Impact of sex and age on carotid plaque instability in asymptomatic patients-results from the Munich Vascular Biobank

Abstract. Background: It is still a controversial issue whether carotid endarterectomy (CEA) for asymptomatic carotid stenosis is superior to best medical treatment. The aim of this study was therefore to analyze the impact of sex and age on carotid plaque instability in asymptomatic patients undergoing CEA. Patients and methods: Atherosclerotic plaques from 465 asymptomatic patients with high-grade carotid artery stenosis (2004 - 2013) at the Munich Vascular Biobank were analyzed. Ascertainment of lesion stability/instability was performed on formalin-fixed paraffin-embedded tissue samples using hematoxylin-eosin and elastic van Gieson staining. Unstable plaques were considered lesions with a fibrous cap < 200 µm overlaying lipid-rich atheroma. Results: The average age of the patients was 69.3 ± 8.2 years. Independent of age, asymptomatic men had in total more frequently unstable plaques in contrast to women (41 % versus 52%, p = 0.042). No differences were found in plaque instability between age-related quartiles (< 65, 65- 69, 70 - 74, > 74 years) for female sex (p = 0.422). In men, a continuous increase in plaque instability with age was observed, without achieving statistical significance (p = 0.125). The greatest differences between male and female sex were found in the last quartile (> 74 years), without achieving statistical significance (p = 0.053). The chance of unstable carotid plaques in men was significantly higher than in women (OR = 1.562, p = 0.040). The probability of age-associated quartiles related to the first quartile demonstrated significant increase in plaque instability in the group of 65- to 69-year-old patients (OR 1.867, p = 0.024) and for patients older than 74 years (OR 1.740, p = 0.040). Conclusions: Asymptomatic men had in total more frequently unstable plaques in contrast to women. Thus, male sex seems to be an additional risk factor for ischemic stroke.

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The Risk of Carotid Plaque Instability in Patients with Metabolic Syndrome: It is Higher in Women with Hypertriglyceridemia

10.21203/rs.3.rs-165616/v1 ◽

2021 ◽

Author(s):

Francesca Servadei ◽

Lucia Anemona ◽

Marina Cardellini ◽

Manuel Scimeca ◽

Manuela Montanaro ◽

...

Keyword(s):

Risk Factors ◽

Metabolic Syndrome ◽

Carotid Plaque ◽

Cerebrovascular Diseases ◽

Plaque Instability ◽

Female Patients ◽

Asymptomatic Patients ◽

Increased Risk ◽

Unstable Plaques ◽

Plaque Destabilization

Abstract Background: Metabolic syndrome certainly favors growth of carotid plaque; however, it is uncertain if it determines plaque destabilization. Furthermore, it is likely that only some components of metabolic syndrome are associated with increased risk of plaque destabilization. Therefore, we evaluated the effect of different elements of metabolic syndrome, individually and in association, on carotid plaques destabilization. Methods: A total of 186 carotid endarterectomies from symptomatic and asymptomatic patients were histologically analysed and correlated with major cardiovascular risk factors. Results: Metabolic syndrome, regardless of the cluster of its components, is not associated with a significant increase in risk of plaque destabilization, rather with the presence of stable plaques. The incidence of unstable plaques in patients with metabolic syndrome is quite low (43.9%), when compared with that seen in the presence of some risk factors, but significantly increases in the subgroup of female patients with hypertriglyceridemia, showing an odds ratio of 3.01 (CI 95% 0.25 - 36.30). Conclusions: Our data may help to identify patients with real increased risk of acute cerebrovascular diseases and may support the hypothesis that the control of hypertriglyceridemia should be a key point on prevention of carotid atherosclerotic plaque destabilization, especially in post-menopausal female patients. Keywords: Metabolic syndrome, carotid, histology, hypertriglyceridemia , post-menopause.

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Abstract 497: Sex Differences in the Relationship Between Pro-Inflammatory Adipokines, Chemerin and Resistin, and Carotid Atherosclerotic Plaque Instability

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.497 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Karina Gasbarrino ◽

Russell Yanofsky ◽

Carina Sancho ◽

Fanny Jaunet ◽

Huaien Zheng ◽

...

Keyword(s):

Sex Differences ◽

Mrna Expression ◽

Vascular Function ◽

Carotid Plaque ◽

Fibrous Tissue ◽

Staining Intensity ◽

Plaque Morphology ◽

Plaque Instability ◽

Unstable Plaques ◽

The Relationship

Introduction: Sex differences in plaque morphology and composition exist; men develop more unstable plaques than women. Yet, stroke kills more women than men. Despite these differences, no sex-specific guidelines for carotid disease management exist. Thus, markers that reflect sex-specific morphological features in the plaque should be explored for better prediction of stroke risk. Pro-inflammatory adipokines, chemerin and resistin, influence vascular function. Herein we are the first to investigate sex differences in the relationship between carotid plaque instability and the expression of these adipokines. Methods: Subjects with ≥50% carotid stenosis scheduled for a carotid endarterectomy were recruited from McGill-affiliated hospitals. Pre-operative plasma chemerin and resistin levels were measured using ELISA. Stability of carotid plaque specimens was assessed by two gold standard histological classifications. Stable and unstable plaques were immunostained for chemerin, chemerin’s receptor (ChemR23), and resistin. Digital and semi-quantifications assessed the % area of expression as well as staining intensity (mild to high) and % of positively stained macrophages/foam cells. Plaque mRNA expression was assessed by quantitative PCR. Sex-hormone analyses are ongoing. Results: Men (n=171) had more unstable plaque features, i.e., greater hemorrhage (P=0.022), lipid core size (P<0.001), inflammation (P=0.007), cap infiltration (P=0.006), and less fibrous tissue (P<0.001) than women (n=79). Circulating chemerin and resistin levels were similar between men and women and no sex differences were observed in relation to plaque instability. The % area of chemerin and resistin staining in the plaque was greater in unstable vs stable plaques in men only (P=0.040; P=0.005, respectively). Similarly, greater intensity in chemerin, ChemR23, and resistin staining was associated with plaque instability in men only (P<0.001; P=0.013; P=0.033, respectively). In contrast, lower resistin plaque mRNA expression was associated with plaque instability in women only (P=0.040). Conclusion: Our results suggest the possibility of a sex-dependent regulatory mechanism underlying the connection between these adipokines and plaque instability.

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Correlation of Carotid Intraplaque Hemorrhage and Stroke Using 1.5 T and 3 T Mri

Magnetic Resonance Insights ◽

10.4137/mri.s23560 ◽

2015 ◽

Vol 8s1 ◽

pp. MRI.S23560 ◽

Cited By ~ 6

Author(s):

Gerald S. Treiman ◽

J. Scott McNally ◽

Seong-Eun Kim ◽

Dennis L. Parker

Keyword(s):

Risk Stratification ◽

Carotid Plaque ◽

The United States ◽

Intraplaque Hemorrhage ◽

Specific Information ◽

Plaque Instability ◽

Asymptomatic Patients ◽

Cerebral Ischemic ◽

Ischemic Events ◽

Current Risk

Carotid therosclerotic disease causes approximately 25% of the nearly 690,000 ischemic strokes each year in the United States. Current risk stratification based on percent stenosis does not provide specific information on the actual risk of stroke for most individuals. Prospective randomized studies have found only 10 to 12% of asymptomatic patients will have a symptomatic stroke within 5 years. Measurements of percent stenosis do not determine plaque stability or composition. Reports have concluded that cerebral ischemic events associated with carotid plaque are intimately associated with plaque instability. Analysis of retrospective studies has found that plaque composition is important in risk stratification. Only MRI has the ability to identify and measure the detailed components and morphology of carotid plaque and provides more detailed information than other currently available techniques. MRI can accurately detect carotid hemorrhage, and MRI identified carotid hemorrhage correlates with acute stroke.

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Evaluation of Serum Biomarkers for Patients at Increased Risk of Stroke

International Journal of Vascular Medicine ◽

10.1155/2012/906954 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Pelisek Jaroslav ◽

Reeps Christian ◽

Ockert Stefan ◽

Zimmermann Alexander ◽

Peter Zepper ◽

...

Keyword(s):

Early Recognition ◽

Serum Levels ◽

Operating Characteristics ◽

Plaque Instability ◽

Asymptomatic Patients ◽

Score Analysis ◽

Increased Risk ◽

Biomarker Analysis ◽

Multiple Receiver ◽

Unstable Plaques

Early recognition of vulnerable patients is an important issue for stroke prevention. In our study, a multiscore analysis of various biomarkers was performed to evaluate its superiority over the analysis of single factors. Study subjects () were divided into four groups: asymptomatic patients with stable () and unstable () plaques and symptomatic patients with stable () and unstable () plaques. Serum levels of MMP-1, -2, -3, -7, -8, -9, TIMP-1, -2, TNF-α, IL-1b, and IL-6, -8, -10, -12 were measured. Multi-score analysis was performed using multiple receiver operating characteristics (ROC) and determination of appropriate cutoff values. Significant differences between the groups were observed for MMP-1, -7, -9 and TIMP-1 in serum of the study subjects (). Multiple biomarker analysis led to a significant increase in the AUC (area under curve). In case of plaque instability, positive predictive value (PPV) for up to 86.4% could be correctly associated with vulnerable plaques. Thus, multiscore analysis might be preferable than the use of single biomarkers.

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Deoxynucleoside therapy for respiratory involvement in adult patients with thymidine kinase 2-deficient myopathy

BMJ Open Respiratory Research ◽

10.1136/bmjresp-2020-000774 ◽

2020 ◽

Vol 7 (1) ◽

pp. e000774

Author(s):

Ana Hernandez-Voth ◽

Javier Sayas Catalan ◽

Marta Corral Blanco ◽

Alba Castaño Mendez ◽

Miguel Angel Martin ◽

...

Keyword(s):

Thymidine Kinase ◽

Respiratory Function ◽

Age At Onset ◽

Ventilatory Support ◽

Old Patients ◽

Respiratory Involvement ◽

Arterial Blood ◽

Asymptomatic Patients ◽

The Impact ◽

Thymidine Kinase 2

BackgroundRecessive mutations in the thymidine kinase 2 (TK2) gene cause a rare mitochondrial myopathy, frequently with severe respiratory involvement. Deoxynucleoside therapy is currently under investigation.Research questionWhat is the impact of nucleosides in respiratory function in patients with TK2-deficient myopathy?Study design and methodsRetrospective observational study of patients treated with deoxycytidine and deoxythymidine. Evaluations were performed every 3 to 4 months after treatment during approximately 30 months. Forced vital capacity (FVC), maximuminspiratory and expiratory pressures (MIP/MEP), sniff nasal inspiratory pressure (SNIP), cough peak flow (CPF), arterial blood gas and nocturnal pulse oximeter (SpO2) were collected.ResultsWe studied six patients, five of which were women, with a median age at onset of symptoms was 35.8 (range 5 to 60) years old. Patients presented a restrictive ventilatory pattern (median FVC of 50 (26 to 71)%) and severe neuromuscular respiratory weakness (MIP 38 (12 to 47)% and SNIP 14 (8 to 19) cmH2O). Four patients required ventilatory support before starting the treatment. FVC improved by 6%, proportion of sleep time with SpO2 <90% diminished from 14% to 0%, CPF increased by 23%, MEP increased by 73%, production and management of bronchial secretions improved and respiratory infections diminished.InterpretationEarly detection of respiratory involvement requires an active search, even in asymptomatic patients. The nucleosides therapy may improve respiratory function, and stabilise the loss of respiratory capacity.

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Evaluation of circulating tumor cells in colorectal cancer using flow cytometry

Journal of International Medical Research ◽

10.1177/0300060520980215 ◽

2021 ◽

Vol 49 (9) ◽

pp. 030006052098021

Author(s):

Ana-Maria Mușină ◽

Mihaela Zlei ◽

Mihaela Mentel ◽

Dragoș-Viorel Scripcariu ◽

Mădălina Ștefan ◽

...

Keyword(s):

Colorectal Cancer ◽

Flow Cytometry ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Statistical Significance ◽

Univariate Analysis ◽

Skin Incision ◽

Curative Surgery ◽

Female Sex ◽

The Impact

Objective We aimed to evaluate the prognostic value of circulating tumor cells (CTCs) and the impact of intraoperative tumor manipulation on CTCs in colorectal cancer (CRC) patients. Methods We performed a prospective study on 40 patients with CRC stages I to IV who received curative surgery using the no-touch technique. Flow cytometry was used to identify CTCs in peripheral blood samples (4 mL/sample) collected at two surgical moments: skin incision (T1) and after surgical resection (T2). A threshold of ≥4 CTCs/4 mL blood was established for considering patients CTC positive. Results In the univariate analysis, CTC evaluation at T2 was correlated with female sex, vascular invasion, tumor localization in the colon and metastatic lymph nodes. In the multivariate analysis, only female sex and colon cancer maintained statistical significance. At a medium follow-up of 15 months (1–25 months), the mortality rate was 10% (n = 4), with no significant differences between the overall survival of T1 or T2 CTC-positive and CTC-negative patients. Conclusions Flow cytometry is a feasible CTC identification technique in CRC, and although surgical manipulation has no influence on CTC numbers, CTCs may serve as a prognostic and predictive factor.

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High Sensitivity C-Reactive Protein Increases the Risk of Carotid Plaque Instability in Male Dyslipidemic Patients

Diagnostics ◽

10.3390/diagnostics11112117 ◽

2021 ◽

Vol 11 (11) ◽

pp. 2117

Author(s):

Manuel Scimeca ◽

Manuela Montanaro ◽

Marina Cardellini ◽

Rita Bonfiglio ◽

Lucia Anemona ◽

...

Keyword(s):

Carotid Plaque ◽

Smoking Habit ◽

Density Lipoprotein ◽

Heart Association ◽

High Sensitivity ◽

C Reactive Protein ◽

Plaque Instability ◽

Reactive Protein ◽

Asymptomatic Patients ◽

Hs Crp

Background: The aim of this study was to evaluate how the high sensitivity C-reactive protein (hs-CRP) values influence the risk of carotid plaque instability in association with other cardiovascular risk factors. Methods: One hundred and fifty-six carotid plaques from both symptomatic and asymptomatic patients requiring surgical carotid endarterectomy were retrospectively collected. According to the modified American Heart Association, atherosclerosis plaques have been histologically distinguished into unstable and stable. The following anamnestic and hematochemical data were also considered: age, gender, hypertension, diabetes mellitus, smoking habit, therapy, low-density lipoprotein (LDL)-C, kidney failure and hs-CRP. Results: The results of our study clearly show that high levels of hs-CRP significantly increase the carotid plaque instability in dyslipidemic patients. Specifically, a 67% increase of the risk of carotid plaque instability was observed in patients with high LDL-C. Therefore, the highest risk was observed in male dyslipidemic patients 2333 (95% CI 0.73–7.48) and in aged female patients 2713 (95% CI 0.14–53.27). Discussion: These data strongly suggest a biological relationship between the hs-CRP values and the alteration of lipidic metabolism mostly in male patients affected by carotid atherosclerosis. The measurement of hs-CRP might be useful as a potential screening tool in the prevention of atheroscletotic disease.

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Abstract TP110: Helicobacter Pylori Infection and Genetic Factors as Determinants of Carotid Plaque Stability

Stroke ◽

10.1161/str.48.suppl_1.tp110 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Eugenia Arias ◽

Naomi Arakaki ◽

Horacio Martinetto ◽

Gustavo E Sevlever ◽

Sebastian F Ameriso

Keyword(s):

Inflammatory Cells ◽

Exact Test ◽

Carotid Plaques ◽

Plaque Instability ◽

Asymptomatic Patients ◽

Human Atherosclerosis ◽

Unstable Plaques ◽

H Pylori ◽

Asymptomatic Subjects

Introduction: Little is known about the role of H pylori in human atherosclerosis. We have previously demonstrated its presence in carotid plaques, especially among asymptomatic patients, with prevalence of cag A-positive strains. Polymorphisms of genes of angiotensin-converting enzyme (ACE), lipoprotein APOE (APOE), IL1 receptor antagonist (IL1Ra) and myeloperoxidase (MPO) are associated with atherosclerosis. We evaluated the role of H pylori in certain features of carotid plaques and assessed allelic and genotypic frequencies and their association with H pylori infection and plaque characteristics. Methods: We studied 137 carotid plaques of patients undergoing endarterectomy. We categorized as stable those predominantly fibrous plaques with scarce inflammatory cells, intact cap and no hemorrhage and unstable those plaques with inflammation, thin cap, ruptured lipid core, thrombi and hemorrhage. We extracted genomic DNA and identified and typified H Pylori DNA. DNA was also obtained from peripheral blood and we identified allelic and genotypic frequencies and susceptibility variants of ACE, APOE, IL1Ra, and MPO genes. Fisher’s exact test (two-tailed) and good fit test were used. Results: There were 72 asymptomatic patients with 47 stable and 25 unstable plaques and 65 symptomatic patients with 13 stable and 52 unstable plaques (p<0.0001). H pylori infection was present in 48 of 60 stable plaques and 31 of 77 unstable plaques (p<0.0001). In addition, stable infected plaques more often carried the more virulent cag A strain. H pylori cag A-negative plaques had larger intima media complex thickness than cag A-positive and H pylori -negative plaques. Stable infected plaques were associated to alleles APOE-33 and IL1RN-11. Unstable noninfected plaques were associated to proatherogenic alleles ACE-DD, APOE*4, APOE*2, IL1RN*2, and MPO-GG. Conclusions: Histopathological features of plaque instability are associated to the presence of recent symptoms. H pylor i infection with the virulent cag A strain is highly prevalent in stable carotid plaques of asymptomatic subjects. Noninflammatory genotypes are present in stable infected plaques whereas proatherogenic polymorphisms are predominant in unstable noninfected plaques.

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Abstract 453: Chemerin and Resistin Expression in Carotid Plaque Instability

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.34.suppl_1.453 ◽

2014 ◽

Vol 34 (suppl_1) ◽

Author(s):

Robert-James Doonan ◽

Samantha Steinmetz-Wood ◽

Karina Gasbarrino ◽

Huaien Zheng ◽

Chi Lai ◽

...

Keyword(s):

Carotid Plaque ◽

Inflammatory Cells ◽

Foam Cells ◽

Plaque Instability ◽

Asymptomatic Patients ◽

Ongoing Work ◽

Hematoxylin And Eosin ◽

Artery Disease ◽

Underlying Mechanisms ◽

The Relationship

Objective: Chemerin and resistin are pro-inflammatory cytokines that have been shown to play a role in atherosclerosis and coronary artery disease. However, their association with carotid atherosclerosis has not been investigated. We sought to assess the relationship between a) circulating chemerin/resistin levels and cerebrovascular symptomatology, and b) chemerin/resistin plaque expression and carotid plaque instability. Methods: Patients scheduled for carotid endarterectomy were recruited from the Royal Victoria and Jewish General hospitals, Montreal, Canada. Blood was drawn pre-operatively and plasma resistin and chemerin were measured using ELISA. Maximum stenosis sections were stained with hematoxylin and eosin and immunostained with anti-CD3 and anti-CD68. Two vascular pathologists used semi-quantitative scales to classify plaque foam cells and inflammatory cells as well as overall plaque instability. RNA was isolated from the area of maximum stenosis, reverse transcribed, and qPCR was performed to measure chemerin and resistin expression. Kruskal-Wallis or Mann-Whitney U tests were used to evaluate differences in resistin and chemerin between groups. Results: In this ongoing study we recruited 169 patients (66.1% men, 74.5% symptomatic) with a mean±SD age of 70.0±9.3 years. To date all 169 patients had blood samples drawn and 100 had plaque chemerin and resistin expression assessed. Symptomatic patients had higher plasma chemerin (230 (179.0-261.3) vs. 201.4 (175.8-228.1) ng/ml, P=0.08) and resistin levels (12.7 (10.2-17.7) vs. 10.8 (7.1-16.0) ng/ml, P=0.02) when compared with asymptomatic patients. Chemerin plaque expression was decreased in plaques with greater number of foam cells and inflammatory cells and in plaques with greater overall instability. Resistin plaque expression was also decreased in plaques with a greater number of foam cells and inflammatory cells. Conclusions: Circulating chemerin and resistin levels are increased in symptomatic patients. Intraplaque chemerin and resistin expression is inversely related to the number of plaque inflammatory cells and instability. Our ongoing work will determine the underlying mechanisms linking chemerin and resistin with atherosclerotic plaque instability.

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The Paradox Effect of Calcification in Carotid Atherosclerosis: Microcalcification Is Correlated with Plaque Instability

International Journal of Molecular Sciences ◽

10.3390/ijms22010395 ◽

2021 ◽

Vol 22 (1) ◽

pp. 395

Author(s):

Manuela Montanaro ◽

Manuel Scimeca ◽

Lucia Anemona ◽

Francesca Servadei ◽

Erica Giacobbi ◽

...

Keyword(s):

Carotid Plaque ◽

Carotid Atherosclerosis ◽

Macrophage Polarization ◽

Inflammatory Biomarkers ◽

Histological Evaluation ◽

M2 Macrophage ◽

Carotid Plaques ◽

Plaque Instability ◽

Asymptomatic Patients ◽

Significant Difference

Background: this study aims to investigate the possible association among the histopathologic features of carotid plaque instability, the presence of micro- or macrocalcifications, the expression of in situ inflammatory biomarkers, and the occurrence of the major risk factors in this process in a large series of carotid plaques. Methods: a total of 687 carotid plaques from symptomatic and asymptomatic patients were collected. Histological evaluation was performed to classify the calcium deposits in micro or macrocalcifications according to their morphological features (location and size). Immunohistochemistry was performed to study the expression of the main inflammatory biomarkers. Results: results here reported demonstrated that calcifications are very frequent in carotid plaques, with a significant difference between the presence of micro- and macrocalcifications. Specifically, microcalcifications were significantly associated to high inflamed unstable plaques. Paradoxically, macrocalcifications seem to stabilize the plaque and are associated to a M2 macrophage polarization instead. Discussion: the characterization of mechanisms involved in the formation of carotid calcifications can lay the foundation for developing new strategies for the management of patients affected by carotid atherosclerosis. Data of this study could provide key elements for an exhaustive evaluation of carotid plaque calcifications allowing to establish the risk of associated clinical events.

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