Stress Management and Biomarkers of Risk in Cardiac Rehabilitation

冠心病（CHD）是美国的主要死亡原因，影响100万人 每年.术语“心血管脆弱患者”已被用于描述易受以下疾病影响的患者： 基于斑块、血液或心肌特征的急性冠状动脉事件。流行病学研究 提示应激是冠心病患者的一个重要的独立危险因素， 与心血管脆弱性增加有关。这一证据为发展 冠心病患者的压力管理训练（SMT）干预。心脏康复（CR） SMT被认为是CHD患者护理的组成部分，目前不是大多数CR的重要组成部分 程序.我们认为，SMT的治疗潜力仍然没有实现，由于缺乏良好的- 在CHD患者中设计的临床研究。因为随机临床试验（RCT）采用“硬” 终点”-死亡或心肌梗死-需要长时间间隔的大样本， 对于大多数心理社会随机对照试验，方法通常不可行。该应用程序开发于 对计划公告（PA-07-322）的回应，该公告邀请了对SMT在以下方面的有效性进行检查的建议： 改善中间结局，由声称在该途径中的心血管风险生物标志物定义 精神压力被认为是通过它来影响临床事件。本申请所建议的研究将 在我们以前的工作中，我们证明了SMT在心血管疾病中的可行性和有效性， 稳定型CHD患者。具体而言，我们建议（a）评估SMT的有效性， （B）检查在心脏脆弱患者中基于运动的CR减少应激的变化; 终点，包括心脏迷走神经控制、血管内皮功能障碍、炎症、血小板计数、 功能和精神压力诱导的心肌缺血，这是公认的心脏病的生物标志物， 临床CHD事件的脆弱性;（c）探索潜在的调节剂和介质，SMT可能 改善风险的生物标志物;以及（d）确定平均随访期间SMT对临床终点的影响 为期30个月。150名患有冠心病的男性和女性将被随机分配到运动组- 基于CR或SMT增强型CR。治疗前后3个月，患者将接受临床 压力评估和心血管风险的生物标志物。后续评估将确定 维持受益并记录心脏事件。这项研究产生的数据将具有重要意义。 通过确定SMT与基于运动的CR结合减少压力的程度来确定临床意义 并改善脆弱心脏病患者的预后。

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 proposals 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.