Posttraumatic Stress and Cardiovascular Risk in Women: Tests of Biological Mechanisms

 描述(申请人提供)：K01职业发展奖将为詹妮弗·萨姆纳博士提供必要的技能，以建立独立的研究生涯，专注于阐明创伤经历导致女性心血管疾病(CVD)的心理和生物机制，心血管疾病是全球主要的死亡原因。创伤后应激障碍(PTSD)是典型的应激相关精神障碍，它预示着心血管疾病发病率的增加。然而，创伤后应激障碍是一种复杂的异质性疾病，其驱动心血管疾病风险的方面尚不清楚。机械性知识，特别是妇女方面的知识也很缺乏。这些限制阻碍了临床应用的发展，以抵消心血管疾病的风险。这份K01提案的总体目标是 开始测试一个以理论为基础的生物学模型，通过该模型，创伤后应激障碍的核心要素--创伤后恐惧反应(例如，高度警惕、重新体验)--与心血管疾病和女性心血管健康的中间标志有关。在一个由专家导师组成的多学科团队的支持下，萨姆纳博士将研究创伤后恐惧反应(通过自我报告和心理生理分析水平进行衡量)与女性心血管健康之间的关系。培训计划将为萨姆纳博士提供几个领域所需的背景和技能，以便成为一名独立调查员，并对创伤的心理后遗症导致女性心血管疾病的机制进行综合研究。通过课程、实践培训和辅导会议，Sumner博士将解决以前培训中的差距，并在1)心血管、神经和临床流行病学、2)流行病学和纵向数据分析的量化方法、3)与心血管疾病相关的生理学和生物标记物以及4)恐惧反应的心理生理学测量方面发展技能。培训计划还包括完成哥伦比亚大学以患者为中心的研究的理学硕士学位。拟议的研究计划利用两项正在进行的具有丰富特征的队列研究，以测试创伤后恐惧反应与女性心血管风险的关系。萨姆纳博士将利用护士健康研究II(NHS II)的数据，确定自我报告的创伤后恐惧症状是否与高血压和心血管疾病的发病率以及与心血管疾病相关的生物标志物有关。NHS II是一项关于女性健康的纵向流行病学研究。在纽约长老会医院的急性护理和住院反应(REACH)研究中，Sumner博士将收集数据，以测试在多个分析水平上的恐惧反应--自我报告症状和心理生理指标(即皮肤电导率和心率)--与住院和心脏事件复发之间的关系。这项研究是关于急性冠状动脉综合征后PTSD的风险及其与心脏事件复发的关系。这些研究和培训活动将为R01应用程序提供信息，该应用程序将全面测试创伤后恐惧症状在多个层次的分析中对女性心血管疾病的影响的生物学机制。

 DESCRIPTION (provided by applicant): This K01 Career Development Award will provide Dr. Jennifer Sumner with the necessary skills to establish an independent research career focused on elucidating the psychological and biological mechanisms by which traumatic experiences contribute to cardiovascular disease (CVD) in women, the leading cause of death worldwide. Posttraumatic stress disorder (PTSD), the quintessential stress-related mental disorder, prospectively predicts increased CVD incidence. However, PTSD is a complex and heterogeneous disorder, and the aspects of PTSD that drive CVD risk are unknown. Mechanistic knowledge, particularly in women, is also lacking. These limitations impede the development of clinical applications to offset CVD risk. The overall aim of this K01 proposal is to begin to test a theoretically based biological model by which a core element of PTSD-posttraumatic fear responses (e.g., hypervigilance, re-experiencing)- relates to CVD and intermediate markers of cardiovascular health in women. Supported by a multidisciplinary team of expert mentors, Dr. Sumner will examine how posttraumatic fear responses (measured across self- report and psychophysiological levels of analysis) relate to cardiovascular health in women. The training plan will provide Dr. Sumner with required background and skills in several domains in order to become an independent investigator with an integrative research program on the mechanisms by which the psychological sequelae of trauma contribute to CVD in women. Through coursework, hands-on training, and mentored meetings, Dr. Sumner will address prior gaps in training and develop skills in 1) cardiovascular, neurological, and clinical epidemiology, 2) quantitative methods for analyzing epidemiologic and longitudinal data, 3) CVD- related physiology and biomarkers, and 4) psychophysiological measures of fear responses. The training plan also includes completion of a Master's of Science degree in Patient-Oriented Research from Columbia University. The proposed research program harnesses two richly characterized ongoing cohort studies to test how posttraumatic fear responses relate to cardiovascular risk in women. Using data from the Nurses' Health Study II (NHS II), a longitudinal epidemiologic study of women's health, Dr. Sumner will determine if self- reported posttraumatic fear symptoms relate to hypertension and CVD incidence and CVD-related biomarkers. In the REactions to Acute Care and Hospitalization (REACH) study, a study of risk for PTSD after acute coronary syndrome and its relation to recurrent cardiac events at New York-Presbyterian Hospital, Dr. Sumner will collect data to test associations between fear responses at multiple levels of analysis-self-report symptoms and psychophysiological indicators (i.e., skin conductance and heart rate)-with hospital readmission and cardiac event recurrence. These research and training activities will inform an R01 application that will comprehensively test the biological mechanisms by which posttraumatic fear symptoms across multiple levels of analysis contribute to CVD in women.