The abdominal aortic aneyrism : Clinical outcomes in EVAR and longitudinal biobank studies

Abstract

This thesis has been divided in 6 parts. Part I of this thesis focuses on AAA wall biology, rupture risk, and the value of AAA biobanks. Endoluminal stenting is currently the treatment of choice for AAA patients because of the relatively low rate of short-term complications. AAA biopsies from a patient treated by endoluminal stenting is not possible. This development underscores the value of AAA Biobanks to investigate AAA pathophysiology (Chapter 2). The second part of this thesis consists out of pathophysiological studies that are related with clinical features. Many studies have identified AAA biomarkers in blood but most of them have not been validated or investigated in AAA specimen. Chapter 3 describes a marker named osteoprotegerin in AAA specimen, and shows its correlation with AAA diameter. Furthermore, the marker seems to be closely associated with the adaptive immune system, which is believed to play an yet unidentified role in (advanced) AAA disease. Chapter 4 focuses on diabetes and AAA disease. Because diabetics seem to be protected against AAA development and growth, we investigated differences in non-diabetics and diabetics with AAA disease. Specifically, the role of glycated cross-linking is investigated via multiple ex vivo studies, and related to non-diabetics versus diabetics with AAA disease. Chapter 5 focuses on the strongest risk factor for AAA development, growth, and rupture to date: smoking. This chapter shows clear distinct features in collagen structure of smokers compared with non-smokers via 3D confocal reconstructions, Picro-Sirius stainings, which might be related to neutrophil activity as shown with biochemical quantifications. Part III of this thesis highlights the association of AAA disease with atherosclerotic events. Patients with AAA disease often have and increased risk for cardiovascular events. In Chapter 6, we have investigated a marker named osteopontin, and related this marker to postoperative cardiovascular events in patients, which underwent an open repair of their AAA. This study was executed in order to identify AAA patients who are at high-risk for cardiovascular events, and thereby could benefit from aggressive treatment. Part IV focuses on association of AAA pathophysiology with imaging features of the AAA. Due to an increasing role of endoluminal stenting there is a need to relate pathophysiological processes with imaging features of the AAA. The results of these studies might be employed in endovascular therapies. Chapter 7 shows that intraluminal thrombus thickness as with CT-angiography associates with AAA wall disruption. Part V of this thesis focuses on endovascular aneurysm repair (EVAR) as an important upcoming treatment method for AAA disease and its clinical outcome. In Chapter 8 the effect of smoking on AAA outcome after EVAR treatment is reported. Chapter 9 describes AAA behavior and rupture risk after EVAR in patients with growing AAA but without a detectable endoleak. Part VI concludes this thesis providing a general discussion, future perspectives, and summary in Chapter 10.