Evaluation of carotid artery elasticity changes in patients with type 2 diabetes

Diabetes is a major contributor to atherosclerosis of the arterial bed [1, 2]. Patients with diabetes are at a high risk of artery atherosclerosis leading to cardiovascular disease (CVD), especially coronary heart disease (CHD), which is the most common complication and the principal cause of death in type 2 diabetes patients. The carotid artery can be considered as a model to reflect conditions common to all infected arteries. Detection of structural and functional disorders of the common carotid artery (CCA) by duplex ultrasonography is most favorite method in evaluating systemic artery atherosclerosis.

CCA intima-media thickness (IMT) measurements are considered a strong predictor of future vascular events and a surrogate marker of atherosclerosis [3‐5], although there are some recent studies that contest this theory [6, 7]. Arterial elasticity assessment is also regarded as an independent predictor of cardiovascular mortality and morbidity in patients with cardiovascular disease as well as in healthy individuals [8, 9].

Ultrasound radio frequency (RF) technology is a newly developed modality used for evaluating vascular elasticity of the carotid artery; the measurement of artery elasticity is based on the monitoring of RF signals transmitted by ultrasound. Data acquired by this technology can reflect changes objectively and accurately both from structural and functional aspects. X-strain technology, a vector strain imaging-VSI™, based on angle independent speckle-tracking technology applied to myocardial strain measurements to reduce error compared to Doppler tissue imaging [10, 11]. In the present study, we adapt this method for carotid arterial stiffness analysis aiming to assess functional artery changes in patients with type 2 diabetes. In addition, we discuss change tendencies in the carotid artery and how they are identified using this superior technology.

Changes in both structural and functional aspects of arteries have been a research interest for several years as they are considered risk factors for cardiovascular events [12‐14]. As diabetes is one of the most common causes of cardiovascular disease, aortic elasticity was impaired in those with impaired fasting glucose [15], in the present study we focused on carotid arterial wall changes induced by type 2 diabetes by evaluating artery lesions using a new method called ultrasound RF data and X-strain technology. By using QIMT and QAS techniques, high resolution ultrasound acquisitions based on RF signals allow us to assess local IMT and stiffness in a rapid and specific manner.

The structural indicators IMT and plaque have been endpoint markers in clinical trials [16‐18]. We discovered that IMT of the RCCA showed no obvious changes in patients with diabetes, whereas some of the elastic parameters showed significant differences in these patients relative to controls. Although our findings differed from other reports [4, 19], it may be one that supports the notion that functional impairment of the arterial wall may occur early in the atherosclerotic process [20], and arterial stiffening may be a process independent of arterial thickening [21].

Many researches showed to us that arterial stiffness is correlated with the presence and severity of arterial atherosclerosis, and also associated with myocardial dysfunction [22‐24]. For functional changes, we assessed both the performance of QAS measurements of vascular stiffness, such as PWV, CC, α, β, and the performance of ultrasonographic speckle tracking-based X-strain measurements. As the most useful and robust index of arterial stiffness [25‐27], PWV measured by QAS likely provides accurate local characteristics of vascular alterations. The local vascular stiffness values PWV and β we measured increased in the patient group, while CC decreased, which validates the hypothesis that arterial remodeling occurring in local and elastic arteries increases the risk for future cardiovascular disease.

Besides the stiffness values acquired by QAS, X-strain techniques, a novel method based on the two-dimensional information obtained directly from the arterial wall itself both for the intima and adventitia at the same time, can give us more information about local arterial stiffness, rather than depending on luminal changes. The quantitative assessment of the regional function of the arterial wall may be based on the mobility of the intima, of the adventitia and on wall thickening. Strain and strain rate imaging provides a quantitative method for assessing the regional function of the arterial wall. The variables include the displacement, strain, and strain rate of the arterial wall movement for circumferential, longitudinal, radial, and rotation movements. Like myocardial movement, the intima and adventitial wall stretch in different sectors at the same time can be showed to us by the real-time X-strain analysis. The final arterial wall movement at that moment is decided by the multi-directional forces on both intima and adventitial wall. Unlike other strain analysis technology, X-strain analysis allows us to evaluate all of the forces at the same time and helps us to comprehensively understand the movement of the arterial wall. To our knowledge, this is the first report in the literature to assess arterial stiffness from multiple angles using the speckle tracking method.

Among all these parameters, circumferential, radial, and rotation variables (CS-DT, RSR-T, and ROT-DT) appeared to be sensitive to CCA stiffness changes compared to the longitudinal variables. In mechanics, Laplace’s law and Poisson’s ratio emphasize that when the force on a circumferential or radial section is two times the force on the longitudinal section, the vascular stretching longitudinally can be neglected, suggesting that the movement of an elastic artery is mainly a type of stretching in the circumferential and radial directions and, as such, the movement of the vascular wall is a vascular diameter change, rather than the vascular length change. Therefore, circumferential and radial strain analysis is capable of accurately reflecting local vascular flexibility. In the study, we introduced time differences for displacement, strain, and strain rate changes as indicators of arterial stiffness because of the specificity of this technology. Neither the intima nor adventitia variables were capable of unilateral reflecting the difference in arterial wall movement between the two groups in the present study. In this study, we, for the first time, validated rotation variables, which was not previously possible to assess because only the elasticity average of the intima and media of the carotid artery wall are calculated using other modalities. Interestingly, the time of rotation peak displacement was much earlier in the patient group than in the control group.

Our study has several limitations, including the small number of patients; patients with hypertension, hyperlipidemia, coronary heart disease, and nephropathy were excluded from the study, which limited the number of patients we could enroll. Secondly, although some clinical measurements were different between two groups’ comparisons in the present study, no obvious relationship was found with the arterial stiffness changes by the statistical correlation analysis, further analyze the data with adjustment was not performed as other studies did [28, 29]. Thirdly, considering the fact that the number of subjects with the presence of plaque was not sufficient for quantitative statistical analysis, the value of plaque score [30] was not evaluated in this study. Although the patients have significant higher TC, LDL, SBP and DBP than controls, but all these laboratory parameters are still in the normal range. Further research with larger populations should be carried out to verify the present results and validate the changes in arterial stiffness in patients with advanced stage diabetes.

In conclusion, the present study demonstrated that patients with diabetes have significantly increased arterial stiffness as assessed by QAS and X-strain assessment. QIMT and QAS techniques can be used to noninvasively and comprehensively assess local elastic arterial remodeling in patients with early stage diabetes.