Female sex and genetic predisposition determine risk of thoracic aneurysms in abdominal aortic aneurysm patients

Abstract Introduction Aneurysms of the thoracic aorta (TAA) occur more frequently in abdominal aortic aneurysm (AAA) patients than in the general population. The aim of the study was to investigate which AAA patients have an increased risk of developing TAA or thoraco-abdominal aortic aneurysm (TAAA), and if sex, genetic susceptibility for aneurysms, or conventional cardiovascular risk factors affect this risk. Methods Repeated CT scans from consecutively diagnosed AAA patients were evaluated retrospectively to determine the prevalence, sequence and location of multiple aortic aneurysms (Figure 1). Effects of sex, genetic predisposition for aneurysms (familial aneurysm, the presence of (likely) pathogenic variants in known aneurysm genes) and cardiovascular risk factors (age, smoking, hypertension, diabetes mellitus and hypercholesterolemia) on risk for TAA were analysed using absolute diameter and aortic size index (ASI). ASI (ASI=diameter (mm)/BSA) was based on the mean BSA in our study population (1.94) and aortic diameter definitions from the ESC and AHA/ACC guidelines. This resulted in an ascending TAA-ASI cut-off value of 23.2 for an aortic diameter of 45 mm, and a descending TAA-ASI cut-off value of 20.5 for an aortic diameter of 40 mm. Five-year survival was used to evaluate the impact of having thoracic aneurysms on survival of AAA patients. Results On the first CT scan 10.8% of AAA patients had a TAA (Figure 1). During a median follow-up of 7 years, an additional 5.1% of AAA patients developed TAA and 2.4% developed TAAA. Only older age (71 vs 74, p=0.043) and no other traditional cardiovascular risk factors affected thoracic aneurysm prevalence. However, female patients had a two- to four-fold increase in risk for TAA (Table 1): for the descending aorta when based on absolute diameters and in all locations when based on ASI. A twofold increase in risk for ascending TAA was observed in AAA patients reporting familial aneurysms when based on absolute diameter (9.8 vs 4.6% p=0.04), but this was not observed when analysed based on ASI. The number of pathogenic variants (n=12) was too small to draw conclusions. The 5-year survival of female TAAA patients was lower than that of female AAA patients (44% vs 72%, p=0.02), independent of having a TAA. Conclusions Female AAA patients had a two-to-four-fold increase in risk for TAA, particularly in the descending aorta. Familial AAA patients had a two-fold increase in aneurysm risk for ascending aortic aneurysms. TAAA patients had a lower survival, compared to AAA±TAA patients, especially among female TAAA patients. As TAA and TAAA could develop during follow-up, follow up imaging of both the ascending and descending aorta after diagnosis of AAA may improve early detection of multiple aneurysms.Figure 1, study population Table 1, prevalence of TAA per location