Abstract 4142622: Circulating biomarkers of collagen type-I degradation are associated with risk of mortality after ST-elevated myocardial infarction.

Introduction: Extracellular matrix (ECM) remodelling is a critical consequence of ST-elevated myocardial infarction (STEMI). Type-I collagen (COL1) is the main constituent of the myocardium, and its’ degradation could result in destabilisation of the cardiac tissue and increase the risk of adverse events. Aim: We sought to quantify circulating peptides reflecting COL1 degradation in STEMI patients. Methods: COL1 degradation was measured using two enzyme-linked immunosorbent assays (ELISA) targeting MMP-generated fragments of COL1 (C1M and C1SIG) in plasma of 1,464 patients admitted with STEMI from the PREDICT-CS study (72.7% male, median age: 63.5) (Rigshospitalet, Denmark). Survival analysis and Cox proportional hazard analysis were used to determine the association the biomarker to mortality within 1-year of STEMI. Results: C1M and C1SIG were lowly correlated (R = 0.204, p < 0.0001). Patients with circulating levels of C1M and C1SIG above the median at a higher mortality risk at 1-year post-admission, compared to those with biomarker levels below the median (C1M: p = 0.0006, C1SIG: p < 0.0001, Log-rank test). Univariate Cox proportional regression analysis showed a 90% increase in risk of death per doubling of C1M and a 120% increased risk of death per doubling of C1SIG over 1-year (C1M: HR 1.9 [1.6-2.4], C1SIG: HR 2.2 [1.6-3.0], both: p <0.001). In Model 1 (adjusment for age, sex, hypercholesterolemia, blood pressure, diabetes, and smoking), C1M and C1SIG retained the association with risk of mortality (C1M: HR 1.6 [1.2-2.0], C1SIG: HR 2.2 [1.5-3.1], both: p <0.001). In Model 2, including Model 1 and the cardiac and inflammatory markers MR pro-adrenomedullin, Copeptin, proANP, ST2 and CRP, C1SIG, but not C1M, continued to remain an independent predictor of mortality over 1-year (HR 1.9 [1.2-3.0], p <0.001 for C1SIG; HR 1.4 [0.9-1.9], p = 0.109 for C1M). Conclusion: Circulating levels of C1M and C1SIG showed a significant and independent association with risk of mortality in STEMI patients after 1 year, in a multivariate model based on the Framingham Score. The association was retained for C1SIG after adjustment for markers of cardiac injury and inflammation. Assessing acute ECM processing in STEMI patients using COL1 biomarkers could be beneficial for predicting mortality and identifying a patient-subset at increased risk of long-term outcome.