Inflammatory and Infectious Burden and Risk of Stroke

描述（由申请人提供）：炎症越来越被认为在动脉粥样硬化和冠状动脉疾病中起核心作用，外周血炎症标志物与心脏事件相关。这些潜在的可改变的风险指标与缺血性卒中风险的关系尚不清楚。另外的流行病学研究表明，过去接触常见传染病的负担可能是导致炎症水平增加的因素之一。拟议的研究将利用正在进行的北曼哈顿研究（N INDS R01 29993, PI RL S acco），这是一项多种族城市人口中风危险因素的前瞻性队列研究，以检验以下假设：(1)高敏C反应蛋白和其他炎症标志物（血清淀粉样蛋白A、白细胞介素6、肿瘤坏死因子受体水平）是白人、黑人和西班牙裔人(A)缺血性卒中和(b)血管结局的独立危险因素；(2)常见感染性血清学负担（肺炎链球菌、幽门螺杆菌、巨细胞病毒、EBV、HSV 1和HSV 2）是这些人群中风和其他血管结局的独立危险因素；(3)这些炎症和感染性标志物与MRI扫描上看到的亚临床血管性脑疾病有关，如白质高信号和无症状性梗死。这些标记物的水平将使用浊度测定法和免疫测定技术对储存的基线血清样本进行测量，这些样本来自2000名3298名最初没有中风的受试者，其中1400人将接受MRI扫描，作为母项目的一部分。还将收集这1400名参与者的后续血清样本。将确定缺血性卒中、总卒中、心肌梗死、血管死亡率和总死亡率的结局。在校正其他危险因素后，采用Cox比例风险模型分析评估主要暴露变量的显著性，当有随访值时，将炎症和感染标志物作为随时间变化的协变量进行分析。炎症和感染标志物与定量MRI异常之间的横断面关联也将被评估。

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 cardiac events. The relationship of these potentially modifiable risk markers to ischemic stroke risk is less clear. Additional epidemiological studies have suggested that the burden of past exposure to common infectious diseases may be one of the factors contributing to increased levels of inflammation. The proposed research study will capitalize on the on-going Northern Manhattan Study (N INDS R01 29993, PI RL S acco), a prospective cohort study of stroke risk factors in a multi-ethnic urban population, to test the following hypotheses: (1) high-sensitivity C -reactive protein and other inflammatory markers (serum amyloid A, interleukin 6, tumor necrosis factor receptor levels) are independent risk factors for (a) ischemic stroke and (b) ot her vascular outcomes in whites, blacks and Hispanics; (2) the burden of common infectious serologies (C. pneumoniae, H.pylori, CMV, EBV, HSV 1 and 2) is an independent risk factor for stroke and other vascular outcomes in these populations; (3) these inflammatory and infectious marker s are associated with sub-clinical vascular brain diseases seen on MRI scanning, such as white matter hyperintensities and silent infarcts. Levels of these markers will be measured using nephelometric and immunoassay techniques on stored baseline serum samples from 2000 of 3298 initially stroke-free subjects, of whom 1400 will undergo MRI scanning as part of the parent project. Follow-up serum samples will also be collected on these 1400 participants. Outcomes of ischemic stroke, total 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, and inflammatory and infectious markers will be analyzed as time dependen t covariates when follow up values are available. The cross-sectional associations between inflammatory and infectious markers and quantitative MRI abnormalities will also be assessed.