Hugo Bernelin1, Nathan Mewton2,3, Salim Si-Mohamed4,5, Pierre Croisille6,7, Gilles Rioufol8,9, Eric Bonnefoy-Cudraz1,9, Philippe Douek4,5, Nathalie Dufay10, Camille Amaz3, Claire Jossan3, Michel Ovize2,3,9, Thomas Bochaton1,9. 1. Unité de Soins Intensifs Cardiologiques, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France. 2. Service d'explorations fonctionnelles Cardiovasculaires, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France. 3. Centre d'Investigation Clinique de Lyon, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France. 4. Imagerie Cardiovasculaire-Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France. 5. INSERM U1044, CREATIS-UMR CNRS 5220 Laboratory, Université de Lyon, Lyon, France. 6. Département de Radiologie, CHU Saint-Etienne, Université Jean-Monnet, Saint-Étienne, France. 7. Univ Lyon, UJM-Saint-Etienne, INSA, CNRS UMR 5520, INSERM U1206, CREATIS, Saint-Étienne, France. 8. Unité de Cardiologie Interventionnelle, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France. 9. INSERM U1060, CarMeN Laboratory, Université de Lyon, Groupement Hospitalier Est, Bron, France. 10. NeuroBioTec, Groupement Hospitalier Est, Hôpital Neurologique Pierre Wertheimer, Lyon, France.
Abstract
BACKGROUND: Several preliminary analyses suggested an association between neprilysin (NEP) levels and myocardial infarction. HYPOTHESIS: The objective was to assess whether NEP plasma levels following reperfusion might be a surrogate for infarct size (IS) or predict adverse outcomes in acute ST-segment elevation myocardial infarction (STEMI) patients. METHODS: We measured NEP levels in a prospective cohort of 203 patients with STEMI referred for primary percutaneous coronary intervention. Circulating soluble NEP was measured by enzyme-linked immunosorbent assay at admission (t0) and 4 hours later (t4) following reperfusion and on 7 times points (t0, t4, t12, t24, t48, day 7 and day 30) in a subset of 21 patients. IS and left ventricular ejection fraction (LVEF) were measured at 1 month by cardiac magnetic resonance. Adverse cardiovascular outcomes were collected at 12-month follow-up. RESULTS: Median t0 and t4 NEP levels in 203 patients were respectively 88.3 pg/mL (interquartile range [IQR] [14; 375.4]) and 101.5 pg/mL (IQR [18.5; 423.8]). These levels remained unchanged over 1 month (P = 0.70). NEP levels did not correlate significantly with IS (P = 0.51) or LVEF (P = 0.34). There was no correlation between NEP and troponin, creatine kinase and interleukin-6 levels at h0 and h4. NEP levels above the median were not associated with adverse outcomes at follow-up (hazard ratio = 1.28, 95% confidence interval [0.69; 2.37]; P = 0.42). CONCLUSIONS: NEP serum levels were widely distributed and did not change significantly in the first hours and 1-month period following reperfusion in STEMI patients. There was no significant relationship with markers of infarct size and inflammation, and 1-year adverse outcomes.
BACKGROUND: Several preliminary analyses suggested an association between neprilysin (NEP) levels and myocardial infarction. HYPOTHESIS: The objective was to assess whether NEP plasma levels following reperfusion might be a surrogate for infarct size (IS) or predict adverse outcomes in acute ST-segment elevation myocardial infarction (STEMI) patients. METHODS: We measured NEP levels in a prospective cohort of 203 patients with STEMI referred for primary percutaneous coronary intervention. Circulating soluble NEP was measured by enzyme-linked immunosorbent assay at admission (t0) and 4 hours later (t4) following reperfusion and on 7 times points (t0, t4, t12, t24, t48, day 7 and day 30) in a subset of 21 patients. IS and left ventricular ejection fraction (LVEF) were measured at 1 month by cardiac magnetic resonance. Adverse cardiovascular outcomes were collected at 12-month follow-up. RESULTS: Median t0 and t4 NEP levels in 203 patients were respectively 88.3 pg/mL (interquartile range [IQR] [14; 375.4]) and 101.5 pg/mL (IQR [18.5; 423.8]). These levels remained unchanged over 1 month (P = 0.70). NEP levels did not correlate significantly with IS (P = 0.51) or LVEF (P = 0.34). There was no correlation between NEP and troponin, creatine kinase and interleukin-6 levels at h0 and h4. NEP levels above the median were not associated with adverse outcomes at follow-up (hazard ratio = 1.28, 95% confidence interval [0.69; 2.37]; P = 0.42). CONCLUSIONS:NEP serum levels were widely distributed and did not change significantly in the first hours and 1-month period following reperfusion in STEMI patients. There was no significant relationship with markers of infarct size and inflammation, and 1-year adverse outcomes.
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