The Effect of Reducing Posttraumatic Stress Disorder Symptoms on Cardiovascular Risk

 描述（由申请人提供）：对于创伤后应激障碍（PTSD）的诊断如何预示冠心病（CHD）的过度风险，存在根本性的理解差距。这主要是因为两个原因：（1）支持PTSD和CHD风险之间相关性的核心研究依赖于长时间的随访，没有重复测量PTSD或其他相关的心血管风险因素;（二）创伤后应激障碍与不良健康行为和精神共病高度共病，这些共病也随时间而变化，可以在很大程度上解释创伤后应激障碍与增加CHD的风险。长期目标是更好地了解PTSD和CHD风险之间是否存在直接联系，以及确定候选病理生理机制的作用。本申请中提出的研究旨在研究在既定的治疗干预（认知加工疗法）后PTSD症状的变化如何影响PTSD患者的CHD疾病途径。该设计将允许评估以下假设：显示PTSD症状显著改善的个体也将显示CHD风险生物标志物的改善，并且未能显示PTSD症状改善或显示PTSD症状恶化的个体将显示CHD生物标志物活性无变化或恶化。该研究还将评估与压力相关的关键CHD生物标志物作为与PTSD相关的CHD风险负担增加的机制的作用。CHD生物标志物的选择集中于PTSD与应激反应系统慢性激活的既定关联，包括自主神经系统失调、慢性全身炎症和血管内皮功能障碍。拟议的研究是重要的，因为它预计将提供的PTSD症状对CHD风险途径的直接影响的作用，以及这些系统的作用作为潜在的PTSD和CHD风险之间的关系的候选机制的知识。通过更好地定义创伤后应激障碍如何成为冠心病的危险因素，以及确定所涉及的疾病途径，拟议的研究将有助于为冠心病预防策略提供信息，并指导创伤后应激障碍弱势男性和女性的最佳医疗管理，特别是那些克制或难以接受精神治疗的人。

 DESCRIPTION (provided by applicant): There is a fundamental gap in the understanding of how a diagnosis of post-traumatic stress disorder (PTSD) portends excess risk of coronary heart disease (CHD). This is primarily because of two reasons: (1) the core studies which provide support for an association between PTSD and CHD risk depended on lengthy follow-up periods with no repeat measurement of either PTSD or other related cardiovascular risk factors; (2) PTSD is highly comorbid with both adverse health behaviors and with psychiatric comorbidity that also vary across time and could largely explain the association between PTSD and increased risk of CHD. The long-term goal is to better understand whether there is a direct link between PTSD and CHD risk, as well as to ascertain the role of candidate pathophysiological mechanisms. The study proposed in this application is designed to examine how changes in PTSD symptoms following an established therapeutic intervention (Cognitive Processing Therapy) affect CHD disease pathways in individuals with PTSD. This design will permit an evaluation of the hypothesis that individuals who show significant improvement in PTSD symptoms will also show improvement in CHD risk biomarkers, and individuals who fail to show improvement or show worsening PTSD symptoms, will show no change or worsening in CHD biomarker activity. The study will also provide an evaluation of the role of key stress-related CHD biomarkers as mechanisms underlying the increased CHD risk burden associated with PTSD. Choice of CHD biomarkers focused on the established association of PTSD with chronic activation of stress response systems and includes autonomic nervous system dysregulation, chronic systemic inflammation, and vascular endothelial dysfunction. The proposed research is significant because it is expected to provide knowledge of the role of both the direct impact of PTSD symptoms on CHD risk pathways and the role of these systems as candidate mechanisms underlying the relationship between PTSD and CHD risk. By better defining how PTSD is a risk factor for CHD, as well as identifying the disease pathways involved, the proposed study will help inform strategies for CHD prevention, as well as guide optimal medical management for vulnerable men and women with PTSD, especially in those who refrain or who are refractory to psychiatric treatment.