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Collagen type I degradation peptide as a predictive biomarker for mortality in ST-elevated myocardial infarction
Emily M Martin1,2, Elisavet Angeli3,4, Federica Genovese3
1Nordic Bioscience A/S, Herlev Hovedgade 205, 2730, Herlev, Denmark. emma@nordicbio.com.
Insights
Collagen type I degradation biomarkers, C1M and C1SIG, increase after ST-elevated myocardial infarction (STEMI). High C1M levels independently predict 1-year mortality in STEMI patients, offering prognostic value beyond existing risk scores.
Area of Science:
- Cardiovascular Medicine
- Biomarker Discovery
- Extracellular Matrix Research
Background:
- ST-elevated myocardial infarction (STEMI) causes significant tissue remodeling and extracellular matrix (ECM) changes, increasing heart failure and mortality risk.
- Collagen type I, a major cardiac ECM component, degrades rapidly at STEMI injury sites.
- Previous research suggests a collagen type I-derived signalling peptide (C1SIG) is involved in left ventricular remodeling post-myocardial infarction (MI).
Purpose of the Study:
- To evaluate the prognostic potential of a novel collagen type I-derived signalling peptide (C1SIG) biomarker in a large STEMI cohort.
- To compare the prognostic capability of C1SIG against the established collagen type I fragment biomarker, C1M.
- To assess the predictive value of these biomarkers for all-cause mortality within one year post-STEMI.
Main Methods:
- Plasma C1SIG and C1M levels were measured using enzyme-linked immunosorbent assays in 1616 STEMI patients upon hospital admission.
- Patients were followed for one year to record all-cause mortality.
- Survival analyses, including univariate and multivariate Cox proportional hazard regression, were performed to assess prognostic significance.
Main Results:
- Both C1M and C1SIG levels significantly increased from admission up to 12 hours post-STEMI.
- Elevated levels of both C1M (highest quartile) and C1SIG (median) were associated with reduced one-year survival probability.
- C1M emerged as an independent predictor of one-year mortality in multivariate analysis (HR [95% CI] 1.46 [1.15-1.85]) and provided added value to the GRACE risk score.
Conclusions:
- C1M and C1SIG are dynamic biomarkers reflecting collagen type I degradation following STEMI.
- C1SIG is also implicated as a potential collagen signaling molecule.
- C1M is a significant independent predictor of all-cause mortality within one year after 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.
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