Vasomotor symptoms of menopause and cardiovascular disease: What is the link?

更年期的血管舒缩症状和心血管疾病：有什么联系？

• 批准号: 10739661
• 负责人: Manda Linea Keller-Ross
• 金额: $ 22.04万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10739661
• 关键词: Adult; Age; Aging; Baroreflex; Blood Pressure; Blood Vessels; Blood flow; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cholesterol; Chronic; Clinical Research; Data; Development; Doctor of Philosophy; Endothelium; Estrogens; Exposure to; Female; Forearm; Goals; Heating; Hot flushes; Impairment; Individual; Laboratories; Lead; Link; Measures; Menopausal Symptom; Menopause; Methodology; Minnesota; Mission; Muscle; Nature; Nerve; Night Sweating; Observational Study; Pathway interactions; Physical Medicine; Physicians; Physiologic pulse; Physiological; Plethysmography; Positioning Attribute; Postmenopause; Premenopause; Prevention strategy; Process; Regulation; Rehabilitation therapy; Research; Risk; Signal Transduction; System; Techniques; Temperature; Testing; United States National Institutes of Health; Universities; Venous; Water; Woman; Women' s Health; associated symptom; blood pressure elevation; blood pressure regulation; cardioprotection; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; design; endothelial dysfunction; experience; improved; innovation; insight; male; medical schools; mortality; novel; novel therapeutics; professor; response; stressor; targeted treatment; tonometry; treatment strategy; vasomotor symptoms

Project Summary/Abstract Aging is a risk factor for cardiovascular disease (CVD), and females who experience vasomotor symptoms (VMS, hot flushes and night sweats) have a 55% greater risk for CVD compared with females who do not experience VMS. Because CVD is the leading cause of mortality in females in the US, the factors contributing to CVD in menopausal females are critical to determine and yet are unclear. Autonomic and vascular dysregulation, often demonstrated in postmenopausal females, is associated with CVD, but whether this dysregulation exists specifically in females with VMS is unknown. Further, how hot flushes, a major VMS, alter autonomic function has not been well defined. This application for a NIH R21 is designed to identify mechanistic pathways to determine how VMS lead to CVD. Dr. Manda L Keller-Ross, DPT, PhD, an Assistant Professor in the Department of Rehabilitation Medicine, in the Medical School at the University of Minnesota, is the PI of the Cardiovascular Research and Rehabilitation Laboratory, where the proposed research will take place. The long-term objectives of this proposal are to determine the link between VMS and CVD in menopausal females. Specifically, Dr. Keller- Ross aims to determine the extent that females who experience VMS demonstrate autonomic and vascular dysregulation (Aim 1). She will then delineate the mechanism by which hot flushes alter autonomic regulation (Aim 2). This proposal is in line with the mission of the NIA, to understand the nature of the aging process in females and how factors associated with menopause contribute to the number-one cause of death in females, CVD. Dr. Keller-Ross seeks to conduct an exploratory study to interrogate the thermoregulatory system in females by inducing hot flushes and investigating how hot flushes alter autonomic function. To accomplish these research objectives, Dr. Keller-Ross and Dr. Blas (Co-I) will use gold-standard techniques combined with an innovative methodological approach to quantify autonomic and vascular dysregulation in females with VMS. Aim 1 will quantify muscle sympathetic activity (MSNA), measured via microneurography; endothelial dysfunction, measured with Endothelial Pulse Amplitude Tonometry; vascular conductance, measured via venous occlusion plethysmography; and baroreflex sensitivity in postmenopausal females who experience VMS. We hypothesize that females with VMS will demonstrate elevated MSNA, reduced vascular conductance and impaired endothelial function, leading to elevated BP, compared with females without VMS. Aim 2 will explore the extent to which a hot flush, induced by a temperature-controlled, water-circulating heating pad, alters autonomic function in postmenopausal females. We hypothesize that a hot flush will cause an increase in MSNA, contributing to chronic autonomic dysregulation of BP in menopausal females. By identifying the link between VMS and CVD, we will set the stage for the development of novel therapies and optimization of current treatments for VMS with the goal of reducing sympathetic activity and restoring autonomic and vascular function to mitigate CVD risk in females, particularly for those who experience VMS.

项目摘要/摘要 衰老是心血管疾病（CVD）的危险因素，也是经历血管舒缩症状的女性（VMS，VMS， 与没有经历的女性相比，CVD的风险高55％，而没有经历 VM。因为CVD是美国女性死亡率的主要原因，所以导致CVD的因素 绝经女性对于确定至关重要，但尚不清楚。自主和血管失调，通常 在绝经后女性中证明，与CVD有关，但是这种失调是否存在 特别是在具有VM的女性中，尚不清楚。此外，如何热潮，主要VM，改变自主功能 尚未得到很好的定义。 NIH R21的此应用旨在确定机械途径 确定VM如何导致CVD。 DPT博士Manda L Keller-Ross博士，该系的助理教授 明尼苏达大学医学院的康复医学是心血管的PI 研究和康复实验室将进行拟议的研究。长期目标 该提议的内容是确定更年期女性中VM和CVD之间的联系。具体而言，凯勒博士 罗斯旨在确定经历VM的女性表现自主和血管的程度 失调（目标1）。然后，她将描述热潮改变自主法规的机制 （目标2）。该提议符合NIA的使命，以了解老化过程的性质 女性以及与更年期有关的因素如何促成女性死亡的第一原因， CVD。凯勒·罗斯（Keller-Ross）博士试图进行探索性研究，以询问温度调节系统 女性通过诱导热潮并研究热冲洗如何改变自主功能。完成 这些研究目标，Keller-Ross博士和Blas博士（CO-I）将使用金色标准技术 通过一种创新的方法论方法来量化女性的自主神经和血管失调 VM。 AIM 1将量化通过微功能学测量的肌肉交感活动（MSNA）；内皮 功能障碍，用内皮脉冲幅度静态分解测量；血管电导，通过 静脉闭塞杂质；以及经历VM的绝经后女性的降压力敏感性。 我们假设患有VMS的女性将显示MSNA升高，血管电导降低和 与没有VM的女性相比，内皮功能受损，导致BP升高。 AIM 2将探索 由温度控制的水循环加热垫诱导的热潮的程度，改变 绝经后女性的自主功能。我们假设一流的冲洗会导致MSNA的增加， 在更年期女性中有助于BP的慢性自主性失调。通过识别 VM和CVD，我们将为开发新疗法和优化当前治疗的阶段 对于VM，目的是减少交感神经活动并恢复自主和血管功能以减轻 女性的CVD风险，特别是对于那些经历VM的人。