StoP STRokE: Sex-Specific Prevention of Stroke Through Reproductive Risk Factors and Sex Hormone Effects

项目摘要/摘要 特蕾西·E·马德森博士是罗德岛大学急诊医学系助理教授 医院和布朗大学阿尔伯特医学院。在提议的研究项目中，马德森博士将 调查女性和男性在缺血性中风风险方面的差异，并将调查潜在原因 中风风险的性别差异，包括性激素和性激素结合球蛋白的影响 (SHBG)关于导致血管疾病的生物机制。马德森博士的职业发展奖 可能导致对缺血性中风风险的性别差异以及更多 了解性激素和SHBG如何影响女性和男性的中风风险。这些发现可能会导致 以更个性化、特定性别的方式预测中风风险和预防中风的新方法 ED患者血管疾病一级和二级预防策略的使用。 在第一阶段，马德森博士将对两个国家数据集(大辛辛那提/ 北肯塔基州中风研究和中风地理和种族差异的原因)调查 随着时间的推移，中风发病率的性别差异和中风严重程度的危险因素性别差异。在 第二个目标是，马德森博士将利用现有的中风队列(妇女健康倡议(WHI)和Framingham 心脏研究(FHS))，以研究SHBG与缺血性中风之间潜在的性别相关性。这 将包括对SHBG和其他血管风险标记物的关系的调查，包括 胰岛素抵抗、炎症和脂类代谢。最后，在第三个目标中，她将制定一种针对性别的 中风风险评分，包括与生育史相关的因素以及性激素生物标志物和 进行试点验证研究。 马德森博士组建了一支由忠诚、合格的联合导师组成的跨学科团队， 合作者：刘思敏博士，在SHBG、性类固醇和分子研究方面具有专业知识的主要导师 导致血管疾病风险的机制，Jo-Ann Manson博士，生殖专业导师 内分泌学，Karen Furie博士，在女性中风预防和中风临床试验方面拥有专业知识 预防，Dawn Kleindorfer博士，全国知名的中风流行病学家，在性别差异方面有专长 中风，以及弗吉尼亚·霍华德博士，另一位中风流行病学家，但在使用纵向数据方面很有专长 从中风队列研究中风流行病学中的性别差异。合作者包括苏达·塞沙德里博士， 弗雷明汉研究的高级研究员MD和该项目的统计学家Jane Khoury博士说。Dr。 马德森将完成她在急诊医学部的拟议研究活动 附属于罗德岛医院，一家综合性的中风中心，布朗的阿尔伯特医学院 和布朗大学公共卫生学院。

PROJECT SUMMARY / ABSTRACT Dr. Tracy E. Madsen is an Assistant Professor in the Department of Emergency Medicine at Rhode Island Hospital and the Alpert Medical School of Brown University. In the proposed research project, Dr. Madsen will investigate differences in ischemic stroke risk between women and men and will investigate potential reasons for sex differences in stroke risk including the influence of sex hormones and sex hormone binding globulin (SHBG) on biologic mechanisms leading to vascular disease. Dr. Madsen's Career Development Award has the potential to lead to a greater understanding of sex differences in ischemic stroke risk as well as more knowledge of how sex hormones and SHBG affect stroke risk in women and men. These findings could lead to novel ways to predict stroke risk and prevent stroke in a more personalized, sex-specific manner and to the use of primary and secondary prevention strategies for vascular disease in ED patients. In the first phase, Dr. Madsen will conduct secondary analyses of two national datasets (Greater Cincinnati/ Northern Kentucky Stroke Study and Reasons for Geographic and Racial Differences in Stroke) to investigate sex differences in stroke incidence over time and sex differences in the severity of stroke risk factors. In the second aim, Dr. Madsen will use existing stroke cohorts (Women's Health Initiative (WHI) and the Framingham Heart Study (FHS)) to study the potential sex-specific association between SHBG and ischemic stroke. This will include the investigation of the relationship between SHBG and other markers of vascular risk including insulin resistance, inflammation, and lipid metabolism. Finally, in the third aim, she will develop a sex-specific stroke risk score that includes factors related to reproductive history as well as sex hormone biomarkers and conduct a pilot validation study. Dr. Madsen has assembled an interdisciplinary team of committed, well-qualified co-mentors and collaborators: Dr. Simin Liu, primary mentor with expertise in the study of SHBG, sex steroids, and molecular mechanisms leading to vascular disease risk, Dr. Jo-Ann Manson, mentor with expertise in reproductive endocrinology, Dr. Karen Furie, with expertise in stroke prevention in women and clinical trials in stroke prevention, Dr. Dawn Kleindorfer, a nationally known stroke epidemiologist with expertise in sex differences in stroke, and Dr. Virginia Howard, another stroke epidemiologist but with expertise in the use of longitudinal data from stroke cohorts to study sex differences in stroke epidemiology. Collaborators include Dr. Sudha Seshadri, MD, a senior investigator of the Framingham Study and Dr. Jane Khoury, PhD, statistician on the project. Dr. Madsen will be completing her proposed research activities in the Department of Emergency Medicine affiliated with Rhode Island Hospital, a comprehensive stroke center, the Alpert Medical School of Brown University, and the Brown University School of Public Health.