Abstract Body: Biologic mechanisms that underpin growth and rupture risk for abdominal aortic aneurysms remain elusive due, in part, to lack of high-fidelity pre-clinical models and decreasing access to pathologic tissue. The gold standard diagnostic practice relies on imaging to measure the maximum transverse diameter (MTD) of the aneurysm. The goal of this study was to identify plasma proteins that predict future aneurysm growth. Using a longitudinal study design where all patients had centrally read computerized tomography scans, we analyzed plasma samples at baseline usiing mass spectrometry and growth rates over two years in patients with AAA. We evaluated 113 baseline samples for proteins predicting 2-year growth rates calculated from MTD change (no or low growth, n=80 vs. high growth, n=33). There were 49 proteins upregulated and 5 downregulated in the high growth group (all p<0.05). Partial Least Squares Discriminant Analysis (PLS-DA, Image 1) showed separation between the two groups. Baseline CRP measured by mass spectrometry was 1.6 fold increased in the high growth group (p=0.04), connecting inflammation and growth. Rab3 GTPase-activating protein non-catalytic subunit (2-fold); Acyl-coenzyme A synthetase ACSM5, mitochondrial (2-fold); and Receptor-type tyrosine-protein phosphatase S (1.8-fold) were the top 3 upregulated proteins in the high growth rate group. ACSM5 also correlated with MTD slope (r=0.36; p=0.00009). Hemoglobin subunit gamma-2 (0.7-fold); Tubulin-specific chaperone A (0.5-fold); and Plakophilin-4 (0.5-fold) were the top 3 downregulated proteins in the high growth rate group. With the exception of CRP, these findings reveal previously unrecognized associations with AAA growth, which demonstrates the potential value of careful AAA longitudinal morphometry to develop new disease insights. Establishing circulating markers of future AAA growth may provide immediate clinical value and may also provide unique insights into biologic mechanisms of the disease itself.