NAFLD is a clinicopathological syndrome characterized by hepatocyte steatosis and abnormal accumulation of fat (mainly TG) in the absence of secondary causes, such as excessive consumption of alcohol and other factors that cause liver injury [1, 5]. Clinically, carotid atherosclerosis is often accidentally discovered in patients with NAFLD on physical examination. Atherosclerosis is a complex disease process, caused by a combination of structural and functional changes occurring in the arterial walls . Structural changes include build-up of lipids, intimal thickening and plaque formation in the arterial walls, which can be observed by conventional ultrasonographic measurement of IMT. Functional changes occur before the structural changes, and include arterial stiffness and medial hypertrophy due to the gradual increase in blood pressure. It is impossible to differentiate between intimal thickening caused by early plaque formation or functional changes occurring in the arterial wall on the basis of IMT measurement. Therefore, PWV needs to be measured to assess early vascular changes .
UFPWV plays an important role in the evaluation of early arteriosclerosis. With a frame rate as high as 10,000 frames/s, ultrafast ultrasound imaging technology can quickly (within 2 seconds) record the pulse wave propagation in the carotid artery wall and measure PWV-BS and PWV-ES . Assuming that the carotid artery acts like a cylindrical elastic tube filled with incompressible fluid, the relationship between Young’s modulus and PWV is calculated by the Moens-Korteweg equation:
, where E is the Young’s modulus of vascular wall, ν is Poisson’s ratio, h is the vessel wall thickness, ρ is the blood density, and R is the vessel radius . According to this formula, PWV is inversely proportional to vascular elasticity, that is, patients with fast PWV have carotid arteries with poor elasticity due to the hardening of the arterial walls . Therefore, PWV can be a useful indicator of arteriosclerosis in the early stage, and can help in evaluating the risk for ASCVD [10, 12, 13].
Increased levels of TG and LDL-C affect liver and blood vessels similarly, and there is a potential linkage between NAFLD and ASCVD . In this study, patients with NAFLD were divided into mild/moderate and severe NAFLD groups on the basis of abdominal ultrasound examination findings. Moreover, a comparison was made between the NAFLD and the control group in terms of the IMT, PWV-BS, and PWV-ES values. Results showed that IMT values increased with the increase in the severity of NAFLD, which is consistent with the findings of a recent 18-month long European study . This study indicated that the improvement in NAFLD severity was independently associated with the decrease in carotid IMT progression. It also showed that the values of PWV-BS and PWV-ES in patients with NAFLD were significantly higher than those in the healthy cohort. In addition, PWV-BS and PWV-ES values in patients with severe NAFLD were higher than those in patients with mild/moderate NAFLD, which proves that the elasticity of the arterial walls in the patients with NAFLD is significantly lower than that of the arteries of healthy people before the morphological changes, characteristic of atherosclerosis, appear in the carotid artery. Moreover, atherosclerosis worsens with the worsening of NAFLD, which is consistent with the findings of Alkhouri et al. . They showed that the increased severity of NAFLD was associated with abnormal lipid metabolism, which resulted in a hypercoagulable state, thus leading to a higher risk of ASCVD. A previous clinical trial  provided evidence that the treatment of NAFLD is beneficial in preventing ASCVD. Moreover, Luan et al. stated that 20–80% of NAFLD cases have dyslipidemia because NAFLD stimulates free fatty acid oxidation and secretion of very-low-density lipoprotein by the liver . Our study also shows that the TC, TG, and LDL-C levels in patients with NAFLD were higher than those in healthy people, while HDL-C level was lower. Increased severity of hepatic steatosis is probably associated with a higher risk of atherosclerosis because of the increase in the plasma levels of TC, TG, and LDL-C and reduction in the HDL-C level, which is consistent with the findings of the previous studies. It is assumed that hyperlipidemia, chronic inflammation, and oxidative stress induced by NAFLD (i.e. accumulation of TG in hepatocytes) activate endothelial and inflammatory cells, which produce local chemokines . These chemokines accelerate vascular endothelial damage and proliferation of the arterial wall smooth muscle cells, resulting in decreased arterial wall compliance. IMT gradually increases with the increased severity of NAFLD, due to the atherosclerotic plaque formation, vascular stenosis, rupture of unstable plaques, and hemodynamic alterations in the carotid blood flow. As a result, turbulence and shear stress cause intimal damage, which together with lipid deposition further accelerate carotid atherosclerosis. Due to decreased perfusion of cerebral tissues, patients may experience transient ischemic attacks or stroke.
This study also evaluates the factors affecting PWV-BS and PWV-ES in the NAFLD group. Results showed that PWV-BS and PWV-ES were positively correlated with age, BMI, FPG, SBP, DBP, TC, TG, and LDL-C (P < 0.05), and negatively correlated with HDL-C. Older age, hypertension, impaired glucose tolerance, dyslipidemia, and obesity are the risk factors for hemodynamic abnormalities, metabolic syndrome, as well as atherosclerosis. These factors lead to vascular endothelial dysfunction through different pathways. Previous studies [13, 20, 21] also show that the abovementioned factors can affect PWV-BS and PWV-ES values to varying degrees. Due to the relatively high sensitivity and specificity of UFPWV, and it quick and non-invasive nature, it may be used in clinical settings when assessing NAFLD patients.
A major limitation of this study is the use of imaging instead of liver biopsy for establishing the diagnosis of NAFLD. Imaging is not the gold standard for NAFLD diagnosis. Another limitation is the small sample size and short study time. A large multicenter study is required in the future to verify this study’s results, and ascertain whether preventing the development of NAFLD or reducing its severity has a positive effect on the vascular wall. Furthermore, future researchers could conduct a comparative study between ultrafast ultrasound and other imaging modalities for measuring PWV in order to determine the most accurate method. Finally, IMT was measured manually rather than automatically, which may lead to errors in measurement. However, inter- and intra-observer reproducibility testing showed that measurements obtained via ultrafast ultrasound were reliable.
In conclusion, increased NAFLD severity may be associated with a higher risk of cardiovascular complications. UFPWV can be used as a parameter for determining a better treatment plan to slow down the progression of NAFLD and ASCVD. It is suggested that high-risk groups should consume a balanced diet, reduce sedentary habits, and exercise regularly in order to improve their quality of life. In addition, regular monitoring of blood lipid levels and liver fat content in patients with NAFLD can help detect risk factors early and delay the occurrence and development of complications.