Aortic aneurysms: an immune disease with a strong genetic component.

In the United States, aortic aneurysms are the 13th leading cause of death.1,2 Approximately 15 000 individuals die every year because of the rupture of aortic aneurysms. On the basis of autopsy studies, it has been estimated that 1% to 2% of the population harbor aneurysms in their aorta, with up to 10% prevalence in older age groups.1,2 Most aortic aneurysms go undetected until rupture, and the mortality from ruptured aneurysms is as high as 90%.1,2 Along the length of the aorta, significant heterogeneity occurs in the distribution of aneurysm disease. The prevalence of abdominal aortic aneurysms (AAAs) located in the infrarenal section of the aorta is at least 3 times higher than that of thoracic aortic aneurysms and dissections (TAADs).1,2 In TAADs, 50% involve the ascending aorta, 10% the arch, and 40% the descending thoracic aorta.1,2 Only 25% of patients with TAAD have a concomitant AAA, and multisegmental disease is found in only 10% of cases.1,2 There are also other differences between TAAD and AAA: (1) Age at onset for TAAD (65 years) is 10 years earlier than for AAA (75 years), and (2) AAAs are predominantly a disease of white men, with a 6:1 male-to-female ratio, whereas TAADs occur only slightly more frequently in men (1.7:1). Additional differences can be found in the pathobiology of these aneurysms. AAAs are characterized by signs of local chronic inflammation of the aortic wall, decrease in the number of smooth muscle cells in the aortic media layer, and fragmentation of the extracellular matrix of the aorta at the site of the aneurysm.3 Increased local expression of proinflammatory cytokines and matrix metalloproteinases (MMPs) have also been demonstrated.3 Furthermore, AAAs can be induced in a surgical experimental model in which elastases are infused into rodent aorta.4 TAADs are characterized by medial necrosis, also known as “Erdheim’s cystic medial necrosis” and more recently referred to as “medial degeneration,” mucoid infiltration, and cyst formation with elastin degradation and vascular smooth muscle cell apoptosis.1 Both TAAD and AAA are silent diseases, often without symptoms.2 They can, however, be readily identified through imaging techniques. TAADs can be detected by echocardiography or computed tomography, and family members of TAAD patients will benefit from imaging by identifying their TAADs before catastrophic consequences. Presently, there are no recommendations about large-scale screening of populations for TAAD. On the other hand, for AAA, ultrasonography screening studies have demonstrated the costeffectiveness of population-based ultrasonography screening programs and a decrease in the number of aneurysm-related deaths.5 Several recommendations have been made, including a recent consensus statement in which Kent et al6 recommended ultrasonography screening for AAA for all individuals aged 60 years and for those aged 50 years with family history of AAA and the recommendation by the US Preventive Service Task Force7 to screen for AAA in men aged 65 to 75 years who have ever smoked.