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Background and Purpose- Breath holding (BH) and hyperventilation are used to assess abnormal cerebrovascular reactivity, often in relation to severity of small vessel disease and risk of stroke with carotid stenosis, but responses may be confounded by blood pressure (BP) changes. We compared effects of BP and end-tidal carbon dioxide (etCO 2 ) on middle cerebral artery mean flow velocity (MFV) in consecutive transient ischemic attack and minor stroke patients. Methods- In the population-based, prospective OXVASC (Oxford Vascular Study) phenotyped cohort, change in MFV on transcranial Doppler ultrasound (ΔMFV, DWL-DopplerBox), beat-to-beat BP (Finometer), and etCO 2 was measured during 30 seconds of BH or hyperventilation. Two blinded reviewers independently assessed recording quality. Dependence of ΔMFV on ΔBP and ΔetCO 2 was determined by general linear models, stratified by quartiles. Results- Four hundred eighty-eight of 602 (81%) patients with adequate bone windows had high-quality recordings, more often in younger participants (64.6 versus 68.7 years; P &lt;0.01), whereas 426 had hyperventilation tests (70.7%). During BH, ΔMFV was correlated with a rise in mean blood pressure (MBP; r 2 =0.15, P &lt;0.001) but not ΔCO 2 (r 2 =0.002, P =0.32), except in patients with ΔMBP &lt;10% (r 2 =0.13, P &lt;0.001). In contrast during hyperventilation, the fall in MFV was similarly correlated with reduction in CO 2 and reduction in MBP (ΔCO 2 : r 2 =0.13, P &lt;0.001; ΔMBP: r 2 =0.12, P &lt;0.001), with a slightly greater effect of ΔCO 2 when ΔMBP was &lt;10% (r 2 =0.15). Stratifying by quartile, MFV increased linearly during BH across quartiles of ΔMBP, with no increase with ΔetCO 2 . In contrast, during hyperventilation, MFV decreased linearly with ΔetCO 2 , independent of ΔMBP. Conclusions- In older patients with recent transient ischemic attack or minor stroke, cerebral blood flow responses to BH were confounded by BP changes but reflected etCO 2 change during hyperventilation. Correct interpretation of cerebrovascular reactivity responses to etCO 2 , including in small vessel disease and carotid stenosis, requires concurrent BP measurement.

Confounding of Cerebral Blood Flow Velocity by Blood Pressure During Breath Holding or Hyperventilation in Transient Ischemic Attack or Stroke