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

体力活动和久坐行为与心血管疾病事件风险和全因死亡率的关联：心率变异性的作用和糖尿病状况的影响

• 批准号: 10249175
• 负责人: MARK A PEREIRA
• 金额: $ 11.63万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249175
• 关键词: Address; Adult; Adverse effects; Advocate; Anti-Inflammatory Agents; Atherosclerosis Risk in Communities; Autonomic nervous system; Biological; Blood Circulation; Cardiac; Cardiac health; Cardiovascular Diseases; Caring; Clinical; Cohort Studies; Coronary Artery Risk Development in Young Adults Study; Data; Diabetes Mellitus; Diabetic Neuropathies; Disease Outcome; Dose; Event; General Population; Gold; Government; Hyperglycemia; Impairment; Individual; Inflammatory; Jackson Heart Study; Lead; Link; Literature; Measurement; Measures; Mediating; Mediation; Mediator of activation protein; Metabolic; Microvascular Dysfunction; Modification; Multi-Ethnic Study of Atherosclerosis; National Heart, Lung, and Blood Institute; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Parasympathetic Nervous System; Participant; Pathway interactions; Persons; Physical activity; Physiological; Population; Population Heterogeneity; Production; Prospective cohort; Prospective cohort study; Public Health; Recommendation; Research; Research Design; Risk; Role; Sampling; autonomic neuropathy; base; behavior influence; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular health; cohort; cytokine; design; glucose disposal; glycemic control; heart rate variability; improved; indexing; insulin sensitivity; macrovascular disease; mortality; novel; offspring; population based; prevent; prospective; scientific organization; sedentary; sedentary lifestyle; standard measure

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.

项目摘要：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、剂量依赖性关系，与身体状况无关 活动（PA）。虽然 PA 与 CVD 存在明显的反向、剂量依赖性关系，但大多数美国成年人并不满足 PA 建议，三分之一的人完全久坐。因此，最新的 PA 建议指出 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 具体的 SB 建议（例如，SB 的最大小时数/天）、与 PA 相关的生理机制的深入研究 SB 到 CVD 至关重要。虽然我们知道 PA 对于降低 2 型糖尿病患者的 CVD 风险至关重要 (T2D)，SB 如何导致该人群的 CVD 风险是一个值得注意的研究空白。 PA和SB的影响 血糖控制已得到充分研究。一种相对未经研究的机制可能将 PA 和 SB 与 CVD 连接起来 这些行为对血糖控制的影响如何影响心脏自主功能 (CAF) 以及 以后的 CVD 风险。心率变异性 (HRV) 是 CAF 的“黄金标准”衡量标准，可以通过以下方式测量 临床医生可以快速、无创地利用 HRV 受损来预测不良 CVD 结局和全因 死亡。对于 T2D 患者，高血糖对副交感神经系统的损害尤其严重，因为 刺激更高的炎症分子循环。较高的炎症分子循环有关 HRV 受损，并假设会增加 T2D 患者的 CVD 风险。重要的是，具有以下特征的个人 相对于不太活跃的个体，较高的 PA 水平具有更好的 HRV 指数（即改善的 CAF）。因此，HRV 可能 是连接 PA 和 SB 与 CVD 的显着生理机制。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 如何影响患有以下疾病的患者的 CVD 风险： 没有 T2D，同时检查 HRV 是否可能是一个重要的因果调节因素。没有已知的研究评估过 这条重要途径。通过汇集六项前瞻性队列研究 (N=44,034) 的个人数据，我们将 解决三个新颖的具体目标。对于目标 1，我们将检查 PA 和 有 CVD 风险的 SB。在目标 2 中，我们将研究 T2D 状态如何改变之间的独立关联 PA 和 SB 有 CVD 风险。这些目标将对关于影响力的小型文献基础做出独特的贡献 SB 对 CVD 风险的影响，特别是对于患有 T2D 的患者。最后，对于目标 3，我们将研究 HRV 是否部分介导 PA 和 SB 与患有和不患有 T2D 的人的 CVD 风险之间的关联。目标 3 接听来自 主要科学组织研究将 PA 和 SB 与 CVD 联系起来的新机制。我们还将评估 以全因死亡率为结果的前述目标（探索性目标）。辨别 HRV 对这些的调节 关联性很重要，因为：(1) HRV 作为非侵入性 CAF 指标，可以纳入常规 T2D 护理中； (2) 观察结果将为促进 PA 和减少 SB 以预防 CVD 提供进一步的机制支持 普通人群，尤其是 T2D 患者。