Inflammatory and neutrophil extracellular trap markers to predict cardiac events after ST-segment elevation myocardial infarction.

<h4>Background and aims</h4>Inflammation plays a pivotal role in the pathophysiology of ST-elevation myocardial infarction (STEMI). This involves neutrophil activation and the local release of pro-inflammatory mediators. The formation of neutrophil extracellular traps (NETs) in coronary...

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Main Authors: Ana Blasco, Axel Rosell, Raquel Castejón, Ana Royuela, Charlotte Thålin, Elvira Ramil, Silvia Elorza, María-José Coronado, Paloma Martín, Javier Vázquez, Carolina González-Andrés, Juan M Escudier, Javier Ortega, Carmen Bellas
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Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0319759
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author Ana Blasco
Axel Rosell
Raquel Castejón
Ana Royuela
Charlotte Thålin
Elvira Ramil
Silvia Elorza
María-José Coronado
Paloma Martín
Javier Vázquez
Carolina González-Andrés
Juan M Escudier
Javier Ortega
Carmen Bellas
author_facet Ana Blasco
Axel Rosell
Raquel Castejón
Ana Royuela
Charlotte Thålin
Elvira Ramil
Silvia Elorza
María-José Coronado
Paloma Martín
Javier Vázquez
Carolina González-Andrés
Juan M Escudier
Javier Ortega
Carmen Bellas
author_sort Ana Blasco
collection DOAJ
description <h4>Background and aims</h4>Inflammation plays a pivotal role in the pathophysiology of ST-elevation myocardial infarction (STEMI). This involves neutrophil activation and the local release of pro-inflammatory mediators. The formation of neutrophil extracellular traps (NETs) in coronary thrombosis has been linked to poor short-term prognosis following STEMI, but the usefulness of specific circulating NET components as prognostic markers is unclear. We aimed to evaluate the NET-specific marker nucleosomal citrullinated histone H3 (H3Cit-DNA) and other classical inflammatory markers to predict adverse events after STEMI.<h4>Methods</h4>This is a single-center retrospective cohort study of patients with STEMI undergoing primary percutaneous coronary intervention (PCI) from 2015 to 2019. We analyzed the association between serum H3Cit-DNA levels, double-stranded DNA, and classical inflammatory markers -such us interleukin (IL) 6 and 1β, TNF-α, and C-reactive protein (CRP)- on admission and the occurrence of major cardiovascular events (MACE), including death, reinfarction, urgent revascularization, or heart failure, after STEMI.<h4>Results</h4>A total of 487 patients were studied, of which 380 were men [78%]; mean [SD] age of patients was 63 [13] years, and median [95%CI] follow-up was 5.4 [5.2-5.5] years. Median [IQR] H3Cit level was 179.30 [105.30-281.47] ng/ml. No relevant association was found between H3Cit-DNA levels and 30-day mortality (OR, 1.03 [95%CI, 0.71-1.50], p = 0.861) or MACE (0.98 [0.72-1.32], p = 0.879), Killip class (0.95 [0.74-1.21], p = 0.664), or left ventricular ejection fraction (ref.cat. > 50%; < 35%, RRR 1.01 [95%CI, 0.74-1.38], p = 0.952; 35-50%, 1.26 [1.07-1.48], p = 0.005]. Adding CRP and IL-6 levels as covariates to a model based on classical risk factors significantly improved the prediction of MACE at 30 days after STEMI (IDI 0.13; NRI 0.32, p < 0.05).<h4>Conclusions</h4>Circulating levels of the NET marker H3Cit-DNA at the time of primary PCI were not predictive of cardiovascular events following STEMI. In contrast, the classical inflammatory markers CRP and interleukin-6 significantly enhanced the discriminative capacity of a clinical 30-day risk prediction model. These findings suggest that measuring circulating NET-specific markers may have limited utility in assessing the inflammatory state during the early stages of STEMI.
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spelling doaj-art-9a00930527cf43b288c15504ef07e0b22025-08-20T02:25:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01204e031975910.1371/journal.pone.0319759Inflammatory and neutrophil extracellular trap markers to predict cardiac events after ST-segment elevation myocardial infarction.Ana BlascoAxel RosellRaquel CastejónAna RoyuelaCharlotte ThålinElvira RamilSilvia ElorzaMaría-José CoronadoPaloma MartínJavier VázquezCarolina González-AndrésJuan M EscudierJavier OrtegaCarmen Bellas<h4>Background and aims</h4>Inflammation plays a pivotal role in the pathophysiology of ST-elevation myocardial infarction (STEMI). This involves neutrophil activation and the local release of pro-inflammatory mediators. The formation of neutrophil extracellular traps (NETs) in coronary thrombosis has been linked to poor short-term prognosis following STEMI, but the usefulness of specific circulating NET components as prognostic markers is unclear. We aimed to evaluate the NET-specific marker nucleosomal citrullinated histone H3 (H3Cit-DNA) and other classical inflammatory markers to predict adverse events after STEMI.<h4>Methods</h4>This is a single-center retrospective cohort study of patients with STEMI undergoing primary percutaneous coronary intervention (PCI) from 2015 to 2019. We analyzed the association between serum H3Cit-DNA levels, double-stranded DNA, and classical inflammatory markers -such us interleukin (IL) 6 and 1β, TNF-α, and C-reactive protein (CRP)- on admission and the occurrence of major cardiovascular events (MACE), including death, reinfarction, urgent revascularization, or heart failure, after STEMI.<h4>Results</h4>A total of 487 patients were studied, of which 380 were men [78%]; mean [SD] age of patients was 63 [13] years, and median [95%CI] follow-up was 5.4 [5.2-5.5] years. Median [IQR] H3Cit level was 179.30 [105.30-281.47] ng/ml. No relevant association was found between H3Cit-DNA levels and 30-day mortality (OR, 1.03 [95%CI, 0.71-1.50], p = 0.861) or MACE (0.98 [0.72-1.32], p = 0.879), Killip class (0.95 [0.74-1.21], p = 0.664), or left ventricular ejection fraction (ref.cat. > 50%; < 35%, RRR 1.01 [95%CI, 0.74-1.38], p = 0.952; 35-50%, 1.26 [1.07-1.48], p = 0.005]. Adding CRP and IL-6 levels as covariates to a model based on classical risk factors significantly improved the prediction of MACE at 30 days after STEMI (IDI 0.13; NRI 0.32, p < 0.05).<h4>Conclusions</h4>Circulating levels of the NET marker H3Cit-DNA at the time of primary PCI were not predictive of cardiovascular events following STEMI. In contrast, the classical inflammatory markers CRP and interleukin-6 significantly enhanced the discriminative capacity of a clinical 30-day risk prediction model. These findings suggest that measuring circulating NET-specific markers may have limited utility in assessing the inflammatory state during the early stages of STEMI.https://doi.org/10.1371/journal.pone.0319759
spellingShingle Ana Blasco
Axel Rosell
Raquel Castejón
Ana Royuela
Charlotte Thålin
Elvira Ramil
Silvia Elorza
María-José Coronado
Paloma Martín
Javier Vázquez
Carolina González-Andrés
Juan M Escudier
Javier Ortega
Carmen Bellas
Inflammatory and neutrophil extracellular trap markers to predict cardiac events after ST-segment elevation myocardial infarction.
PLoS ONE
title Inflammatory and neutrophil extracellular trap markers to predict cardiac events after ST-segment elevation myocardial infarction.
title_full Inflammatory and neutrophil extracellular trap markers to predict cardiac events after ST-segment elevation myocardial infarction.
title_fullStr Inflammatory and neutrophil extracellular trap markers to predict cardiac events after ST-segment elevation myocardial infarction.
title_full_unstemmed Inflammatory and neutrophil extracellular trap markers to predict cardiac events after ST-segment elevation myocardial infarction.
title_short Inflammatory and neutrophil extracellular trap markers to predict cardiac events after ST-segment elevation myocardial infarction.
title_sort inflammatory and neutrophil extracellular trap markers to predict cardiac events after st segment elevation myocardial infarction
url https://doi.org/10.1371/journal.pone.0319759
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