Plasma Desmosine and Abdominal Aortic Aneurysm Disease

Ify Mordi; Rachael  Forsythe; Corry  Gellatly; Zaid Iskandar; Olivia  McBride; Athanasios  Saratzis; Rod  Chalmers; Calvin W. L. Chin; Matthew J. Bown; David E. Newby; Chim Lang; Jeffrey Huang; Anna Choy

doi:10.1161/JAHA.119.013743

Plasma Desmosine and Abdominal Aortic Aneurysm Disease

Ify Mordi, Rachael Forsythe, Corry Gellatly, Zaid Iskandar, Olivia McBride, Athanasios Saratzis, Rod Chalmers, Calvin W. L. Chin, Matthew J. Bown, David E. Newby, Chim Lang, Jeffrey Huang (Lead / Corresponding author), Anna Choy (Lead / Corresponding author)

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Abstract

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.

Original language	English
Article number	e013743
Number of pages	9
Journal	Journal of the American Heart Association Cardiovascular and Cerebrovascular Disease (JAHA)
Volume	8
Issue number	20
Early online date	9 Oct 2019
DOIs	https://doi.org/10.1161/JAHA.119.013743
Publication status	Published - 15 Oct 2019

Keywords

abdominal aortic aneurysm
aortic rupture
desmosine
elastin

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1161/JAHA.119.013743Licence: CC BY-NC

Final Published VersionFinal published version, 572 KBLicence: CC BY-NC

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Mordi, I., Forsythe, R., Gellatly, C., Iskandar, Z., McBride, O., Saratzis, A., Chalmers, R., Chin, C. W. L., Bown, M. J., Newby, D. E., Lang, C., Huang, J., & Choy, A. (2019). Plasma Desmosine and Abdominal Aortic Aneurysm Disease. Journal of the American Heart Association Cardiovascular and Cerebrovascular Disease (JAHA), 8(20), Article e013743. https://doi.org/10.1161/JAHA.119.013743

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title = "Plasma Desmosine and Abdominal Aortic Aneurysm Disease",

abstract = "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.",

keywords = "abdominal aortic aneurysm, aortic rupture, desmosine, elastin",

author = "Ify Mordi and Rachael Forsythe and Corry Gellatly and Zaid Iskandar and Olivia McBride and Athanasios Saratzis and Rod Chalmers and Chin, {Calvin W. L.} and Bown, {Matthew J.} and Newby, {David E.} and Chim Lang and Jeffrey Huang and Anna Choy",

note = "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.",

year = "2019",

month = oct,

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doi = "10.1161/JAHA.119.013743",

language = "English",

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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

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DO - 10.1161/JAHA.119.013743

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JO - Journal of the American Heart Association Cardiovascular and Cerebrovascular Disease (JAHA)

JF - Journal of the American Heart Association Cardiovascular and Cerebrovascular Disease (JAHA)

IS - 20

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ER -

Plasma Desmosine and Abdominal Aortic Aneurysm Disease

Abstract

Keywords

ASJC Scopus subject areas

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Desmosine as a Prognostic Marker in Aortic Aneurysm (joint with University of Edinburgh)

Identifying Novel Opportunities for Translational Research, Precision Medicine and Drug Repurposing in Cardiovascular Disease using Pharmacoepidemiology, Genetic Epidemiology and Bioinformatics

Blood test raises hopes of tackling 'silent killer'

Amino acid blood test illuminates abdominal aneurysms

Huang, Jeffrey

Cite this

Plasma Desmosine and Abdominal Aortic Aneurysm Disease

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Projects

Desmosine as a Prognostic Marker in Aortic Aneurysm (joint with University of Edinburgh)

Identifying Novel Opportunities for Translational Research, Precision Medicine and Drug Repurposing in Cardiovascular Disease using Pharmacoepidemiology, Genetic Epidemiology and Bioinformatics

Press/Media

Blood test raises hopes of tackling 'silent killer'

Amino acid blood test illuminates abdominal aneurysms

Profiles

Huang, Jeffrey

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