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Background: Patients with transient ischaemic attacks (TIAs) or minor disabling ischaemic stroke associated with an internal carotid artery (ICA) occlusion have a high risk of recurrent stroke in case of compromised cerebral blood flow. Recent studies showed that increased oxygen extraction fraction measured by positron emission tomography (PET) is still an independent predictor of subsequent stroke under current medical treatment, but PET facilities are not widely available. Transcranial Doppler (TCD) ultrasonography CO2 reactivity is a cheap and non-invasive alternative to measure haemodynamic compromise. The aim of our study was to investigate whether TCD CO2 reactivity is an independent predictor of recurrent ischaemic stroke in a large cohort of patients with symptomatic ICA occlusion in a time where rigorous control of vascular risk factors has been widely implemented in clinical practice. Methods: Between July 1995 and December 2009, we included consecutive patients with TIAs or minor disabling ischaemic stroke (modified Rankin Scale ≤3) associated with ICA occlusion who were referred to the University Medical Centre Utrecht, The Netherlands. All patients were treated with antiplatelet therapy and received rigorous control of vascular risk factors, including statins, treatment for diabetes and hypertension and lifestyle advices. CO2 reactivity was measured with TCD within 3 months after presentation. We determined the predictive value of TCD CO2 reactivity for recurrent ischaemic stroke using Cox proportional hazard analysis. Results: We included 201 patients with a median follow-up time of 7.1 years. Mean CO2 reactivity was 15% (±20 standard deviation). The annual rate for ipsilateral ischaemic stroke was 2.2% [95% confidence interval (CI) 1.4-3.2] and for any recurrent stroke 3.2% (95% CI 2.3-4.4). We did not find a significant relationship between CO2 reactivity and the risk of ipsilateral [hazard ratio (HR) for every increase in percentage point 1.01, 95% CI 0.99-1.02] or any recurrent ischaemic stroke (HR 1.01, 95% CI 0.998-1.02). Multivariable analysis showed a significant relationship with history of stroke (HR 4.0, 95% CI 1.8-9.0) for ipsilateral recurrent stroke, and age (HR for increase per year 1.05, 95% CI 1.01-1.09) and a history of stroke (HR 3.4, 95% CI 1.7-6.6) for any recurrent stroke. Conclusions: In patients with TIAs or non-disabling stroke associated with occlusion of the carotid artery, the long-term annual risk of stroke is generally low with careful control of vascular risk factors. Impaired CO2 reactivity measured within 3 months after presentation does not identify the subgroup of patients at high risk of recurrent ischaemic stroke. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]