INFLAMMATION, INFECTION AND FUTURE CARDIOVASCULAR RISK

炎症、感染和未来的心血管风险

• 批准号: 6183302
• 负责人: Paul M. Ridker
• 金额: $ 17.38万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-21 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6183302
• 关键词: Chlamydiaceae; Helicobacter; acute phase protein; antibacterial antibody; antiviral antibody; aspirin; biomarker; blood banks; cardiovascular disorder epidemiology; cell adhesion molecules; chlamydial disease; clinical research; cytomegalovirus; disease /disorder proneness /risk; herpes simplex virus 1; human tissue; infection; inflammation; interleukin 6; longitudinal human study; male; myocardial infarction; stroke; thromboembolism; tumor necrosis factor alpha

DESCRIPTION: (Adapted from Investigator's Abstract) The plan is to examine markers of underlying chronic inflammation and infection as potential risk factors for future myocardial infarction (MI), stroke (CVA), and venous thromboembolism (VTE) in plasma samples collected at baseline from healthy participants in the Physicians' Health Study (PHS). The PHS is a cohort of 12 years duration which included 14,916 men initially free of cardiovascular disease and cancer who provided plasma samples at study entry in 1982. These men were randomly assigned in a factorial design to aspirin or beta-carotene therapy, and have been followed prospectively for the occurrence of vascular disease. Employing a nested case-control design, baseline plasma samples will be assayed for four markers of inflammation (interleukin-6, TNF-alpha, soluble ICAM, soluble VCAM) and four markers of chronic infection (antibody titers directed against Chlamydia pneumoniae, Helicobacter pylori, Herpes simplex virus, and cytomegalovirus). Case subjects will be those study participants who have subsequently developed MI (N=550), CVA (N=400), or VTE (N=200). Control subjects will be selected from those study participants who remained healthy during follow-up and will be matched to the cases by age, smoking status, and follow-up time. Data on usual cardiovascular risk factors, lipid parameters, and hemostatic markers of risk are already available in the PHS and will be used to evaluate the results for potential confounding and effect modification. Since the PHS was a randomized trial of low-dose aspirin for its initial 5 years, this cohort also provides the unique opportunity to investigate whether the use of an agent with anti-inflammatory properties modifies the risk of subsequent thrombosis among those with underlying inflammation. Indeed, this intriguing hypothesis has recently been raised regarding data relating another marker of inflammation, C-reactive protein, to future risks of myocardial infarction and stroke. These analyses will take advantage of an existing blood bank from a well-characterized large cohort with already over 12 years of follow-up and high quality end-point verification. Thus, this study could provides an efficient and cost-effective mechanism to evaluate the posited, but unproven roles of inflammation and infection as risk factors for future cardiovascular disease.

描述：（改编自研究者摘要）该计划旨在检查 潜在慢性炎症和感染的标志物是潜在风险 未来发生心肌梗塞 (MI)、中风 (CVA) 和静脉血栓的因素 基线时从健康人身上采集的血浆样本中存在血栓栓塞 (VTE) 医生健康研究 (PHS) 的参与者。 PHS 是一个队列 为期 12 年，其中包括 14,916 名最初没有心血管疾病的男性 疾病和癌症患者在 1982 年进入研究时提供了血浆样本。 这些人在析因设计中被随机分配服用阿司匹林或 β-胡萝卜素疗法，并已进行前瞻性随访 血管疾病的发生。 采用嵌套案例控制设计， 将检测基线血浆样本的四种炎症标志物 （白细胞介素 6、TNF-α、可溶性 ICAM、可溶性 VCAM）和四种标记物 慢性感染（针对肺炎衣原体的抗体滴度， 幽门螺杆菌、单纯疱疹病毒和巨细胞病毒）。 案件 受试者将是那些随后发生心肌梗死的研究参与者 (N=550)、CVA (N=400) 或 VTE (N=200)。 将选择控制对象 来自那些在随访期间保持健康并将 按年龄、吸烟状况和随访时间与病例相匹配。 数据于 常见的心血管危险因素、血脂参数和止血标志物 风险已经在 PHS 中提供，并将用于评估 潜在混杂和效果修改的结果。 自从有了小灵通 是一项在最初 5 年中使用低剂量阿司匹林的随机试验， 队列还提供了独特的机会来调查是否使用 具有抗炎特性的药物可以降低以下风险： 患有潜在炎症的人随后会形成血栓。 的确， 最近有人提出了这个有趣的假设，涉及相关数据 炎症的另一个标志物 C 反应蛋白，可预测未来的风险 心肌梗塞和中风。 这些分析将利用现有的血库 具有良好特征的大型队列，已经进行了超过 12 年的随访 高质量的终点验证。 因此，这项研究可以提供 有效且具有成本效益的机制来评估假设的但未经证实的 炎症和感染作为未来危险因素的作用 心血管疾病。

项目成果

C-reactive protein gene polymorphisms and the risk of venous thromboembolism: a haplotype-based analysis.

C反应蛋白基因多态性和静脉血栓栓塞的风险：基于单倍型的分析。

• DOI: 10.1111/j.1538-7836.2004.00773.x
• 发表时间: 2004
• 期刊: Journal of thrombosis and haemostasis : JTH
• 作者: Zee,RYL;Hegener,HH;Cook,NR;Ridker,PM
• 通讯作者: Ridker,PM

Haplotype analysis of the beta2 adrenergic receptor gene and risk of myocardial infarction in humans.

β2 肾上腺素受体基因的单倍型分析和人类心肌梗死的风险。

• DOI: 10.1534/genetics.104.037812
• 发表时间: 2005
• 期刊: Genetics.
• 作者: Zee,RobertYL;Cook,NancyR;Reynolds,Rebecca;Cheng,Suzanne;Ridker,PaulM
• 通讯作者: Ridker,PaulM

Purinergic receptor P2Y, G-protein coupled, 12 gene variants and risk of incident ischemic stroke, myocardial infarction, and venous thromboembolism.

嘌呤能受体 P2Y、G 蛋白偶联、12 种基因变异以及发生缺血性中风、心肌梗死和静脉血栓栓塞的风险。

• DOI: 10.1016/j.atherosclerosis.2007.07.001
• 发表时间: 2008
• 期刊: Atherosclerosis
• 影响因子: 5.3
• 作者: Zee,RobertYL;Michaud,SherriE;Diehl,KirstiA;Chasman,DanielI;Emmerich,Joseph;Gaussem,Pascale;Aiach,Martine;Ridker,PaulM
• 通讯作者: Ridker,PaulM

A prospective evaluation of the CD14 C(-260)T gene polymorphism and the risk of myocardial infarction.

• DOI: 10.1016/s0021-9150(00)00698-5
• 发表时间: 2001-02
• 期刊: Atherosclerosis
• 影响因子: 5.3
• 作者: R. Zee;K. Lindpaintner;B. Struk;C. Hennekens;P. Ridker

Prospective evaluation of the alcohol dehydrogenase gamma1/gamma2 gene polymorphism and risk of stroke.

乙醇脱氢酶γ1/γ2基因多态性与中风风险的前瞻性评估。

• DOI: 10.1161/01.str.0000114202.86942.61
• 发表时间: 2004
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Zee,RobertYL;Ridker,PaulM;Cook,NancyR
• 通讯作者: Cook,NancyR