Thromboinflammation is associated with clinical outcome after ST-elevation myocardial infarction

Platelets are crucial in thrombus formation during ST-elevation myocardial infarction (STEMI). In addition, they also play an important role in postischemic thromboinflammation, which is determined by the interplay between activated platelets and neutrophils. The latter form neutrophil extracellular traps, which are detectable in plasma as citrullinated histone H3-deoxyribonucleic acid-DNA complexes. Prediction of the risk of recurrent events is important in precision medicine. Therefore, we investigated whether circulating thromboinflammatory markers predict clinical outcome after STEMI. We performed a prospective, multicentric, observational, all-comer study of patients with STEMI (n = 361). Thromboinflammation, measured as H3Cit-DNA complexes, was assessed on day 1 after presentation with STEMI as well as 5 days and 6 months after STEMI by enzyme-linked immunosorbent assay. Twelve months of clinical follow-up was conducted. Multivariate analysis was performed investigating which variables were independently associated with major adverse cardiac events (MACEs). Patients were aged 64 ± 12 years; 80% were male; and 40% had diabetes mellitus. Thromboinflammation was enhanced during index hospitalization compared with 6-months follow-up (137.4 ± 100.0 μg/L vs 53.7 ± 54.7 μg/L; P < .001). Additionally, patients within the highest tertile of thromboinflammation at day 1 after STEMI showed worse outcome during follow-up (hazard ratio, 2.57; 95% confidence interval, 1.72-3.85; P < .001). Receiver operating characteristic analysis revealed a cutoff value of 219.3 μg/L. In multivariate logistic regression analysis, thromboinflammation was independently associated with outcome after STEMI. To sum it up, thromboinflammation is enhanced in STEMI. It identifies patients at high risk of MACE. Therefore, thromboinflammation might be a promising target and marker in precision medicine. The trial was registered at www.clinicaltrials.gov as #NCT03539133.

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Publication Details

Journal
Blood Advances
Published
2024-09-03
DOI
https://doi.org/10.1182/bloodadvances.2024014273
Citations
13
Primary Topic
Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Type
article
Field-Weighted Citation Impact
3.13

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article

Thromboinflammation is associated with clinical outcome after ST-elevation myocardial infarction

Tobias Petzold, Dragos Andrei Duse, Malte Kelm, Christian Jung et al.
13 citations
Blood Advances
Neutrophil, Myeloperoxidase and Oxidative Mechanisms
3.13
article

Thromboinflammation is associated with clinical outcome after ST-elevation myocardial infarction

Tobias Petzold, Dragos Andrei Duse, Malte Kelm, Christian Jung, Vincent Ehreiser, Daniel Metzen, Jean Marc Haurand, Marcel Benkhoff, Karin Alde, Jana Dahlmanns, Amin Polzin
article en
13 citations

Abstract

Platelets are crucial in thrombus formation during ST-elevation myocardial infarction (STEMI). In addition, they also play an important role in postischemic thromboinflammation, which is determined by the interplay between activated platelets and neutrophils. The latter form neutrophil extracellular traps, which are detectable in plasma as citrullinated histone H3-deoxyribonucleic acid-DNA complexes. Prediction of the risk of recurrent events is important in precision medicine. Therefore, we investigated whether circulating thromboinflammatory markers predict clinical outcome after STEMI. We performed a prospective, multicentric, observational, all-comer study of patients with STEMI (n = 361). Thromboinflammation, measured as H3Cit-DNA complexes, was assessed on day 1 after presentation with STEMI as well as 5 days and 6 months after STEMI by enzyme-linked immunosorbent assay. Twelve months of clinical follow-up was conducted. Multivariate analysis was performed investigating which variables were independently associated with major adverse cardiac events (MACEs). Patients were aged 64 ± 12 years; 80% were male; and 40% had diabetes mellitus. Thromboinflammation was enhanced during index hospitalization compared with 6-months follow-up (137.4 ± 100.0 μg/L vs 53.7 ± 54.7 μg/L; P < .001). Additionally, patients within the highest tertile of thromboinflammation at day 1 after STEMI showed worse outcome during follow-up (hazard ratio, 2.57; 95% confidence interval, 1.72-3.85; P < .001). Receiver operating characteristic analysis revealed a cutoff value of 219.3 μg/L. In multivariate logistic regression analysis, thromboinflammation was independently associated with outcome after STEMI. To sum it up, thromboinflammation is enhanced in STEMI. It identifies patients at high risk of MACE. Therefore, thromboinflammation might be a promising target and marker in precision medicine. The trial was registered at www.clinicaltrials.gov as #NCT03539133.

Blood AdvancesVol. 8(21)
University of Vienna (AT), Düsseldorf University Hospital (DE), Lung Institute (US), Deutsches Herzzentrum der Charité (DE), German Centre for Cardiovascular Research (DE), Heinrich Heine University Düsseldorf (DE), Hochschule Düsseldorf University of Applied Sciences (DE), Charité - Universitätsmedizin Berlin (DE)
Deutsche Forschungsgemeinschaft, Deutsche Herzstiftung, Medizinische Fakultät, Heinrich-Heine-Universität Düsseldorf
Good health and well-being
Openalex Percentile: Top 8%
Neutrophil, Myeloperoxidase and Oxidative Mechanisms
3.13
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