The novel collagen matrikine, endotrophin, is associated with mortality and cardiovascular events in patients with atherosclerosis. (5th May 2021)

• Record Type: Journal Article
• Authors: Holm Nielsen, S.; Edsfeldt, A.; Tengryd, C.; Gustafsson, H.; Shore, A. C.; Natali, A.; Khan, F.; Genovese, F.; Bengtsson, E.; Karsdal, M.; Leeming, D. J.; Nilsson, J.; Goncalves, I.
• Is Part Of: Journal of internal medicine. Volume 290:Number 1(2021)
• Page Start: 179
• Page End: 189
• Publication Date: 2021-05-05
• Subjects: atherosclerosis -- biomarkers -- collagen -- endotrophin -- extracellular matrix -- inflammation; Internal medicine -- Periodicals; Medicine -- Periodicals; 616
• DOI: 10.1111/joim.13253
• Languages: English
• ISSNs: 0954-6820

Abstract

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 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. Abstract :