Relationship between 'on-treatment platelet reactivity', shear stress, and micro-embolic signals in asymptomatic and symptomatic carotid stenosis.

BACKGROUND: Assessment of 'high on-treatment platelet reactivity (HTPR)' could enhance understanding of the pathophysiology of first or recurrent vascular events in carotid stenosis patients on antiplatelet therapy. METHODS: This prospective, multi-centre study assessed antiplatelet-HTPR status and its relationship with micro-emboli signals (MES) in asymptomatic vs. symptomatic ≥ 50-99% carotid stenosis. Platelet function/reactivity was assessed under 'moderately high shear stress' with the PFA-100® and 'low shear stress' with VerifyNow® and Multiplate® analysers. Bilateral 1-h transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES + ve or MES - ve. RESULTS: Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 patients in the 'late phase' (≥ 3 months) after TIA/ischaemic stroke. Median daily aspirin doses were higher in early symptomatic (225 mg; P < 0.001), but not late symptomatic (75 mg; P = 0.62) vs. asymptomatic patients (75 mg). There was a lower prevalence of aspirin-HTPR in early (28.6%; P = 0.028), but not late symptomatic (38.9%; P = 0.22) compared with asymptomatic patients (56.7%) on the PFA-100®, but not on the VerifyNow® or Multiplate® (P ≤ 0.53). Early symptomatic patients had a higher prevalence of aspirin-HTPR on the PFA-100® (28.6%) vs. VerifyNow® (9.5%; P = 0.049), but not Multiplate® assays (11.9%, P = 0.10). There was no difference in aspirin-HTPR prevalence between any symptomatic vs. asymptomatic MES + ve or MES - ve subgroup. DISCUSSION: Recently symptomatic moderate-severe carotid stenosis patients had a lower prevalence of aspirin-HTPR than their asymptomatic counterparts on the PFA-100®, likely related to higher aspirin doses. The prevalence of antiplatelet-HTPR was positively influenced by higher shear stress levels, but not MES status.

Syncope causes transient focal neurological symptoms.

AIMS: The prevalence of focal neurology (FN) as a consequence of syncope is unknown. The aim of the study was to determine its prevalence, risk factors and short-term consequences. METHODS: A consecutive sample of syncope-unit attendees during a 9-month period had detailed diagnostic syncope evaluation as per European Cardiac Society guidelines coupled with assessment for FN present during syncope/pre-syncope by screening questionnaire, follow-up interview and neuroimaging (1.5T magnetic resonance imaging [MRI]). All participants were followed up for 24 months. Risk factors for FN were identified by comparing FN cases with syncope controls without FN (3:1 ratio). RESULTS: Five-hundred and forty consecutively attended for investigation of syncope (n = 401) and pre-syncope (n = 139). Thirty-one (5.7%) had FN events during hypotensive symptoms, mean age 49 years (19-85). The majority of FN cases had vasovagal syncope (VVS); 22 (71%), whereas eight had OH (25.8%) and one (3.2%) had cardiac arrhythmia. Median duration of FN was 15 min (IQR: 34.5). MRI in 28 (90%) was normal and in 3, old cerebral infarction was evident. Risk factors for FN/syncope were frequent syncope (P = 0·008), childhood syncope (P < 0.0005) and delayed diastolic recovery during active stand (P = 0·02). During 24-month follow-up and targeted intervention, no patients developed recurrence of FN. CONCLUSION: One in 20 patients with syncope/pre-syncope have co-extant FN, which during 24-month follow-up, does not progress to a persistent deficit (>24 h). Awareness of co-occurrence of FN and syncope is important as stroke misdiagnosis results in aggressive anti-hypertensive management and future events may ensue.

Increased thrombin generation potential in symptomatic versus asymptomatic moderate or severe carotid stenosis and relationship with cerebral microemboli.

INTRODUCTION: The importance of thrombin generation in the pathogenesis of TIA or stroke and its relationship with cerebral microembolic signals (MES) in asymptomatic and symptomatic carotid stenosis has not been comprehensively assessed. METHODS: Plasma thrombin generation parameters from patients with moderate or severe (≥ 50%) asymptomatic carotid stenosis were compared with those from patients with symptomatic carotid stenosis in the early (≤ 4 weeks) and late phases (≥ 3 months) after TIA or stroke in this prospective, pilot observational study. Thrombin generation profile was longitudinally assessed in symptomatic patients with data at each time point. Bilateral transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed whenever possible to classify patients as MES-positive or MES-negative. RESULTS: Data from 31 asymptomatic, 46 'early symptomatic' and 35 'late symptomatic' patients were analysed. Peak thrombin (344.2 nM vs 305.3 nM; p = 0.01) and endogenous thrombin potential (1772.4 vs 1589.7; p = 0.047) were higher in early symptomatic than asymptomatic patients. Peak thrombin production decreased in symptomatic patients followed up from the early to late phase after TIA or stroke (339.7 nM vs 308.6 nM; p = 0.02). Transcranial Doppler ultrasound data were available in 25 asymptomatic, 31 early symptomatic and 27 late symptomatic patients. Early symptomatic MES-positive patients had a shorter 'time-to-peak thrombin' than asymptomatic MES-positive patients (p=0.04), suggesting a more procoagulant state in this early symptomatic subgroup. DISCUSSION: Thrombin generation potential is greater in patients with recently symptomatic than asymptomatic carotid stenosis, and decreases over time following TIA or stroke associated with carotid stenosis. These data improve our understanding of the haemostatic/thrombotic biomarker profile in moderate-severe carotid stenosis.

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

BACKGROUND AND PURPOSE: 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.

Hypertension and daytime hypotension found on ambulatory blood pressure is associated with fatigue following stroke and TIA.

BACKGROUND: Fatigue affects up to 68% of subjects following stroke. In non-stroke patients, associations are reported between chronic fatigue and both hypertension and hypotension. We hypothesized that, in patients with stroke or transient ischaemic attack (TIA), an association may exist between fatigue and abnormal blood pressure (BP) detected on ambulatory monitoring. METHODS: Subjects recruited from a secondary prevention clinic underwent 24-h ambulatory BP monitoring and completed a questionnaire including the Fatigue Severity Scale (FSS). RESULTS: One hundred subjects were included (51% female, mean age 69 years). Mean FSS was 3.6 and 42 has a FSS >4 indicative of significant fatigue. Mean daytime BP for all subjects was 134/74 (SD 16/11 mmHg). There was no significant difference in mean BP between patients with and those without significant fatigue. Patients with stroke suffered worse fatigue than those with TIA (mean FSS 3.8 vs. 3.0, P = 0.03). Twenty-four subjects were hypertensive (mean 24-h BP >145/90 mmHg), 26 had a lowest daytime diastolic BP (DBP) <50 mmHg and 4 had both. Fifty-four subjects were normotensive and these had a significantly lower mean FSS than either those with hypertension (mean FSS 3.2 vs. 4.2, P = 0.02, t-test) or those with low DBP (mean FSS 3.2 vs. 4.2, P = 0.01, t-test). Hypertensive subjects were more likely to be significantly fatigued [chi(2) 3.8, P = 0.05, OR 3.1 (1.1-8.3)] as were subjects with low daytime DBP [chi(2) 8.4, P = 0.004, OR 4.2 (1.5-11.1)]. CONCLUSION: In subjects who have suffered a stroke or TIA, fatigue is associated with measures of both hypertension and hypotension on ambulatory monitoring. Patients with stroke suffered worse fatigue than those with TIA.