SBHW-PREDICT (The role of PRoteomics, gEnetics, and Directed Imaging using CT)

 描述(申请人提供)：在我们建议的研究SBHW-Forecast(蛋白质组学、遗传学和使用CT的定向成像的作用)中，我们将评估使用成像标记物、生物标记物概况或两者的组合来识别高危个体是否能改善对传统危险因素的重新分类和区分，特别是在那些有冠心病家族史或冠心病遗传易感性较高的人中。我们使用了美国国立卫生研究院资助的第一项CAC预测价值研究-南湾心脏观察(SBHW)研究-的1312名参与者的数据来计算斑块密度。在初步分析中，我们发现较高的斑块密度与该队列中较低的心血管事件发生率有关。在拟议的研究中，我们将使用20年前从SBHW收集的基线血清和细胞样本，并使用联邦医疗保险和国家死亡指数的管理数据来回顾评估结果，以解决以下目的和目标：1)使用联邦医疗保险索赔和国家死亡指数数据评估基线CAC的预后价值，以及冠状动脉钙密度对长期(20年)冠心病事件发生率的预测价值；2)使用基线收集的血清和细胞样本，评估使用来自不同生物途径的循环标志物的多生物标志物方法是否会比传统危险因素具有额外的重新分类价值；3)确定与家族史相比，CHD遗传风险评分是否更能预测事件；以及4)在CHD易感性较高(基于家族史或遗传评分)的人群中，与遗传风险较低的人群相比，确定基因评分是否改变了成像标记物(CAC)或多个生物标记物评分或两者的组合的预后价值。我们多学科研究团队的经验、基线CAC后独特的20年随访期、与联邦医疗保险索赔数据和死亡指数数据的联系、使用冷冻血清和细胞样本的遗传和生物标记物概况以及对原始队列幸存者的跟踪是这项建议的主要优势。该项目的结果将评估互补遗传标记、多生物标记和成像方法在风险评估中的应用。

 DESCRIPTION (provided by applicant): In our proposed study, SBHW-PREDICT (The role of PRoteomics, gEnetics, and Directed Imaging using CT), we will assess whether identification of at-risk individuals, using imaging markers, a biomarker profile or a combination of the two, improves reclassification and discrimination over traditional risk factors, particularly in those wth either a family history of coronary heart disease (CHD) or higher genetic predisposition for CHD. We have used data from 1312 participants of the first NIH-funded study of predictive value of CAC, the South Bay Heart Watch (SBHW) study, to calculate plaque density. In preliminary analyses, we have found that higher plaque density is related to lower incidence of CVD events in this cohort. In the proposed study, we will use serum and cell samples collected at baseline, 20 years ago, from the SBHW and retrospectively assess outcomes using administrative data from Medicare and the National Death Index to address the following aims and objectives: 1) Using Medicare Claims and National Death Index data assess prognostic value of baseline CAC, as well as coronary calcium density for long-term (20 year) CHD event rate; 2) Using serum and cell samples collected at baseline, assess whether a multi-biomarker approach using circulating markers from different biological pathways would have additional reclassification value over traditional risk factors; 3) Determine whether compared to family history a CHD genetic risk score is more predictive of events; and 4) Determine whether a genetic score modifies the prognostic value of an imaging marker (CAC) or a multiple biomarker score or a combination of the two in those at higher predisposition (based on either family history or genetic score) for CHD versus those at low genetic risk. The experience of our multidisciplinary research team, unique 20 year follow-up period after baseline CAC, linkage to Medicare claims data and Death Index data, genetic and biomarker profiles using frozen serum and cell samples, and follow-up of the original cohort survivors are major strengths of this proposal. Results of thi project will assess the utility of a complementary genetic marker, multi-biomarker, and imaging approach to risk assessment.