Department of Hematology, Erasmus MC Rotterdam, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Experimental Cardiology, Erasmus MC Rotterdam, University Medical Center Rotterdam, Rotterdam, The Netherlands.
PLoS One. 2022 Jun 9;17(6):e0269805. doi: 10.1371/journal.pone.0269805. eCollection 2022.
Carotid atherosclerotic plaque rupture and its sequelae are among the leading causes of acute ischemic stroke. The risk of rupture and subsequent thrombosis is, among others, determined by vulnerable plaque characteristics and linked to activation of the immune system, in which neutrophil extracellular traps (NETs) potentially play a role. The aim of this study was to investigate how plaque vulnerability is associated with NETs levels. We included 182 patients from the Plaque At RISK (PARISK) study in whom carotid imaging was performed to measure plaque ulceration, fibrous cap integrity, intraplaque hemorrhage, lipid-rich necrotic core, calcifications and plaque volume. Principal component analysis generated a 'vulnerability index' comprising all plaque characteristics. Levels of the NETs marker myeloperoxidase-DNA complex were measured in patient plasma. The association between the vulnerability index and low or high NETs levels (dependent variable) was assessed by logistic regression. No significant association between the vulnerability index and NETs levels was detected in the total population (odds ratio 1.28, 95% confidence interval 0.90-1.83, p = 0.18). However, in the subgroup of patients naive to statins or antithrombotic medication prior to the index event, this association was statistically significant (odds ratio 2.08, 95% confidence interval 1.04-4.17, p = 0.04). Further analyses revealed that this positive association was mainly driven by intraplaque hemorrhage, lipid-rich necrotic core and ulceration. In conclusion, plaque vulnerability is positively associated with plasma levels of NETs, but only in patients naive to statins or antithrombotic medication prior to the index event.
颈动脉粥样硬化斑块破裂及其后果是急性缺血性脑卒中的主要原因之一。斑块破裂和随后的血栓形成的风险除其他外，取决于易损斑块的特征，并与免疫系统的激活有关，其中中性粒细胞胞外陷阱（NETs）可能发挥作用。本研究旨在探讨斑块易损性与 NETs 水平之间的关系。我们纳入了 Plaque At RISK（PARISK）研究中的 182 名患者，对这些患者进行颈动脉成像以测量斑块溃疡、纤维帽完整性、斑块内出血、富含脂质的坏死核心、钙化和斑块体积。主成分分析生成了一个包含所有斑块特征的“易损性指数”。测量患者血浆中 NETs 标志物髓过氧化物酶-DNA 复合物的水平。通过逻辑回归评估易损性指数与低或高 NETs 水平（因变量）之间的关系。在总人群中，未发现易损性指数与 NETs 水平之间存在显著相关性（优势比 1.28，95%置信区间 0.90-1.83，p = 0.18）。然而，在索引事件前未接受他汀类药物或抗血栓药物治疗的患者亚组中，这种相关性具有统计学意义（优势比 2.08，95%置信区间 1.04-4.17，p = 0.04）。进一步的分析表明，这种正相关主要是由斑块内出血、富含脂质的坏死核心和溃疡驱动的。总之，斑块易损性与 NETs 血浆水平呈正相关，但仅在索引事件前未接受他汀类药物或抗血栓药物治疗的患者中。
