Identifying Epidemiological Risk Factors for Abdominal Aortic Aneurysm

描述（由申请人提供）：腹主动脉瘤（AAA）是老年人的常见疾病，也是重要的公共卫生问题。AAA破裂与65%至85%的死亡率相关，是老年人死亡的主要原因之一。已确定的大型AAA的择期手术或腔内修复术是AAA的唯一有效干预措施，并且在一般人群中，没有特定的药理学药物可有效预防或减少AAA进展。腹主动脉瘤的病因很复杂，尚未得到很好的理解。尽管传统的心血管危险因素与AAA的风险相关，但其在AAA病因学中的重要性尚未得到充分证实。此外，新的致病机制，如细胞外基质重塑和降解，炎症，血栓形成已被假设，但他们的角色没有适当确定。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，对腹主动脉进行超声检查，以识别这个大型人群队列中未诊断的AAA病例。此外，这些病例将与通过医院记录已经确定的265例现有病例和通过医疗保险联系确定的病例合并。利用ARIC基线时已收集的风险因素和血浆样本，我们将在这个已随访20多年的大型前瞻性队列中进行AAA的流行病学研究。本申请的具体目的是：1）对约6，886名ARIC参与者（25%为非洲裔美国人）进行腹主动脉超声检查，这些参与者年龄为67-89岁，预计将于2011-13年参加下一次ARIC检查。基于65岁以上男性中6.1%和女性中1.7%的无症状AAA患病率估计，我们预计在ARIC队列中确定235例未诊断的AAA病例。加上1987-2011年期间先前诊断的临床病例，我们预计总共有475例AAA。2)研究AAA与先前在ARIC中测量的潜在新风险因素或在1987- 89年ARIC基线时收集的储存血液样本中测量的潜在新风险因素的相关性。具体而言，我们将评估以下类别中的新生物标志物：（a）细胞外基质重塑;（B）细胞外基质降解;（c）炎症;和（d）血栓形成。本研究将是第一项在随访超过20年的大型、基于人群的中年成人队列中全面评价新风险因素在AAA病因学中的作用的研究。在ARIC内进行这项研究利用了ARIC广泛表征的队列，现有的生物样本对当前项目来说是免费的，并且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 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.