Date of Award
Open Access Thesis
Medical Doctor (MD)
John A. Elefteriades
This project investigates the clinical occurrence of concurrent thoracic aortic aneurysms (TAA) and intracranial aneurysms (ICA). We hypothesized that patients with a TAA have an increased risk of harboring a concurrent ICA, and likewise that patients with an ICA have an increased risk of harboring a concurrent TAA relative to the general population. In a separate arm of this project, we hypothesized that a pre-defined gene expression profile, based on the expression levels of 41 specific genes measured in peripheral blood cells, will exhibit a characteristic expression pattern in ICA patients and thereby have utility in detecting the presence of ICA.
To accomplish the first objective of this project, we reviewed the charts of patients with TAA who also had recent intracranial imaging to document the prevalence of concurrent ICA and compared this rate to the ICA prevalence in the general population. Likewise, we reviewed the charts of patients with ICA who also had recent thoracic imaging to document the prevalence of concurrent TAA. To investigate the gene expression profile for detecting ICA, we collected peripheral blood samples from ICA patients and non- aneurysmal controls and measured the expression levels of 39 pre-defined genes in a signature aneurysm profile using real-time PCR. The observed pattern of expression of these genes was compared to a pre-defined signature aneurysm pattern to predict the aneurysm status of each sample.
We found that 9.0% of 212 TAA patients we studied harbor a concurrent ICA. Patients with descending TAA and hypertension had significantly higher rates of concurrent ICA. We also found that 4.5% of 359 ICA patients we studied harbor a concurrent TAA. ICA patients over 70 years of age had an increased rate of concurrent TAA. We also analyzed gene expression in the blood samples of 17 ICA patients and 15 controls. By comparing the observed pattern of gene expression to a predefined signature aneurysm pattern, we were able to detect ICA from a peripheral blood test with an 88% sensitivity and overall accuracy of 63%.
In conclusion, this project finds that patients with TAA are at an increased risk relative to the general population of harboring a concurrent ICA. Likewise, patients with ICA are at an increased risk relative to the general population of harboring a concurrent TAA. Our early results show that a peripheral blood test based on the gene expression pattern of 39 genes holds promise as a sensitive screening test for ICA.
Kuzmik, Gregory, "Correlations Between Intracranial Aneurysms And Thoracic Aortic Aneurysms" (2013). Yale Medicine Thesis Digital Library. 1812.