The novel biomarker plasma desmosine, a marker of elastin breakdown, is an independent predictor of abdominal aortic aneurysm events independent of aneurysm size

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

Research output: Contribution to journalMeeting abstract

Abstract

ntroduction: Abdominal aortic aneurysm (AAA) is the thirteenth leading cause of death and occurs in 5% of men between the ages of 65 and 74 years. Currently, patients at risk for AAA are offered ultrasound screening and surveillance, and when appropriate (size >55mm or expansion rate >10mm/year), elective AAA repair. Despite this surveillance, prediction of patients likely to have AAA rupture is difficult, with many AAAs rupturing before reaching 55mm or having unpredictable expansion rates. A serum biomarker that could predict AAA events would be extremely valuable. Desmosine is an amino acid cross-link that is released into the bloodstream when there is elastin breakdown. We hypothesised that plasma desmosine (pDES) might be associated with events in patients with AAA. Methods: We evaluated pDES levels in 239 patients with AAA recruited to the MA3RS study (NCT01749280). Patients had 6 monthly visits with abdominal ultrasound performed at each visit. A panel of biomarkers related to vascular integrity was also obtained. Patients were followed up for clinical events including AAA rupture, repair and mortality. Results: The cohort was predominantly male (87.4%). Mean AAA diameter was 50.6±8.0mm. pDES was significantly correlated with ultrasound AAA diameter (r=0.27, p<0.0001). In total 13 patients had an emergency AAA event and 20 had MACE (AAA event+CV mortality). pDES was a major predictor of both AAA events (HR 4.97, 95% CI 1.05–23.64, p=0.044) and MACE (HR 5.92, 95% CI 1.73–20.26, p=0.005) independent of AAA diameter, with patients with the highest tertiles of pDES having the worst outcome. pDES was significantly more associated with AAA events than the next best biomarker, MMP-9 (AUC 0.70 vs. 0.60, p<0.001). pDES was associated with improvement in risk prediction when added to AAA diameter with a significant improvement in both net reclassification index (p=0.013) and integrative discrimination increment (p<0.001). Conclusion: pDES was an independent predictor of adverse outcome in patients with AAA and may be the first non-invasive serum biomarker to predict events in this group of patients.
Original languageEnglish
Article numberehy566.P6040
Pages (from-to)1253-1254
JournalEuropean Heart Journal
Volume39
Issue numberSuppl 1
DOIs
Publication statusPublished - Aug 2018
EventESC Congress 2018 - Munich, Germany
Duration: 25 Aug 2018 → …
https://academic.oup.com/eurheartj/issue/39/suppl_1

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Desmosine
Elastin
Abdominal Aortic Aneurysm
Aneurysm
Biomarkers
Aortic Rupture

Cite this

Mordi, Ify ; Forsythe, Rachael ; Bown, Matthew ; Lang, Chim ; Newby, David E. ; Gellatly, Corry ; Chin, Calvin W. L. ; McBride, Olivia ; Saratzis, Athanasios ; Iskandar, Zaid ; Chalmers, Rod ; Huang, Jeffrey ; Choy, Anna. / The novel biomarker plasma desmosine, a marker of elastin breakdown, is an independent predictor of abdominal aortic aneurysm events independent of aneurysm size. In: European Heart Journal. 2018 ; Vol. 39, No. Suppl 1. pp. 1253-1254.
@article{311128cacac84bc6a607687d8372f4ac,
title = "The novel biomarker plasma desmosine, a marker of elastin breakdown, is an independent predictor of abdominal aortic aneurysm events independent of aneurysm size",
abstract = "ntroduction: Abdominal aortic aneurysm (AAA) is the thirteenth leading cause of death and occurs in 5{\%} of men between the ages of 65 and 74 years. Currently, patients at risk for AAA are offered ultrasound screening and surveillance, and when appropriate (size >55mm or expansion rate >10mm/year), elective AAA repair. Despite this surveillance, prediction of patients likely to have AAA rupture is difficult, with many AAAs rupturing before reaching 55mm or having unpredictable expansion rates. A serum biomarker that could predict AAA events would be extremely valuable. Desmosine is an amino acid cross-link that is released into the bloodstream when there is elastin breakdown. We hypothesised that plasma desmosine (pDES) might be associated with events in patients with AAA. Methods: We evaluated pDES levels in 239 patients with AAA recruited to the MA3RS study (NCT01749280). Patients had 6 monthly visits with abdominal ultrasound performed at each visit. A panel of biomarkers related to vascular integrity was also obtained. Patients were followed up for clinical events including AAA rupture, repair and mortality. Results: The cohort was predominantly male (87.4{\%}). Mean AAA diameter was 50.6±8.0mm. pDES was significantly correlated with ultrasound AAA diameter (r=0.27, p<0.0001). In total 13 patients had an emergency AAA event and 20 had MACE (AAA event+CV mortality). pDES was a major predictor of both AAA events (HR 4.97, 95{\%} CI 1.05–23.64, p=0.044) and MACE (HR 5.92, 95{\%} CI 1.73–20.26, p=0.005) independent of AAA diameter, with patients with the highest tertiles of pDES having the worst outcome. pDES was significantly more associated with AAA events than the next best biomarker, MMP-9 (AUC 0.70 vs. 0.60, p<0.001). pDES was associated with improvement in risk prediction when added to AAA diameter with a significant improvement in both net reclassification index (p=0.013) and integrative discrimination increment (p<0.001). Conclusion: pDES was an independent predictor of adverse outcome in patients with AAA and may be the first non-invasive serum biomarker to predict events in this group of patients.",
author = "Ify Mordi and Rachael Forsythe and Matthew Bown and Chim Lang and Newby, {David E.} and Corry Gellatly and Chin, {Calvin W. L.} and Olivia McBride and Athanasios Saratzis and Zaid Iskandar and Rod Chalmers and Jeffrey Huang and Anna Choy",
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The novel biomarker plasma desmosine, a marker of elastin breakdown, is an independent predictor of abdominal aortic aneurysm events independent of aneurysm size. / Mordi, Ify; Forsythe, Rachael ; Bown, Matthew ; Lang, Chim; Newby, David E.; Gellatly, Corry ; Chin, Calvin W. L.; McBride, Olivia ; Saratzis, Athanasios ; Iskandar, Zaid; Chalmers, Rod ; Huang, Jeffrey; Choy, Anna.

In: European Heart Journal, Vol. 39, No. Suppl 1, ehy566.P6040, 08.2018, p. 1253-1254.

Research output: Contribution to journalMeeting abstract

TY - JOUR

T1 - The novel biomarker plasma desmosine, a marker of elastin breakdown, is an independent predictor of abdominal aortic aneurysm events independent of aneurysm size

AU - Mordi, Ify

AU - Forsythe, Rachael

AU - Bown, Matthew

AU - Lang, Chim

AU - Newby, David E.

AU - Gellatly, Corry

AU - Chin, Calvin W. L.

AU - McBride, Olivia

AU - Saratzis, Athanasios

AU - Iskandar, Zaid

AU - Chalmers, Rod

AU - Huang, Jeffrey

AU - Choy, Anna

PY - 2018/8

Y1 - 2018/8

N2 - ntroduction: Abdominal aortic aneurysm (AAA) is the thirteenth leading cause of death and occurs in 5% of men between the ages of 65 and 74 years. Currently, patients at risk for AAA are offered ultrasound screening and surveillance, and when appropriate (size >55mm or expansion rate >10mm/year), elective AAA repair. Despite this surveillance, prediction of patients likely to have AAA rupture is difficult, with many AAAs rupturing before reaching 55mm or having unpredictable expansion rates. A serum biomarker that could predict AAA events would be extremely valuable. Desmosine is an amino acid cross-link that is released into the bloodstream when there is elastin breakdown. We hypothesised that plasma desmosine (pDES) might be associated with events in patients with AAA. Methods: We evaluated pDES levels in 239 patients with AAA recruited to the MA3RS study (NCT01749280). Patients had 6 monthly visits with abdominal ultrasound performed at each visit. A panel of biomarkers related to vascular integrity was also obtained. Patients were followed up for clinical events including AAA rupture, repair and mortality. Results: The cohort was predominantly male (87.4%). Mean AAA diameter was 50.6±8.0mm. pDES was significantly correlated with ultrasound AAA diameter (r=0.27, p<0.0001). In total 13 patients had an emergency AAA event and 20 had MACE (AAA event+CV mortality). pDES was a major predictor of both AAA events (HR 4.97, 95% CI 1.05–23.64, p=0.044) and MACE (HR 5.92, 95% CI 1.73–20.26, p=0.005) independent of AAA diameter, with patients with the highest tertiles of pDES having the worst outcome. pDES was significantly more associated with AAA events than the next best biomarker, MMP-9 (AUC 0.70 vs. 0.60, p<0.001). pDES was associated with improvement in risk prediction when added to AAA diameter with a significant improvement in both net reclassification index (p=0.013) and integrative discrimination increment (p<0.001). Conclusion: pDES was an independent predictor of adverse outcome in patients with AAA and may be the first non-invasive serum biomarker to predict events in this group of patients.

AB - ntroduction: Abdominal aortic aneurysm (AAA) is the thirteenth leading cause of death and occurs in 5% of men between the ages of 65 and 74 years. Currently, patients at risk for AAA are offered ultrasound screening and surveillance, and when appropriate (size >55mm or expansion rate >10mm/year), elective AAA repair. Despite this surveillance, prediction of patients likely to have AAA rupture is difficult, with many AAAs rupturing before reaching 55mm or having unpredictable expansion rates. A serum biomarker that could predict AAA events would be extremely valuable. Desmosine is an amino acid cross-link that is released into the bloodstream when there is elastin breakdown. We hypothesised that plasma desmosine (pDES) might be associated with events in patients with AAA. Methods: We evaluated pDES levels in 239 patients with AAA recruited to the MA3RS study (NCT01749280). Patients had 6 monthly visits with abdominal ultrasound performed at each visit. A panel of biomarkers related to vascular integrity was also obtained. Patients were followed up for clinical events including AAA rupture, repair and mortality. Results: The cohort was predominantly male (87.4%). Mean AAA diameter was 50.6±8.0mm. pDES was significantly correlated with ultrasound AAA diameter (r=0.27, p<0.0001). In total 13 patients had an emergency AAA event and 20 had MACE (AAA event+CV mortality). pDES was a major predictor of both AAA events (HR 4.97, 95% CI 1.05–23.64, p=0.044) and MACE (HR 5.92, 95% CI 1.73–20.26, p=0.005) independent of AAA diameter, with patients with the highest tertiles of pDES having the worst outcome. pDES was significantly more associated with AAA events than the next best biomarker, MMP-9 (AUC 0.70 vs. 0.60, p<0.001). pDES was associated with improvement in risk prediction when added to AAA diameter with a significant improvement in both net reclassification index (p=0.013) and integrative discrimination increment (p<0.001). Conclusion: pDES was an independent predictor of adverse outcome in patients with AAA and may be the first non-invasive serum biomarker to predict events in this group of patients.

UR - https://doi.org/10.1093/eurheartj/ehy566.P6040

U2 - 10.1093/eurheartj/ehy566.P6040

DO - 10.1093/eurheartj/ehy566.P6040

M3 - Meeting abstract

VL - 39

SP - 1253

EP - 1254

JO - European Heart Journal

JF - European Heart Journal

SN - 0195-668X

IS - Suppl 1

M1 - ehy566.P6040

ER -