Circadian and behavioral factors of cardiovascular risk

心血管风险的昼夜节律和行为因素

基本信息

批准号：
7114283
负责人：
STEVEN A SHEA
金额：
$ 49.65万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-15 至 2009-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Numerous epidemiological studies have established that there is a disproportionately high frequency of adverse cardiovascular events around 9 AM (e.g., sudden cardiac death, myocardial infarction). The mechanisms have been loosely attributed to behavioral stressors occurring at specific times of day (e.g., change in posture or activity). But, the independent role of the internal body clock (circadian pacemaker) in this day/night pattern has never been studied with appropriate techniques. Our preliminary data show a marked endogenous circadian rhythm in some markers of cardiovascular risk that may be implicated in the day/night pattern of adverse cardiovascular events. Thus, we have two Specific Aims: (1) Determine the effect upon cardiovascular risk markers of the circadian pacemaker (independent from behaviors); (2) Determine the interaction between circadian and behavioral influences upon cardiovascular risk markers (i.e., an interaction by which behavioral stressors have different effects at different circadian phases). To achieve these aims, we will utilize an intensive 12-day "Forced Desynchrony" protocol, wherein subjects' standardized behaviors and sleep occur at all phases of the circadian cycle. As this will be the first formal study in this area, we will begin by studying healthy individuals to define the normal human physiological rhythms and responses that could be implicated in the day/night pattern of cardiovascular risk. During the protocol standardized behavioral stressors include changes in posture (tilt table), activity (bicycle exercise) and sleep/wake state. The measures that can be implicated in triggering adverse cardiovascular events in vulnerable individuals, will include (i) autonomic nervous system activity (catecholamines, sympatho-vagal balance); (ii) hemodynamic factors (heart rate, blood pressure); (iii) Hemostatic factors (platelet aggregability and count); and (iv) vascular endothelial function (flow mediated vasodilatation). Based on preliminary data, we anticipate that behavioral stressors will have different effects at specific phases of the circadian cycle revealing vulnerable times for certain behaviors (likely corresponding to the peak in cardiovascular vulnerability from epidemiological studies). This project may ultimately help us to rationalize chronobiological therapies for cardiovascular diseases in terms of modification of behavior and timed pharmacological intervention.

描述（由申请人提供）：许多流行病学研究表明，在上午9点左右，患不良心血管事件的频率不成比例（例如心脏猝死，心肌梗塞）。这些机制已被松散地归因于在一天中特定时间发生的行为应力源（例如，姿势或活动的变化）。但是，从来没有使用适当的技术研究了这一天/夜间模式中内部时钟（昼夜节奏起搏器）的独立作用。我们的初步数据表明，在心血管风险的某些标志物中，内源性昼夜节律明显，可能与不良心血管事件的白天/夜间模式有关。因此，我们有两个具体的目的：（1）确定对昼夜节奏起搏器心血管风险标记的影响（独立于行为）；（2）确定昼夜节律对心血管风险标志物的影响（即行为应力源在不同昼夜节相的相互作用的相互作用）。为了实现这些目标，我们将利用一个密集的为期12天的“强迫性”方案，其中受试者的标准化行为和睡眠发生在昼夜节律的所有阶段。由于这将是该领域的首次正式研究，因此我们将首先研究健康的个体，以定义正常的人类生理节奏和反应，这可能与心血管风险的白天/夜晚模式有关。在协议期间，标准化行为应力源包括姿势（倾斜表），活动（自行车运动）和睡眠/唤醒状态。可能涉及触发脆弱个体的不良心血管事件的措施将包括（i）自主神经系统活动（儿茶酚胺，交感神经平衡）；（ii）血液动力学因素（心率，血压）；（iii）止血因子（血小板的聚集性和计数）；（iv）血管内皮功能（流动介导的血管扩张）。基于初步数据，我们预计行为压力源在昼夜节律周期的特定阶段会产生不同的影响，这揭示了某些行为的脆弱时间（可能与流行病学研究中心血管脆弱性的峰值相对应）。该项目最终可能会帮助我们在行为修改和定时药理干预方面合理化心血管疾病的时间生物学疗法。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors.

DOI：
10.1371/journal.pone.0024549
发表时间：
2011
期刊：
PloS one
影响因子：
3.7
作者：
Scheer FA;Michelson AD;Frelinger AL 3rd;Evoniuk H;Kelly EE;McCarthy M;Doamekpor LA;Barnard MR;Shea SA
通讯作者：
Shea SA