NET-associated immunothrombosis as a predictor of adverse cardiovascular events in patients with ischemic heart disease

Coronary heart disease remains the leading cause of death worldwide, requiring a study of its pathogenesis in view of the immunothrombosis concept. A key role in these events is attributed to neutrophil extracellular traps, with citrullinated histone H3a being a highly specific marker The systemic levels of H3a have been insufficiently studied in various forms of coronary heart disease. Objective of the present work was to compare the level of circulating CitН3 in the groups of patients with acute myocardial infarction complicated by coronary occlusions; patients with stable ischemic heart disease, and generally healthy individuals. The study included patients with acute myocardial infarction with occlusion of the coronary arteries (group 1), stable ischemic heart disease (group 2), and generally healthy individuals matched for gender and age. The level of CitН3 in the blood serum was determined by enzyme-linked immunosorbent assay. Statistical processing was performed using the StatTech software. The highest CitН3 level was detected in patients of group 2 (median 8500 ng/mL), which was significantly higher than the values in patients with acute myocardial infarction (p = 0.004). In group 1, the CitН3 concentration (median 3000 ng/mL) was lower than in the control (4650 ng/ mL), but the differences did not reach statistical significance. An inverse correlation was revealed between the CitН3 level and the white blood cell counts (ρ = -0.612; p = 0.002). ROC analysis confirmed that CitН3 is a statistically significant predictor for differentiating stable and acute coronary heart disease (AUC = 0.875; p = 0.003). The systemic CitН3 level varies significantly in different forms of coronary heart disease. The paradoxically low CitН3 concentration in myocardial infarction is likely explained by its local deposition in the area of coronary thrombosis. High CitН3 levels in stable myocardial infarction may reflect chronic immunothrombosis and subclinical inflammation, making this marker a promising tool for risk stratification and disease activity assessment.