School of Medicine Publications and Presentations
Document Type
Article
Publication Date
4-12-2022
Abstract
Background
The underlying mechanisms of arterial stiffness remain not fully understood. This study aimed to identify a urinary proteomic profile to illuminate its pathogenesis and to determine the prognostic value of the profile for adverse outcomes.
Methods and Results
We measured aortic stiffness using pulse wave velocity (PWV) and analyzed urinary proteome using capillary electrophoresis coupled with mass spectrometry in 669 randomly recruited Flemish patients (mean age, 50.2 years; 51.1% women). We developed a PWV‐derived urinary proteomic score (PWV‐UP) by modeling PWV with proteomics data at baseline through orthogonal projections to latent structures. PWV‐UP that consisted of 2336 peptides explained the 65% variance of PWV, higher than 36% explained by clinical risk factors. PWV‐UP was significantly associated with PWV (adjusted β=0.73 [95% CI, 0.67–0.79]; P<0.0001). Over 9.2 years (median), 36 participants died, and 75 experienced cardiovascular events. The adjusted hazard ratios (+1 SD) were 1.46 (95% CI, 1.08–1.97) for all‐cause mortality, 2.04 (95% CI, 1.07–3.87) for cardiovascular mortality, and 1.39 (95% CI, 1.11–1.74) for cardiovascular events (P≤0.031). For PWV, the corresponding estimates were 1.25 (95% CI, 0.97–1.60), 1.35 (95% CI, 0.85–2.15), and 1.22 (95% CI, 1.02–1.47), respectively (P≥0.033). Pathway analysis revealed that the peptides in PWV‐UP mostly involved multiple pathways, including collagen turnover, cell adhesion, inflammation, and lipid metabolism.
Conclusions
PWV‐UP was highly associated with PWV and could be used as a biomarker of arterial stiffness. PWV‐UP, but not PWV, was associated with all‐cause mortality and cardiovascular mortality, implying that PWV‐UP–associated peptides may be multifaceted and involved in diverse pathological processes beyond arterial stiffness.
Recommended Citation
Wei, D., Melgarejo, J. D., Thijs, L., Temmerman, X., Vanassche, T., Van Aelst, L., ... & Zhang, Z. Y. (2022). Urinary proteomic profile of arterial stiffness is associated with mortality and cardiovascular outcomes. Journal of the American Heart Association, 11(8), e024769. https://doi.org/10.1161/JAHA.121.024769
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Publication Title
Journal of the American Heart Association
DOI
10.1161/JAHA.121.024769
Academic Level
faculty
Mentor/PI Department
Neuroscience
Comments
© 2022 The Authors.