Project Summary Cardiovascular disease (CVD) mortality has declined significantly over the past two decades, but there has been a recent rise in CVD deaths among younger women (ages 35–54), for reasons yet unknown. The prevalence of poor sleep has steadily increased and is more common among women. There is a growing body of compelling evidence linking poor quality and short duration sleep to increased CVD risk. Poor sleep could be a potential cause for the higher incidence of CVD-related deaths among younger women, yet the mechanisms are not known. Women may be particularly vulnerable to the effects of poor sleep on cardiac health, as they face unique sleep challenges at different life stages, including inadequate sleep in the childbearing and/or postpartum periods, and sleep disturbances due to hormonal changes during the menopausal transition and post- menopause. Women may also differentially experience psychosocial risk factors such as depression and increased strain due to caregiving responsibilities, which have been linked to poor sleep and increased CVD risk. Our preliminary data shows that short sleep duration and poor quality sleep are associated with CVD risk factors among women, including obesity, blood pressure, and inflammation. A majority of women now report irregular sleep, a high day-to-day variability in sleep duration and timing, as their habitual sleep pattern. Whereas the association between short and long sleep duration and obesity, hypertension, and CVD has long been recognized, irregular sleep has been mostly overlooked as a possible contributor to CVD. Sleep timing and variability has also been disproportionately understudied in racial/ethnic minorities and women. Capitalizing on our two racially and ethnically diverse cohorts of women that have been well-characterized for sleep patterns, we propose to investigate variability in sleep timing as a potential new risk factor for CVD among women at two planned follow-up time points. We will leverage the ongoing Go Red for Women community-based cohort study of 506 women and the national Research Goes Red weight study cohort of 300 women to conduct analyses of the link between objectively-measured variable sleep timing, a highly modifiable lifestyle behavior, and CVD risk among women (Aim 1); determine if there are differences associated with ethnicity and menopausal status, and if caregiving, stress, and depression may mediate the sleep irregularity-CVD risk association (Aim 1a); and determine whether variable sleep is associated with low brachial artery flow-mediated dilation, a precursor to CVD (Aim 2). Variable sleep timing may be an unrecognized contributor to increased CVD risk among women. Variable sleep timing is a highly prevalent, easily modifiable behavior, that could be targeted in public health campaigns to reduce the risk of CVD. Findings from our proposed data would inform the development of public health guidelines and clinical recommendations addressing sleep sch...