Supplementary Material for: Ultrasound Characteristics of Symptomatic Carotid Plaques: A Systematic Review and Meta-Analysis

<b><i>Background:</i></b> Ultrasound is the most commonly used imaging modality for assessing carotid artery stenosis. A number of studies have demonstrated that surface irregularities, heterogeneous echotexture and hypoechoic plaques are risk factors for acute ischemic stroke. We performed a systematic review and meta-analysis of the literature to better define the risk of stroke based on the sonographic characteristics of carotid plaques. <b><i>Materials and Methods:</i></b> We performed a comprehensive search for studies reporting imaging findings of symptomatic and asymptomatic carotid plaques on ultrasound using MEDLINE and EMBASE. We included both case-control and cohort studies examining the relationship between complex plaque and acute ischemic stroke or transient ischemic attack. Complex plaque was defined as plaque that had any of the following characteristics: heterogeneous echogenicity, echolucency, neovascularization, surface irregularity, ulceration, and intraplaque motion. Meta-analyses using the random-effects model were performed for complex plaque and each of the individual complex plaque characteristics. p &lt; 0.05 was considered statistically significant. We explored the impact of publication bias by constructing funnel plots and testing their symmetry. We conducted the meta-analysis using Comprehensive Meta-analysis version 2.2, Englewood, N.J., USA. <b><i>Results:</i></b> A total of 1,013 articles were screened and 23 studies with 6,706 carotid plaques were included. Ultrasound plaque characteristics with a higher prevalence in individuals with symptomatic compared to asymptomatic carotid artery stenosis included plaque neovascularity (OR = 19.68, 95% CI = 3.14-123.16), complex plaque (OR = 5.12, 95% CI = 3.42-7.67), plaque ulceration (OR = 3.58, 95% CI = 1.66-7.71), plaque echolucency (OR = 3.99, 95% CI = 3.06-5.19) and intraplaque motion (OR = 1.57, 95% CI = 1.02-2.41). Variables not associated with symptom status included heterogenous echotexture (OR = 2.68, 95% CI = 0.56-12.80) and surface irregularity without ulceration (OR = 2.38, 95% CI = 0.70-8.11). No evidence of publication bias was observed based on Eggers test (p value of 0.05 for complex plaque and 0.53 for plaque echolucency). The remaining plaque features had insufficient data to assess for publication bias. <b><i>Conclusions:</i></b> Our meta-analysis and systematic review of the literature demonstrated that plaques with complex features, particularly those with echolucency, neovascularization, ulceration and intraplaque motion are associated with ischemic symptoms. Assessment of carotid plaque on ultrasound may provide stroke risk information beyond measurement of luminal stenosis. Thus, sonographic evaluation of carotid artery stenosis should focus on the detection of these plaque characteristics in addition to quantifying the degree of stenosis.

<b><i>背景：</i></b> 超声（ultrasound）是评估颈动脉狭窄（carotid artery stenosis）最常用的成像方式。多项研究已证实，斑块表面不规则（surface irregularities）、回声不均质（heterogeneous echotexture）及低回声斑块（hypoechoic plaques）是急性缺血性卒中（acute ischemic stroke）的危险因素。本研究针对相关文献开展系统评价（systematic review）与荟萃分析（meta-analysis），旨在基于颈动脉斑块的超声特征（sonographic characteristics）更明确地界定卒中风险。<b><i>材料与方法：</i></b> 本研究通过MEDLINE与EMBASE数据库，全面检索报道有症状及无症状颈动脉斑块超声影像学表现的相关研究。纳入探索复杂斑块（complex plaque）与急性缺血性卒中或短暂性脑缺血发作（transient ischemic attack, TIA）相关性的病例对照研究（case-control study）与队列研究（cohort study）。复杂斑块定义为具备以下任意一项特征的斑块：回声异质性（heterogeneous echogenicity）、透声性（echolucency）、新生血管（neovascularization）、表面不规则、溃疡（ulceration）及斑块内活动（intraplaque motion）。针对复杂斑块及其各项独立特征，采用随机效应模型（random-effects model）开展荟萃分析，以p<0.05作为具有统计学显著性的判定标准。通过绘制漏斗图（funnel plot）并检验其对称性，探讨发表偏倚（publication bias）的影响。本研究采用美国新泽西州恩格尔伍德市Comprehensive Meta-analysis软件2.2版本完成荟萃分析。<b><i>结果：</i></b> 最终共筛选1013篇文献，纳入23项研究，合计涉及6706个颈动脉斑块。与无症状颈动脉狭窄患者相比，有症状患者中检出率更高的超声斑块特征包括：斑块新生血管（比值比（odds ratio, OR）=19.68，95%置信区间（confidence interval, CI）=3.14~123.16）、复杂斑块（OR=5.12，95%CI=3.42~7.67）、斑块溃疡（OR=3.58，95%CI=1.66~7.71）、斑块透声性（OR=3.99，95%CI=3.06~5.19）及斑块内活动（OR=1.57，95%CI=1.02~2.41）。与症状状态无显著关联的变量包括：回声不均质斑块（OR=2.68，95%CI=0.56~12.80）及无溃疡的表面不规则斑块（OR=2.38，95%CI=0.70~8.11）。基于Egger检验（Egger test），未观察到发表偏倚（复杂斑块的p值为0.05，斑块透声性的p值为0.53）。其余斑块特征因数据不足，无法评估发表偏倚。<b><i>结论：</i></b> 本项荟萃分析与系统评价显示，具备复杂特征的斑块，尤其是存在透声性、新生血管、溃疡及斑块内活动的斑块，与缺血性症状显著相关。超声评估颈动脉斑块，可在管腔狭窄（luminal stenosis）程度测量之外提供卒中风险相关信息。因此，针对颈动脉狭窄的超声评估，除量化狭窄程度外，还应重点检测上述斑块特征。