Vascular regulation in postmenopausal females

绝经后女性的血管调节

基本信息

批准号：
10462980
负责人：
Emma J Lee
金额：
$ 7.43万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-16 至 2024-10-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10462980
关键词：
Age Aging Award Blood Pressure Blood Vessels Blood flow Cardiac Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Cause of Death Communities Data Development Development Plans Discrimination Environment Estrogens Ethnic Origin Fellowship Female Forearm Foundations Functional disorder Future Goals Gonadal Steroid Hormones Grant Hand Health Hypertension Impairment Individual Knowledge Link Measures Mediator of activation protein Menopause Mentors Minnesota Mission Morbidity - disease rate Muscle National Heart, Lung, and Blood Institute Nerve Outcome Participant Patients Persons Physiological Physiology Play Plethysmography Population Heterogeneity Postmenopause Premature Menopause Premenopause Prevalence Prevention approach Prevention strategy Regulation Research Rest Risk Risk Factors Role Scholarship Stress Sympathetic Nervous System Techniques Testing Therapeutic Training United States United States National Institutes of Health Universities Vascular resistance Venous Work blood pressure control blood pressure elevation blood pressure regulation burden of illness cardiovascular disorder risk cardiovascular health cardiovascular risk factor career career development coping economic impact ethnic diversity experience health economics health equity high risk improved indexing insight medical schools mortality perceived discrimination prophylactic racial population resilience response stressor targeted treatment treatment strategy vasoconstriction

项目摘要

Project Summary/Abstract The goal of the proposed study is to elucidate mechanisms contributing to the heightened risk of cardiovascular disease (CVD) and hypertension (HTN) in early-menopausal compared to typical-age- menopausal females. The risks of CVD and HTN increase steeply after menopause, but females who complete menopause early (< age 46 yrs.) are more likely to experience HTN and CVD-related morbidity and mortality than those who complete menopause at a typical age (~ 51 yrs.) Furthermore, sympathetic increases in females after menopause, and higher sympathetic drive is associated with cardiovascular mortality and HTN. Postmenopausal females have shown dysregulation in autonomic control of blood pressure (BP), but it is unknown whether BP dysregulation occurs similarly in early-menopausal and typical-age-menopausal females. Moreover, altered vascular transduction, whereby an increase in sympathetic activity causes vasoconstriction, may play a role in the development of HTN. This proposal will investigate sympathetic regulation of blood flow and blood pressure in early- and typical-age-menopausal females. Additionally, individuals who are racialized as non-white have higher cardiovascular risks than white people, and this study will explore perceived discrimination and coping as potential mediators of CVD and HTN in postmenopausal females of diverse backgrounds. To evaluate vascular regulation, forearm vascular conductance (FVC) and muscle sympathetic nerve activity (MSNA) will be measured via venous occlusion plethysmography and microneurography, respectively, in postmenopausal females, ages 50-70 yrs., who completed menopause early or at a typical age. Conductance and MSNA will be measured at rest (SA1) and during a two-minute cold pressor test (CPT) of the hand (SA2). Importantly, BP responses to a CPT can predict future HTN, and greater sympathetic reactivity to a stressor may indicate a higher risk for future CVD. Further, physiological responses and correlations between discrimination and coping scores will be explored (SA3). The hypotheses are that early- menopausal females will have lower resting FVC and higher resting MSNA, and larger changes in FVC and MSNA with CPT, than typical-age-menopausal females; and that higher perceived discrimination and lower coping ability will be associated with higher sympathetic outflow. Dr. Lee will be trained in techniques of microneurography and venous occlusion plethysmography and will engage in career development activities, including grant and scholarship development. In addition, she will be trained in community-engagement strategies during the fellowship duration. She will receive training from an exemplary team in a research-rich environment within the Medical School at the University of Minnesota. This proposal aligns with the NHLBI’s mission, identifying mechanisms contributing to HTN and CVD for development of prevention and treatment strategies to reduce CVD risk in early-menopausal females, while also striving toward health equity. The proposed study will provide foundational knowledge along with exceptional fellowship training for the applicant.

项目概要/摘要拟议研究的目的是阐明导致重大风险的机制与典型年龄相比，绝经早期的心血管疾病（CVD）和高血压（HTN）更年期女性患心血管疾病和高血压的风险在绝经后急剧增加，但绝经后的女性。过早绝经（< 46 岁）更有可能出现高血压和心血管疾病相关的发病率和死亡率与那些在典型年龄（〜51岁）完成更年期的人相比，交感神经的增加绝经后的女性，较高的交感神经驱动力与心血管死亡率和高血压有关。绝经后女性在血压（BP）的自主控制方面表现出失调，但尚不清楚血压失调是否同样发生在绝经早期和典型年龄绝经女性中。此外，血管转导改变，因此交感神经活动增加导致血管收缩，可能在 HTN 的发展中发挥作用该提案将研究血流的交感调节。以及早期和典型绝经期女性的血压。因为非白人比白人有更高的心血管风险，这项研究将探讨感知到的歧视和应对作为不同绝经后女性 CVD 和 HTN 的潜在中介因素评估血管调节、前臂血管电导 (FVC) 和肌肉交感神经。神经活动（MSNA）将通过静脉闭塞体积描记法和显微神经描记法测量，分别在年龄 50-70 岁的绝经后女性中，她们提前或在典型的情况下完成了更年期。电导和 MSNA 将在静息 (SA1) 和两分钟冷加压测试 (CPT) 期间进行测量。重要的是，BP 对 CPT 的反应可以预测未来的 HTN 和更大的交感神经。对压力源的反应可能表明未来患心血管疾病的风险更高。将探讨歧视和应对分数之间的相关性（SA3）。更年期女性的静息 FVC 较低，静息 MSNA 较高，FVC 和 MSNA 变化较大。 MSNA 与 CPT 相比，比典型年龄的绝经女性更高，感知歧视程度更低；应对能力将与更高的交感神经流出有关。李博士将接受以下技术的培训。显微神经造影和静脉闭塞体积描记术并将从事职业发展活动，此外，她还将接受社区参与方面的培训。在奖学金期间，她将接受来自研究丰富的模范团队的培训。该提案与 NHLBI 的要求一致。使命，确定导致 HTN 和 CVD 的机制，以制定预防和治疗措施降低绝经早期女性心血管疾病风险的策略，同时努力实现健康公平。拟议的研究将为申请人提供基础知识以及特殊的奖学金培训。