Does Impaired Cerebrovascular Reactivity Predict Stroke Risk in Asymptomatic Carotid Stenosis? A Prospective Substudy of the Asymptomatic Carotid Emboli Study

Background and Purpose-Improved methods are required to identify the subgroup of patients with asymptomatic carotid stenosis who will have stroke develop. It has been suggested that impaired cerebral reactivity (CVR) may predict high risk, but no multicenter studies have examined this. Methods-In a preplanned substudy of Asymptomatic Carotid Emboli Study, 106 patients were recruited with >= 70% asymptomatic carotid stenosis. Transcranial Doppler was used to measure CVR with a vasodilatory response of carbon dioxide or acetazolamide. A meta-analysis of the data with previously published studies was performed. Results-Thirty-two of 106 (30.2%) had severely impaired CVR ipsilateral to the study artery. Mean follow-up was 680 days. There were no ipsilateral strokes. There was a nonsignificant trend to more secondary end points of any stroke/TIA in patients with severely impaired CVR. Three of 32 (9.4%) had impaired CVR compared with 2 of 74 (2.7%) without (hazard ratio, 2.54; 95% CI, 0.61-21.74; P = 0.158). On meta-analysis of the Asymptomatic Carotid Emboli Study data with previous studies, impaired CVR was associated with increased risk of ipsilateral stroke alone (OR, 6.14; 95% CI, 1.27-29.5; P = 0.02), ipsilateral stroke or TIA (OR, 4.76; 95% CI, 1.86-12.16; P = 0.001), and any stroke (OR, 4.66; 95% CI, 1.69-12.85; P = 0.003). Conclusions-In this international multicenter study, we found no association between impaired CVR and recurrent events, but the study was underpowered because of the low event rate. Meta-analysis of available data suggested an association between impaired CVR and future risk. However, currently there are insufficient data to justify the routine clinical use of CVR to stratify risk in patients with asymptomatic carotid stenosis for selection for carotid endarterectomy. (Stroke. 2011;42:1550-1555.)