Targeted plasma multi-omics propose glutathione, glycine and serine as biomarkers for abdominal aortic aneurysm growth on serial CT scanning
Alexander Vanmaele, Elke Bouwens, Sanne E. Hoeks, Alida Kindt, Lieke Lamont, Bram Fioole, Ricardo P.J. Budde, Sander Ten Raa, Burhan Hussain, José Oliveira‐Pinto, Arne IJpma, Felix van Lier, K. Martijn Akkerhuis, Daniëlle Majoor‐Krakauer, Jorg L. de Bruin, Thomas Hankemeier, Yolanda B. de Rijke, Hence J.M. Verhagen, Eric Boersma, Isabella Kardys
Abstract
Abdominal aortic aneurysm (AAA) patients undergo uniform imaging surveillance until reaching the surgical threshold. In spite of the ongoing exploration of AAA pathophysiology, biomarkers for personalized surveillance are lacking. This study aims to identify potential circulating biomarkers for AAA growth on serial CT scans. Patients with an AAA (maximal diameter ≥40 mm) were included in this multicentre, prospective cohort study. Participants underwent baseline blood sampling and yearly CT-imaging to determine AAA diameter and volume. Proteins and metabolites were measured using proximity extension assay (Olink Cardiovascular III) or separate ELISA panels, and mass-spectrometry (LC-TQMS), respectively. Linear mixed-effects, orthogonal partial least squares, and Cox regression were used to explore biomarker associations with AAA volume growth rate and the risk of surpassing the surgical threshold, as formulated by current guidelines. 271 biomarkers (95 proteins, 176 metabolites) were measured in 109 (90.8 % male) patients with mean age 72. Median baseline maximal AAA diameter was 47.8 mm, volume 109 mL. Mean annual AAA volume growth rate was 11.5 %, 95 % confidence interval (CI) (10.4, 12.7). Median follow-up time was 23.2 months, 49 patients reached the surgical threshold. Patients with one standard deviation (SD) higher glutathione and glycine levels at baseline had an AAA volume growth rate that respectively was 1.97 %, 95%CI (0.97, 2.97) and 1.74 %, 95%CI (0.78, 2.71) larger, relative to the actual aneurysm size. Serine was associated with the risk of reaching the surgical threshold, independent of age and baseline AAA size (cause-specific hazard ratio per SD difference 1.78, 95%CI (1.30, 2.44)). Among multiple intertwined biomarkers related to AAA pathophysiology and progression, glutathione, glycine and serine were most promising. • Plasma multi-omics in 109 AAA patients identified potential biomarkers for AAA progression, measured on serial CT imaging. • Multiple intertwined biomarkers involved in selenoamino acid metabolism were related to the AAA volume growth rate. • Among these markers, glutathione and glycine might be of future interest to predict AAA growth. • Serine could be a promising biomarker for AAA progression beyond the surgical threshold, additional to maximal diameter.