Collagen type I degradation peptide as a predictive biomarker for mortality in ST-elevated myocardial infarction

Background and aims Tissue remodelling and extracellular matrix (ECM) changes are primary consequences of ST-elevated myocardial infarction (STEMI), leading to an increased risk of developing heart failure and mortality. Collagen type I is the top constituent of the cardiac ECM and is rapidly degraded at sites of tissue injury occurring in STEMI. We aimed to investigate the prognostic potential of a novel biomarker of a collagen type I-derived signalling peptide (C1SIG) shown to be involved in left ventricular remodelling after MI and compare this against another collagen type I fragment quantified by the established C1M assay in a large STEMI cohort. Methods Plasma C1SIG and C1M were quantified using specific enzyme-linked immunosorbent assays in 1616 individuals upon admittance to hospital with STEMI. Patients were then followed up for all-cause mortality over 1 year, and survival analyses were performed. Results Short-term biomarker changes assessed in a subgroup ( n = 140) showed increased circulating C1M and C1SIG in the short period from admission with STEMI up to 12 h post-admission (both, p < 0.0001). High C1M levels, defined by the highest quartile, and high C1SIG levels, defined by the median, were associated with reduced survival probability at 1 year (both, p < 0.0001) post-admission. The association was further supported in univariate and maintained for C1M only in multivariate Cox proportional hazard regression models adjusted for multiple confounders (HR [95% CI] 1.46 [1.15–1.85]). Added value analysis determined the additional predictive value of C1M to the clinically used GRACE risk score for cardiovascular event prediction ( p = 0.0002). Conclusion C1M and C1SIG are dynamic biomarkers of collagen type I degradation, where C1SIG is also suspected to be a collagen signal. C1M is an independent predictor of all-cause mortality within a year of a MI.