Evaluation of Serum Biomarkers for Patients at Increased Risk of Stroke

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

VASA ◽

10.1024/0301-1526/a000557 ◽

2016 ◽

Vol 45 (5) ◽

pp. 411-416 ◽

Cited By ~ 11

Author(s):

Carina Wendorff ◽

Heiko Wendorff ◽

Andreas Kuehnl ◽

Pavlos Tsantilas ◽

Michael Kallmayer ◽

...

Keyword(s):

Carotid Plaque ◽

Statistical Significance ◽

Old Patients ◽

Continuous Increase ◽

Plaque Instability ◽

Female Sex ◽

Asymptomatic Patients ◽

Unstable Plaques ◽

The Impact ◽

Asymptomatic Men

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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Atherosclerotic plaque instability in carotid arteries: miR-200c as a promising biomarker

Clinical Science ◽

10.1042/cs20180684 ◽

2018 ◽

Vol 132 (22) ◽

pp. 2423-2436 ◽

Cited By ~ 13

Author(s):

Alessandra Magenta ◽

Sara Sileno ◽

Marco D’Agostino ◽

Francesca Persiani ◽

Sara Beji ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Atherosclerotic Plaque ◽

Early Recognition ◽

Monocyte Chemoattractant Protein 1 ◽

Carotid Plaques ◽

Plaque Instability ◽

Atherosclerosis Progression ◽

E Box ◽

Unstable Plaques ◽

Endothelial Nitric Oxide

Early recognition of vulnerable carotid plaques could help in identifying patients at high stroke risk, who may benefit from earlier revascularisation. Nowadays, different biomarkers of plaque instability have been unravelled, among these miRNAs are promising tools for the diagnosis and treatment of atherosclerosis. Inflammation, reactive oxygen species (ROS) and endothelial dysfunction play a key role in unstable plaques genesis. We showed that miR-200c induces endothelial dysfunction, ROS production and a positive mechanism among miR-200c and miR-33a/b, two miRNAs involved in atherosclerosis progression. The goal of the present study was to determine whether miR-200c could be an atherosclerosis biomarker. Carotid plaques of patients that underwent carotid endarterectomy (CEA) were assayed for miR-200c expression. miR-200c was up-regulated in carotid plaques (n=22) and its expression was higher in unstable (n=12) compared with stable (n=10) plaques. miR-200c positively correlated with instability biomarkers (i.e. monocyte chemoattractant protein-1, cicloxigenase-2 (COX2), interleukin 6 (IL6), metalloproteinase (MMP) 1 (MMP1), 9 (MMP9)) and miR-33a/b. Moreover, miR-200c negatively correlated with stability biomarkers (i.e. zinc finger E-box binding homoeobox 1 (ZEB1), endothelial nitric oxide (NO) synthase (eNOS), forkhead boxO1 (FOXO1) and Sirtuin1 (SIRT1)) (stable plaques = 15, unstable plaques = 15). Circulating miR-200c was up-regulated before CEA in 24 patients, correlated with miR-33a/b and decreased 1 day after CEA. Interestingly, 1 month after CEA, circulating miR-200c is low in patients with stable plaques (n=11) and increased to control levels, in patients with unstable plaques (n=13). Further studies are needed to establish whether miR-200c represents a circulating biomarker of plaque instability. Our results show that miR-200c is an atherosclerotic plaque progression biomarker and suggest that it may be clinically useful to identify patients at high embolic risk.

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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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Interleukin-4, hemopexin, and lipoprotein-associated phospholipase A2 are significantly increased in patients with unstable carotid plaque

Open Chemistry ◽

10.1515/chem-2019-0125 ◽

2019 ◽

Vol 17 (1) ◽

pp. 1105-1115

Author(s):

Peter Stefanic ◽

Vladimir Sihotsky ◽

Zdenka Hertelyova ◽

Ivan Kopolovets ◽

Abraham John Mathews ◽

...

Keyword(s):

Carotid Artery ◽

Phospholipase A2 ◽

Carotid Plaque ◽

Serum Levels ◽

Neurological Symptoms ◽

Interleukin 4 ◽

Histopathological Analysis ◽

Carotid Artery Atherosclerosis ◽

Asymptomatic Patients ◽

Unstable Plaques

AbstractObjectiveThis study aimed to compare the plasma levels of lipoprotein-associated phospholipase A2 (Lp-PLA2), hemopexin (Hpx), and interleukin-4 (IL-4) in patients with carotid artery atherosclerosis based on neurological symptoms and plaque histopathology and to find association between plaque stability and neurological symptoms. This single-center study included patients treated surgically for significant stenosis of the internal carotid artery. Serum levels of biomarkers were determined, and a histopathological analysis of the carotid plaques was performed. Within 70 patients, 40 asymptomatic and 30 symptomatic; 38 patients (54.3%) were diagnosed with unstable carotid plaque and 32 patients (45.7%) had a stable carotid plaque. Significantly higher incidence of unstable carotid plaque was detected in symptomatic patients (p <0.001). Compared to asymptomatic patients, higher expression of Lp-PLA2 (285.30 ± 2.05 μg/l), Hpx (0.38 ± 0.01 ng/l), and IL-4 (65.77 ± 3.78 ng/l) in plasma were detected in symptomatic patients. Subsequently, higher expression of Lp-PLA2 (297.34 ± 2.3 μg/l), Hpx (0.41 ± 0.02 ng/l), and IL-4 (64.74 ± 4.47 ng/l) in plasma was observed in patients with unstable plaques (n=38). Statistically significant (p <0.001) differences in expression of Lp-PLA2, Hpx, and IL-4 between patients with unstable and stable plaques were detected. Moreover, only the differences between symptomatic and asymptomatic patients in the expression of Lp-PLA2 and IL-4 in plasma were statistically significant (p <0.001). This study showed that Lp-PLA2, IL-4, and Hpx levels are significantly increased in patients with an unstable carotid plaque.

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Myocardial Noncompaction

Revista de Chimie ◽

10.37358/rc.18.8.6500 ◽

2018 ◽

Vol 69 (8) ◽

pp. 2209-2212

Author(s):

Alexandru Radu Mihailovici ◽

Vlad Padureanu ◽

Carmen Valeria Albu ◽

Venera Cristina Dinescu ◽

Mihai Cristian Pirlog ◽

...

Keyword(s):

Ventricular Arrhythmias ◽

Specific Treatment ◽

Left Ventricular ◽

Left Ventricular Noncompaction ◽

Ventricular Noncompaction ◽

Genetic Transmission ◽

Asymptomatic Patients ◽

Increased Risk ◽

Patients With Heart Failure

Left ventricular noncompaction is a primary cardiomyopathy with genetic transmission in the vast majority of autosomal dominant cases. It is characterized by the presence of excessive myocardial trabecularities that generally affect the left ventricle. In diagnosing this condition, echocardiography is the gold standard, although this method involves an increased risk of overdiagnosis and underdiagnosis. There are also uncertain cases where echocardiography is inconclusive, a multimodal approach is needed, correlating echocardiographic results with those obtained by magnetic resonance imaging. The clinical picture may range from asymptomatic patients to patients with heart failure, supraventricular or ventricular arrhythmias, thromboembolic events and even sudden cardiac death. There is no specific treatment of left ventricular noncompaction, but the treatment is aimed at preventing and treating the complications of the disease. We will present the case of a young patient with left ventricular noncompactioncardiomyopathy and highlight the essential role of transthoracic echocardiography in diagnosing this rare heart disease.

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Association between Vitamins and Minerals with Antioxidant Effects and Coronary Artery Calcification in Adults and Older Adults: A Systematic Review

Current Pharmaceutical Design ◽

10.2174/1381612825666190722101954 ◽

2019 ◽

Vol 25 (22) ◽

pp. 2474-2479 ◽

Cited By ~ 1

Author(s):

Alisson Diego Machado ◽

Gustavo Rosa Gentil Andrade ◽

Jéssica Levy ◽

Sara Silva Ferreira ◽

Dirce Maria Marchioni

Keyword(s):

Systematic Review ◽

Older Adults ◽

Coronary Artery ◽

Coronary Artery Calcification ◽

Serum Levels ◽

Antioxidant Compounds ◽

Increased Risk ◽

Coronary Events ◽

Antioxidant Effects

Background: Coronary Artery Calcification (CAC) is considered an important cardiovascular risk factor. There is evidence that CAC is associated with an increased risk of atherosclerosis, coronary events and cardiovascular mortality. Inflammation is one of the factors associated with CAC and despite the interest in antioxidant compounds that can prevent CAC, its association with antioxidants remains unclear. Objective: This study aimed to systematically review the association between vitamins and minerals with antioxidant effects and CAC in adults and older adults. Methods: We conducted a systematic review using PubMed for articles published until October 2018. We included studies conducted in subjects aged 18 years and older with no previous cardiovascular disease. Studies involving animal or in vitro experiments and the ones that did not use reference methods to assess the CAC, dietary intake or serum levels of vitamin or mineral were excluded. Results: The search yielded 390 articles. After removal of duplicates, articles not related to the review, review articles, editorials, hypothesis articles and application of the inclusion and exclusion criteria, 9 articles remained. The results of the studies included in this systematic review suggest that magnesium is inversely associated with CAC and results on the association between CAC and vitamin E have been conflicting. Conclusion: Additional prospective studies are needed to elucidate the role of these micronutrients on CAC.

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Discovery of predictors of sudden cardiac arrest in diabetes: rationale and outline of the RESCUED (REcognition of Sudden Cardiac arrest vUlnErability in Diabetes) project

Open Heart ◽

10.1136/openhrt-2020-001554 ◽

2021 ◽

Vol 8 (1) ◽

pp. e001554

Author(s):

Laura H van Dongen ◽

Peter P Harms ◽

Mark Hoogendoorn ◽

Dominic S Zimmerman ◽

Elisabeth M Lodder ◽

...

Keyword(s):

Cardiac Arrest ◽

Prognostic Model ◽

Early Recognition ◽

Sudden Cardiac Arrest ◽

Clinical Genetic ◽

Innovative Strategy ◽

Rare Variant Analysis ◽

Increased Risk ◽

Gp Care

IntroductionEarly recognition of individuals with increased risk of sudden cardiac arrest (SCA) remains challenging. SCA research so far has used data from cardiologist care, but missed most SCA victims, since they were only in general practitioner (GP) care prior to SCA. Studying individuals with type 2 diabetes (T2D) in GP care may help solve this problem, as they have increased risk for SCA, and rich clinical datasets, since they regularly visit their GP for check-up measurements. This information can be further enriched with extensive genetic and metabolic information.AimTo describe the study protocol of the REcognition of Sudden Cardiac arrest vUlnErability in Diabetes (RESCUED) project, which aims at identifying clinical, genetic and metabolic factors contributing to SCA risk in individuals with T2D, and to develop a prognostic model for the risk of SCA.MethodsThe RESCUED project combines data from dedicated SCA and T2D cohorts, and GP data, from the same region in the Netherlands. Clinical data, genetic data (common and rare variant analysis) and metabolic data (metabolomics) will be analysed (using classical analysis techniques and machine learning methods) and combined into a prognostic model for risk of SCA.ConclusionThe RESCUED project is designed to increase our ability at early recognition of elevated SCA risk through an innovative strategy of focusing on GP data and a multidimensional methodology including clinical, genetic and metabolic analyses.

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Comparison of non-myeloablative lymphodepleting preconditioning regimens in patients undergoing adoptive T cell therapy

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001743 ◽

2021 ◽

Vol 9 (5) ◽

pp. e001743

Author(s):

Abraham Nissani ◽

Shaked Lev-Ari ◽

Tomer Meirson ◽

Elad Jacoby ◽

Nethanel Asher ◽

...

Keyword(s):

Bone Marrow ◽

T Cell ◽

Adverse Events ◽

Cell Therapy ◽

Clinical Response ◽

Serum Levels ◽

Bone Marrow Suppression ◽

Maximum Effect ◽

Operating Characteristics ◽

Lymphocyte Ratio

BackgroundAdoptive cell therapy with T cells genetically engineered to express a chimeric antigen receptor (CAR-T) or tumor-infiltrating T lymphocytes (TIL) demonstrates impressive clinical results in patients with cancer. Lymphodepleting preconditioning prior to cell infusion is an integral part of all adoptive T cell therapies. However, to date, there is no standardization and no data comparing different non-myeloablative (NMA) regimens.MethodsIn this study, we compared NMA therapies with different doses of cyclophosphamide or total body irradiation (TBI) in combination with fludarabine and evaluated bone marrow suppression and recovery, cytokine serum levels, clinical response and adverse events.ResultsWe demonstrate that a cumulative dose of 120 mg/kg cyclophosphamide and 125 mg/m2 fludarabine (120Cy/125Flu) and 60Cy/125Flu preconditioning were equally efficient in achieving deep lymphopenia and neutropenia in patients with metastatic melanoma, whereas absolute lymphocyte counts (ALCs) and absolute neutrophil counts were significantly higher following 200 cGyTBI/75Flu-induced NMA. Thrombocytopenia was most profound in 120Cy/125Flu patients. 30Cy/75Flu-induced preconditioning in patients with acute lymphoblastic leukemia resulted in a minor ALC decrease, had no impact on platelet counts and did not yield deep neutropenia. Following cell infusion, 120Cy/125Flu patients with objective tumor response had significantly higher ALC and significant lower inflammatory indexes, such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Receiver-operating characteristics curve analysis 7 days after cell infusion was performed to determine the cut-offs, which distinguish between responding and non-responding patients in the 120Cy/125Flu cohort. NLR≤1.79 and PLR≤32.7 were associated with clinical response and overall survival. Cytokine serum levels did not associate with clinical response in patients with TIL. Patients in the 120Cy/125Flu cohort developed significantly more acute NMA-related adverse events, including thrombocytopenia, febrile neutropenia and cardiotoxicity, and stayed significantly longer in hospital compared with the 60Cy/125Flu and TBI/75Flu cohorts.ConclusionsBone marrow depletion and recovery were equally affected by 120Cy/125Flu and 60Cy/125Flu preconditioning; however, toxicity and consequently duration of hospitalization were significantly lower in the 60Cy/125Flu cohort. Patients in the 30Cy/75Flu and TBI/75Flu groups rarely developed NMA-induced adverse events; however, both regimens were not efficient in achieving deep bone marrow suppression. Among the regimens, 60Cy/125Flu preconditioning seems to achieve maximum effect with minimum toxicity.

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Clinical Stratification of Pregnant COVID-19 Patients based on Severity: A Single Academic Center Experience

American Journal of Perinatology ◽

10.1055/s-0041-1723761 ◽

2021 ◽

Vol 38 (05) ◽

pp. 515-522

Author(s):

Marissa Berry ◽

Amanda Wang ◽

Shannon M. Clark ◽

Hassan M. Harirah ◽

Sangeeta Jain ◽

...

Keyword(s):

Pregnant Women ◽

Disease Severity ◽

Gestational Age ◽

Laboratory Data ◽

Population Characteristics ◽

Neonatal Outcomes ◽

P Value ◽

Asymptomatic Patients ◽

Increased Risk ◽

Maternal And Neonatal Outcomes

Objective This study aimed to describe baseline characteristics of a cohort of pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and determine if these correlate with disease severity and perinatal outcomes. Study Design This was a retrospective cohort trial conducted at the University of Texas Medical Branch Galveston, Texas. All pregnant women presented to our medical center, who were screened and tested positive for SARS-CoV-2 virus, were included. We stratified our study population in three groups: asymptomatic, symptomatic not requiring oxygen therapy, and patients requiring oxygen support to maintain oxygen saturation >94%. Relevant population characteristics, laboratory data, and maternal and neonatal outcomes were abstracted. A p-value <0.05 was considered statistically significant. Results Between March and July 2020, 91 women tested positive for SARS-CoV-2 upon admission to our labor and delivery unit. Among these, 61.5% were asymptomatic, 34.1% were symptomatic, and 4.4% required oxygen support. Our population was mainly Hispanic (80.2%), multiparous (76.9%), obese (70.3%), and with a median age of 27 years. Median gestational age at symptom onset or diagnosis was 36 weeks. Significant differences were found between gestational age and disease severity. Maternal characteristics including age, body mass index (BMI), and presence of comorbid conditions did not appear to influence severity of SARS-CoV-2 infection. Significant laboratory findings associated with increasing disease severity included decreasing hemoglobin and white blood cell count, lymphopenia, and increasing levels of inflammatory markers including CRP, ferritin, and procalcitonin. Maternal and neonatal outcomes did not differ among groups. No SARS-CoV-2 was detected by polymerase chain reaction testing in neonates of mothers with COVID-19. Conclusion Pregnant patients with COVID-19 infection are predominantly asymptomatic. Patients appear to be at increased risk for more severe infection requiring oxygen support later in pregnancy. Key Points

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