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: 10046429
• 负责人: MARK A PEREIRA
• 金额: $ 11.56万
• 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 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10046429
• 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