Identifying Epidemiological Risk Factors for Abdominal Aortic Aneurysm

描述(申请人提供)：腹主动脉瘤(AAA)是老年人的常见病，也是一个重要的公共卫生问题。腹主动脉破裂与65%至85%的死亡率有关，是老年人死亡的主要原因之一。对于已确定的大型AAA，选择性手术或血管内修复是唯一有效的干预措施，目前还没有特定的药物被证明能有效地预防或减少普通人群的AAA进展。AAA的病因很复杂，目前还不清楚。虽然传统的心血管危险因素已经与AAA的风险相关，但它们在AAA的病因学中的重要性还没有得到很好的确定。此外，细胞外基质重塑和降解、炎症和血栓形成等新的致病机制已经被假设，但它们的作用还没有得到适当的确定。我们建议利用社区动脉粥样硬化风险(ARIC)研究中计划的心脏超声检查来对腹主动脉进行超声检查，以确定这一基于人群的大型队列中未诊断的AAA病例。此外，这些病例将与265例现有病例合并在一起，这些病例已经通过医院记录确定，而那些将通过医疗保险联系确定。利用ARIC在基线时已经收集的危险因素和血浆样本，我们将在这一已跟踪20多年的大型前瞻性队列中进行AAA的流行病学研究。这项申请的具体目标是：1)对大约6886名ARIC参与者进行腹主动脉超声检查，其中25%是非洲裔美国人，他们的年龄将在67-89岁之间，预计将参加2011-13年的下一次ARIC检查。基于男性中6.1%的无症状AAA和65岁以上女性中1.7%的患病率估计，我们预计在ARIC队列中发现235例未诊断的AAA病例。加上1987-2011年间以前诊断的临床病例，我们预计总共有475例AAA。2)调查AAA与潜在的新危险因素之间的关系，这些新危险因素以前在ARIC中测量过或将在1987-89年ARIC基线采集的储存血液样本中测量。具体地说，我们将评估以下类别的新生物标志物：(A)细胞外基质重塑；(B)细胞外基质降解；(C)炎症；(D)血栓形成。这项研究将首次全面评估新的危险因素在AAA病因学中的作用，对一大批以人群为基础的中年人进行了20多年的跟踪调查。在ARIC内进行这项研究利用了ARIC的广泛特点的队列，现有的生物样本免费提供给当前项目，并提供了一种特别快速和具有成本效益的方法来建立AAA队列，因为腹部超声方案很容易添加到2011-13年ARIC检查中进行的心脏超声中。

DESCRIPTION (provided by applicant): Abdominal aortic aneurysm (AAA) is a common disease in the elderly and an important public health problem. Ruptured AAA is associated with a 65% to 85% mortality rate and ranked one of the leading causes of death in the elderly. Elective surgery or endovascular repair for identified large AAA are the only effective interventions for AAA and there are no specific pharmacological agents that have been shown to be effective in preventing or reducing AAA progression in the general population. The etiology of AAA is complex and not well understood. Although traditional cardiovascular risk factors have been associated with the risk of AAA, their importance in the etiology of AAA is not well established. Furthermore, the novel etiopathogenic mechanisms such as extracellular matrix remodeling and degradation, inflammation, and thrombosis have been hypothesized but their roles are not appropriately determined. We propose to take advantage of the planned cardiac ultrasound exams in the Atherosclerosis Risk in Communities (ARIC) Study to perform an ultrasound examination of the abdominal aorta to identify undiagnosed AAA cases in this large population-based cohort. In addition, these will be pooled with 265 existing cases already identified through hospital records and those to be identified through Medicare linkage. Utilizing the risk factor and plasma samples already collected in ARIC at baseline, we will conduct epidemiological studies of AAA in this large prospective cohort that has been followed for more than 20 years. The specific aims of this application are: 1) to perform an ultrasound examination of the abdominal aorta in approximately 6,886 ARIC participants, 25% African-Americans, who will be 67-89 years and expected to attend the next ARIC exam in 2011-13. Based on a prevalence estimate of 6.1% asymptomatic AAA in men and 1.7% in women older than 65 years, we anticipate to identify 235 undiagnosed AAA cases in the ARIC cohort. With the previously diagnosed clinical cases during 1987-2011, we expect a total of 475 AAAs. 2) To investigate the associations of AAA with potential novel risk factors previously measured in ARIC or to be measured in stored blood samples collected at ARIC baseline in 1987- 89. Specifically, we will evaluate novel biomarkers in the following categories: (a) extracellular matrix remodeling; (b) extracellular matrix degradation; (c) inflammation; and (d) thrombosis. This study will be the first to comprehensively evaluate the role of novel risk factors in the etiology of AAA in a large, population- based cohort of middle-aged adults followed for more than 20 years. Conducting this study within ARIC takes advantage of ARIC's extensively characterized cohort, existing biological samples available at no cost to the current project, and provides a particularly rapid and cost-effective way to establish an AAA cohort as the abdominal ultrasound protocol is readily added to the cardiac ultrasound to be performed in the 2011-13 ARIC exam.