Complicated Carotid Artery Plaques as a Cause of Cryptogenic Stroke

Background: The underlying etiology of ischemic stroke remains unknown in up to 30% of patients. Objectives: This study explored the causal role of complicated (American Heart Association−lesion type VI) nonstenosing carotid artery plaques (CAPs) in cryptogenic stroke (CS). Methods: CAPIAS (Carotid Plaque Imaging in Acute Stroke) is an observational multicenter study that prospectively recruited patients aged older than 49 years with acute ischemic stroke that was restricted to the territory of a single carotid artery on brain magnetic resonance imaging (MRI) and unilateral or bilateral CAP (≥2 mm, NASCET [North American Symptomatic Carotid Endarterectomy Trial] <70%). CAP characteristics were determined qualitatively and quantitatively by high-resolution, contrast-enhanced carotid MRI at 3T using dedicated surface coils. The pre-specified study hypotheses were that that the prevalence of complicated CAP would be higher ipsilateral to the infarct than contralateral to the infarct in CS and higher in CS compared with patients with cardioembolic or small vessel stroke (CES/SVS) as a combined reference group. Patients with large artery stroke (LAS) and NASCET 50% to 69% stenosis served as an additional comparison group. Results: Among 234 recruited patients, 196 had either CS (n = 104), CES/SVS (n = 79), or LAS (n = 19) and complete carotid MRI data. The prevalence of complicated CAP in patients with CS was significantly higher ipsilateral (31%) to the infarct compared with contralateral to the infarct (12%; p = 0.0005). Moreover, the prevalence of ipsilateral complicated CAP was significantly higher in CS (31%) compared with CES/SVS (15%; p = 0.02) and lower in CS compared with LAS (68%; p = 0.003). Lipid-rich and/or necrotic cores in ipsilateral CAP were significantly larger in CS compared with CES/SVS (p < 0.05). Conclusions: These findings substantiate the role of complicated nonstenosing CAP as an under-recognized cause of stroke.