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

项目摘要/摘要 衰老是心血管疾病(CVD)的风险因素，而女性出现血管运动症状(VMS， 潮热和盗汗)与没有经历过的女性相比，患心血管疾病的风险高55% VMS。由于心血管疾病是美国女性死亡的主要原因，导致心血管疾病的因素 绝经期女性是确定的关键，但目前尚不清楚。自主神经和血管调节失调，通常 在绝经后女性中表现出来，与心血管疾病有关，但这种失调是否存在 尤其是患有VMS的女性，这一点尚不清楚。此外，主要的VMS热刷新如何改变自主神经功能 还没有得到很好的定义。NIH R21的这一应用旨在识别机械路径，以 确定VMS是如何导致CVD的。曼达·L·凯勒-罗斯博士，系助理教授 明尼苏达大学医学院的康复医学博士，是心血管的PI 研究和康复实验室，拟议的研究将在那里进行。长期目标 这项建议的目的是确定更年期女性VMS和心血管疾病之间的联系。具体来说，凯勒博士- 罗斯的目标是确定经历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神经调节的机制 (目标2)。这项建议符合国家情报局的使命，即了解#年老龄化过程的性质。 以及与更年期相关的因素如何导致女性死亡的头号原因， 心血管疾病。凯勒-罗斯博士试图进行一项探索性研究，以询问 雌性通过诱导潮热和研究潮热如何改变自主神经功能。要完成 这些研究目标，凯勒-罗斯博士和布拉斯博士(Co-I)将使用黄金标准技术相结合 通过一种创新的方法来量化女性患者的自主神经和血管调节障碍 VMS。目标1将量化肌肉交感神经活动(MSNA)，通过显微神经摄影术测量；内皮细胞 功能障碍，用内皮脉冲幅度眼压计测量；血管电导，通过 患有VMS的绝经后女性的静脉闭塞体积描记术和压力反射敏感性。 我们假设患有VMS的女性将表现出MSNA升高，血管传导性降低和 与没有VMS的女性相比，血管内皮功能受损，导致血压升高。《目标2》将探索 由温度控制、水循环的加热垫引起的热冲洗的改变程度 绝经后女性的自主神经功能。我们假设热冲洗会导致MSNA增加， 导致更年期女性血压的慢性自主神经失调。通过确定两者之间的联系 VMS和CVD，我们将为开发新的治疗方法和优化现有治疗方法奠定基础 以减少交感神经活动和恢复自主神经和血管功能为目标的VMS患者 女性的心血管疾病风险，特别是那些经历过VMS的人。

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.