1 Center for Clinical Heart Research, Oslo University Hospital Ullevål, Norway.
2 Faculty of Medicine, University of Oslo, Norway.
Eur J Prev Cardiol. 2018 May;25(7):762-769. doi: 10.1177/2047487318760618. Epub 2018 Feb 23.
Background 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.
背景 中性粒细胞胞外诱捕网（NETs）由染色质和颗粒蛋白组成，与动脉粥样血栓形成有关。
设计和方法 我们研究了稳定型冠状动脉疾病患者的循环中性粒细胞胞外诱捕网标志物（双链 DNA 和髓过氧化物酶-DNA）与临床结局和高凝状态的相关性。纳入了经血管造影证实的稳定型冠状动脉疾病患者（n=1001）。随访时间为 2 年，记录了 106 个临床终点事件（不稳定型心绞痛、非出血性卒中和心肌梗死或死亡）。基线时采集的血清用于确定双链 DNA 和髓过氧化物酶-DNA 水平。
结果 中性粒细胞胞外诱捕网标志物之间呈弱相关性（r=0.103，P=0.001）。双链 DNA 四分位最高的患者存在弱但显著升高的高凝状态标志物（凝血酶原片段 1+2、D-二聚体、游离和总组织因子途径抑制剂（所有 P<0.001））。男性、吸烟者、代谢综合征患者和有心肌梗死病史的患者，双链 DNA 水平显著升高（所有 P≤0.002）。与无临床终点事件组相比，发生临床终点事件组的双链 DNA 水平明显升高（P=0.019）。将双链 DNA 分为四分位数后，在最低四分位数和最高三分位数之间观察到明显的分界。在校正相关混杂因素后，上三个四分位数的患者发生临床终点事件的比值比为 2.01（95%置信区间 1.12，3.58，P=0.019）。髓过氧化物酶-DNA 与临床结局或高凝状态无显著相关性。
结论 双链 DNA 水平与 2 年后的不良临床结局显著相关，但与高凝状态仅呈弱相关。这些观察结果表明，中性粒细胞胞外诱捕网在冠状动脉疾病中的不良影响可能超出与高凝状态相关的影响。
