Thrombogenic Factors and Recurrent Coronary Events

这项继续资助的主要目的是确定在心肌梗死后患者的丰富人群中，在长期随访期间，编码凝血-脂质风险机制相关蛋白质的18个预先指定的遗传位点（多态性）是否对时间依赖性复发性冠状动脉事件（不稳定型心绞痛、非致死性心肌再梗死或冠状动脉死亡）的发生有显著的附加风险。 次要目的是确定预先规定的循环脂质因子和脂质相关基因型是否与止血激活增加相关。研究人群包括1，045名梗死后患者，平均2年随访期间发生了202例首次复发心脏事件。 将对该队列入组前采集并在零下70 ℃下冷冻的白色血细胞样本、血浆和血清进行基因检测和其他凝血和血脂检测。 基因型鉴定将包括6个与凝血蛋白相关的基因座，3个与血栓形成相关的粘附分子相关的基因座，9个与载脂蛋白和富脂蛋白代谢相关的基因座。 在初步分析中将使用一种创新的遗传携带者方法，以确定在这个明确定义的无关患者队列中，18种预先指定的基因型是否对时间依赖性复发性心脏事件有额外的易感性。 确定的遗传风险将表示为每个个体存在的风险基因座数量的平均风险比，并对生物学、疾病严重程度和环境协变量进行适当调整。 该研究有90%的把握度检测到在心肌梗死后队列中，每个个体存在的每个数量或预先指定的风险位点（范围0至8加）的平均风险显著增加15%或更高（风险比大于1.15）。识别由有限的风险基因型库在复发性冠状动脉事件中构成的加性风险将是有用的，作为一种筛查技术，在未来的识别和量化的作用，个别风险基因型在这种寡基因疾病。

The primary objective of this continuation grant is to determine if 18 prespecified genetic loci (polymorphisms)that code for proteins involved in coagulation-lipid-risk mechanisms contribute significant additive risk for the occurrence of time-dependent recurrent coronary events (unstable angina, non-fatal myocardial reinfarction, or coronary death) during long-term follow-up in an enriched population of post-myocardial infarction patients. The secondary objective is to determine if prespecified circulating lipid factors and lipid related genotypes are associated with increased hemostatic activation. The study population involves 1,045 post-infarction patents with 202 first recurrent cardiac events that occurred during an average 2-year follow-up. Genetic testing and additional coagulation and lipid tests will be performed on white blood cell samples, plasma, and serum that were collected and frozen at minus 70 Celsius during the prior enrollment of this cohort. Genotype identification will include 6 loci related to coagulation proteins, 3 related to adhesion molecules involved in thrombosis, and 9 involved in apolipoproteins and metabolism of triglyceride-rich lipoproteins. An innovative genetic carriership approach will be used in the primary analysis to determine if a pool of the 18 prespecified genotypes contributes additive susceptibility for time-dependent recurrent cardiac events in this well-defined cohort of unrelated patents. The identified genetic risk will be expressed as an average hazard ratio per number of risk loci present per individual, with appropriate adjustment for biologic, disease severity, and environmental covariates. The study has 90 percent power to detect a significantly increased average risk of 15percent or greater (hazard ratio greater than 1.15) per number or prespecified risk loci present (range 0 to 8 plus) per individual in this post-myocardial infarction cohort. Identification of an additive risk posed by a limited pool of risk genotypes in recurrent coronary events will be useful as a screening technique in the future identification and quantification of the role played by individual risk genotypes in this oligogenic disorder.