Maximum Principal Stress at the Superficial Calcification-Tissue Interface in Carotid Plaque Predicts Long-Term Adverse Events After Carotid Artery Stenting: A Case-Control Study (version1)

Maximum Principal Stress at the Superficial Calcification-Tissue Interface in Carotid Plaque Predicts Long-Term Adverse Events After Carotid Artery Stenting: A Case-Control Study (version1) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Maximum Principal Stress at the Superficial Calcification-Tissue Interface in Carotid Plaque Predicts Long-Term Adverse Events After Carotid Artery Stenting: A Case-Control Study (version1) Jiaqi Zhu, Hanfei Tang, Tonglei Han, Xiao Tang, Daqiao Guo, Chao Fang, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8257570/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract To investigate whether the number of superficial calcification clusters in target carotid plaque influences the prognosis of patients undergoing carotid artery stenting (CAS) by altering intraplaque stress distribution. Patients receiving CAS and occurring major adverse cardiovascular events (MACEs) more than 30 days after discharge during follow-up were screened from the carotid stenosis database. These were matched 1:2 with controls based on age, sex, BMI, symptom status, alcohol abuse, smoking history, and > 3 superficial calcification clusters in the target plaque. Finite element analysis simulated intraplaque stress distribution during balloon inflation and revealed significantly elevated intraplaque maximum principal stress in patients with numerous superficial calcification clusters. Subsequent analysis of all 42 patients in the case-control study using Conditional logistic regression demonstrated that maximum principal stress at the superficial calcification-tissue interface (PSSCT) > 110 kPa was significantly associated with MACEs [P = 0.0429; odds ratio (OR) = 5.31; 95% confidence interval (CI): 1.05–26.8]. Finally, analysis of maximum PSSCT in target plaques containing varying numbers of superficial calcification clusters revealed that plaques with more superficial calcification clusters exhibited an increased probability of developing elevated maximum PSSCT. Therefore, elevated maximum PSSCT is significantly associated with MACEs in patients receiving CAS, representing a likely mediating pathway through which the number of superficial calcification cluster influences long-term prognosis after CAS. carotid stenosis Stress Mechanical vascular calcification Stents Case-Control Studies Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction With the continuous progression of population aging, the incidence of cerebrovascular diseases is rising substantially.(The GBD 2016 Lifetime Risk of Stroke Collaborators, 2018 ) Among all cerebrovascular pathologies, ischemic stroke accounts for the highest burden of disability and mortality.(Feigin et al., 2020 ) Meanwhile, patients with > 70% carotid stenosis face a stroke incidence rate as high as 26%.(Jose Rafael Romero, 2007 ) Carotid artery stenting (CAS) serves as an effective intervention for stroke prevention in patients with carotid stenosis. However, concerns regarding its safety persist due to two inherent limitations: the retention of the culprit plaque and the secondary structural damage to the vascular wall resulting from plaque compression during balloon dilation and stent deployment. These reservations were largely addressed by the CREST trial, which demonstrated no significant difference in the occurrence of major adverse cardiovascular events (MACEs) between CAS and conventional carotid endarterectomy (CEA).(Brott et al., 2010 ) Nevertheless, heterogeneous plaque composition differentially impacts CAS outcomes. Our prior retrospective cohort study revealed that patients with > 3 superficial calcification clusters in target carotid plaques exhibited significantly higher rates of major adverse cardiovascular events (MACEs) after CAS compared to other patients receiving CAS.(Zhu et al., 2024 ) However, this finding appears elusive. Plaque calcification has a Young's modulus of approximately 10 MPa, while surrounding soft tissues exhibit a modulus of only 0.6 MPa.(Benitez et al., 2021 ) When this > 16-fold difference combined with substantial tensile stresses generated during CAS balloon inflation, this stark tissue mismatch may cause dramatic stress redistribution around superficial calcification clusters during CAS. As a technique for simulating stress distribution, Finite element analysis (FEA) has been applied to simulate the effects of endovascular interventions on vessels. The simulation of planned TAVR procedures in 14 patients with severe aortic stenosis revealed that the distance between the coronary ostium and the closest structure (i.e., native valve leaflet, calcium nodule or Venus-A frame) was lower in patients who experienced coronary occlusion during TAVR.(Fan et al., 2024 ) To investigate these biomechanical changing in CAS, a case-control study was conducted by selecting patients who occurred MACEs from Prior carotid stenosis cohort, matching them 1:2 with controls. Subsequently, FEA would simulate stress distributions within target plaques. By comparing stress in tissue around superficial calcification, this study aimed to reveal the mechanism through which the number of superficial calcification cluster in target plaque influences long-term prognosis after CAS. Methods Patients: Between January 2020 to December 2021, a total of 292 patients with carotid bifurcation stenosis receiving CAS were consecutively recorded to construct a carotid stenosis database. Patients with a history of collateral stroke, TIA, syncope, amaurosis fugax within 180 days before surgery and meanwhile with carotid bifurcation stenosis > 50% measured by NASCET criteria were determined as patients with symptomatic carotid stenosis; other patient whose target carotid artery has a stenosis > 70% were determined as patients with asymptomatic carotid stenosis.(Naylor et al., 2023 ) All patients were free of malignant cancer, infection and autoimmune disease. This study was approved by the Ethics Committee of the clinical center. The study protocol was carried out in accordance with the ethical guidelines of the 1975 Declaration of Helsinki. Each patient provided written informed consent before hospitalization. Procedures: The procedures of establishment of retrospective carotid database has mentioned in previous study.(Zhu et al., 2024 ) As shown in Fig. 1 , Using 1:2 matching based on age, sex, BMI, symptom status, alcohol abuse, smoking history, and > 3 superficial calcification clusters in target plaques, 28 matched controls were selected from the carotid stenosis database. This case-control study ultimately comprised 42 patients. Carotid CTA: All CT examinations were performed on a 320-row CT system (Aquilion ONE; Canon Medical Systems Corporation, Otawara, Japan). Scans were collimated at 0.5 mm, with a peak kilovoltage of 120 and auto milliampere, and a rotation time of 0.5 seconds. The scan range was from the aortic arch to the skull vertex. Through use of a power injector, 50–70 mL (according to the patient’s body weight) of contrast media (iopamidol, Iopamiron 370; Bracco, Milan, Italy) was injected into the antecubital vein at a flow rate of 5 mL/s followed by a 25 mL saline flush. A bolustracking technique was used in CTA scans with a threshold of 100 Hounsfield unit (HU) measured in the aortic arch.(Lv et al., 2021 ) Construction of finite element stress model for carotid plaque: Stenotic carotid lumens and calcification within target plaques were segmented using 3D Slicer software according to a threshold of CT value > 130 HU. The window width was adjusted to 120 and window level to 720 to differentiate vascular lumens from superficial calcification. Finally, the outer vascular walls were delineated. (Supplementary Fig. 1) The reconstructed models were subsequently imported into HyperMesh. Rotation (increment step: 1°) and translation (increment step: 0.05 mm) operations were performed in HyperMesh to ensure no overlapping between calcification clusters and carotid lumens. Subsequently, boolean operations were implemented to remove calcification clusters from the carotid arterial walls. Finally, 2D triangular meshes were generated for vascular walls and calcified plaque surfaces with the element size = 0.2 mm and followed by the construction of 3D tetrahedral meshes. (Supplementary Fig. 2) The resultant 3D meshes were then imported into Abaqus. Material properties in Abaqus were defined with Young's modulus set to 10 MPa for calcification and 0.6 MPa for vascular walls, both assigned a Poisson's ratio of 0.48.(Benitez et al., 2021 ) After merging into a single part according to shared nodes, the luminal surfaces of common carotid arteries and internal carotid arteries were selected for application of a 0.0065 MPa uniform pressure load to simulate balloon dilation during CAS. (Supplementary Fig. 3) Due to the low elastic modulus of the soft tissue in vascular wall, applying 4 atmospheres of pressure, based on the internal pressure of balloons in CAS, directly to the inner surface of the vascular lumen may cause significant deformation of the vascular wall, adversely affecting the accuracy of finite element analysis. Therefore, the value of 0.0065 MP was chosen, which is close to the general pulse pressure difference. After computation completed, maximum principal stress and maximum shear stress at centroids of tetrahedral elements on vascular wall surfaces contacting superficial calcification clusters were exported, which was called “maximum principal stress at the superficial calcification-tissue interface” (maximum PSSCT) and “maximum shear stress at the superficial calcification-tissue interface” (maximum SSSCT). Statistical analysis Discrete variables are presented as counts, and continuous variables are expressed as the means for both the MACE and non-MACE groups. To analyze the differences in variables between subjects with and without MACEs, the χ2 test was employed to compare discrete variables, while Student’s t test was used for continuous variables with a normal distribution, and the Wilcoxon test was used for variables with a nonnormal distribution. A conditional logistic regression model was employed to assess the correlation between MACEs and maximum principal stress at the superficial calcification-tissue interface. Optimal dichotomous cutoff values for maximum PSSCT and SSSCT were determined via ROC analysis. All the statistical analysis were performed using the R programming language. Results 3.1 Stress distribution in finite element analysis : To investigate the biomechanical impact of superficial calcification clusters, this study selected two representative carotid plaques: one with > 3 superficial calcification clusters in target carotid plaque that occurred MACEs during 2-year follow-up, and another with ≤ 3 superficial calcification clusters remaining MACE-free. Finite element analysis revealed significantly elevated maximum principal stress in the high-risk plaque. As shown in Fig. 2 A-C, distinct yellow-to-red maximum principal stress specifically located around superficial calcification clusters, substantially exceeding stress values in other arterial wall regions. In contrast, the low-risk plaque exhibited uniformly low stress distribution and the maximum principal stress around superficial calcification clusters was also presented in blue. (Fig. 2 D-F) 3.2 Patient characteristics : Upon observing that patients with > 3 superficial calcification clusters in target plaques within the MACE group exhibited significantly higher maximum PSSCT compared to those with sparse superficial calcification clusters in the non-MACE group, a 1:2 matched case-control study was conducted, which is selected from a retrospective carotid stenosis database to elucidate the prognostic impact of stress characteristics at the superficial calcification-tissue interface. The study comprised 14 patients in MACE group and 28 controls in no MACE group, with baseline characteristics presented in Table 1 demonstrating no significant differences between these 2 group. Table 1 Baseline Characteristics of MACE and no MACE Groups. eGFR: estimated glomerular filtration rate. non MACE (n = 28) MACE (n = 14) all p Gender 26 13 39 1.000 Age 70.4 73.1 71.3 0.331 Symptom status 18 10 28 0.908 Stenosis(%) 73.3 77.5 74.7 0.238 BMI 24.4 24.5 24.5 0.913 Hypertension 19 9 28 1.000 Diabetes mellitus 12 5 17 0.912 Smoking 13 7 20 1.000 Alcohol abuse 9 6 15 0.733 Lipid disorder 10 5 15 1.000 Statin usage 24 14 38 0.353 Antiplatelet usage 24 14 38 0.353 eGFR 79.8 72.6 77.4 0.191 Type I aortic arch 13 9 22 Type II aortic arch 13 4 17 0.424 Type III aortic arch 2 1 3 1.000 Step-by-step predilation 23 12 35 1.000 Usage of closed-loop stent 17 9 26 1.000 Postdilation 12 4 16 0.574 number of superficial calification clusters 2.25 2.43 2.31 0.722 Table 2 the difference of PSSCT and SSSCT between non MACE group and MACE group. PSSCT: principal stress at the superficial calcification-tissue interface; SSSCT: shear stress at the superficial calcification-tissue interface. * p 110 kPa 3 6 9 0.0461* Maximum SSSCT > 11.7 kPa 6 6 12 0.277 Table 3 the association between stress at the superficial calcification-tissue interface and MACE. PSSCT: principal stress at the superficial calcification-tissue interface; SSSCT: shear stress at the superficial calcification-tissue interface.* p 110 kPa 5.31 0.043* 1.05 26.8 Maximum SSSCT > 11.7 kPa 5.16 0.141 0.581 45.9 3.3 Association between PSSCT and MACEs : Finite element analyses were then conducted on target plaques from all 42 patients, with the exportation of maximum PSSCT and SSSCT. For patients with no superficial calcification cluster within the target plaque, both of PSSCT and SSSCT were assigned a value of 0 Pa. As shown in Table. 2, while maximum PSSCT (85.5 ± 51.0 kPa vs. 72.5 ± 37.8 kPa) and SSSCT (11.1 ± 6.03 kPa vs. 9.81 ± 4.92 kPa) were higher in the MACE group than in no MACE group, these differences lacked statistic significance in student’s t tests. In univariate conditional logistic regression, PSSCT and SSSCT also showed non-significant effects on MACEs (Table. 3) Consequently, ROC analysis was used to identify the optimal thresholds for maximum PSSCT and SSSCT which were 110 kPa and 11.7 kPa respectively. (Fig. 3 ) After dichotomizing stress variables using these thresholds, there were 3 patients with elevated PSSCT (> 110 kPa) and 6 patients with elevated SSSCT (> 11.7 kPa) in no MACE group and 6 patients with elevated PSSCT and with elevated SSSCT respectively in MACE group. (Table. 2) Univariate conditional logistic regression revealed a significant association between elevated PSSCT (> 110 kPa) and MACEs occurrence [p = 0.043; odds ratio (OR) = 5.31; 95% confidence interval (CI): 1.05–26.8]. (Table. 3) 3.4 relationship between the number of superficial calcification clusters and PSSCT : Building upon prior evidence establishing the number of superficial calcification clusters within target plaques as an independent risk factor of MACEs, maximum PSSCT was stratified by the number of superficial calcification cluster in all 42 cases. Quantitative analysis revealed a positive association between the number of superficial calcification clusters and average of maximum PSSCT as shown in Fig. 4A. After dichotomization of PSSCT at the 110 kPa, a positve proportional relationship was emerged between the number of superficial calcification clusters and the probability of elevated maximum PSSCT. (Fig. 4B) Figure 4: Detailed average of maximum PSSCT (A) and frequency of elevated PSSCT (B) for different numbers of superficial calcification clusters in target carotid plaque. Discussion Atherosclerotic plaques consist of heterogeneous components including fibrous caps, lipid-rich necrotic cores, intraplaque hemorrhage, fibrotic tissue, and calcium deposition. The compositional profile critically influences selection between different strategies for carotid revascularization. Among these components in plaque, predominant hyperintensity areas within target plaque on preprocedural T1-weighted black-blood MRI were associated with significantly higher incidence of new ipsilateral silent ischemic lesions after CAS compared to CEA.(Yamada et al., 2011 ) Moreover, the radiomic characteristics of pericarotid adipose tissue under CTA image could also provide incremental value in predicting in-stent restenosis after CAS and serve as a valuable biomarker for restenosis risk assessment.(Ren et al., 2025 ) As the most radiographically conspicuous plaque component on CT image, vascular calcification also possesses prognostic implications for outcomes of patients receiving CAS. Patients with calcification arc > 180° at target plaque exhibited significantly higher incidence of new ipsilateral lesions after CAS compared to those with arc < 180°.(Lv et al., 2021 ) Additionally, our prior study suggested that the number of superficial calcification clusters on CTA as an independent risk factor for MACEs during 2-year follow-up in patients with carotid stenosis receiving CAS.(Zhu et al., 2024 ) The significant Young's modulus disparity between calcification clusters and other soft tissue components fundamentally effects intraplaque stress distribution. The presence of plaque calcification inherently elevates wall shear stress on fibrous caps, with morphological variations differentially modulating WSS distribution.(Benitez et al., 2021 ) Except WSS, calcification also amplifies maximum principal stress within plaques. Computational simulations demonstrate diffuse calcification patterns could elevate principal stress up to 80 kPa in peri-calcification regions.(Mahmoud et al., 2019 ) In this study, finite element analysis aiming to simulate intraplaque stress distribution during balloon angioplasty also showed a significant increase of principal stress in peri-calcification regions of plaque with > 3 superficial calcification clusters compared to plaque with < 3 superficial calcification clusters. In coronary artery disease, the implantation of stents could cause intimal tears in the arterial segment where the stents employed. (Yang et al., 2024 ) As a plastic material, the tunica intima would not be torn until the maximum tensile stress exceeds a certain threshold, which may result in the lack of correlation between MACEs and PSSCT before threshold-stratified in this case-control analysis. After dichotomizing, Maximum PSSCT exceeding 110 kPa was identified as an risk factor for MACEs occurrence in patients receiving CAS. This may be due to the impact of superficial calcification exposed to the bloodstream after intimal tear on coagulation function. In the future, a more automated procedure for finite element analysis would be developed, and the correlation between MACEs and PSSCT would be further demonstrated on a prospective cohort study. Conclusion Superficial calcification clusters significantly altered intraplaque stress distribution. Finite element analysis suggested a positive correlation between the number of superficial calcification clusters and the probability of elevated PSSCT. Mechanical simulations revealed that exceeding the critical threshold of 110 kPa in maximum PSSCT was associated with occurrence of MACEs after CAS. Abbreviations CAS carotid artery stenting MACE major adverse cardiovascular event CEA carotid endarterectomy NASCET North American Symptomatic Carotid Endarterectomy Trial CTA computed tomography angiography OR odds ratio CI confidence interval eGFR estimated glomerular filtration rate PSSCT principal stress at the superficial calcification-tissue interface SSSCT shear stress at the superficial calcification-tissue interface ROC Receiver Operating Characteristic WSS wall shear stress Declarations Declaration of generative AI and AI-assisted technologies in the writing process During the preparation of this work the authors used deepseek-R1 in order to improve readability and language. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article. 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16:28:51","extension":"html","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":73032,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8257570/v1/2d42a5637c47e5eabe2d4565.html"},{"id":97346807,"identity":"e65c0c9a-ef17-4ab5-a783-f3f70c414cab","added_by":"auto","created_at":"2025-12-03 11:50:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":84283,"visible":true,"origin":"","legend":"\u003cp\u003ethe procedure of this nested case-control study.\u003c/p\u003e","description":"","filename":"2figure1studyprocedure.png","url":"https://assets-eu.researchsquare.com/files/rs-8257570/v1/272bc287f92fed2b473a569f.png"},{"id":97346808,"identity":"7b0debd7-6261-4c46-b02e-66a94c112400","added_by":"auto","created_at":"2025-12-03 11:50:14","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":172988,"visible":true,"origin":"","legend":"\u003cp\u003eMaximum principal stress distribution in typical carotid plaque including. (A-C) the coronal position, axial position and optimal axial position of maximum principal stress distribution in target plaque with \u0026gt;3 superficial calcification clusters in MACE group; (D-F) the coronal position, axial position and optimal axial position of maximum principal stress distribution in target plaque with ≤3 superficial calcification clusters in no MACE group. The red arrows point to the maximum principal stress around superficial calcification clusters.\u003c/p\u003e","description":"","filename":"2figure2stressdistribution.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8257570/v1/1bbfa16e08cfe64256eeff0b.jpg"},{"id":97346810,"identity":"d9b99d8b-b1e9-4eb9-8b1e-6cf72447ad0c","added_by":"auto","created_at":"2025-12-03 11:50:14","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":654321,"visible":true,"origin":"","legend":"\u003cp\u003ethe ROC curve between MACEs and stress at the superficial calcification-tissue interface. (A) the ROC curve between MACEs and maximum PSSCT; (B) the ROC curve between MACEs and maximum SSSCT.\u003c/p\u003e","description":"","filename":"2figure3stressAUC.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8257570/v1/97bb19e2e1f65adf62195742.jpg"},{"id":97371242,"identity":"12ce20c3-416f-4358-9317-40fc40daff21","added_by":"auto","created_at":"2025-12-03 16:28:34","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":849035,"visible":true,"origin":"","legend":"\u003cp\u003eDetailed average of maximum PSSCT (A) and frequency of elevated PSSCT (B) for different numbers of superficial calcification clusters in target carotid plaque.\u003c/p\u003e","description":"","filename":"2figure4PSSCTsuperficialcalci.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8257570/v1/03b342337d908fdf8418352f.jpg"},{"id":97372993,"identity":"ce4b8362-7ccf-4392-ae1d-aa7b2379693b","added_by":"auto","created_at":"2025-12-03 16:33:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2395479,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8257570/v1/e1c97a00-e6ab-4952-96b6-41a0695533e0.pdf"},{"id":97346811,"identity":"0dbdb906-f1b6-4410-af10-382af2438e04","added_by":"auto","created_at":"2025-12-03 11:50:14","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1363217,"visible":true,"origin":"","legend":"","description":"","filename":"3supplementarydata.docx","url":"https://assets-eu.researchsquare.com/files/rs-8257570/v1/7a20b8b410f63547c8a8b46a.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eMaximum Principal Stress at the Superficial Calcification-Tissue Interface in Carotid Plaque Predicts Long-Term Adverse Events After Carotid Artery Stenting: A Case-Control Study (version1)\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eWith the continuous progression of population aging, the incidence of cerebrovascular diseases is rising substantially.(The GBD 2016 Lifetime Risk of Stroke Collaborators, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2018\u003c/span\u003e) Among all cerebrovascular pathologies, ischemic stroke accounts for the highest burden of disability and mortality.(Feigin et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) Meanwhile, patients with \u0026gt;\u0026thinsp;70% carotid stenosis face a stroke incidence rate as high as 26%.(Jose Rafael Romero, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2007\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eCarotid artery stenting (CAS) serves as an effective intervention for stroke prevention in patients with carotid stenosis. However, concerns regarding its safety persist due to two inherent limitations: the retention of the culprit plaque and the secondary structural damage to the vascular wall resulting from plaque compression during balloon dilation and stent deployment. These reservations were largely addressed by the CREST trial, which demonstrated no significant difference in the occurrence of major adverse cardiovascular events (MACEs) between CAS and conventional carotid endarterectomy (CEA).(Brott et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2010\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eNevertheless, heterogeneous plaque composition differentially impacts CAS outcomes. Our prior retrospective cohort study revealed that patients with \u0026gt;\u0026thinsp;3 superficial calcification clusters in target carotid plaques exhibited significantly higher rates of major adverse cardiovascular events (MACEs) after CAS compared to other patients receiving CAS.(Zhu et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2024\u003c/span\u003e) However, this finding appears elusive. Plaque calcification has a Young's modulus of approximately 10 MPa, while surrounding soft tissues exhibit a modulus of only 0.6 MPa.(Benitez et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) When this\u0026thinsp;\u0026gt;\u0026thinsp;16-fold difference combined with substantial tensile stresses generated during CAS balloon inflation, this stark tissue mismatch may cause dramatic stress redistribution around superficial calcification clusters during CAS.\u003c/p\u003e\u003cp\u003eAs a technique for simulating stress distribution, Finite element analysis (FEA) has been applied to simulate the effects of endovascular interventions on vessels. The simulation of planned TAVR procedures in 14 patients with severe aortic stenosis revealed that the distance between the coronary ostium and the closest structure (i.e., native valve leaflet, calcium nodule or Venus-A frame) was lower in patients who experienced coronary occlusion during TAVR.(Fan et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2024\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eTo investigate these biomechanical changing in CAS, a case-control study was conducted by selecting patients who occurred MACEs from Prior carotid stenosis cohort, matching them 1:2 with controls. Subsequently, FEA would simulate stress distributions within target plaques. By comparing stress in tissue around superficial calcification, this study aimed to reveal the mechanism through which the number of superficial calcification cluster in target plaque influences long-term prognosis after CAS.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatients:\u003c/h2\u003e\u003cp\u003eBetween January 2020 to December 2021, a total of 292 patients with carotid bifurcation stenosis receiving CAS were consecutively recorded to construct a carotid stenosis database. Patients with a history of collateral stroke, TIA, syncope, amaurosis fugax within 180 days before surgery and meanwhile with carotid bifurcation stenosis\u0026thinsp;\u0026gt;\u0026thinsp;50% measured by NASCET criteria were determined as patients with symptomatic carotid stenosis; other patient whose target carotid artery has a stenosis\u0026thinsp;\u0026gt;\u0026thinsp;70% were determined as patients with asymptomatic carotid stenosis.(Naylor et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2023\u003c/span\u003e) All patients were free of malignant cancer, infection and autoimmune disease.\u003c/p\u003e\u003cp\u003e This study was approved by the Ethics Committee of the clinical center. The study protocol was carried out in accordance with the ethical guidelines of the 1975 Declaration of Helsinki. Each patient provided written informed consent before hospitalization.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eProcedures:\u003c/h3\u003e\n\u003cp\u003eThe procedures of establishment of retrospective carotid database has mentioned in previous study.(Zhu et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2024\u003c/span\u003e) As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Using 1:2 matching based on age, sex, BMI, symptom status, alcohol abuse, smoking history, and \u0026gt;\u0026thinsp;3 superficial calcification clusters in target plaques, 28 matched controls were selected from the carotid stenosis database. This case-control study ultimately comprised 42 patients.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003eCarotid CTA:\u003c/h3\u003e\n\u003cp\u003eAll CT examinations were performed on a 320-row CT system (Aquilion ONE; Canon Medical Systems Corporation, Otawara, Japan). Scans were collimated at 0.5 mm, with a peak kilovoltage of 120 and auto milliampere, and a rotation time of 0.5 seconds. The scan range was from the aortic arch to the skull vertex. Through use of a power injector, 50\u0026ndash;70 mL (according to the patient\u0026rsquo;s body weight) of contrast media (iopamidol, Iopamiron 370; Bracco, Milan, Italy) was injected into the antecubital vein at a flow rate of 5 mL/s followed by a 25 mL saline flush. A bolustracking technique was used in CTA scans with a threshold of 100 Hounsfield unit (HU) measured in the aortic arch.(Lv et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2021\u003c/span\u003e)\u003c/p\u003e\n\u003ch3\u003eConstruction of finite element stress model for carotid plaque:\u003c/h3\u003e\n\u003cp\u003eStenotic carotid lumens and calcification within target plaques were segmented using 3D Slicer software according to a threshold of CT value\u0026thinsp;\u0026gt;\u0026thinsp;130 HU. The window width was adjusted to 120 and window level to 720 to differentiate vascular lumens from superficial calcification. Finally, the outer vascular walls were delineated. (Supplementary Fig.\u0026nbsp;1) The reconstructed models were subsequently imported into HyperMesh.\u003c/p\u003e\u003cp\u003eRotation (increment step: 1\u0026deg;) and translation (increment step: 0.05 mm) operations were performed in HyperMesh to ensure no overlapping between calcification clusters and carotid lumens. Subsequently, boolean operations were implemented to remove calcification clusters from the carotid arterial walls. Finally, 2D triangular meshes were generated for vascular walls and calcified plaque surfaces with the element size\u0026thinsp;=\u0026thinsp;0.2 mm and followed by the construction of 3D tetrahedral meshes. (Supplementary Fig.\u0026nbsp;2) The resultant 3D meshes were then imported into Abaqus.\u003c/p\u003e\u003cp\u003eMaterial properties in Abaqus were defined with Young's modulus set to 10 MPa for calcification and 0.6 MPa for vascular walls, both assigned a Poisson's ratio of 0.48.(Benitez et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) After merging into a single part according to shared nodes, the luminal surfaces of common carotid arteries and internal carotid arteries were selected for application of a 0.0065 MPa uniform pressure load to simulate balloon dilation during CAS. (Supplementary Fig.\u0026nbsp;3) Due to the low elastic modulus of the soft tissue in vascular wall, applying 4 atmospheres of pressure, based on the internal pressure of balloons in CAS, directly to the inner surface of the vascular lumen may cause significant deformation of the vascular wall, adversely affecting the accuracy of finite element analysis. Therefore, the value of 0.0065 MP was chosen, which is close to the general pulse pressure difference.\u003c/p\u003e\u003cp\u003eAfter computation completed, maximum principal stress and maximum shear stress at centroids of tetrahedral elements on vascular wall surfaces contacting superficial calcification clusters were exported, which was called \u0026ldquo;maximum principal stress at the superficial calcification-tissue interface\u0026rdquo; (maximum PSSCT) and \u0026ldquo;maximum shear stress at the superficial calcification-tissue interface\u0026rdquo; (maximum SSSCT).\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eDiscrete variables are presented as counts, and continuous variables are expressed as the means for both the MACE and non-MACE groups. To analyze the differences in variables between subjects with and without MACEs, the χ2 test was employed to compare discrete variables, while Student\u0026rsquo;s t test was used for continuous variables with a normal distribution, and the Wilcoxon test was used for variables with a nonnormal distribution.\u003c/p\u003e\u003cp\u003eA conditional logistic regression model was employed to assess the correlation between MACEs and maximum principal stress at the superficial calcification-tissue interface. Optimal dichotomous cutoff values for maximum PSSCT and SSSCT were determined via ROC analysis.\u003c/p\u003e\u003cp\u003eAll the statistical analysis were performed using the R programming language.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003e3.1 Stress distribution in finite element analysis\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eTo investigate the biomechanical impact of superficial calcification clusters, this study selected two representative carotid plaques: one with \u0026gt;\u0026thinsp;3 superficial calcification clusters in target carotid plaque that occurred MACEs during 2-year follow-up, and another with \u0026le;\u0026thinsp;3 superficial calcification clusters remaining MACE-free. Finite element analysis revealed significantly elevated maximum principal stress in the high-risk plaque. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA-C, distinct yellow-to-red maximum principal stress specifically located around superficial calcification clusters, substantially exceeding stress values in other arterial wall regions. In contrast, the low-risk plaque exhibited uniformly low stress distribution and the maximum principal stress around superficial calcification clusters was also presented in blue. (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD-F)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e3.2 Patient characteristics\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eUpon observing that patients with \u0026gt;\u0026thinsp;3 superficial calcification clusters in target plaques within the MACE group exhibited significantly higher maximum PSSCT compared to those with sparse superficial calcification clusters in the non-MACE group, a 1:2 matched case-control study was conducted, which is selected from a retrospective carotid stenosis database to elucidate the prognostic impact of stress characteristics at the superficial calcification-tissue interface. The study comprised 14 patients in MACE group and 28 controls in no MACE group, with baseline characteristics presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e demonstrating no significant differences between these 2 group.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline Characteristics of MACE and no MACE Groups. eGFR: estimated glomerular filtration rate.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003enon MACE\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMACE\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eall\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e70.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e73.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e71.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.331\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSymptom status\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.908\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStenosis(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e73.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e77.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e74.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.238\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.913\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.912\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlcohol abuse\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.733\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLipid disorder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStatin usage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.353\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntiplatelet usage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.353\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eeGFR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e79.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e72.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e77.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.191\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eType I aortic arch\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eType II aortic arch\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.424\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eType III aortic arch\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStep-by-step predilation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUsage of closed-loop stent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePostdilation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.574\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003enumber of superficial calification clusters\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.722\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ethe difference of PSSCT and SSSCT between non MACE group and MACE group. PSSCT: principal stress at the superficial calcification-tissue interface; SSSCT: shear stress at the superficial calcification-tissue interface. * p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003enon MACE\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMACE\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eall\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaximum PSSCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0725\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0855\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0768\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.408\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaximum SSSCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.00981\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0111\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0102\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.494\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaximum PSSCT\u0026thinsp;\u0026gt;\u0026thinsp;110 kPa\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.0461*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaximum SSSCT\u0026thinsp;\u0026gt;\u0026thinsp;11.7 kPa\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.277\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ethe association between stress at the superficial calcification-tissue interface and MACE. PSSCT: principal stress at the superficial calcification-tissue interface; SSSCT: shear stress at the superficial calcification-tissue interface.* p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCI 0.025\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCI 0.975\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaximum PSSCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.51E3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.317\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.20E-4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.92E11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaximum SSSCT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.12E26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.413\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.80E-37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.61E88\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaximum PSSCT\u0026thinsp;\u0026gt;\u0026thinsp;110 kPa\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.043*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e26.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaximum SSSCT\u0026thinsp;\u0026gt;\u0026thinsp;11.7 kPa\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.141\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.581\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e45.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e3.3 Association between PSSCT and MACEs\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eFinite element analyses were then conducted on target plaques from all 42 patients, with the exportation of maximum PSSCT and SSSCT. For patients with no superficial calcification cluster within the target plaque, both of PSSCT and SSSCT were assigned a value of 0 Pa.\u003c/p\u003e\u003cp\u003eAs shown in Table. 2, while maximum PSSCT (85.5\u0026thinsp;\u0026plusmn;\u0026thinsp;51.0 kPa vs. 72.5\u0026thinsp;\u0026plusmn;\u0026thinsp;37.8 kPa) and SSSCT (11.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.03 kPa vs. 9.81\u0026thinsp;\u0026plusmn;\u0026thinsp;4.92 kPa) were higher in the MACE group than in no MACE group, these differences lacked statistic significance in student\u0026rsquo;s t tests. In univariate conditional logistic regression, PSSCT and SSSCT also showed non-significant effects on MACEs (Table. 3)\u003c/p\u003e\u003cp\u003eConsequently, ROC analysis was used to identify the optimal thresholds for maximum PSSCT and SSSCT which were 110 kPa and 11.7 kPa respectively. (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) After dichotomizing stress variables using these thresholds, there were 3 patients with elevated PSSCT (\u0026gt;\u0026thinsp;110 kPa) and 6 patients with elevated SSSCT (\u0026gt;\u0026thinsp;11.7 kPa) in no MACE group and 6 patients with elevated PSSCT and with elevated SSSCT respectively in MACE group. (Table. 2) Univariate conditional logistic regression revealed a significant association between elevated PSSCT (\u0026gt;\u0026thinsp;110 kPa) and MACEs occurrence [p\u0026thinsp;=\u0026thinsp;0.043; odds ratio (OR)\u0026thinsp;=\u0026thinsp;5.31; 95% confidence interval (CI): 1.05\u0026ndash;26.8]. (Table. 3)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e3.4 relationship between the number of superficial calcification clusters and PSSCT\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eBuilding upon prior evidence establishing the number of superficial calcification clusters within target plaques as an independent risk factor of MACEs, maximum PSSCT was stratified by the number of superficial calcification cluster in all 42 cases. Quantitative analysis revealed a positive association between the number of superficial calcification clusters and average of maximum PSSCT as shown in Fig.\u0026nbsp;4A. After dichotomization of PSSCT at the 110 kPa, a positve proportional relationship was emerged between the number of superficial calcification clusters and the probability of elevated maximum PSSCT. (Fig.\u0026nbsp;4B)\u003c/p\u003e\u003cp\u003eFigure\u0026nbsp;4: Detailed average of maximum PSSCT (A) and frequency of elevated PSSCT (B) for different numbers of superficial calcification clusters in target carotid plaque.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAtherosclerotic plaques consist of heterogeneous components including fibrous caps, lipid-rich necrotic cores, intraplaque hemorrhage, fibrotic tissue, and calcium deposition. The compositional profile critically influences selection between different strategies for carotid revascularization. Among these components in plaque, predominant hyperintensity areas within target plaque on preprocedural T1-weighted black-blood MRI were associated with significantly higher incidence of new ipsilateral silent ischemic lesions after CAS compared to CEA.(Yamada et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2011\u003c/span\u003e) Moreover, the radiomic characteristics of pericarotid adipose tissue under CTA image could also provide incremental value in predicting in-stent restenosis after CAS and serve as a valuable biomarker for restenosis risk assessment.(Ren et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2025\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eAs the most radiographically conspicuous plaque component on CT image, vascular calcification also possesses prognostic implications for outcomes of patients receiving CAS. Patients with calcification arc\u0026thinsp;\u0026gt;\u0026thinsp;180\u0026deg; at target plaque exhibited significantly higher incidence of new ipsilateral lesions after CAS compared to those with arc\u0026thinsp;\u0026lt;\u0026thinsp;180\u0026deg;.(Lv et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) Additionally, our prior study suggested that the number of superficial calcification clusters on CTA as an independent risk factor for MACEs during 2-year follow-up in patients with carotid stenosis receiving CAS.(Zhu et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2024\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eThe significant Young's modulus disparity between calcification clusters and other soft tissue components fundamentally effects intraplaque stress distribution. The presence of plaque calcification inherently elevates wall shear stress on fibrous caps, with morphological variations differentially modulating WSS distribution.(Benitez et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) Except WSS, calcification also amplifies maximum principal stress within plaques. Computational simulations demonstrate diffuse calcification patterns could elevate principal stress up to 80 kPa in peri-calcification regions.(Mahmoud et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2019\u003c/span\u003e) In this study, finite element analysis aiming to simulate intraplaque stress distribution during balloon angioplasty also showed a significant increase of principal stress in peri-calcification regions of plaque with \u0026gt;\u0026thinsp;3 superficial calcification clusters compared to plaque with \u0026lt;\u0026thinsp;3 superficial calcification clusters.\u003c/p\u003e\u003cp\u003eIn coronary artery disease, the implantation of stents could cause intimal tears in the arterial segment where the stents employed. (Yang et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2024\u003c/span\u003e) As a plastic material, the tunica intima would not be torn until the maximum tensile stress exceeds a certain threshold, which may result in the lack of correlation between MACEs and PSSCT before threshold-stratified in this case-control analysis. After dichotomizing, Maximum PSSCT exceeding 110 kPa was identified as an risk factor for MACEs occurrence in patients receiving CAS. This may be due to the impact of superficial calcification exposed to the bloodstream after intimal tear on coagulation function.\u003c/p\u003e\u003cp\u003eIn the future, a more automated procedure for finite element analysis would be developed, and the correlation between MACEs and PSSCT would be further demonstrated on a prospective cohort study.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSuperficial calcification clusters significantly altered intraplaque stress distribution. Finite element analysis suggested a positive correlation between the number of superficial calcification clusters and the probability of elevated PSSCT. Mechanical simulations revealed that exceeding the critical threshold of 110 kPa in maximum PSSCT was associated with occurrence of MACEs after CAS.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCAS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecarotid artery stenting\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMACE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emajor adverse cardiovascular event\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCEA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecarotid endarterectomy\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNASCET\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNorth American Symptomatic Carotid Endarterectomy Trial\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCTA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecomputed tomography angiography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eodds ratio\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003econfidence interval\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eeGFR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eestimated glomerular filtration rate\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePSSCT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eprincipal stress at the superficial calcification-tissue interface\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSSSCT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eshear stress at the superficial calcification-tissue interface\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eROC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eReceiver Operating Characteristic\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eWSS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ewall shear stress\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eDeclaration of generative AI and AI-assisted technologies in the writing process\u003c/h2\u003e\n\u003cp\u003eDuring the preparation of this work the authors used deepseek-R1 in order to improve readability and language. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBenitez J, Fontanarosa D, Wang J, Paritala PK, McGahan T, Lloyd T, Li Z (2021) Evaluating the Impact of Calcification on Plaque Vulnerability from the Aspect of Mechanical Interaction Between Blood Flow and Artery Based on MRI. Ann Biomed Eng 49(4):1169\u0026ndash;1182. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s10439-020-02655-1\u003c/span\u003e\u003cspan address=\"10.1007/s10439-020-02655-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrott TG, Hobson RW, Howard G, Roubin GS, Clark WM, Brooks W, Mackey A, Hill MD, Leimgruber PP, Sheffet AJ, Howard VJ, Moore WS, Voeks JH, Hopkins LN, Cutlip DE, Cohen DJ, Popma JJ, Ferguson RD, Cohen SN, Meschia JF (2010) Stenting versus Endarterectomy for Treatment of Carotid-Artery Stenosis. 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Patients receiving CAS and occurring major adverse cardiovascular events (MACEs) more than 30 days after discharge during follow-up were screened from the carotid stenosis database. These were matched 1:2 with controls based on age, sex, BMI, symptom status, alcohol abuse, smoking history, and \u0026gt;\u0026thinsp;3 superficial calcification clusters in the target plaque. Finite element analysis simulated intraplaque stress distribution during balloon inflation and revealed significantly elevated intraplaque maximum principal stress in patients with numerous superficial calcification clusters. Subsequent analysis of all 42 patients in the case-control study using Conditional logistic regression demonstrated that maximum principal stress at the superficial calcification-tissue interface (PSSCT)\u0026thinsp;\u0026gt;\u0026thinsp;110 kPa was significantly associated with MACEs [P\u0026thinsp;=\u0026thinsp;0.0429; odds ratio (OR)\u0026thinsp;=\u0026thinsp;5.31; 95% confidence interval (CI): 1.05\u0026ndash;26.8]. Finally, analysis of maximum PSSCT in target plaques containing varying numbers of superficial calcification clusters revealed that plaques with more superficial calcification clusters exhibited an increased probability of developing elevated maximum PSSCT. Therefore, elevated maximum PSSCT is significantly associated with MACEs in patients receiving CAS, representing a likely mediating pathway through which the number of superficial calcification cluster influences long-term prognosis after CAS.\u003c/p\u003e","manuscriptTitle":"Maximum Principal Stress at the Superficial Calcification-Tissue Interface in Carotid Plaque Predicts Long-Term Adverse Events After Carotid Artery Stenting: A Case-Control Study (version1)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-03 11:50:10","doi":"10.21203/rs.3.rs-8257570/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4ea321e2-ae63-4a1f-91ff-9c209e133c1f","owner":[],"postedDate":"December 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-03T11:50:10+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-03 11:50:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8257570","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8257570","identity":"rs-8257570","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}