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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
Publishing year: 2019-01
Language: English
Pages: 118-123
Publication/Series: Journal of Internal Medicine
Volume: 285
Issue: 1
Document type: Journal article
Publisher: Wiley-Blackwell Publishing Ltd

Abstract english

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.


  • Cardiac and Cardiovascular Systems
  • atherosclerosis
  • biomarkers
  • collagen
  • extracellular matrix
  • inflammation


  • Cardiovascular Research - Immunity and Atherosclerosis
  • Cardiovascular Research - Matrix and Inflammation in Atherosclerosis
  • ISSN: 0954-6820
E-mail: jan [dot] nilsson [at] med [dot] lu [dot] se

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