Abstract
Neutrophil extracellular traps (NETs) have been implicated in atherothrombosis; however, their potential role as markers of risk is unclear. We investigated whether circulating NETs-related components associated with clinical outcome and hypercoagulability in ST-elevation myocardial infarction (STEMI). In this observational cohort study, STEMI patients admitted for PCI (n = 956) were followed for median 4.6 years, recording 190 events (reinfarction, unscheduled revascularization, stroke, heart failure hospitalization, or death). Serum drawn median 18 hours post-PCI was used to quantify double-stranded DNA (dsDNA) and the more specific NETs markers myeloperoxidase-DNA and citrullinated histone 3. Levels of the NETs markers did not differ significantly between groups with/without a primary composite endpoint. However, patients who died (n = 76) had higher dsDNA compared to survivors (p < 0.001). Above-median dsDNA was associated with an increased number of deaths (54 vs. 22, p < 0.001). dsDNA in the upper quartiles (Q) was associated with increased mortality (Q3 vs. Q1 + 2 adjusted HR: 1.89 [95% CI 1.03 to 3.49], p = 0.041 and Q4 vs. Q1 + 2 adjusted HR: 2.28 [95% CI 1.19 to 4.36], p = 0.013). dsDNA was weakly correlated with D-dimer (rs = 0.17, p < 0.001). dsDNA levels associated with increased all-cause mortality, yet weakly with hypercoagulability in STEMI patients. The prognostic significance of potentially NETs-related markers requires further exploration.
Highlights
Neutrophil extracellular traps (NETs) were first described in 2004 by Brinkmann and colleagues, who documented the expulsion of extracellular webbed structures comprising deoxyribonucleic acid (DNA) and histones, studded with neutrophil granule proteins[2]
We aimed to characterize any association between the levels of double-stranded DNA (dsDNA), the more NETs-specific MPO-DNA and citrullinated histone 3 (CitH3), and clinical outcome in a population with ST-segment elevation myocardial infarction (STEMI)
Characteristics according to above- and below-median levels of MPO-DNA and CitH3 are displayed in Supplementary Table S2
Summary
Neutrophil extracellular traps (NETs) were first described in 2004 by Brinkmann and colleagues, who documented the expulsion of extracellular webbed structures comprising deoxyribonucleic acid (DNA) and histones, studded with neutrophil granule proteins[2]. The process of NETs release, or NETosis, is initiated by granular proteins such as myeloperoxidase (MPO), neutrophil elastase, and peptidylarginine deiminase 43 The latter mediates the citrullination of histone 3, inducing chromatin decondensation before extracellular release[3]. Circulating NETs-associated components may contribute to endothelial dysfunction and plaque instability[4], as well as coronary thrombus formation[5] by activating platelets, triggering the coagulation cascade, and trapping thrombus constituents[6,7]. It is not yet clear how NETs per se are implicated in the fine balance between beneficial and deleterious effects of inflammation after revascularization. We assessed any relation to selected markers of hypercoagulability
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