Identifying Epidemiological Risk Factors for Abdominal Aortic Aneurysm

描述（申请人提供）：腹主动脉瘤（AAA）是老年人常见病，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。选择性手术或血管内修复是唯一有效的AAA干预措施，目前还没有特定的药物被证明对预防或减少普通人群的AAA进展有效。AAA的病因是复杂的，并不是很清楚。虽然传统的心血管危险因素与AAA的风险相关，但它们在AAA病因学中的重要性尚未得到很好的确定。此外，新的发病机制如细胞外基质重塑和降解、炎症和血栓形成已被假设，但它们的作用尚未适当确定。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，以在这个以人群为基础的大队列中识别未确诊的AAA病例。此外，这些病例将与已经通过医院记录确定的265例现有病例和将通过医疗保险联系确定的病例汇总在一起。利用ARIC基线时已收集的危险因素和血浆样本，我们将在这一随访超过20年的大型前瞻性队列中开展AAA的流行病学研究。该应用程序的具体目的是：1)对约6,886名ARIC参与者进行腹主动脉超声检查，其中25%是非裔美国人，年龄在67-89岁之间，预计在2011-13年参加下一次ARIC检查。根据65岁以上男性无症状AAA患病率估计为6.1%，女性为1.7%，我们预计在ARIC队列中发现235例未确诊的AAA病例。结合1987-2011年之前诊断的临床病例，我们预计总共有475例AAAs。2)探讨AAA与ARIC中先前测量的潜在新危险因素或1987- 1989年ARIC基线收集的储存血液样本中测量的潜在新危险因素的关系。具体来说，我们将评估以下类别的新型生物标志物：(a)细胞外基质重塑；(b)细胞外基质降解；(c)炎症;(d)血栓形成。这项研究将是第一个全面评估新的危险因素在AAA病因学中的作用的研究，该研究是在一个大型的、以人群为基础的中年人队列中进行的，随访超过20年。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经济有效的方法来建立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.