Stress Management and Biomarkers of Risk in Cardiac Rehabilitation

描述(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。术语“心血管脆弱患者”被用来描述基于斑块、血液或心肌特征而易患急性冠状动脉事件的患者。流行病学研究表明，应激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)干预提供了理论基础。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，由于缺乏针对冠心病患者的精心设计的临床研究，SMT的治疗潜力仍未得到充分发挥。由于采用“硬终点”--死亡或心肌梗死--的随机临床试验(RCT)需要长时间的跟踪大样本，因此这种方法对于大多数心理社会RCT通常是不可行的。此应用程序是根据计划公告(PA-07-322)开发的，该计划邀请应用程序检查SMT在改善中期结果方面的有效性，该结果由心血管风险生物标记物定义，据称是在精神应激被认为影响临床事件的途径中。本申请中提出的这项研究将建立在我们之前的工作的基础上，在这项工作中，我们证明了SMT在稳定性冠心病心血管患者中的可行性和有效性。具体地说，我们建议(A)评估SMT联合运动CR在降低脆弱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诱导的心肌缺血的测量，这些都是公认的心脏易感性的临床CHD事件的生物标志物；(C)探索SMT可能通过其改善风险生物标志物的潜在调节剂和介体；以及(D)确定SMT在平均30个月的随访期内对临床终点的影响。150名冠心病患者将被随机分配到基于运动的CR组或SMT增强CR组。在治疗前和治疗3个月后，患者将接受压力和心血管风险生物标记物的临床评估。后续评估将确定益处的维持并记录心脏事件。这项研究产生的数据将具有重要的临床意义，通过确定SMT与基于运动的CR相结合在多大程度上减轻易受伤害的心脏病患者的压力并改善预后。公共卫生相关性：冠心病(CHD)是美国和全世界的一个重大健康问题，也是美国男性和女性的主要死亡原因。这项研究将考察压力管理训练计划与以运动为基础的心脏康复相结合对冠心病患者风险和无事件生存的心血管生物标记物的影响。

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.