ARRA IMPACT REPORT:
Aortic Aneurysms: Development of Technologies to Assess Vulnerability of Aortic Aneurysms for Rupture or Dissection
Public Health Burden
Thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) are unpredictable and life-threatening conditions. The most common cause of mortality in TAA is acute dissection of the aorta; in AAA, it is rupture. About 40 percent of individuals with acute dissection die immediately, and another 5-20 percent die during emergency repair surgery or shortly thereafter. Sixty percent of patients presenting at an emergency room with a ruptured AAA die regardless of intervention.
Prognostic Tests for Aortic Aneurysms
In current medical practice, aneurysm diameter is the major factor guiding the timing of elective surgery or endovascular repair for both TAA and AAA. Intervention is recommended for aneurysms larger than 5.5 cm. However, size is not a reliable predictor of potential dissection or rupture; small aortic aneurysms may rupture or dissect unexpectedly, and larger aneurysms may remain stable. More specific methods are needed to determine the optimal timing of surgical and endovascular treatment of aortic aneurysms to avoid emergency or unnecessary major surgery and decrease mortality associated with the conditions.
Measuring Fibrillin and Fibulin Levels to Assess Aortic Dissection Risk: The proteins fibrillin and fibulin are major contributors to the structure and function of the aortic elastic lamellae that characteristically appear damaged in dissected and ruptured aneurysms. ARRA-funded investigators at the University of Washington assayed (analyzed the biochemical activity of) plasma samples from 1,265 individuals with aortic aneurysms to measure the levels of fibrillin-1, fibrillin-2, and fibulin-4 fragments (fibrillin is an important protein in connective tissue). They found that the risk for dissection increased linearly with increasing levels of fibrillin-1 fragments among patients who had only TAAs. The association between fibrillin-1 level and dissection status was not present in patients with mixed aortic aneurysms. Levels of fibrillin-2 or fibulin-4 fragments were not associated with aneurysm type or dissection status1.
New Assays to Measure TGF–ß Levels: Increased transforming growth factor beta (TGF–ß) signaling is a signature of various conditions associated with TAA such as Marfan and Loeys-Dietz syndromes, familial TAA, and bicuspid aortic valve with aortic root aneurysm. ARRA-funded investigators at the Johns Hopkins University developed assays to measure all three TGF–ß isoforms (TGF–ß -1, -2, and - 3) simultaneously in the plasma of patients and mouse models of the conditions. An assay that can measure TGF–ß in human saliva was also developed with ARRA funds. Some of these assays have already been used to generate data for a recent report, published in Nature Genetics.2
Contributing NIH Institutes & Centers
- National Heart, Lung, and Blood Institute (NHLBI)