Responses of Myocardial Ischemia to Sertraline Treatment

描述（由申请人提供）：心肌缺血是缺血性心脏病（IHD）临床活动的重要指标，发生在心肌因冠状动脉收缩或高需求或两者兼而有之而得不到足够的血液供应时。精神压力已被证明是诱发心肌缺血的诱因。精神应激性心肌缺血（MSIMI）可能是由于冠状动脉供血减少而不是心肌需求增加。MSIMI在临床上具有重要意义，因为它对增加的不良心脏事件具有很高的可预测性。尽管如此，还没有药理方法被证明可以改善MSIMI。先前的研究表明，压力管理和锻炼可能是有益的。抑郁症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一个危险因素，独立于传统的心脏风险。我们最近的研究表明，抑郁症状与MSIMI的可能性增加有关，这可能是抑郁症对IHD预后不利的潜在机制。选择性血清素再摄取抑制剂（SSRIs）可能改善心脏预后，但可能与抑郁症的改善无关。SSRIs可能具有心脏保护作用的一种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，研究人员计划确定MSIMI的修饰是否与抑郁症状、心血管对压力的反应性和/或血小板聚集的改善有关。为了实现这些目标，我们提出了一项随机、安慰剂对照的单中心研究，使用舍曲林和安慰剂治疗临床稳定的IHD合并MSIMI患者。共有120名患有MSIMI的IHD患者将被随机分为舍曲林组或安慰剂组，为期6周。将在基线和6周干预结束时评估精神压力和运动测试期间的缺血性活动、心血管反应性、血小板活性、抑郁、焦虑、敌意和感知压力水平。这项研究将通过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来改善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.