Background and Purpose-Improved methods of identifying patients at high risk of thromboembolism would allow improved targeting of therapy. One such situation is carotid artery stenosis. This is associated with an increased risk of stroke, which can be reduced by carotid endarterectomy. However, the risk-benefit ratio is low in patients with tight asymptomatic stenosis and moderate symptomatic stenosis. Most stroke in patients with carotid stenosis is believed to be embolic. Therefore, the detection of asymptomatic cerebral emboli using Doppler ultrasound may allow identification of a high-risk group. Methods-Transcranial Doppler ultrasound was used to record for 1 hour the ipsilateral middle cerebral artery in 111 patients with Ͼ60% carotid artery stenosis (69 symptomatic, 42 asymptomatic). The Doppler audio signal was recorded onto digital audio tape for later analysis for embolic signals (ES) by an individual blinded to clinical details. In 67 subjects the relationship between ES and angiographically determined plaque ulceration was investigated. All subjects were followed up prospectively, and the relationship between ES and risk of future ipsilateral carotid artery territory ischemic events (TIA and stroke) was determined. Results-ES were detected in 41(36.9%) subjects. In symptomatic patients there was a significant inverse relationship between the number of ES per hour and time elapsed since last symptoms (Spearman's ϭϪ0.2558, Pϭ0.034). ES were more common in subjects with plaque ulceration, with a relative risk of 4.94 (95% CI, 1.23 to 19.84; Pϭ0.025) after controlling for both symptomatic status and degree of stenosis. The presence of ES at entry was predictive of TIA and stroke risk during follow up in both symptomatic (Pϭ0.02) and asymptomatic patients (Pϭ0.007). Considering all 111 patients, the presence of asymptomatic embolization was predictive of a further ischemic event, with an adjusted OR of 8.10 (95% CI, 1.58 to 41.57; Pϭ0.01) after controlling for other cardiovascular risk factors, degree of stenosis, symptomatic status, and aspirin or warfarin use. Conclusions-Asymptomatic embolization in patients with carotid artery stenosis correlates with known markers of increased stroke risk and is an independent predictor of future stroke risk in patients with both symptomatic and asymptomatic carotid stenosis. It may allow identification of a high-risk group of patients who will particularly benefit from carotid endarterectomy. A large multicenter study is now required to confirm these findings. (Stroke. 1999;30:1440-1443.)

In patients with CVD we confirmed a relationship between the MTHFR genotype and serum homocysteine concentration and an interaction with serum folate concentration. We found no association between CVD and genotype. However, the interaction with serum folate suggests that the genotype could still be a risk factor in populations with a low folic acid intake.

Despite the administration of aspirin and heparin, frequent embolization occurred and was markedly reduced after the administration of GSNO. This demonstrates the potential use of platelet-specific nitric oxide donors in the treatment of thromboembolic disease. This model of cerebral embolism may allow determination of the effectiveness of new antiplatelet agents in humans.

Angio-oedema occurs more frequently than previously reported and is associated with preceding ACE-I treatment. Angio-oedema may be delayed and progress to life-threatening airway compromise, which has implications for the assessment and delivery of thrombolysis.