Prevalence and Risk Factors of Carotid Artery Stenosis (CAS) Among Cardiac Surgery Patients

Introduction: Cardiac disease and carotid atherosclerosis rates have increased in recent years. Carotid artery stenosis (CAS) has been recognized as a high-risk factor of perioperative stroke among cardiac surgery patients. Aims: The aims of the study are to identify the prevalence and common risk factors of CAS among patients undergoing cardiac surgery that include coronary artery bypass surgery or valvular cardiac surgery. Materials and Methods: This retrospective cross-sectional study was conducted in the radiology department at Medina Cardiac Center, Al Madinah Al-Munawara. The inclusion criteria for the study were patients aged ≥ 20 years who were scheduled for coronary artery bypass surgery or valvular cardiac surgery and had carotid duplex examination before surgery. A Philips X matrix IU22 linear-array ultrasound probe (Philips, Bothell, WA) was used to scan the common carotid artery (CCA), internal carotid artery (ICA), external carotid artery (ECA), and vertebral artery. Results: Of the 261 patients in this study, 78.5% (n = 205) were male. The mean age of patients was 61.6 ± 11.3 years (median: 62.0; range: 55.5-68.0). The overall prevalence of CAS was 71% (n = 187): 52% (n = 136) with bilateral CAS and 19.5% (n = 51) with unilateral CAS. Age group was significantly associated with bilateral CAS and the severity of CAS (p = 0.001). Diabetes mellitus, hypertension and both diabetes mellitus and hypertension together were significantly associated with CAS status (p < 0.05, for all). A significantly higher proportion of smokers had a mild level of CAS on the left side compared to non-smokers (55.8% vs. 46.5%, p = 0.033). Gender and weight status were not linked to severity of CAS. Conclusion: This study shows a high prevalence of CAS among cardiac surgery patients. In addition, older age, diabetes mellitus, and hypertension were found to be major risk factors for CAS. Gender and weight status were not associated with CAS. Preoperative carotid duplex scan is a useful exam to identify CAS among cardiac surgery patients and, therefore, to predict and reduce postoperative neurological complications.


Introduction
The term atherosclerosis refers to a biological event characterized by disease of the vascular intima layer that can potentially affect the entire arterial system from the aorta to the coronary arteries [1]. The term atherosclerosis is derived from the Greek words atherosis (meaning an accumulation of fat in the core of the plaque) and sclerosis (which describes the thickening of the intima layer of the arterial wall) [2]. Atherosclerosis is a common disease that is characterized by fatty deposits called intimal plaques. The development of these plaques starts with the deposition of cholesterol crystals in the intimal layer. The plaque then grows as apoptotic cells and smooth muscle accumulates to form a bulge inside of the vessels, which consequently decreases blood flow. This bulge then accumulates calcium and additional dead cells inside the lesion, which causes the hardening of the artery. A ruptured plaque will lead to the obstruction of blood flow [3]. Atherosclerosis is the most common underlying cause of coronary, peripheral, and carotid artery disease. According to reports, atherosclerosis alone is rarely lethal, unless the atherosclerotic plaque is ruptured and thrombosed, which will lead to life-threatening clinical events, such as acute coronary syndrome and stroke [4][5]. Atherosclerosis is a systematic inflammatory disease and, therefore, a strong relation between coronary atherosclerosis and carotid artery stenosis (CAS) has commonly been assumed [6][7]. Moreover, there is evidence to suggest that significant CAS is common among patients undergoing cardiac surgery with a high risk of critical neurological events [8][9]. Approximately 30% of annual global mortality is attributable to cardiovascular disease, while an additional 10% is attributable to cerebrovascular events [10][11].
According to Vranic (2017), the factors that play a major role in the pathogenesis and prediction of treatment for cardiovascular and cerebrovascular diseases are: hyperlipidemia, diabetes mellitus, hypertension, and smoking [12]. It has been reported that patients undergoing coronary bypass surgery usually have atherosclerosis in the carotid artery. Therefore, significant CAS is a critical cause of strokes among patients with heart disease, who have undergone cardiac revascularization surgery [13][14]. In Western countries, the prevalence of CAS among heart surgery patients in recent decades has risen from 12.8% to 22% [10][11]. It is believed that the extent of coronary artery illness is directly related to the severity of CAS. Zhang et al. (2015) hold the view that around 20% of patients suffering from multivessel coronary artery disease had significant CAS [15]. Several potential risk factors for CAS have been demonstrated, such as hypertension, smoking, diabetes, age, gender, peripheral vascular disease, and coronary artery disease [12,15]. According to the World Health Organization (2018), there is a higher prevalence of diabetes mellitus, being overweight, and smoking among the Saudi population [16], thus exposing them to a higher risk of atherosclerosis. Furthermore, very few studies, including those conducted on the Saudi population, have assessed the preponderance of CAS among cardiac surgery patients [17]. Therefore, the primary aim of this study is to identify the prevalence of CAS among cardiac surgery patients, with the secondary aim of determining the common risk factors of CAS among patients undergoing heart surgery in Madinah Cardiac Center.

Materials And Methods
A retrospective cross-sectional study was conducted in the radiology department at Medina Cardiac Center in Al Madinah Al-Munawara between February 2021 and August 2022. The inclusion criteria for this study were patients aged ≥ 20 years who were scheduled for coronary artery bypass surgery or valvular cardiac surgery and underwent a carotid duplex examination before surgery. The study was approved by the Scientific and Health Research Ethics Committee in Madinah. This study excluded patients under 20 years old who did not undergo heart surgery or who had heart surgery without undergoing a carotid examination. All patients underwent a carotid duplex examination using a Philips X matrix IU22 linear-array ultrasound probe with a frequency of 9-3 MHz. All ultrasound examinations were performed by an experienced radiologist. Patients were examined in the supine position with their head slightly tilted to the side. The carotid vascular preset was activated on the ultrasound machine. The scanning process began with a B-mode transverse view of the common carotid artery (CCA) from its proximal segment to its bifurcation into the internal carotid artery (ICA) and external carotid artery (ECA) as high in the neck as possible and then continued in the longitudinal view. The carotid arteries were scanned to assess anatomical variation and abnormal findings, which include increased intima media thickness, plaque or calcification, stenosis, and occlusion.
Ultrasound color doppler was used to detect the direction of blood flow, filling of blood flow in the vascular lumen, aliasing artifacts, and the status of blood flow. Moreover, spectral analysis was employed to measure the following blood flow velocities: peak systolic velocity (PSV), end diastolic velocity (EDV), and ICA/CCA PSV ratio. The severity of CAS was calculated by measuring the patent lumen at the stenotic site (diameter redaction), PSV, EDV, and ICA/CCA PSV ratio. The vertebral artery was also scanned during the carotid examination. Patients were classified into groups according to the level of severity. This classification was based on the diagnostic criteria of the Society of Radiologists in Ultrasound Consensus Conference in

Statistical analysis
Suitable purposive sampling with a standardized datasheet (Microsoft ExcelTM, Microsoft Corporation, One Microsoft Way, Redmond, WA) was utilized to collect crucial information on the study population. Data in this study were analyzed using IBM SPSS Statistics for Windows (Version 20.0; IBM Corp., Armonk, NY). Descriptive data for categorical variables were presented as frequencies (percentages). The normality of the distribution of continuous variables [age in years; body mass index (BMI) in kg/m2; ICA/CCA PSV ratio (right and left)] was assessed using the Shapiro-Wilk test and all variables were skewed (p < 0.05). Data concerning age and BMI were presented as the mean ± standard deviation (SD) and median (interquartile range). Fisher's exact test was used to assess the link between two categorical variables and post-hoc tests were used to further investigate significant findings. The Kruskal-Wallis test was used to compare median age and BMI across the different groups (patients with and without CAS) and pairwise comparisons were conducted to further explore the associations found. Multinomial logistic regression analysis was performed to investigate determinants of bilateral and unilateral CAS. Variables were coded as follows: gender (Female = 0, Male = 1); age group (≤ 50 years = 1, 51-60 years = 2, 61-70 years = 3, > 70 years = 4); diabetes (No diabetes = 0, Diabetes = 1); hypertension (No hypertension = 0, Hypertension = 1); diabetes and hypertension (No = 0, Yes = 1); smoking status (Non-smoker = 0, Smoker = 1); weight status (Underweight = 1, Healthy weight = 2, Overweight = 3, Obese = 4); and severity of CAS (Normal = 0, Mild = 1, Moderate = 2, Severe = 3, Total occlusion = 4). All tests used were two-tailed and with a significance of 95%.

Sample characteristics
The total number of patients included in this study was 261 and 78.5% (n = 205) were male. The mean age of patients was 61.6 ± 11.3 years (median: 62.0; range: 55.5-68.0), with 57.9% (n = 151) > 60 years old. Forty percent of the study sample were smokers (n = 104

Description of clinical data
Descriptive clinical data linked to bilateral and unilateral CAS among the study sample are shown in Table 3. Among the study sample: 61% (n = 160) have increased intima media thickness of the right carotid artery and 64.0% (n = 167) have increased intima media thickness of the left carotid artery; plaque of the right carotid artery was reported among 59.8% (n = 156) and plaque of the left carotid artery among 64.0% (n = 167); and the mean right side ICA/CCA PSV ratio was

Prevalence of bilateral and unilateral CAS and association with characteristics of the study sample
The prevalence of CAS among the study population was 71% (n = 187): 52% (n = 136) with bilateral CAS and 19.5% (n = 51) with unilateral CAS. Over half of the patients included in this study had bilateral CAS (n = 136) whereas 7.70% (n = 20) had right unilateral CAS and 11.9% (n = 31) had left unilateral CAS (see Figure 1).

FIGURE 1: Prevalence of bilateral and unilateral carotid stenosis among the study sample.
The characteristics of the study sample and associations with bilateral and unilateral CAS are shown in Table 4. Gender was not linked to bilateral or unilateral CAS status (p = 0.259) but age group was significantly associated (p = 0.001

Determinants of bilateral and unilateral CAS
Results obtained from the logistic regression analysis that aim to investigate determinants of bilateral and unilateral CAS are shown in Table 5  *Significant at the 95% confidence level. One underweight patient was eliminated from the analysis to avoid error in output. Reference category for outcome in all models was "normal carotid artery"

Association between sample characteristics and severity of CAS
The associations between sample characteristics and severity of CAS among the study sample are shown in

Discussion
Significant CAS among patients undergoing coronary artery bypass graft (CABG) increases the risk of a cerebrovascular event [19]. Therefore, a preoperative carotid ultrasound examination is critical to predict perioperative stroke. Carotid ultrasonography is noninvasive, cost effective, and valuable for assessing the carotid artery and improving quality of life [20]. This study aimed to determine the prevalence and common risk factors of CAS among cardiac surgery patients.
In our study, the prevalence of overall CAS among the study population was 71% (n = 187): 52% (n = 136) with bilateral CAS and 19.5% (n =51) with unilateral CAS. The results of our study are consistent with other previous research studies, in which the prevalence of CAS was found to be 77% [21]. Moreover, Zhang et al. (2015) classified the incidence of CAS based on its severity and found 54.5% with mild CAS, 13% with moderate CAS, 4.7% with severe CAS, and 0.8% with occlusion of the carotid artery [15]. These findings are consistent with our study, in which the prevalence of mild (< 50%), moderate (50-69%), severe (>70%), and occlusion was 54.8% (n = 43), 14.6% (n = 38), 1.5% (n = 4), and 1.1% (n = 3), respectively. However, Ranjan et al. (2022) found the overall prevalence of CAS to be 13% lower than the findings in our study. This study contrasts with the aforementioned study, in which there were specific selection criteria and the prevalence of CAS was only found in patients undergoing CABG, with other types of cardiac surgery excluded [11]. Several studies reported the risk factors of significant CAS, such as a history of cerebrovascular accident, diabetes mellitus, hypertension, dyslipidemia, and obesity [10][11]17]. Our study demonstrates a positive relationship between age and the severity of CAS, with older patients displaying a significant association (p < 0.001). Age group was also significantly associated with bilateral CAS.
This study supports the evidence of a relationship between age and CAS from several previous studies [15,[22][23] [10].
The results of this study indicate a significant association between hypertension, diabetes mellitus, and a combination of both diseases and CAS (p < 0.05, for all). Furthermore, our study supports evidence that hypertension is another risk factor associated with the severity and bilateral CAS from previous observations, in which high blood pressure leads to the accumulation of cholesterol in the arterial wall, which increases the risk of a plaque rupture [10-11, 15-17, 23]. This study confirms that diabetic mellitus is associated with severity and bilateral CAS. Lu et al. (2020) reported that diabetic mellitus complications affect the microvascular structures, which increase carotid intima media thickness [24]. These results corroborate the findings of numerous previous reports [10][11]15].
In addition, our study, in contrast to previous studies, found that BMI is not related to the severity and bilateral CAS. This suggests that severe CAS is significantly associated with obesity [10][11]25]. Another obvious finding to emerge from the analysis is that gender is not associated with the severity or bilateral CAS, which is consistent with other previous studies [10,25]. However, Zhang et al. (2015) found that being male is one of the independent predictors of severe CAS [15], while Ranjan et al. (2022) found that being female is a potential risk factor associated with significant CAS [11]. These findings do not support our research, but this could be due to the different populations and smaller sample sizes being used in different studies. With that said, this study has several limitations. First, we did not follow up with the patients after their cardiac surgery to evaluate the impact of CAS on perioperative stroke and the outcome of cardiac bypass surgery among patients with CAS. Moreover, ultrasonography is highly operator dependent and the results may be affected by technical factors.

Conclusions
A high prevalence of CAS was found among patients undergoing cardiac surgery. Age, diabetes mellitus, and hypertension were found to be major risk factors for CAS, as these conditions are significantly associated with the severity and bilateral CAS. Gender and weight status were not associated to CAS. In addition, a preoperative carotid duplex scan is a useful exam to identify CAS among cardiac surgery patients and, therefore, to predict and reduce postoperative neurological complications. Further studies are required to assess the efficacy of ultrasound duplex for evaluating CAS in comparison with CT angiography and for determining the impact of CAS on perioperative stroke.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board , General Directorate of Health Affairs in Madinah issued approval 22-080. Institutional Review Board , General Directorate of Health Affairs in Madinah is pleased to inform that , the study mentioned below has been reviewed and approved . Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.