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.

项目概要/摘要 衰老是心血管疾病 (CVD) 的危险因素，而经历血管舒缩症状 (VMS、 与没有经历过潮热和盗汗的女性相比，罹患 CVD 的风险增加 55% 虚拟管理系统。由于 CVD 是美国女性死亡的主要原因，导致 CVD 的因素 更年期女性对于确定这一点至关重要，但目前尚不清楚。自主神经和血管失调，经常 在绝经后女性中得到证实，与 CVD 相关，但这种失调是否存在 特别是在患有 VMS 的女性中，尚不清楚。此外，潮热（一种主要的 VMS）如何改变自主神经功能 还没有得到很好的定义。 NIH R21 的此应用程序旨在识别机械途径 确定 VMS 如何导致 CVD。 Manda L Keller-Ross 博士，DPT，博士，系助理教授 明尼苏达大学医学院康复医学系 PI 研究和康复实验室，拟议的研究将在此进行。长期目标 该提案的目的是确定更年期女性 VMS 和 CVD 之间的联系。具体来说，凯勒博士- Ross 旨在确定经历 VMS 的女性表现出自主神经和血管神经的程度 失调（目标 1）。然后她将描述潮热改变自主调节的机制 （目标 2）。该提案符合 NIA 的使命，即了解老龄化过程的本质 女性以及与更年期相关的因素如何导致女性死亡的第一大原因， 化学气相沉积。凯勒-罗斯博士试图进行一项探索性研究来询问体温调节系统 通过诱发潮热并研究潮热如何改变自主神经功能来研究女性。为了完成 Keller-Ross 博士和 Blas 博士 (Co-I) 将结合使用黄金标准技术来实现这些研究目标 采用创新的方法来量化女性的自主神经和血管失调 虚拟管理系统。目标 1 将量化通过显微神经造影测量的肌肉交感神经活动 (MSNA)；内皮细胞 功能障碍，用内皮脉搏振幅张力计测量；血管电导，通过测量 静脉阻塞体积描记法；以及经历 VMS 的绝经后女性的压力感受反射敏感性。 我们假设患有 VMS 的女性会表现出 MSNA 升高、血管电导降低以及 与没有 VMS 的女性相比，内皮功能受损，导致血压升高。目标2将探索 由温度控制的水循环加热垫引起的潮热改变的程度 绝经后女性的自主神经功能。我们假设潮热会导致 MSNA 增加， 导致更年期女性血压慢性自主神经失调。通过识别之间的联系 VMS 和 CVD，我们将为新疗法的开发和现有疗法的优化奠定基础 VMS 的目标是减少交感神经活动并恢复自主神经和血管功能，以减轻 女性的 CVD 风险，尤其是经历过 VMS 的女性。