Severely impaired cerebrovascular reactivity predicts stroke and TIA risk in patients with carotid artery stenosis and occlusion

Abstract

Cross-sectional studies suggest that impaired cerebral haemodynamics is associated with symptomatic status in patients with carotid stenosis and occlusion, but there is relatively little prospective data confirming this association. Transcranial Doppler ultrasonography was used to determine the reactivity of the middle cerebral artery to 8% carbon dioxide in air in 107 patients with either carotid occlusion (n = 48) or asymptomatic carotid stenosis (n = 59). Subjects were followed prospectively until stroke, transient ischaemic attack (TIA), death or study end. Mean duration of follow-up was 635 days. No patients dropped out due to operation before an end-point was reached, or were lost to follow-up. There were 11 ipsilateral ischaemic events during follow-up (six strokes, five TIAs). Exhausted ipsilateral middle cerebral artery reactivity (>20% increase in ipsilateral middle cerebral flow velocity in response to 8% carbon dioxide) predicted ipsilateral stroke and TIA risk in the whole group (P: < 0.00001) and in the carotid occlusion (P: = 0.019) and carotid stenosis (P: = 0.015) groups alone. It also predicted the risk of ipsilateral stroke alone in all three groups. Cox regression was performed, controlling for age, gender, hypertension, diabetes, smoking, ipsilateral CT infarct, degree of contralateral stenosis and the presence of ipsilateral stenosis versus occlusion. Exhausted reactivity remained an independent predictor of ipsilateral stroke and TIA (odds ratio 14.4, 95% confidence interval 2.63-78.74, P: = 0.0021). In contrast, the pulsatility index of the middle cerebral artery was a poor predictor of the risk of stroke. Reactivity to 6% carbon dioxide also predicted the risk of stroke and TIA, but slightly less effectively than reactivity to 8% carbon dioxide. Severely reduced cerebrovascular reactivity predicts the risk of ipsilateral stroke and TIA in patients with carotid occlusion, and to a lesser extent in asymptomatic carotid stenosis. Particularly in the former group, a study is required to determine whether revascularization reduces the risk of stroke in patients with exhausted reactivity.

Quantitative mapping of cerebrovascular reactivity using resting-state BOLD fMRI: Validation in healthy adults

“…Clinically, impaired CVR has been associated with risk for stroke and transient ischemic attacks (Liu et al, 2012;Zirak et al, 2014). Given similar diagnoses, individuals with CVR impairment have a much higher risk of disabling stroke than those without (Blaser et al, 2002;Bokkers et al, 2011;Kuroda et al, 2004;Mandell et al, 2011;Mandell et al, 2008;Markus and Cullinane, 2001;Schoof et al, 2007;Silvestrini et al, 2000 ;Tsivgoulis and Alexandrov, 2008). In addition, reduced CVR has also been cited as a marker for lacunar infarction (Birns et al, 2009;Mandell et al, 2011), microbleeding (Birns et al, 2009;Conijn et al, 2012), as well as cortical atrophy (Fierstra et al, 2010) and cognitive decline in individuals at risk of stroke (Hurford et al, 2014;Kovács et al, 2010).…”

Cerebral blood flow and cerebrovascular reactivity at rest and during sub-maximal exercise: Effect of age and 12-week exercise training

“…A reduced absolute cerebral blood flow may result in stroke (Markus 2004) and is a major risk factor for Alzheimer's disease and dementia (de la Torre 2010). In addition, an impaired ability of the cerebral vasculature to respond to changes in PaCO 2 (termed cerebrovascular reactivity) is a risk factor forand a consequence of-cerebrovascular disease (Gur et al 1996;Markus and Cullinane 2001;Silvestrini et al 2000). Assessment of the cerebrovascular response to alterations in PaCO 2 (by measuring changes in middle cerebral artery blood flow velocity (MCAv)) is a wellestablished means to estimate the physiological 'reserve' of cerebral perfusion (Ainslie and Duffin 2009).…”

Tissue Pulsatility Imaging of Cerebral Vasoreactivity During Hyperventilation

“…Measurement of CVR has been used to evaluate cerebral vascular function over a broad range of clinical applications including to monitor the severity of brain damage after an ischemic event (Dohmen et al 2007), to predict the risk of a cerebral ischemic event in patients with carotid occlusive disease (Diehl 2002;Kleiser and Widder 1992;Markus and Cullinane 2001;Vernieri et al 1999, Webster et al 1995Yonas et al 1993), to assess the efficacy of a carotid endarterectomy (Herzig et al 2004), and to study anxiety disorders (Giardino et al 2007;Mathew and Wilson 1997) and migraine attacks (Akin and Bilensoy 2006).…”