Levels of Inflammatory Markers in Treatment of Stroke

描述（由申请人提供）：越来越多的人认识到炎症在动脉粥样硬化和冠状动脉疾病中起核心作用，并且炎症的外周血标志物与心脏事件的发生和复发相关。这些潜在的可改变的危险标志物与缺血性卒中预后的关系尚不清楚。拟议中的研究，炎症标志物在中风治疗中的水平（LIMITS），是正在进行的NINDS资助的<小皮质下中风二级预防或SPSS试验的辅助研究（NINDS UO 1 NS 038529 04 A1，主要研究者O贝纳文特），一项大型、III期、多中心、2X2析因研究，腔隙性脑卒中患者抗血小板治疗和抗高血压治疗的随机临床试验。该辅助研究将检验以下假设：（1）高敏C反应蛋白、血清淀粉样蛋白A和CD 40配体水平是（a）复发性缺血性卒中和（B）其他血管结局（包括死亡）的独立危险因素;（二）氯吡格雷和阿司匹林双重抗血小板治疗与阿司匹林单药治疗相比，在降低卒中复发风险方面，这些标志物的水平;（3）炎症标志物水平是腔隙性脑梗死患者认知功能下降的独立危险因素;（4）在腔隙性脑卒中患者中，氯吡格雷联合阿司匹林治疗比单独使用阿司匹林更能降低这些标志物的水平。将使用比浊法和免疫测定技术对入组时和1年时从1440例SPSS受试者中采集的血清样本测量这些标志物的水平。还将收集可能导致炎症的伴随感染性、肿瘤性和炎性疾病的信息。将确定复发性缺血性卒中、心肌梗死、血管死亡率和总死亡率的结局。将使用考克斯比例风险模型分析评估调整其他风险因素、他汀类药物治疗、中心和SPSS治疗组后主要暴露变量的显著性。还将按照双联与单药抗血小板治疗进行分层分析。本研究将通过利用SPSS的现有方案和组织结构进行招募、与研究中心的互动、随访和事件确定，最大限度地提高解决这些问题的效率。

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.