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

doi:10.1093/eurheartj/ehy566.P6040

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 language	English
Article number	ehy566.P6040
Pages (from-to)	1253-1254
Journal	European Heart Journal
Volume	39
Issue number	Suppl 1
DOIs	https://doi.org/10.1093/eurheartj/ehy566.P6040
Publication status	Published - Aug 2018
Event	ESC Congress 2018 - Munich, Germany Duration: 25 Aug 2018 → … https://academic.oup.com/eurheartj/issue/39/suppl_1

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Mordi, I., Forsythe, R., Bown, M., Lang, C., Newby, D. E., Gellatly, C., Chin, C. W. L., McBride, O., Saratzis, A., Iskandar, Z., Chalmers, R., Huang, J., & Choy, A. (2018). The novel biomarker plasma desmosine, a marker of elastin breakdown, is an independent predictor of abdominal aortic aneurysm events independent of aneurysm size. European Heart Journal, 39(Suppl 1), 1253-1254. Article ehy566.P6040. https://doi.org/10.1093/eurheartj/ehy566.P6040

@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",

year = "2018",

month = aug,

doi = "10.1093/eurheartj/ehy566.P6040",

language = "English",

volume = "39",

pages = "1253--1254",

journal = "European Heart Journal",

issn = "0195-668X",

publisher = "Oxford University Press",

number = "Suppl 1",

note = "ESC Congress 2018 ; Conference date: 25-08-2018",

url = "https://academic.oup.com/eurheartj/issue/39/suppl\_1",

}

Mordi, I, Forsythe, R, Bown, M, Lang, C, Newby, DE, Gellatly, C, Chin, CWL, McBride, O, Saratzis, A, Iskandar, Z, Chalmers, R, Huang, J & Choy, A 2018, 'The novel biomarker plasma desmosine, a marker of elastin breakdown, is an independent predictor of abdominal aortic aneurysm events independent of aneurysm size', European Heart Journal, vol. 39, no. Suppl 1, ehy566.P6040, pp. 1253-1254. https://doi.org/10.1093/eurheartj/ehy566.P6040

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

Research output: Contribution to journal › Meeting abstract › peer-review

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

SN - 0195-668X

VL - 39

SP - 1253

EP - 1254

JO - European Heart Journal

JF - European Heart Journal

IS - Suppl 1

M1 - ehy566.P6040

T2 - ESC Congress 2018

Y2 - 25 August 2018

ER -

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

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