A biomarker of collagen type I degradation is associated with cardiovascular events and mortality in patients with atherosclerosis

S. Holm Nielsen*, C. Tengryd, A. Edsfeldt, S. Brix, F. Genovese, E. Bengtsson, M. Karsdal, D. J. Leeming, J. Nilsson, I. Goncalves

*Corresponding author for this work

Research output: Contribution to journalJournal articleCommunication

Abstract

Objective Atherosclerosis is characterized by accumulation of lipids, cells and extracellular matrix (ECM) proteins in the arterial wall. Collagen type I (COL1), a component of the arterial ECM, is cleaved by matrix metalloproteinases (MMPs) and known to be remodelled in atherosclerosis. We explored whether the MMP-mediated COL1 biomarker, C1M, was associated with cardiovascular events, cardiovascular mortality and all-cause mortality in a large prospective cohort of patients with known atherosclerosis. Methods Serum from 787 patients who underwent a carotid endarterectomy was included. Circulating levels of C1M were measured in serum. A total of 473 patients were followed for 6 years after surgery. Associations between C1M and incidence of cardiovascular events, cardiovascular mortality and all-cause mortality were assessed by Kaplan-Meier curves and Cox regression analysis. Results A total of 101 (21.4%) patients suffered from nonfatal cardiovascular events during the follow-up period, and 64 (13.5%) patients died. Of these, 39 (60.9%) died from cardiovascular diseases. Patients with C1M levels above the median were significantly associated with cardiovascular events, cardiovascular mortality and all-cause mortality (P < 0.001, P = 0.004 and P < 0.001, respectively). C1M was included in the final model for prediction of cardiovascular events (HR 2.15, 95% CI 1.40-3.32, P = 0.001), cardiovascular mortality (HR 2.20, 95% CI 1.07-4.51, P = 0.031) and all-cause mortality (HR 2.98 95% CI 1.67-5.33, P = < 0.001). Conclusions In patients with atherosclerotic carotid lesions, high levels of C1M predicted cardiovascular events, cardiovascular mortality and all-cause mortality. These findings emphasize the importance of remodelling mechanisms in atherosclerosis that are now becoming more and more explored.
Original languageEnglish
JournalJournal of Internal Medicine
Volume285
Issue number1
Pages (from-to)118-123
Number of pages6
ISSN0954-6820
DOIs
Publication statusPublished - 2019

Keywords

  • Atherosclerosis
  • Biomarkers
  • Collagen
  • Extracellular matrix
  • Inflammation

Cite this

Nielsen, S. Holm ; Tengryd, C. ; Edsfeldt, A. ; Brix, S. ; Genovese, F. ; Bengtsson, E. ; Karsdal, M. ; Leeming, D. J. ; Nilsson, J. ; Goncalves, I. / A biomarker of collagen type I degradation is associated with cardiovascular events and mortality in patients with atherosclerosis. In: Journal of Internal Medicine. 2019 ; Vol. 285, No. 1. pp. 118-123.
@article{91dac2402db741d6a7b54ef63d1be733,
title = "A biomarker of collagen type I degradation is associated with cardiovascular events and mortality in patients with atherosclerosis",
abstract = "Objective Atherosclerosis is characterized by accumulation of lipids, cells and extracellular matrix (ECM) proteins in the arterial wall. Collagen type I (COL1), a component of the arterial ECM, is cleaved by matrix metalloproteinases (MMPs) and known to be remodelled in atherosclerosis. We explored whether the MMP-mediated COL1 biomarker, C1M, was associated with cardiovascular events, cardiovascular mortality and all-cause mortality in a large prospective cohort of patients with known atherosclerosis. Methods Serum from 787 patients who underwent a carotid endarterectomy was included. Circulating levels of C1M were measured in serum. A total of 473 patients were followed for 6 years after surgery. Associations between C1M and incidence of cardiovascular events, cardiovascular mortality and all-cause mortality were assessed by Kaplan-Meier curves and Cox regression analysis. Results A total of 101 (21.4{\%}) patients suffered from nonfatal cardiovascular events during the follow-up period, and 64 (13.5{\%}) patients died. Of these, 39 (60.9{\%}) died from cardiovascular diseases. Patients with C1M levels above the median were significantly associated with cardiovascular events, cardiovascular mortality and all-cause mortality (P < 0.001, P = 0.004 and P < 0.001, respectively). C1M was included in the final model for prediction of cardiovascular events (HR 2.15, 95{\%} CI 1.40-3.32, P = 0.001), cardiovascular mortality (HR 2.20, 95{\%} CI 1.07-4.51, P = 0.031) and all-cause mortality (HR 2.98 95{\%} CI 1.67-5.33, P = < 0.001). Conclusions In patients with atherosclerotic carotid lesions, high levels of C1M predicted cardiovascular events, cardiovascular mortality and all-cause mortality. These findings emphasize the importance of remodelling mechanisms in atherosclerosis that are now becoming more and more explored.",
keywords = "Atherosclerosis, Biomarkers, Collagen, Extracellular matrix, Inflammation",
author = "Nielsen, {S. Holm} and C. Tengryd and A. Edsfeldt and S. Brix and F. Genovese and E. Bengtsson and M. Karsdal and Leeming, {D. J.} and J. Nilsson and I. Goncalves",
year = "2019",
doi = "10.1111/joim.12819",
language = "English",
volume = "285",
pages = "118--123",
journal = "Journal of Internal Medicine",
issn = "0954-6820",
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Nielsen, SH, Tengryd, C, Edsfeldt, A, Brix, S, Genovese, F, Bengtsson, E, Karsdal, M, Leeming, DJ, Nilsson, J & Goncalves, I 2019, 'A biomarker of collagen type I degradation is associated with cardiovascular events and mortality in patients with atherosclerosis', Journal of Internal Medicine, vol. 285, no. 1, pp. 118-123. https://doi.org/10.1111/joim.12819

A biomarker of collagen type I degradation is associated with cardiovascular events and mortality in patients with atherosclerosis. / Nielsen, S. Holm; Tengryd, C.; Edsfeldt, A.; Brix, S.; Genovese, F.; Bengtsson, E.; Karsdal, M.; Leeming, D. J.; Nilsson, J.; Goncalves, I.

In: Journal of Internal Medicine, Vol. 285, No. 1, 2019, p. 118-123.

Research output: Contribution to journalJournal articleCommunication

TY - JOUR

T1 - A biomarker of collagen type I degradation is associated with cardiovascular events and mortality in patients with atherosclerosis

AU - Nielsen, S. Holm

AU - Tengryd, C.

AU - Edsfeldt, A.

AU - Brix, S.

AU - Genovese, F.

AU - Bengtsson, E.

AU - Karsdal, M.

AU - Leeming, D. J.

AU - Nilsson, J.

AU - Goncalves, I.

PY - 2019

Y1 - 2019

N2 - Objective Atherosclerosis is characterized by accumulation of lipids, cells and extracellular matrix (ECM) proteins in the arterial wall. Collagen type I (COL1), a component of the arterial ECM, is cleaved by matrix metalloproteinases (MMPs) and known to be remodelled in atherosclerosis. We explored whether the MMP-mediated COL1 biomarker, C1M, was associated with cardiovascular events, cardiovascular mortality and all-cause mortality in a large prospective cohort of patients with known atherosclerosis. Methods Serum from 787 patients who underwent a carotid endarterectomy was included. Circulating levels of C1M were measured in serum. A total of 473 patients were followed for 6 years after surgery. Associations between C1M and incidence of cardiovascular events, cardiovascular mortality and all-cause mortality were assessed by Kaplan-Meier curves and Cox regression analysis. Results A total of 101 (21.4%) patients suffered from nonfatal cardiovascular events during the follow-up period, and 64 (13.5%) patients died. Of these, 39 (60.9%) died from cardiovascular diseases. Patients with C1M levels above the median were significantly associated with cardiovascular events, cardiovascular mortality and all-cause mortality (P < 0.001, P = 0.004 and P < 0.001, respectively). C1M was included in the final model for prediction of cardiovascular events (HR 2.15, 95% CI 1.40-3.32, P = 0.001), cardiovascular mortality (HR 2.20, 95% CI 1.07-4.51, P = 0.031) and all-cause mortality (HR 2.98 95% CI 1.67-5.33, P = < 0.001). Conclusions In patients with atherosclerotic carotid lesions, high levels of C1M predicted cardiovascular events, cardiovascular mortality and all-cause mortality. These findings emphasize the importance of remodelling mechanisms in atherosclerosis that are now becoming more and more explored.

AB - Objective Atherosclerosis is characterized by accumulation of lipids, cells and extracellular matrix (ECM) proteins in the arterial wall. Collagen type I (COL1), a component of the arterial ECM, is cleaved by matrix metalloproteinases (MMPs) and known to be remodelled in atherosclerosis. We explored whether the MMP-mediated COL1 biomarker, C1M, was associated with cardiovascular events, cardiovascular mortality and all-cause mortality in a large prospective cohort of patients with known atherosclerosis. Methods Serum from 787 patients who underwent a carotid endarterectomy was included. Circulating levels of C1M were measured in serum. A total of 473 patients were followed for 6 years after surgery. Associations between C1M and incidence of cardiovascular events, cardiovascular mortality and all-cause mortality were assessed by Kaplan-Meier curves and Cox regression analysis. Results A total of 101 (21.4%) patients suffered from nonfatal cardiovascular events during the follow-up period, and 64 (13.5%) patients died. Of these, 39 (60.9%) died from cardiovascular diseases. Patients with C1M levels above the median were significantly associated with cardiovascular events, cardiovascular mortality and all-cause mortality (P < 0.001, P = 0.004 and P < 0.001, respectively). C1M was included in the final model for prediction of cardiovascular events (HR 2.15, 95% CI 1.40-3.32, P = 0.001), cardiovascular mortality (HR 2.20, 95% CI 1.07-4.51, P = 0.031) and all-cause mortality (HR 2.98 95% CI 1.67-5.33, P = < 0.001). Conclusions In patients with atherosclerotic carotid lesions, high levels of C1M predicted cardiovascular events, cardiovascular mortality and all-cause mortality. These findings emphasize the importance of remodelling mechanisms in atherosclerosis that are now becoming more and more explored.

KW - Atherosclerosis

KW - Biomarkers

KW - Collagen

KW - Extracellular matrix

KW - Inflammation

U2 - 10.1111/joim.12819

DO - 10.1111/joim.12819

M3 - Journal article

VL - 285

SP - 118

EP - 123

JO - Journal of Internal Medicine

JF - Journal of Internal Medicine

SN - 0954-6820

IS - 1

ER -