Levels of Inflammatory Markers in Treatment of Stroke

描述(由申请人提供)：炎症在动脉粥样硬化和冠状动脉疾病中起着核心作用，炎症的外周血液标记物与心脏事件的发生和复发有关。这些潜在的可改变的危险标记物与缺血性卒中后预后的关系尚不清楚。这项名为《中风治疗中的炎症标志物水平(LIMITS)》的研究是正在进行的NINDS资助的小脑皮质下中风二级预防或SPSS试验(NINDS UO1 NS038529 04A1，首席研究员O Benavente)的一项获得批准的辅助研究，这是一项针对腔隙性中风患者进行的大型、3期、多中心、2X2因素随机临床试验。这项辅助研究将检验下列假设：(1)高敏C-反应蛋白、血清淀粉样蛋白A和CD40配体水平是(A)复发缺血性中风和(B)包括死亡在内的其他血管结果的独立危险因素；(2)在这些标志物水平升高的患者中，氯吡格雷和阿司匹林联合抗血小板治疗在降低中风复发风险方面的疗效比单用阿司匹林更有效；(3)炎症标志物水平是腔隙梗死患者认知功能下降的独立危险因素；(4)在腔隙性中风患者中，氯吡格雷和阿司匹林联合治疗将比单用阿司匹林更能降低这些标志物的水平。这些标记物的水平将使用散射比浊法和免疫分析技术在注册时和一年后从1440名SPSS受试者中收集的血清样本上进行测量。还将收集可能导致炎症的伴随传染病、肿瘤和炎症性疾病的信息。将确定复发的缺血性中风、心肌梗死、血管死亡率和总死亡率的结果。使用COX比例风险模型分析，在调整其他危险因素、他汀类药物治疗组、CENTER组和SPSS治疗组后，评估主要暴露变量的显著性。分析还将通过双重抗血小板治疗与单一抗血小板治疗进行分层。本研究将最大限度地提高解决这些问题的效率，方法是利用战略规划和战略规划的现有程序和组织结构，进行征聘、与各地点的互动、后续行动和确定活动。

DESCRIPTION (provided by applicant): Inflammation is increasingly recognized to play a central role in atherosclerosis and coronary artery disease, and peripheral blood markers of inflammation have been associated with incident and recurrent cardiac events. The relationship of these potentially modifiable risk markers to prognosis after ischemic stroke is less clear. The proposed study, Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS), is an approved ancillary study to the on-going NINDS-funded Secondary Prevention of <Small Subcortical Strokes, or SPSS trial (NINDS UO1 NS038529 04A1, Principal Investigator O Benavente), a large, Phase 3, multicenter, 2X2 factorial, randomized clinical trial of anti-platelet therapy and anti-hypertensive therapy in patients with lacunar stroke. This ancillary study will test the following hypotheses: (1) high sensitivity C-reactive protein, serum amyloid A, and CD40 ligand levels are independent risk factors for (a) recurrent ischemic stroke and (b) other vascular outcomes including death; (2) the efficacy of dual antiplatelet treatment with clopidogrel and aspirin versus aspirin alone in reducing risk of recurrent stroke is greater among those patients with elevated levels of these markers; (3) inflammatory marker levels are independent risk factors for cognitive decline in patients with lacunar infarcts; (4) treatment with clopidogrel plus aspirin will reduce levels of these markers more than aspirin alone in patients with lacunar stroke. Levels of these markers will be measured using nephelometric and immunoassay techniques on serum samples collected at enrollment and at one year from 1440 SPSS subjects. Information on concomitant infectious, neoplastic, and inflammatory diseases that might contribute to inflammation will also be collected. Outcomes of recurrent ischemic stroke, myocardial infarction, vascular mortality and total mortality will be ascertained. Cox proportional hazard model analysis will be used to assess the significance of the main exposure variables after adjustment for other risk factors, statin treatment, center, and SPSS treatment group. Analysis will also be performed stratified by dual versus single antiplatelet therapy. The present study will maximize efficiency in addressing these questions by utilizing the existing protocol and organizational structure of SPSS for recruitment, interaction with sites, follow-up, and event ascertainment.