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

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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.