Targeting growth rate of abdominal aortic aneurysm

Abstract

This thesis focuses on growth inhibition of small abdominal aortic aneurysms (AAA), which is a potentially lethal, pathological dilatation of 30 mm or more of the infrarenal aorta. The main clinical challenges are currently: Can we predict aneurysm growth? Is it possible to keep small aneurysms small? Can we translate the preclinical evidence into a medical therapy? On theoretical grounds and preclinical data, doxycycline appears an excellent lead-candidate for the medical stabilization of growing AAA. However, this randomized placebo controlled multicentre trial revealed that doxycycline treatment did not inhibit aneurysm progression but increased the growth rate. These highly remarkable findings fundamentally challenge the current paradigm that inflammation per se is harmful in AAA progression. In this context, other findings of this thesis gain importance, showing that patients with diabetes mellitus have slower aneurysm growth and that aneurysm patients are more likely to develop COPD. The responsible pathophysiological mechanisms contain undoubtedly important clues, but have to be unraveled yet.