Responses of Myocardial Ischemia to Sertraline Treatment

描述(申请人提供)：心肌缺血是衡量缺血性心脏病(IHD)临床活动性的重要指标，当心肌因冠状动脉狭窄或高需求或两者兼而有之而无法获得足够的血液供应时，就会发生心肌缺血。精神应激已被证明是引发心肌缺血的诱因。精神应激诱导的心肌缺血(MSIMI)被认为是由于冠状动脉供血减少而不是心肌需求增加。MSIMI对增加不良心脏事件具有很高的可预测性，因此具有重要的临床意义。尽管如此，还没有任何药理方法被证明可以改善MSIMI。之前的研究表明，压力管理和锻炼可能是有益的。抑郁是心血管疾病患者中特别普遍的问题，已被证明是IHD患者不良心脏结局增加的危险因素，与传统的心脏风险无关。我们最近的研究表明，抑郁症状与MSIMI的可能性增加有关，这可能是抑郁对IHD预后产生不利影响的潜在机制。有研究表明，选择性5-羟色胺再摄取抑制剂(SSRIs)可以改善心脏结局，这可能与抑郁症的改善无关。SSRI可能具有心脏保护作用的一个机制与其降低血小板活性的能力有关。拟议的项目计划调查MSIMI对舍曲林和安慰剂的反应。此外，它计划确定MSIMI的修改是否与改善抑郁症状、心血管对压力的反应性和/或血小板聚集有关。为了实现这些目标，我们建议对临床稳定的患有MSIMI的IHD患者进行一项随机、安慰剂对照的单中心研究，使用舍曲林和安慰剂。总共120名患有MSIMI的IHD患者将被随机分为舍曲林或安慰剂，为期6周。在心理压力和运动测试期间的缺血活动、心血管反应性、血小板活性、抑郁、焦虑、敌意和感觉到的压力水平将在基线和6周干预结束时进行评估。这项研究将帮助我们更好地了解舍曲林治疗如何成功地影响心血管系统，从而改善IHD患者的预后。

DESCRIPTION (provided by applicant): Myocardial ischemia, an important measure of the clinical activity of ischemic heart disease (IHD), occurs when the myocardium does not receive enough blood supply resulting from either coronary constriction or high demand or both. Mental stress has been shown to be a trigger inducing myocardial ischemia. Mental stress-induced myocardial ischemia (MSIMI) is suggested due to reduction of coronary blood supply rather than increased myocardium demand. MSIMI is clinically important as to its high predictability for increased adverse cardiac events. Despite this, no pharmacological modalities have been proven to improve MSIMI. Previous studies suggest stress management and exercise may be beneficial. Depression, a particularly prevalent problem in patients with cardiovascular diseases, is proven to be a risk factor for increased adverse cardiac outcomes in patients with IHD, independent of conventional cardiac risks. Our recent study demonstrated that depression symptoms were associated with increased likelihood of MSIMI, which is possibly an underlying mechanism of depression adversely affect the prognosis of IHD. It has been suggested that selective serotonin reuptake inhibitors (SSRIs) may improve cardiac outcome which may not be related to improvement of depression. One mechanism of SSRIs that may be cardiac protective is related to their ability of reducing platelet activity. The proposed project plans to investigate the response of MSIMI to sertraline compared to placebo. Further, it plans to determine whether the modification of MSIMI is related to improvement of depression symptoms, cardiovascular reactivity to stress, and/or of platelet aggregation. To achieve these goals, we propose a randomized, placebo-controlled single center study using sertraline versus placebo for clinically stable IHD patients with MSIMI. A total of 120 IHD patients with MSIMI will be equally randomized into sertraline or placebo for 6 weeks. Ischemic activity during mental stress and exercise testing, cardiovascular reactivity, platelet activity, depression, anxiety, hostility, and level of perceived stress will be assessed at baseline and at the end of the 6-week intervention. This study will improve the outcome of IHD patients by helping us to better understand how successful the treatment of sertraline affects the cardiovascular system.