title: Carotid atherosclerotic plaques in patients with transient ischemic attacks and stroke have unstable characteristics compared with plaques in asymptomatic and amaurosis fugax patients.
abstract: BACKGROUND
  Atherosclerotic carotid artery disease is responsible for a variety of clinical presentations, ranging from asymptomatic to cerebral ischemic events. Considering the upcoming use of noninvasive imaging modalities, plaque characteristics could serve as a marker in the selection of patients eligible for carotid endarterectomy (CEA). This would be more likely if characteristics corresponded with clinical manifestations and were predictive of future events. In this study, we hypothesized that plaque characteristics correlate with the clinical presentation of carotid artery disease.
  
  
  METHODS
  We included 404 patients undergoing a carotid endarterectomy (CEA). Ipsilateral clinical symptoms and duplex measurements were recorded. Patients could be asymptomatic (23.5%) or symptomatic with stroke (26.5%), transient ischemic attack (TIA) (36.1%), or amaurosis fugax (AFX) (13.9%). Plaques were stained and semi-quantitatively analyzed for the presence of macrophages, smooth muscle cells, collagen, calcifications, and thrombus. Plaques were categorized in three phenotypes by their overall presentation and the amount of fat. In addition, plaque matrix metalloproteinase (MMP) activity and cytokines expressions were measured.
  
  
  RESULTS
  Fibrous, fibro-atheromatous, and atheromatous plaques were observed in 30.2%, 35.6%, and 34.2%, respectively. Atheromatous plaques were more prevalent in patients with stroke and TIA compared with asymptomatic patients or patients with AFX (P = .001). Collagen staining was less evident in patients with TIA and stroke compared with asymptomatic patients or patients with AFX (P < .001). Plaques of patients with TIA and stroke showed significantly higher activity levels of MMP-8 and MMP-9 and higher levels of interleukin-8 compared with asymptomatic and AFX patients.
  
  
  CONCLUSIONS
  Plaque phenotype of patients with TIA is comparable to that of patients with stroke; whereas, the plaque phenotype of patients with AFX resembles the plaque phenotype of asymptomatic patients. Follow-up studies should be encouraged to determine whether plaque characteristics visualized by imaging techniques might help to identify patients most likely to benefit from CEA.
authors.affiliation: Department of Vascular Surgery, University Medical Centre Utrecht, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Verhoeven
authors.forename: Willem E
authors.initials: WE
authors.lastname: Hellings
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: de Vries
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
authors.forename: Peter
authors.initials: P
authors.lastname: de Bruin
authors.forename: Els
authors.initials: E
authors.lastname: Busser
authors.forename: Arjen H
authors.initials: AH
authors.lastname: Schoneveld
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
mesh_terms: D000368:Aged; D020757:Amaurosis Fugax / Q000209:etiology* / Q000378:metabolism; D000792:Angiography; D015415:Biomarkers / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000209:etiology* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D020521:Stroke / Q000209:etiology* / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D018608:Ultrasonography, Doppler
chemical_list: D015415:Biomarkers; D016209:Interleukin-8; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9