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状动脉综合征（ACS）患者 随后发生主要不良冠状动脉事件（MACE）的风险更高。重度抑郁症是 与炎症蛋白水平升高有关，但仅限于某些个体。一项前瞻性 ACS患者的队列研究，采用巢式病例对照组，我们建议检测 抑郁症与炎症蛋白基因相互作用的生物行为模型 多态性导致炎症蛋白水平的增加甚至比那些引起的炎症蛋白水平的增加更大。 抑郁症或基因多态性我们希望找到一个明确的，高风险的 ACS患者中抑郁症和遗传多态性的相互作用 已确定的后续MACE（心肌梗死，血运重建手术， 中风和死亡）比这些因素中的任何一个都要多，部分原因是它们的组合 增加炎症蛋白的作用。测量的炎症蛋白和基因包括： 白细胞介素（IL）6、C反应蛋白（CRP）、肿瘤坏死因子α（TNF？），E-选择素（SELE）， 和单核细胞趋化蛋白-1（MCP-1）。重度抑郁症，炎症蛋白水平 和基因型来自随后的主要不良冠状动脉事件（MACE）阳性患者 将12个月研究期间的这些因素（病例）与以下受试者的这些因素进行比较 MACE阴性（对照）。 为了验证这些假设，将对来自单个大型三级护理中心的符合条件的患者进行评估。 在因ACS住院期间确定、同意并入组研究。血样 因为基因只收集一次;而炎症蛋白测量、抑郁和 将在出院后6-8周和7个月收集混杂因素数据。在12 个月，将通过电话访谈收集MACE的随访数据。抑郁症访谈 和结构性汉密尔顿（DISH）将用于诊断重度抑郁症。将对数据进行分析 使用多元逻辑回归。公共卫生相关性 抑郁症、遗传学、炎症蛋白水平和 ACS亚组中随后发生的MACE将为研究环境触发因素提供依据 抑郁症和抑郁症干预措施的影响（不同的药物，心理治疗， 治疗和自我管理技术（如锻炼）的组合）对炎症 蛋白质水平对未来MACE的影响。降低ACS死亡率和发病率的能力 患者将受益于公共卫生工作，特别是改善老年人健康的努力， 更容易发生冠心病

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.