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血浆中白细胞衍生的微颗粒水平与无症状的高分级颈动脉狭窄患者的不稳定斑块有关。

Plasmatic level of leukocyte-derived microparticles is associated with unstable plaque in asymptomatic patients with high-grade carotid stenosis.

机构信息

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.

出版信息

J Am Coll Cardiol. 2013 Oct 15;62(16):1436-41. doi: 10.1016/j.jacc.2013.03.078. Epub 2013 May 22.

Abstract

OBJECTIVES

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.

摘要

目的

本研究旨在分析白细胞衍生的微颗粒(LMP)的血浆水平是否与高分级颈动脉狭窄患者的不稳定斑块相关。

背景

鉴于医学治疗的改善,目前对于无症状患者的预防性颈动脉手术存在争议。因此,需要能够预测斑块不稳定性的非侵入性生物标志物。LMP 源自激活或凋亡的白细胞,是人类颈动脉斑块提取物中主要的微颗粒(MP)亚群。

方法

纳入 42 例颈动脉狭窄>70%的患者。在血栓内膜切除术之前,使用新的标准化高灵敏度流式细胞术检测 LMP。根据美国心脏协会的标准,通过组织学分析将切除的斑块特征化为稳定或不稳定。根据斑块形态分析 LMP 水平。

结果

不稳定斑块患者(n=28)的中位 LMP 水平明显高于稳定斑块患者(n=14)(CD11bCD66b+ MP/μl 240 [25 至 75 百分位数:147 至 394],CD15+ MP/μl 147 [60 至 335] 和 CD15+ MP/μl 55 [36 至 157];p<0.001 和 p<0.01)。当仅考虑不稳定斑块的无症状患者组(n=10)时,LMP 水平的增加也具有统计学意义(CD11bCD66b+ MP/μl 199 [153 至 410],CD15+ MP/μl 78 [56 至 258]与稳定斑块患者(n=14)相比,分别为 20 [0 至 251] 和 55 [34 至 102];p<0.05 和 p<0.05)。在逻辑回归后,神经症状(优势比:48.7,95%置信区间:3.0 至 788,p<0.01)和 CD11bCD66b+ MPs 水平(优势比:24.4,95%置信区间:2.4 至 245,p<0.01)独立预测斑块不稳定。

结论

LMP 是与高分级颈动脉狭窄患者斑块脆弱性相关的有前途的生物标志物。这些数据为识别最易发生神经事件的无症状患者提供了线索。

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