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

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.