Risk stratification in asymptomatic and symptomatic patients with carotid artery stenosis

The overall aim of this thesis is to explore and assess the risks that patients with carotid artery disease, whether asymptomatic or symptomatic, are exposed to, and to explore whether patients that may be subject to relatively higher risk can be identified by imaging. Although large randomized trials have proven carotid endarterectomy (CEA) to be beneficial compared to best medical treatment alone, revascularization of patients with asymptomatic carotid artery stenosis (ACAS) remains a matter of debate. Therefore risk stratification of these patients is clinically important. First we identified that patients who suffered from ipsilateral cerebrovascular symptoms, but underwent CEA longer than 6 months after the index event, have a relatively unstable plaque composition compared to patients who never experienced ipsilateral symptoms. Second, patients with ACAS have a low risk of developing ischemic stroke. Patients with severe ACAS developing an occlusion were rare during long-term follow-up. However, occlusion was an independent prognostic risk factor for occurrence of stroke in this study. We showed in a pilot study of patients with severe ACAS that revascularisation slightly improved perfusion of the ipsilateral hemisphere as measured by ASL perfusion. However, clinical implication of this improved perfusion needs to be investigated in larger cohorts. For patients with symptomatic carotid artery stenosis CEA is the treatment of choice in patients with a severe (≥70%) stenosis. Surgery has been shown to be most effective in recurrent stroke prevention when performed within two weeks after transient ischemic attack (TIA) or ischemic stroke. In the UMC Utrecht delay to carotid surgery has shortened significantly over the years, but still exceeds 14 days in majority of patients. For further shortening of this delay specific attention should be paid to the pre-hospital phase. In literature, both CAS and CEA proved to be feasible revascularization techniques with low risk for TIA or stroke in patients with previous irradiation. Therefore the choice for revascularization therapy should be considered on an individual basis. Besides, we identified carotid stenotic lesions in patients with previous cervical radiation are less inflammatory and more fibrotic than carotid atherosclerotic lesions in non-radiated patients. The final part of this thesis outlines imaging of carotid artery stenosis. Before MRI can be routinely implemented in diagnostic work-up for these patients, clinical application for plaque characterisation would require consensus regarding MRI settings and confirmation by histology. This thesis has given more insight in risk management of the patient with carotid artery stenosis. Still, more research is warranted to accurately identify the specific risk groups in patients with carotid artery stenosis. Our studies and the suggested new research might result in more precise risk stratification for patients with carotid artery stenosis. We believe diagnosing and treating patients with carotid artery stenosis is a multidisciplinary, complex and ongoing process, which needs to be evaluated over time to keep up-to-date and sufficient