From April 2014 to May 2015, 121 patients who underwent carotid ultrasonography for the evaluation of atherosclerosis status were enrolled in this single-center study. Patients were divided into the following groups according to their renal function and history of dialysis: normal renal function, defined as estimated glomerular filtration rate (eGFR) > 90 mL/min/1.73m², group (control) and the ESRD group according to the guidelines of the Kidney Disease: Improving Global Outcomes (KDIGO).8) Patients with eGFR ≤ 90 mL/min/1.73m² but not undergoing dialysis, patients with significant CCA stenosis (>50%), and patients with CCA stent or prior history of CCA surgery were excluded. The study design was approved by the institution's human research committee, and the study protocol conformed to the ethical guideline of the 1975 Declaration of Helsinki and informed consent was provided by the patients to participate in the study. Clinical characteristics and laboratory results at the time of carotid ultrasound were collected.

High-resolution carotid ultrasound images were acquired using a linear array transducer (nominal bandwidth of 3–12 MHz) with an 8-MHz center frequency (RS80A and HS70A, Samsung Medison, Seoul, Korea). To acquire a high frame rate (>120 fps), the view angle was reduced to ensure accurate measurements of CCA movements. Patients' heads were tilted slightly upward to the midline position, and both CCAs were examined using recordings at ≥2 consecutive beats.

The images showing the multidirectional movements of the CCA were analyzed using commercially available software (Samsung Medison Co., Ltd., Seoul, Korea). The software assesses the functional property of CCAs by automatically calculating the displacement of the CCA walls (Figure 1).

For the analysis, ≥5 mm of the CCA below the origin of the carotid bulb was selected. The user-defined control points, the blood-intima boundaries of the CCA, were manually traced from a still frame image with the best image quality and were automatically tracked by the software based on an optical flow algorithm.9) The control points are constrained to maintain the global shape and to move within a local range, to ensure stability in tracking the motion of vessels. At least four speckles on the CCA wall were identified, and the movements of each speckle during the cardiac cycle were traced at the near and far walls. Radial movement of the CCA in the longitudinal plane and radial circumferential movements in the transverse plane were automatically calculated using the speckle-tracking technique. Peak radial and circumferential displacements, strain, and strain rate were also calculated.

For the calculation of conventional arterial stiffness parameters,10) the central blood pressure, derived from the aortic pulse wave, was measured after ≥5 min of resting in supine position by a trained technician with pulse wave analysis of the radial artery using a tonometry (SphygmoCor; AtCorMedical, Sydney, Australia). The SphygmoCor software calculated the aortic pulse wave by means of a generalized transfer function from the radial signal. The measured central blood pressure was entered into the software, and all arterial stiffness parameters were then automatically calculated from the software according to the pre-defined formula for each parameter. β stiffness index was defined as the ratio of the natural logarithm of central systolic/diastolic pressure to relative change in diameter. Arterial compliance was defined as the absolute change in CCA diameter for a given change in pressure (e.g., difference between the diastolic and systolic diameters [ΔD]/difference between the systolic and diastolic blood pressures [ΔP]). Distensibility refers to the relative change in vessel diameter for a given change in pressure (e.g., ΔD/[ΔP × CCA diameter in the diastolic phase (D)] in mmHg). The elastic modulus index was defined as the pressure change required for the theoretical stretch from the resting vessel diameter (e.g., [ΔP × D]/ΔD in mmHg). (e.g., log [systolic blood pressure/diastolic blood pressure]/[ΔD/D]). Pulse wave velocity β (PWV) was defined as the speed with which the pulse wave travels along the length of the artery (e.g., stiffness index × diastolic blood pressure/[2 × blood density]), while assuming the blood density to be 1.050 g/cm³.

The presence of carotid plaque was defined as a focal structure that protrudes into the arterial lumen and measured ≥1.5 mm or ≥50% of the surrounding intima-media thickness (IMT). Additional images were acquired at another location close to the CCA that does not contain the plaque for patients with carotid plaques for the analysis. Carotid IMT was measured in a semiautomatic manner in the end-diastole phase for bilateral CCAs in the longitudinal plane, and the mean value of the right and left IMTs was used in the analysis. In patients with carotid plaque, IMT was measured at a location where the plaque was not included.

Parametric continuous variables were presented as mean ± standard deviation, and categorical variables were expressed as count (%). Differences between continuous variables were compared using Student's t-test or Mann Whitney U test, as appropriate, whereas the Pearson's chi-squared or Fisher's exact test was employed, as appropriate, for categorical variables. To assess the impact of ESRD on the carotid strain values and conventional aortic stiffness parameters, multivariate linear regression analyses were constructed and adjusted for age, male sex, hypertension, diabetes mellitus, body mass index, creatinine level, high-density lipoprotein level, the presence of carotid plaque, and the maximal diameter of CCA. A two-tailed p-value <0.05 was considered statistically significant. All analyses were performed using SPSS (Version 23.0, IBM Corp., Armonk, NY, USA).

A total of 85 control patients (61 ± 12 years old, 53% were male) and 36 with ESRD (55 ± 3 years old, 61% were male) were enrolled (Table 1). There was no difference in the percentage of male sex (p = 0.431), but patients with ESRD were younger and had more hypertension than control patients (89% vs. 47%, p < .001). Central systolic and diastolic blood pressures were also higher in the ESRD group (all p < 0.05), but there were no differences in body mass index and the presence of diabetes mellitus or hyperlipidemia (all p > 0.05). The level of total cholesterol was higher in the ESRD group (180.8 ± 40.5 mg/dL vs. 160.8 ± 40.0 mg/dL, p = 0.016), but there were no differences in the level of high-density lipoprotein, low-density lipoprotein, and triglyceride (all p > 0.05).

Carotid ultrasonography and subsequent strain analysis were successfully performed on all participating patients. Atherosclerotic carotid plaques were detected in 82.4% of the controls and 31.4% of patients with ESRD (p = 0.002) (Table 2). The mean maximal diameter of CCAs in the longitudinal plane were greater in patients with ESRD than in the controls (7.54 ± 1.32 mm vs. 6.54 ± 0.91 mm, p < .001), but the IMT was not different (0.76 ± 0.15 mm vs. 0.81 ± 0.17 mm, p = 0.121). There were no differences in the β stiffness index and arterial compliance (all p > 0.05) between groups, but the arterial distensibility was lower and the elastic modulus and PWV were higher in the ESRD group (all p < 0.05). When the strain parameters were compared, the radial strain rate in patients with ESRD was significantly lower than that in the controls (0.711 ± 0.298 /s vs. 1.005 ± 0.508 /s, p = 0.001), although there were no differences in displacement and strain.

The results of the assessment of the transverse plane were also consistent (Table 3). The minimal and maximal CCA diameters were greater in patients with ESRD (all p < 0.05). β stiffness index and arterial compliance were not different, but the patients with ESRD exhibited lower arterial distensibility and higher elastic modulus and PWV compared with the controls (all p < 0.05). The speckle-tracking carotid strain analysis revealed that while there were no differences in displacement and strain between both the radial and circumferential methods, both radial and circumferential strain rates were significantly reduced in patients with ESRD (0.72 ± 0.47 /s vs. 0.97 ± 0.45 /s and 0.74 ± 0.54 /s vs. 0.99 ± 0.47 /s, all p < .001).

In the multivariate linear regression analyses adjusted for age, male sex, hypertension, diabetes mellitus, body mass index, creatinine level, high-density lipoprotein level, the presence of carotid plaque, and the maximal diameter of CCA, ESRD had no impact on both conventional aortic stiffness parameters, including distensibility, elastic modulus, and PWV, and strain parameters assessed in the longitudinal plane (all p > 0.05) (Table 4). ESRD also had no impact on distensibility, elastic modulus, and PWV assessed in the transverse plane (all p > 0.05).

In contrast, ESRD was negatively and independently associated with both transverse radial strain and strain rate (β: -6.087 (95% confidence interval [CI]: -10.790 to -1.384) and β: -0.833 (95% CI: -1.390 to -0.275), respectively, all p < 0.05). ESRD also independently reduced the transverse circumferential strain and strain rate (β: -6.771 (95% CI: -11.525 to -2.018) and β: -0.976 (95% CI: -1.582 to -0.371), respectively, all p < 0.05). There was no correlation between male sex and strain values in all models.