Assessment of Plaque Vulnerability in Diabetic and Non-Diabetic Patients with Coronary Artery Disease Using Multi-slice CT Angiography

Article information Background: Coronary artery disease [CAD] is a major determinant of the long-term prognosis among patients with diabetes mellitus [DM]. The aim of the work: The aim of this study was to investigate coronary plaque vulnerability using multi-slice computed tomography [MSCT-CA] coronary angiography in diabetic and non-diabetic patients. Methods: 200 patients who underwent MSCT-CA were evaluated for the vulnerability of atherosclerotic coronary plaques. Patients were divided into Group I [100 patients with Type II DM] and Group II [100 non-diabetic patients]. Results: The DM group's mean age was greater [P 0.003]. In groups I and II, hypertension was present in 71% vs. 47%, and history of previous PCI was present in 6% vs. 0% [P values 0.001 and 0.029, respectively]; smoking history revealed a barely statistically significant difference [P 0.059], and the mean serum LDL-c level in the two groups was 154.25±34.11 vs. 191.66±16.829, respectively [P <0.001]. Positive remodeling of plaques [100% vs. 33%] and Napkin’s ring [66% vs. 40%] and spotty calcification [45% vs. 35%] were more evident in the diabetic group than the non-diabetic group [P <0.001, <0.001, and 0.005, respectively]. Low-attenuation plaques were present [100% vs. 95%] in groups I and II with borderline statistical significance [P 0.059]. The most affected vessels in the diabetic group were the right coronary artery [RCA] and ramus intermedius [RI] at 36% and 13%, respectively [P <0.001], whereas the most affected vessel with severe luminal narrowing was the LAD [51% vs. 30%], which was more evident in the DM group than the non-DM group [P 0.002]. Conclusion: Vulnerable coronary plaques were more evident in the diabetic group compared to the non-diabetic group. Positive remodeling of plaques, Napkin’s ring, spotty calcification, and severe luminal narrowing were the most significant signs of plaque vulnerability in the diabetic group.


INTRODUCTION
In 2017, coronary artery disease [CAD] accounted for 46.2 % of the overall mortality in Egypt [1] .Patients with DM have plaques with larger necrotic cores, inflammation, and advanced coronary artery calcification [2] .The presence of DM was found to be a predictor of plaque progression despite very low levels of LDL-c [3] .
The presence of vulnerable plaque features as detected by MSCT [positive remodeling, low attenuation, spotty calcification, and napkin's ring sign] may identify patients at increased risk for future ACS [4] .Studies on the identification and characterization of coronary atherosclerotic plaque stated that MSCT angiography allows for the determination of the degree of stenosis and has a strong correlation with intravascular ultrasound measurements [IVUS] [5] .

THE AIM OF THE WORK
This work aimed to investigate and compare coronary plaque composition and vulnerability using MSCT coronary angiography in diabetic and non-diabetic patients.

PATIENTS AND METHODS
The current study included 200 patients who underwent MSCT coronary angiography with suspected CAD [based on the presence of symptoms, abnormal or inconclusive previous treadmill exercise electrocardiography [ECG], and/or nuclear testing].All cases were evaluated for the vulnerability of atherosclerotic plaques.Patients were divided into two groups [according to presence and absence of DM]: group I, 100 patients with type II DM, and group II, 100 nondiabetic patients.The following patients were included; DM II and non-diabetics with suspected CAD with no contra-indications to MSCT.The following conditions were excluded; DM I, arrhythmia, Renal insufficiency, known allergy to contrast media, Pregnancy.The study was approved by the ethics committee for research involving human subjects at the Faculty of Medicine at Al-Azhar University.All scans were preceded by the noncontrast enhanced scan for coronary calcium score.In each patient, 70 mL of iodinated contrast is followed by 50 mL of normal saline solution.Contrast was given in two phases: the first phase was a test bolus in the ascending aorta [the scan delay was 12 seconds].
The second phase included the administration of the main contrast material, and images following the san were acquired after the scan to identify motion-free coronary artery images and affected vessels by motion and artefacts were discarded.Then the CT-acquired images were transferred to the Vitrea workstation for postprocessing.The image data sets were analyzed using multi-planar reformatted images [axial, coronal, and sagittal views], curved multi-planar reformatted images [cMPR], thin-slab maximumintensity projection images [thin MIP], and volume-rendered images [VRI].
Atherosclerotic plaque was defined as any clearly discernable structure larger than 1-2 mm that was assigned to the coronary artery wall in two perpendicular imaging planes.Remodelling index was obtained by dividing the vessel diameter at the plaque site by the diameter at the reference site.Positive remodeling was reported when the remodeling index was greater than 1.1.The plaque was referred to as a "low attenuation plaque" [LAP] with a radiodensity lower than the surrounding tissue.LAPs are classified according to density into vulnerable plaques with Hounsfield Units [HU] equal to or less than 30 HU and nonvulnerable plaques with HU greater than 30 HU.
The severity of luminal diameter stenosis was classified according to the percentage of luminal narrowing as absent [0%], mild [25-49%], moderate [50-69%], and severe [70-99%].Coronary lesions in the diagonal branches, obtuse marginal branches, and posterolateral branches were considered to be part of the LAD, LCX, and RCA arteries, respectively.Depending on the dominance of the coronary artery, the posterior descending artery was considered to be part of the RCA or LCX arteries.Coronary artery calcium was identified as a dense area in the coronary artery exceeding the threshold of 130 HU; accordingly, plaques were divided into calcific with more than 130 HU, non-calcified with less than 130 HU, or mixed with >50% of non-calcified plaque area.
Statistical analysis: All data were collected and statistically analyzed using Microsoft Office Excel 2010 and SPSS 22.0 for Windows.Categorical data were compared using the Chisquare test or Fisher's exact test when appropriate.A p-value less than 0.05 was considered statistically significant; and a p-value more than or equal to 0.05 was considered statistically insignificant.

RESULTS
The demographic characteristics of the study population are summarized in

DISCUSSION
According to our results, as regards the risk factors, hypertension as an effective risk factor was more prevalent in the DM population than in the non-diabetic population, showing a statistically significant difference; the average age of diabetic patients was higher compared to the non-diabetic population [Although the age group were not previously determined in the study for each group]; smoking history for both groups, however, exhibited marginally statistically significant differences between both groups; and prior PCI revealed a statistically significant difference, which was in concordance with Esteghamati et al. [6] .There were also no statistically significant differences between the diabetic and non-diabetic groups for positive family history, history of dyslipidemia, history of CABG surgery, or prior CVS or TIA, which was in discordance with the same study.Most patients had at least one cardiovascular risk factor [hypertension, smoking, DM, and high cholesterol].
In our study results, the HBA1C level in the diabetic group was high, suggesting that poor DM control may have an impact on the pathology of increased plaque vulnerability.Also, the mean LDL-c levels in the DM group were greater than those in the non-diabetic group, showing highly statistically significant differences between both groups, which was also indicating that a large sector of the study population had dyslipidemia; however, many were giving a negative history of dyslipidemia, recommending dyslipidemia screening in all diabetic patients with CAD even if they are asymptomatic.These results were in correlation with Shenouda et al. [7] .
In our study, we found that the MVD pattern is higher in the diabetic group and showed a statistically significant difference between the two groups, which means that DM tends to affect a larger number of vessels in CAD if compared to non-DM patients.This is in accordance with Zand Parsa et al. [8] .
In our study, we discovered that the RCA and RI were the most affected vessels with vulnerable plaques, which was also consistent with Dar et al. [9] .
There was also a statistically significant difference between DM and the non-diabetic groups in the degree of luminal narrowing of the LAD and RI but not in the degree of luminal narrowing of the LCX and RCA, which was in discordance with Tesche et al. [10] and Zhang et al. [11] .
As regards plaque vulnerability characters, between DM and the non-diabetic groups, there were statistically significant differences in positive remodeling and napkin's ring, and this is in correlation with Reddy et al. [12] .There were no statistically significant changes in low attenuation between DM and the non-diabetic groups, which was in discordance with the same study.It was also noticeable that spotty calcification was more prevalent in the DM group than the non-diabetic group, showing a statistically significant difference.Poor glucose control can cause intimal and medial calcification in the form of spotty calcification, according to Tomizawa et al. [13] .
As regards plaque analysis and calcium scoring in both groups, between the DM and the non-diabetic groups, calcium score and plaque eccentricity exhibited statistically significant differences, and this is in accordance with Budoff et al. [14] and Kwon et al. [15] .There was also no statistically significant difference between the diabetic and non-diabetic groups with regard to the type of plaque.
Limitations : The majority of selected patients were at moderate to high risk of having CAD, so some of the results could be affected by bias.Also, IVUS, which is considered the gold standard for studying plaque composition, was not used.Future large-scale studies are recommended, as the limited size of the study population may affect the final result.

Conclusion:
In diabetic patients with long history of the disease and moderate risk of CAD, MSCT angiography is recommended for the identification of CAD extent, severity and risk stratification.MSCT angiography has a great ability to determine atherosclerotic plaque composition and vulnerability in diabetic and non-diabetic patients which could limit the major dependence on Unnecessary invasive modalities.Also, it obviously can help in the early detection of high-risk patients, early prevention and management either with medical treatment or elective intervention, and prevent acute events, this may help in decreasing the Mortality and morbidity for both DM and CAD.
Disclosure: None to be disclosed

Figure [ 1 ]:
Figure [1]: Example of vulnerable plaques assigned on MSCT-CA: A: spotty calcium, LAP, and positive remodeling in a DM patient.B: Low attenuation plaque and positive remodeling in a non-diabetic patient

Table 1 .
The mean age was 56.49±9.71 vs. 51.70±8.23 in groups I and II, respectively [P=0.003].Hypertension was present [71% vs. 47%] in groups I and II, respectively [P 0.001].History of PCI was 6% vs. 0% in groups I and II, respectively [P 0.029].Family history of CAD, history of dyslipidemia, history of previous CABG, and CVS/TIA showed no statistically significant differences between both groups [P = 0.852, 1.000, 1.000, and 0.621, respectively].History of smoking showed borderline statistical significance between both groups [P = 0.059].

Table 5 .
Criteria of plaque vulnerability were compared in both groups, including positive remodeling, napkin's ring, plaque attenuation, and spotty calcification.Added to these criteria, plaque screening, total calcium score, plaque eccentricity, severity of luminal stenosis, and plaque type.Positive remodeling was present in 100% vs. 33%, napkin's ring was seen in 66% vs. 40%, and spotty calcification was also more prevalent in DM than non-diabetic patients [45% vs. 35%], with a statistically significant difference between both groups [P 0.005].While low attenuation showed no statistically significant difference between both groups [100% vs. 95%, P 0.059] [Table4].

Table [ 1
]: Demographic criteria of the study population Table [2]: Key LAB findings in groups I and II

Table [ 4
]: Criteria of plaque vulnerability in both groups

Table [ 5
]: Screening of other plaque criteria in both groups