• Miriam Sjåstad Langseth, Trine Baur Opstad, Vibeke Bratseth, Svein Solheim, Harald Arnesen, Alf Åge Pettersen, Ingebjørg Seljeflot, and Ragnhild Helseth.
• 1 Center for Clinical Heart Research, Oslo University Hospital Ullevål, Norway.
• Eur J Prev Cardiol. 2018 May 1; 25 (7): 762-769.

AbstractBackground Neutrophil extracellular traps, comprising chromatin and granule proteins, have been implicated in atherothrombosis. Design and methods We investigated whether the circulating neutrophil extracellular traps markers, double-stranded DNA and myeloperoxidase-DNA were associated with clinical outcome and hypercoagulability in patients with stable coronary artery disease. Patients with angiographically verified stable coronary artery disease ( n = 1001) were included. Follow-up was 2 years, recording 106 clinical endpoints (unstable angina, non-haemorrhagic stroke, myocardial infarction or death). Serum collected at baseline was used to determine double-stranded DNA and myeloperoxidase-DNA levels. Results The neutrophil extracellular traps markers were weakly intercorrelated ( r = 0.103, P = 0.001). Patients with the highest quartile of double-stranded DNA had weakly but significantly elevated hypercoagulability markers (prothrombin fragment 1+2, D-dimer, free and total tissue factor pathway inhibitor ( P < 0.001 for all)). Men, smokers, patients with metabolic syndrome and patients with a previous myocardial infarction had significantly elevated double-stranded DNA levels ( P ≤ 0.002 for all). Significantly higher double-stranded DNA levels were observed in the group experiencing a clinical endpoint compared to the group without ( P = 0.019). When categorising double-stranded DNA into quartiles, a distinct cut-off between the lowest and upper three quartiles was observed. Adjusting for relevant covariates, patients in the upper three quartiles had an odds ratio of 2.01 (95% confidence interval 1.12, 3.58, P = 0.019) for experiencing a clinical endpoint. Myeloperoxidase-DNA was not significantly associated with clinical outcome or hypercoagulability. Conclusions Double-stranded DNA levels were significantly related to adverse clinical outcome after 2 years, but only weakly associated with hypercoagulability. These observations suggest that the detrimental effects of neutrophil extracellular traps in coronary artery disease might extend beyond those related to hypercoagulability.

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