Abstract
Objective: Cerebral autoregulation (CA) is critical to maintenance of cerebral perfusion but its relevance to the risk of stroke and dementia has been under-studied due to small study sizes and a lack of consensus as to the optimal method of measurement. We determined the reliability and reproducibility of multiple CA indices and the effect of intensive data-processing in a large population with transient ischaemic attack or minor stroke. Approach: Consecutive, consenting patients in the population-based Oxford Vascular Study (OXVASC) Phenotyped cohort underwent up to 10-min supine continuous blood pressure monitoring (Finometer) with bilateral middle cerebral artery (MCA) transcranial ultrasound (DWL-Dopplerbox). Un-processed waveforms (Un-A) were median-filtered, systematically reviewed, artefacts corrected and their quality blindly graded (optimal (A) to worst (E)). CA metrics were derived in time-domain (autoregulatory index (ARI), Pearson’s Mx, Sx, Dx) and in very-low (VLF) and low-frequency (LF) domains (WPS-SI: wavelet phase synchronisation, transfer function analysis), stratified by recording quality. Reliability and reproducibility (Cronbach’s alpha) were determined comparing MCA sides and the first vs. second 5-min of monitoring. Main results: In 453 patients, following manual data-cleaning, there was good reliability of indices when comparing MCA sides (Mx: 0.77; WPS-SI-VLF: 0.85; WPS-SI-LF 0.84), or repeated five minute epochs (Mx: 0.57; WPS-SI-VLF: 0.69; WPS-SI-LF 0.90), with persistently good reliability between sides even in lower quality Groups (Group D: Mx: 0.79; WPS-SI-VLF: 0.92; WPS-SI-LF: 0.91). Reliability was greatest for Pearson’s Mx and wavelet synchronisation index, with reasonable reliability of transfer function analyses, but ARI was prone to occasional, potentially defective, extreme estimates (left vs right MCA: 0.68). Significance: Resting-state measures of CA were valid, reproducible and robust to moderate noise, but require careful data-processing. Mx and wavelet synchronisation index were the most reliable indices for determining the prognostic value of CA in large epidemiological cohorts and its potential as a treatment target.
Highlights
Cerebral autoregulation (CA) is a vital physiological mechanism to maintain constant cerebral perfusion despite changes in systemic blood pressure (BP) (Donnelly et al 2016, Xiong et al 2017)
Study population and research ethics approval Consecutive patients were recruited between September 2010 and September 2017 from the Oxford Vascular Study (OXVASC) transient ischaemic attack (TIA) and minor stroke clinic (Rothwell et al 2004)
For the pre-processed Groups A–E, the proportion of problematic and un-usable recordings and variability of measures was higher in the worse quality groups (p-trend < 0.0001 for CV% of mean ABP (MABP); and p-trend < 0.0001 and
Summary
Cerebral autoregulation (CA) is a vital physiological mechanism to maintain constant cerebral perfusion despite changes in systemic blood pressure (BP) (Donnelly et al 2016, Xiong et al 2017). Dynamic CA in response to rapid BP changes can be estimated from direct physiological challenges or from resting-state fluctuations in BP, with previous studies showing a symmetry and a significant correlation between CA indices derived from the contralateral middle cerebral arteries (MCAs) (Schmidt et al 2003). Dynamic CA in transient ischaemic attack (TIA) or minor stroke has not been adequately investigated. Studies that have assessed CA in TIA have reported a preserved CA in bilateral MCAs acutely and sub-acutely, with impaired CA in major stroke (Atkins et al 2010, Allan et al 2015), but the smaller study sizes may limit the understanding of its relevance to the risk of stroke and its importance as a risk factor and target for treatment
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