Physical Activity to Improve CV Health in Older Women: A Pragmatic Trial

这是妇女健康倡议（WHI）强与健康（WHISH）的竞争性续期申请 审判美国65岁及以上的人口预计将从今天的4900万增加到2010年的9500万， 2060年，女性人数远远超过男性，特别是85岁及以上的成年人。令人信服的证据 支持体力活动（PA）减少心血管（CV）疾病（CVD）， 身体功能（PF），并促进老年人CV健康的其他方面。WHISH是一个里程碑， 实用的随机对照试验测试是否集中，公共卫生干预， 增加和/或维持PA水平并减少久坐行为将减少主要CVD（MI、中风、CV 死亡，在老年妇女。使用随机同意设计来模拟真实世界的程序 在WHI扩展研究中，WHISH将49，333名符合条件的参与者随机分配到一个行为 2015年5月干预与常规随访。干预组的被动同意过程 （n= 24 663）导致<4%的妇女“选择退出”接受干预材料。WHISH提供一个 根据2008年和2018年DHHS PA指南，有针对性的，适应性的，指导性干预，旨在 补充国家老龄化研究所（NIA）的Go 4Life ®运动，使用季节性通讯，手册， 计步器、阻力带、电话和电子邮件激励信息，以及为老年人设计的网站。 妇女干预措施根据年度调查的参与者反馈和其他活动投入进行调整 根据他们当前的PF和PA水平进行定制和定位。主要有效性和安全性 在整个随机队列中使用意向治疗评价结局（CVD、骨折）。年底前 在当前的资助期（2020年2月），将提供4年的随访。根据WHISH观察到的CVD 事件发生率，对PA和久坐行为的干预效果，以及与PA行为相关的新WHI数据， 对于CVD终点，修订的把握度计算表明，我们只有65%的把握度来评估 WHISH干预CVD事件。我们估计，额外4年的随访（总共8年）将产生 85-89%的把握度提供主要WHISH假设的确定性检验。本申请建议 将WHISH干预和随访结果延长4年，以便试验能够达到 关于PA干预的获益和风险的明确结论。我们还建议利用数据， 在计划的WHI扩展研究家庭访视中采集生物标本，以评价 健康的心血管疾病老化，包括身体表现，睡眠时间和失眠症状，以及抑郁 症状将进行试点研究，以探索WHISH干预对以下变化的长期影响： 已知或假定受PA水平影响并指示各种 与CVD老化相关的潜在机制。WHISH的结果，无论是积极的，无效的，还是不利的， 可能对PA传播计划的未来产生巨大的转化影响，以促进健康的CV老化。

This is a competitive renewal application for the Women’s Health Initiative (WHI) Strong & Healthy (WHISH) trial. America’s 65-and-older population is projected to double in size from 49 million today to 95 million by 2060, with women far outnumbering men, particularly among adults aged 85-and-older. Compelling evidence supports the hypothesis that physical activity (PA) reduces cardiovascular (CV) disease (CVD), preserves physical function (PF) and promotes other aspects of CV health in older adults. WHISH is a landmark, pragmatic randomized controlled trial testing whether a centralized, public health intervention designed to increase and/or maintain PA levels and reduce sedentary behavior will reduce major CVD (MI, stroke, CV death) in older women. Using a randomized consent design to simulate real-world programmatic implementation, WHISH randomized 49,333 eligible participants in the WHI Extension Study to a behavioral intervention versus usual follow-up in May 2015. A passive consent process in the Intervention group (n=24,663) resulted in <4% of women “opting out” of receiving intervention materials. WHISH delivers a targeted, adaptive, instructional intervention, based on 2008 and 2018 DHHS PA guidelines and designed to complement the National Institute on Aging’s (NIA) Go4Life® campaign, using seasonal newsletters, manuals, pedometers, resistance bands, telephone and e-mail motivational messages, and a website designed for older women. The intervention adapts to participant feedback from annual surveys and other input regarding activity preferences and is customized and targeted to their current PF and PA levels. Primary effectiveness and safety outcomes (CVD, fracture) are evaluated using intention-to-treat in the entire randomized cohort. By the end of the current grant period (Feb. 2020), 4 years of follow-up will be available. Based on WHISH observed CVD event rates, intervention effects on PA and sedentary behavior, and new WHI data relating PA behaviors to CVD endpoints, revised power calculations suggest we will have only 65% power to evaluate the impact of the WHISH intervention on CVD events. We estimate that 4 additional years of follow-up (8 years overall) will yield 85-89% power to provide a definitive test of the primary WHISH hypothesis. This application proposes to extend the WHISH intervention and follow-up of outcomes for 4 additional years so that the trial can reach a definitive conclusion on the benefits and risks of the PA intervention. We also propose to leverage data and biospecimen collections in a planned WHI Extension Study home visit to enable evaluation of key markers of healthy CVD aging including physical performance, sleep duration and insomnia symptoms, and depressive symptoms. Pilot studies will be executed to explore long-term effects of the WHISH intervention on changes in established and novel biomarkers known or postulated to be influenced by PA levels and indicative of various underlying mechanisms related to CVD aging. The outcomes of WHISH, whether positive, null, or adverse, could have immense translational impact on the future of PA dissemination programs for healthy CV aging.