Oxygen extraction fraction and stroke risk in patients with carotid stenosis or occlusion: a systematic review and meta-analysis

Abstract

Background and purpose: Increased oxygen extraction fraction on PET has been considered a risk factor for stroke in patients with carotid stenosis or occlusion, though the strength of this association has recently been questioned. We performed a systematic review and meta-analysis to summarize the association between increased oxygen extraction fraction and ipsilateral stroke risk.

Materials and methods: A comprehensive literature search was performed. We included studies with baseline PET oxygen extraction fraction testing, ipsilateral stroke as the primary outcome, and at least 1 year of follow-up. A meta-analysis was performed by use of a random-effects model.

Results: After screening 2158 studies, 7 studies with 430 total patients with mean 30-month follow-up met inclusion criteria. We found that 6 of 7 studies were amenable to meta-analysis. Although 4 of the 6 studies independently did not reach statistical significance, meta-analysis revealed a significant positive relationship between abnormal oxygen extraction fraction and future ipsilateral stroke, with a pooled OR of 6.04 (95% CI, 2.58-14.12). There was no statistically significant difference in OR in the subgroup analyses according to testing method or disease site.

Conclusions: Abnormal oxygen extraction fraction remains a powerful predictor of stroke in carotid stenosis or occlusion and is a valuable reference standard to compare and validate MR imaging-based measures of brain oxygen metabolism. However, there is a need for further evaluation of oxygen extraction fraction testing in patients with high-grade but asymptomatic carotid disease.

Fig 1.

Study selection flow diagram. Figure adapted from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) group statement.

Fig 2.

Forest plot of the association between increased OEF and ipsilateral first-ever or recurrent stroke determined by a random effects (RE) model. Squares represent point estimates for effect size expressed as log of the OR, with the size proportional to the inverse variance of the estimate (note, OR = exp [log OR]). Diamonds represent pooled estimate. Lines represent 95% CIs. Vertical line indicates null effect (OR = 1 or log odds = 0). I² and Breslow-Day statistic for heterogeneity is listed below the forest plot.

Fig 3.

A, Symptomatic patients only, with the OR representing the strength of association between increased OEF and risk of either recurrent stroke or stroke preceded by prior TIA in the symptomatic territory. B, Carotid artery disease only. C, Carotid and MCA disease. Log OR and 95% CI for studies divided by the presence of disease in symptomatic patients only (A), in the carotid artery only (B), or in the carotid artery and MCA (C). Note that a Breslow-Day statistic could not be calculated for the forest plot in B, given the small outcome events. Squares represent point estimates for effect size expressed as log of the OR, with the size proportional to the inverse variance of the estimate (note, OR = exp [log OR]). Diamonds represent pooled estimate. Lines represent 95% CIs. Vertical line indicates null effect (OR = 1 or log odds = 0). I² and Breslow-Day statistic for heterogeneity is listed below the forest plot.

Fig 4.

A, Testing by use of absolute OEF measures. B, Testing by use of hemispheric ratio–based measures. Log OR and 95% CI for studies divided by the OEF testing by use of absolute measures of OEF (A) or hemispheric ratio–based measure of OEF (B). Squares represent point estimates for effect size expressed as log of the OR, with the size proportional to the inverse variance of the estimate (note, OR = exp [log OR]). Diamonds represent pooled estimate. Lines represent 95% CIs. Vertical line indicates null effect (OR = 1 or log odds = 0). I² and Breslow-Day statistic for heterogeneity is listed below the forest plot.