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Research ArticleExtracranial Vascular

The Risk of Stroke and TIA in Nonstenotic Carotid Plaques: A Systematic Review and Meta-Analysis

N. Singh, M. Marko, J.M. Ospel, M. Goyal and M. Almekhlafi
American Journal of Neuroradiology August 2020, 41 (8) 1453-1459; DOI: https://doi.org/10.3174/ajnr.A6613

Abstract

BACKGROUND: Severe carotid stenosis carries a high risk of stroke. However, the risk of stroke with nonstenotic carotid plaques (<50%) is increasingly recognized.

PURPOSE: We aimed to summarize the risk of TIA or stroke in patients with nonstenotic carotid plaques.

DATA SOURCES: We performed a comprehensive systematic review and meta-analysis in patients with acute ischemic stroke in whom carotid imaging was performed using MEDLINE and the Cochrane Database, including studies published up to December 2019.

STUDY SELECTION: Included studies had >10 patients with <50% carotid plaques on any imaging technique and reported the incidence or recurrence of ischemic stroke/TIA. High-risk plaque features and the risk of progression to stenosis >50% were extracted if reported.

DATA SYNTHESIS: We identified 31 studies reporting on the risk of ipsilateral stroke/TIA in patients with nonstenotic carotid plaques. Twenty-five studies (n = 13,428 participants) reported on first-ever stroke/TIA and 6 studies (n = 122 participants) reported on the recurrence of stroke/TIA.

DATA ANALYSIS: The incidence of first-ever ipsilateral stroke/TIA was 0.5/100 person-years. The risk of recurrent stroke/TIA was 2.6/100 person-years and increased to 4.9/100 person-years if intraplaque hemorrhage was present. The risk of progression to severe stenosis (>50%) was 2.9/100 person-years (8 studies, n = 448 participants).

LIMITATIONS: Included studies showed heterogeneity in reporting stroke etiology, the extent of stroke work-up, imaging modalities, and classification systems used for characterizing carotid stenosis.

CONCLUSIONS: The risk of recurrent stroke/TIA in nonstenotic carotid plaques is not negligible, especially in the presence of high-risk plaque features. Further research is needed to better define the significance of nonstenotic carotid plaques for stroke etiology.

ABBREVIATIONS:

ASyNC
asymptomatic nonstenotic carotid plaques
ESUS
embolic stroke of undetermined source
PICOS
Population, Intervention; Control or comparator; Outcomes
SyNC
symptomatic nonstenotic carotid plaques
ECST
European Carotid Surgery Trial

The etiology of acute ischemic stroke is crucial to guide further management and for the prevention of recurrent events. Carotid stenosis as the underlying etiology is found in up to 20% of cerebrovascular ischemic events.1,2 Current American Heart Association/American Stroke Association guidelines recommend carotid revascularization only in patients with symptomatic carotid stenosis of >50%.3 This recommendation is supported by data from the European Carotid Surgery Trial (ECST) and North America Symptomatic Carotid Endarterectomy Trial (NASCET), which showed a significant reduction of future strokes after revascularization of symptomatic severe carotid stenoses but modest benefit in moderate stenoses.4,5 Thus, the management of symptomatic patients with <50% stenosis is undetermined. In addition, the risk of stroke and TIA with carotid plaques of <50% is not well-defined, though recent evidence suggests their potential role in stroke,6⇓⇓-9 especially in those classified as cryptogenic. Moreover, certain morphologic features of carotid plaques are independent risk factors of stroke/TIA, irrespective of the degree of stenosis.6,10,11 In a recent meta-analysis, mild carotid stenosis with “high-risk plaque features” was significantly more common in patients with an embolic stroke of undetermined source (ESUS) ipsilateral to the side of stroke compared with the contralateral side.12 Moreover, there are studies proposing carotid revascularization as a treatment option in patients with nonstenotic carotid plaques with recurrent ipsilateral strokes despite adequate medical treatment.13,14

We conducted a meta-analysis to estimate the risk of incident ischemic stroke/TIA in asymptomatic nonstenotic carotid plaques (ASyNC) as well as the risk of recurrent stroke/TIA in patients with symptomatic nonstenotic carotid plaques (SyNC).

MATERIALS AND METHODS

Our strategy to address the primary question above was informed by the Population, Intervention; Control or comparator; Outcomes (PICOS) framework recommended by the Cochrane Collaboration Handbook for Systematic Reviews of Interventions.15 Details are provided in the On-line Appendix.

Briefly, we included studies of individuals with asymptomatic or symptomatic nonstenotic carotid plaques (<50%) measured with any imaging technique (sonography/CT angiography/MR angiography/DSA). The primary outcome was the future risk of stroke/TIA in the ASyNC group and the risk of recurrent stroke/TIA in those with symptomatic nonstenotic carotid plaques. Retinal ischemic events (such as amaurosis fugax) were infrequently mentioned in the included studies and, if mentioned, were included in the subgroup of TIAs.

Search Strategy

We performed and reported this review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.16 We registered our protocol a priori in the PROSPERO international prospective register of systematic reviews (https://www.crd.york.ac.uk/PROSPERO; No. 162497). Data were collected from published studies; hence, ethics approval and consent were not required.

Our primary question was to describe the natural history of ASyNC and the risk of recurrent stroke/TIA in patients with symptomatic nonstenotic carotid plaques (SyNC). Natural history incorporates both the risk of ischemic stroke/TIA on follow-up and the risk of progression to severe stenosis in patients with asymptomatic, nonstenotic carotid plaques. We defined nonstenotic carotid plaques as carotid plaques with <50% stenosis. SyNC was defined as a carotid plaque with <50% luminal stenosis and an ipsilateral stroke/TIA. In studies that grouped patients into <30%, 30%–70%, and >70% stenosis, only the group of patients with <30% stenosis was included in the analysis to avoid overestimation of the predefined outcome by including a subgroup of patients with 50%–70% carotid stenosis.

Secondary questions included the effects of plaque features on the risk of stroke/TIA. Plaque features include intraplaque hemorrhage, lipid-rich necrotic core, ulceration, fibrous cap, calcification, and thrombus. Additionally, we aimed to assess whether treatment affects the risk of future or recurrent ischemic stroke/TIA. Treatments included medical (antiplatelets, statins) and interventional (endarterectomy or stent placement) management. Details of the framework, search strategy, study selection with inclusion and exclusion criteria, and bias assessment, including publication bias, are mentioned in the On-line Appendix (On-line Figs 1–7).

Fig 1.
Fig 1.

Incidence rate (per 100 person-years) of stroke in patients with ASyNC. ES indicates effect size.

Fig 2.
Fig 2.

Incidence rate (per 100 person-years) of recurrent stroke in patients with SyNC. ES indicates effect size.

Fig 3.
Fig 3.

Incidence rate (per 100 person-years) of recurrent stroke in patients with SyNC, with intraplaque hemorrhage (IPH). ES indicates effect size.

Fig 4.
Fig 4.

Risk of progression of <50% stenosis to >50% stenosis in ASyNC. ES indicates effect size.

Statistical Analysis

Analyses were performed using STATA/IC, Version 14.0 (StataCorp). The meta-analyses were performed using a random-effects model of variance. Heterogeneity was calculated using the Higgins I2 statistic (with associated P values). We also evaluated the primary outcomes through subgroup analyses using a stratified random-effects meta-analysis. Publication bias was assessed using the Egger test.

RESULTS

Summary findings of key data-extraction elements are presented in On-line Tables 1 and 2.

Risk of First-Ever Stroke/TIA in Asymptomatic Nonstenotic Carotid Plaques

Of the total 25 studies involving 24,847 participants (18 prospective, 2 randomized trials, 6 retrospective), the mean age was 67.5 years (range, 58.1–78.7 years), and men represented 50.4%. The classification of stroke etiology using the Trial of Org 10172 in Acute Stroke Treatment criteria was mentioned in only 3 studies.17-19 Grading of the degree of stenosis was predominantly based on the NASCET criteria5 and other United States–based classification systems. The average follow-up, reported in 20 studies, was 4.8 years.

Of 24,847 participants, 13,428 (54%) had ASyNC at baseline; the remaining 11,419 (45.9%) were not included in the analysis because they either had no stenosis or were classified into a 30%–70% stenosis group in the study. During a mean follow-up of 4.4 years, 730 subjects (5.4%) with ASyNC developed ischemic stroke/TIA. The incidence rate of stroke/TIA in ASyNC was 0.5/100 person-years (Fig 1).

Risk of Recurrent Stroke/TIA in Symptomatic Nonstenotic Carotid Plaques

Of a total of 680 participants with SyNC in 14 studies, the mean age was 70.2 years, and most were men (n = 454, 66.7%). Classification per the Trial of Org 10172 in Acute Stroke Treatment criteria was mentioned in 8 studies.6,20⇓⇓⇓⇓⇓-26 Most studies (n = 9) used the NASCET criteria5 to define the degree of stenosis.

Six studies8,13,14,20,27,28 (n = 122) reported recurrence of ischemic stroke/TIA (n = 20, 16.4%) during a mean follow-up of 3.1 years. The incidence rate of recurrent stroke in this population was 2.6/100 person-years (Fig 2).

All except 4 studies13,14,20,27 reported plaque features that were associated with a higher risk of recurrent stroke/TIA. These were intraplaque hemorrhage,29 ulceration,25,29 echolucent plaques,10 hyperintense plaque,19 irregular plaque,30 and fibrous cap with a lipid-rich core.31 Three studies13,14,27 found intraplaque hemorrhage associated with a high rate of recurrent ischemic events: 4.9/100 person-years (95% CI, 1.6–8.1 person-years; Fig 3). For the remaining plaque features, the data were insufficient for a meta-analysis.

Ten studies reported treatment strategies for patients with SyNC. Of those, 5 used medical treatment (antiplatelets, statins) alone,6,21,23,26,27 3 reported a combination of medical treatment and carotid revascularization,8,20,28 1 study reported both surgical and endovascular management,14 and 1 study reported only surgical outcomes.13 The low numbers in these arms were insufficient to perform a meta-analysis.

Risk of Progression to >50% Stenosis in ASyNC

Eight studies (n = 2223 participants) assessed stenosis progression from <50% to >50%. Overall, 448 of 2223 (20.2%) patients with ASyNC had stenosis progression. The pooled risk of progression was 11% (95% CI, 10%–12%; I2 = 0, P < .01) during a mean follow-up of 6.0 years (Fig 4).

Sensitivity Analyses

Detailed analyses as per study design and imaging technique for both ASyNC and SyNC are provided in the On-line Appendix (On-line Figs 8–11).

DISCUSSION

Carotid stenosis with >50% luminal narrowing accounts for 10%–20% of all strokes.32,33 The long-term risk of ipsilateral stroke in patients with >70% stenosis was 28.3% at 3 years in NASCET5 and 19% at 5 years in the ECST.4 These risks were significantly reduced after carotid revascularization. The long-term risk of ipsilateral stroke in carotid stenosis of <50% during 5 years was 18.7% in the NASCET and 8.2% in the ECST.4,5 Recently, multiple studies have shown an association between nonstenotic (<50%) carotid plaques and ischemic stroke,7,13,19 suggesting that certain carotid plaques might be an important source of stroke irrespective of the degree of stenosis. Our reported incidence of recurrent ipsilateral stroke/TIA in symptomatic, nonstenotic (<50%) carotid plaques, which substantially increases in the presence of high-risk plaque features, is comparable with the risk of recurrent strokes in stenotic (>50%) carotid plaques per NASCET and the ECST (around 9% and 4% per year, respectively).4,5 In contrast, the incidence of first-ever TIA or stroke in asymptomatic nonstenotic carotid plaques is lower compared with a 3%–4% annual incidence of stroke with severe (>70%) carotid stenosis per the Asymptomatic Carotid Atherosclerosis Study in the United States and the Asymptomatic Carotid Surgery Trial in Europe.34,35

In this meta-analysis, the relatively high rate of recurrent strokes in SyNC can be explained by the high-risk patients who already had at least 1 stroke with associated risk factors. In addition, because most studies included strokes of different etiologies, nonstenotic plaques might be an incidental finding in many cases, and these recurrent strokes are due to other unidentified etiologies (eg, cardioembolic). Also, the stroke etiology work-up was not uniform, and none of the studies that reported stroke recurrence outlined the investigations performed to rule out a cardioembolic source. On the other hand, with the increasing use of CTA to investigate stroke etiology, symptomatic nonstenotic carotid lesions are now recognized more frequently, and the risk of recurrent events might indeed be high. However, given the small sample size, selection bias and biases in reporting results cannot be ruled out.

Eight of the 14 studies with SyNC reported stroke etiology, and in all of these, ESUS was the predominant etiology. As of today, data supporting nonstenotic carotid lesions as a possible etiology of stroke are not robust, and most of these patients are currently classified as having ESUS if other sources of stroke are ruled out.9,28 The incidence of recurrent strokes was 2.6/100 person-years in patients with nonstenotic carotid lesions and otherwise unknown etiology, which may suggest that SyNC is potentially the etiology of these cryptogenic strokes.

Apart from the measurement of the degree of stenosis, growing literature uses high-definition vessel wall imaging of high-risk plaque features to identify patients at increased risk of recurrent stroke, despite low-grade stenosis.11,36 In this metanalysis, studies in both populations (especially SyNC) reported specific plaque features that predict a high recurrence rate, the most common being intraplaque hemorrhage. We found that the incidence rate of recurrent strokes is the same as that in symptomatic severe carotid stenosis, which should raise awareness of this high-risk subgroup. However, these studies are relatively small (total n = 31) and few in number (n = 3). Also, our search strategy did not include specific terms like “intraplaque hemorrhage” and so forth because this was not our primary outcome, which may have led to under-reporting of these specific features. Even though the representation of the subgroup of patients with SyNC and high-risk plaque features in the currently existing literature is limited, these findings are thought-provoking and support the need for larger studies and further validation.

Another important aspect is the treatment of patients with symptomatic nonstenotic carotid plaques. Current guidelines rely on the measurement of the degree of stenosis to recommend carotid revascularization.3 However, there is increasing evidence to suggest that unstable, inflamed, carotid plaques could rupture, causing stroke irrespective of the degree of stenosis.37 Furthermore, studies have also demonstrated that certain subgroups of patients with nonstenotic carotid stenosis tend to have recurrent strokes despite the best medical management.28,37,38 These observations suggest a limited efficacy of medical therapy in a subgroup of patients with SyNC with high-risk plaque features. Recent studies using high-resolution imaging to detect high-risk patients with SyNC have shown a benefit of carotid revascularization with almost no recurrence on follow-up.8,13 These studies indicate that the degree of stenosis alone may not be sufficient to determine treatment strategies, and plaque features and vulnerability may become important considerations in the treatment decision-making.

Limitations

This meta-analysis has several limitations: First, many of the included studies for assessing the risk of first-ever stroke/TIA in nonstenotic carotid plaques were relatively old: Ten of 25 were published before 2000, and the oldest study was published in 1984. Also, many of these studies traditionally classified the degree of stenosis as <30%, 30%–70%, and >70% before the NASCET definition. Because this classification system incorporates 50%–70% stenosis along with nonstenotic plaques, we excluded them to avoid the overestimation of results. Furthermore, there is heterogeneity both in the imaging technique and the underlying classification system used for characterizing carotid stenosis in the included studies. We addressed this issue using sensitivity analyses, stratifying by imaging technique. Last, only a few publications reported stroke etiology, and overall, the number of patients with ESUS and nonstenotic carotid plaques was provided infrequently. Even though our results are overall comparable with numbers reported in prior studies7 of patients with ESUS and nonstenotic carotid plaques, overestimation of recurrent events might have occurred because other etiologies of stroke (eg, cardioembolic) could not be excluded.

CONCLUSIONS

The risk of first-ever stroke/TIA with ASyNC in our meta-analysis was low, but once the patient was symptomatic, the risk of recurrent stroke/TIA in SyNC increased substantially, particularly when high-risk features such as intraplaque hemorrhage were present. Given the emerging evidence for an association between nonstenotic carotid plaques and stroke, one must consider it an etiology and investigate further to assess high-risk features. Presently, there is insufficient evidence to support a treatment strategy for this high-risk subgroup of patients with SyNC. Further research is needed to better investigate the natural history, progression from <50% to >50% stenosis, and potential treatment options such as more aggressive medical management or carotid revascularization of patients with nonstenotic carotid plaques.

Footnotes

  • N. Singh and M. Marko contributed equally to this publication.

  • Disclosures: Mayank Goyal—UNRELATED: Consultancy: Medtronic, Stryker, Mentice, MicroVention; Grants/Grants Pending: Medtronic, Stryker, Cerenovus*; Patents (Planned, Pending or Issued): GE Healthcare, Comments: systems of acute stroke diagnosis; Royalties: GE Healthcare. *Money paid to the institution.

References

  1. 1.↵
    1. Mortimer R,
    2. Nachiappan S,
    3. Howlett DC
    . Carotid artery stenosis screening: where are we now? Br J Radiology 2018;91:20170380 doi:10.1259/bjr.20170380 pmid:29770736
    CrossRefPubMed
  2. 2.↵
    1. Cheng SF,
    2. Brown MM,
    3. Simister RJ, et al
    . Contemporary prevalence of carotid stenosis in patients presenting with ischaemic stroke. Br J Surg 2019;106:872–78 doi:10.1002/bjs.11136 pmid:30938840
    CrossRefPubMed
  3. 3.↵
    1. Brott TG,
    2. Halperin JL,
    3. Abbara S, et al
    . 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. Developed in collaboration with the American Academy of Neurology and Society of Cardiovascular Computed Tomography. Catheter Cardiovasc Interv 2013;81:E76–123 doi:10.1002/ccd.22983 pmid:23281092
    CrossRefPubMed
  4. 4.↵
    Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998;351:1379–87 pmid:9593407
    CrossRefPubMed
  5. 5.↵
    1. Ferguson GG,
    2. Eliasziw M,
    3. Barr HW, et al
    . The North American Symptomatic Carotid Endarterectomy Trial. Stroke 1999;30:1751–58 doi:10.1161/01.str.30.9.1751 pmid:10471419
    Abstract/FREE Full Text
  6. 6.↵
    1. Coutinho JM,
    2. Derkatch S,
    3. Potvin ARJ, et al
    . Nonstenotic carotid plaque on CT angiography in patients with cryptogenic stroke. Neurology 2016;87:665–72 doi:10.1212/WNL.0000000000002978 pmid:27412144
    CrossRefPubMed
  7. 7.↵
    1. Ntaios G,
    2. Swaminathan B,
    3. Berkowitz SD, et al
    ; NAVIGATE ESUS Investigators. Efficacy and safety of rivaroxaban versus aspirin in embolic stroke of undetermined source and carotid atherosclerosis. Stroke 2019;50:2477–85 doi:10.1161/STROKEAHA.119.025168 pmid:31401971
    CrossRefPubMed
  8. 8.↵
    1. Yoshida K,
    2. Fukumitsu R,
    3. Kurosaki Y, et al
    . Carotid endarterectomy for medical therapy-resistant symptomatic low-grade stenosis. World Neurosurg 2019;123:e543–48 doi:10.1016/j.wneu.2018.11.208 pmid:30521960
    CrossRefPubMed
  9. 9.↵
    1. Singh TD,
    2. Kramer CL,
    3. Mandrekar J, et al
    . Asymptomatic carotid stenosis: risk of progression and development of symptoms. Cerebrovasc Dis 2015;40:236–43 doi:10.1159/000439179 pmid:26484542
    CrossRefPubMed
  10. 10.↵
    1. Bock RW,
    2. Gray-Weale AC,
    3. Mock PA, et al
    . The natural history of asymptomatic carotid artery disease. J Vasc Surg 1993;17:160–71 doi:10.1016/0741-5214(93)90020-M
    CrossRefPubMed
  11. 11.↵
    1. Hosseini AA,
    2. Simpson RJ,
    3. Altaf N, et al
    . Magnetic resonance imaging plaque hemorrhage for risk stratification in carotid artery disease with moderate risk under current medical therapy. Stroke 2017;48:678–85 doi:10.1161/STROKEAHA.116.015504 pmid:28196937
    Abstract/FREE Full Text
  12. 12.↵
    1. Kamtchum-Tatuene J,
    2. Wilman A,
    3. Saqqur M, et al
    . Carotid plaque with high-risk features in embolic stroke of undetermined source: systematic review and meta-analysis. Stroke 2020;51:311–14 doi:10.1161/STROKEAHA.119.027272 pmid:28196937
    CrossRefPubMed
  13. 13.↵
    1. Kashiwazaki D,
    2. Shiraishi K,
    3. Yamamoto S, et al
    . Efficacy of carotid endarterectomy for mild (<50%) symptomatic carotid stenosis with unstable plaque. World Neurosurg 2019;121:e60–69 doi:10.1016/j.wneu.2018.09.013 pmid:30244188
    CrossRefPubMed
  14. 14.↵
    1. Takai H,
    2. Uemura J,
    3. Yagita Y, et al
    . Plaque characteristics of patients with symptomatic mild carotid artery stenosis. J Stroke Cerebrovasc Dis 2018;27:1930–36 doi:10.1016/j.jstrokecerebrovasdis.2018.02.032 pmid:29571763
    CrossRefPubMed
  15. 15.↵
    1. Cumpston M,
    2. Li T,
    3. Page MJ, et al
    . Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev 2019;10:ED000142 doi:10.1002/14651858.ED000142 pmid:31643080
    CrossRefPubMed
  16. 16.↵
    1. Moher D,
    2. Liberati A,
    3. Tetzlaff J, et al
    ; PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. PLoS Med 2009;6:e1000097 doi:10.1371/journal.pmed.1000097 pmid:19621072
    CrossRefPubMed
  17. 17.↵
    1. AbuRahma AF,
    2. Cook CC,
    3. Metz MJ, et al
    . Natural history of carotid artery stenosis contralateral to endarterectomy: results from two randomized prospective trials. J Vasc Surg 2003;38:1154–61 doi:10.1016/j.jvs.2003.07.028 pmid:14681599
    CrossRefPubMed
  18. 18.
    1. Goessens BM,
    2. Visseren FL,
    3. Kappelle LJ, et al
    . Asymptomatic carotid artery stenosis and the risk of new vascular events in patients with manifest arterial disease: the SMART study. Stroke 2007;38:1470–75 doi:10.1161/STROKEAHA.106.477091 pmid:17363718
    Abstract/FREE Full Text
  19. 19.↵
    1. Yamada K,
    2. Yoshimura S,
    3. Shirakawa M, et al
    . Asymptomatic moderate carotid artery stenosis with intraplaque hemorrhage: progression of degree of stenosis and new ischemic stroke. J Clin Neurosci 2019;63:95–99 doi:10.1016/j.jocn.2019.01.033 pmid:30732983
    CrossRefPubMed
  20. 20.↵
    1. de Haro J,
    2. Rodriguez-Padilla J,
    3. Bleda S, et al
    . Carotid stenting with proximal cerebral protection in symptomatic low-grade vulnerable recurrent carotid stenosis. Ther Adv Chronic Dis 2018;9:125–33 doi:10.1177/2040622318765727 pmid:29854374
    CrossRefPubMed
  21. 21.↵
    1. Freilinger TM,
    2. Schindler A,
    3. Schmidt C, et al
    . Prevalence of nonstenosing, complicated atherosclerotic plaques in cryptogenic stroke. JACC Cardiovasc Imaging 2012;5:397–405 doi:10.1016/j.jcmg.2012.01.012 pmid:22498329
    Abstract/FREE Full Text
  22. 22.↵
    1. Gupta A,
    2. Mushlin AI,
    3. Kamel H, et al
    . Cost-effectiveness of carotid plaque MR imaging as a stroke risk stratification tool in asymptomatic carotid artery stenosis. Radiology 2015;277:927 doi:10.1148/radiol.2015154030 pmid:26599936
    CrossRefPubMed
  23. 23.↵
    1. Hyafil F,
    2. Schindler A,
    3. Sepp D, et al
    . High-risk plaque features can be detected in non-stenotic carotid plaques of patients with ischaemic stroke classified as cryptogenic using combined 18F-FDG PET/MR imaging. Eur J Nucl Med Mol Imaging 2016;43:270–79 doi:10.1007/s00259-015-3201-8
    CrossRef
  24. 24.↵
    1. Komatsu T,
    2. Iguchi Y,
    3. Arai A, et al
    . Large but nonstenotic carotid artery plaque in patients with a history of embolic stroke of undetermined source. Stroke 2018;49:3054–56 doi:10.1161/STROKEAHA.118.022986 pmid:30571401
    CrossRefPubMed
  25. 25.↵
    1. Singh N,
    2. Moody AR,
    3. Panzov V, et al
    . Carotid intraplaque hemorrhage in patients with embolic stroke of undetermined source. J Stroke Cerebrovasc Dis 2018;27:1956–59 doi:10.1016/j.jstrokecerebrovasdis.2018.02.042 pmid:29571754
    CrossRefPubMed
  26. 26.↵
    1. Xu Y,
    2. Yuan C,
    3. Zhou Z, et al
    . Co-existing intracranial and extracranial carotid artery atherosclerotic plaques and recurrent stroke risk: a three-dimensional multicontrast cardiovascular magnetic resonance study. J Cardiovasc Magn Reson 2016;18:90 doi:10.1186/s12968-016-0309-3 pmid:27908279
    CrossRefPubMed
  27. 27.↵
    1. Altaf N,
    2. Daniels L,
    3. Morgan PS, et al
    . Detection of intraplaque hemorrhage by magnetic resonance imaging in symptomatic patients with mild to moderate carotid stenosis predicts recurrent neurological events. J Vasc Surg 2008;47:337–42 doi:10.1016/j.jvs.2007.09.064 pmid:18164171
    CrossRefPubMed
  28. 28.↵
    1. Yoshida K,
    2. Sadamasa N,
    3. Narumi O, et al
    . Symptomatic low-grade carotid stenosis with intraplaque hemorrhage and expansive arterial remodeling is associated with a high relapse rate refractory to medical treatment. Neurosurgery 2012;70:1143–51 doi:10.1227/NEU.0b013e31823fe50b pmid:22076530
    CrossRefPubMed
  29. 29.↵
    1. Lee SK,
    2. Yun CH,
    3. Oh JB, et al
    . Intracranial ictal onset zone in nonlesional lateral temporal lobe epilepsy on scalp ictal EEG. Neurology 2003;61:757–64 doi:10.1212/01.wnl.0000086377.94037.80 pmid:14504317
    Abstract/FREE Full Text
  30. 30.↵
    1. Ballotta E,
    2. Da Giau G,
    3. Meneghetti G, et al
    . Progression of atherosclerosis in asymptomatic carotid arteries after contralateral endarterectomy: a 10-year prospective study. J Vasc Surg 2007;45:516–22 doi:10.1016/j.jvs.2006.11.011 pmid:17275244
    CrossRefPubMed
  31. 31.↵
    1. Wintermark M,
    2. Arora S,
    3. Tong E, et al
    . Carotid plaque computed tomography imaging in stroke and nonstroke patients. Ann Neurol 2008;64:149–57 doi:10.1002/ana.21424 pmid:18756475
    CrossRefPubMed
  32. 32.↵
    1. Adams HP,
    2. Bendixen BH,
    3. Kappelle LJ, et al
    . Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. TOAST—Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35–41 doi:10.1161/01.str.24.1.35 pmid:7678184
    Abstract/FREE Full Text
  33. 33.↵
    1. Petty GW,
    2. Brown RD,
    3. Whisnant JP, et al
    . Ischemic stroke subtypes. Stroke 2000;31:1062–68 doi:10.1161/01.STR.31.5.1062
    Abstract/FREE Full Text
  34. 34.↵
    [No authors listed] Endarterectomy for asymptomatic carotid artery stenosis: Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 1995;273:1421–28 pmid:7723155
    CrossRefPubMed
  35. 35.↵
    1. Halliday A,
    2. Mansfield A,
    3. Marro J, et al
    ; MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet 2004;363:1491–1502 doi:10.1016/S0140-6736(04)16146-1 pmid:15135594
    CrossRefPubMed
  36. 36.↵
    1. Gupta A,
    2. Baradaran H,
    3. Schweitzer AD, et al
    . Carotid plaque MRI and stroke risk. Stroke 2013;44:3071–77 doi:10.1161/STROKEAHA.113.002551 pmid:23988640
    Abstract/FREE Full Text
  37. 37.↵
    1. Truijman MT,
    2. Kooi ME,
    3. van Dijk AC, et al
    . Plaque at RISK (PARISK): prospective multicenter study to improve diagnosis of high-risk carotid plaques. Int J Stroke 2014;9:747–54 doi:10.1111/ijs.12167 pmid:24138596
    CrossRefPubMed
  38. 38.↵
    1. Karlsson L,
    2. Kangefjärd E,
    3. Hermansson S, et al
    . Risk of recurrent stroke in patients with symptomatic mild (20-49% NASCET) carotid artery stenosis. Eur J Vasc Endovasc Surg 2016;52:287–94 doi:10.1016/j.ejvs.2016.05.014 pmid:27369293
    CrossRefPubMed
  39. 39.
    1. Alexandrova NA,
    2. Gibson WC,
    3. Norris JW, et al
    . Carotid artery stenosis in peripheral vascular disease. J Vasc Surg 1996;23:645–49 doi:10.1016/S0741-5214(96)80045-0 pmid:8627901
    CrossRefPubMed
  40. 40.
    1. Chen Q,
    2. Liu Y,
    3. Pei L, et al
    . Characteristics of carotid artery disease (CAD) and presenting cerebrovascular symptoms in an aged group. Int J Cardiovasc Imaging 2009;25:127–32 doi:10.1007/s10554-008-9367-4 pmid:18853278
    CrossRefPubMed
  41. 41.
    1. Högberg D,
    2. Björck M,
    3. Mani K, et al
    . Five year outcomes in men screened for carotid artery stenosis at 65 years of age: a population based cohort study. Eur J Vasc Endovasc Surg 2019;57:759–66 doi:10.1016/j.ejvs.2019.02.005 pmid:31142437
    CrossRefPubMed
  42. 42.
    1. Johnson BF,
    2. Verlato F,
    3. Bergelin RO, et al
    . Clinical outcome in patients with mild and moderate carotid artery stenosis. J Vasc Surg 1995;21:120–26 doi:10.1016/S0741-5214(95)70250-4 pmid:7823350
    CrossRefPubMed
  43. 43.
    1. Jungquist G,
    2. Nilsson B,
    3. Ostberg H, et al
    . Carotid artery blood flow velocity related to transient ischemic attack and stroke in a population study of 69-year-old men. Stroke 1989;20:1327–30 doi:10.1161/01.str.20.10.1327 pmid:2678611
    Abstract/FREE Full Text
  44. 44.
    1. Kaul S,
    2. Alladi S,
    3. Mridula KR, et al
    . Prevalence and risk factors of asymptomatic carotid artery stenosis in Indian population: an 8-year follow-up study. Neurol India 2017;65:279–85 doi:10.4103/neuroindia.NI_523_16 pmid:28290390
    CrossRefPubMed
  45. 45.
    1. Lewis RF,
    2. Abrahamowicz M,
    3. Côté R, et al
    . Predictive power of duplex ultrasonography in asymptomatic carotid disease. Ann Intern Med 1997;127:13–20 doi:10.7326/0003-4819-127-1-199707010-00003 pmid:9214247
    CrossRefPubMed
  46. 46.
    1. Mackey AE,
    2. Abrahamowicz M,
    3. Langlois Y, et al
    . Outcome of asymptomatic patients with carotid disease: Asymptomatic Cervical Bruit Study Group. Neurology 1997;48:896–903 doi:10.1212/WNL.48.4.896 pmid:9109874
    Abstract/FREE Full Text
  47. 47.
    1. Masoomi R,
    2. Shah Z,
    3. Dawn B, et al
    . Progression of external and internal carotid artery stenosis is associated with a higher risk of ischemic neurologic events in patients with asymptomatic carotid artery stenosis. Vasc Med 2017;22:418–23 doi:10.1177/1358863X17722626 pmid:28830296
    CrossRefPubMed
  48. 48.
    1. Moore WS,
    2. Boren C,
    3. Malone JM, et al
    . Natural history of nonstenotic, asymptomatic ulcerative lesions of the carotid artery. Arch Surg 1978;113:1352–59 doi:10.1001/archsurg.1978.01370230142018 pmid:708257
    CrossRefPubMed
  49. 49.
    1. Noh M,
    2. Kwon H,
    3. Jung CH, et al
    . Impact of diabetes duration and degree of carotid artery stenosis on major adverse cardiovascular events: a single-center, retrospective, observational cohort study. Cardiovasc Diabetol 2017;16:74:06 doi:10.1186/s12933-017-0556-0 pmid:28587650
    CrossRefPubMed
  50. 50.
    1. Polak JF,
    2. Shemanski L,
    3. O'Leary DH, et al
    . Hypoechoic plaque at US of the carotid artery: an independent risk factor for incident stroke in adults aged 65 years or older: Cardiovascular Health Study. Radiology 1998;208:649–54 doi:10.1148/radiology.208.3.9722841 pmid:9722841
    CrossRefPubMed
  51. 51.
    1. Prabhakaran S,
    2. Rundek T,
    3. Ramas R, et al
    . Carotid plaque surface irregularity predicts ischemic stroke: the northern Manhattan study. Stroke 2006;37:2696–701 doi:10.1161/01.STR.0000244780.82190.a4 pmid:17008627
    Abstract/FREE Full Text
  52. 52.
    1. Roederer GO,
    2. Langlois YE,
    3. Jager KA, et al
    . The natural history of carotid arterial disease in asymptomatic patients with cervical bruits. Stroke 1984;15:605–13 doi:10.1161/01.STR.15.4.605 pmid:6464052
    Abstract/FREE Full Text
  53. 53.
    1. Tong Y,
    2. Royle J
    . Outcome of patients with symptomless carotid bruits: a prospective study. Cardiovasc Surg 1996;4:174–80 doi:10.1016/0967-2109(96)82310-6 pmid:8861432
    CrossRefPubMed
  54. 54.
    1. Yamada N,
    2. Higashi M,
    3. Otsubo R, et al
    . Association between signal hyperintensity on T1-weighted MR imaging of carotid plaques and ipsilateral ischemic events. AJNR Am J Neuroradiol 2007;28:287–92 pmid:17296997
    Abstract/FREE Full Text
  55. 55.
    1. Underhill HR,
    2. Yuan C,
    3. Yarnykh VL, et al
    . Arterial remodeling in [corrected] subclinical carotid artery disease. JACC Cardiovasc Imaging 2009;2:1381–89 doi:10.1016/j.jcmg.2009.08.007 pmid:20083072
    Abstract/FREE Full Text
  56. 56.
    1. Zhang Y,
    2. Fang X,
    3. Hua Y, et al
    . Carotid artery plaques, carotid intima-media thickness, and risk of cardiovascular events and all-cause death in older adults: a 5-year prospective, community-based study. Angiology 2018;69:120–29 doi:10.1177/0003319717716842 pmid:28675103
    CrossRefPubMed
  57. 57.
    1. Zierler RE,
    2. Kohler TR,
    3. Strandness DE
    . Duplex scanning of normal or minimally diseased carotid arteries: correlation with arteriography and clinical outcome. J Vasc Surg 1990;12:447–55 doi:10.1067/mva.1990.22603 pmid:2214040
    CrossRefPubMed
  58. 58.
    1. Ishikawa M,
    2. Sugawara H,
    3. Tsuji T, et al
    . Clinical significance of the coexistence of carotid artery plaque and white matter disease in patients with symptomatic cerebral infarction. Clin Neurol Neurosurg 2017;163:179–85 doi:10.1016/j.clineuro.2017.10.027 pmid:29132058
    CrossRefPubMed
  • Received March 7, 2020.
  • Accepted after revision April 29, 2020.
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The Risk of Stroke and TIA in Nonstenotic Carotid Plaques: A Systematic Review and Meta-Analysis
N. Singh, M. Marko, J.M. Ospel, M. Goyal, M. Almekhlafi
American Journal of Neuroradiology Aug 2020, 41 (8) 1453-1459; DOI: 10.3174/ajnr.A6613
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