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The novel collagen matrikine, endotrophin, is associated with mortality and cardiovascular events in patients with atherosclerosis

Holm Nielsen, S. ; Edsfeldt, A. LU ; Tengryd, C. LU ; Gustafsson, H. LU ; Shore, A. C. ; Natali, A. ; Khan, F. ; Genovese, F. ; Bengtsson, E. LU orcid and Karsdal, M. , et al. (2021) In Journal of Internal Medicine 290(1). p.179-189
Abstract

Background: Rupture of atherosclerotic plaques is the major cause of acute cardiovascular events. The biomarker PRO-C6 measuring Endotrophin, a matrikine of collagen type VI, may provide valuable information detecting subjects in need of intensified strategies for secondary prevention. Objective: In this study, we evaluate endotrophin in human atherosclerotic plaques and circulating levels of PRO-C6 in patients with atherosclerosis, to determine the predictive potential of the biomarker. Methods: Sections from the stenotic human carotid plaques were stained with the PRO-C6 antibody. PRO-C6 was measured in serum of patients enrolled in the Carotid Plaque Imagining Project (CPIP) (discovery cohort, n = 577) and the innovative medicines... (More)

Background: Rupture of atherosclerotic plaques is the major cause of acute cardiovascular events. The biomarker PRO-C6 measuring Endotrophin, a matrikine of collagen type VI, may provide valuable information detecting subjects in need of intensified strategies for secondary prevention. Objective: In this study, we evaluate endotrophin in human atherosclerotic plaques and circulating levels of PRO-C6 in patients with atherosclerosis, to determine the predictive potential of the biomarker. Methods: Sections from the stenotic human carotid plaques were stained with the PRO-C6 antibody. PRO-C6 was measured in serum of patients enrolled in the Carotid Plaque Imagining Project (CPIP) (discovery cohort, n = 577) and the innovative medicines initiative surrogate markers for micro- and macrovascular hard end-points for innovative diabetes tools (IMI-SUMMIT, validation cohort, n = 1,378). Median follow-up was 43 months. Kaplan–Meier curves and log-rank tests were performed in the discovery cohort. Cox proportional hazard regression analysis (HR with 95% CI) was used in the discovery cohort and binary logistic regression (OR with 95% CI) in the validation cohort. Results: PRO-C6 was localized in the core and shoulder of the atherosclerotic plaque. In the discovery cohort, PRO-C6 independently predicted future cardiovascular events (HR 1.089 [95% CI 1.019 −1.164], p = 0.01), cardiovascular death (HR 1.118 [95% CI 1.008 −1.241], p = 0.04) and all-cause death (HR 1.087 [95% CI 1.008 −1.172], p = 0.03). In the validation cohort, PRO-C6 predicted future cardiovascular events (OR 1.063 [95% CI 1.011 −1.117], p = 0.017). Conclusion: PRO-C6 is present in the atherosclerotic plaque and associated with future cardiovascular events, cardiovascular death and all-cause mortality in two large prospective cohorts.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
atherosclerosis, biomarkers, collagen, endotrophin, extracellular matrix, inflammation
in
Journal of Internal Medicine
volume
290
issue
1
pages
179 - 189
publisher
Wiley-Blackwell
external identifiers
  • scopus:85105079011
  • pmid:33951242
ISSN
0954-6820
DOI
10.1111/joim.13253
language
English
LU publication?
yes
id
56283a0a-3ea4-43ae-91cd-825600af64d3
date added to LUP
2021-05-31 12:02:32
date last changed
2024-06-15 11:46:28
@article{56283a0a-3ea4-43ae-91cd-825600af64d3,
  abstract     = {{<p>Background: Rupture of atherosclerotic plaques is the major cause of acute cardiovascular events. The biomarker PRO-C6 measuring Endotrophin, a matrikine of collagen type VI, may provide valuable information detecting subjects in need of intensified strategies for secondary prevention. Objective: In this study, we evaluate endotrophin in human atherosclerotic plaques and circulating levels of PRO-C6 in patients with atherosclerosis, to determine the predictive potential of the biomarker. Methods: Sections from the stenotic human carotid plaques were stained with the PRO-C6 antibody. PRO-C6 was measured in serum of patients enrolled in the Carotid Plaque Imagining Project (CPIP) (discovery cohort, n = 577) and the innovative medicines initiative surrogate markers for micro- and macrovascular hard end-points for innovative diabetes tools (IMI-SUMMIT, validation cohort, n = 1,378). Median follow-up was 43 months. Kaplan–Meier curves and log-rank tests were performed in the discovery cohort. Cox proportional hazard regression analysis (HR with 95% CI) was used in the discovery cohort and binary logistic regression (OR with 95% CI) in the validation cohort. Results: PRO-C6 was localized in the core and shoulder of the atherosclerotic plaque. In the discovery cohort, PRO-C6 independently predicted future cardiovascular events (HR 1.089 [95% CI 1.019 −1.164], p = 0.01), cardiovascular death (HR 1.118 [95% CI 1.008 −1.241], p = 0.04) and all-cause death (HR 1.087 [95% CI 1.008 −1.172], p = 0.03). In the validation cohort, PRO-C6 predicted future cardiovascular events (OR 1.063 [95% CI 1.011 −1.117], p = 0.017). Conclusion: PRO-C6 is present in the atherosclerotic plaque and associated with future cardiovascular events, cardiovascular death and all-cause mortality in two large prospective cohorts.</p>}},
  author       = {{Holm Nielsen, S. and Edsfeldt, A. and Tengryd, C. and Gustafsson, H. and Shore, A. C. and Natali, A. and Khan, F. and Genovese, F. and Bengtsson, E. and Karsdal, M. and Leeming, D. J. and Nilsson, J. and Goncalves, I.}},
  issn         = {{0954-6820}},
  keywords     = {{atherosclerosis; biomarkers; collagen; endotrophin; extracellular matrix; inflammation}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{1}},
  pages        = {{179--189}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Internal Medicine}},
  title        = {{The novel collagen matrikine, endotrophin, is associated with mortality and cardiovascular events in patients with atherosclerosis}},
  url          = {{http://dx.doi.org/10.1111/joim.13253}},
  doi          = {{10.1111/joim.13253}},
  volume       = {{290}},
  year         = {{2021}},
}