CAROTID ARTERIES
Atherosclerosis is the most common cause of both carotid and coronary artery stenotic disease. The plaques were detected in carotids in 31% of patients during the PESA (Progression of Early Subclinical Atherosclerosis) Study 23. Ruptures of atherosclerotic plaques, which can lead to thrombus formation, can clinically manifest as stroke or as ACS 24. Many reports suggest a correlation between the presence of atherosclerosis in the coronary arteries and carotid arteries. Proving such correlations can help identify the presence of atherosclerotic plaques in the coronary arteries using a non-invasive imaging modality - CAUS. Reports of an association between the presence of atherosclerotic plaques in the carotid arteries in CAUS and the presence of atherosclerotic plaques in the coronary arteries have been demonstrated in observational studies - prospective and cohort studies (Table 2).
There are also reports that carotid atherosclerosis, and carotid artery stenosis (CAS), are independent predictors of major adverse cardiovascular events in patients without preexisting CAD (respectively, HR=1.69; p=0.07 and HR=3.17; p<0.01) 25. They also showed that the incidence of clinically significant severe CAS (>50%) was progressively increased among patients with non-obstructive CAD, single vessel disease (VD), double VD, triple VD, and left main coronary artery disease. In the Japanese population, the prevalence of carotid stenosis diagnosed in CAUS was 14.5% in single VD and 29.8% in multivessel disease (p<0.0001)16. Also, in patients with confirmed CAD, the majority (about 95%) showed atherosclerotic changes in the carotid arteries, with 15% showing hemodynamically significant CAS 8. The result of the study by Puz et al. is also significant, as they found no differences in the incidence of carotid atherosclerosis between patients with stable and unstable CAD (15.3% vs. 19%, respectively)15. Another study also confirmed the hypothesis that critical CAS is more common in patients with CAD 26. It has also been shown that maximal plaque area can reflect the clinical severity of CAD and can be used as a simple, non-invasive indicator of the severity of coronary atherosclerosis 27. One study confirmed that the presence of plaques is a better predictor of CAD and the Framingham risk scale than intima-media thickness (IMT). This study found that patients with CAD had a higher rate of clinical (referred to as the presence of plaque) or subclinical (referred to as IMT) carotid atherosclerosis 28. In the study by Morito et al. also IMT and plaque score (PS) were assessed in a population of Japanese patients and compared with CA data 29. It was shown that a high PS showed the strongest predictive value for the presence and/or severity of CAS. A study by Kandasi et al. examined the relationship between CAD and common carotid artery (CCA) wall morphology also using CAUS. They showed that the strongest predictor of CAD was the presence of calcified atherosclerotic plaque compared to the presence of fibrous plaque and thickened IMT 30. Moreover, in the study group, none of the subjects with normal CCA wall morphology had significant coronary artery lesions. Another meta-analysis confirmed that atherosclerosis affects both the carotid and coronary systems, although not always in identical phenotypes 31. It confirmed that carotid artery testing is useful in any case of suspected CAD. It cites publications showing a correlation between CAS and significant CAD (r=0.53, P<0.001) and between carotid and coronary calcification (r=0.61, P<0.001). The studies cited in this meta-analysis 32-36 and others are summarized in Table 2.
Reduction of Atherothrombosis for Continued Health (REACH) registry with 4-year follow-up (23 364 patients) showed that the risk of coronary events increased by 22% in patients with versus without carotid atherosclerosis 37. The prevalence of critical CAS has been shown to correlate with the number of critically stenosed coronary arteries. Patients (n=109) with severe CAD (three-vessel disease) were also examined for CAS with CCT 38. Significant lesions included cervical and intracranial segments of both the internal carotid artery (ICA) and the right vertebral artery. An autopsy study by Molnár et al. comparing the extent of atherosclerosis in the carotid, coronary and femoral arteries showed correlations among patients who died of ischemic stroke. The authors found a significant correlation between the external carotid and left anterior descended coronary artery (r=0.458, p=0.028) 39.
Advances in the US have also increased the role of this method in the stratification of patients with CAD. The US is used to detect subclinical atherosclerosis, particularly by evaluating the plaque (height, total area) in the carotid arteries, and is increasingly used in making clinical decisions regarding the treatment of atherosclerosis40-42. This method is now standardized in the 2020 American Society of Echocardiography (ASE) guidelines43. The benefits of arterial US can also be achieved in asymptomatic patients. As described in a systematic review by Peters et al. who showed that imaging of subclinical atherosclerosis as an adjunct to conventional risk factor assessment can improve risk prediction of cardiovascular events (CVE) in asymptomatic individuals44. Relevant evidence includes: CIMT, carotid plaques, and/or coronary arteries calcium score (CACS). In addition to the mere co-occurrence of plaques in the mentioned arteries, the phenotype of the plaques may also be effective in patient risk stratification. A closer analysis of plaques was also studied by Zhao et al. in which they found a significant correlation between plaque phenotype and carotid artery plaque composition 45. They also found that mixed coronary plaque may suggest high-risk carotid plaque. In addition, a study was conducted to investigate plaque composition concerning the incidence of stroke and CAD in a group of asymptomatic individuals who had subclinical atherosclerosis in CAUS 46. Plaque features were assessed by resonance imaging - the presence of specific plaque components (intimal hemorrhage [IPH], lipid-rich necrotic core, and calcification, and measures of plaque size). A study showed that the presence of IPH in carotid atherosclerotic plaque is an independent risk factor for stroke and CAD. The article by Uematsu et al. on ultrasound evaluation of the carotid artery highlighted the assessment of atherosclerotic plaque echo lucent as a predictor of coronary events 47. Echolucent carotid artery plaques are characterized by being rich in macrophages and lipids. Susceptible plaques can be stabilized by statins. The study aimed to identify patients who are at high risk but could benefit from lipid-lowering therapy for secondary prevention. As it turned out, the evaluation of carotid artery echolucency was useful in this selection and made it possible to predict secondary coronary events in patients with CAD after statin therapy. The study also showed that the prognostic effect of lipid-lowering therapy depends on the echolucency of atherosclerotic plaque in the carotid artery 48. In addition to phenotypic plaque characteristics, it has been shown that assessment of neovascularization can be useful in risk stratification of patients at cardiovascular risk. This can be assessed by quantitative analysis by contrast-enhanced ultrasound of the carotid artery. Based on the common underlying pathology of atherosclerosis in the 2 arterial systems, the study of carotid arteries in CAD and vice versa became clinically important to accurately identify patients who could benefit from aggressive preventive therapy as well as prompt treatment49, 50.