Abstract Body (Do not enter title and authors here): Introduction: The prevalence of abdominal aortic aneurysms(AAA) is at least twice as high in patients with coronary artery disease(CAD), and about half of the AAA-patients have clinically relevant CAD. Detecting concomitant disease and intervening on pathophysiological mechanisms could potentially improve survival in these patients.
Research Questions: Which circulating biomarkers and biological mechanisms can distinguish AAA and CAD?
Aims: To differentiate the circulating proteomic profiles and biological pathways associated with AAA and CAD.
Methods: Patients with AAA and/or stable CAD from two prospective cohort studies were age, sex, and comorbidity matched 1:1:1 (AAA only, AAA and CAD, CAD only). 369 plasma proteins were simultaneously measured in both cohorts using the Olink Explore Cardiometabolic I panel. We investigated differences in proteomic profiles using univariable linear regression and multivariable logistic elastic net regression. Differences in biomarker interactions(pathways) were studied through differential network analysis.
Results: Each matched group consisted of 53 patients. Overall, the mean age was 70 years and 92% were men. In AAA-patients, the baseline median(25^th-75^th percentile) maximum diameter was 46(43,50) mm. The proteins IRAG2 and CORO1A were significantly downregulated in AAA-patients with CAD, compared to AAA only. After multivariable selection, only IRAG2 was independently associated with the presence of CAD in AAA-patients. Protein interactions in six pathways differed in AAA-patients with CAD, compared to AAA only(Figure 1A). Moreover, the IGFBP7, CD59, REG1A and CST3 proteins were univariably, significantly upregulated in CAD-patients with AAA, compared to CAD only. Multivariable selection in the proteomic profile proposed PLA2G2A, CD59 and REG1A as independently informative biomarkers for the presence of AAA in CAD-patients. In 14 biological pathways, proteins interacted differently in CAD-patients with AAA, compared to CAD only(Figure 1B).
Conclusion(s): A small set of proteins differed between phenotypes. While the average level of most biomarkers was the same, many protein interactions, in pathways implied in AAA by basic research, differed between AAA- and CAD-patients.