Kinsella J A, Tobin W O, Kavanagh G F, O'Donnell J S, McGrath R T, Tierney S, Feeley T M, Egan B, O'Neill D, Collins R D, Coughlan T, Harbison J A, Doherty C P, Madhavan P, Moore D J, O'Neill S M, Colgan M-P, Saqqur M, Murphy R P, Moran N, Hamilton G, McCabe D J H
Department of Neurology, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland.
Eur J Neurol. 2014 Jul;21(7):969-e55. doi: 10.1111/ene.12403. Epub 2014 Apr 9.
von Willebrand factor propeptide (VWF:Ag II) is potentially a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). These biomarkers have not been simultaneously assessed in asymptomatic versus symptomatic carotid stenosis patients. The relationship between endothelial activation and cerebral microembolic signals (MESs) detected on transcranial Doppler ultrasound is unknown.
In this multicentre observational analytical study, plasma VWF:Ag and VWF:Ag II levels in patients with ≥50% asymptomatic carotid stenosis were compared with those from patients with ≥50% symptomatic carotid stenosis in the 'early' (≤4 weeks) and 'late' (≥3 months) phases after transient ischaemic attack or ischaemic stroke. Endothelial activation was also longitudinally assessed in symptomatic patients during follow-up. Transcranial Doppler ultrasound monitoring classified patients as MES-positive or MES-negative.
Data from 31 asymptomatic patients were compared with those from 46 early symptomatic and 35 late phase symptomatic carotid stenosis patients, 23 of whom had undergone carotid intervention. VWF:Ag II levels were higher in early (12.8 μg/ml; P < 0.001), late (10.6 μg/ml; P = 0.01) and late post-intervention (10.6 μg/ml; P = 0.038) symptomatic patients than asymptomatic patients (8.9 μg/ml). VWF:Ag levels decreased in symptomatic patients followed up from the early to late phase after symptom onset (P = 0.048). Early symptomatic MES-negative patients had higher VWF: Ag II levels (13.3 vs. 9.0 μg/ml; P < 0.001) than asymptomatic MES-negative patients.
Endothelial activation is enhanced in symptomatic versus asymptomatic carotid stenosis patients, in early symptomatic versus asymptomatic MES-negative patients, and decreases over time in symptomatic patients. VWF:Ag II levels are a more sensitive marker of endothelial activation than VWF:Ag levels in carotid stenosis. The potential value of endothelial biomarkers and concurrent cerebral MES detection at predicting stroke risk in carotid stenosis warrants further study.
血管性血友病因子前肽（VWF:Ag II）可能是比血管性血友病因子抗原（VWF:Ag）更敏感的急性内皮激活标志物。在无症状与有症状的颈动脉狭窄患者中，尚未同时对这些生物标志物进行评估。经颅多普勒超声检测到的内皮激活与脑微栓塞信号（MESs）之间的关系尚不清楚。
在这项多中心观察性分析研究中，将无症状性颈动脉狭窄≥50%患者在短暂性脑缺血发作或缺血性卒中后的“早期”（≤4周）和“晚期”（≥3个月）阶段的血浆VWF:Ag和VWF:Ag II水平，与有症状性颈动脉狭窄≥50%患者的相应水平进行比较。还对有症状患者在随访期间进行了内皮激活的纵向评估。经颅多普勒超声监测将患者分为MES阳性或MES阴性。
将31例无症状患者的数据与46例早期有症状和35例晚期有症状颈动脉狭窄患者的数据进行比较，其中23例患者接受了颈动脉干预。早期（12.8μg/ml；P<0.001）、晚期（10.6μg/ml；P=0.01）和干预后晚期（10.6μg/ml；P=0.038）有症状患者的VWF:Ag II水平高于无症状患者（8.9μg/ml）。有症状患者从症状发作的早期到晚期随访期间，VWF:Ag水平下降（P=0.048）。早期有症状MES阴性患者的VWF:Ag II水平（13.3对9.0μg/ml；P<0.001）高于无症状MES阴性患者。
有症状的颈动脉狭窄患者与无症状患者相比，早期有症状的MES阴性患者与无症状MES阴性患者相比，内皮激活增强，且有症状患者的内皮激活随时间下降。在颈动脉狭窄中，VWF:Ag II水平是比VWF:Ag水平更敏感的内皮激活标志物。内皮生物标志物和同时检测脑MES在预测颈动脉狭窄患者中风风险方面的潜在价值值得进一步研究。
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