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

StoP STRokE：通过生殖危险因素和性激素影响进行针对性别的中风预防

• 批准号: 10460151
• 负责人: Tracy Madsen
• 金额: $ 18.44万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10460151
• 关键词: Accident and Emergency department; Activities of Daily Living; Acute; Affect; Age; Age at Menarche; Atrial Fibrillation; Biological; Biological Markers; Blood Vessels; Body mass index; Breast Feeding; Case-Control Studies; Cause of Death; Cessation of life; Clinic; Clinical Trials; Data; Data Analyses; Data Set; Derivation procedure; Diabetes Mellitus; Diastolic blood pressure; Disabled Persons; Disease Outcome; Doctor of Philosophy; Dyslipidemias; Emergency Department patient; Emergency Medicine; Epidemiologist; Epidemiology; Estradiol; First Births; Framingham Heart Study; Future; Glycosylated hemoglobin A; Goals; Gonadal Steroid Hormones; High Density Lipoproteins; Hormonal; Hormone replacement therapy; Hormone use; Hospitals; Hypertension; Impairment; Incidence; Inflammation; Insulin Resistance; Investigation; Irregular Menstruation; Ischemic Stroke; K-Series Research Career Programs; Kentucky; Knowledge; Lead; Link; Low-Density Lipoproteins; Measurement; Measures; Mediation; Menopause; Mentors; Metabolic Diseases; Methods; Migraine; Mission; Molecular; National Heart, Lung, and Blood Institute; Obesity; Oral Contraceptives; Participant; Patients; Phase; Phenotype; Population Heterogeneity; Pre-Eclampsia; Pregnancy Outcome; Prevalence; Prevention strategy; Primary Health Care; Primary Prevention; Proteins; Public Health Schools; Reasons for Geographic And Racial Differences in Stroke; Reproductive Endocrinology; Reproductive History; Research; Research Activity; Research Personnel; Research Project Grants; Rhode Island; Risk; Risk Assessment; Risk Factors; Risk Marker; Role; Secondary Prevention; Severities; Sex Differences; Sex Hormone-Binding Globulin; Standardization; Stroke; Stroke prevention; Time; Universities; Validation; Vascular Diseases; Virginia; Woman; Women' s Health; cigarette smoke; cigarette smoking; clinical research site; cohort; disability; disorder risk; improved; innovation; lifetime risk; lipid metabolism; medical schools; men; multi-ethnic; novel; novel strategies; potential biomarker; professor; reproductive; risk stratification; secondary analysis; sex; stroke incidence; stroke outcome; stroke risk; validation studies; vascular risk factor

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.

项目总结/摘要 Tracy E.博士马德森是罗得岛急诊医学系的助理教授 医院和布朗大学阿尔珀特医学院。在拟议的研究项目中，马德森博士将 研究男女之间缺血性卒中风险的差异，并将研究潜在的原因 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）的生物学机制导致血管疾病。马德森博士的职业发展奖 可能导致更好地理解缺血性卒中风险的性别差异，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。这些发现可能导致 新的方法来预测中风风险和预防中风在一个更个性化的，性别特异性的方式， 在艾德患者中使用血管疾病的一级和二级预防策略。 在第一阶段，Madsen博士将对两个国家数据集（大辛辛那提/ 北方肯塔基州卒中研究和卒中的地理和种族差异的原因）进行调查 随着时间的推移，中风发病率的性别差异和中风危险因素严重程度的性别差异。在 第二个目标是，Madsen博士将使用现有的中风队列（妇女健康倡议（WHI）和Fragrance 心脏研究（FHS）），研究SHBG与缺血性中风之间潜在的性别特异性相关性。这 将包括SHBG和其他血管风险标志物之间关系的研究，包括 胰岛素抵抗、炎症和脂质代谢。最后，在第三个目标中，她将制定一个性别特异性的 中风风险评分，包括与生殖史相关的因素以及性激素生物标志物， 进行试点验证研究。 马德森博士组建了一支由忠诚的、合格的共同导师组成的跨学科团队， Simin Liu博士，主要导师，在SHBG，性类固醇和分子生物学研究方面具有专业知识。 导致血管疾病风险的机制，Jo-Ann曼森博士，生殖领域专业知识导师 内分泌学，卡伦Furie博士，在预防妇女中风和中风临床试验的专业知识 Dawn Kleindorfer博士是一位全国知名的中风流行病学家，他在性别差异方面具有专业知识。 弗吉尼亚霍华德博士，另一位中风流行病学家，但在使用纵向数据的专业知识 研究中风流行病学中的性别差异。合作者包括Sudha Seshadri博士， 医学博士，Fragrance研究的高级研究员和Jane Khoury博士，博士，该项目的统计学家。博士 马德森将在急诊医学系完成她提出的研究活动 附属于罗得岛医院，一个综合中风中心，布朗的阿尔珀特医学院 大学和布朗大学公共卫生学院。

项目成果

Impact of a Pandemic on Early Career Women.

流行病对早期职业女性的影响。

• DOI: 10.1161/strokeaha.121.035186
• 发表时间: 2022
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Nobleza,ChristaO'HanaS;Inoa,Violiza;Mittal,Shilpi;Zachrison,KoriS;Madsen,TracyE
• 通讯作者: Madsen,TracyE

Evidence for Decreasing Stroke Incidence Among Mexican Americans During Midlife and Implications for Targeted Stroke Prevention Efforts.

墨西哥裔美国人中年期间中风发病率降低的证据以及有针对性的中风预防工作的影响。

• DOI: 10.1212/wnl.0000000000012880
• 发表时间: 2021
• 期刊: Neurology
• 影响因子: 9.9
• 作者: Madsen,TracyE

Substance Use and Performance of Toxicology Screens in the Greater Cincinnati Northern Kentucky Stroke Study.

• DOI: 10.1161/strokeaha.121.038311
• 发表时间: 2022-10
• 期刊: Stroke
• 影响因子: 8.3

Sex differences in modifiable stroke risk factors: The next step in personalized stroke prevention.

可改变的中风危险因素的性别差异：个性化中风预防的下一步。

• DOI: 10.1212/wnl.0000000000010983
• 发表时间: 2020
• 期刊: Neurology
• 影响因子: 9.9
• 作者: Madsen,TracyE;Guo,Daoxia
• 通讯作者: Guo,Daoxia

Advancing Secondary Stroke Prevention Strategies: Optimal Timing of Dual Antiplatelet Therapy With Cilostazol.

推进二级中风预防策略：西洛他唑双重抗血小板治疗的最佳时机。

• DOI: 10.1212/wnl.0000000000200103
• 发表时间: 2022
• 期刊: Neurology
• 影响因子: 9.9
• 作者: Madsen,TracyE;deHavenon,Adam
• 通讯作者: deHavenon,Adam