无症状性颈动脉狭窄程度与卒中风险的关系：基于人群的队列研究、系统评价和荟萃分析。
Risk of stroke in relation to degree of asymptomatic carotid stenosis: a population-based cohort study, systematic review, and meta-analysis.
机构信息
Wolfson Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; Department of Vascular Surgery, Oxford University Hospitals NHS Trust, Oxford, UK.
Wolfson Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
出版信息
Lancet Neurol. 2021 Mar;20(3):193-202. doi: 10.1016/S1474-4422(20)30484-1.
BACKGROUND
There is uncertainty around which patients with asymptomatic carotid stenosis should be offered surgical intervention. Although stroke rates were unrelated to the degree of stenosis in the medical-treatment-only groups in previous randomised trials, this could simply reflect recruitment bias and there has been no systematic analysis of a stenosis-risk association in cohort studies. We aimed to establish whether there is any association between the degree of asymptomatic stenosis and ipsilateral stroke risk in patients on contemporary medical treatment.
METHODS
We did a prospective population-based study (Oxford Vascular Study; OxVasc), and a systematic review and meta-analysis. All patients in OxVasc with a recent suspected transient ischaemic attack or stroke, between April 1, 2002, and April 1, 2017, who had asymptomatic carotid stenosis were included in these analyses. We commenced contemporary medical treatment and determined ipsilateral stroke risk in this cohort by face-to-face follow-up (to Oct 1, 2020). We also did a systematic review and meta-analysis of all published studies (from Jan 1, 1980, to Oct 1, 2020) reporting ipsilateral stroke risk in patients with asymptomatic carotid stenosis. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, and included both observational cohort studies and medical treatment groups of randomised controlled trials if the number of patients exceeded 30, ipsilateral stroke rates (or the raw data to calculate these) were provided, and were published in English.
FINDINGS
Between April 1, 2002, and April 1, 2017, 2354 patients were consecutively enrolled in OxVasc and 2178 patients underwent carotid imaging, of whom 207 had 50-99% asymptomatic stenosis of at least one carotid bifurcation (mean age at imaging: 77·5 years [SD 10·3]; 88 [43%] women). The 5-year ipsilateral stroke risk increased with the degree of stenosis; patients with 70-99% stenosis had a significantly greater 5-year ipsilateral stroke risk than did those with 50-69% stenosis (six [14·6%; 95% CI 3·5-25·7] of 53 patients vs none of 154; p<0·0001); and patients with 80-99% stenosis had a significantly greater 5-year ipsilateral stroke risk than did those with 50-79% stenosis (five [18·3%; 7·7-29·9] of 34 patients vs one [1·0%; 0·0-2·9] of 173; p<0·0001). Of the 56 studies identified in the systematic review (comprising 13 717 patients), 23 provided data on ipsilateral stroke risk fully stratified by degree of asymptomatic stenosis (in 8419 patients). Stroke risk was linearly associated with degree of ipsilateral stenosis (p<0·0001); there was a higher risk in patients with 70-99% stenosis than in those with 50-69% stenosis (386 of 3778 patients vs 181 of 3806 patients; odds ratio [OR] 2·1 [95% CI 1·7-2·5], p<0·0001; 15 cohort studies, three trials) and a higher risk in patients with 80-99% stenosis than in those with 50-79% stenosis (77 of 727 patients vs 167 of 3272 patients; OR 2·5 [1·8-3·5], p<0·0001; 11 cohort studies). Heterogeneity in stroke risk between studies for patients with severe versus moderate stenosis (p<0·0001) was accounted for by highly discrepant results (p<0·0001) in the randomised controlled trials of endarterectomy compared with cohort studies (trials: pooled OR 0·8 [95% CI 0·6-1·2], p=0·89; cohorts: 2·9 [2·3-3·7], p=0·54).
INTERPRETATION
Contrary to the assumptions of current guidelines and the findings of subgroup analyses of previous randomised controlled trials, the stroke risk reported in cohort studies was highly dependent on the degree of asymptomatic carotid stenosis, suggesting that the benefit of endarterectomy might be underestimated in patients with severe stenosis. Conversely, the 5-year stroke risk was low for patients with moderate stenosis on contemporary medical treatment, calling into question any benefit from revascularisation.
FUNDING
NIHR Oxford Biomedical Research Centre, Wellcome Trust, Wolfson Foundation, and the British Heart Foundation.
背景
无症状颈动脉狭窄患者应接受何种治疗存在不确定性。尽管此前的随机试验中，仅接受药物治疗的各亚组患者的卒中发生率与狭窄程度无关，但这可能只是反映了招募偏倚，且尚未对队列研究中的狭窄风险相关性进行系统分析。我们旨在确定在接受当代药物治疗的患者中，无症状狭窄的严重程度与同侧卒中风险之间是否存在关联。
方法
我们进行了一项前瞻性基于人群的研究（牛津血管研究；OxVasc）和系统评价及荟萃分析。OxVasc 中所有近期疑似短暂性脑缺血发作或卒中的患者，且具有无症状颈动脉狭窄，均纳入这些分析。我们开始进行当代药物治疗，并通过面对面随访（截至 2020 年 10 月 1 日）来确定该队列中的同侧卒中风险。我们还对所有发表的研究（1980 年 1 月 1 日至 2020 年 10 月 1 日）进行了系统评价和荟萃分析，这些研究报告了无症状颈动脉狭窄患者的同侧卒中风险。我们检索了 MEDLINE、Embase 和 Cochrane 对照试验中心注册库，纳入了随机对照试验的观察性队列研究和药物治疗组，如果患者人数超过 30 例、同侧卒中发生率（或提供计算这些发生率的原始数据）、且以英文发表，则将其纳入。
发现
2002 年 4 月 1 日至 2017 年 4 月 1 日期间，2354 例患者连续入组 OxVasc，2178 例患者接受颈动脉成像，其中 207 例至少一侧颈动脉分叉处有 50%-99%的无症状狭窄（影像学检查时的平均年龄：77.5 岁[10.3 岁]；88 例[43%]为女性）。随着狭窄程度的增加，5 年同侧卒中风险增加；70%-99%狭窄的患者 5 年同侧卒中风险显著高于 50%-69%狭窄的患者（53 例中的 6 例[14.6%；95%CI 3.5-25.7] vs 154 例中的 0 例；p<0.0001）；80%-99%狭窄的患者 5 年同侧卒中风险显著高于 50%-79%狭窄的患者（34 例中的 5 例[18.3%；7.7-29.9] vs 173 例中的 1 例[1.0%；0.0-2.9]；p<0.0001）。在系统评价中确定的 56 项研究中（共包括 13717 例患者），23 项研究提供了完全按无症状狭窄程度分层的同侧卒中风险数据（8419 例患者）。卒中风险与狭窄程度呈线性相关（p<0.0001）；70%-99%狭窄的患者风险高于 50%-69%狭窄的患者（3778 例患者中的 386 例 vs 3806 例患者中的 181 例；比值比[OR] 2.1[95%CI 1.7-2.5]，p<0.0001；15 项队列研究，3 项试验），80%-99%狭窄的患者风险高于 50%-79%狭窄的患者（727 例患者中的 77 例 vs 3272 例患者中的 167 例；OR 2.5[1.8-3.5]，p<0.0001；11 项队列研究）。严重狭窄与中度狭窄患者之间的卒中风险存在异质性（p<0.0001），这归因于随机对照试验与队列研究之间的结果差异极大（试验：汇总 OR 0.8[95%CI 0.6-1.2]，p=0.89；队列：2.9[2.3-3.7]，p=0.54）。
解释
与当前指南的假设和之前的随机对照试验的亚组分析结果相反，队列研究报告的卒中风险高度依赖于无症状颈动脉狭窄的程度，这表明严重狭窄患者的颈动脉内膜切除术获益可能被低估。相反，在接受当代药物治疗的中度狭窄患者中，5 年卒中风险较低，这使得颈动脉内膜切除术获益的必要性受到质疑。
资助
英国牛津大学国家卫生研究院生物医学研究中心、威康信托基金会、沃尔夫森基金会和英国心脏基金会。
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