|Ahead of print publication
Sonographic evaluation of carotid intima-media thickness and carotid plaques in coronary artery disease patients
BA Muthanna1, Ratan Kumar Sadangi1, Bharat Hosur1, Narendra Kumar Jain1, Inderjeet Singh Monga2
1 Department of Radiodiagnosis, Command Hospital Chandimandir, Panchkula, Haryana, India
2 Department of Medicine, Command Hospital Chandimandir, Panchkula, Haryana, India
|Date of Submission||05-May-2022|
|Date of Decision||13-Aug-2022|
|Date of Acceptance||22-Aug-2022|
|Date of Web Publication||11-Nov-2022|
Narendra Kumar Jain,
Senior Adviser (Radiodiagnosis) & Interventional Radiologist, Department of Radiodiagnosis, Command Hospital Chandimandir, Panchkula, Haryana
Source of Support: None, Conflict of Interest: None
Background: Coronary artery disease (CAD) is associated with significant mortality and morbidity. Atherosclerosis is the most common pathophysiology behind this condition. This manifests as an increase in arterial wall intima-media thickness and subsequent plaque formation in the asymptomatic phase. Objectives: To measure the carotid intima-media thickness (CIMT) value of carotid arteries in patients with angiographically diagnosed CAD and also asses the carotids for the presence of plaques and if present to characterize them. Materials and Methods: A total of 100 angiographically diagnosed CAD patients were included in the descriptive study and data were analyzed regarding the increased CIMT, and plaques in the carotid arteries in relation to the corresponding coronary disease. Results: Raised CIMT values were found in 47 out of 100 patients. A linear proportional relationship of mean CIMT values with the number of involved coronary arteries was also observed. A total of 62 plaques were demonstrated in 43 patients. Majority of the plaques (65%) had a smooth surface with uniform outlines. Eighteen plaques were found to have irregular surface outlines (29%), whereas four out of 62 plaques (6%) had ulcerated surfaces. Conclusion: There is increased CIMT prevalence and its linear proportional relationship with an increased number of affected coronary vessels in patients with CAD. Furthermore, an increased prevalence of carotid plaques is present in these patients. Hence, the increased CIMT and the presence of carotid plaques may act as surrogate markers for risk stratification in a patient with CAD.
Keywords: Carotid plaque, coronary artery disease, intima-media thickness, ultrasound
|How to cite this URL:|
Muthanna B A, Sadangi RK, Hosur B, Jain NK, Monga IS. Sonographic evaluation of carotid intima-media thickness and carotid plaques in coronary artery disease patients. J Mar Med Soc [Epub ahead of print] [cited 2023 Mar 21]. Available from: https://www.marinemedicalsociety.in/preprintarticle.asp?id=360903
| Introduction|| |
Coronary artery disease (CAD) happens to be a multifactorial entity often having a catastrophic clinical outcome. Identifying high-risk asymptomatic individuals is imperative in the prevention of the morbidity and mortality. Arterial wall imaging has been advocated to identify and quantify vascular disease in asymptomatic patients which can augment the overall cardiovascular risk assessment. Increase in thickness of the arterial wall due to subintimal fat deposition is one of the earliest changes in the pathophysiology of atherosclerotic disease. This manifests as an increase in arterial wall intima-media thickness and subsequent plaque formation in the asymptomatic phase. Examination of carotid arteries in CAD patients has been an important clinical practice to accurately identify the hitherto asymptomatic patients who may benefit from aggressive prevention and timely treatment.,
Multiple studies and meta-analyses have proposed that carotid intima-media thickness (CIMT) measurement and identifying the details of the carotid plaque can be helpful for risk assessment in patients having intermediate cardiovascular disease (CVD) risk. Inclusion of plaque assessment to CIMT measurement has been consistently shown to improve the predictive power for CVD and adverse coronary events. Carotid plaque burden along with adverse morphologic features such as surface irregularity and lipid-rich necrotic core is associated with the severity of CAD. Our study aims at measuring the CIMT value of bilateral carotid arteries in patients with angiographically diagnosed CAD, using B-mode ultrasound. The carotid arteries would also be evaluated for the presence of plaques. If present, the plaques would be further characterized with regard to their morphological parameters such as surface contour and sonographic consistency. Multiple prior studies have evaluated the CIMT and carotid plaque characteristics in a patient with CAD. Most have found a positive correlation between them. However, there are very limited large-scale studies specific to the Indian population that address this important aspect. The present study is aimed to validate the data existing in the literature and to assess if it holds in the Indian population. The study population recruited in our study are pan-Indian and has different demographic characteristics. Our study can provide new insight into the association of CIMT and carotid plaque characteristics in a patient with CAD by providing valuable data in filling this research gap.
| Materials and Methods|| |
This was a descriptive study conducted in a tertiary care hospital in North India for 2 years. It was cleared by the institutional ethics committee. Informed consent was obtained from all the participants.
A total of 100 angiographically proven CAD patients reporting to the hospital, who provided informed written consent were included in the study. Only the patients whose sonographic evaluation of carotids was performed in the department of radiodiagnosis within the 2 weeks of coronary angiogram were included to avoid confounding factors related to the treatment of CAD. The patients who had suffered a stroke or recurrent transient ischemic attacks in the past, those who had undergone any type of revascularization surgery/interventional procedure involving the carotid artery (even on one side), such as carotid endarterectomy, carotid stenting, and carotid bypass were strictly excluded from the study. The patients with any head-and-neck malignancy infiltrating the carotid vessel wall, and those with a history of radiotherapy to the neck for any cause were excluded. Furthermore, those with neck deformity or inadequate neck positioning for sonographic assessment due to any reason were not enrolled. The CAD-related treatment and interventions pertaining to the coronary arteries continued unaffected by our carotid assessment. Demographic characteristics and relevant clinical inputs were noted. Coronary angiograms were evaluated in terms of the number of vessels involved and documentation of the involved major coronary vessels.
The scans were performed using the Logiq-E ultrasound machine (GE Medical Systems, Milwaukee, Wisconsin, USA), using the 7–12 Hz high-frequency linear array transducer probe. The far wall of the common carotid artery (CCA) was used to measure the CIMT. The intima on the luminal side and the medial-adventitial interfaces of the carotid artery appeared as a double-line echo pattern on a B-mode ultrasound image [Figure 1]. A value ≥0.8 mm was defined as raised CIMT. This was in congruence with the Consensus Statement from the American Society of Echocardiography CIMT Task Force. CIMT was measured at three different segments of the carotid artery on either side namely at mid-CCA, at the level of the carotid bulb, and the proximal internal carotid artery. The highest value on either side was taken as the CIMT of that vessel. Carotid arteries on both sides were also evaluated for the presence of plaques. If present, the plaques were further evaluated for their surface characteristics (smooth, irregular, ulcerated) and their B mode echogenicity as per Gray-Weale classification.
|Figure 1: Schematic line diagram. (a) Showing layers of the carotid arterial wall and the “intima media thickness” (white arrow) which can be accurately measured on ultrasound. Longitudinal B mode scan of the right common carotid artery. (b) Showing corroborative normal carotid intima-media thickness|
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Study data were compiled in specific formats in the patient information sheets. Relevant images were stored in the form of digital images in external storage devices and PACS in DICOM as well as JPEG format. Descriptive statistics analysis tools were used to describe the data. For categorical variables, frequencies, and percentages were reported. P < 0.05 was considered statistically significant. The Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, Version 21.0. Armonk, NewYork) was used to perform all the data analyses.
| Results|| |
A total of 100 cases of angiographically diagnosed CAD patients were included in the study and data was analyzed regarding the prevalence of increased CIMT thickness and the presence of plaques in the carotid arteries. The average age of the patients enrolled in our study was 50.3 years with a standard deviation (SD) of 14.2. The majority of the patients were from the age group of <45 years (44%). The age of the youngest patient was 27 years and the oldest patient was 85 years old [Figure 2]. The majority of the population in this study was male, with a male-to-female ratio of 87:13. While 32 had chronic stable angina, 68 patients had presented with the acute coronary syndrome (ACS) among whom 40 patients had ST-elevation myocardial infarction and the rest had non-ST elevation myocardial infarction. Out of the hundred patients, the history of smoking was present in 66, 32 had diabetes and 44 had hypertension. None of the patients presenting with ACS and 28 (92%) with chronic stable angina were on oral statins. None of the included patients had suffered a stroke or transient ischemic attack in the past.
|Figure 2: The graphical representation showing the age distribution of patients having with age group intervals (in years) on X-axis and number of patients on Y-axis|
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Major coronary vessels involved in atherosclerotic disease as observed in the coronary angiography were the left circumflex (LCX), left anterior descending (LAD), and right coronary artery (RCA). Based on the number of coronary vessels involved, the study groups were divided into having single, double, or triple vessel disease [Figure 3]. Out of the total number of patients with CAD, 64 had single-vessel disease, whereas 18 patients each had double and triple-vessel diseases. Out of these 64 patients having single-vessel disease, 36 had involvement of LAD, 22 had involvement of RCA, and four had isolated LCX artery involvement. Two patients had involvement of only the epicardial vessels. The 18 patients having double-vessel disease were further categorized into subgroups based on the combination of vessels that were found diseased in coronary angiography. Seven patients had involvement of both LAD and LCX arteries. An equal number of patients had involvement of LAD and RCA. Rest four patients had involvement of RCA and LCX. 18 out of 64 patients had involvement of all three vessels, i.e., LAD, LCX, and RCA.
|Figure 3: Distribution of patients with increased CIMT amongst the groups based on the involved coronary arteries in patients with coronary artery disease. CIMT: Carotid intima media thickness|
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A total of 47 out of 100 patients were found to have raised CIMT values (cut-off values for raised CIMT >/= 0.8 mm). Hence, the prevalence of raised CIMT in angiographically proven CAD patients was found to be 47% (95% confidence interval: 46.90–47.10) with an SD of 0.05. Out of these, 32 patients had raised values in carotid arteries on both sides of the neck. Unilateral involvement of right-sided and left-sided carotids were 12 and 3, respectively. In our study group, the mean CIMT value amongst all the patients with angiographically diagnosed CAD was 1.13 mm with an SD of 0.43 mm. Raised CIMT value above this mean value was found in all of the patients having double and triple vessel involvement [Figure 4]. A linear proportional relationship of mean CIMT values with the number of involved coronary arteries was also observed. The mean CIMT values increased gradually with the reduction in the number of abnormal coronary vessels [Table 1].
|Figure 4: Unsubtracted left Coronary angiogram (a) of a patient with double-vessel disease showing complete occlusion of the left circumflex artery (arrow) and oblique marginal artery (arrowhead). Microwire access of the distal vessel beyond the steno-occlusive disease denotes the course of the distal vessel (b). Longitudinal B-mode (c) scan of the patient's right common carotid artery showing increased carotid intima-media thickness|
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|Table 1: Distribution of increased carotid intima media thickness in various coronary artery disease groups|
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Plaques were demonstrated in a total of 43 patients in our study group. Out of these, 19 patients had plaque on bilateral carotid arteries. Consequently, a total of 62 plaques were analyzed in this study. These 62 plaques in 43 patients were further analyzed for their surface characteristics and overall echogenicity. The majority of the plaques (65%), i.e., 40 out of 62 had a smooth surface with a uniform outline. Eighteen plaques were found to have irregular surface outlines (29%) in greyscale evaluation on B mode ultrasound. Only four out of 62 plaques (6%) had a demonstrable ulcerated surface in grayscale [Figure 5]. On Doppler insonation, there was aliasing of colors within the core of the ulcer suggestive of turbulent flow patterns within them.
|Figure 5: Unsubtracted left (a) and right (b) Coronary angiogram of a patient with triple vessel disease showing complete occlusion of the left anterior descending artery (thick arrow), stenosis of the left circumflex artery (arrowhead), and right coronary artery (thin arrow). Microwire access beyond the occlusion denotes the course of the distal vessel. (a) Longitudinal B mode scan (c) of the patient's left common carotid artery showing a noncalcified ulcerated plaque|
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Plaque echogenicity was assessed by evaluating their greyscale appearance in B mode ultrasound. The plaques were categorized into five categories from Type I to Type V based on increased levels of their echogenicity in accordance with the modified Gray-Weale classification. The frequency distribution of plaques as per their morphological characteristics was tabulated [Table 2]. The dominant morphological pattern in our study was Type III (20 out of 62 plaques; 32%). This was followed by Type V plaques which were in 15 patients (24%). Type 1 plaques had the lowest occurrence at three out of 62 (5%). The frequency of Type II and type IV was at 10 (16%) and 14 (23%), respectively. Within our subgroups, 24 out of 64 cases with single-vessel CAD had developed carotid plaques (37.5%). Among these 64 cases, 10 (16%) patients had involvement of plaques on both carotid arteries. Out of 18 patients who were found to have double-vessel disease 9 cases (50%) were found to have carotid plaques including two cases (11%) with bilateral involvement. Out of 18 patients who were found to have triple-vessel disease 10 were found to have carotid plaques (56%) and seven out of them (39%) had plaques affecting both carotid vessels. Triple-vessel disease was associated with a higher plaque burden with an increased incidence of bilateral carotid artery involvement.
| Discussion|| |
CAD is gaining epidemic dimensions in both developing and developed countries. Pathophysiologically majority of them occur due to inadequate blood supply by stenosed atherosclerotic coronary arteries. Atherosclerosis is a pathology that afflicts both coronary as well as carotid arterial systems simultaneously. This was the underlying principle on which the present study was based.
In our study, a total of 100 subjects with angiographically proven CAD were inducted for evaluation. These patients were measured for CIMT thickness in the carotid arteries on both sides and evaluated for the presence of plaques and if present their characterization. Our study included a predominantly young population with a median age of 47 years ranging from 25 to 87 years. The study group constituted mainly of males (87%) as compared to females who were 13%. This was inherent to the referral system and broad group of dependent patient clientele of the tertiary care hospital, in which this study was undertaken.
The categorization of CAD patients in our study according to the number of coronary vessels involved showed more involvement of single vessel, i.e., in 64% cases, followed by double and triple vessels at 18% each. A similar study conducted by Vieweg et al. on 500 patients with CAD found the single-vessel disease in 20% (103 cases), double-vessel disease in 23% (119 cases), and triple-vessel disease in 55% (278 cases) of the study population. A meta-analysis by Fabrizio D'Ascenzo et al. studied a total of 22,740 patients with ACS and found the distribution of triple-vessel disease to be 25% (95% CI 23.1% to 27.0%) in the symptomatic group.
Our study found LAD as the most commonly affected vessel affecting 68% of the CAD cases, in comparison to the rest of the coronary vessels. RCA was the second most commonly affected vessel constituting about 51%, followed by LCX (33%). A similar study on demography and angiographic profile of CAD in the year 2021 by Mohammad et al. found that LAD (61%) was the most frequently involved artery, followed by RCA (46%) and LCX (43%). A similar trend was also noted by several other workers namely Patil et al. (78.3% in LAD), Pinto et al. (82% in LAD) and a study by Beig (65.9% in LAD). CIMT measurement has been recommended by the American Heart Association as a reliable investigation to identify atherosclerosis for various interventional and noninterventional uses (72). In the present study, CIMT was raised in 47% of cases. The average CIMT of our study population was 1.13 mm with an SD of 0.43 mm. The mean CIMT in the single-vessel disease population was 1 mm, double-vessel disease 1.3 mm, and triple-vessel disease 1.4 mm.
Holland et al. had conducted a prospective study of 53 South African patients with angiographically proven CAD, in which CIMT was measured by B mode ultrasound. They found increased CIMT in 29 out of 38 (76%) patients with an average of 1.13 mm. The positive linear trend between the number of coronary vessels involved and CIMT was also statistically significant (P < 0.0001, r = 0.44); corroborating our results in this study. Adams et al. in their study on 350 patients found the mean CIMT to be 0.83 ± 0.20 mm. They also found that mean CIMT was correlated significantly with CAD severity, and modified Gensini score (r = 0.29, P < 0.0001). Singhal et al. studied the same parameters in their study in a tertiary care set-up in northern India and found the mean CIMT to be 1.11 mm. In the same study, they also recorded higher mean CIMT values in a single-vessel, double-vessel, and triple-vessel disease and left main coronary artery (LMCA) groups which were 0.96 mm, 1.15 mm, 1.34 mm, and 1.25 mm, respectively. Univariate and multivariate linear regression analysis showed a significant correlation between the severity of CAD and CIMT with r = 0.3 and P ≤ 0.001. The results in the above-mentioned study also corroborate our findings.
In this study, carotid plaque was demonstrated in 43% of the patients. A study conducted by Limbu et al. in Nepal included 54 patients with angiographically documented CAD out of which 46 patients had either increased CIMT or the presence of carotid plaques. They found the presence of carotid plaque in 29 cases out of 46 patients (63%). Kwon et al. conducted a study on 1027 patients who underwent coronary angiography for finding the prevalence of carotid plaque. They found carotid plaques to be present in 26% of cases (267 out of 1705 patients).
Our study further found that the frequency of occurrence of carotid plaques was 37.5% in the single-vessel group, 50% in the double-vessel group, and 56% in the triple-vessel group. Within the single-vessel group, LMCA was the most common (18/24; 75%) vessel to be associated with a carotid plaque. Furthermore, it was the commonest coronary artery to be involved across all the subgroups, to be associated with a carotid plaque. In addition to the above findings, it was also noted that the triple-vessel disease group had more involvement in bilateral carotid disease (39%) as compared to the double- and single-vessel groups. Keeping this in mind, we hypothesize that the increase in the number of carotid vessels affected by atherosclerosis may be associated with an increased risk for the development of future cardiac and cerebrovascular events in form of myocardial infarction or stroke. Similar studies with larger sample sizes and randomized control trials evaluating the correlation between the presence of carotid plaques with the number of vessels involved in the CAD disease may throw more light on this.
The morphology of carotid plaque has a prognostic indicator. Irregular carotid plaque surface morphology and associated ulceration are believed to play an important role in ischemic cerebrovascular events like stroke. The North American Carotid Endarterectomy Trial results showed the risk of ipsilateral stroke for the nonulcerated plaque was 21.3% in patients with 85% carotid stenosis; compared with 43.9% in patients with the ulcerated carotid plaques. In our study, we found that out of the 62 plaques that were evaluated, 22 plaques (35%) had either irregular or ulcerated surfaces. Ciccone et al., in their study, concluded that soft plaques with a large necrotic core are more predictive of an increased risk of acute cerebrovascular events and in contrast, a heavily calcific plaque may be suggestive of a higher risk of coronary events. In our study Type-5, calcified plaques constituted approximately 24% of all the plaques; this was the second-most dominant form among all other types.
Our study had a few limitations pertaining to the study design. It was a single-center study with a limited sample size and limited representation of female subjects. Furthermore, the average age of the included patients is younger, which may not represent the usual trend among CAD patients in general. This was because the overall patient clientele, of the hospital, in which the study was undertaken consisted of predominantly working males. Furthermore, the study did not take into account the various risk factors which restricted our ability to do a risk factor analysis assessment for the carotid atherosclerosis disease process. Further larger studies are recommended to carry out a detailed subgroup analysis.
| Conclusion|| |
Measurement of CIMT with the gray-scale ultrasound is a simple, sensitive, and reliable technique for identifying and quantifying the association of atherosclerotic burden with CAD. Our study not only shows the prevalence of increased CIMT in patients with CAD but also a linear proportional relationship of CIMT with the increased number of affected coronary vessels. Further, it also shows an increased prevalence of carotid plaques in a patient with CAD. Hence, the increased CIMT and the presence of carotid plaques may act as surrogate markers for risk stratification in a patient with CAD.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]