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

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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.; Edsfeldt, A.; Brix, S.; Genovese, F.; Bengtsson, E.; Karsdal, M.; Leeming, D. J.; Nilsson, J.; Goncalves, I.

I: Journal of Internal Medicine, Vol. 285, Nr. 1, 01.2019, s. 118-123.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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

AU - Holm Nielsen, S.

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 - 2019/1

Y1 - 2019/1

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 - Article

VL - 285

SP - 118

EP - 123

JO - Journal of Internal Medicine

T2 - Journal of Internal Medicine

JF - Journal of Internal Medicine

SN - 1365-2796

IS - 1

ER -