Association of Physical Activity and Sedentary Behavior with Incident Cardiovascular Disease Event Risk and All-Cause Mortality: Role of Heart Rate Variability and Influence of Diabetes Status

项目概述：久坐行为(SB)是一个新兴的公共卫生问题。最近的研究表明 SB与心血管疾病(CVD)存在正向、剂量依赖关系，与身体无关 活动量(PA)。虽然PA与CVD有明显的相反的、剂量依赖的关系，但大多数美国成年人不会 PA推荐，其中三分之一完全久坐不动。因此，最新的巴勒斯坦权力机构建议注意到 除了增加PA外，还需要减少SB。然而，SB的建议仍然不具体。发展，发展 具体的SB建议(例如，SB的最大小时数/天)，深入研究PA链接的生理机制 而SB对CVD是至关重要的。虽然我们知道PA对降低2型糖尿病患者的心血管疾病风险至关重要 (T2D)，SB如何导致这一人群的心血管疾病风险是一个著名的研究空白。PA和Sb对环境的影响 血糖控制已经得到了充分的研究。一种相对未被研究的机制可能将PA和SB与CVD联系起来 这些行为对血糖控制的影响可能如何影响心脏自主神经功能和 后来发生心血管疾病的风险。心率变异性(HRV)是CAF的黄金标准，可通过以下方式测量 临床医生快速和非侵入性地，HRV受损可预测不利的CVD结局和全原因 死亡率。在那些患有T2D的人中，高血糖对副交感神经系统的损害尤其严重，因为 以刺激更高级的炎症分子循环。更高的炎症分子循环与 与心率变异性受损有关，并假设T2D患者有更高的心血管风险。重要的是，拥有 与不太活跃的个体相比，PA水平较高的个体具有更好的HRV指数(即改善的CAF)。因此，心率变异性可能 是将PA和SB与CVD联系起来的重要生理机制。由于PA和SB具有重要的独立性 对于血糖控制的影响，我们需要研究PA和SB如何影响患有和 在检查HRV是否可能是一个重要的因果中介时，不使用T2D。目前还没有已知的研究评估 这条重要的道路。通过汇集来自六项前瞻性队列研究(N=44,034)的个人水平数据，我们将 提出三个新的具体目标。对于目标1，我们将检查PA和PA之间的独立关联 有心血管疾病风险的人。在目标2中，我们将调查T2D状态如何修改相互之间的独立关联 有心血管疾病风险的PA和SB。这些目标将独特地促进关于影响的小型文献基础 在心血管疾病风险方面，特别是在患有T2D的人。最后，对于目标3，我们将研究心率变异性是否部分地调节 在患有和不伴有T2D的患者中，PA和SB与心血管疾病风险的关系。AIM 3解决来自 主要科学组织研究将PA和SB与心血管疾病联系起来的新机制。我们亦会评估 以全死因死亡率为结局的前向目标(探索性目标)。洞察HRV对这些问题的调解 关联性很重要，因为：(1)HRV作为无创性CAF指标，可以纳入常规的T2D护理； (2)观察结果将为PA的促进和SB的减少提供进一步的机械支持，以预防CVD 在普通人群中，特别是那些患有T2D的人中。

PROJECT SUMMARY: Sedentary behavior (SB) is an emerging public health concern. Recent studies indicate SB to have a positive, dose-dependent relationship with cardiovascular disease (CVD), independent of physical activity (PA). While PA has a clear inverse, dose-dependent relationship with CVD, most U.S. adults do not meet PA recommendations, with one-third completely sedentary. The newest PA recommendations therefore note the need to reduce SB in addition to increasing PA. Yet, SB recommendations remain non-specific. To develop specific SB recommendations (e.g., max hrs/d of SB), in-depth studies of physiological mechanisms linking PA and SB to CVD are crucial. While we know PA is critical to lowering CVD risk in persons with type 2 diabetes (T2D), how SB contributes to this population’s CVD risk is a noted research gap. The influence of PA and SB on glycemic control is well-researched. One relatively unstudied mechanism possibly connecting PA and SB to CVD is how the influence of these behaviors on glycemic control may impact cardiac autonomic function (CAF) and later CVD risk. Heart rate variability (HRV) is a ‘gold standard’ measure of CAF that can be measured by clinicians quickly and non-invasively, with impaired HRV predictive of adverse CVD outcomes and all-cause mortality. In those with T2D, hyperglycemia is particularly damaging to the parasympathetic nervous system due to the stimulation of higher inflammatory molecule circulation. Higher inflammatory molecule circulation is related to impaired HRV and hypothesized to promote higher CVD risk in those with T2D. Importantly, individuals with higher PA levels have better HRV indices (i.e., improved CAF) relative to less active individuals. Thus, HRV may be a salient physiological mechanism linking PA and SB to CVD. As PA and SB have important independent influences on glycemic control, we need to investigate how PA and SB may impact CVD risk in those with and without T2D while examining whether HRV may be an important causal mediator. No known study has assessed this important pathway. By pooling individual-level data from six prospective cohort studies (N=44,034), we will address three novel specific Aims. For Aim 1, we will examine the independent associations between PA and SB with CVD risk. In Aim 2, we will investigate how T2D status modifies the independent associations between PA and SB with CVD risk. These Aims will uniquely contribute to the small literature base regarding the influence of SB on CVD risk, particularly in those with T2D. Finally, for Aim 3, we will study whether HRV partially mediates the associations between PA and SB with CVD risk in those with and without T2D. Aim 3 addresses calls from major scientific organizations to study novel mechanisms linking PA and SB to CVD. We will also assess the preceding Aims with all-cause mortality as the outcome (Exploratory Aim). Discerning HRV’s mediation of these associations is important as: (1) HRV, as a non-invasive CAF indicator, could be included in routine T2D care; and (2) Observations would lend further mechanistic support for PA promotion and SB reduction to prevent CVD in the general population and, especially, those with T2D.