Sitting Interruption and Whole-body Cardiovascular Health: Linking Physiological Responses to Risk Behaviors

摘要 久坐行为（SB）是生物学上不同的，但研究不足的心血管疾病（CVD）的危险因素。 国家和国际机构推测，总体和剂量反应的证据水平 SB和CVD死亡率之间的关联是中等-强的。这些机构不提供具体的 建议拆分SB，但确实呼吁研究界促进政策 通过建立生物相容性，确定SB替代策略的最佳剂量， 并进行随机临床试验，以测试这些策略的有效性。我们的目标是确定 机制知情，社会生态为基础的SB替代建议，以减轻心血管疾病的风险。 目的1A将确定一种可行的SB替代策略，以预防 不良心血管反应将使用主动脉僵硬度（AS）， 非侵入性测试可以预测未来的CVD。为了实现这一目标，在56个中年（36-55岁） 参与者，我们将在4小时内测量主动脉AS和对以下内容的相关机械反应：（i） SB，每小时1次5分钟步行休息;（ii）SB，每小时1次15分钟站立休息;（iii）SB，每小时2次休息 （交替5分钟步行和15分钟站立）;和（iv）SB，无休息（对照）。这些策略被选中 基于我们小组先前的大量工作，因为它们是可行的，这是其中的一个关键组成部分。 提议如果人们愿意坚持未来的SB，SB减少策略只会降低CVD风险 替代建议。为了提高可行性和长期坚持的可能性，目标1B将 使用社会生态模型评估SB的决定因素。这就认识到行为改变很可能 如果物理和社会文化环境不支持行为改变，则限制。完成 目标1B，将采用归纳-演绎相结合的定性方法。完成目标1A的参与者 将参加6个焦点小组之一（6-8名参与者/小组）。目标2A将测试以下可行性： 通过12周的个体化单臂干预在现实世界中实施该策略（n=40，36-64 年）。来自目标1的机制（目标1A）和定性（目标1B）数据将指导干预设计。 我们将测试以下可行性领域：需求，可接受性，实施，实用性，集成， 有限的功效。最后，目标2B将调查干预措施的哪些组成部分起作用， 组件不工作。所有完成目标2A的参与者将被要求完成问卷调查 与我们的行为模式有关，并参加焦点小组。焦点小组将被用来增加 定量可行性数据的背景。具体来说，我们将解决可接受性，采用，适当性， 可持续性，以及感知的社会生态决定因素。重要的是，这项提案的结果将 有助于促进后续临床试验的设计，以测试一种知情但可行的机制 减少SB的干预措施，并在这样做时直接支持SB政策的制定。

ABSTRACT Sedentary behaviors (SB) are biologically distinct but understudied cardiovascular disease (CVD) risk factors. National and international agencies have surmised that the level of evidence for an overall and dose-response association between SB and CVD mortality is moderate-strong. These agencies do not provide specific recommendations for breaking-up SB, though do call on the research community to facilitate policy development by establishing biological plausibility, identifying the optimal dose for SB substitution strategies, and conducting randomized clinical trials to test the efficacy of these strategies. Our goal is to identify mechanism-informed, socioecological-based SB substitution recommendations to mitigate CVD risk. Aim 1A will identify a feasible SB substitution strategy to prevent the adverse cardiovascular responses to prolonged SB. Adverse cardiovascular responses will be measured using aortic arterial stiffness (AS), a noninvasive test that predicts future CVD. To accomplish this aim, in 56 middle-aged (36-55 years) participants, we will measure aortic AS and associated mechanistic responses to the following over 4 hours: (i) SB with once/hour 5 min walk break; (ii) SB with once/hour 15 min stand break; (iii) SB with twice/hour breaks (alternating 5 min walk and 15 min stand); and (iv) SB with no breaks (control). These strategies were selected based on extensive prior work by our group, and because they are feasible, which is a key component of this proposal. SB reduction strategies will only decrease CVD risk if people are willing to adhere to future SB substitution recommendations. To increase the likelihood of feasibility and long-term adherence, Aim 1B will evaluate the determinants of SB using a socioecological model. This recognizes that behavior change is likely to be limited if the physical and sociocultural environments do not support the behavior change. To accomplish Aim 1B, a combined inductive-deductive qualitative approach will be used. Participants who complete Aim 1A will be participate in one of 6 focus groups (6-8 participants/group). Aim 2A will then test the feasibility of implementing the strategy in the real-world via an individualized single-arm 12-week intervention (n=40, 36-64 years). The mechanistic (Aim 1A) and qualitative (Aim 1B) data from Aim 1 will guide the intervention design. We will test the following feasibility domains: demand, acceptability, implementation, practicality, integration, and limited-efficacy. Lastly, Aim 2B will investigate which components of the intervention worked and which components did not work. All participants who complete Aim 2A will be asked to complete questionnaires pertaining to our behavioral model as well as participate in a focus group. The focus groups will be used to add context to the quantitative feasibility data. Specifically, we will address acceptability, adoption, appropriateness, sustainability, and the perceived socioecological determinants. Crucially, the outcomes from this proposal will be instrumental in facilitating the design of a subsequent clinical trial to test a mechanism-informed yet feasible SB reduction intervention, and in doing so directly support the development of SB policy.