Identifying Early Intervention Targets for Reducing Cardiovascular Risk in Posttraumatic Stress

确定降低创伤后应激中心血管风险的早期干预目标

基本信息

批准号：
10453467
负责人：
Jennifer A Sumner
金额：
$ 74.14万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10453467
关键词：
Adult Atherosclerosis Attention Autonomic nervous system Biological Cardiotoxicity Cardiovascular Diseases Cardiovascular Physiology Cause of Death Communities Complex Diagnosis Dimensions Disease Surveillance Early Intervention Emotions Endothelial Cells Endothelium Event Exposure to Extinction (Psychology)Fright Functional disorder Future Galvanic Skin Response Goals Health Impairment Individual Inflammation Intervention Interview Knowledge Link Measurement Measures Mediating Mental disorders Modeling Numbness Oxidative Stress Participant Pathologic Police officer Population Post-Traumatic Stress Disorders Psychophysiology Public Health Recording of previous events Risk Risk Factors Role Sampling Stimulus Stress Symptoms Testing Trauma United States Vasodilation Veterans Woman Work associated symptom attentional bias base cardiovascular disorder risk cardiovascular risk factor cell injury conditioned fear conditioning dysphoria endothelial dysfunction experience follow-up male men mortality population based post-traumatic stress prospective response stress related disorder trauma exposure traumatic event treatment trial

项目摘要

PROJECT SUMMARY Posttraumatic stress disorder (PTSD) increases risk of incident cardiovascular disease (CVD) by 25-50%. Most individuals (50-90%) experience a traumatic event in their lifetime, and PTSD is the fifth most common psychiatric disorder. Experts have now called for increased CVD surveillance after trauma and for PTSD treatment trials powered to reduce CVD risk. However, both CVD risk and PTSD are complex phenomena that likely interact in nuanced ways. Therefore, for such efforts to be successful, we must first identify the mechanisms by which PTSD influences incident CVD risk. Further, we must understand which of the dimensions underlying PTSD activate those CVD risk mechanisms. This study will determine which PTSD dimension(s) contribute to endothelial dysfunction, one of the earliest modifiable precursors to CVD. Only three studies in select trauma-exposed populations (male veterans and police officers) have tested the association of PTSD symptoms with flow-mediated dilation (FMD), a functional measure of endothelial dysfunction. This early work points to endothelial dysfunction as a potential mechanism of the PTSD-CVD link, but the limited generalizability and lack of nuanced measurement of both posttraumatic stress and endothelial dysfunction in those studies has limited their impact. Indeed, we still do not know whether PTSD and endothelial dysfunction are associated in individuals from the broader community. Knowledge of which aspects of PTSD are most “cardiotoxic” is also lacking, so we do not know which posttraumatic stress dimensions to target. Fear responses are a core component of PTSD with direct biological relevance to cardiovascular function, whereas the dysphoria dimension of PTSD is considered more auxiliary. In this study, we will examine cross-sectional and longitudinal associations of PTSD and its underlying dimensions with functional and, secondarily, cellular measures of endothelial dysfunction (FMD and circulating endothelial cell-derived microparticles, respectively) in a community-dwelling sample of CVD-free adult men and women with a history of trauma (50% with current PTSD). In Primary Aim 1, we will test the association of PTSD diagnosis with endothelial dysfunction. In Primary Aim 2, we will examine which PTSD dimensions (objective measures of fear and dysphoria, as well as interview-assessed lower-order symptom dimensions) are most strongly associated with endothelial dysfunction. In a Secondary Aim, we will examine how these PTSD dimensions predict change in endothelial dysfunction over 2 years in a subset of the sample. Finally, we will explore the role of stress-related biological mechanisms, including autonomic imbalance, inflammation, and oxidative stress, in the associations of PTSD dimensions with endothelial dysfunction. This study will provide the strongest evidence to date for a biologically plausible mechanistic model of PTSD’s influence on incident CVD risk. If our hypotheses are supported, future interventions will be optimized to reduce posttraumatic fear or another PTSD dimension so as to reduce early endothelial damage and offset CVD risk, making CVD surveillance and intervention after trauma worthwhile.

项目概要创伤后应激障碍 (PTSD) 会使心血管疾病 (CVD) 的风险增加 25-50%。个体（50-90%）在一生中经历过创伤性事件，PTSD 是第五大最常见的事件专家们现在呼吁加强对创伤后心血管疾病和创伤后应激障碍（PTSD）的监测。治疗试验有助于降低 CVD 风险然而，CVD 风险和 PTSD 都是复杂的现象。因此，为了使这些努力取得成功，我们必须首先确定此外，我们必须了解 PTSD 影响 CVD 风险的机制。 PTSD 的潜在维度会激活那些 CVD 风险机制。这项研究将确定哪些 PTSD 会被激活。维度导致内皮功能障碍，这是 CVD 最早可改变的前兆之一。对特定遭受创伤的人群（男性退伍军人和警察）的研究测试了 PTSD 症状伴有血流介导的扩张（FMD），这是一种早期内皮功能障碍的功能测量。工作指出内皮功能障碍是 PTSD-CVD 联系的潜在机制，但有限的创伤后应激和内皮功能障碍的普遍性和缺乏细致入微的测量事实上，这些研究的影响有限，我们仍然不知道 PTSD 是否与内皮功能障碍有关。与来自更广泛社区的个体有关 PTSD 的哪些方面最重要的知识。也缺乏“心脏毒性”，因此我们不知道要针对哪些创伤后压力维度。反应是 PTSD 的核心组成部分，与心血管功能有直接的生物学相关性，而 PTSD 的烦躁维度被认为更具辅助性。在本研究中，我们将检查横截面。 PTSD 及其潜在维度与功能以及其次是细胞的纵向关联内皮功能障碍的测量（分别为 FMD 和循环内皮细胞衍生微粒）在社区居住样本中，有外伤史的无 CVD 成年男性和女性（50% 目前患有在主要目标 1 中，我们将测试 PTSD 诊断与内皮功能障碍的关联。主要目标 2，我们将研究 PTSD 的哪些维度（恐惧和烦躁的客观测量，以及访谈评估的低阶症状维度）与内皮细胞最密切相关在次要目标中，我们将研究这些 PTSD 维度如何预测内皮细胞的变化。最后，我们将探讨与压力相关的生物功能的作用。与 PTSD 相关的机制，包括自主神经失衡、炎症和氧化应激这项研究将为生物学上的证据提供迄今为止最有力的证据。如果我们的假设得到支持，那么 PTSD 对 CVD 风险影响的合理机制模型。将优化干预措施，以减少创伤后恐惧或其他 PTSD 维度，从而减少早期内皮损伤并抵消 CVD 风险，使得创伤后 CVD 监测和干预变得有价值。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Stressful life events and accelerated biological aging over time in youths.

DOI：
10.1016/j.psyneuen.2023.106058
发表时间：
2023-05
期刊：
PSYCHONEUROENDOCRINOLOGY
影响因子：
3.7
作者：
Sumner, Jennifer A.;Gao, Xu;Gambazza, Simone;Dye, Christian K.;Colich, Natalie L.;Baccarelli, Andrea A.;Uddin, Monica;McLaughlin, Katie A.
通讯作者：
McLaughlin, Katie A.

Posttraumatic stress disorder (PTSD), sleep, and cardiovascular disease risk: A mechanism-focused narrative review.

DOI：
10.1037/hea0001143
发表时间：
2022-10
期刊：
HEALTH PSYCHOLOGY
影响因子：
4.2
作者：
Meinhausen, Corinne;Prather, Aric A.;Sumner, Jennifer A.
通讯作者：
Sumner, Jennifer A.

Understanding trajectories of underlying dimensions of posttraumatic psychopathology.

DOI：
10.1016/j.jad.2021.01.086
发表时间：
2021-04-01
期刊：
Journal of affective disorders
影响因子：
6.6
作者：
Sumner JA;Rünger D;Robles TF;Lowe SR;Elashoff D;Shetty V
通讯作者：
Shetty V

Key dimensions of post-traumatic stress disorder and endothelial dysfunction: a protocol for a mechanism-focused cohort study.

DOI：
10.1136/bmjopen-2020-043060
发表时间：
2021-05-05
期刊：
BMJ open
影响因子：
2.9
作者：
Cleveland S;Reed K;Thomas JL;Ajijola OA;Ebrahimi R;Hsiai T;Lazarov A;Montoya AK;Neria Y;Shimbo D;Wolitzky-Taylor K;Sumner JA
通讯作者：
Sumner JA

Psychological and biological mechanisms linking trauma with cardiovascular disease risk.