Response to Letter Regarding Article, “High Levels of Systemic Myeloperoxidase Are Associated With Coronary Plaque Erosion in Patients With Acute Coronary Syndromes: A Clinicopathological Study”

Abstract

We thank Dr Schindhelm for his constructive comments and interest in our study. 1 In a further analysis using a multiple linear regression model where plaque erosion and smoking status were entered as independent variables and the myeloperoxidase (MPO) level was entered as the dependent variable, with the assumptions of normality of residuals, absence of heteroscedasticity, and presence of linearity all met, plaque erosion (coefficient 1195. Dr Schindhelm's second comment addresses the experience that MPO concentrations in EDTA-plasma are lower than those in serum, where the latter suggests uncontrolled ex vivo release of MPO from leukocytes during and after sample collection. 2 A more recent study by Wendland et al, 3 however, reports the opposite findings, concluding that the collection of MPO in tubes containing EDTA "alters in expressive way the results." In our study, we used serum collection tubes as they had been used in a previous large observational study enrolling patients with acute coronary syndromes where MPO levels were found to predict the clinical outcome. 4 Similar studies have also reported an association between serum MPO levels and myocardial reperfusion after thrombolysis 5 and systemic inflammation after a primary percutaneous coronary intervention, 6 thus indicating that MPO measured in serum is clinically meaningful. Finally, the findings in our clinical study are consistent with those in our postmortem tissues from sudden coronary deaths that showed a higher density of MPO-positive cells in thrombi overlying eroded lesions relative to plaque rupture. DisclosuresNone.

Prognostic Implications of Neutrophil Extracellular Traps in Coronary Thrombi of Patients with ST-Elevation Myocardial Infarction

“…The finding of lower local and systemic MPO levels in patients with culprit plaque rupture 7 may reflect lower inflammatory activity associated with coronary thrombosis triggered by this type of lesion compared with erosive lesions in STEMI. This would be in line with our findings in a small series of patients with STEMI and COVID-19, with a large thrombotic component and abundant NETs but no plaque debris in coronary aspirates.…”

“…Moreover, in superficially eroded lesions, which contain few macrophages or T lymphocytes, neutrophil activation seems to play a pivotal role. 7…”

Coronary plaque instability assessed by positron emission tomography and optical coherence tomography

“…In the last decades, invasive and non-invasive innovative biotechnologies have been developed to characterize coronary plaque instability. Mechanisms leading to ACS may complicate plaques with variable characteristics [9]. Patients with ACS and evidence of plaque rupture by OCT show widespread features of vulnerability of the entire coronary circulation [5].…”

“…Indeed, it is known that FDG uptake is increased not only at the coronary culprit site, but also within the ascending aorta and coronary non-culprit sites [6,17]. The absence of significant difference in TBR values between plaques with rupture and erosion is not surprising, as inflammatory cell activation is a key component in both cases, although macrophages play a key role in plaque fissure while neutrophils play a key role in erosion [9,27,28].…”