Ancillary Investigation of Mental Stress Biomarkers in Coronary Heart Disease

描述(由申请人提供)： 冠心病(CHD)患者心理应激可导致心肌缺血。心理应激诱导的缺血预示着不良心脏事件风险的增加，其预后的临床意义已经建立在运动应激试验引起的缺血之上。尽管心理应激测试作为一种临床工具有很大的前景，但精神应激缺血的潜在机制仍需确定，应激诱导的扰动在其他心脏风险生物标志物中的预后价值尚不清楚。该应用程序是为响应RFA-HL-09-001而开发的，作为即将进行的一项临床试验的辅助研究，该试验包括在压力管理干预前后对冠心病患者心理应激引起的心肌缺血进行评估。拟议的辅助研究扩展了母公司的研究，重点关注心理应激测试期间血管内皮功能的一过性损害和心脏的自主神经调节。这些心血管调节系统中的一过性损害可能是缺血性活动的表现，也可能独立地对不良临床结果的风险做出贡献。以心率变异性(HRV)为指标的副交感神经心脏控制在精神应激时减弱，导致心脏电不稳定和事件风险增加。根据血流介导性扩张(FMD)的测量，精神应激也被证明对血管内皮功能有不利影响。冠心病患者的特点是内皮功能障碍，即使在静息状态下也是如此，这一关键的血管调节机制进一步受损，特别是在冠状动脉中，可能会引发精神应激性缺血，增加心脏事件的风险。这项拟议的辅助研究旨在评估这些应激生物标志物是否与心肌缺血的发生有关，并评估它们的预后价值。通过建立包括临床随访阶段的母公司临床试验的基础设施，有可能采用一种符合成本效益的方法来解决以下研究假设：(I)精神应激引起的HRV和FMD损害将预测精神应激缺血的发生；(Ii)精神应激引起的HRV和FMD损害将预测不利的心血管结果；以及(Iii)压力管理干预将导致改善HRV和FMD对精神应激的反应。这项辅助研究产生的数据将具有重要的临床意义，因为它将促进心理压力测试在心脏病患者风险分层中的应用。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。这项研究旨在开发精神应激生物标记物，以完善CHD的风险分层，并为临床医生提供评估工具，使他们更好地装备他们优化患者管理。

DESCRIPTION (provided by applicant): Myocardial Ischemia can be induced by mental stress in patients with coronary heart disease (CHD). Mental stress-induced ischemia is predictive of increased risk of adverse cardiac events, and its prognostic clinical significance has been established over and above ischemia induced during exercise stress testing. Although mental stress testing holds much promise as a clinical tool, the mechanisms underlying mental stress ischemia need to be identified, and the prognostic value of stress-induced perturbations in other biomarkers of cardiac risk are unknown. This application was developed in response to RFA-HL-09-001, as an ancillary study to an upcoming clinical trial that includes the assessment of mental stress induced myocardial ischemia in CHD patients, both before and after a stress management intervention. The proposed ancillary study extends the parent study by focusing on transient impairment of vascular endothelial function and autonomic regulation of the heart during mental stress testing. Transient impairment in these cardiovascular regulatory systems may be responsible for the manifestation of ischemic activity, and also may contribute independently to risk of adverse clinical outcomes. Parasympathetic cardiac control, indexed by heart rate variability (HRV), is attenuated during mental stress, resulting in cardiac electrical instability and heightened risk of events. Mental stress also has been shown to have an adverse impact on vascular endothelial function as measured by flow-mediated dilation (FMD). CHD patients are characterized by endothelial dysfunction, even under resting conditions, and further compromise of this critical vascular regulatory mechanism, especially in the coronary vessels, may provoke mental stress ischemia and increase the risk for cardiac events. The proposed ancillary study is designed to evaluate whether these stress biomarkers are related to the occurrence of myocardial ischemia and to assess their prognostic value. By building upon the infrastructure of the parent clinical trial, which includes a clinical follow-up phase, a cost-effective approach to addressing the following research hypotheses is possible: (i) Mental stress-induced impairment of HRV and FMD will predict the occurrence of mental stress ischemia; (ii) Mental stress-induced impairment of HRV and FMD will predict adverse cardiovascular outcomes, and; (iii) a stress management intervention will result in improved HRV and FMD response to mental stress. The data generated by the ancillary study will have important clinical significance by advancing the use of mental stress testing for risk stratification in 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 is designed to develop mental stress biomarkers that will refine risk stratification in CHD, and provide clinicians with assessment tools that will better equip them to optimize patient management.