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）有阳性的剂量依赖性关系，独立于物理 活动（PA）。尽管PA与CVD有明显的逆剂量依赖性关系，但大多数美国成年人都不满足 PA建议，三分之一完全久坐。因此，最新的PA建议注意 除了增加PA外，还需要减少SB。但是，SB建议仍然非特异性。发展 特定的SB建议（例如，SB的最大HRS/D），深入研究与PA的物理机制 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如何为该人群的CVD风险做出贡献是一个著名的研究差距。 PA和SB对 血糖控制经过深入研究。一种相对未研究的机制，可以将PA和SB连接到CVD 这些行为对血糖控制的影响可能会影响心脏自主神经功能（CAF）和 后来CVD风险。心率变异性（HRV）是CAF的“黄金标准”量度，可以通过 临床医生迅速且无创地，HRV可预测不良CVD结果和全因素 死亡。在患有T2D的人中，高血糖尤其损害了副交感神经系统 刺激较高的炎症分子循环。较高的炎性分子循环与 为了损害HRV并被假设以促进T2D患者的更高CVD风险。重要的是，有个人 相对于活跃的个体，较高的PA水平具有更好的HRV指数（即改善CAF）。那是人力资源管理 是将PA和SB与CVD联系起来的显着物理机制。因为PA和SB具有重要的独立 对血糖控制的影响，我们需要调查PA和SB如何影响患有和的患者的CVD风险 在检查HRV是否可能是重要的因果介体时，没有T2D。尚未评估已知的研究 这个重要的途径。通过汇总六项前瞻性队列研究（n = 44,034）的个人级别数据，我们将 解决三个新颖的特定目标。对于AIM 1，我们将研究PA和PA之间的独立关联 具有CVD风险的SB。在AIM 2中，我们将研究T2D状态如何修改独立关联 具有CVD风险的PA和SB。这些目标将为有关影响的小文学基础唯一贡献 CVD风险的SB，特别是在T2D的人中。最后，对于AIM 3，我们将研究HRV是否部分介导 PA和SB之间的关联与具有T2D和没有T2D的人的CVD风险。 AIM 3地址来自 研究将PA和SB与CVD联系起来的新型机制的主要科学组织。我们还将评估 以全因死亡率为结果的目标（探索目的）。辨别HRV对这些的调解 关联很重要，因为：（1）HRV作为非侵入性CAF指标，可以包括在常规T2D护理中； （2）观察将为PA促进和SB降低提供进一步的机械支持，以防止CVD 在一般人群中，尤其是患有T2D的人群中。