Cerebrovascular Reserve and Stroke Risk in Patients with Carotid Stenosis or Occlusion: A Systematic Review and Meta-Analysis

Background and Purpose— Impairments in cerebrovascular reserve (CVR) have been variably associated with increased risk of ischemic events and may stratify stroke risk in patients with high-grade internal carotid artery stenosis or occlusion. The purpose of this study is to perform a systematic review and meta-analysis to summarize the association of CVR impairment and stroke risk. Methods— We performed a literature search evaluating the association of impairments in CVR with future stroke or transient ischemic attack in patients with high-grade internal carotid artery stenosis or occlusion. We included studies with a minimum of 1-year patient follow-up with baseline CVR measures performed by any modality and primary outcome measures of stroke and/or transient ischemic attack. A meta-analysis with assessment of study heterogeneity and publication bias was performed. Results were presented in a forest plot and summarized using a random-effects model. Results— Thirteen studies met the inclusion criteria, representing a total of 1061 independent CVR tests in 991 unique patients with a mean follow-up of 32.7 months. We found a significant positive relationship between impairment of CVR and development of stroke with a pooled random effects OR of 3.86 (95% CI, 1.99–7.48). Subset analysis showed that this association between CVR impairment and future risk of stroke/transient ischemic attack remained significant regardless of ischemic outcome measure, symptomatic or asymptomatic disease, stenosis or occlusion, or CVR testing method. Conclusions— CVR impairment is strongly associated with increased risk of ischemic events in carotid stenosis or occlusion and may be useful for stroke risk stratification.