Medical and Dental Consultantsí Association of Nigeria
Home - About us - Editorial board - Search - Ahead of print - Current issue - Archives - Submit article - Instructions - Subscribe - Advertise - Contacts - Login 
  Users Online: 2292   Home Print this page Email this page Small font sizeDefault font sizeIncrease font size
 

  Table of Contents 
ORIGINAL ARTICLE
Year : 2019  |  Volume : 22  |  Issue : 3  |  Page : 393-398

Hemoglobin A1c-related histologic characteristics of symptomatic carotid plaques


1 Department Pathology, School of Medicine, Inonu University, Malatya, Turkey
2 Department of Pathology, Malatya State Hospital, Malatya, Turkey

Date of Acceptance14-Dec-2018
Date of Web Publication6-Mar-2019

Correspondence Address:
Dr. M Tecellioglu
Department of Neurology, Inonu University, School of Medicine, Malatya, 44280
Turkey
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_386_18

Rights and Permissions
   Abstract 


Background: The aims of our study were to compare the histomorphological characteristics of carotid plaques and glycosylated hemoglobin (HbA1c), which are risk factors for ischemic stroke, in patients who underwent carotid endarterectomy for carotid artery stenosis. Moreover, we aimed to identify the structures that were histologically affected by symptomatic carotid plaques in cases with elevated HbA1c. Materials and Methods: A total of 64 patients who presented with ischemic stroke and had not previously been diagnosed with diabetes were retrospectively evaluated. All stroke risk factors were reviewed. Carotid plaques were graded separately by two different pathologists through microscopic assessment of the following parameters: plaque rupture, lipid core, fibrous cup thickness, inflammation, intraplaque hemorrhage, thrombus, calcification, necrotic core, and neovascularization. An HbA1c value <6.3% was accepted as normal or indicative of prediabetes (group 1), whereas patients with values ranging between 6.3-7.4%, 7.5-8.4%, and >8.4% were categorized into the effectively controlled (group 2), less effectively controlled (group 3), and uncontrolled (group 4) groups, respectively. Results: The mean age of the patients was 73.0 ± 4.5 years in group 1, 69.7 ± 2.3 years in group 2, 66.0 ± 8.5 years in group 3, and 62.7 ± 7.1 years in group 4. A negative correlation was present between age and HbA1c. Smoking, hypertension, low-density lipoprotein cholesterol levels, and triglyceride levels were not significantly different among the four groups. According to the HbA1c classifications, the fibrous cup thickness was 2.64 ± 0.3 mm in group 1, 1.85 ± 0.4 mm in group 2, 1.68 ± 0.5 mm in group 3, and 1.45 ± 0.6 mm in group 4. The fibrous cup became thinner as the HbA1c value increased. Other parameters of unstable carotid plaques did not differ among the HbA1c groups. Conclusions: Increased HbA1c values seem to contribute to plaque instability through the formation of a thin fibrous cup. Thus, of the carotid artery plaque parameters including fibrous cup thickness, plaque rupture, lipid core, inflammation, intraplaque hemorrhage, thrombus, calcification, necrotic core, and neovascularization, fibrous cup thickness is the only histomorphological feature that affected by HbA1c.

Keywords: Carotid plaque, carotid plaque histology, fibrous cup thickness, HbA1c


How to cite this article:
Tecellioglu M, Alan S, Kamisli S, Tecellioglu F S, Kamisli O, Ozcan C. Hemoglobin A1c-related histologic characteristics of symptomatic carotid plaques. Niger J Clin Pract 2019;22:393-8

How to cite this URL:
Tecellioglu M, Alan S, Kamisli S, Tecellioglu F S, Kamisli O, Ozcan C. Hemoglobin A1c-related histologic characteristics of symptomatic carotid plaques. Niger J Clin Pract [serial online] 2019 [cited 2019 Mar 22];22:393-8. Available from: http://www.njcponline.com/text.asp?2019/22/3/393/253457




   Introduction Top


Ischemic stroke and transient ischemic attack (TIA) usually develop because of unstable carotid lesions that lead to thrombus formation or occlusion of the carotid arteries.[1] Carotid endarterectomy (CEA) has been shown to decrease absolute ipsilateral stroke risk by 16% compared to the best medical treatment in symptomatic patients with severe carotid artery stenosis (≥70%).[2]

The histologic characteristics of unstable carotid plaques have been identified in numerous studies.[3],[4] A thin or ruptured fibrous cup, intraplaque hemorrhage, large lipid-rich necrotic core, inflammation, thrombus, intimal smooth muscle cells, calcification, and neovascularization are unstable plaque characteristics associated with stroke development.[1],[5],[6],[7]

Diabetes is one of the classic risk factors of stroke. Stroke is more common in patients with diabetes and is responsible for approximately 25% of diabetes-related deaths.[8] The majority of strokes in diabetic patients are ischemic. The elevation of glycosylated hemoglobin (HbA1c) is reported to be a risk factor for ischemic stroke.[9]

The aim of this study was to compare the post-CEA histomorphological characteristics of the carotid plaques of patients who experienced a stroke due to carotid artery stenosis and to determine HbA1c values, one of the risk factors for ischemic stroke.


   Materials and Methods Top


Patient selection

A total of 64 patients without a previous diagnosis of diabetes, and who presented to the Inonu University Neurology Department with ischemic stroke and underwent CEA, were retrospectively evaluated. CEA was performed in patients with ≥70% stenosis according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria.[10] Carotid stenosis was determined by intra-arterial cerebral angiography. All patients were symptomatic. Routine cardiologic and medical evaluations were conducted and possible cardioembolism or systemic infectious diseases were ruled out before CEA. Antiplatelet treatment and oral anticoagulants were discontinued at least 6 days before surgery, and the routine coagulation parameters on the day of surgery were normal in all patients. Only patients who had undergone surgery within 30 days after the stroke were included, whereas patients who had undergone CEA for restenosis or carotid stenosis because of radiotherapy were excluded.

Patients were stratified into groups according to five long-term randomized controlled studies conducted to determine treatment strategies in adults with diabetes, as follows: HbA1c <6.3%, normal or prediabetic (group 1); HbA1c 6.3-7.4%, effectively controlled (group 2); HbA1c 7.5-8.4%, less effectively controlled (group 3); and HbA1c >8.4%, uncontrolled (group 4).[11]

Histologic evaluation

Routine procedures for carotid plaques were performed in all patients. All carotid plaques were excised en bloc. The plaques were washed with saline and fixed with 10% formalin after the surgery, and the calcified lesions were decalcified. Transverse macroscopic specimens of 2-mm thickness were obtained. Each 2-mm tissue was embedded in a separate paraffin block. Sections 4-5 μm thick were taken from the paraffinized blocks, transferred to slides, and stained with the elastica van Gieson (EVG) and hematoxylin & eosin (H&E) tissue stains, followed by quantitative analysis. The slides were evaluated with light microscopy (BX50®; Olympus).

The following characteristics were then graded separately by two pathologists on microscopic examination using simple and repeatable semi-quantitative scales, as previously described: plaque rupture, lipid core, fibrous cup thickness, inflammation (macrophage infiltration), intraplaque hemorrhage, thrombus (platelet and macrophage adhesion), calcification, necrotic core, and neovascularization. A lipid core was defined as amorphous material containing cholesterol crystals and was considered “large” when it accounted for 50% of the plate thickness or 25% of the total cross-sectional area. Intraplaque hemorrhage was defined as erythrocyte accumulation within the plaque causing deterioration of the plaque structure or iron- or hemosiderin-loaded macrophages within the plaque connective tissue. Calcification was defined as nodular or calcific nodules. Inflammation was defined as groups of more than 50 macrophages in the plaque or core. Plaque rupture was recorded if there was a clear association between the lipid core and the lumen. Thrombus was defined as the organization of fibrin and red blood cells in the lumen [Figure 1]. For evaluating the thickness of the fibrous cup, the thickest fibrous cup section between the necrotic core and the lumen was used and measured in mm [Figure 2].[12]
Figure 1: K: Calcification, N: Neovascularization, T: Thrombus

Click here to view
Figure 2: PR: Plaque rupture, NC: Necrotic core, FC: Fibrous cup

Click here to view


This study was approved by the ethics review committee of the University of Inonu.

Statistical analysis

All analyses were performed using SSPS for Windows statistical software (ver. 17.0; SSPS Inc., Chicago, IL, USA). A power analysis indicated that at least 60 patients were required. Parametric statistical tests were used because our variables conformed to a normal distribution. Analysis of variance (ANOVA) was used to compare more than two groups, and the post-hoc Tukey test was used for multiple comparisons. The Chi-square test was used to compare qualitative variables. The Pearson correlation coefficient was calculated to determine the direction and strength of the relationship between constant variables. A P value <0.05 was considered to indicate statistical significance.


   Results Top


The study participants consisted of 24 females (37.5%) and 40 males (62.5%). The mean age was 67.3 ± 7.2 years. A small lipid core was found in 44 (68.8%) patients, and a large lipid core in 20 (31.2%) patients. There was no macrophage infiltration in two (3.1%) patients, <50 macrophages in 28 (43.8%) patients, and ≥50 macrophages in 34 (53.1%) patients. Plaque rupture, calcification, intimal smooth muscle cells, and a necrotic core were present in all patients. Intraplaque hemorrhage was also present in all patients and was mild in 16 (25%), moderate in 36 (56.2%), and severe in 12 (18.8%) patients. A thrombus was present in 62 (96.1%) patients, and absent in 2 (3.1%) patients. Neovascularization was present in 60 (93.8%) patients, and absent in 4 (6.2%) patients. The mean fibrous cup thickness was 1.85 ± 0.6 mm [Table 1].
Table 1: Plaque morphologic characteristics in the 64 patients

Click here to view


According to the HbA1c classification, 14 (21.9%) patients were in group 1, 14 (21.9%) patients were in group 2, 16 (25%) patients were in group 3, and 20 (31.2%) patients were in group 4. The mean HbA1c value was 7.2% ± 1.2%. The mean age of the patients was 73.0 ± 4.5 years in group 1, 69.7 ± 2.3 years in group 2, 66.0 ± 8.5 years in group 3, and 62.7 ± 7.1 years in group 4. A negative correlation was present between age and HbA1c (P = 0.042). Smoking, hypertension, low-density lipoprotein (LDL) cholesterol levels, and triglyceride levels were not significantly different among the groups (P > 0.5 for all). The fibrous cup value was 2.64 ± 0.3 mm in group 1, 1.85 ± 0.4 mm in group 2, 1.68 ± 0.5 mm in group 3, and 1.45 ± 0.6 mm in group 4. The fibrous cup became thinner as the HbA1c value increased (P = 0.021) [Table 2]. The parameters other than a thin fibrous cup were not significantly different among the groups according to HbA1c values.
Table 2: Comparison of HbA1c values, mean age, and mean fibrous cup thickness

Click here to view



   Discussion Top


In this study, when evaluating carotid plaque histomorphological characteristics according to HbA1c values, fibrous cup thickness was inversely associated with HbA1c and directly correlated with age in stroke patients.

Advanced age is an unmodifiable risk factor for both hemorrhagic and ischemic stroke. The risk of stroke doubles in women and men every 10 years after the age of 55 years. It has been reported that approximately 75-80% of strokes occur in individuals >65 years, whereas 50% occur in those >70 years, and 25% in those aged >85 years.[13],[14] In patients with diabetes, age at the time of stroke is lower, and the overall prognosis is worse.[15] In the current study, age at the time of stroke decreased as HbA1c values increased. Other risk factors for stroke such as smoking, hypertension, LDL levels, and triglyceride levels were not different among the groups according to HbA1c values.

Stroke is 2-6-fold more common in patients with diabetes, and the majority of cases are of the ischemic type.[9] Metabolic and hemodynamic abnormalities in diabetic patients are associated with risk of stroke.[16] Diabetes plays an important role in stroke pathogenesis by increasing peripheral resistance and atherosclerosis progression, and thus also atherosclerotic complications due to diabetic microangiopathy.[9],[17],[18]

HbA1c levels are an alternative diagnostic method for diabetes, as they are associated with diabetes-related retinopathy. In addition, they are independent of fasting status and reflect the glycemic level in the last 3 months.[19] HbA1c elevation is accepted as a risk factor for stroke and is associated with a two-fold higher stroke rate.[8] HbA1c levels are also an independent indicator of cardiovascular mortality in patients who have not been diagnosed with diabetes.[20] They are believed to be related not only to microvascular but also to macrovascular results.[21] In fact, carotid intima media thickness was found to be high in patients with low HbA1c values.[22] HbA1c is also associated with coronary and peripheral atherosclerosis in non-diabetic patients with normal fasting blood glucose.[23],[24] Among patients with type 2 diabetes, the incidence of coronary artery disease and unstable atherosclerotic coronary plaque are higher in those with HbA1c levels ≥7% compared to individuals with lower values.[25] Moderate HbA1c elevation has also been reported to contribute to the development of carotid plaques.[26] Similarly, previous studies reported a strong association between HbA1c and carotid atherosclerosis.[24] The HbA1c level can, therefore, be said to be an independent and modifiable risk factor for carotid and coronary atherosclerosis.[24] The main aim of our study was to determine the components of symptomatic carotid plaques that are histomorphologically affected by HbA1c elevation.

Ischemic strokes and TIA usually develop because of unstable carotid lesions. Plaque rupture, a thin fibrous cup, calcification within the fibrous cup, plaque thrombus, macrophage infiltration, and intraplaque neovascularization are independent risk factors for symptomatic unstable carotid plaques.[1],[3]

A necrotic core has been found in 94% of symptomatic carotid plaques.[1] Plaque rupture is more common in symptomatic carotid plaques than in asymptomatic plaques, and its prevalence is higher in patients presenting with stroke than in those with TIA or who are asymptomatic.[7],[27] Microcalcifications within the fibrous cup increase structural stress on the plaque and are reported to be an independent risk factor for symptomatic plaques.[1],[28] Atherosclerotic plaque intimal smooth muscle cell content is associated with plaque instability.[29] Neovascularization,[30] intraplaque hemorrhage,[27],[31] lipid core,[32] and macrophage infiltration [27],[33] have been reported to be among the major characteristics of unstable atherosclerotic plaques in previous studies. However, parameters other than a thin fibrous cup did not show a statistically significant difference among the groups according to HbA1c values in our study. In other words, fibrous cup thickness is the only unstable plaque characteristic affected by HbA1c levels independent of other stroke risk factors.

The lipid index was higher, and a thin fibrous cup and macrophage infiltration were more common, among diabetic patients with HbA1c values ≥8% in a study evaluating coronary artery plaque characteristics.[34] A thin fibrous cup together with a necrotic lipid core in coronary arteries of patients with type 2 diabetes was associated with increased plaque instability.[35] Minimum fibrous cup thickness was reported as the most accurate pathologic factor when evaluating plaque instability in a previous study.[1] The mean maximal fibrous cup diameter was also found to be significantly lower in symptomatic carotid plaque patients than in asymptomatic ones.[36] Moreover, the fibrous cup was reported to be thinner in symptomatic patients with macroscopically high levels of carotid stenosis on carotid ultrasonography and magnetic resonance imaging compared to asymptomatic patients.[37] Although the incidence of a thin fibrous cup was high in our patient group, who were all symptomatic, it increased even further with increasing HbA1c values.

In conclusion, among fibrous cup thickness, plaque rupture, lipid core, inflammation, intraplaque hemorrhage, thrombus, calcification, necrotic core, and neovascularization, fibrous cup thickness was the only histological parameter of unstable carotid plaques associated with HbA1c levels. In other words, HbA1c elevation was independently associated with carotid plaque instability using a thin fibrous cup.


   Limitations of the Study Top


This study was retrospective in nature, and the number of patients included was low. Our results should be supported by studies including a larger number of patients. Although the patients included herein were operated on within 30 days after the last clinical stroke-related event, guidelines suggest an optimal time period of 14 days. Moreover, all patients were symptomatic, and we did not include an asymptomatic patient group. In addition, this study was quantitative in nature and included a morphological analysis of carotid plaque specimens but no enzymatic tests, such as for matrix metalloproteinase. Other carotid plaque characteristics useful for predicting plaque instability, such as wall shear stress, were not evaluated, and plaque instability evaluation was limited to pathology indices.

Financial support and sponsorship

This study was supported by the İnönü University Scientific Project Unit (Project no. 2016-64).

Conflict of interest

There is no conflict of interest

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (name of institute/committee) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.



 
   References Top

1.
Konishi T, Funayama N, Yamamoto T, Morita T, Hotta D, Nomura R, et al. Pathological quantification of carotid artery plaque instability in patients undergoing carotid endarterectomy. Circ J. 2017:82:258-66.  Back to cited text no. 1
    
2.
Rothwell PM, Eliasziw M, Gutnikov SA, Warlow CP, Barnett HJ, Carotid Endarterectomy Trialists Collaboration. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet 2004;363:915-24.  Back to cited text no. 2
    
3.
Howard DP, van Lammeren GW, Rothwell PM, Redgrave JN, Moll FL, de Vries JP, et al. Symptomatic carotid atherosclerotic disease: Correlations between plaque composition and ipsilateral stroke risk. Stroke 2015;46:182-9.  Back to cited text no. 3
    
4.
Kolodgie FD, Yahagi K, Mori H, Romero ME, Trout HH Rd, Finn AV, et al. High-risk carotid plaque: lessons learned from histopathology. Semin Vasc Surg 2017;30:31-43.  Back to cited text no. 4
    
5.
Takaya N, Yuan C, Chu B, Saam T, Underhill H, Cai J, et al. Association between carotid plaque characteristics and subsequent ischemic cerebrovascular events: A prospective assessment with MRI – initial results. Stroke 2006;37:81823.  Back to cited text no. 5
    
6.
Hellings WE, Pasterkamp G, Verhoeven BA, De Kleijn DP, De Vries JP, Seldenrijk KA, et al. Gender-associated differences in plaque phenotype of patients undergoing carotid endarterectomy. J Vasc Surg 2007;45:289-7.  Back to cited text no. 6
    
7.
Spagnoli LG, Mauriello A, Sangiorgi G, Fratoni S, Bonanno E, Schwartz RS, et al. Extracranial thrombotically active carotid plaque as a risk factor for ischemic stroke. JAMA 2004;292:1845-52.  Back to cited text no. 7
    
8.
Idris I, Thomson GA, Sharma JC. Diabetes mellitus and stroke. Int J Clin Pract 2006;60:48-56.  Back to cited text no. 8
    
9.
Merel JA, Biessels GJ. Diabetes, hyperglycaemia, and acute ischaemic stroke. Lancet Neurol 2012;11:261-71.  Back to cited text no. 9
    
10.
No Authors. North American symptomatic carotid endarterectomy trial. Methods, patient characteristics, and progress. Stroke 1991;22:711-20.  Back to cited text no. 10
    
11.
Qaseem A, Wilt TJ, Kansagara D, Horwitch C, Barry MJ, Forciea MA, Clinical Guidelines Ccommittee of the American College of Physicians. Hemoglobin A1c targets for glycemic control with pharmacologic therapy for nonpregnant adults with type 2 diabetes mellitus: A guidance statement update from the American College of Physicians. Ann Intern Med 2018168:569-76.  Back to cited text no. 11
    
12.
Trostdorf F, Buchkremer M, Harmjanz A, Kablau M, Jander S, Geiger K, et al. Fibrous cap thickness and smooth muscle cell apoptosis in high-grade carotid artery stenosis. Eur J Vasc Endovasc Surg 2005;29:528-35.  Back to cited text no. 12
    
13.
Feigin VL, Lawes CM, Bennett DA, Anderson CS. Stroke epidemiology: A review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century. Lancet Neurol 2003;2:43-53.  Back to cited text no. 13
    
14.
Russo T, Felzani G, Marini C. Stroke in the very old: A systematic review of studies on incidence, outcome, and resource use. J Aging Res 2011;2011:108785.  Back to cited text no. 14
    
15.
Juneja R, Meakem T. Inpatient hyperglycemia management: The voyage continues. Crit Care Med 2009;37:3165-6.  Back to cited text no. 15
    
16.
Unal E, Akan O, Ucler S. Diyabet ve Norolojik Hastalıklar. Okmeydanı Tıp Dergisi 31(Ek sayı) 2015;45-51. doi: 10.5222/otd. 2015.045  Back to cited text no. 16
    
17.
Moreno PR, Fuster V. New aspects in the pathogenesis of diabetic atherothrombosis. J Am Coll Cardiol 2004;44:2293-300.  Back to cited text no. 17
    
18.
Schwartz SM, Bornfeldt KE. How does diabetes accelerate atherosclerotic plaque rupture and arterial occlusion? Front Biosci 2003;8:s1371-83.  Back to cited text no. 18
    
19.
No Authors. International Expert Committee. International expert committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 2009;32:1327-34.  Back to cited text no. 19
    
20.
Silbernagel G, Grammer TB, Winkelmann BR, Boehm BO, März W. Glycated hemoglobin predicts all-cause, cardiovascular, and cancer mortality in people without a history of diabetes undergoing coronary angiography. Diabetes Care 2001;34:1355-61.  Back to cited text no. 20
    
21.
Selvin E, Steffes MW, Zhu H, Matsushita K, Wagenknecht L, Pankow J, et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med 2010;362:800-11.  Back to cited text no. 21
    
22.
Toulis KA, Jiang CQ, Hemming K, Nirantharakumar K, Cheng KK, Lam TH, et al. Glycated hemoglobin, albuminuria and surrogate markers of macrovascular disease: The Guangzhou Biobank cohort study, cardiovascular disease subcohort. Can J Diabetes 2017;S1499-267130687-6.  Back to cited text no. 22
    
23.
Scicali R, Giral P, Gallo A, Di Pino A, Rabuazzo AM, Purrello F, et al. HbA1c increase is associated with higher coronary and peripheral atherosclerotic burden in non diabetic patients. Atherosclerosis 2016;255:102-8.  Back to cited text no. 23
    
24.
Zhu W, Sun T, Shi H, Li J, Zhu J, Qi W, et al. Combined effects of glycated hemoglobin A1c and blood pressure on carotid artery atherosclerosis in nondiabetic patients. Clin Cardiol 2010;33:542-7.  Back to cited text no. 24
    
25.
Tavares CA, Rassi CH, Fahel MG, Wajchenberg BL, Rochitte CE, Lerario AC. Relationship between glycemic control and coronary artery disease severity, prevalence and plaque characteristics by computed tomography coronary angiography in asymptomatic type 2 diabetic patients. Int J Cardiovasc Imaging 2016;32:1577-85.  Back to cited text no. 25
    
26.
Jørgensen L, Jenssen T, Joakimsen O, Heuch I, Ingebretsen OC, Jacobsen BK. Glycated hemoglobin level is strongly related to the prevalence of carotid artery plaques with high echogenicity in nondiabetic individuals: The Tromsø study. Circulation 2004;110:466-70.  Back to cited text no. 26
    
27.
Redgrave JN, Lovett JK, Gallagher PJ, Rothwell PM. Histological assessment of 526 symptomatic carotid plaques in relation to the nature and timing of ischemic symptoms: The Oxford plaque study. Circulation 2006;113:2320-8.  Back to cited text no. 27
    
28.
Imoto K, Hiro T, Fujii T, Murashige A, Fukumoto Y, Hashimoto G, et al. Longitudinal structural determinants of atherosclerotic plaque vulnerability: A computational analysis of stress distribution using vessel models and three-dimensional intravascular ultrasound imaging. J Am Coll Cardiol 2005;46:1507-15.  Back to cited text no. 28
    
29.
Sevuk U, Bahadir MV, Altindag R, Baysal E, Altintas B, Yaylak B, et al. Relationship between thyroid function and carotid artery plaque ulceration. Acta Neurol Belg 2015;115:581-7.  Back to cited text no. 29
    
30.
Willems S, Vink A, Bot I, Quax PH, de Borst GJ, de Vries JP, et al. Mast cells in human carotid atherosclerotic plaques are associated with intraplaque microvessel density and the occurrence of future cardiovascular events. Eur Heart J 2013;34:3699-706.  Back to cited text no. 30
    
31.
Kolodgie FD, Gold HK, Burke AP, Fowler DR, Kruth HS, Weber DK, et al. Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med 2003;349:2316-25.  Back to cited text no. 31
    
32.
Kedhi E, Kennedy MW, Maehara A, Lansky AJ, McAndrew TC, Marso SP, et al. Impact of TCFA on unanticipated ischemic events in medically treated diabetes mellitus: Insights from the prospect study. JACC Cardiovasc Imaging 2017;10:451-8.  Back to cited text no. 32
    
33.
Childs BG, Baker DJ, Wijshake T, Conover CA, Campisi J, van Deursen JM. Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science 2016;354:472-7.  Back to cited text no. 33
    
34.
Kato K, Yonetsu T, Kim SJ, Xing L, Lee H, McNulty I, et al. Comparison of nonculprit coronary plaque characteristics between patients with and without diabetes: A 3-vessel optical coherence tomography study. JACC Cardiovasc Interv 2012;5:1150-8.  Back to cited text no. 34
    
35.
Milzi A, Burgmaier M, Burgmaier K, Hellmich M, Marx N, Reith S. Type 2 diabetes mellitus is associated with a lower fibrous cap thickness but has no impact on calcification morphology: An intracoronary optical coherence tomography study. Cardiovasc Diabetol 2017;16:152.  Back to cited text no. 35
    
36.
Dhume AS, Soundararajan K, Hunter III WJ, Agrawal DK. Comparison of vascular smooth muscle cell apoptosis and fibrous cap morphology in symptomatic and asymptomatic carotid artery disease. Ann Vasc Surg 2003;17:1-8.  Back to cited text no. 36
    
37.
Yuan C, Zhang SX, Polissar NL, Echelard D, Ortiz G, Davis JW, et al. Identification of fibrous cap rupture with magnetic resonance imaging is highly associated with recent transient ischemic attack or stroke. Circulation 2002;105:181-5.  Back to cited text no. 37
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]



 

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

 
  In this article
    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
    Limitations of t...
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed40    
    Printed0    
    Emailed0    
    PDF Downloaded20    
    Comments [Add]    

Recommend this journal