Project 2: Menopause, Midlife and Cardiovascular Health in Early Old Age

项目2：更年期、中年和早年心血管健康

• 批准号: 10471457
• 负责人: REBECCA C THURSTON
• 金额: $ 129.63万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10471457
• 关键词: Affect; African American; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Attention; Blood Vessels; Brain natriuretic peptide; Cardiac; Cardiac health; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Characteristics; Chinese; Clinical; Cohort Studies; Dementia; Diabetes Mellitus; EFRAC; Elderly; Epidemic; Equilibrium; Estradiol; Etiology; Event; Failure; Female; Follicle Stimulating Hormone; Follow-Up Studies; Functional disorder; Goals; Gonadal Steroid Hormones; Health; Health Personnel; Heart failure; Hispanic; Hormones; Hospitalization; Hypertension; Impaired cognition; Impairment; Inflammatory; Intervention; Japanese; Knowledge; Life; Life Experience; Link; Longevity; Longitudinal cohort study; Measures; Menopause; Myocardial dysfunction; N-terminal; Natural History; Not Hispanic or Latino; Outcome; Participant; Pattern; Phenotype; Physical Function; Play; Population; Prevention; Provider; Resources; Risk; Risk Factors; Role; Seminal; Structure; Study of Women' s Health Across the Nation; Symptoms; Testing; Thinking; Translating; Vascular Dementia; Vasomotor; Woman; Women' s Health; Work; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular health; cognitive function; cohort; critical period; dementia risk; disability; disability risk; effective therapy; ethnic difference; experience; follow-up; functional disability; healthy aging; heart function; high risk; human old age (65+); improved; indexing; men; middle age; mild cognitive impairment; mortality; multi-ethnic; multi-racial; physically handicapped; poor sleep; pre-clinical; preservation; prevent; prospective; psychosocial; racial and ethnic; risk stratification; socioeconomics

The overall goal of this U19 application, SWAN-Aging, is to determine the impact of midlife health and the menopause transition (MT) on health and function in women in early old age (66-75 years), a pivotal period when declines in cardiac health and physical and mild cognitive impairment begin to accumulate. SWAN-Aging capitalizes on the rich resources of the Study of Women’s Health Across the Nation (SWAN), a multi-ethnic longitudinal cohort study that provided seminal information on the MT. By extending follow up of the SWAN cohort, SWAN-Aging can fill critical knowledge gaps by linking prospectively-assessed features of the MT to health and function as women enter early old age. Cardiovascular disease (CVD) is the leading cause of death and a major risk factor for physical impairment, Alzheimer’s disease, and vascular dementia in women. CVD has unique features in women, including a role of the MT that is poorly understood. Project 2 will test how the MT relates to CVD events and cardiac health in women in early old age and test how cardiac health relates to early markers of physical impairment, Alzheimer’s disease, and vascular dementia risk at a critical period in the lifespan. Early work indicates that multiple aspects of the MT are critical to CVD risk, yet few studies have the extended follow up from midlife to older ages required to test whether the MT relates to CVD. Further, a major form of CVD, heart failure, is an emerging epidemic. It is the leading cause of hospitalization and may increase risk of physical impairment, Alzheimer’s disease, and vascular dementia in women. Its female-predominant phenotype, heart failure with preserved ejection faction, is poorly understood. Whether the MT is linked to later heart failure risk, and the role that cardiac function plays in risk for disability, cognitive decline, and cognitive impairment is not known. Understanding the role of cardiac health as a remediable risk factor for Alzheimer’s disease and vascular dementia early in the natural history of dementia is critical. Leveraging the strengths of the SWAN-Aging cohort, Cores, and Projects, Project 2 will test the relations of the MT to CVD events in early old age, adding a focus on markers of cardiac dysfunction (echocardiographic indices of cardiac function, serial measures of N-terminal pro-brain natriuretic peptide, NTproBNP) and its links to indices of physical and cognitive impairment. Project 2 aims are to: 1) Test whether the MT predicts cardiac dysfunction, higher NTproBNP across the MT, CVD events, and mortality; 2) Test whether cardiac dysfunction and NTproBNP relate to early markers of physical disability and mild cognitive impairment in women, placing women at risk for disability and dementia; 3) Test racial/ethnic differences in preclinical cardiac dysfunction and its links to early markers of disability and cognitive impairment; 4) Translate findings to women and providers to improve CVD, disability, Alzheimer’s disease, and vascular dementia prevention. Findings can inform midlife risk stratification and interventions to reduce CVD, disability, and dementia in women. CVD is the leading cause of death in women and is linked to functional impairment, Alzheimer’s disease, and vascular dementia as women age.

该 U19 应用程序 SWAN-Aging 的总体目标是确定中年健康和更年期过渡 (MT) 对老年早期（66-75 岁）女性健康和功能的影响，这是心脏健康状况下降以及身体和轻度认知障碍开始累积的关键时期。 SWAN-Aging 利用了全国妇女健康研究 (SWAN) 的丰富资源，这是一项多种族纵向队列研究，提供了有关 MT 的开创性信息。通过延长 SWAN 队列的随访，SWAN-Aging 可以将前瞻性评估的 MT 特征与女性进入老年时的健康和功能联系起来，从而填补关键的知识空白。心血管疾病（CVD）是导致女性死亡的主要原因，也是导致女性身体损伤、阿尔茨海默病和血管性痴呆的主要危险因素。 CVD 在女性中具有独特的特征，其中 MT 的作用尚不清楚。项目 2 将测试 MT 如何与早年女性的 CVD 事件和心脏健康相关，并测试心脏健康如何与生命周期关键时期的身体损伤、阿尔茨海默病和血管性痴呆风险的早期标志物相关。早期研究表明，MT 的多个方面对 CVD 风险至关重要，但很少有研究进行从中年到老年的长期随访，以测试 MT 是否与 CVD 相关。此外，心血管疾病的一种主要形式——心力衰竭，是一种新出现的流行病。它是导致住院的主要原因，并可能增加女性身体损伤、阿尔茨海默病和血管性痴呆的风险。其以女性为主的表型，即伴有射血分数保留的心力衰竭，人们对其知之甚少。 MT 是否与后期心力衰竭风险相关，以及心功能在残疾、认知能力下降和认知障碍风险中所起的作用尚不清楚。在痴呆自然史的早期，了解心脏健康作为阿尔茨海默病和血管性痴呆的可治愈危险因素的作用至关重要。利用 SWAN-Aging 队列、核心和项目的优势，项目 2 将测试 MT 与老年早期 CVD 事件的关系，并重点关注心功能障碍标志物（心功能的超声心动图指数、N 端脑钠肽前体 NTproBNP 的系列测量）及其与身体和认知障碍指数的联系。项目 2 的目标是： 1) 测试 MT 是否可以预测心功能障碍、整个 MT 中较高的 NTproBNP、CVD 事件和死亡率； 2) 测试心脏功能障碍和 NTproBNP 是否与女性身体残疾和轻度认知障碍的早期标志物相关，使女性面临残疾和痴呆的风险； 3) 测试临床前心功能障碍的种族/民族差异及其与残疾和认知障碍早期标志的联系； 4) 将研究结果转化为女性和医疗服务提供者，以改善心血管疾病、残疾、阿尔茨海默病和血管性痴呆的预防。研究结果可以为中年风险分层和干预措施提供信息，以减少女性的心血管疾病、残疾和痴呆症。 CVD 是女性死亡的主要原因，并且与女性随着年龄增长而出现的功能障碍、阿尔茨海默病和血管性痴呆有关。