Abdominal aortic aneurysm (AAA) rupture is the 13th leading cause of death among individuals aged 65-85.1 Small AAA growth and rupture are highly variable between patients and over time. 2,3 Individual AAA growth is typically discontinuous, characterized by alternating periods of growth and non-growth,4-9 with a higher rate of rupture noted in women.10-14 As an alternative, we hypothesize that AAA contrast ultrasound (CUS) microbubble imaging will detect AAA wall inflammation and neovascularization with vasa vasorum (VV). Along with serum biomarker testing, it will allow the early identification of patients with a vulnerable AAA wall at risk for growth or rupture. Our team is uniquely equipped to test this hypothesis, given the expertise of my collaborators in this line f work. Specifically, Dr. Vorp, in collaboration with the division of Vascular Surgery at the University of Pittsburgh, has extensive expertise in AAA imaging and pathobiology, and Drs. Reis and Villanueva have extensive expertise in CUS, with nearly 850 patients imaged with carotid CUS as part of ongoing clinical trials. In addition, Dr. Makaroun is a renowned aortic surgeon with a high volume clinical practice, and Dr. Resnick is an established geriatrician investigator. Their clinical and scientific collaborations will provide the necessary expertise in aging related aortic research.
The aims of this study include: The unpredictable behavior of AAA makes the current ultrasound surveillance standard unreliable in predicting AAA growth or rupture, since it relies on absolute AAA diameter as a marker of disease severity.
Aim#1 : To prospectively study a cohort of patients with AAA of 4-5.4cm in major axis diameter with CUS imaging at 6 month intervals for 18 months, to determine the relationship between growth rate and VV density. Hypothesis: unstable AAA has a higher VV density on CUS.
Aim#2 : To test gender differences in CUS and biomarker findings, and rate of growth and rupture. Hypothesis: women are at higher risk of AAA growth and rupture, and have higher aortic wall VV density than men.
Aim#3 : To test AAA specific serum biomarkers. CUS findings will be correlated with serum biomarkers, as well as AAA wall histology in patients who require surgical repair. Hypothesis: levels of serum biomarkers correlate with VV density and are more elevated in unstable AAA. Impact and significance: Non-invasively detecting areas of neovascularization within the aneurysm wall identifies regional inflammation, and propensity for weakening, enlargement or rupture. This novel longitudinal evaluation of the aortic wall in patients with an AAA will advance the understanding of aging-related AAA behavior, and will allow individualized treatment based on the biologic potential for growth and rupture.

Public Health Relevance

This novel longitudinal evaluation of the aortic wall in patients with an AAA will advance the understanding of aging-related AAA behavior. It will improve the care of the geriatric patient with AAA by allowing individualized treatment based on the biologic potential for growth and rupture.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Small Research Grants (R03)
Project #
1R03AG042352-01
Application #
8341058
Study Section
Special Emphasis Panel (ZAG1-ZIJ-9 (M1))
Program Officer
Zieman, Susan
Project Start
2012-08-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
1
Fiscal Year
2012
Total Cost
$76,250
Indirect Cost
$26,250
Name
University of Pittsburgh
Department
Surgery
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213