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

Holm Nielsen, S.; Tengryd, C. LU ; Edsfeldt, A. LU ; Brix, S.; Genovese, F.; Bengtsson, E. LU ; Karsdal, M.; Leeming, D. J.; Nilsson, J. LU and Goncalves, I. LU (2019) In Journal of Internal Medicine 285(1). p.118-123
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
atherosclerosis, biomarkers, collagen, extracellular matrix, inflammation
in
Journal of Internal Medicine
volume
285
issue
1
pages
118 - 123
publisher
Wiley-Blackwell Publishing Ltd
external identifiers
  • scopus:85052818491
ISSN
0954-6820
DOI
10.1111/joim.12819
language
English
LU publication?
yes
id
42b889de-6a9b-4567-b72c-253d20080bcf
date added to LUP
2018-09-28 07:00:28
date last changed
2019-02-20 11:28:08
@article{42b889de-6a9b-4567-b72c-253d20080bcf,
  abstract     = {<p>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 &lt; 0.001, P = 0.004 and P &lt; 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 = &lt; 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.</p>},
  author       = {Holm Nielsen, S. and Tengryd, C. and Edsfeldt, A. and Brix, S. and Genovese, F. and Bengtsson, E. and Karsdal, M. and Leeming, D. J. and Nilsson, J. and Goncalves, I.},
  issn         = {0954-6820},
  keyword      = {atherosclerosis,biomarkers,collagen,extracellular matrix,inflammation},
  language     = {eng},
  number       = {1},
  pages        = {118--123},
  publisher    = {Wiley-Blackwell Publishing Ltd},
  series       = {Journal of Internal Medicine},
  title        = {A biomarker of collagen type I degradation is associated with cardiovascular events and mortality in patients with atherosclerosis},
  url          = {http://dx.doi.org/10.1111/joim.12819},
  volume       = {285},
  year         = {2019},
}