Vascular regulation in postmenopausal females

绝经后女性的血管调节

• 批准号: 10708786
• 负责人: Emma J Lee
• 金额: $ 7.82万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 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/10708786
• 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; Estrogen deficiency; Estrogens; Fellowship; Female; Forearm; Foundations; Functional disorder; Future; Goals; Gonadal Steroid Hormones; Grant; Hand; Health; Hypertension; Impairment; Individual; Knowledge; Link; Measures; Mediator; 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; Race; 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; decrease resilience; economic impact; ethnic diversity; experience; health equity; high risk; improved; indexing; insight; medical schools; mortality; perceived discrimination; prophylactic; racial population; response; stressor; targeted treatment; treatment strategy; vasoconstriction

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.

项目摘要/摘要 拟议的研究的目的是阐明有助于增加风险的机制 与典型的年龄 - 年龄相比 绝经女性。更年期后，CVD和HTN的风险急剧增加，但是完成的女性 更年期早期（<46岁）更有可能体验HTN和CVD相关的发病率和死亡率 比那些在典型年龄（〜51岁）完成更年期的人。 更年期后的女性和更高的交感神经驱动与心血管死亡率和HTN有关。 绝经后女性在血压（BP）的自主控制中表现出失调，但它是 尚不清楚BP失调是否在早期和典型的年绝经期女性中发生类似。 此外，血管转导的改变，交感神经活动的增加会导致血管收缩， 可能在HTN的发展中发挥作用。该提案将调查血流的交感神经调节 以及早期和典型的年绝经症中的血压。此外，种族化的个人 由于非白人的心血管风险高于白人，这项研究将探索所感知的 在潜水员的绝经后女性中，歧视和应对作为CVD和HTN的潜在介体 背景。评估血管调节，前臂血管电导（FVC）和肌肉交感神经 神经活性（MSNA）将通过静脉闭塞杂质和微功能学测量， 分别在50 - 70岁的绝经后女性中，早期或典型完成了绝经 年龄。电导和MSNA将在静止（SA1）和两分钟的冷压测试（CPT）时测量 手（SA2）。重要的是，BP对CPT的反应可以预测未来的HTN，并且更加同情 对压力源的反应性可能表明将来CVD的风险更高。此外，身体反应和 将探索歧视与应对分数之间的相关性（SA3）。假设是早期 更年期女性的静息FVC和静息MSNA的静息较低，FVC和FVC的变化更大 具有CPT的MSNA，而不是典型的年龄段女性；以及更高的感知歧视和较低的歧视 应对能力将与较高的交感神经相关。 Lee博士将接受有关技术的培训 微功能学和静脉闭塞物质图，并将从事职业发展活动， 包括赠款和奖学金开发。此外，她将接受社区参与的培训 团契期间的策略。她将在研究丰富的研究中获得一个示例团队的培训 明尼苏达大学医学院内的环境。该建议与NHLBI的 任务，确定有助于HTN和CVD的机制，以开发预防和治疗 降低早期女性女性CVD风险的策略，同时也朝着健康公平努力。 拟议的研究将为申请人提供基础知识以及卓越的奖学金培训。