Inserm, Institut national de la santé et de la recherche médicale
Faculté de pharmacie, Aix Marseille Université

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Plasmatic levels of leukocyte-derived microparticles predict unstable plaque in asymptomatic patients with high-grade carotid stenosis

Sarlon-Bartoli G., Bennis Y., Lacroix R., Piercecchi-Marti MD., Bartoli MA., Arnaud L., Boudes A., Sarlon E., Thevenin B., Leroyer AS., Squarcioni C., Magnan PE., Dignat-George F. and Sabatier F. J Am Coll Cardiol. 2013. In press.

Objectives

To analyze whether 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, non-invasive biomarkers that can predict plaque instability are needed. LMP, originating from activated or apoptotic leukocytes are the major microparticle subset in human carotid plaque extracts.
Methods Forty-two patients with greater than 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 AHA criteria. 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 [147-394] [25th percentile - 75th percentile], and CD15+MP/µl : 147 [60-335]) compared to those with stable plaque (16 [0-234] and 55 [36-157], 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 [153-410] and CD15+MP/µl : 78 [56-258] compared to those with stable plaque (n=14, 20 [0-251] and 55 [34-102], p<0.05 and p<0.05, respectively). After logistic regression, the neurologic symptoms (OR 48.7, 95% CI 3.0-788, p<0.01) and the level of CD11bCD66b+MPs (OR 24.4, 95% CI 2.4-245, 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.