Supplementary Material for: Long-Term Survival of Ischemic Cerebrovascular Disease in the Acute Inflammatory Stroke Study, a Hospital-Based Cohort Described by TOAST and ASCO

<b><i>Background:</i></b> Ischemic cerebrovascular disease (ICVD) comprises multiple etiological phenotypes that share common clinical characteristics. Etiological classification of patients with ICVD is of major clinical interest to achieve optimal medical treatment and predict prognosis. The TOAST classification system has been widely used to describe stroke etiology but provides restricted phenotypic homogeneity within groups. The ASCO classification system has introduced a new approach in phenotypic classification, and aims to describe clinical characteristics without merging concurrent comorbidities. Inflammatory processes have been suggested to mediate stroke etiology and pathology. The Acute Inflammatory Stroke Study (AISS), a hospital-based cohort, is here introduced and described by TOAST and ASCO classification systems. The aim of this first analysis of AISS was to investigate long-term mortality in relation to ischemic stroke subtypes, and clinical and biochemical markers. <b><i>Methods:</i></b> AISS consecutively follows patients on 6 occasions up to 1 year after stroke onset. Complete workup according to ASCO comprised CT or MRI of the head, ECG, duplex of the extracranial arteries or CT/MR angiography and ultrasound of the heart. Level 2 evidence was required in each domain to obtain a comparable system to TOAST (ASCO2). Clinical and biochemical characteristics and mortality rates were documented and compared by the two classification systems. <b><i>Results:</i></b> Of 142 patients consecutively evaluated and recruited in the study, a total of 101 ICVD patients (ischemic stroke, n = 84; transient ischemic attack, n = 17) were included in the final analysis. Agreement between ASCO2 and TOAST was very good. During the mean observation period of 28 months, 26 patients died. The 1- and 4-year mortality rates were 0 and 4% for large artery atherosclerosis (LAA); 23 and 36% for cardioembolism (CE); 0% for small artery occlusion (SAO); 63 and 100% for the subtype with unknown etiology due to incomplete workup (Unknown), and 12 and 29% for the cryptogenic subtype. As for the ASCO2 groups, the 1- and 4-year mortality rates were 0 and 6% in LAA, 25 and 36% in CE, 0% in SAO, 0 and 14% in LAA + CE, 0% in SAO + CE, 16 and 36% in the subgroup with undetermined etiology despite complete workup, and 56 and 100% in Unknown. Regression analysis showed that age, white blood cell count, fibrinogen and bilirubin, but not etiological subgroup, were independent predictors of mortality. <b><i>Conclusion:</i></b> Our findings indicate that clinical and biochemical markers may differentiate phenotypically homogeneous etiological subtypes and predict long-term mortality. Further studies with larger patient numbers are needed to investigate possible causative mechanisms.

<b><i>背景：</i></b> 缺血性脑血管病（Ischemic cerebrovascular disease, ICVD）包含多种共享共同临床特征的病因表型。对ICVD患者进行病因分型，对于实现优化药物治疗与预测预后具有重要临床意义。TOAST分类系统已被广泛用于描述卒中病因，但组内表型同质性受限。ASCO分类系统则提出了一种全新的表型分型方法，旨在在不合并共存合并症的前提下描述临床特征。已有研究提示炎症过程可介导卒中的病因与病理生理过程。本研究介绍了一项基于医院的队列研究——急性炎症性卒中研究（Acute Inflammatory Stroke Study, AISS），并采用TOAST与ASCO分类系统对其进行描述。本项AISS首次分析的目的，是探究缺血性卒中亚型、临床及生化标志物与长期死亡率的相关性。<b><i>方法：</i></b> AISS队列对卒中发病后1年内的患者进行6次连续随访。按照ASCO分型标准完成的完整检查包括头部CT或MRI、心电图、颅外动脉多普勒超声或CT/MR血管造影，以及心脏超声检查。为构建与TOAST系统可比的分型体系，各维度均需达到2级证据水平（即ASCO2分型）。记录并比较两种分类系统下的临床与生化特征及死亡率。<b><i>结果：</i></b> 本研究共连续评估并招募142例患者，最终纳入101例ICVD患者（缺血性卒中84例，短暂性脑缺血发作17例）进行最终分析。ASCO2与TOAST分型系统一致性极佳。在平均28个月的随访观察期内，共计26例患者死亡。大动脉粥样硬化（large artery atherosclerosis, LAA）亚型的1年及4年死亡率分别为0%与4%；心源性栓塞（cardioembolism, CE）亚型分别为23%与36%；小动脉闭塞（small artery occlusion, SAO）亚型为0%；因检查不全导致病因不明的亚型（Unknown）分别为63%与100%；隐源性亚型分别为12%与29%。在ASCO2分型组别中，LAA亚型的1年及4年死亡率分别为0%与6%，CE亚型为25%与36%，SAO亚型为0%，LAA+CE亚型为0%与14%，SAO+CE亚型为0%，经完整检查仍病因未明的亚组为16%与36%，病因不明亚型为56%与100%。回归分析显示，年龄、白细胞计数、纤维蛋白原及胆红素为死亡率的独立预测因素，而病因亚组并非独立预测因素。<b><i>结论：</i></b> 本研究结果表明，临床与生化标志物可区分表型均一的病因亚型，并可预测长期死亡率。未来仍需开展更大样本量的研究，以探究其潜在的致病机制。