Abdominal aortic aneurysms : identification by self-examination and analysis of variation in matrix metalloproteinases with peak wall stress

Heng, Michael Sern Tser

November 2011

Thesis or dissertation

© 2011 Michael Sern Tser Heng. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.

Abdominal aortic aneurysms (AAAs) cause 5,000 deaths a year in the UK. Self-examination for AAAs may provide an economic and practical solution. Matrix metalloproteinase (MMP) concentration is elevated and levels of their natural inhibitors - Tissue Inhibitors of Matrix Metalloproteinases (TIMPs) are reduced at sites of AAA rupture. Finite element analysis (FEA) of AAAs can define the area of peak wall stress area, the most likely site of rupture in engineering terms.

Study 1
Aim: To assess the effectiveness of self-examination for detection of AAAs compared to ultrasound measurement. The psychological consequences were also evaluated.

6,888(65%) of 10,591 male patients aged ≥65 years who were invited to participate, joined the study.

The sensitivity of self-examination for all AAAs (≥3cm) was 37% and for clinically significant AAAs (≥5cm) was 49%. Specificities were 80% and 79% respectively.

The psychological consequences of screening were assessed with the HAD (Hospital Anxiety and Depression) scale. There was no clinical anxiety or depression but there was a statistically significant reduction in both domains on completion.

Self-examination for AAAs cannot be recommended as an effective screening tool.

Study 2
Aim: To assess the tissue concentration of MMPs & TIMPs in AAAs at the site of peak wall stress.

22 patients undergoing elective AAA repair had FEA performed on their CT scans, identifying the peak stress site. Biopsies from this site and the arteriotomy site were stored at -80°C, and tested for MMP & TIMP concentrations with an enzyme linked immunosorbent assay (ELISA).

No significant difference was found between the 2 sites for MMP2, 8, 9, TIMP1 or 2.

These findings suggest either that the peak stress and rupture sites are geographically different, or that the event of rupture is temporally related to a fundamental biochemical change.

Postgraduate Medical Institute, The University of Hull
Chetter, Ian
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