EPIDEMIOLOGY OF CORONARY ARTERY CALCIFICATION

冠状动脉钙化的流行病学

• 批准号: 6721478
• 负责人: Patricia Ann PEYSER
• 金额: $ 59.8万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-15 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6721478
• 关键词: adult human (21+); age difference; atherosclerosis; biomarker; blood tests; calcification; cardiovascular disorder epidemiology; clinical research; computed axial tomography; coronary artery; coronary disorder; disease /disorder proneness /risk; family genetics; gender difference; genetic polymorphism; human data; human subject; longitudinal human study; questionnaires; statistics /biometry

DESCRIPTION: Coronary artery disease (CAD) is a major cause of morbidity and mortality in the US. Since half of those who suffer myocardial infarctions (MIs) and sudden death are previously asymptomatic, studies of individuals with atherosclerosis but without symptoms will contribute to understanding sub clinical disease. Coronary artery calcification (CAC), part of the atherosclerosis process, can be accurately and non-invasively quantified by electron beam computed tomography (EBCT). CAC quantity correlates with plaque area and predicts coronary artery stenosis better than established CAD risk factors. In the first nine years of our study, we determined the distribution of CAC quantity in 1,647 asymptomatic adults (including 956 sib pairs) from Rochester, MN who were not physician-referred, self-referred, or high risk and had no history of MI, stroke, or revascularization (i.e., asymptomatic). Specific genes contributed to inter-individual variation in presence and quantity of CAC after accounting for traditional CAD risk factors. In pilot studies, CAC quantity significantly predicted MI, CAD death, and revascularization and CAC quantity increased 24 percent per year with considerable inter-individual variation in extent of change in quantity of CAC. New CAD risk factors (i.e., fibrinogen, C-reactive protein ad antibodies to infective agents) predicted CAC quantity after accounting for traditional CAD risk factors. These findings motivate the aims of this continuation application to determine whether CAC quantity and/or change in CAC quantity predicts clinical events as well as to locate genes that influence progression of CAC quantity. Our proposed study takes advantage of already available EBCT measures of CAC quantity, traditional CAD risk factors, more than 60 candidate genes and 375 highly polymorphic anonymous markers and stored samples to be used for new CAD risk factors. New data will be collected on clinical endpoints on all 1,647 asymptomatic adults as well as progression of CAC quantity in a subsample of 1,000 asymptomatic adults (550 sib pairs). We will determine whether CAC quantity predicts clinical events after 7.5 years of active follow-up (Aim 1), determine whether change in CAC quantity over 7.5 years predicts future events after an additional 2.5 years of follow-up (Aim 2), identify genetic determinants of change in CAC quantity, and assess whether these genes act through measurable CAD risk factors (Aims 3 and 4). Understanding relationships between sub clinical atherosclerosis and future events, progression in sub clinical atherosclerosis and future events, as well as factors predicting progression of sub clinical atherosclerosis will improve early identification of individuals who will benefit most from existing or new interventions.

描述：冠状动脉疾病（CAD）是发病率和 在美国的死亡率。由于一半遭受心肌梗塞的人 （MIS）和猝死以前是无症状的 动脉粥样硬化但没有症状将有助于理解子 临床疾病。冠状动脉钙化（CAC），一部分 动脉粥样硬化过程，可以准确且非侵入性地量化 电子束计算机断层扫描（EBCT）。 CAC数量与斑块相关 区域并预测冠状动脉狭窄比已建立的CAD风险更好 因素。在我们研究的前九年中，我们确定了分布 来自1,647名无症状成年人（包括956个SIB对）的CAC数量 罗切斯特（Rochester），明尼苏达州，没有医生参考，自我引用或高风险，并且 没有MI，中风或血运重建史（即无症状）。 特定基因在存在和 考虑传统CAD风险因素后的CAC数量。在飞行员中 研究，CAC数量显着预测了MI，CAD死亡和 血运重建和CAC数量每年增加24％， CAC数量变化程度的个体间差异很大。 新的CAD危险因素（即纤维蛋白原，C反应蛋白AD抗体 感染剂）预测传统CAD后的CAC数量 风险因素。这些发现激发了此继续应用的目标 确定CAC数量和/或CAC数量的变化是否预测 临床事件以及定位影响CAC进展的基因 数量。我们提出的研究利用已经可用的EBCT措施 CAC数量，传统CAD危险因素，60多个候选基因和 375高度多态匿名标记和存储的样品用于新 CAD风险因素。将在所有1,647的临床终点上收集新数据 无症状的成年人以及CAC数量的进展 1,000名无症状成年人（550 SIB对）。我们将确定CAC是否 数量预测7。5年的主动随访后的临床事件（AIM 1）， 确定7。5年以上CAC数量的变化是否预测未来事件 经过2。5年的随访（AIM 2），识别遗传 CAC数量变化的决定因素，并评估这些基因是否作用 通过可测量的CAD危险因素（目标3和4）。了解关系 在亚临床动脉粥样硬化和未来事件之间，子进展 临床动脉粥样硬化和未来事件，以及预测的因素 亚临床动脉粥样硬化的进展将改善早期鉴定 从现有或新干预措施中受益最多的个人。