• Users Online: 77
  • Print this page
  • Email this page

 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 10  |  Issue : 4  |  Page : 267-273

The relation between atherosclerosis plaque composition and plaque rupture


1 Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky, USA
2 Department of Biomedical Engineering, University of Isfahan, Isfahan, Iran
3 Department of Internal Medicine, School of Medicine, Islamic Azad University of Medical Sciences, Tehran, Iran
4 Department of Internal Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Date of Submission16-Sep-2019
Date of Decision11-Apr-2020
Date of Acceptance19-Jul-2020
Date of Web Publication11-Nov-2020

Correspondence Address:
Dr. Parto Babaniamansour
317 Transylvania Park, Lexington, Kentucky
USA
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jmss.JMSS_48_19

Rights and Permissions
  Abstract 


Background: Intima, media, and adventitia are three layers of arteries. They have different structures and different mechanical properties. Damage to intima layer of arteries leads to an inflammatory response, which is usually the reason for atherosclerosis plaque formation. Atherosclerosis plaques mainly consist of smooth muscle cells and calcium. However, plaque geometry and mechanical properties change during time. Blood flow is the source of biomechanical stress to the plaques. Maximum stress that atherosclerosis plaque can burden before its rupture depends on fibrous cap thickness, lipid core, calcification, and artery stenosis. When atherosclerotic plaque ruptures, the blood would be in contact with coagulation factors. That is why plaque rupture is one of the main causes of fatality. Method: In this article, the coronary artery was modeled by ANSYS. First, fibrous cap thickness was increased from 40 μm to 250 μm by keeping other parameters constant. Then, the lipid pool percentage was incremented from 10% to 90% by keeping other parameters unchanged. Furthermore, for investigating the influence of calcium in plaque vulnerability, calcium was modeled in both agglomerated and microcalcium form. Results: It is proved that atherosclerosis plaque stress decreases exponentially as cap thickness increases. Larger lipid pool leads to more vulnerable plaques. In addition, the analysis showed maximum plaque stress usually increases in calcified plaque as compared with noncalcified plaque. Conclusion: The plaque stress is dependent on whether calcium is agglomerated near the lumen or far from it. However, in both cases, the deposition of more calcium in calcified plaque reduces maximum plaque stress.

Keywords: Atherosclerosis plaque, biomechanical stress, calcification, fibrous cap thickness, lipid core


How to cite this article:
Babaniamansour P, Mohammadi M, Babaniamansour S, Aliniagerdroudbari E. The relation between atherosclerosis plaque composition and plaque rupture. J Med Signals Sens 2020;10:267-73

How to cite this URL:
Babaniamansour P, Mohammadi M, Babaniamansour S, Aliniagerdroudbari E. The relation between atherosclerosis plaque composition and plaque rupture. J Med Signals Sens [serial online] 2020 [cited 2020 Nov 24];10:267-73. Available from: https://www.jmssjournal.net/text.asp?2020/10/4/267/300502




  Introduction Top


The arteries are composed of three distinct layers with different structures and functions. The sequence of layers from outside to inside is adventitia, media, and intima. Adventitia is an outermost layer that provides support and strength for the artery. Media plays a pivotal role in changes of vascular diameter and the maintenance of vascular tone.[1] Intima includes endothelium, sub-endothelium, and internal elastic lamina. Cells in the innermost layer of intima are in contact with the blood stream. Damage to the intima can initiate the process of atherosclerosis.[2] Atherosclerosis is one of the main causes of death worldwide, which accounts for around two-thirds of all death.[3],[4] The exact cause of atherosclerosis is unknown. Recently, it is understood as an inflammatory/proliferative disease. Usually, the atherosclerotic process starts from childhood and progresses slowly.[5]

Atherosclerosis is identified by the accumulation of pathologically activated cells. The cellular players in atherosclerotic plaque formation include endothelial cells, immune cells, lipid-laden cells, smooth muscle cells.[4] In atherosclerosis, artery's wall thickens because of the accumulation of fat, fibrous tissue, and calcium deposit. As intima thickens, arterial lumen narrows. The plaque hardens gradually and ultimately ruptures. Rupture of plaques initiates the thrombotic cascade.[4] Rupture of plaques makes blood be in contact with subendothelial coagulation factors. Clot formation leads to heart diseases such as acute myocardial infarction and Angina pectoris. The question is “What leads to plaque rupture?” According to researches plaque rupture is a biomechanical phenomenon that depends on the complex interplay between plaque composition and applied stresses.[6],[7] Atherosclerosis plaques mainly include lipid pool, fibrous tissue, and calcium. The fibrous cap is stiffer than lipid core so it can sustain more stress. The cap thickness of 60–250 μm contributes to plaque stability. At the shoulders, the plaque becomes thinner, so the abrupt transition between mildly and highly stressed areas makes the shoulders more vulnerable areas.[7],[8] Furthermore, pulsatile blood flow gradually weakens the fibrous cap and causes fatigue.

Finite element analysis of atherosclerosis

The coronary artery wall is constantly exposed to flow-induced wall shear stress.[9] Researches have demonstrated that high mechanical stress condition over the plaque surface results in plaque vulnerability. Furthermore, circumferential stress may play an important role in plaque rupture.[10],[11] Furthermore, plaque rupture locations may be related to maximal stress conditions on the plaque.[12],[13] Similarly, it has been suggested that pulsatile blood pressure results in plaque fatigue failure.[10] There are some relationships between plaque vulnerability and its composition.[14],[15] According to previous studies, the overall average plaque rupture threshold is around 300 kPa.[11],[16] Both Finite Element Method and experimental analysis demonstrated that thinning of fibrous cap is associated with increased plaque rupture vulnerability.[16],[17] Moreover, fluid-structure interaction simulations reconstructed from intravascular ultrasound imaging indicated that mechanical stress (Von Mises Stresses) increases exponentially with thinning of the fibrous cap.[18] In another study, different mechanical properties of plaque components were examined to find maximum plaque stress. In that simulation, eliminating the lipid pool and replacing it by fibrous cap resulted in a dramatic decrease in maximum stress in the plaque. Therefore, lipid core was shown to have a remarkable effect in the vulnerability of the plaques.[19] Furthermore, it was revealed that maximum stress is not correlated with the percentage of calcification. In stable plaques with a high amount of calcium, the calcium gets the intensity of pressure. Hence, eliminating a great amount of calcium from atherosclerosis plaques leads to the vulnerability of plaques.[19] Li et al. used ABAQUS finite element analysis to understand whether calcium increases stress in lesions or not. In their study, blood pressure was time-dependent, and the calcium was placed in different locations of atherosclerosis plaques such as artery's wall, lipid pool, and fibrous cap to find Von Mises stress. They concluded calcium in fibrous cap may lead to stress concentration in it. In addition, the difference between mechanical properties of fibrous cap and calcium contributes to crack propagation. Therefore, atherosclerosis plaques with a calcified fibrous cap are classified as vulnerable plaque. On the other hand, calcium in lipid core far from the fibrous cap does not enhance biomechanical stress and may result in the stability of plaques.[11] Similarly, it was shown that microcalcification in cap considerably increases the risk of plaque rupture.[18]

In summary, previous studies suggest that altering plaque composition changes plaque vulnerability. In this paper, the maximum peripheral stress, maximum peripheral strain, maximum radial stress, and maximum radial strain caused by a blood pressure of 120 mmHg were found by considering different compositions of fibrous cap thickness, lipid pool percentage, and calcification.


  Methods Top


The goal of this project is to find the maximum stress in atherosclerosis plaque with various compositions. The plaque composition, including fibrous cap, lipid pool, and calcium, are considered as key players for finding the maximum peripheral stress. Plaque stability depends on its morphology, components, and hemodynamic stress. Plaque stress is influenced by these factors altogether. To analyze the influence of plaque geometry, ANSYS 2014 was used. ANSYS is a general-purpose finite element software for numerically solving a variety of mechanical properties.[20] The finite element solution may be broken into three stages of preprocessing, solution, and postprocessing.[20] In preprocessing stage, the ideal coronary plaque was designed. Atherosclerosis plaques with different cap thicknesses, lipid pool percentage, and calcification are modeled. First, atherosclerotic plaques with different fibrous cap thicknesses were modeled. Then, groups of atherosclerotic plaque with different lipid core percentage were modeled. Similarly, plaques with the different distribution of calcium were designed. For modeling each group, only one parameter was changed while keeping others constant. In this two-dimensional modeling, tetra type mesh was used with dimensions of 0.00004 mm. Mechanical properties, including Young's Modulus and Poisson's ratio, are assigned to the plaque segments according to the [Table 1]. In the solution stage, the plaque geometry was constrained in two dimensional, and the blood pressure of 120 mmHg was applied to the plaque. In post-processing stage, maximum stresses and strains were found.
Table 1: Mechanical properties of plaque components

Click here to view



  Results and Discussion Top


Relationship between fibrous cap thickness and plaque maximum stress

By increasing cap thickness from 40 to 250 μm, and keeping stenosis and lipid percentage constant, the relationship between maximum plaque stress and fibrous cap thickness is found. According to [Figure 1], maximum peripheral stress is reduced exponentially as it thickens. Furthermore, maximum peripheral stress occurs at the shoulders of atherosclerosis plaque. Maximum peripheral strain, maximum radial stress, and maximum radial strain are shown in [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8].
Figure 1: (a) Relationship between fibrous cap thickness and maximum peripheral stress in luminal stenosis of 50%. (b) Relationship between fibrous cap thickness and maximum peripheral stress in luminal stenosis of 70%

Click here to view
Table 2: Maximum stress and strain in arteries with constant lipid core of 10% and stenosis of 50% (S1) and stenosis of 70% (S2)

Click here to view
Table 3: Maximum stress and strain in arteries with constant lipid core of 20% and stenosis of 50% (S1) and stenosis of 70% (S2)

Click here to view
Table 4: Maximum stress and strain in arteries with constant lipid core of 30% and stenosis of 50% (S1) and stenosis of 70% (S2)

Click here to view
Table 5: Maximum stress and strain in arteries with constant lipid core of 40% and stenosis of 50% (S1) and stenosis of 70% (S2)

Click here to view
Table 6: Maximum stress and strain in arteries with constant lipid core of 50% and stenosis of 50% (S1) and stenosis of 70% (S2)

Click here to view
Table 7: Maximum stress and strain in arteries with constant lipid core of 60% and stenosis of 50% (S1) and stenosis of 70% (S2)

Click here to view
Table 8: Maximum stress and strain in arteries with constant lipid core of 70% and stenosis of 50% (S1) and stenosis of 70% (S2)

Click here to view


Relationship between lipid percentage and maximum plaque stress

By increasing lipid percentage and keeping stenosis and fibrous cap thickness constant, the relationship between maximum plaque stress and lipid percentage was found.

According to [Figure 2] by increasing lipid percentage, maximum peripheral stress enhances. Therefore, more lipid leads to more vulnerable atherosclerosis plaque. Maximum peripheral strain, maximum radial stress, and maximum radial strain are shown in [Table 9] and [Table 10].
Figure 2: (a) Relationship between lipid pool percentage and maximum peripheral stress in luminal stenosis of 50%. (b) Relationship between lipid pool percentage and maximum peripheral stress in luminal stenosis of 70%

Click here to view
Table 9: Maximum stress and strain in arteries with constant fibrous cap of 40 mm and stenosis of 50% (S1) and stenosis of 70% (S2)

Click here to view
Table 10: Maximum stress and strain in arteries with constant fibrous cap of 65 mm and stenosis of 50% (S1) and stenosis of 70% (S2)

Click here to view


Relationship between calcium and maximum plaque stress

To investigate the role of calcium in plaque stress, calcium was considered in both agglomerate and microcalcium forms.

  1. Examining agglomerate calcium formed near lumen: according to [Figure 3], when calcium is formed near the lumen, maximum peripheral stress increases as compared with noncalcified plaque. However, [Table 11] shows plaque stress decreases as calcium percentage increases. Hence, calcium presence enhances maximum plaque stress significantly, but fully calcified plaque is less vulnerable than fully lipid plaque
  2. Examining agglomerate calcium formed far from the lumen: according to [Table 12], increasing calcium leads to a continuous decline in plaque stress. Thus, calcium formed far from the lumen contributes to plaque stability. Comparison between maximum stress when calcium is agglomerated near and far from the lumen shows that atherosclerosis plaque is exposed to higher stress when calcium is agglomerated near the lumen.
Figure 3: Schematic of atherosclerosis plaque when calcium is agglomerated near the lumen

Click here to view
Table 11: Relation between plaque stress and calcium percentage when calcium is agglomerated near the lumen

Click here to view
Table 12: Relation between plaque stress and calcium percentage when calcium is agglomerated far from the lumen

Click here to view


Relationship between size of microcalciums and maximum plaque stress

For finding the relationship between size and maximum stress, microcalciums with radiuses of 2.5, 5, 10, 15, 20, and 30 were modeled. According to [Table 13], maximum peripheral stress increases by increasing of microcalcium size, so there is more probability of plaque rupture.
Table 13: Relation between size of microcalcium and the maximum stress

Click here to view


Validation

To validate the numerical solution, calculated strains of the current research were compared with the analysis of Baldewsing et al.[21] In Baldewsing study, cap thickness is considered 50 μm and Young's modulus is between 500 and 2500 kpa. In this section, geometry, boundary conditions, and blood flow were exactly modeled the same as Baldewsing's work. In [Figure 4], Young's modulus-strain curve below compares the present study with Baldewsing results.
Figure 4: Comparison between Baldewsing study and present study

Click here to view


In summary, in this project, ideal atherosclerotic plaque geometry was modeled, and analysis was done based on mechanical properties of each component. The results of the analysis are collected in [Table 14].
Table 14: Summary of results

Click here to view


Financial support and sponsorship

None.

Conflicts of interest

There are no conflicts of interest.


  Biographies Top




Parto Babaniamansour received her Master's degree in biomedical engineering in 2016 from the AmirKabir university of technology. She is currently a PhD student at University of Kentucky. Her research interests are focused on tissue engineering and computational modeling.

Email: [email protected]



Maryam Mohammadi received her bachelor's degree in biomedical engineering in 2014 from University of Isfahan. Her research interests are focused on cardiovascular modeling.

Email: [email protected]



Sepideh Babaniamansour received her MD degree in 2019 from Islamic Azad University, Tehran medical branch. Her research interests are focused on internal medicine and cardiology.

Email: [email protected]



Ehsan Aliniagerdroudbari received his MD degree in 2015 from Shahid Beheshti University of Medical Sciences. He is currently a physician in Golestan University of Medical Sciences. His research interests are focused on Internal Medicine, Cardiology and Pathology.

Email: [email protected]



 
  References Top

1.
Alves-Lopes R, Touyz RM, Montezano AC. Cell Biology of Vessels. In Touyz R., Delles C. (eds) Textbook of Vascular Medicine. Springer, Cham; 2019. p. 23-30.  Back to cited text no. 1
    
2.
Saxton A, Manna B. Anatomy, Thorax, Heart Right Coronary Arteries. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2019.  Back to cited text no. 2
    
3.
Moroni F, Ammirati E, Norata GD, Magnoni M, Camici PG. The role of monocytes and macrophages in human atherosclerosis, plaque neoangiogenesis, and atherothrombosis. Mediators Inflamm 2019;2019:7434376.  Back to cited text no. 3
    
4.
Mercer J, Guzik TJ, Atherosclerosis. In: Touyz RM, Delles C, editors. Textbook of Vascular Medicine. Cham: Springer International Publishing; 2019. p. 215-28.  Back to cited text no. 4
    
5.
Da Luz PL, Libby P, Laurindo FR, Chagas AC. Chapter 33-Endothelium in Atherosclerosis: Plaque Formation and Its Complications. In Endothelium and Cardiovascular Diseases: Vascular biology and clinical syndromes, Da Luz PL, Libby P, Laurindo FR, Chagas AC (eds.). Elsevier, London, UK; 2018. p. 493-512.  Back to cited text no. 5
    
6.
Peña E, Cilla M, Latorre ÁT, Martínez MA, Gómez A, Pettigrew RI.et al. Chapter 16-Emergent biomechanical factors predicting vulnerable coronary atherosclerotic plaque rupture. In Biomechanics of Coronary Atherosclerotic Plaque Peña E, Cilla M, Latorre ÁT, Martínez MA, Gómez A, Pettigrew RI. et al. (eds.). Elsevier, London, UK; 2020. p. 367-87.  Back to cited text no. 6
    
7.
Stefanadis C, Antoniou CK, Tsiachris D, Pietri P. Coronary atherosclerotic vulnerable plaque: Current Perspectives. J Am Heart Assoc 2017;6:e005543.  Back to cited text no. 7
    
8.
Fishbein MC. The vulnerable and unstable atherosclerotic plaque. Cardiovasc Pathol 2010;19:6-11.  Back to cited text no. 8
    
9.
Ohayon J, Finet G, Le Floc'h S, Cloutier G, Gharib AM, Heroux J, et al. Biomechanics of atherosclerotic coronary plaque: Site, stability and in vivo elasticity modeling. Ann Biomed Eng 2014;42:269-79.  Back to cited text no. 9
    
10.
Rezvani-Sharif A, Tafazzoli-Shadpour M, Kazemi-Saleh D, Sotoudeh-Anvari M. Stress analysis of fracture of atherosclerotic plaques: Crack propagation modeling. Med Biol Eng Comput 2017;55:1389-400.  Back to cited text no. 10
    
11.
Li ZY, Howarth S, Trivedi RA, U-King-Im JM, Graves MJ, Brown A, et al. Stress analysis of carotid plaque rupture based on in vivo high resolution MRI. J Biomech 2006:39:2611-22.  Back to cited text no. 11
    
12.
Teng Z, Sadat U, Ji G, Zhu C, Young VE, Graves MJ, et al. Lumen irregularity dominates the relationship between mechanical stress condition, fibrous-cap thickness, and lumen curvature in carotid atherosclerotic plaque. J Biomech Eng 2011;133:034501.  Back to cited text no. 12
    
13.
Tang D, Yang C, Zheng J, Woodard PK, Saffitz JE, Petruccelli JD, et al. Local maximal stress hypothesis and computational plaque vulnerability index for atherosclerotic plaque assessment. Ann Biomed Eng 2005;33:1789-801.  Back to cited text no. 13
    
14.
Libby P, Pasterkamp G. Requiem for the 'vulnerable plaque'. Eur Heart J 2015;36:2984-7.  Back to cited text no. 14
    
15.
Cilla M, Peña E, Martínez MA. 3D computational parametric analysis of eccentric atheroma plaque: Influence of axial and circumferential residual stresses. Biomech Model Mechanobiol 2012;11:1001-13.  Back to cited text no. 15
    
16.
Thondapu V, Bourantas CV, Foin N, Jang IK, Serruys PW, Barlis P. Biomechanical stress in coronary atherosclerosis: Emerging insights from computational modelling. Eur Heart J 2017;38:81-92.  Back to cited text no. 16
    
17.
Akyildiz AC, Speelman L, Nieuwstadt HA, van Brummelen H, Virmani R, van der Lugt A, et al. The effects of plaque morphology and material properties on peak cap stress in human coronary arteries. Comput Methods Biomech Biomed Engin 2016;19:771-9.  Back to cited text no. 17
    
18.
Liang X, Xenos M, Alemu Y, Rambhia SH, Lavi I, Kornowski R, et al. Biomechanical factors in coronary vulnerable plaque risk of rupture: Intravascular ultrasound-based patient-specific fluid-structure interaction studies. Coron Artery Dis 2013;24:75-87.  Back to cited text no. 18
    
19.
Huang H, Virmani R, Younis H, Burke AP, Kamm RD, Lee RT. The impact of calcification on the biomechanical stability of atherosclerotic plaques. Circulation 2001;103:1051-6.  Back to cited text no. 19
    
20.
Stolarski, T, Nakasone Y, Yoshimoto S. Engineering Analysis with ANSYS Software. 2nd ed. Butterworth-Heinemann, Oxford, UK; 2018.  Back to cited text no. 20
    
21.
Baldewsing RA, de Korte CL, Schaar JA, Mastik F, van der Steen AF. Finite element modeling and intravascular ultrasound elastography of vulnerable plaques: Parameter variation. Ultrasonics 2004;42:723-9.  Back to cited text no. 21
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11], [Table 12], [Table 13], [Table 14]



 

Top
 
 
  Search
 
Similar in PUBMED
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
   Abstract
  Introduction
  Methods
   Results and Disc...
  Biographies
   References
   Article Figures
   Article Tables

 Article Access Statistics
    Viewed101    
    Printed2    
    Emailed0    
    PDF Downloaded19    
    Comments [Add]    

Recommend this journal