Data_Sheet_1_Presence of Extra-Criteria Antiphospholipid Antibodies Is an Independent Risk Factor for Ischemic Stroke.docx

Background: Ischemic stroke is the most common and severe arterial thrombotic event in Antiphospholipid syndrome (APS). APS is an autoimmune disease characterized by the presence of thrombosis and antiphospholipid antibodies (aPL), which provide a pro-coagulant state. The aPL included in the classification criteria are lupus anticoagulant, anti-cardiolipin (aCL) and anti-β2-glycoprotein-I antibodies (aB2GPI) of IgG and IgM isotypes. Extra-criteria aPL, especially IgA aB2GPI and IgG/IgM anti-phosphatidylserine/prothrombin antibodies (aPS/PT), have been strongly associated with thrombosis. However, their role in the general population suffering from stroke is unknown. We aim (1) to evaluate the aPL prevalence in ischemic stroke patients, (2) to determine the role of aPL as a risk factor for stroke, and (3) to create an easy-to-use tool to stratify the risk of ischemic stroke occurrence considering the presence of aPL and other risk factors.
Materials and Methods: A cohort of 245 consecutive ischemic stroke patients was evaluated in the first 24 h after the acute event for the presence of classic aPL, extra-criteria aPL (IgA aB2GPI, IgG, and IgM aPS/PT) and conventional cardiovascular risk factors. These patients were followed-up for 2-years. A group of 121 healthy volunteers of the same age range and representative of the general population was used as reference population. The study was approved by the Ethics Committee for Clinical Research (Reference numbers CEIC-14/354 and CEIC-18/182).
Results: The overall aPL prevalence in stroke patients was 28% and IgA aB2GPI were the most prevalent (20%). In the multivariant analysis, the presence of IgA aB2GPI (OR 2.40, 95% CI: 1.03–5.53), dyslipidemia (OR 1.70, 95% CI: 1.01–2.84), arterial hypertension (OR 1.82, 95% CI: 1.03–3.22), atrial fibrillation (OR 4.31, 95% CI: 1.90–9.78), and active smoking (OR 3.47, 95% CI: 1.72–6.99) were identified as independent risk factors for ischemic stroke. A risk stratification tool for stroke was created based on these factors (AUC: 0.75).
Conclusions: IgA aB2GPI are an important independent risk factor for ischemic stroke. Evaluation of aPL (including extra-criteria) in cardiovascular risk factor assessment for stroke can potentially increase the identification of patients at risk of thrombotic event, facilitating a decision on preventive treatments.

背景：缺血性脑卒中是抗磷脂综合征（Antiphospholipid Syndrome, APS）中最常见且严重的动脉血栓事件。APS是以血栓形成与抗磷脂抗体（antiphospholipid antibodies, aPL）阳性为特征的自身免疫病，此类抗体可诱导机体处于促凝状态。符合分类标准的aPL包括狼疮抗凝物、IgG与IgM亚型的抗心磷脂抗体（anti-cardiolipin, aCL）及抗β2糖蛋白I抗体（anti-β2-glycoprotein I, aB2GPI）。而标准外aPL，尤其是IgA型aB2GPI与IgG/IgM型抗磷脂酰丝氨酸/凝血酶原抗体（anti-phosphatidylserine/prothrombin antibodies, aPS/PT），已被证实与血栓形成密切相关，但此类抗体在普通脑卒中人群中的作用尚不明确。本研究旨在达成以下目标：（1）评估缺血性脑卒中患者的aPL检出率；（2）明确aPL作为脑卒中危险因素的作用；（3）构建一款易用的风险分层工具，综合aPL阳性情况与其他危险因素，对缺血性脑卒中的发生风险进行分层。

材料与方法：本研究纳入245例连续入组的急性缺血性脑卒中患者，于发病后24小时内检测其经典aPL、标准外aPL（IgA型aB2GPI、IgG及IgM型aPS/PT）与常规心血管危险因素，并对所有患者进行为期2年的随访。同时纳入121名同年龄段、具有普通人群代表性的健康志愿者作为对照人群。本研究已通过临床研究伦理委员会审批（审批编号：CEIC-14/354与CEIC-18/182）。

结果：脑卒中患者整体aPL检出率为28%，其中以IgA型aB2GPI的检出率最高（20%）。多变量分析显示，IgA型aB2GPI阳性（比值比OR=2.40，95%置信区间CI：1.03~5.53）、血脂异常（OR=1.70，95%CI：1.01~2.84）、高血压（OR=1.82，95%CI：1.03~3.22）、心房颤动（OR=4.31，95%CI：1.90~9.78）以及主动吸烟（OR=3.47，95%CI：1.72~6.99）均为缺血性脑卒中的独立危险因素。基于上述因素构建的脑卒中风险分层工具的曲线下面积（AUC）为0.75。

结论：IgA型aB2GPI是缺血性脑卒中的重要独立危险因素。在脑卒中的心血管危险因素评估中纳入aPL（包括标准外aPL）检测，或可提高血栓事件高风险患者的识别率，有助于指导预防性治疗的决策。