Stress Management and Biomarkers of Risk in Cardiac Rehabilitation

描述（由申请人提供）：冠心病（CHD）是美国的主要死亡原因，每年影响100万人。“心血管易感患者”一词用于描述基于斑块、血液或心肌特征易发生急性冠状动脉事件的患者。流行病学研究表明，压力是冠心病患者重要的独立危险因素，也可能与心血管易感性增加有关。这一证据为冠心病患者开展压力管理训练（SMT）干预提供了理论依据。虽然心脏康复（CR）被认为是冠心病患者护理不可或缺的一部分，但SMT目前并不是大多数CR计划的必要组成部分。我们认为，由于缺乏精心设计的冠心病患者临床研究，SMT的治疗潜力仍未实现。由于采用“硬终点”（死亡或心肌梗死）的随机临床试验（rct）需要长时间跟踪大量样本，因此这种方法通常不适用于大多数社会心理随机对照试验。本应用程序是根据项目公告（PA-07-322）开发的，该公告邀请应用程序检查SMT在改善中间结果方面的功效，中间结果由心血管风险的生物标志物定义，据称是精神压力影响临床事件的途径。本申请中提出的研究将建立在我们之前的工作基础上，我们在之前的工作中证明了SMT在稳定型冠心病心血管患者中的可行性和有效性。具体而言，我们建议(a)评估SMT联合基于运动的CR在减轻易感心脏病患者压力方面的有效性；(b)检查中间终点的变化，包括心脏迷走神经控制、血管内皮功能障碍、炎症、血小板功能和精神应激引起的心肌缺血的测量，这些是公认的心脏易受临床冠心病事件影响的生物标志物；(c)探索SMT可能改善风险生物标志物的潜在调节因子和中介因子；(d)在平均30个月的随访期间确定SMT对临床终点的影响。150名患有冠心病的男性和女性将被随机分配到以运动为基础的CR组或smt增强的CR组。在治疗前和治疗后3个月，患者将接受压力和心血管风险生物标志物的临床评估。随访评估将确定获益的维持并记录心脏事件。本研究产生的数据对于确定SMT联合基于运动的CR在多大程度上减轻心脏易危患者的应激和改善预后具有重要的临床意义。公共卫生相关性：冠心病（CHD）在美国和全世界都是一个重要的健康问题，是美国男性和女性死亡的主要原因。本研究将检查压力管理训练计划结合基于运动的心脏康复对冠心病患者风险和无事件生存的心血管生物标志物的影响。

DESCRIPTION (provided by applicant): Coronary heart disease (CHD) is the leading cause of death in the United States, affecting 1 million people each year. The term "cardiovascular vulnerable patient" has been used to describe patients susceptible to acute coronary events based upon plaque, blood, or myocardial characteristics. Epidemiological studies have shown that stress is a significant and independent risk factor for patients with CHD, and also may be associated with increased cardiovascular vulnerability. This evidence has provided a rationale for developing stress management training (SMT) interventions for CHD patients. Although cardiac rehabilitation (CR) is regarded as integral to the care of patients with CHD, SMT is currently not an essential component of most CR programs. We believe that the therapeutic potential of SMT has remained unfulfilled due to a paucity of well- designed clinical studies in CHD patients. Because randomized clinical trials (RCTs) employing "hard endpoints"-death or myocardial infarction-require large samples followed over long time intervals, such approaches are generally not feasible for most psychosocial RCTs. This application was developed in response to Program Announcement (PA-07-322), which invited applications to examine the efficacy of SMT in improving intermediate outcomes, defined by biomarkers of cardiovascular risk purported to be in the pathway through which mental stress is thought to influence clinical events. The study proposed in this application will build upon our previous work in which we demonstrated the feasibility and efficacy of SMT in cardiovascular patients with stable CHD. Specifically, we propose to (a) evaluate the effectiveness of SMT combined with exercise-based CR in reducing stress in vulnerable cardiac patients; (b) examine changes in intermediate endpoints, including measures of cardiac vagal control, vascular endothelial dysfunction, inflammation, platelet function, and mental stress-induced myocardial ischemia, which are recognized biomarkers of cardiac vulnerability to clinical CHD events; (c) explore potential moderators and mediators by which SMT may improve biomarkers of risk; and (d) determine the impact of SMT on clinical endpoints over a mean follow-up period of 30 months. One hundred fifty men and women with CHD will be randomly assigned to exercise- based CR or to SMT-enhanced CR. Before and after 3 months of treatment, patients will undergo clinical assessments of stress and biomarkers of cardiovascular risk. Follow-up assessments will determine the maintenance of benefit and document cardiac events. The data generated from this study will have important clinical significance by determining the extent to which SMT combined with exercise-based CR reduces stress and improves prognosis in vulnerable cardiac patients. PUBLIC HEALTH RELEVANCE: Coronary Heart Disease (CHD) is a significant health problem in the United States and throughout the world, and is the leading cause of death for men and women in the US. This study will examine the effects of a Stress Management Training program combined with exercise-based cardiac rehabilitation on cardiovascular biomarkers of risk and event-free survival in CHD patients.