Interactions among Depressive Symptoms and Genetic Influences on Cardiac Outcomes

摘要 被诊断为重度抑郁症的急性冠脉综合征(ACS)患者包括 有更大的风险发生后续的主要不良冠状动脉事件(MACE)。严重的抑郁症是 与炎性蛋白水平升高有关，但仅限于某些人。在未来 对急性冠脉综合征患者的队列研究，采用嵌套病例对照成分，我们建议测试一个 抑郁症与炎性蛋白基因相互作用的生物行为模型 导致炎性蛋白水平增加的基因多态甚至比导致的 抑郁症或仅由基因多态引起。我们希望确定一个定义明确的、高风险的 抑郁与基因多态性交互作用的急性冠脉综合征患者亚组 确诊会增加后续MACE(心肌梗死、血管重建术、 中风和死亡)比这两个因素中的任何一个单独作用更大，部分原因是它们结合在一起 增加炎性蛋白的作用。测量的炎性蛋白和基因包括： 白介素6、C反应蛋白、肿瘤坏死因子α、E-选择素、 单核细胞趋化蛋白-1(MCP-1)。严重抑郁，炎性蛋白水平 和来自后续主要不良冠状动脉事件(MACE)阳性患者的基因 (病例)在12个月的研究期间，将与以下受试者的这些因素进行比较 Mace阴性(对照)。 为了检验这些假设，来自一家大型三级护理中心的合格患者将是 在他们因急性冠脉综合征住院期间，确定、同意并登记参加研究。血液样本 因为基因只收集一次；而炎性蛋白测量、抑郁和 混杂因素数据将在出院后6-8周和7个月收集。在12岁时 几个月后，将通过电话采访的方式收集MACE的后续数据。大萧条的采访 结构化汉密尔顿(DISH)将被用来诊断重度抑郁症。将对数据进行分析 采用多元Logistic回归分析。公共卫生相关性 发现抑郁、遗传、炎性蛋白水平和 急性冠脉综合征亚组中的后续MACE将为研究环境触发因素提供理论基础 抑郁症和抑郁症干预措施的效果(不同的药物、心理疗法、 结合治疗和自我管理技术(如锻炼)治疗炎症 蛋白质水平对未来Mace的影响。降低急性冠脉综合征死亡率和发病率的能力 病人将有益于公共卫生努力，特别是改善老年人健康的努力， 他们更容易发生冠状动脉事件。

ABSTRACT Patients with acute coronary syndromes (ACS) who are diagnosed with major depression are at greater risk for subsequent major adverse coronary events (MACE). Major depression is associated with increased inflammatory protein levels, but only in certain individuals. In a prospective cohort study of ACS patients, with a nested case-control component, we propose to test a biobehavioral model in which major depression interacts with inflammatory protein gene polymorphisms resulting in even greater increases in inflammatory protein levels than those caused by either depression or gene polymorphisms alone. We expect to identify a well-defined, high-risk subgroup of ACS patients in which the interaction of depression and the genetic polymorphisms identified increases risk of subsequent MACE (myocardial infarctions, revascularization procedures, strokes, and death) more than does either of these factors alone, in part because of their combined effect of increasing inflammatory proteins. Inflammatory proteins and genes measured include: Interleukin (IL) 6, C-reactive Protein (CRP), Tumor Necrosis Factor Alpha (TNF?), E-Selectin (SELE), and Monocyte Chemoattractant Protein-1 (MCP-1). Major depression, inflammatory protein levels and genotype from patients who are positive for subsequent major adverse coronary events (MACE) (cases) during the 12 month study will be compared with these factors from subjects who are negative for MACE (controls). To test these hypotheses, eligible patients from a single large tertiary care center will be identified, consented, and enrolled into the study during their hospitalization for ACS. Blood samples for genes will be collected once only; whereas inflammatory protein measurements, depression, and confounding factor data will be collected at 6-8 weeks and 7 months after hospital discharge. At 12 months, follow-up data for MACE will be collected by telephone interview. The Depression Interview and Structured Hamilton (DISH) will be used to diagnose major depression. Data will be analyzed using multiple logistic regression. PUBLIC HEALTH RELEVANCE The discovery of a relationship among depression, genetics, inflammatory protein levels, and subsequent MACE in an ACS subgroup would provide a rationale for studying environmental triggers of depression and the effects of depression interventions (different medications, psychotherapies, combinations of treatment, and self-management techniques such as exercise) on inflammatory protein levels for their effects on future MACE. The ability to decrease mortality and morbidity in ACS patients would benefit public health efforts, particularly efforts to improve the health of older persons, who are more prone to coronary events.