Abstract Number: LPB0048
Meeting: ISTH 2021 Congress
Background: 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.
Aims: To investigate how plaque vulnerability is associated with plasma levels of NETs.
Methods: In this study, we included 182 patients from the Plaque At RISK (PARISK) study in whom carotid imaging was performed to determine the presence and size of plaque ulceration, the presence of a thin or ruptured fibrous cap, and the presence and volume of intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC) and calcifications. The PARISK study was approved by the medical ethics committee and informed consent was obtained from patients. Principal component analysis generated a ‘vulnerability index’ comprising all measured vulnerable plaque characteristics. Plasma levels of the highly specific NETs marker myeloperoxidase-DNA complex were measured using ELISA and patients were divided in two groups based on these levels. The association between the vulnerability index (independent variable) and low or high plasma levels of NETs (dependent variable) was assessed by logistic regression, adjusted for age, sex and time between event and blood sampling.
Results: No significant association between the vulnerability index and NETs levels was detected in the total population (OR 1.28, 95% CI 0.90-1.83). However, in the subgroup of patients naive to statins or antithrombotic medication before the index event, this association was statistically significant (OR 2.08, 95% CI 1.04-4.17). Further analyses revealed that this positive association was mainly driven by IPH, LRNC and ulceration (Table).
|Patients without statins or antithrombotic medication (n=72)||Patients with statins or antithrombotic medication (n=109)|
|Plaque characteristic||OR [95% CI]||p-value||OR [95% CI]||p-value|
|IPH presence||5.29 [1.54-18.06]||0.01*||0.72 [0.30-1.71]||0.46|
|Relative IPH volume (%)||1.19 [1.04-1.35]||0.01*||1.00 [0.94-1.06]||0.91|
|LRNC presence||2.45 [0.78-7.69]||0.13||0.61 [0.26-1.47]||0.27|
|Relative LRNC volume (%)||1.12 [1.03-1.21]||0.01*||0.98 [0.94-1.02]||0.36|
|Ulceration presence||5.93 [1.38-25.37]||0.02*||2.04 [0.81-5.13]||0.13|
|Ulceration size||1.70 [0.97-3.00]||0.07||1.14 [0.77-1.69]||0.52|
|Thin or ruptured fibrous cap||1.51 [0.55-4.13]||0.42||0.75 [0.31-1.80]||0.51|
|Calcification presence||0.85 [0.18-3.95]||0.84||–||0.99|
|Relative calcification volume (%)||1.01 [0.92-1.11]||0.86||1.02 [0.95-1.10]||0.59|
Conclusions: In patients with symptomatic carotid atherosclerotic plaques, plaque vulnerability is positively associated with NETs levels, but only in patients naive to statins or antithrombotic medication before the index event.
To cite this abstract in AMA style:de Vries JJ, Autar AS, van Dam-Nolen DH, Donkel SJ, Kassem M, van der Kolk AG, van Velzen TJ, Kooi M, Hendrikse J, Nederkoorn PJ, Bos D, van der Lugt A, de Maat MP, van Beusekom HM. Association between Plaque Vulnerability and Neutrophil Extracellular Traps (NETs) Levels: The Plaque at RISK Study [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/association-between-plaque-vulnerability-and-neutrophil-extracellular-traps-nets-levels-the-plaque-at-risk-study/. Accessed August 19, 2022.
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