Sex Differences in Vascular Markers of Stroke Risk

中风风险血管标志物的性别差异

• 批准号: 7847487
• 负责人: CHERYL D BUSHNELL
• 金额: $ 17.93万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-15 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7847487
• 关键词: 2 year old; Acceleration; Ankle; Atherosclerosis; Atrial Fibrillation; Biological; Biological Markers; Biological Markers; Blood Pressure; Blood Vessels; Carotid Arteries; Cause of Death; Climacteric; Coronary heart disease; Development; Disease; Enrollment; Estradiol; Estrogens; Follicle Stimulating Hormone; Forearm; Functional disorder; Future; Gelatinase B; Generations; Goals; Gonadal Steroid Hormones; Hormones; Hypertension; Incidence; Inflammation; Investigation; Ischemia; Ischemic Stroke; Knowledge; Lead; Lipids; Measures; Mediating; Menopausal Status; Menopause; Modeling; Outcome; Outcome Study; Peripheral Vascular Diseases; Physiologic pulse; Physiological; Prevention; Prevention strategy; Preventive Intervention; Process; ROC Curve; Research; Risk; Risk Factors; Sex Characteristics; Sex Hormone-Binding Globulin; Stress; Stroke; Testosterone; Thrombin; Thromboplastin; Time; Tobacco smoking; Vascular Cell Adhesion Molecule-1; Vascular Diseases; Weight Gain; Woman; Women' s Group; Work; acute coronary syndrome; antithrombin III-protease complex; arterial stiffness; brachial artery; cardiovascular risk factor; case control; cohort; design; disability; fasting glucose; indexing; men; middle age; novel; response; sex; von Willebrand Factor

DESCRIPTION (provided by applicant): The cause of stroke in women is frequently unknown, despite recognition of cardiovascular risk factors and appropriate prevention treatment. The reason may be related to unrecognized subclinical disease, which may be manifested by ongoing thrombin generation, inflammation, endothelial dysfunction, and abnormal responses to vascular stresses. In addition, endogenous hormones such as estradiol and sex hormone binding globulin, as well as menopausal status impact cardiovascular risk. The aims of this K02 project are to: 1) Identify biological and physiological markers associated with ischemic stroke in women, and 2) Establish which biological and physiological markers are influenced by sex hormones and/or menopausal status in women with stroke. The working hypotheses are that women with ischemic stroke will have evidence of ongoing inflammation, thrombin generation, endothelial dysfunction, quantified by functional responses to forearm ischemia and measures of arterial stiffness, low sex hormone binding globulin, or a combination of the above processes. Using a case-control cohort design, 75 women with an ischemic stroke and 75 without ischemic stroke matched by age 2 years, menopausal status, and cardiovascular risk factors will be enrolled. Biological markers include tissue factor, matrix metalloproteinase-9 (MMP-9), vascular cell adhesion molecule-1 (VCAM-1), von Willebrand Factor (vWF), and thrombin-antithrombin III complex (TAT). Vascular studies include brachial artery flow-mediated dilation (measure of endothelial response to ischemia), carotid-femoral pulse wave velocity (measure of arterial stiffness), and ankle-brachial index (measure of peripheral vascular disease). Estradiol, testosterone, sex hormone binding globulin, and follicle stimulating hormone (for menopausal status determination) will also be measured. The significance of each marker will be assessed by plotting ROC curves for each marker, and then entering the significant markers into a multivariable model to determine the best combination of markers of stroke. Both groups of women will be followed for a minimum of two years after enrollment for any vascular outcomes, such as stroke, TIA, or acute coronary syndromes. The expected outcomes of this study will be the discovery of novel biological and vascular markers for stroke, and how endogenous sex hormones impact those markers. This could naturally lead to development of a predictive panel of markers for future stroke risk.

描述（由申请人提供）：尽管认识到心血管危险因素和适当的预防治疗，但女性中风的原因通常是未知的。原因可能与未识别的亚临床疾病有关，这些疾病可能由持续的凝血酶产生，炎症，内皮功能障碍以及对血管应激的异常反应表现出来。此外，雌二醇和性激素结合球蛋白等内源激素以及更年期状态影响心血管风险。该K02项目的目的是：1）确定与女性缺血性中风相关的生物学和生理标记，以及2）确定哪些生物学和生理标志物受性激素和/或中风女性的绝经状态的影响。有效的假设是，缺血性中风的女性将有持续的炎症，凝血酶产生，内皮功能障碍，通过对前臂缺血的功能反应和动脉僵硬，低性激素结合蛋白或上述过程的组合来量化。使用病例对照队列设计，将招募75名缺血性中风的女性，而75名无缺血性中风的女性将符合2岁，绝经状态和心血管危险因素。生物学标记包括组织因子，基质金属蛋白酶-9（MMP-9），血管细胞粘附分子-1（VCAM-1），von Willebrand因子（VWF）和凝血酶 - 抗凝血酶III复合物（TAT）。血管研究包括肱动脉流介导的扩张（对缺血的内皮反应的度量），颈动脉脉搏波速度（动脉刚度的度量）和脚踝 - 抗毛指数（外周血管疾病的量度）。还将测量雌二醇，睾丸激素，性激素结合球蛋白和卵泡刺激激素（用于绝经状态确定）。每个标记的意义​​将通过绘制每个标记的ROC曲线，然后将显着标记进入多变量模型来评估，以确定中风标记的最佳组合。入学后至少要遵循两组妇女的任何血管结局，例如中风，TIA或急性冠状动脉综合征。这项研究的预期结果将是发现中风的新生物学和血管标记，以及内源性性激素如何影响这些标记。这自然会导致为未来中风风险的预测小组开发。