INFECTION AND CARDIOVASCULAR DISEASE

感染和心血管疾病

• 批准号: 6390265
• 负责人: MICHAEL DAVIDSON
• 金额: $ 26.75万
• 依托单位: MEDSTAR HEALTH RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6390265
• 关键词: Chlamydiaceae; Helicobacter; Hepatovirus; Native Americans; acute phase protein; angiocardioultrasonography; atherosclerosis; cardiovascular disorder epidemiology; carotid artery; chlamydial disease; clinical research; coronary disorder; cytomegalovirus; disease /disorder proneness /risk; hemostasis; hepatitis A; herpes simplex virus 1; herpes simplex virus 2; human subject; inflammation; lymphocyte proliferation; myocardial infarction; prognosis; serology /serodiagnosis; stroke

Recent studies have associated evidence of Chlamydia pneumoniae infection with coronary and carotid atherosclerosis and evidence of increased infection with cytomegalovirus (CMV) in patients developing restenosis or with atherosclerosis. Several other common pathogens have been less consistently associated with atherosclerosis. Altered parameters of inflammation and hemostasis have been identified as prognostic factors of myocardial infarction and have been linked as possible pathogenetic mechanisms. Recent studies have indicated that peripheral blood mononuclear cells (PBMC) from patients with coronary artery disease frequently called Chlamydia pneumoniae DNA and stimulation of PBMCs can reflect an unsuccessful host cellular immune response to CMV associated with elevated C-reactive protein (CRP). This proposed study is both a nested case-cohort study and a nested cohort analysis within the Strong Heart Study (SHS), an ongoing cohort study of 4,549 American Indians. This study will utilize previously collected specimens, baseline data, and the planned ultrasound measurement of carotid wall thickness (IMT) in SHS participants. Within the initial SHS cohort, 400 definite cases of incident myocardial infarction, coronary heart disease, and stroke will be compare with 400 control individuals with no such diagnoses and matched for age, gender, and residence. Their prior serum specimens will be analyzes for Chlamydia pneumoniae-specific IgG, IgM antibody, for cytomegalovirus-specific IgG antibody, and for CRP. In addition, assays will be performed for antibodies to Helicobacter pylori, hepatitis A virus, (HAV) and herpes simplex virus (HSV) type 1 and 2. Correlations will be made with baseline parameters of lipids, coagulation, and adjusted for potential confounding variables of tobacco use, pneumonia, and altered pulmonary function. An additional analysis of a subcohort, the above 400 controls, will be performed looking at the outcome of their carotid IMT, a parameter of subclinical atherosclerosis, in relation to serologic results indicating a prior exposure to CMV, Chlamydia pneumoniae, and/or other pathogens approximately 8 years preceding ultrasound testing. Both case-control and cohort analysis will be stratified by levels of hemostasis and inflammation, including CRP, fibrinogen, Lp(a), and plasminogen- activator inhibitor-1. A separate nested substudy performed on PBMCs, prospectively collected from 80 cases and 80 controls, will examine the host T-cell proliferative response to CMV and other pathogens in relation to disease and also search for a chronic persistent infection with Chlamydia pneumoniae evidence by DNA detection. Thus, this study will assemble a prognostic profile of infectious, inflammatory, and hemostatic factors and provide a foundation for possible future primary prevention trials.

最近的研究与肺炎衣原体有关 感染冠状动脉和颈动脉粥样硬化和证据 患者的巨细胞病毒（CMV）感染增加 再狭窄或动脉粥样硬化。 其他几种常见的病原体有 与动脉粥样硬化相关的不一致。改变 炎症和止血的参数已被确定为 心肌梗塞的预后因素，并已将其联系在一起 可能的致病机制。最近的研究表明 冠状动脉患者的外周血单核细胞（PBMC） 动脉疾病通常称为衣原体肺炎DNA和 PBMC的刺激会反映出失败的宿主细胞免疫 对CMV的反应与C升高的C反应蛋白（CRP）有关。这 拟议的研究既是嵌套的病例研究研究，又是嵌套队列 强大心脏研究（SHS）中的分析，一项正在进行的队列研究 4,549美国印第安人。这项研究将利用先前收集的 标本，基线数据和计划的超声测量 SHS参与者中的颈动脉壁厚（IMT）。在初始sh中 队列，400例确定的事件心肌梗死，冠状动脉 心脏病和中风将与400个对照个体进行比较 没有这样的诊断，并且适合年龄，性别和居住。他们的 先前的血清标本将分析肺炎特异性衣原体 IgG，IgM抗体，用于巨细胞病毒特异性IgG抗体，用于 CRP。此外，将对抗体进行测定 幽门螺杆菌，乙型肝炎病毒（HAV）和单纯疱疹病毒 （HSV）1型和2。将使用基线参数建立相关性 脂质，凝结和调整以进行潜在的混杂变量 烟草的使用，肺炎和肺功能改变。另一个 将对子体细胞（将进行上述400个对照）进行分析 查看其颈动脉IMT的结果，这是亚临床的参数 关于血清学结果的动脉粥样硬化，表明先验 暴露于CMV，衣原体肺炎和/或其他病原体 超声测试前约8年。两个病例对照 并将队列分析按止血水平和 炎症，包括CRP，纤维蛋白原，LP（A）和纤溶酶原 - 激活剂抑制剂1。在PBMC上执行的单独的嵌套物质， 从80例和80个对照中收集的前瞻性收集，将检查 宿主对CMV和其他病原体的宿主T细胞增殖反应 与疾病有关，还寻找慢性持续感染 通过DNA检测，与肺炎衣原体证据。因此，这项研究 将组装感染性，炎症性和 止血因素，并为未来的主要初选奠定了基础 预防试验。