Thoracic aortic aneurysms in abdominal aortic aneurysm patients and their relatives

This thesis aims to explore the frequency of TAA in AAA patients and their relatives, and
whether family history and DNA testing can help predict TAA in these groups. As only a small
fraction of AA patients with a family history can be explained with pathogenic gene variants,
many additional aneurysm-related P/LPs should still be identified. While collagens are known
to play a critical role in aortic integrity, the precise types and quantities of collagens within the
aortic wall remain poorly characterized. Systematic investigation of collagen diversity in the
aorta may provide new insights into collagens which function in the aorta, thereby expanding
our understanding of potential genetic susceptibilities in AAs.
In Chapter 2, we retrospectively include 516 consecutively diagnosed AAA and TAAA
patients who underwent multiple CT scans—with or without contrast—of the entire aorta at
Erasmus MC between 2009 and 2018. We examine the effects of sex, genetic predisposition
for aneurysms (familial aneurysm or P/LP in known aneurysm genes), and cardiovascular risk
factors (age, smoking, hypertension, hypercholesterolemia) on the risk of TAA. Five-year
survival is used to assess whether TAAs influence survival in AAA patients. Chapter 3 presents
a retrospective analysis of non-contrast CT scans of the entire aorta from 301 relatives of 115
AAA index patients at Erasmus MC (2016–2021). Systematic measurements of these scans
help identify aneurysms. Family histories and DNA testing of AAA index cases were used to
classify relatives as having high genetic risk (multiple aneurysm patients in the family or an
index case with a P/LP in an aneurysm gene) or unknown genetic risk (a single aneurysm index case without a P/LP). This chapter explores whether relatives of AAA patients might also face
an elevated risk of TAA, which could provide important insights that might contribute to new
guideline recommendations for TAA screening in this population.
Chapter 4 explores the current knowledge of the different types of collagens present in
the aorta, including their structure, functions and interactions to provide novel understanding
on how these collagens might play a role in the homeostasis of the aorta and how pathogenic
variants in the genes could potentially contribute to aortic aneurysm disease. This chapter also
reviews which factors regulate expression of these collagens and which of their genetic
variants are associated with disease to further support exploring such new genetic variants as
they might relate to aortic diseases. Finally, Chapter 5 and 6 summarize and discuss the key
findings of these studies and provides future perspectives.