Jolink Wilmar M T, Heinen Rutger, Persoon Suzanne, van der Zwan Albert, Kappelle L Jaap, Klijn Catharina J M
Utrecht Stroke Center, Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center, Utrecht, The Netherlands.
Cerebrovasc Dis. 2014;37(1):30-7. doi: 10.1159/000356349. Epub 2013 Dec 17.
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.
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.
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.
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.
短暂性脑缺血发作（TIA）或与颈内动脉（ICA）闭塞相关的轻度致残性缺血性卒中患者，在脑血流量受损时发生复发性卒中的风险很高。最近的研究表明，正电子发射断层扫描（PET）测量的氧摄取分数增加仍然是当前药物治疗下后续卒中的独立预测指标，但PET设备尚未广泛普及。经颅多普勒（TCD）超声检查二氧化碳反应性是一种廉价且无创的测量血流动力学受损的替代方法。我们研究的目的是调查在临床实践中已广泛实施严格控制血管危险因素的时期，TCD二氧化碳反应性是否是一大群有症状ICA闭塞患者复发性缺血性卒中的独立预测指标。
1995年7月至2009年12月期间，我们纳入了连续的因TIA或轻度致残性缺血性卒中（改良Rankin量表≤3）并伴有ICA闭塞而转诊至荷兰乌得勒支大学医学中心的患者。所有患者均接受抗血小板治疗，并接受严格的血管危险因素控制，包括他汀类药物、糖尿病和高血压治疗以及生活方式建议。在就诊后3个月内用TCD测量二氧化碳反应性。我们使用Cox比例风险分析确定TCD二氧化碳反应性对复发性缺血性卒中的预测价值。
我们纳入了201例患者，中位随访时间为7.1年。平均二氧化碳反应性为15%（±20标准差）。同侧缺血性卒中的年发生率为2.2%[95%置信区间（CI）1.4 - 3.2]，任何复发性卒中的年发生率为3.2%（95%CI 2.3 - 4.4）。我们未发现二氧化碳反应性与同侧[每增加一个百分点的风险比（HR）为1.01，95%CI 0.99 - 1.02]或任何复发性缺血性卒中（HR 1.01，95%CI 0.998 - 1.02）的风险之间存在显著关系。多变量分析显示，同侧复发性卒中与卒中病史（HR 4.0，95%CI 1.8 - 9.0）、任何复发性卒中与年龄（每年增加的HR为1.05，95%CI 1.01 - 1.09）和卒中病史（HR 3.4，95%CI 1.7 - 6.6）之间存在显著关系。
对于伴有颈动脉闭塞的TIA或非致残性卒中患者，通过仔细控制血管危险因素，卒中的长期年风险通常较低。就诊后3个月内测量的二氧化碳反应性受损并不能识别复发性缺血性卒中高危患者亚组。
