Abstract
BackgroundRupture 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.ObjectiveIn 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.MethodsSections 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.ResultsPRO‐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).ConclusionPRO‐C6 is present in the atherosclerotic plaque and associated with future cardiovascular events, cardiovascular death and all‐cause mortality in two large prospective cohorts.
Highlights
Despite recent advancements in treatments for atherosclerotic diseases, the clinical consequences of stroke and myocardial infarction are still the major causes of mortality and morbidity worldwide [1]
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
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
Summary
Despite recent advancements in treatments for atherosclerotic diseases, the clinical consequences of stroke and myocardial infarction are still the major causes of mortality and morbidity worldwide [1]. There is a need for novel biomarkers which may reflect plaque vulnerability and the risk for recurrent events, and which may help the design of individually tailored treatment strategies [2]. The rupture of an atherosclerotic plaque is the major cause of acute cardiovascular events These events tend to occur in patients with vulnerable plaques, of the rupture-prone type, which have a large lipid-rich core, a thin fibrous cap and an increased inflammatory cell infiltration [3, 4]. 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
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