|Year : 2019 | Volume
| Issue : 1 | Page : 1-7
Close association between carotid and coronary atherosclerosis analyzed through SYNTAX score
P Levantino1, G Polizzi2, S Evola1, G Leone1, G Evola1, G Novo1, S Novo1
1 Department of Cardiology, University Hospital Paolo Giaccone, Palermo, Italy
2 Department of Cardiology, University Campus Bio-Medico, Rome, Italy
|Date of Submission||10-Mar-2018|
|Date of Acceptance||01-Mar-2019|
|Date of Web Publication||24-Jul-2019|
Department of Cardiology, University Hospital Paolo Giaccone, Palermo
Source of Support: None, Conflict of Interest: None
AIM: This study analyzed the association between carotid and coronary atherosclerosis, particularly in terms of the severity as well as the extension of the disease.
MATERIALS AND METHODS: We have recruited a consecutive series of 478 patients (admitted to the Cardiology Unit of University Hospital Paolo Giaccone during 2004–2014). These patients underwent both carotid Doppler ultrasound and coronary angiography. Sex, age, and traditional cardiovascular risk factors were considered. The SYNTAX score was used to grade the complexity of coronary disease.
RESULTS: The present study revealed a clear association between carotid atherosclerosis and coronary disease: 68.2% of the examined population showed atherosclerosis in both carotid and coronary arteries. The absence of carotid atherosclerosis was predominantly associated with angiographically normal coronary arteries (37.6%) rather than a single-vessel disease (22.8%), a two-vessel disease (21.8%), or a three-vessel disease (17.8%). When carotid atherosclerosis was present, a normal coronary angiography was uncommon (13.5%), while the detection of a single-vessel disease was more frequent (17.2%), a two-vessel disease was even more frequent (27.6%), and the highest rate described was related to a three-vessel coronary artery disease (CAD) (41.6%). The thickness of the carotid lesion was directly proportional to the number of diseased coronary vessels, and it was also related to the severity of coronary involvement measured by the SYNTAX score.
CONCLUSIONS: This study has shown a strong correlation between carotid atherosclerosis and CAD, in terms of extension, and most importantly, severity. It is fundamental to consider a systemic approach to atherosclerosis to obtain an adequate stratification of patients with cardiovascular risk factors and an appropriate therapeutic management and reduce the incidence of adverse events, improving the quality of life and prolonging survival.
Keywords: Atherosclerosis, carotid lesion, coronary artery disease, SYNTAX score
|How to cite this article:|
Levantino P, Polizzi G, Evola S, Leone G, Evola G, Novo G, Novo S. Close association between carotid and coronary atherosclerosis analyzed through SYNTAX score. Vasc Invest Ther 2019;2:1-7
|How to cite this URL:|
Levantino P, Polizzi G, Evola S, Leone G, Evola G, Novo G, Novo S. Close association between carotid and coronary atherosclerosis analyzed through SYNTAX score. Vasc Invest Ther [serial online] 2019 [cited 2019 Oct 15];2:1-7. Available from: http://www.vitonline.org/text.asp?2019/2/1/1/263389
| Introduction|| |
Although scientific research has done much progress in terms of prevention, diagnosis, and treatment of cardiovascular diseases, they still represent, nowadays, one of the main problems in public health: they are, in fact, the leading cause of death in industrialized countries and one of the most important sources of morbidity, disability, and hospitalization.
The main process causing cardiovascular diseases is the atherosclerosis, a chronic inflammatory process of multifactorial etiology, characterized by the formation of fibrolipid plaques in the artery wall. Rupture and fissure plaque results in the formation of a thrombus occluding arterial lumen and leading to ischemia of the tissue.
Clinical manifestations depend by localization of atherosclerotic process; for example, the formation of plaques in the carotid artery can lead to a transient ischemic attack or ischemic ictus, in the coronary artery to angina or myocardial infarction and in the artery of inferior limbs to the chronic obstructive vascular disease of the inferior limbs (peripheral chronic obliterative arteriopathy).
Given the great impact of these diseases on the population, it is important to identify the factors associated with its development and progression. Beyond traditional risk factors such as age, gender, family history of cardiovascular disease, hypertension, hypercholesterolemia, diabetes, and smoking, other important conditions are emerging risk factors such as fibrinogen, high-sensitivity C-reactive protein and other markers of inflammation, metabolic syndrome, hyperhomocysteinemia, a burden of previous infections, and instrumental markers of preclinical atherosclerosis, as intima–media thickness (IMT) or asymptomatic carotid plaque (ACP), ankle–brachial pressure index measurement, evaluation of endothelial dysfunction by flow-mediated dilatation vasodilation, and multidetector computed tomography of coronary arteries.
Several clinical studies have reported a variable prevalence of concomitant carotid and coronary lesions in patients with or without clinically evident cardiovascular disease.,,
In our study, we want to analyze the association between carotid and coronary atherosclerosis, particularly in terms of severity as well as the extent of the disease.
| Materials and Methods|| |
Data were collected from 478 patients (admitted to the Cardiology Unit of University Hospital Paolo Giaccone during 2004–2014) who underwent both carotid Doppler ultrasound and coronary angiography. Sex, age, and traditional cardiovascular risk factors were considered.
Carotid Doppler ultrasound identified the presence of IMT and eventual atherosclerotic plaques. In particular, B-mode real-time ultrasound was used to evaluate the arterial wall thickness in the carotid arteries using a machine Toshiba 270 SS with a probe of 7.5–10.0 MHz. The power output, focus, depth of measurement, and gain were standardized using the preset program incorporated within the software package of the ultrasound equipment. The IMT was defined as the distance between the echogenic line representing the intima–blood interface and the outer echogenic line representing the adventitia junction. After freezing the image, the measurement was made with electronic calipers. According to the most recent guidelines of the joint European Society of Hypertension/European Society of Cardiology (ESC), we considered “normal” patients to be those with IMT <0.9 mm, “with IMT” to be those with IMT between 0.9 and 1.5 mm, and “with asymptomatic carotid plaque” to be those with IMT >1.5 mm.
Coronary angiography is the radiographic visualization of the coronary vessels after the injection of radiopaque contrast media. Percutaneous techniques, usually from the femoral or brachial artery, were used for insertion of special intravascular catheters with which we obtained selective cannulation of the ostium of the left and right coronary arteries. The radiographic images were permanently recorded for future review with digital recording. In particular, digital angiographic images were acquired by Philips Integris 2000 angiography or by Siemens Artis Zee, at rate of 12.5 frames/s. Coronary angiography resulted in a stratification that separated patients with normal arteries and patients with coronary disease localized in one, two, or three vessels, thus only considering the extent of the disease itself. The severity of the disease was instead examined using the SYNTAX score. The SYNTAX score has been developed based on the following: the American Heart Association (AHA) classification modified for the ARTS study,, the Leaman score, the American College of Cardiology/AHA lesion classification system, the total occlusion classification system, and the Duke and International Classification for Patient Safety classification systems for bifurcation lesions. Subsequently, the Medina classification of bifurcation lesions was introduced. Each of these classifications has been focusing on specific functional and anatomical parameters of the lesions.
The SYNTAX score results from the sum of the individual scorings of each separated lesion defined as >50% stenosis in vessels with a diameter >1.5 mm. This score is weighed on the location of the disease in different coronary segments (e.g. a higher score is assigned to a lesion involving the proximal left anterior descending artery or the left main compared to one involving a small peripheral vessel). A multiplication factor of 2 is used for nonocclusive lesions and 5 is used for total occlusions, which reflects the difficulty of the revascularization procedure through angioplasty. A computer algorithm calculates the total score based on 12 key questions, divided into two groups: the first group consisting of three questions determining the coronary dominance, the total number of lesions, and coronary segments involved and the second group consisting of questions related to the morphological characteristics of the lesions (total occlusion, trifurcation, bifurcation, aorto-ostial lesion, severe tortuosity, length >20 mm, heavy calcification, thrombus, and small vessel/diffuse coronary artery disease [CAD]).
The scores obtained with the SYNTAX score can be divided into three tertiles: low (score ≤22), intermediate (23–32), and high (≥33). A high score indicates a more complex coronary anatomy and suggests a high risk of subjecting the patient to a strategy of mechanical revascularization and is associated with a poor prognosis (then better with coronary artery bypass grafting). An average or low score indicates the intervention of percutaneous angioplasty as a preferable treatment.
Statistical analysis was performed with MedCalc v. 15.8 is a statistical software (MedCalc Software, Broekstraat 52, 9030 Mariakerke, Belgium) for Windows. Categorical variables are presented as absolute frequency (n) and percentage (%) and compared using the Chi-squared test. Continuous variables are presented as standard deviation and compared with the categorical ones using the ANOVA test. The SYNTAX score was related to other variables using the linear regression test. P < 0.05 was considered statistically significant.
| Results|| |
Epidemiological characteristics of the population of our study are reported in [Table 1]. In brief, we have collected data from 478 patients. In this population, there were 264 men (55.2%) and mean age was 68.4 years (68.4 ± 10.68). Regarding cardiovascular risk factors, we have found that 174 people (36.4%) had a family history, 417 (87.2%) hypertension, 304 (63.6%) dyslipidemia, 212 (44.4%) diabetes, 189 (39.5%) tobacco smoke, and 57 (11.9%) obesity. Three hundred and seventy-seven patients had carotid atherosclerosis and 390 had coronary atherosclerosis.
As regards the correlation between carotid and coronary atherosclerosis [Figure 1], 36 patients (7.5%) had neither carotid atherosclerosis (atherosclerotic plaques, excluding IMT) nor coronary atherosclerosis, 51 patients (10.7%) had carotid atherosclerosis but normal coronary arteries, 65 patients (13.6%) had coronary atherosclerosis but normal carotid arteries, and 326 patients (68.2%) had both carotid and coronary atherosclerosis.
|Figure 1: Association between carotid and coronary atherosclerosis (P < 0.0001)|
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Between 101 patients with normal carotid arteries [Figure 2], 38 had normal coronary arteries (37.6%), 23 had a one-vessel disease (22.8%), 22 had a two-vessel disease (21.8%), and 18 had a three-vessel disease (17.8%).
|Figure 2: Correlation between carotid atherosclerosis and number of diseased coronary vessels (P < 0.0001)|
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Between 377 patients with carotid atherosclerosis [Figure 2], 51 patients had normal coronary arteries (13.5%), 65 patients had a one-vessel disease (17.2%), 104 patients had a two-vessel disease (27.6%), and 157 patients had a three-vessel disease (41.7%).
Between 112 patients with unilateral carotid atherosclerosis [Figure 3], 26 had normal coronary arteries (23.2%), 24 had a one-vessel disease (21.4%), 23 had a two-vessel disease (20.5%), and 39 had a three-vessel disease (34.9%).
|Figure 3: Correlation between number of carotid plaques and number of diseased coronary vessels (P < 0.0001)|
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Furthermore, among 265 patients with bilateral carotid atherosclerosis [Figure 3], 25 had normal coronary arteries (9.4%), 41 had a one-vessel disease (15.5%), 81 had a two-vessel disease (30.6%), and 118 had a three-vessel disease (44.5%).
Finally, in our study, we found that the thickness of carotid plaque is significantly correlated with the number of diseased coronary vessels [Figure 4] and that there is a significant correlation between the thickness of carotid plaque and the severity of coronary disease [Figure 5].
|Figure 4: Correlation between thickness of carotid plaque and number of diseased coronary vessels (P < 0.007)|
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|Figure 5: Correlation between thickness of carotid plaque and severity of coronary disease (P < 0.033)|
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| Discussion|| |
The present study revealed a clear association between carotid atherosclerosis and CAD, with high statistical significance (P < 0.0001). A high percentage of the examined population showed evidence of atherosclerosis in both carotid and coronary arteries, underlining the multifocal feature of the disease. Of course, the absence of carotid atherosclerosis did not exclude the presence of CAD or vice versa. However, if it was present, carotid atherosclerosis was strongly associated with atherosclerosis in the coronary district, representing a significant positive predictor of CAD.
Furthermore, the absence of carotid atherosclerosis was predominantly associated with angiographically normal coronary arteries (37.6%) rather than a single-vessel disease (22.8%), a two-vessel disease (21.8%), or even a three-vessel disease (17.8%). The opposite was observed when carotid atherosclerosis was present. In this case, a normal coronary angiography report is uncommon (13.5%), while the detection of a single-vessel disease was more frequent (17.2%), a two-vessel disease was even more frequent (27.6%), and the highest rate described was related to a three-vessel CAD (41.7%).
We must also consider an increasing number of coronary arteries affected by stenosis gradually moving from a normal condition of the carotid arteries to unilateral carotid atherosclerosis, up until bilateral carotid atherosclerosis.
In our study, the thickness of the carotid lesion was proven to be directly proportional to the number of diseased coronary vessels; moreover, the width of carotid stenosis is closely linked to the severity of coronary involvement, measured by the SYNTAX score. This study has, therefore, found an association between carotid and coronary atherosclerosis, regarding the anatomical extent of the disease as well as its severity. A pattern of severe atherosclerosis in the carotid district is most likely associated with severe atherosclerosis in the coronary district. The findings were in line with international researches and literature data. In fact, a study by Kabłak-Ziembicka et al. showed that the IMT was significantly correlated to the number of coronary vessels with stenoses (P < 0.001) as well as the study by Amato et al. showed a significant correlation between values of carotid IMT and of coronary IMT evaluated by intravascular ultrasound (P = 0.0001), as well as between carotid IMT and percentage of coronary stenosis as evaluated by coronary angiography (P = 0.03), supporting the concept that carotid IMT is a good surrogate marker of coronary atherosclerosis.
These findings have a clinical impact, as demonstrated by various studies. In a study, performed in asymptomatic high-risk patients followed for 5 years, a significant increase of fatal and nonfatal cerebro- and cardiovascular events in those patients that at baseline present with IMT or ACPs in comparison to participants with normal carotid arteries at baseline was shown. The Asymptomatic Carotid Stenosis and Risk of Stroke study determined the risk of ipsilateral ischemic neurological events in relation to the degree of carotid stenosis and other risk factors, showing a linear relationship between stenosis and risk. The evidence of ACP is associated with a four-fold higher risk of acute coronary syndrome. The presence of carotid plaques is associated with an increased risk of cardiovascular events in patients with CAD, regardless of the strategy of treatment (medical therapy or revascularization).
In further support of the weight that carotid disease has on overall risk, the ESC guidelines on cardiovascular prevention consider patients with carotid plaque on ultrasound as patients at very high risk.
Another confirmation of the close relationship between carotid atherosclerosis and coronary disease comes from a study of asymptomatic patients at high risk (observed for 5 years), which showed a significant increase of cardiovascular and cerebrovascular events in patients with underlying ACP at the beginning of the follow-up, compared with those who had no carotid stenosis.
In the Reduction of Atherothrombosis for Continued Health Registry, 4-year age- and sex-adjusted coronary event rates were higher among patients with versus without carotid atherosclerosis (23.2% vs. 19.3%). The presence of carotid atherosclerosis predicted the risk of coronary events in patients with a history of atherothrombotic events, irrespective of the arterial bed involved (cerebrovascular disease [CVD], CAD, or peripheral arterial disease). In addition, its predictive value increased with the number of affected arterial beds.
The patients with polyvascular disease (PVD) were found to have a greater degree of cardiovascular risk factors and a higher rate of inhospital mortality, myocardial infarction, stroke, and congestive heart failure. There was a significant, graded increase in risk of ischemic events as well as transfusion, moving from 1 to 2 to 3 prior arterial territories involved compared with 0 arterial territories involved. Future efforts should be directed toward better identification of patients with PVD and targeted therapies to reduce their excess risk. Patients with PVD may represent a population for intensive secondary prevention, both in clinical trial and real-world populations.
Furthermore, in Subherwal et al.'s study, patients with non-ST-segment elevation myocardial infarction (NSTEMI) patients without PVD had the lowest long-term mortality and composite ischemic rates, followed by patients with two-arterial bed involvement (CAD + PVD or CAD + CVD), while those with three-arterial bed involvement (CAD + PVD + CVD) had the highest mortality and composite ischemic rates. These findings indicate that not only PVD increases long-term risk but also there is a gradation of long-term risk associated with increasing burden of atherosclerosis.
These data suggest an important consideration – carotid lesions are predictive of both adverse events in the cerebral circulation and in the coronary circulation, thus proving themselves to be an expression of systemic atherosclerosis.
The ultrasound exploration of the carotid arteries might be useful in the diagnostic algorithm of CAD. It would be able to improve, if associated with the stress test, the ability of the latter to predict the CAD. The presence of ACP, in fact, would increase the chance of observing a stenosis higher than 50% at coronary angiography, thus representing a helpful diagnostic tool in case of a doubtful stress test, as well as for the selection of patients who should undergo more invasive investigations such as coronary angiography.
The evidence of carotid atherosclerosis is, on the one hand, a possible spy of coronary disease and should induce to consider further diagnostic tests aimed to confirm or exclude its presence; on the other hand, the patient's prognosis is worse than the condition in which the CAD is not accompanied by the carotid involvement, so the evaluation of carotid atherosclerosis should be considered in all patients diagnosed with CAD. The identification of carotid disease may influence the treatment strategy in these patients. For example, a more aggressive medical therapy may be indicated in case of preclinical carotid atherosclerosis, while combined surgery could represent a therapeutic option in patients with critical stenosis in both districts.
| Conclusions|| |
This study has shown a marked correlation between carotid atherosclerosis and coronary disease, in terms of extension, and most importantly, severity (thanks to the SYNTAX score). The typical tendency of carotid atherosclerosis accompanied by the coronary involvement explains the increased risk of cardiovascular events in this subset of patients.
It is, therefore, fundamental to consider a global approach to atherosclerosis and cardiovascular diseases in order to obtain an adequate stratification of patients with cardiovascular risk factors, a more appropriate therapeutic management in relation to their overall cardiovascular risk, with the ultimate goal of reducing the incidence of adverse events, improving the quality of life and prolonging survival.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]