Aortic Aneurysm Formation

The development of a saccular (nondissecting) aortic aneurysm follows the destruction of the connective tissue in the media, in particular the elastic lamellae. The vessel wall is then unable to withstand the expansile force of each systolic contraction. The current view is that the great majority of aortic aneurysms, .90% of which are below the renal arteries, are associated with atherosclerosis. This view is based on the fact that the lower abdominal aorta is the site at which atherosclerosis first develops and confluent intimal involvement becomes common by middle age. Resected abdominal aortic aneurysms show advanced atherosclerosis with mural thrombus in the wall. This view, however, is a paradox in that atherosclerosis is an intimal disease, whereas in the abdominal aorta, aneurysms are due to major medial damage. There are also other reasons to believe that aortic aneurysms have an additional component to their pathogenesis. Abdominal aortic aneurysms are familial and under genetic influences unrelated to lipid-related risk factors for atherosclerosis. First-degree relatives of index cases with abdominal aortic aneurysms have a significantly higher risk of developing a similar lesion when compared with the general population. Prospective family studies suggest a figure of 14.5% for offspring and 13% to 32% for siblings compared with the general population risk of 2% to 5%. Risk factors such as elevated plasma cholesterol, hypertriglyceridemia, hypertension, and smoking are found in many subjects with abdominal aortic aneurysms, yet 60% of cases have plasma cholesterol levels of ,240 mg/dL. Smoking is the single largest external contributor to the risk of aortic aneurysm formation. These data suggest that there are additional factors involved in aortic aneurysm formation. Some of the factors are genetic. A very small subgroup of saccular aneurysms are due to genes controlling connective tissue structural proteins. The fibrillin gene is largely responsible for dissection of the aorta, but occasional families with saccular abdominal aneurysms are known. Defects in the collagen III gene, responsible for the Ehlers Danlos type IV syndrome, occasionally lead to isolated aortic aneurysms, but a large genetic survey suggested that ,2% of human aortic abdominal aneurysms were due to defects in type III collagen. A potential locus for aortic saccular aneurysms has been identified on chromosome 16 at or close to the haptoglobin gene, which might enhance elastic degradation, but the exact mechanism is unclear.