The role of computed tomography angiography in assessing the correlation between properties of coronary atherosclerotic plaque and blood lipids

2.1 Case collection

A total of 83 patients with coronary heart disease (males 50, females 33; average age [59 ± 8] years old; BMI: 18.5 ∼ 22.9) treated at the Affiliated Hospital of Beihua University from 2020 to 2022 were included in this study. Diagnose stable angina and unstable angina according to Chest pain of recent onset (NICE clinical guideline 95). Among them, 36 cases diagnosed with stable angina were enrolled in to stable angina (SA) group (males 28, females 8; non-calcified plaques 35 pieces, calcified plaques 90 pieces), and 47 cases diagnosed with unstable angina were enrolled into unstable angina (UA) group (males 38, females 9; non-calcified plaques 135 pieces, calcified plaques 16 pieces). All patients reported symptoms of chest tightness or discomfort in the precordial region after exertion and had not recently received lipid-lowering treatments. None of the patients included in this study had myocardial infarction.

2.2 CTA examination method

We used computed tomography scanner (128-slice multi-slice spiral CT, Brilliance iCT, Siemens AG, Erlangen, Germany). Before scanning, a routine iodine allergy test and breath-holding training were performed and the heart rate of the participants was maintained below 70 beats per minute. Patients with heart rates above 70 beats per minute received oral 25–50 mg of metoprolol tartrate to maintain the rate below 70 beats per minute. Sublingual nitroglycerin 0.5 mg was administered to dilate the coronary arteries for better lesion display. Using a double-barreled high-pressure injector, 75–80 mL of contrast agent (Ultravist [iopromide] 370 mg/mL, Bayer Schering Pharma) was injected into the antecubital vein at a rate of 4.0 mL/s followed by injection of 50 mL of saline at the same rate. The ascending aorta root plane was selected for closure monitoring, with a threshold value of 100 HU. A scan was performed at the ascending aorta root plane for comparison before injection of the contrast agent. An image of the same plane was obtained every second after injection of the contrast agent. The coronary artery scan was delayed by 5 seconds after the CT closure value at the ascending aorta root reached 100 HU. The level below the tracheal prominence to the level of the heart base was selected for scanning. Scanning parameters: Tube voltage 120 kV, tube current 870 mAs, collimation 64 × 0.6 mm, pitch 0.2, and rotation speed 0.33 s/360^∘. Image analysis: Siemens MMWP system processes the reconstructed image; If the stenosis degree of the patient is more than 25%, the reconstruction index, plaque composition and volume are automatically calculated. CT values were used to determine whether the plaque was calcified. Using magnetic suspension rack drive technology, 360-degree scanning takes only 0.3 seconds, the spatial resolution reaches 30 line pairs/cm, the Z-axis resolution is 0.33 MM, and the thinnest layer can be scanned up to 0.6MM, which can provide a fast synchronous scanning of 128 layers and can scan a range of 200 cm at a time. Using the retrospective electrocardiogram (ECG) gating method, the phase with the clearest display of the coronary artery (65% to 75% R-R interval) was selected for transverse thin-layer reconstruction (layer thickness 0.75 mm and layer spacing 0.5 mm). The three-dimensional reconstruction methods included volume rendering technology, maximum intensity projection (MIP), and curved planar reconstruction.

2.3 Clinical data

Total cholesterol (TC), triglycerides (TG), low-density lipoprotein, high-density lipoprotein, apolipoprotein A, apolipoprotein B, and other biochemical tests were conducted. All these tests were conducted on venous blood collected from the patients on the second day after admission to the hospital, on an empty stomach.

2.4 Classification of coronary atherosclerotic plaques

CT values of the plaques were measured using the point pixel capabilities of the PACS (Picture Archiving and Communication System) workstation on thin slice reconstructed images of the transverse axis. Measurement and calculation of parameters of calcium-containing plaque in coronary arteries: The measurement and calculation of calcium-containing plaque in this study refer to Moselewski’s method. Calcifying lesions were defined as CT values ⩾ 130 HU and ⩾ 3 contiguous voxels. Measurement and segmentation of CT values: Each calcium-containing plaque was selected as the study object, and the average CT value was calculated automatically by software according to the histogram of the distribution of CT values of all calcified voxels in calcium-containing plaques. Each calcium-containing plaque was divided into four parts according to the range of CT values, and the proportion (%) of each part after segmentation was calculated, that is, the composition ratio of each segment. The plaques were classified into three types based on their CT values: Fatty plaques (soft plaques), fibrous plaques, and calcified plaques, with CT values less than 50 HU, 70 HU–100 HU, and greater than 130 HU, respectively [2]. CT values ranging from 50 HU–70 HU and 100 HU–130 HU were abandoned. During data analysis, plaques were categorized as non-calcified, calcified, or mixed plaques. Non-calcified plaques included fatty and fibrous plaques. As CTA only revealed a small thickness or roughness of the coronary artery wall in certain patients and CT values were difficult to measure, these plaques were classified as non-calcified plaques. Mixed plaques referred to atherosclerotic plaques with both non-calcified and calcified components.

2.5 Analysis of biochemical test indicators of blood lipids

Cases with coronary artery atherosclerotic plaques prompted by CTA were classified as the case group. We analyzed how the degree of coronary artery stenosis caused by atherosclerotic plaques in the case group (taking the maximum degree of stenosis of coronary arteries) correlated to the levels of total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein.

2.6 Statistical software

SPSS 17.0 statistical software was used for all statistical analyses with a significance level of α = 0.05. Chi-squared test for a 2 × 2 contingency table or for a larger contingency table was used for rate or proportion test. If both these two indicators were normally distributed, the t -test was used; Spearman’s rank correlation coefficient was used if one of these two indicators was not normally distributed.

3.1 Comparison of the properties of lesion plaques and angina based on CTA examination

CTA demonstrated 1,162 segments of coronary arteries in these 83 patients. Mixed plaques with greater than 50% non-calcified plaque composition were classified as non-calcified plaques for the purpose of statistical analysis. In total, we found 170 non-calcified plaques, 106 calcified plaques, and 276 atherosclerotic plaques. There were 90 calcified plaques and 35 non-calcified plaques in patients with stable angina, and 16 calcified plaques and 135 non-calcified plaques in patients with unstable angina. The comparison of plaque properties between these two groups is shown in Table 1.

OPEN IN VIEWER

The stable and unstable plaques using CTA were shown in Fig. 1. The CT density values of lesions in the two groups were measured separately during CTA examinations (Table 2).

Analysis results: There was a significant difference in CT density values of lesions based on CTA examination between the two groups.

3.3 Correlation between angina properties and blood lipid levels

Lipid-lowering drugs were not administered systematically before hospitalization in both groups (Tables 3 and 4).

Table 5 displays the relationship between plaque properties and various indicators of blood lipids. Calcified plaques were negatively correlated with TC, low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), and positively correlated with high-density lipoprotein cholesterol (HDL-C). Non-calcified plaques were negatively correlated with HDL-C and positively correlated with TC, LDL-C, and TG.

4.1 CTA in the assessment of the properties of angina plaque

The degree of coronary artery stenosis and the properties of coronary atherosclerotic plaque are the primary indicators in imaging techniques used in clinical settings to diagnose CAHD. The severity of CAHD can be predicted using these standards as indicators. Even though coronary artery CTA cannot be used to measure fibrous cap thickness or detect whether a plaque is prone to rupture, CT values can be used to ascertain plaque composition through coronary artery CTA measurements. Due to its ability to determine plaque properties, CTA technology can be used to determine coronary artery stenosis and plaque composition by observing coronary artery lesions of patients with coronary artery disease from multiple angles and spatial perspectives [30].

As shown by previous research, CTA sensitivity and specificity in diagnosing CAHD can reach 92% and 93%, respectively [31]. Furthermore, there are extensive studies that have demonstrated that spiral CT is relatively highly consistent with IVUS in determining plaque properties [32]. According to the findings of our study, the local average CT values of coronary artery plaques differed significantly between stable angina patients and unstable angina patients ( 0.01). The study by Inoue et al. also confirmed that CTA has a certain degree of accuracy in determining the properties of coronary plaque [33]. CTA can therefore be used for preliminary screening of patients with high-risk of coronary heart disease. However, Pohle et al. Reported that the differentiation of “vulnerable” and “stable” plaques based on their CT attenuation is doubtful [34]. CT images are often affected by blooming artifacts and tend to overestimate the appearance of calcific stenosis. Post-processing calcium subtraction method could minimize stenosis-overestimation by blooming artifact [35]. In addition, optical coherence tomography (OCT) can provide a clear and detailed view of diseased plaques to assess the patient’s condition [36].

4.2 Correlation between properties of plaque and levels of blood lipids

Coronary artery plaque formation is a long-term process and includes multiple risk factors. There are many theories regarding its pathogenesis, however, the theory of injury response is currently accepted by most scholars. This theory can generally be divided into the following three processes: (1) Arterial intimal injury. Coronary heart disease risk factors can damage the coronary artery intima, leading to easier adherence of blood lipids to the vascular wall. (2) Fat deposition. Blood lipids deposit on the damaged arterial intima, which can further stimulate the worsening of coronary artery intimal injury, leading to increased lipid deposition. (3) Fibrosis. Lipid deposition can stimulate the proliferation of smooth muscle cells and fibroblasts in the coronary artery wall, which eventually develop into fibrous plaques. Therefore, abnormal blood lipids play an important role in the formation of coronary atherosclerosis. According to extensive clinical research conducted in recent years, coronary plaque rupture and thrombosis formation are the leading causes of acute cardiovascular adverse events, with calcified plaques being the potential cause of negative remodeling of local vessel lumens [37]. Consequently, exploring blood biochemical markers that reflect plaque vulnerability has become a current research focus. Based on the findings in this study, calcified plaques are negatively correlated with TC, LDL-C, and TG, and positively correlated with HDL-C, while non-calcified plaques are negatively correlated with HDL-C and positively correlated with TC, LDL-C, and TG. As a result, regular blood lipid level checks are simple, feasible, and effective measures for the prevention and early intervention of coronary atherosclerosis. Lipid-lowering therapy is crucial for the prevention and treatment of cardiovascular diseases, and early detection and intervention of blood lipid levels can delay and reverse the development of atherosclerosis.

4.3 Correlation between blood lipid levels and properties of angina

The pathological basis of coronary heart disease is an imbalance between lipid inflow and outflow, which causes coronary atherosclerosis and the formation of atherosclerotic plaques. According to recent clinical studies, plaque stability is more important than plaque size in predicting the development of acute coronary syndrome [38, 39]. The most important factor in the development of acute coronary syndrome is the rupture of the atherosclerotic plaque, with abnormal blood lipid metabolism also playing a significant role. The stability of the plaque depends on the level of blood lipids. Studies indicate that coronary plaques whose lipid content accounts for more than 40% of the total plaque are more prone to rupture [40]. These types of plaques typically possess a necrotic lipid core, also known as a lipid pool, which contains foam cells and other atherogenic lipids. In the event that such a plaque ruptures, its foam cells are released into the bloodstream causing platelet aggregation and activation of the coagulation system, which results in the formation of a blood clot. As high LDL-C levels increase the amount of lipid that enters the plaque and LDL-C has a chemotactic effect on monocytes, phagocytic cells then consume huge amounts of lipid to form foam cells. This can cause endothelial damage and allow inflammatory mediators to infiltrate, resulting in an inflammatory response. HDL-C, on the other hand, can transport excessive lipids from the coronary artery wall to the liver for decomposition and metabolism, thus delaying or reversing the progression of coronary plaques. Therefore, HDL-C is negatively correlated with the occurrence of cardiovascular adverse events. The findings of this study revealed that lipid levels differed significantly between patients with unstable angina and stable angina, and that angina properties were positively correlated with calcified plaques and negatively correlated with non-calcified plaques. Therefore, to improve lipid metabolism and stabilize plaques in patients with unstable angina, early use of lipid-lowering therapy is recommended.

4.4 Comparison between the properties of angina and the properties of plaque

Coronary artery calcification is often used as a risk marker to predict cardiovascular risk. There was a linear relationship between the degree of coronary artery calcification and plaque progression [41]. Different amounts, sizes, shapes, and positions of calcification may play different roles in plaque stability [42]. Many experts have reached a consensus on the pathological characteristics of calcified and noncalcified plaques after extensive clinical research. Non-calcified plaques, also known as vulnerable plaques, are prone to rupture, leading to thrombosis and acute cardiovascular adverse events. Numerous studies have demonstrated that CTA is reliable due to its high diagnostic accuracy for coronary stenosis and plaque characteristics [43, 44]. Calcified plaques, on the other hand, have a thick fibrous cap, a small or absent lipid necrotic center, more matrix and smooth muscle cells, and fewer inflammatory cells than non-calcified plaques. Calcified plaques have less influence on the occurrence and progression of coronary heart disease because they are stronger and less likely to rupture. According to the findings of our study, patients with unstable angina have significantly more non-calcified plaques in their coronary arteries and a significantly greater risk of thrombosis than patients with stable angina. These findings suggest that thrombosis caused by the rupture of non-calcified plaques is a significant pathological cause of acute cardiovascular events. Therefore, early intervention for non-calcified plaques has profound implications for the long-term prognosis of patients with coronary heart disease.

There were some limitations in the present study. This was a retrospective study, not blinded and no follow up is performed. Future studies will follow up the patients to explore the changes of coronary plaque after controlling blood lipids.