Exercise, Depression, and Cardiac Risk

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。最近的证据也表明，抑郁是冠心病患者的一个重要的独立危险因素，也可能与心血管易感性增加有关。这一证据为开发治疗心脏病患者抑郁的干预策略提供了理论基础。抗抑郁药物，特别是选择性5-羟色胺再摄取抑制剂，在这方面特别有效。然而，对于许多患者来说，药物治疗不能充分缓解抑郁症状，或者以不想要的副作用为代价。因此，有必要确定治疗抑郁症的替代方法，特别是在冠心病患者中。现在有充分的理由相信，锻炼可能就是这样一种方法。然而，到目前为止，运动的治疗潜力仍然没有得到充分发挥，因为缺乏精心设计的抑郁症患者临床研究的数据，而且几乎没有针对抑郁症CHD患者的随机对照试验。本申请中提出的这项研究将建立在我们之前的工作基础上，在这些工作中，我们证明了运动作为一种治疗抑郁症的可行性和有效性。具体地说，我们建议：(A)评估运动训练在减少脆弱心脏病患者抑郁方面的有效性；(B)检查中间终点的变化，包括自主神经系统失调、内皮功能障碍、慢性炎症和血小板激活的测量，这些指标也是心脏易受心律失常、斑块破裂和血栓形成影响的生理标志；以及(C)探索干预措施减轻抑郁的可能机制。200名患有冠心病和抑郁症状加重的男性和女性将被随机分配到运动、药物或安慰剂组。在治疗前和治疗3个月后，患者将接受抑郁的临床评估，并测量心率变异性、压力反射控制、内皮功能、C反应蛋白和血小板活性。6个月的随访将评估受益的维持情况，并评估心脏事件和医疗费用利用情况。这项研究产生的数据将具有重要的临床意义，通过确定运动可以在多大程度上减少易受影响的心脏病患者的抑郁并改善CHD风险的中间标志。

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. Recent evidence also has suggested that depression 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 interventional strategies for treating depression in cardiac patients. Antidepressant medications, especially selective serotonin reuptake inhibitors, have been particularly effective in this regard. However, for many patients medication fails to adequately relieve depressive symptoms or does so at the cost of unwanted side effects. Thus, there is a need to identify alternative approaches for treating depression, particularly in patients with CHD. There is now good reason to believe that exercise may be one such approach. To date, however, the therapeutic potential of exercise has remained unfulfilled due to a paucity of data from well-designed clinical studies of depressed patients, and virtually no randomized controlled trials of depressed CHD patients. The study proposed in this application will build upon our previous work in which we demonstrated the feasibility and efficacy of exercise as a treatment for depression. Specifically, we propose to (a) evaluate the effectiveness of exercise training in reducing depression in vulnerable cardiac patients; (b) examine changes in intermediate endpoints, including measures of autonomic nervous system dysregulation, endothelial dysfunction, chronic inflammation, and platelet activation, which also serve as physiologic markers of cardiac vulnerability to arrhythmias, plaque rupture, and thrombosis; and (c) explore possible mechanisms by which the interventions reduce depression. Two hundred men and women with CHD and elevated symptoms of depression will be randomly assigned to Exercise, Medication, or Placebo. Before and after 3 months of treatment, patients will undergo clinical assessments of depression and measures of heart rate variability, baroreflex control, endothelial function, C-reactive protein, and platelet activity. A six month follow-up will assess maintenance of benefit and evaluate cardiac events and medical cost utilization. The data generated from this study will have important clinical significance by determining the extent to which exercise may reduce depression and improve intermediate markers of CHD risk in vulnerable cardiac patients.