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

这项名为Swan-Aging的U19应用程序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，提供了关于MT的开创性信息。通过扩大对Swan队列的跟踪，Swan-Aging可以通过将预期评估的MT特征与妇女进入早年时的健康和功能联系起来，填补关键的知识空白。心血管疾病(CVD)是女性死亡的主要原因，也是导致身体损伤、阿尔茨海默病和血管性痴呆的主要危险因素。心血管疾病在女性中有独特的特征，包括MT的作用，人们对此知之甚少。项目2将测试MT如何与老年早期女性的心血管疾病事件和心脏健康有关，并测试心脏健康如何与生命关键时期的身体损害、阿尔茨海默病和血管性痴呆症的早期标记物相关。早期工作表明MT的多个方面对心血管疾病的风险至关重要，但很少有研究从中年到老年进行延长的随访，以测试MT是否与CVD有关。此外，心力衰竭是心血管疾病的一种主要形式，是一种新的流行病。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--心力衰竭伴保留射血功能，目前知之甚少。MT是否与后来的心力衰竭风险有关，以及心功能在残疾、认知能力下降和认知损害风险中所起的作用尚不清楚。在痴呆症的自然病程早期，了解心脏健康作为阿尔茨海默病和血管性痴呆的可补救危险因素的作用是至关重要的。利用Swan-Aging队列、核心和项目的优势，项目2将测试MT与老年早期心血管事件的关系，增加对心脏功能障碍标记物(心功能超声心动图指数，N末端脑利钠肽原系列测量，NTproBNP)及其与身体和认知损害指数的联系的关注。项目2的目标是：1)测试MT是否预测心脏功能障碍、整个MT、心血管事件和死亡率中更高的NTproBNP；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有关，使女性面临残疾和痴呆的风险；3)测试临床前心脏功能障碍的种族/民族差异及其与残疾和认知障碍的早期标志的联系；4)将研究结果翻译给妇女和提供者，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。心血管疾病是女性死亡的主要原因，随着女性年龄的增长，它与功能障碍、阿尔茨海默病和血管性痴呆有关。

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.