**3. The role of inflammation in the process of the formation of atherosclerosis**

Atherosclerosis is a chronic inflammatory disease [9, 32–34]. Due to the damage to the vascular endothelium and the development of inflammatory lesions in the vessel wall, there is a tendency to create blood clots leading to the occurrence of the thromboembolism evolving from atherosclerotic plaques or closing of the artery lumen at the site of inflamed plaque rupture, i.e. thrombotic vessel occlusion. Acute coronary syndromes (ACS) are in the form of unstable coronary artery disease (unstable angina—UA) and acute myocardial infarction (AMI)—which includes STEMI and NSTEMI or sudden cardiac death (SCD). Atherosclerosis in carotid arteries can lead to transient ischemic attacks (TIA) or ischemic stroke. The cause for these complexes, known as cardiovascular syndromes, is a blood thrombosis, forming on the surface of the damaged endothelium, a narrowed coronary artery or carotid artery, most frequently internal carotid artery (ICA) [9, 32].

Pathophysiological studies have shown that the most common cause of formation of a blood clot is rupture of the fibrous cap, which separates the contents of the plaque from the blood [9, 13, 33, 35]. This was confirmed in intravascular ultrasound (IVUS) with virtual histology (VH-IVUS), optical coherence tomography (OCT) and magnetic resonance imaging (MRI) [36, 37]. This mechanism applies to approximately 55–60% (in some studies dating back to the 80%) cases of ACS [33, 35, 36]. Other mechanisms are damage of endothelial cells known as erosion on the surface of atherosclerotic plaque (plaque erosion) consisting of 30–35% of the ACS and of approximately 2–7% endovascular calcifications (calcified nodules) [33, 35]. Inflammatory changes ongoing in the atherosclerotic plaque cause a loss of stability making it vulnerable to rupture, the so-called unstable atherosclerotic plaque (vulnerable plaque). Unstable plaque is characterized by a thin fibrous cap (thin cap fibroatheroma—TCFA) covering the big necrotic core around which revolves the inflammatory process and positive remodeling of the artery [9, 32, 33, 35]. A similar transformation in the atherosclerotic plaque has also been observed in the ICA. This location is responsible for TIA and strokes [9]. Positive remodeling of the artery proves that narrowing of its lumen does not have to be relevant, and it may not exceed 50–70% [9, 33]. The widespread use of statin drugs, especially atorvastatin and rosuvastatin, also likely ACE inhibitors, and lifestyle changes in developed countries have resulted in better control of inflammatory changes ongoing inside atherosclerotic plaque. This results in reduction in the incidence of strokes (primary stroke prevention) and ACS in the form of STEMI, but higher prevalence of NSTEMI and UA [9, 13, 32]. As a result, this has led to decreased cardiovascular mortality in many countries. It cannot be excluded that control of inflammation in the vessel wall by commonly used statins lowers the incidence of share in causes for destabilizing plaque rupture leading to occlusion of the artery. Because the total number of ACS and cerebral ischemic events remains at a similar level, this finding probably reveals other mechanisms leading to intravascular thrombosis with a smaller share of acute inflammation within the plaque rupture-induced accumulation of oxygen-modified LDL cholesterol (oxy-LDL) leading to destabilization. These mechanisms include endothelial injury by vascular flow disorders caused by artery stenosis, abnormal healing processes of the damaged endothelium, infectious pathogens as well as autoimmune responses against modified plaque components [9, 13, 35, 38, 39].
