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.

项目总结/摘要 衰老是心血管疾病（CVD）的危险因素，经历血管痉挛症状的女性（VMS， 潮热和盗汗）的女性患心血管疾病的风险比没有经历过的女性高55%。 VMS。由于CVD是美国女性死亡的主要原因，因此， 绝经期女性是关键的，但还不清楚。自主神经和血管失调，通常 在绝经后女性中证实，与CVD相关，但这种失调是否存在 特别是女性VMS患者的情况尚不清楚。此外，潮热，一个主要的VMS，如何改变自主功能， 还没有很好的定义。NIH R21的这一应用旨在确定以下机制途径： 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主任，是心血管科的PI。 研究和康复实验室，拟议的研究将在那里进行。远景目标 这项建议的目的是确定绝经期女性VMS和CVD之间的联系。具体来说凯勒医生 Ross旨在确定经历VMS的女性在多大程度上表现出自主神经和血管 失调（目标1）。然后她将描述潮热改变自主调节的机制 (Aim 2）。这一建议符合NIA的使命，即了解老龄化过程的性质， 女性以及与更年期相关的因素如何导致女性死亡的头号原因， CVD。Keller-Ross博士试图进行一项探索性研究，以询问体温调节系统， 通过诱导潮热和研究潮热如何改变自主神经功能。完成 为了实现这些研究目标，Keller-Ross博士和Blas博士（Co-I）将结合使用黄金标准技术 采用创新的方法学方法来量化女性的自主神经和血管失调， VMS。目标1将量化肌肉交感神经活动（MSNA），通过显微神经描记术测量;内皮 功能障碍，用内皮脉冲幅度张力测定法测量;血管传导性，通过 静脉闭塞体积描记法和压力反射敏感性在绝经后女性经历VMS。 我们假设患有VMS的女性将表现出MSNA升高，血管传导减少， 与无VMS的女性相比，内皮功能受损，导致血压升高。Aim 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， 导致绝经期女性血压的慢性自主神经失调。通过识别 VMS和CVD，我们将为开发新疗法和优化当前治疗方法奠定基础 目的是减少交感神经活动，恢复自主神经和血管功能， 女性CVD风险，特别是经历VMS的女性。