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ANEURYSM PREVENTION PROJECT
An aneurysm is a focal dilation of a blood vessel involving an increase in diameter of at least 50% as compared to the expected normal diameter. Abdominal aortic aneurysms (AAA) represent one of the most common types of aneurysms encountered in clinical practice. The primary diagnostic code for AAA accounts for approximately 150,000 inpatient admissions per year in the United States . The most recent published data on deaths from the year 2000 show that AAA's composed the tenth leading cause of death among people 55 years of age or older. During the same year more than 30,000 operations for repair of AAA were performed. Most reports cite dramatic differences in mortality rates between elective and emergency operations. However, AAA's are even more lethal in their behavior as a silent killer. Up to 62% of patients with ruptured AAA die before reaching the hospital. Therefore when these prehospital deaths are counted, the overall mortality rate after rupture may exceed 90%.
In addition, thoracic aortic aneurysms (TAA) are defined as involving any portion of the thoracic aorta, while thoracoabdominal aortic aneurysms (TAAA) are more extensive with the distal portion involving all or part of the abdominal aorta. The incidence of TAA are over five cases per 100,000 person-years, thus patients with this entity are not infrequently evaluated by the physician in the outpatient or hospital setting. Since the majority of all types of aneurysms are asymptomatic treatment is directed at the most devastating event, which is aortic rupture. Among patients with TAA who did not undergo surgery, approximately 40% died from rupture (and 30% from coronary artery disease) and the mean survival was less than 3 years.
The modern treatment of all types of aneurysms once diagnosed is surgical replacement of the aneurysm. However, the operation carries a considerable risk for mortality or serious complications, especially in TAA and TAAA. In these categories the operative mortality can be as high as 12% and a particularly troubling complication, paraplegia which related to intraoperative and postoperative spinal cord ischemia can range up to 30%.
The exact pathogenesis of aortic aneurysms has not completely unraveled. It is clear, however, that it involves a series of known and unknown environmental and genetic factors acting over time. A constitutional predisposition to aortic dilation seems to be important, but it is not known exactly which genetic risk factors make a person prone to aortic dilation. Immunohistochemical, biochemical and molecular biological studies on samples of human aneurysms taken at operation have consistently shown large numbers of inflammatory cells in the aortic wall and increase cytokine and protease activity. Matrix metalloproteinases and fibrinolytic enzymes have been found to be more active in aneurysm walls and may be at least in part responsible for the destruction of the elastin and collagen structural matrix. Furthermore, a protein, the aortic aneurysm- associated protein may be chemotactic and through an unknown immunologic mechanism, likely attracts inflammatory cells into the aortic wall. These observations have led to the concept that an inflammatory process and active proteolysis weaken the structural matrix of the aortic wall and the high transmural pulse pressure causes aneurysmal dilation. However, the studies on tissue samples from human aneurysms inevitably deal with a late stage of disease and do not necessarily reflect the conditions that initiated aortic dilation in the first place.
All the above underscore that understanding the cause of aortic aneurysms becomes an important undertaking and particularly if our primary aim is the prevention of any dilation of the aorta. A better understanding of the mechanisms that initiate and contribute to aortic dilation may allow effective pharmacological agents to be developed and reduce the need for surgery.
The aneurysm prevention project at St. Luke's-Roosevelt Hospital presently is involved in the following research projects aimed at the prevention of aneurysm formation and growth:
The identification of genes linked to abdominal and thoracic aortic aneurysm
Evaluation of novel agents for the medical inhibition of aneurysm formation in animal models of abdominal and thoracic aneurysms
The use of special echocardiographic techniques in for the early prediction of aneurysm rupture susceptibility
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