In their work, published in this issue of Polish Archives of Internal Medicine, Stępień et al¹ highlighted a potential link between serum concentration of neutrophil extracellular traps (NETs) in coronary artery disease and high doses of rosuvastatin or atorvastatin. A novel aspect of this study is to show that statins favorably modify fibrin clot properties in coronary atherosclerosis, a finding that could significantly impact future research and clinical practice.

Neutrophils are elements of the first‑line immunological response, and play an active role in atherosclerotic plaque formation, as they promote low‑density lipoprotein vascular deposition and oxidation.² Activated neutrophils release web‑like structures known as NETs, composed of histones, myeloperoxidase (MPO), and decondensed DNA, provoking procoagulant and proinflammatory endothelial cell phenotypes.³ The NET‑related immunothrombotic etiopathology relies on the formation of fiber and histone network that accumulates platelets, erythrocytes, leukocytes, and plasma proteins, which interact with von Willebrand factor.⁴ NETs are postulated to activate endothelial cells, leading to their structure and function impairment via MPO/H₂O₂-dependent activation of toll‑like receptor 4 / nuclear factor κ-light‑chain enhancer of activated B cell signaling and overexpression of adhesion molecules.⁵

The inflammatory background of atherosclerosis and its role in acute cardiovascular events⁶ points to a possible modulatory role of NETs in clinical practice. Increased NET formation is associated with chronic and acute syndromes related to plaque rupture and myocardial impairment.⁷ MPO, neutrophil elastase, and cell‑free DNA complexes are among specific NET biomarkers, and the presence of NET formation–related citrullinated H3 histones (H3cit) indicates activation of protein arginase deiminase 4.

A relation between H3cit representing the NET marker and right ventricular performance in patients with left ventricular assist device was recently suggested.⁸

Lipid‑lowering agents, such as statins (3‑hydroxy‑3‑methylglutaryl coenzyme A‑reductase inhibitors) have multiple pleiotropic properties, including anti‑inflammatory ones.⁹ Some works suggest statin effects on plaque stability, thrombosis reduction, and their possible role in oxidative stress reduction.¹⁰ Vavlukis et al¹¹ identified a possible impact of rosuvastatin therapy on the concentration of vascular endothelial growth factor and epidermal growth factor, which may modify cardiovascular risk independently of lipid homeostasis. Atorvastatin administration may result in anti‑inflammatory and antiatherogenic effects through modulation of the early stages of plaque formation triggered by lipoprotein influx into the arterial wall, which is facilitated by signaling pathways via reactive oxygen species and downstream phosphorylation of extracellular signal‑regulated kinase 1/2 and Smad2L.¹²

The analysis by Stępień et al¹ emphasizes the unique antithrombotic properties of high doses of statins, which may provide novel insights into atherosclerosis pathophysiology and possible targets for future therapies. In a collaborative analysis,¹³ aggressive lipid‑lowering therapy combined with its anti‑inflammatory effect was suggested as a new target in cardiovascular risk reduction. In another recent study,¹⁴ the antithrombotic effect of statin therapy was noticed, resulting in less severe prothrombotic fibrin clot phenotype.