cessation, Standard of Care, Stents, Stroke, Tomography, Uncertainty, Unnecessary Procedures
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