Novel Technologies to Identify Preclinical Coronary Disease in High Risk Families

识别高危家庭临床前冠心病的新技术

• 批准号: 7937729
• 负责人: Lewis C Becker
• 金额: $ 50万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7937729
• 关键词: 9p21; Adult; Adult Children; Age-Years; Angiography; Area; Atherosclerosis; Baltimore; Calcified; Calcium; Cities; Clinical; Contrast Media; Coronary; Coronary Angiography; Coronary artery; Coronary heart disease; Data; Detection; Economics; Effectiveness; Employee; Employment; Event; Exposure to; Family; Family Study; Family history of; Funding; General Population; Genetic; Genetic Determinism; Genetic Risk; Genetic Variation; Genotype; Goals; Gold; Grant; Imaging technology; Individual; Institution; Maryland; Measurement; Methods; Modeling; Occupations; Outcome; Patients; Persons; Phase; Population; Positioning Attribute; Preventive; Preventive Intervention; Preventive Medicine; Primary Prevention; Radiation; Reference Values; Relative (related person); Risk; Risk Factors; Science; Siblings; Stratification; Subjects Selections; Symptoms; Testing; Time; Variant; Work; X-Ray Computed Tomography; aggressive therapy; atherogenesis; base; cardiovascular risk factor; comparative effectiveness; coronary artery calcification; disorder risk; effectiveness research; follow-up; high risk; imaging modality; improved; inflammatory marker; innovation; new technology; pre-clinical; premature; prevention clinical trial; proband; prospective; public health relevance

DESCRIPTION (provided by applicant): Summary Challenge Area, 05 Comparative Effectiveness Research (CER): Challenge Topic NHLBI-05-HL-104* Reducing Cardiovascular Risk in Moderate-Risk and Asymptomatic Patients." Our project is entitled "Novel Technologies to Identify Preclinical Coronary Disease in High Risk Families." Its prime purpose is to compare an innovative coronary artery imaging technology with a standard imaging method in the detection of very early coronary disease in people who are at high risk but who have not had symptoms or a clinical coronary disease event. Coronary atherogenesis begins well before manifest clinical coronary disease (CAD). If occult CAD and its extent could be accurately identified during the preclinical phase, targeted intensive preventive therapies could be tested that may mitigate CAD events. In this study we will apply a comparative effectiveness research paradigm to a susceptible population of asymptomatic first degree adult relatives of persons with known premature CAD, all easily identifiable by family history, with a CAD risk that is 2-5 times that of the general population. We have extensive genotyping in ~3000 individuals in a prospective family study, GeneSTAR (Genetic Determinants of Atherosclerosis Risk). The goal of this proposed challenge grant study is to advance personalized preventive medicine using a comparative effectiveness research model. We will compare the relative effectiveness of CT CAC and MDCTA for identifying subjects with latent preclinical CAD who would represent appropriate targets for intensive preventive therapies. Our primary specific aims are to (1) evaluate both (the extent of calcified and noncalcified coronary plaque using MDCTA, and coronary calcium score (CAC) in 1000 22 to 75 year old apparently healthy siblings and adult offspring of probands with known premature CAD (< 60 years of age) from the GeneSTAR study. (2) determine the relationship of traditional risk factors (Framingham Global Risk Score), and hsCRP to outcomes to determine the optimal identification of persons with significant preclinical CAD, and (3) determine whether the addition of known genetic risk variants for CAD improve selection of subjects for CT or MDCTA. Data will be used to general reference values for plaque volumes and to determine the value of MDCTA as a method to track responsiveness to therapy in a subsequent primary prevention trial. The goal is also to create jobs and advance science more quickly. We plan to do this by creating 2 new jobs, supporting 2-4 others, and by providing funds to retain people in their current positions. Our work is also predicated on the tenet that the project should yield data that will provide for subsequent follow-up and for a larger primary prevention clinical trial. Every year The Johns Hopkins Institutions directly generate about $10 billion in economic activity in the State of Maryland, a 43% increase from the $7 billion generated in 2002 and the equivalent of one of every twenty-four dollars in the state's economy today. In 2008, Johns Hopkins Institutions provided 45,000 jobs and created 700 new jobs each year since 2002. Directly and indirectly Johns Hopkins Institutions support more than 100,000 jobs in Maryland, one of every 29 in the state. In Baltimore City alone Johns Hopkins directly and indirectly supports 60,000 jobs, or 16.7% of all City employment. This application will create or retain at least 7-10 jobs, including 2 direct new full-time employees. Public Health Relevance: The goal of this proposed challenge grant study is to advance personalized preventive medicine using a comparative effectiveness research model to compare the relative effectiveness two methods for looking at coronary artery plaque. The purpose is to identify subjects with latent preclinical CAD who would represent appropriate targets for intensive preventive therapies.

描述(由申请人提供)： 挑战领域摘要，05比较有效性研究(CER)：挑战主题NHLBI-05-HL-104*降低中等风险和无症状患者的心血管风险。我们的项目名为“在高危家庭中识别临床前冠状动脉疾病的新技术”。它的主要目的是比较创新的冠状动脉成像技术和标准成像方法在检测高危但没有症状或临床冠状动脉疾病事件的人中非常早期的冠状动脉疾病。冠状动脉粥样硬化的形成早在临床表现为冠心病(CAD)之前就开始了。如果在临床前阶段能够准确地识别隐匿性CAD及其范围，就可以测试有针对性的强化预防性治疗，以减轻CAD事件。在这项研究中，我们将把比较有效性研究范式应用于易感人群，这些人是已知的早产儿冠心病患者的无症状的一级成年亲属，这些人都很容易通过家族史识别，其冠心病风险是普通人群的2-5倍。我们在一项名为GeneSTAR(动脉粥样硬化风险的遗传决定因素)的前瞻性家庭研究中，对大约3000名个体进行了广泛的基因分型。这项拟议的挑战拨款研究的目标是使用比较有效性研究模型来推进个性化预防医学。我们将比较CT、CAC和MDCTA在识别潜在的临床前CAD患者方面的相对有效性，这些患者将代表强化预防性治疗的合适靶点。我们的主要目标是(1)评估(使用MDCTA的钙化和非钙化冠状动脉斑块的范围)，以及来自GeneSTAR研究的1000名22至75岁表面健康的兄弟姐妹和患有早产儿(60岁)的先证者的成年后代的冠状动脉钙化评分(CAC)。(2)确定传统风险因素(Framingham Global Risk Score)和hsCRP与结果的关系，以确定对有显著临床前CAD的人的最佳识别；以及(3)确定添加已知的CAD遗传风险变量是否改善了CT或MDCTA受试者的选择。数据将被用于斑块体积的一般参考值，并在随后的一级预防试验中确定MDCTA作为一种跟踪治疗反应的方法的价值。目标也是为了创造就业机会，更快地推动科学进步。我们计划通过创造2个新的就业机会，支持2-4个其他工作岗位，并提供资金留住现有职位的人来做到这一点。我们的工作还基于这样一个原则，即该项目应该产生数据，为后续的随访和更大规模的一级预防临床试验提供数据。约翰霍普金斯大学的机构每年在马里兰州直接创造约100亿美元的经济活动，比2002年的70亿美元增加了43%，相当于今天该州经济每24美元中就有1美元。2008年，约翰霍普金斯大学提供了4.5万个工作岗位，自2002年以来，每年创造700个新工作岗位。约翰霍普金斯大学的机构直接和间接地支持了马里兰州10万多个工作岗位，该州每29个工作岗位中就有一个。仅在巴尔的摩市，约翰斯·霍普金斯就直接和间接支持了60,000个工作岗位，占整个城市就业人数的16.7%。这项申请将创造或保留至少7-10个工作岗位，包括2个直接新的全职员工。 公共卫生相关性： 这项拟议的挑战拨款研究的目标是利用比较有效性研究模型来比较两种观察冠状动脉斑块的方法的相对有效性，以促进个性化预防医学的发展。目的是确定潜在的临床前冠心病患者，谁是强化预防性治疗的合适靶点。