Mechanisms linking hot flashes to cardiovascular risk

潮热与心血管风险的关联机制

• 批准号: 8512775
• 负责人: REBECCA C THURSTON
• 金额: $ 61.69万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8512775
• 关键词: Accounting; Acute; Address; Affect; Age; Algorithms; Ambulatory Electrocardiography; Atherosclerosis; Attention; Behavioral; Benign; Blood Pressure; Blood specimen; Body mass index; Cardiac; Cardiovascular Diseases; Cardiovascular system; Carotid Arteries; Cause of Death; Cessation of life; Coagulation Process; Development; Diabetes Mellitus; Estradiol; Estrogens; Event; Frequencies; Functional disorder; Health; Heart; Heart Diseases; Hemostatic Agents; Hormones; Hot flushes; Hour; Hypertension; Inflammation; Inflammatory; Investigation; Linear Regressions; Link; Lipids; Measurement; Measures; Mediating; Menopausal Symptom; Menopause; Modeling; Monitor; Obesity; Participant; Pathway interactions; Patient Self-Report; Perimenopause; Pharmaceutical Preparations; Physiological; Physiology; Postmenopause; Process; Progestins; Quality of life; Relative (related person); Reliance; Reporting; Research; Research Design; Research Personnel; Risk; Risk Factors; Sampling; Smoking; Symptoms; Testing; Text; Thick; Ultrasonography; Vasomotor; Woman; Women' s Health; Work; aged; brachial artery; calcification; cardiovascular disorder risk; cardiovascular risk factor; design; diaries; experience; heart rate variability; improved; indexing; intima media; men; middle age; mortality; non-smoker; novel; novel marker; older women; reproductive; reproductive hormone

DESCRIPTION (provided by applicant): Two major health issues facing women as they age are cardiovascular disease (CVD) and menopausal hot flashes. CVD is the leading cause of death among women. Hot flashes are experienced by many midlife women, and for 30% of women, they are frequent or severe. Although hot flashes are traditionally regarded as a benign midlife symptom, recent research has linked a high burden of hot flashes to CVD risk. Several large trials have indicated that the greatest risk of cardiovascular events with hormone use appears concentrated among women reporting moderate to severe hot flashes. Our research shows elevated subclinical CVD among women reporting frequent hot flashes. Important mechanisms linking a high burden of hot flashes to CVD risk may be changes in endothelial function, inflammation/coagulation and cardiac vagal control. However, findings linking hot flashes to cardiovascular risk are just emerging. None of these studies was designed to examine associations between hot flashes and cardiovascular risk. Most have notable limitations, including the reliance upon crude, self-report measures of hot flashes vulnerable to multiple biases. The aim of this investigation is to examine whether women with daily hot flashes have adverse indicators of cardiovascular risk, including poorer endothelial function, higher carotid intima media thickness, lower cardiac vagal control, and an adverse inflammatory and hemostatic profile, relative to women without hot flashes. It is hypothesized that these differences will be independent of traditional CVD risk factors. Secondary aims include testing acute changes in cardiac vagal control during hot flashes and examining key pathways involved in these associations. The proposed sample includes 300 perimenopausal and postmenopausal women aged 40-60, half with daily hot flashes and half without hot flashes. Participants will be nonsmokers, free of heart disease and treated diabetes or hypertension, and free of medications impacting hot flashes. All women will undergo 3 days of physiologic hot flash monitoring, 24 hours of which will include ambulatory electrocardiography for measurement of cardiac vagal control (high frequency heart rate variability), a brachial artery ultrasound for measurement of endothelial function (flow mediated dilation), a carotid artery ultrasound for measurement of intima media thickness, and a blood sample for assessment of inflammatory/hemostatic markers and estradiol concentrations. Relations between hot flashes and cardiovascular risk indicators will be examined using linear regression and linear mixed models. This study represents the first study specifically designed to examine relations between hot flashes and CVD risk, and is an important first step in better understanding links between hot flashes and CVD risk. Addressing these aims may inform a better understanding of the physiology of hot flashes and support the development of a novel marker of cardiovascular risk among midlife women. This work has the potential to challenge the way that this presumably benign menopausal symptom is understood by researchers, clinicians, and women.

描述（由申请人提供）：随着年龄的增长，女性面临的两个主要健康问题是心血管疾病（CVD）和更年期潮热。 CVD 是女性死亡的主要原因。许多中年女性都会经历潮热，其中 30% 的女性潮热频繁或严重。尽管潮热传统上被认为是一种良性的中年症状，但最近的研究将潮热的高负担与心血管疾病风险联系起来。几项大型试验表明，使用激素引起心血管事件的最大风险似乎集中在患有中度至重度潮热的女性中。我们的研究表明，经常出现潮热的女性的亚临床心血管疾病发病率较高。将潮热高负担与 CVD 风险联系起来的重要机制可能是内皮功能、炎症/凝血和心脏迷走神经控制的变化。然而，将潮热与心血管风险联系起来的研究结果才刚刚出现。这些研究都不是旨在检查潮热与心血管风险之间的关联。大多数方法都有明显的局限性，包括依赖于粗略的、自我报告的潮热测量方法，容易受到多种偏见的影响。这项调查的目的是检查每天潮热的女性是否具有心血管风险的不良指标，包括与没有潮热的女性相比，内皮功能较差、颈动脉内膜中层厚度较高、心脏迷走神经控制较低以及不良的炎症和止血特征。据推测，这些差异将独立于传统的 CVD 危险因素。次要目标包括测试潮热期间心脏迷走神经控制的急性变化，并检查参与这些关联的关键通路。拟议的样本包括 300 名 40-60 岁的围绝经期和绝经后女性，其中一半每天有潮热症状，一半没有潮热症状。参与者必须是不吸烟者、没有心脏病、没有接受过治疗的糖尿病或高血压，并且没有服用影响潮热的药物。所有女性都将接受 3 天的生理潮热监测，其中 24 小时包括用于测量心脏迷走神经控制（高频心率变异性）的动态心电图、用于测量内皮功能（血流介导的扩张）的肱动脉超声检查、用于测量内膜中层厚度的颈动脉超声检查以及用于评估炎症/止血标志物和炎症/止血标志物的血液样本。 雌二醇浓度。将使用线性回归和线性混合模型检查潮热和心血管风险指标之间的关系。这项研究是第一项专门旨在检查潮热与 CVD 风险之间关系的研究，也是更好地了解潮热与 CVD 风险之间联系的重要的第一步。解决这些目标可能有助于更好地了解潮热的生理学，并支持开发中年女性心血管风险的新标志物。这项工作有可能挑战研究人员、临床医生和女性对这种可能是良性的更年期症状的理解方式。