With the development of imaging modalities, imaging parameters of vascular changes might reflect the long-lasting effects of some disease such as CAD, diabetes and so on. Thus, the guidelines for assessment of CV risk published in 2010 recommended some vascular imaging parameters should be used as the biomarkers [12, 13]. Extra-cranial carotid artery is the most widely accepted window to predict CV disease, especially when IMT measurement and arterial stiffness evaluation by ultrasonographic method became available.
IMT has long been measured in routine clinical examinations, and is considered a good indicator of any future CV disease. An increase in carotid IMT has been reported to be associated with an increased risk of ischemic heart disease and cerebrovascular disease [14–17], but other studies have disagreed [18–20]. Nowadays, RF-based devices provide more accurate measurement because they are based on the signals with higher spatial resolution [21, 22]. Previous studies suggested that IMT measurements should be proposed for screening of CV events. While, in population with different risk profiles (e.g. with vs. without previous cerebrovascular disease (CVD) or diabetes mellitus (DM), on vs. off treatment), these parameters need to be verified the added value in individual risk prediction. For that reason, in the present study, we choose to include the variable only to comparison carotid properties and angiographic coronary lesions. In the present study, vascular morphological changes in IMT differed greatly between groups and were also found to be positively correlated with angiographic coronary lesions. Each 20 µm increment in IMT increased the risk of atherosclerosis of coronary artery increased by 78% after adjustment. Similar reports by Hodis et al [23] showed that they performed serial carotid IMT measurement and quantitative coronary angiography on 146 patients with history of coronary artery bypass graft surgery for an average follow-up of 8.8 years and found that for each 0.03 mm increase per year in CIMT there was an increase in the relative risk of coronary event of 3.1. Another study by a meta-analysis of 8 large, prospective studies found that each 0.1 mm increment in carotid IMT was associated with a 10–15% to increase the risk of myocardial infarction [24]. Current guidelines state that a common carotid IMT > 900 µm can be regarded as a conservative estimate of existing abnormalities [25]. The cut-off value of carotid IMT for predicting CAD in our study was 821.5 µm, which was much lower than previous reports. When the IMT increased to 905.6 µm, the patients became prone to have multiple coronary damages. As discussed before, the technique of measuring carotid IMT measurement could be sufficiently standardized before widespread clinical screening, particularly when the sub-millimeter difference in IMT will be treated as an important factor to separate low-risk and high-risk groups [26]. Nevertheless, as a measurement, IMT has the benefit of standardized acquisition to be considered as one of the best predictor of arterial atherosclerotic disease.
Arterial distensibility, defined as the change in arterial lumen diameter during the cardiac cycle and contract with cardiac pulsation and relaxation, can be evaluated by ultrasound imaging using wall-tracking systems. Reduced compliance in large arteries reflects structural remodeling in response to elevated pressure, aging, or disease. The arterial remodeling of local and elastic arteries increases the risk for future CV disease. The QAS technique provides a series of standard parameters for assessing arterial stiffness by vessel-wall echo tracking technique [8, 11, 27]. As the most useful and robust index of arterial stiffness [21, 28–30], the assessment of PWV is considered to be the “gold standard” measurement of aortic stiffness. Stiffness parameters α and β are the elastic coefficients from Meinders Hoeks exponential formula, the latter is normalized on the diameters. CC, the fractional change in cross-sectional area relative to the change in arterial pressure, is a good parameter identifying changed arterial compliance. The local vascular stiffness values we measured (PWV, α, and β) increased and CC decreased with increasing severity of CALs.
It has been suggested that clinical features and circulating biomarkers sometimes may be incapable of predicting the risk of CV disease for the past few years [26, 31]. In present study, independent of all the clinical and laboratory variables, each ultrasonographic variable was associated with CALs. The OR values were similar when with or without adjustment analyses. A literature search highlighted that high PWV was associated with roughly two-fold risks of cardiovascular events [32]. Statistical analysis showed that each increment of 0.5m/s in PWV, 1.5 in α and 1.0 in β measurements was associated with a 67%, 68%, and 51% increase in the risk of angiographic coronary atherosclerosis. The reduction of CC with each 0.2 mm2/ kPa meant the increased risk of coronary lesion by 44%. A threshold PWV value of greater than 10m/s could be considered as an indicator of sub-clinical organ damage in hypertensive patients [13]. The QAS variables were correlated with each other in all patients in a dose-dependent manner, showing that the technology provided consistent reference for the evaluation of arterial stiffness. Some reports indicated that functional impairment of the arterial wall may occur early in the atherosclerotic process [33], and arterial stiffening may be a process independent of arterial thickening [34]. Although the relationship between carotid structural and functional changes was obvious, the mechanism of the interaction still remained to be elucidated.
Besides IMT, PWV, α, β, and CC did show good diagnostic performance of in discriminating different coronary lesion in our study. However, there was still a little difference. At an earlier stage, for the patients with only coronary atherosclerosis, β presented the highest diagnostic accuracy, even higher than that of IMT, which might be a support that functional impairment of the arterial wall may occur early in the atherosclerotic process [33]. Furthermore, β also exhibited excellent diagnostic accuracy of single-lesion with sensitivity of 90.91% and specificity of 92.59%. Functional arterial changes may be a marker for the onset of vascular disease before manifestation of symptoms or for the detection of preclinical atherosclerotic lesions [35, 36]. PWV was found to have the high diagnostic accuracy for the prediction of multiple coronary lesions (AUC = 0.9637). The results, for the first time, raised the concern that different stage during coronary atherosclerotic changes might need different biomarkers to predict or diagnose.
There were some limitations to our study. First, the IMT measurement site in the study was plaque-free. Total 43 (14%) subjects were found to have plaques locating exactly right the measurement site in the posterior wall of carotid wall. We had to choose an adjacent site as the ROIs. Considering that both the effect of plaque and different hemodynamics, the stiffness would be different. Second, we did not account the presence of plaques and the value of plaque scores, which was confirmed to be strongly correlated with CAD by several studies [37–39]. Further research with quantitative analysis of carotid plaques should be carried out to verify the present results and validate the predictive value of CCA morphological and functional variables in diagnosing CAD. Last, the number of patients in each group was relatively small, resulting in low statistical power.
Ultrasonographic modalities provide great opportunity to non-invasive imaging both vascular structural and functional changes in large-scale population study. The changes were closely related with detectable coronary lesions. Both QIMT and QAS techniques applied in carotid artery are likely to play a role in CV risk prediction of patients with CAD.