Hormones and Biomarkers Predicting Stroke in Women

描述：（由申请人提供）妇女健康倡议用于预防健康绝经后妇女心血管疾病的雌激素加黄体酮临床试验，最近因副作用而停止，以及其他二级预防临床试验，发现雌激素加黄体酮使用者中风的风险增加。我们希望通过研究止血/炎症的生物标志物作为缺血性卒中的危险因素，以及激素替代疗法和其他危险因素（包括高血压和生活方式变量）对卒中相关影响的介质，来研究这种增加的可能机制。该研究的目的是确定与全身炎症和/或动脉粥样硬化血栓形成/止血/凝血相关的基于血液的生物标志物是否可能是老年妇女缺血性卒中和缺血性卒中亚型的重要危险因素。我们将在妇女健康倡议（WHI-OS）的观察性研究组成部分的参与者中进行一项基于人群的巢式病例对照研究，包括1050例缺血性卒中病例和1050例匹配的对照。WHI-OS在美国40个中心的多种族队列中进行，是一项对93,676名绝经后妇女进行的前瞻性研究，随访8至12年，收集了广泛的基线和随访数据，包括血液和DNA样本，并在基线处保存。多变量建模技术将用于研究选定的生物标志物、高血压、激素使用和生活方式变量与缺血性卒中风险和中央裁判员分类的特定卒中亚型之间的关联。我们还将确定既定危险因素（高血压、吸烟、糖尿病）和特定药物（他汀类药物、阿司匹林、非甾体抗炎药、雌激素和黄体酮）的使用是否会在存在炎症和/或动脉粥样硬化血栓形成/止血标志物的情况下改变对卒中风险的影响。

DESCRIPTION: (provided by applicant) The Women's Health Initiative clinical trial of estrogen plus progestin for the prevention of cardiovascular disease in healthy, postmenopausal women, which was recently stopped due to adverse effects, as well as other secondary prevention clinical trials, have found increased risk of stroke in users of estrogen plus progestin. We wish to investigate possible mechanisms for such an increase by studying biomarkers of hemostasis /inflammation as risk factors for ischemic stroke and as mediators of stroke related effects of hormone replacement therapy and other risk factors, including hypertension and lifestyle variables. The goal of the proposed study is to determine whether blood-based biomarkers related to systemic inflammation, and/or atherothrombosis/hemostasis/coagulation may be important risk factors for ischemic stroke and subtypes of ischemic stroke among older women. We will conduct a population based nested case-control study of 1050 ischemic stroke cases and 1050 matched controls among participants in the Observational Study component of the Women's Health Initiative (WHI-OS). The WHI-OS, conducted in a multi-ethnic cohort in 40 centers throughout the United States, is a prospective study of 93,676 postmenopausal women, followed for 8 to 12 years, with extensive baseline and follow-up data including blood and DNA specimens collected and stored at baseline. Multivariate modeling techniques will be used to investigate the associations of selected biomarkers, hypertension, hormone use and lifestyle variables, with risk of ischemic stroke and specific stroke subtypes as classified by central adjudicators. We will also determine whether the effects on stroke risk of established risk factors (hypertension, smoking, diabetes) and use of specific medications (statins, aspirin, non-steroidal anti-inflammatory agents, estrogen and progesterone) will be modified in the presence of markers of inflammation and/or of atherothrombosis/hemostasis.