TY - JOUR
T1 - Plasma Desmosine and Abdominal Aortic Aneurysm Disease
AU - Mordi, Ify
AU - Forsythe, Rachael
AU - Gellatly, Corry
AU - Iskandar, Zaid
AU - McBride, Olivia
AU - Saratzis, Athanasios
AU - Chalmers, Rod
AU - Chin, Calvin W. L.
AU - Bown, Matthew J.
AU - Newby, David E.
AU - Lang, Chim
AU - Huang, Jeffrey
AU - Choy, Anna
N1 - 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.
PY - 2019/10/15
Y1 - 2019/10/15
N2 - 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.
AB - 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.
KW - abdominal aortic aneurysm
KW - aortic rupture
KW - desmosine
KW - elastin
UR - http://www.scopus.com/inward/record.url?scp=85073049986&partnerID=8YFLogxK
U2 - 10.1161/JAHA.119.013743
DO - 10.1161/JAHA.119.013743
M3 - Article
C2 - 31595818
VL - 8
SP - 1
EP - 9
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
SN - 2047-9980
IS - 20
M1 - e013743
ER -