3.2. Data Interpretation
Calcium formation can be found in any arterial bed. It may be present in the lumen as a calcified plaque cap or may also invade the intima or media [10
]. It has been shown that the amount of calcification quantified by carotid CT correlated with respective histology sections [11
]. Carotid US is an easy and economically favorable method to study different plaque features and their potential association with symptoms [13
]. Although it was previously reported that carotid plaque echogenicity, evaluated by US, may not adequately reflect the degree of carotid plaque calcification [14
], our study is the first to demonstrate the accuracy of carotid US in identifying calcification deposits and showing that non-detectable calcification is of lower volume and is dispersed throughout the plaque. It was reported that calcification of the carotid plaque is associated with adverse outcomes, such as ipsilateral ischemic stroke, 30 days after carotid artery stenting [15
]. Thus, CEA could be feasible in such cases. As many centers now rely mainly on the carotid US findings before intervention, identification of calcification may guide towards better patient risk stratification.
Our findings show that US was accurate in identifying carotid plaques, which after excision proved to have a calcification volume of at least 8 mm3
. This accuracy was seen in both the two technologies used to assess carotid calcification, CBCT, which directly quantified the calcification volume of extirpated carotid plaques, and US, which qualitatively evaluated plaque echogenicity and posterior shadowing as indirect evidence for plaque calcification. The calcium volume detectable by US (≥8 mm3
) is relatively significant when compared with normal intima-media thickness, which is usually less than 1 mm, highlighting the accuracy of the US examination in detecting sizable carotid masses. In contrast, the same method failed to detect carotid calcification below a volume of 8 mm3
with reliable accuracy. In addition, our findings did not show any statistical difference in the presence of calcification between symptomatic and asymptomatic patients, in keeping with our previous findings [9
The exact mechanism behind carotid calcification as a potential risk for cerebrovascular events and in predicting strokes still remains controversial [5
]. A systematic review suggested that clinically symptomatic plaques have a lower degree of calcification than asymptomatic plaques [7
]. This review had some potential limitations due to the wide range of methods used, highlighting the need for a well-validated, accurate and reproducible technique for calcium quantification. The relationship between arterial calcification and vascular events is more thoroughly studied in the setting of coronary artery disease because of the widely available CT scans performed on patients in cardiology units. Many studies have already shown that the extent of coronary calcification correlates with future development of cardiac events and disease burden [17
]. This of course does not refute the presence of a subgroup of patients with calcific coronary artery disease in whom extensive calcification, based on Agatston score classification, is associated with recurrent angina but stable plaques [10
]. Finally, it has recently been shown that statin therapy increases plaque echogenicity [19
] and coronary artery calcification [20
]. In our cohort 87.3% of patients were using statin therapy, limiting us in carrying out a reliable comparison between groups.
3.3. Clinical Implications
Our findings support the use of US optimum grey scale echogenicity and plaque shadowing as an accurate manifestation of sizable calcification of a minimum volume of 8 mm3. US does not appear well suited for the detection of smaller calcium deposits, although they might play a role in plaque vulnerability. Although this method of calcification detection by US is subjective in nature, it establishes a potential foundation for the future development of quantitative models, which could guide towards improved identification of plaque characteristics as a step towards achieving plaque stabilization through optimum treatment. This approach, however, is not sufficiently accurate to detect early calcification pathology based on this biased patient selection. Further development of US plaque studies using methods which quantify echogenicity (grey scale median) could enable detection of earlier stages of calcification and reduce the need for advanced CT examinations and the resultant radiation for patients.
3.4. Study Limitations
Because almost all (98.9%) carotid plaques were calcified, as assessed by CBCT, evaluation of US positive and negative predictive value was not possible. We cannot be sure if all calcified material was excised during the CEA procedure but we are working on the assumption that the largest plaque with the largest calcium volume was removed and assessed by CBCT. Furthermore, we cannot be sure that the calcification quantified by CBCT was the same hyperechogenic calcium nodule seen by US in cases with multiple calcifications but we made a further assumption that the nodule with the largest volume was the same nodule as caused the posterior shadowing. In addition, the number of patients with asymptomatic carotid stenosis was small compared with the symptomatic patients, therefore weakening our conclusion in this subgroup. The exact role of stenosis severity in determining accuracy of US in detecting calcification cannot be established since most of our patients had significant (>50%) stenosis.