Increased endothelial activation in recently symptomatic versus asymptomatic carotid artery stenosis and in cerebral microembolic-signal-negative patient subgroups.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Neurology, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland.
J A
JA
Kinsella
W O
WO
Tobin
G F
GF
Kavanagh
J S
JS
O'Donnell
R T
RT
McGrath
S
S
Tierney
T M
TM
Feeley
B
B
Egan
D
D
O'Neill
R D
RD
Collins
T
T
Coughlan
J A
JA
Harbison
C P
CP
Doherty
P
P
Madhavan
D J
DJ
Moore
S M
SM
O'Neill
M-P
MP
Colgan
M
M
Saqqur
R P
RP
Murphy
N
N
Moran
G
G
Hamilton
D J H
DJ
McCabe
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000209:etiology; D016893:Carotid Stenosis / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging; D004727:Endothelium / Q000378:metabolism*; D006801:Humans; D020766:Intracranial Embolism / Q000097:blood* / Q000000981:diagnostic imaging; D002546:Ischemic Attack, Transient / Q000209:etiology; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000209:etiology; D014463:Ultrasonography; D014841:von Willebrand Factor
D015415:Biomarkers; C029417:Von Willebrand antigen; D014841:von Willebrand Factor
carotid stenosis; cerebral microemboli; stroke; transient ischaemic attack; von Willebrand factor