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Plasma Desmosine and Abdominal Aortic Aneurysm Disease.

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posted on 23.10.2019, 11:33 by IR Mordi, RO Forsythe, C Gellatly, Z Iskandar, OM McBride, A Saratzis, R Chalmers, C Chin, MJ Bown, DE Newby, CC Lang, JTJ Huang, A-M Choy
Background It is recognized that factors beyond aortic size are important in predicting outcome in abdominal aortic aneurysm (AAA) disease. AAA is characterized by the breakdown of elastin within the aortic tunica media, leading to aortic dilatation and rupture. The aim of this study was to investigate the association of plasma desmosine (pDES), an elastin-specific degradation product, with disease severity and clinical outcome in patients with AAA. Methods and Results We measured pDES and serum biomarker concentrations in 507 patients with AAAs (94% men; mean age, 72.4±6.1 years; mean AAA diameter, 48±8 mm) and 162 control subjects (100% men; mean age, 71.5±4.4 years) from 2 observational cohort studies. In the longitudinal cohort study (n=239), we explored the incremental prognostic value of pDES on AAA events. pDES was higher in patients with AAA compared with control subjects (mean±SD: 0.46±0.22 versus 0.33±0.16 ng/mL; P<0.001) and had the strongest correlation with AAA diameter (r=0.39; P<0.0001) of any serum biomarker. After adjustment for baseline AAA diameter, pDES was associated with an AAA event (hazard ratio, 2.03 per SD increase [95% CI, 1.02-4.02]; P=0.044). In addition to AAA diameter, pDES provided incremental improvement in risk stratification (continuous net reclassification improvement, 34.4% [95% CI, -10.8% to 57.5%; P=0.09]; integrated discrimination improvement, 0.04 [95% CI, 0.00-0.15; P=0.050]). Conclusions pDES concentrations predict disease severity and clinical outcomes in patients with AAA. Clinical Trial Registration http://www.isrctn.com. Unique identifier: ISRCTN76413758.

Funding

This study was supported by a Tenovus Scotland Major Research Grant (T17/22) and a Chief Scientist Office Catalytic Grant (CGA/17/07). Dr Mordi is supported by a National Health Service Education for Scotland/Chief Scientist Office Postdoctoral Clinical Lectureship (PCL 17/07). Dr Iskandar is supported by a Tenovus Scotland Major Research Grant (T17/22). The MA3RS (Magnetic Resonance Imaging for Abdominal Aortic Aneurysms to Predict Rupture or Surgery) study was funded by the Medical Research Council and managed by the National Institute of Healthcare Research on behalf of the Medical Research Council–National Institute of Healthcare Research partnership (National Institute of Healthcare Research Efficacy and Mechanism Evaluation Program: funding reference 11/20/03). Dr Newby is supported by the British Heart Foundation (CH/09/002, RE/13/3/30183, and RM/13/2/30158) and is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr McBride is supported by the Academic Department of Military Surgery and Trauma. The UKAGS (UK Aneurysm Growth Study) was funded by the British Heart Foundation (CS/14/2/30841) and the Circulation Foundation. Dr Saratzis is funded by the National Institute for Health Research and Academy of Medical Sciences (SGCL13). Dr Bown is funded by the British Heart Foundation, National Institute for Health Research, and The Dunhill Trust.

History

Citation

Journal of the American Heart Association, 2019;8:e013743.

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

Version

VoR (Version of Record)

Published in

Journal of the American Heart Association

Publisher

Wiley, American Heart Association: JAHA , American Stroke Association

eissn

2047-9980

Acceptance date

06/09/2019

Copyright date

2019

Available date

23/10/2019

Publisher version

https://www.ahajournals.org/doi/10.1161/JAHA.119.013743

Language

en

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