title: Plasmatic level of leukocyte-derived microparticles is associated with unstable plaque in asymptomatic patients with high-grade carotid stenosis.
abstract: OBJECTIVE
  This study sought to analyze whether the plasmatic level of leukocyte-derived microparticles (LMP) is associated with unstable plaques in patients with high-grade carotid stenosis.
  
  
  BACKGROUND
  Preventive carotid surgery in asymptomatic patients is currently debated given the improvement of medical therapy. Therefore, noninvasive biomarkers that can predict plaque instability are needed. The LMPs, originating from activated or apoptotic leukocytes, are the major microparticle (MP) subset in human carotid plaque extracts.
  
  
  METHODS
  Forty-two patients with >70% carotid stenosis were enrolled. Using a new standardized high-sensitivity flow cytometry assay, LMPs were measured before thromboendarterectomy. The removed plaques were characterized as stable or unstable using histological analysis according to the American Heart Association criteria. The LMP levels were analyzed according to the plaque morphology.
  
  
  RESULTS
  The median LMP levels were significantly higher in patients with unstable plaque (n = 28; CD11bCD66b+ MP/μl 240 [25th to 75th percentile: 147 to 394], and CD15+ MP/μl 147 [60 to 335]) compared to patients with stable plaque (16 [0 to 234] and 55 [36 to 157]; p < 0.001 and p < 0.01, respectively). The increase in LMP levels was also significant when considering only the group of asymptomatic patients with unstable plaque (n = 10; CD11bCD66b+ MP/μl 199 [153 to 410] and CD15+ MP/μl 78 [56 to 258] compared with patients with stable plaque (n = 14; 20 [0 to 251] and 55 [34 to 102]; p < 0.05 and p < 0.05, respectively). After logistic regression, the neurologic symptoms (odds ratio: 48.7, 95% confidence interval: 3.0 to 788, p < 0.01) and the level of CD11bCD66b+ MPs (odds ratio: 24.4, 95% confidence interval: 2.4 to 245, p < 0.01) independently predicted plaque instability.
  
  
  CONCLUSIONS
  LMP constitute a promising biomarker associated with plaque vulnerability in patients with high-grade carotid stenosis. These data provide clues for identifying asymptomatic subjects that are most at risk of neurologic events.
authors.affiliation: Service de Chirurgie Vasculaire, Faculté de Médecine de Marseille, Aix-Marseille Université, Assistance Publique Hôpitaux de Marseille-Hôpital de la Timone, Marseille, France; INSERM UMR-1076, Faculté de Pharmacie, Aix-Marseille Université, Marseille, France.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Sarlon-Bartoli
authors.forename: Youssef
authors.initials: Y
authors.lastname: Bennis
authors.forename: Romaric
authors.initials: R
authors.lastname: Lacroix
authors.forename: Marie Dominique
authors.initials: MD
authors.lastname: Piercecchi-Marti
authors.forename: Michel A
authors.initials: MA
authors.lastname: Bartoli
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnaud
authors.forename: Julien
authors.initials: J
authors.lastname: Mancini
authors.forename: Audrey
authors.initials: A
authors.lastname: Boudes
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Sarlon
authors.forename: Benjamin
authors.initials: B
authors.lastname: Thevenin
authors.forename: Aurelie S
authors.initials: AS
authors.lastname: Leroyer
authors.forename: Christian
authors.initials: C
authors.lastname: Squarcioni
authors.forename: Pierre Edouard
authors.initials: PE
authors.lastname: Magnan
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
authors.forename: Florence
authors.initials: F
authors.lastname: Sabatier
mesh_terms: D000368:Aged; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000378:metabolism; D002339:Carotid Arteries / Q000473:pathology / Q000601:surgery; D016893:Carotid Stenosis / Q000097:blood* / Q000150:complications / Q000503:physiopathology / Q000601:surgery; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D016894:Endarterectomy, Carotid / Q000379:methods*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control*; D058226:Plaque, Atherosclerotic / Q000473:pathology / Q000503:physiopathology; D011237:Predictive Value of Tests; D011300:Preoperative Care / Q000379:methods; D018570:Risk Assessment / Q000379:methods; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers
keywords: LMP; MP; NPV; PPV; atherosclerosis; high-grade carotid stenosis; leukocyte-derived microparticle; leukocyte-derived microparticles; microparticle; negative predictive value; positive predictive value; unstable plaque