## 2 Materials and Methods
### Study Procedures
#### 2.2.5 Index Calculation  
The plaques were divided according to the Modified American Heart Association (AHA) classification of advanced coronary atherosclerosis [11], allowing for differentiation of the 3 main types of ATS plaque--SP, VP, and USP--depending on their histological structure and their progression toward thrombosis. The stable plaque is known to be a fibrous cap atheroma [7]. As [PERSON] noted, the plaque is stable when the fibrous cap is 2 mm thick [13]. The plaques that have a high risk of rupture are called vulnerable plaques [7; 14]. The characteristic VP is called thin cap fibroatheroma (TCFA), which is considered the precursor of the ruptured plaque [15]. It has a thin fibrous cap infiltrated by macrophages and lymphocytes with rare smooth muscle cells (SMCs) and an underlying necrotic core [16]. According to [PERSON] et al. [11], there are 3 main types of unstable plaques: plaque erosion (PE), PR (plaque rupture), and calcified nodule (CN). Plaque erosion is defined as the presence of thrombosis with the absence of an endothelial layer at the thrombosed sites [2]. There is no communication of the thrombus with the necrotic core. Thrombus is mostly mural and infrequently occlusive [11]. Nevertheless, eroded plaques do not have specific distinct morphological characteristics, making the identification of erosion-prone plaques a challenge. Plaque rupture is the result of disruption of a thin fibrous cap that overlies a large necrotic core, causing the thrombogenic contents of the necrotic core to trigger thrombus formation. In contrast to eroded plaques, plaques undergoing rupture have distinct morphological characteristics, including a large necrotic core, a thin and inflamed fibrous cap thin (<200 \(\upmu\)m thickness), and intimal vascularization, inflammatory cell infiltration, and spotty calcification [6; 17; 18]. Calcified nodules are characterized by thrombus formation over nodular calcification protruding into the lumen through a disrupted thin fibrous cap. These nodules are charac terized by an eruptive nodular calcification with underlying fibrocalcific plaque. Thrombus usually is non-occlusive [11]. The applied AHA morphological classification suggests that atherosclerotic changes depend on their histological structure and progression toward thrombosis [11]. The histological variables taken into consideration for plaque assessment are destabilized components of the plaque, including the thin fibrous cap, large lipid core, plaque inflammation and neovascularization, intraplaque hemorrhage, plaque calcification, and thrombi formation. A fibrous cap thickness under \(\leq\)200 \(\upmu\)m (0.2 mm) indicates a high risk for plaque rupture [13; 18]. A large lipid core having a size of more than 2 mm\({}^{2}\) indicates a high risk for plaque rupture [19]. The presence of inflammatory cells in atherosclerotic lesions is a sign of plaque growth and appears to play a role in the process of plaque progression [20]. Intraplaque neovascularization arises from newly formed microvessels that grow from adventitial vasa vasorum into the intima; they are characterized by leaky capillaries with an endothelial lining that is immature [21]. The neovascularization within carotid artery plaques is associated with neoveless rupture and intraplaque hemorrhage [22]. Plaque calcification represents the deposition of calcium salts within the atheromatous core, either in small spotty amounts or in large amounts as nodular deposits [23]. According to [PERSON] et al., the thrombus can develop on CN luminal surface as fibrin deposits and erythrocytes [24]. No plaque rupture was recorded in our study cases; we did not find any clear communication between the lipid core and the lumen because there was no break in the fibrous cap. We took into consideration 10 risk factors present in the advanced ATS plaque, which can present different values: values with low risk or score 0 (lesional grade 1) or values with high risk or score 1 (lesional grade 2).