Atherosclerosis research: the impact of physiological parameters on vascular wall stress
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In the clinic, atherosclerosis has been associated with abnormal physiological conditions, such as high cholesterol level, high blood pressure and diabetes, but the mechanisms by which they are linked have not yet been determined. In recent years, hemodynamic factors have been found to have a great influence on atherosclerosis. In particular, wall shear stress (WSS), an important factor in atherosclerosis from the development of early lesions to the rupture of later plaques, is now one of the most important risk indicators of atherosclerosis. Here, we used a numerical investigation to determine the impact of four physiological parameters on vascular wall stress (including WSS and wall pressure) in the right coronary arteries, in order to assess their influence on atherosclerosis risk. Each parameter was investigated both separately and in integrated models. The results indicate that the blood flow rate has the most significant influence on WSS and plays a decisive role in the variation of WSS under normal physiological conditions. Blood pressure had a minor influence on WSS under conditions of a flexible vessel wall, but this effect was lost in the absence of flexibility. Blood viscosity and vascular elasticity could also affect WSS directly, but in vivo their influences were negligible.
KeywordsHydrodynamics Wall shear stress Blood pressure Blood flow rate Vascular elasticity
Atherosclerosis is an inflammatory disease occurring principally in large-and medium-sized elastic and muscular arteries. It can lead to ischemia of the heart, brain or extremities, resulting in infarction . Nowadays, it has become the leading cause of morbidity and mortality in the world . The process of atherogenesis involves multiple systems and can last for decades; the earliest lesions are even found in infants and young children . Finding the cause of atherosclerosis has become one of the toughest missions in modern medical research.
One of the important research questions is how atherosclerosis is linked with physiological conditions, such as blood pressure and viscosity. In previous investigations, it has been found that hypertension is associated with not only the formation of atherosclerosis [4, 5] but also the development of atherosclerotic plaques [6, 7, 8]. A three-year follow-up study  showed an additional 0.005–0.012 mm/y progression of intima-media wall thickness (IMT) for every mmHg increase in blood pressure. There are also several lines of evidence suggesting that elevated blood viscosity can increase the risk of atherosclerosis [10, 11, 12]. All of these studies were conducted through clinical investigations; their results show a relationship between an abnormal physiological condition and atherosclerosis, but do not explain the mechanism by which this occurs.
Over recent decades, hemodynamic factors, particularly WSS [13, 14, 15, 16], have been proven to play an important role in atherosclerosis. The changes to hemodynamics caused by physiological parameters could be the key to explaining the connection between abnormal physiological conditions and atherosclerosis risk. In order to explore this theory, we examined the impact of four common physiological parameters on VWS. These included blood pressure, blood flow rate, vascular elasticity and blood viscosity. They were investigated separately under steady flow and together under normal physiological conditions. The findings can provide important theoretical guidance and beneficial biophysical insights into atherosclerosis prevention and treatment.
2 Materials and methods
2.1 Model geometry
2.2 Computational method
2.3 Boundary conditions
The density of blood was 1060 kg/m3, and the vessel wall was considered a linear elastic, isotropic and homogeneous material with a density of 1150 kg/m3.
The default parameters under steady flow
Blood pressure (KPa)
Blood flow rate (ml/s)
Vascular elasticity (MPa)
Blood viscosity (Pa s)
3.1 Blood pressure
3.2 Blood flow rate
3.3 Vascular elasticity
From the study of blood pressure, it can be seen that vascular elasticity could impact WSS. Besides aging, lifestyle factors can also affect the flexibility of vessel walls, such as diet, drinking and smoking. The loss of elasticity might contribute to the growing incidence of atherosclerosis among young people.
3.4 Blood viscosity
3.5 Combined influence
When blood flow rate decreased, the lower limit of WSS went down by 0.46 Pa. Given the fact that blood pressure decreased and blood viscosity increased during the process, blood pressure and viscosity would both lead to an increase in WSS. In Fig. 8d, the biggest difference of lower limit between the normal model and rigid-wall model was around 0.15 Pa when flow rate reached its highest. The difference between normal model and Newtonian-blood model was about 0.1 Pa at both moments, and since the viscosity of non-Newtonian blood is always higher than Newtonian blood, the effect on WSS caused by blood shear-thinning properties should be smaller than 0.1 Pa. Therefore, the total reduction of WSS caused by a lower flow rate should be around 0.71 Pa, indicating blood flow rate played a decisive role in the changes of WSS under a normal physiological state.
4 Discussion and conclusion
The human body is a unified whole and a small change can have a huge impact over time. After decades of accumulation of lipids in the intima, atherosclerosis can clog the vessel and endanger life. The formation of atherosclerosis is very complicated and associated with many factors, such as age, gender, diet and certain diseases [28, 29]. There are studies showing that people with hypertension and hyperlipidemia are more likely to develop atherosclerosis [30, 31]; however, the mechanism by which these physiological conditions are linked to atherosclerosis is still unclear. In this work, by investigating the influence of physiological parameters on VWS, we were able to establish a connection between these parameters and hemodynamic factors. The link between abnormal physiological conditions and atherosclerosis risk was explained in terms of hemodynamics.
Our data show that even though blood pressure can directly affect the pressure on the vessel wall, alone it had no influence on WSS. Nonetheless, when combined with a deformable vessel wall, blood pressure could indirectly influence WSS. However, the effect was very limited, only about 0.036 Pa for every kPa increase. Blood flow rate changes constantly in vivo, and it had a great impact on both WSS and wall pressure. When flow rate went down, WSS decreased in a near linear fashion. Additionally, in a normal physiological state, blood flow rate played a decisive role in the variation of WSS, indicating that it is a principal risk factor for atherosclerosis. Although vascular elasticity deterioration has long been recognized as an important cause of atherosclerosis in the elderly, the data showed only a minor effect of vascular elasticity on WSS. When the vessel wall became stiff, low WSS increased slightly and then leveled off, which could explain the limited effect of blood pressure on WSS. Similar to the blood flow rate, blood viscosity also had a great influence on WSS and wall pressure. A higher viscosity was associated with a notable increase in WSS; however, because of the shear-thinning behavior of blood, variations in viscosity in vivo only had a minor influence on WSS.
So through the results, it can be seen that high blood pressure, low blood flow rate, good elasticity of vessel wall and low blood viscosity could decrease WSS, which according to the low WSS theory [32, 33, 34, 35] will promote the formation of atherosclerosis. The first two parameters are in accordance with what is observed in patients, while the latter two are not. That is because these parameters do not work in isolation in the body. Although a loss of elasticity and increased blood viscosity can cause slight increases in WSS, they also notably increase blood pressure (Figs. 6c, 7c) which would increase the load on the heart, causing the blood flow rate to decrease. And since the blood flow rate is the dominant factor in WSS, these changes in elasticity and viscosity will decrease WSS more than they will increase it, and along with it, the risk of atherosclerosis. Moreover, besides the effect on WSS, high blood pressure can also affect the permeability of lipids by dilating blood vessels, increasing the space between endothelial cells. One fact is that atherosclerotic lesions do not develop in veins, but they do indeed when the veins are used as arterial bypass grafts where they are subjected to high pressure . Thus, low blood flow rate and high blood pressure are both critical risk factors for atherosclerosis.
There are several limitations to our study. Although WSS is considered a major factor of atherosclerosis, there are still some other views and theories [1, 37]. Our conclusion is based on the low-WSS theory, and it matches well with clinical research. Even if there is new evidence in the future to support other theories, the influences of physiological parameters on wall stress, as in this study, are still valid. Moreover, we have made some simplifications to the calculation, such as ignoring side-branches and the assumption of vascular isotropic elasticity, which may have caused a certain deviation from the actual. However, the influence is limited; consistent with other research. This shows that our results are credible.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 3.Napoli C, D’Armiento FP, Mancini FP et al (1997) Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Investig 100(11):2680–2690CrossRefGoogle Scholar
- 10.Carallo C, Pujia A, Irace C et al (1998) Whole blood viscosity and haematocrit are associated with internal carotid atherosclerosis in men. Coron Artery Dis 9(2–3):113–117Google Scholar
- 11.Vosseler M, Beutel A, Schäfer S et al (2012) Parameters of blood viscosity do not correlate with the extent of coronary and carotid atherosclerosis and with endothelial function in patients undergoing coronary angiography. Clin Hemorheol Microcirc 52(2–4):245Google Scholar
- 26.Liu GY (2014) Computational simulation of hemodynamic characteristics in human right coronary arteries. Southern Medical University, GuangdongGoogle Scholar
- 34.Clowes AW, Clowes MM, Reidy MA (1987) Role of acute distension in the induction of smooth muscle proliferation after endothelial denudation [Abstract]. Fed Proc 46:720Google Scholar