scholarly journals Circulating Th22 and Th9 Levels in Patients with Acute Coronary Syndrome

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Ying-zhong Lin ◽  
Bang-wei Wu ◽  
Zheng-de Lu ◽  
Ying Huang ◽  
Ying Shi ◽  
...  
Keyword(s):  
Angina Pectoris ◽  
Flow Cytometric Analysis ◽  
Control Groups ◽  
Th22 Cells ◽  
Coronary Syndrome ◽  
Flow Cytometric ◽  
Th9 Cells ◽  
Coronary Syndromes ◽  
And Control ◽  
Progression Of Atherosclerosis

Background. CD4+ T helper (Th) cells play critical roles in the development and progression of atherosclerosis and the onset of acute coronary syndromes (ACS, including acute myocardial infarction (AMI) and unstable angina pectoris (UAP)). In addition to Th1, Th2, and Th17 cells, Th22 and Th9 subsets have been identified in humans. In the present study, we investigated whether Th22 cells and Th9 cells are involved in the onset of ACS.Methods. The frequencies of Th22 and Th9 cells were detected using a flow cytometric analysis and their related cytokine and transcription factor were measured in the AMI, UAP, stable angina pectoris (SAP), and control groups.Results. The results revealed a significant increase in the peripheral Th22 number, AHR expression, and IL-22 levels in patients with ACS compared with those in the SAP and control groups. Although there was no difference in the peripheral Th9 number among the four groups, the PU.1 expression and IL-9 levels were significantly increased in patients with ACS compared with the SAP and control groups.Conclusions. Circulating Th22 and Th9 type responses may play a potential role in the onset of ACS symptom.

scholarly journals Downregulation of CD4+LAP+ and CD4+CD25+ Regulatory T Cells in Acute Coronary Syndromes

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Ying-zhong Lin ◽  
Shan-he Lu ◽  
Zheng-de Lu ◽  
Ying Huang ◽  
Ying Shi ◽  
...  
Keyword(s):  
Acute Coronary Syndromes ◽  
Flow Cytometric Analysis ◽  
Treg Cells ◽  
Protective Role ◽  
Control Group ◽  
Flow Cytometric ◽  
Coronary Syndromes ◽  
St Elevation ◽  
And Control ◽  
Elevation Acute Myocardial Infarction

Background. Regulatory T (Treg) cells play a protective role in atherosclerosis prone models and are related to the onset of acute coronary syndromes (ACS, including non-ST-elevation ACS (NSTEACS) and ST-elevation acute myocardial infarction (STEAMI)). CD4+LAP+ Treg cells are a novel subset of Tregs that have been found to ameliorate atherosclerosis inApoE-/-mice, and these cells also exist in humans. The present study was designed to investigate whether CD4+LAP+ Treg cells are involved in the onset of ACS.Methods. The frequencies of CD4+LAP+ and CD4+CD25+ Treg cells were detected using flow cytometric analysis, and the plasma IL-10 and TGF-β1 levels were measured using an ELISA in 29 stable angina (SA) patients, 30 NSTEACS patients, 27 STEAMI patients, and a control group (30 cases).Results. The results revealed a significant decrease in the frequencies of CD4+LAP+ and CD4+CD25+ Treg cells and in the levels of IL-10 and TGF-β1 in patients with ACS compared with those in the SA and control groups.Conclusions. The decrease in the frequencies of CD4+LAP+ and CD4+CD25+ Treg cells may play a role in the onset of ACS.

scholarly journals Changes in interleukin-27 levels in patients with acute coronary syndrome and their clinical significance

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e5652 ◽  
Author(s):  
Lin Zhang ◽  
Junfeng Zhang ◽  
Shaohong Su ◽  
Suyan Luo
Keyword(s):  
Acute Coronary Syndrome ◽  
Angina Pectoris ◽  
Th17 Cells ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Groups ◽  
Coronary Syndrome ◽  
Significant Difference ◽  
Ifn Γ ◽  
And Control

Background This study evaluated changes in interleukin (IL)-27 levels in patients with acute coronary syndrome (ACS) and their influence on Th1, Th2, and Th17 cells. Methods Serum levels of IL-27, IL-4, IL-17, and interferon (IFN)-γ in healthy subjects as well as patients with ACS, including stable angina pectoris (SA), unstable angina pectoris (UA), and acute myocardial infarction (AMI), were determined using an enzyme-linked immunosorbent assay. The proportions of Th1, Th2, and Th17 cells among peripheral blood mononuclear cells (PBMCs), were measured using flow cytometry, after incubation with phorbol myristate acetate (PMA) for 4 h. The proportions of Th1 and Th17 cells among PBMCs in AMI and UA were detected after stimulation with IL-27 or PMA + IL-27 for 4, 8, and 12 h. Results Serum levels of IL-27 in patients with AMI and UA were significantly lower than those in SA and control groups, while serum levels of IL-17 and IFN-γ in AMI and UA groups were dramatically increased compared to those in SA and healthy control groups. However, there were no statistically significant differences in serum IL-4. The proportions of Th1 and Th17 cells among PBMCs were statistically significantly higher in the AMI and UA groups than those in the SA and control groups, while there was no statistically significant difference in the proportion of Th2 cells among different groups. For patients with AMI and UA, the effect of co-stimulation of PBMCs with PMA and IL-27 was not significantly different from that of PMA single stimulation, while PMA + IL-27 co-stimulation lowered the Th17 cell proportion significantly compared to PMA single stimulation. Discussion Compared to SA patients and healthy controls, patients with ACS (AMI + UA) had lower serum levels of IL-27 and higher proportions of PBMC Th1 and Th17 cells, which could be attributed to the inhibitory effects of IL-27 on the proliferation of Th17 cells. These results indicated that IL-27 could be a novel therapeutic target in ACS patients.

Glycogen phosphorylase BB in acute coronary syndromes

2005 ◽  
Vol 43 (12) ◽  
Author(s):  
Dirk Peetz ◽  
Felix Post ◽  
Helmut Schinzel ◽  
Rosemarie Schweigert ◽  
Caroline Schollmayer ◽  
...  
Keyword(s):  
Angina Pectoris ◽  
Acute Coronary Syndromes ◽  
Glycogen Phosphorylase ◽  
Troponin T ◽  
Plasma Concentrations ◽  
High Specificity ◽  
Cardiac Markers ◽  
Potential Candidate ◽  
Coronary Syndrome ◽  
Coronary Syndromes

AbstractThe diagnosis of myocardial damage is preferably based on measurement of the cardiac-specific troponins. However, there is an emerging need for early, specific cardiac markers. One potential candidate is the glycogen phosphorylase BB isoenzyme (GPBB). We investigated the use of a new, commercially available GPBB ELISA assay in 61 patients presenting with an acute coronary syndrome (37 acute myocardial infarction, 24 unstable angina pectoris) in comparison to established cardiac markers such as troponin T, creatine kinase isoenzyme MB (CKMB) mass, and myoglobin. Blood samples were obtained on arrival, as well as 1, 2, 3, 4, 8, 12 and 24h later. GPBB plasma concentrations were elevated in 90.9% of patients 1h after onset of chest pain and increased to 100% at 4–5h. Within the first 6h, GPBB showed the highest sensitivity (95.5–100%) and high specificity (94–96%) compared to myoglobin (85–95% sensitivity) and CKMB mass (71.4–91.3% sensitivity). As expected, troponin T showed high specificity (100%) and sensitivity >95% later in the time course (≥3h). In un-stable angina pectoris patients, a very high rate of elevated GPBB was observed (93.9% at 3h) compared to myoglobin (66.7%). Cardiac troponin T and CKMB were only elevated in 33.8% and 55.0% of these patients, respectively. In conclusion, GPBB is a promising marker for the early diagnosis of acute coronary syndromes and could probably act as a marker of ischemia. However, further studies on specificity and development of a fast, automated assay are necessary before GPBB can be recommended as a routine diagnostic tool.

scholarly journals Cell Autonomous Defects of Mesenchymal Stem Progenitor Cells of Patients with CMML Contribute to Impaired Hematopoietic Supportive Activity

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3599-3599
Author(s):  
Hui Shi ◽  
Rong Li ◽  
Wen Xing ◽  
Jie Bai ◽  
Xiaohui Si ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Adipocyte Differentiation ◽  
Flow Cytometric Analysis ◽  
Flow Cytometric ◽  
Cd34 Cells ◽  
Cytokine Array ◽  
Cord Blood Cells ◽  
And Control

Abstract Objective: Increasing evidence indicates a critical role of the hematopoietic microenvironment in the pathophysiology of myeloid malignancies. Mesenchymal stem/progenitor cells (MSPCs) represent an indispensible cellular component of the bone marrow microenvironment and play an important role in supporting and regulating the proliferation and differentiation of hematopoietic stem/progenitor cells (HSPCs). Abnormal biological characteristics of MSPCs involved in the initiating and development of hematopoietic disorders, such as chronic myelogenous leukemia and myelodysplastic syndromes. However, the characteristics and the role of primary MSPC defects in the pathogenesis of chronic myelomonocytic leukemia (CMML) remain poorly understood. Methods: MSPCs were generated from bone marrow aspirates of patients with CMML and that of healthy controls. To investigate the frequency of the MSPCs in the bone marrow of CMML patients and healthy controls in vivo, a colony-forming unit fibroblast (CFU-F) assay was performed. The phenotypic evaluation of the MSPCs was performed with flow cytometric analysis after staining with a cocktail of cell surface markers, including CD34, CD45, CD29, CD44, CD73 and CD105. To determine the functional difference between the CMML- and control-MSPCs, senescence, cell proliferation, and cell cycle were assessed by EDU incorporation assays, β-galactosidase activity, and flow cytometric analysis (following BrdU/7AAD staining, respectively. To determine the multi-lineage potential of MSPCs, MSPCs were subjected osteoblast, chondrocyte and adipocyte differentiation cultures. The hematopoietic supportive activity was assessed using cobblestone-area forming cell (CAFC) assays by coculturing of CD34+ cord blood cells with CMML- or control- MSPCs. Furthermore, to evaluate the soluble factors of these MSPCs in HSPC supportive activity, the transwell assay was performed with a subsequent flow cytometric analysis further determine the multi-lineage differentiation alteration. Cytokine array was used to determine the cytokines/growth factors in the MSPC conditioned media. Results: The expression levels of the surface markers were identical between CMML-MSPCs and control MSPCs. The frequency of CFU-F is identical between healthy control and CMML patients. However, CMML-MSPCs exhibited a poor proliferative capacity compared to controls MSPCs. CMML MSPCs exhibited an increased senescence and a S phase retardation in the cell cycle as assessed microscopically and flow cytometrically, respectively. Differentiation assay revealed that CMML MSPCs had increased chondrocyte differentiation and reduced adipocyte differentiation, while no alteration of osteoblast differentiation was noticed. In vitro co-cultures of MSPCs and CD34+ umbilical cord blood cells demonstrated that CMML-MSPCs had an impaired hematopoietic supportive capability as compared to control MSPCs as evidenced by reduced numbers of cobble-stone and reduced numbers of CFU-C. Furthermore, a reduced CFU-C and a reduced CFU-GEMM were observed in CAFC and transwell cultures containing CMML-MSPCs compared to that of control MSPCs. In contrast, an increased myeloid cells (CD33+/CD14-/CD15+) and an increased CFU-GM were observed in CD34+ cells and CMML-MSPC co-cultures as compared to that in CD34+ cells and control-MSPC co-cultures. Cytokine array showed that the conditional media of CMML-MSPCs has lower levels of multiple cytokines (IL-6, IL-8, and GRO-β) compared to that of control MSPC conditional media. Conclusion: Collectively, our study indicated that MSPCs of CMML patients had reduced proliferation, increased senescence and reduced cytokine production, while differentiation was not markedly altered. CMML-MSPCs display less hematopoietic supportive activity. Furthermore, CMML-MSPCs induced CD34+ cell differentiation favoring granulomonocytic lineage over erythroid cells. Our study suggests that the cell autonomous defects of CMML-MSPCs contribute to the pathogenesis of CMML and the interaction between hematopoietic compartment and microenvironment could serve as targets for therapeutic interventions. Disclosures No relevant conflicts of interest to declare.

scholarly journals Serum Metabolomics Profiling to Identify Biomarkers for Unstable Angina

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Wei Yao ◽  
Yuxia Gao ◽  
Zheng Wan
Keyword(s):  
Angina Pectoris ◽  
Unstable Angina ◽  
Unstable Angina Pectoris ◽  
Control Groups ◽  
Serum Samples ◽  
Mortality And Morbidity ◽  
H Nmr ◽  
And Control ◽  
Insight Into ◽  
Serum Metabolomics

Although statistical evidence is clear regarding the dangerousness of unstable angina (UA), a form of coronary heart disease (CHD) characterised by high mortality and morbidity globally, it is important to recognise that diagnostic precision for the condition is unfavourable. In the present research, to gain insight into candidate biomarkers, the author draws on1H NMR-based serum metabolic profiling to analyze the unstable angina pectoris (UAP) metabolic signatures; this constitutes an effective way to produce medical diagnosis. 101 unstable angina pectoris patients and 132 healthy controls were enrolled and 22 serum samples from each group were analyzed. Effective separation was noted regarding the UAP and control groups, and, for the former group considered in relation to their counterpart, the serum concentrations of Lac, m-I, lipid, VLDL, 3-HB, and LDL were higher whereas the concentrations of Thr, Cr, Cho, PC/GPC, Glu, Gln, Lys, HDL, Ile, Leu, and Val were lower. The conclusion drawn in view of the results is that the plasma metabolomics examined by1H NMR displayed promise for biomarker identification for UA. In addition to this, the analysis illuminated the metabolic processes of UA.

scholarly journals The Effect of Foot Reflexology on Hospital Anxiety and Depression in Female Older Adults: a Randomized Controlled Trial

2019 ◽  
Vol 12 (3) ◽  
pp. 16-21 ◽  
Author(s):  
Tahereh Bahrami, MScN ◽  
Nahid Rejeh, PhD, MScN, BScN ◽  
Majideh Heravi-Karimooi, PhD, MScN, BScN ◽  
Seyed Davood Tadrisi, MScN ◽  
Mojtaba Vaismoradi, PhD, MScN, BScN
Keyword(s):  
Older Adults ◽  
Acute Coronary Syndrome ◽  
Controlled Trial ◽  
Depression Scale ◽  
Anxiety And Depression ◽  
Hospital Anxiety ◽  
Control Groups ◽  
Coronary Syndrome ◽  
Randomized Controlled ◽  
And Control

Background: Patients with cardiovascular diseases usually suffer from hospital anxiety and depression. Aim: This study aimed to investigate the effect of foot reflexology massage on anxiety and depression in female older adults suffering from acute coronary syndrome.Participants: Ninety older women with acute coronary syndrome were randomly assigned into intervention and control groups (n=45 in each group).Research Design: A randomized controlled trial.Intervention: The intervention and control groups received foot reflexology massage and routine care, respectively.Main Outcomes Measures: The levels of anxiety and depression were evaluated using the hospital’s anxiety and depression scale (HADS) before and immediately after foot reflexology massage.Results: Foot reflexology massage reduced both anxiety (F(1.44)=19.11, p = .001) and depression (F(1.44)=16.76, p = .001) in acute coronary patients relative to control patients. The intervention had a large effect on hospital anxiety and depression.Conclusions: Foot reflexology massage is an efficient and safe intervention for alleviating psychological responses among female older adults suffering from acute coronary syndrome during hospitalization.

Mer Receptor Tyrosine Kinase Is A Potential Therapeutic Target in Acute Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1317-1317
Author(s):  
Alisa B. Lee-Sherick ◽  
Kelly Menachof ◽  
Kristen M. Eisenman ◽  
Amy McGranahan ◽  
Colleen McGary ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Tyrosine Kinase ◽  
Cell Lines ◽  
Propidium Iodide ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Control Cell ◽  
Flow Cytometric Analysis ◽  
Flow Cytometric ◽  
And Control

Abstract Abstract 1317 Acute myelogenous leukemia (AML) is difficult to treat successfully in both adult and pediatric patients using conventional chemotherapy. Mutated or aberrantly expressed proteins on the cell surface of myeloblasts provide a focus for targeted therapy which could potentially augment therapeutic outcome, decrease toxicity to normal tissues, and/or provide a therapy option for those who are not able to tolerate conventional therapy. We report here that the Mer receptor tyrosine kinase is upregulated in approximately 80% of AML cell lines and patient samples, and explore the therapeutic potential of Mer inhibition. We assessed the prevalence of Mer expression in AML. Western blot and flow cytometric analysis demonstrated expression of Mer in greater than 85% (12/14) of AML cell lines. Mer expression was also assessed at the time of diagnosis and relapse in both pediatric and adult patient samples using flow cytometry. We found that Mer was expressed on leukemic blasts in 80% of 36 pediatric and 100% of 10 adult patients at the time of diagnosis with AML. Additionally, 100% of 11 patients expressed Mer at the time of relapse. Furthermore, when analyzing patient samples at relapse compared to the same patient's diagnostic sample, there was a trend toward increased Mer expression. This is in contrast to normal bone marrow myeloid progenitors from healthy donors, which express little or no Mer. Using two independent shRNA constructs directed against Mer, we analyzed the effects of Mer inhibition in two Mer expressing AML cell lines. Mer knock-down and control cell lines were assessed for apoptosis by flow cytometry after serum starvation and staining with Yo-Pro-1 iodide and propidium iodide. Compared to AML cell lines transduced with a non-silencing control shRNA (shControl), cell lines expressing reduced levels of Mer protein demonstrated significantly more apoptosis (p<0.05). Additionally, when these cell lines were plated in equal number in methylcellulose, cell lines with reduced Mer expression demonstrated decreased colony forming potential compared to shControl cells (p<0.01). Mer knock-down and control cell lines were injected into NOD-SCID-gamma mice after sublethal irradiation and the mice were monitored for development of leukemia. Mice injected with myeloblasts expressing decreased levels of Mer demonstrated significantly prolonged symptom-free survival compared to mice transplanted with shControl AML cells (p<0.001). To further explore the effects of Mer inhibition in AML, we used a novel small molecule tyrosine kinase inhibitor (UNC1666), which has high specificity to Mer. Three Mer expressing AML cell lines were treated with UNC1666 in vitro; treatment reduced phosphorylation of Mer and the downstream signaling molecules ERK1/2 and STAT6. Additionally, treatment with UNC1666 resulted in significant induction of apoptosis (p<0.05) by flow cytometric analysis after staining with Yo-Pro-1 iodide and propidium iodide, and dose-dependent inhibition of colony formation in soft agar, when compared to vehicle treated cells In summary, the upregulation of Mer expression in patient samples and the functional effects on survival with Mer shRNA knockdown help validate Mer as a new and attractive AML therapeutic target. Furthermore, a novel Mer tyrosine kinase inhibitor decreased myeloblast cell survival, providing evidence that Mer is a druggable target in AML. Disclosures: Kireev: WO: Pyrazolopyrimidine Compounds for the Treatment of Cancer. WO Patent 2011146313, 2011, Pyrazolopyrimidine Compounds for the Treatment of Cancer. WO Patent 2011146313, 2011 Patents & Royalties. Liu:WO: Pyrazolopyrimidine Compounds for the Treatment of Cancer. WO Patent 2011146313, 2011, Pyrazolopyrimidine Compounds for the Treatment of Cancer. WO Patent 2011146313, 2011 Patents & Royalties. Wang:WO: Pyrazolopyrimidine Compounds for the Treatment of Cancer. WO Patent 2011146313, 2011, Pyrazolopyrimidine Compounds for the Treatment of Cancer. WO Patent 2011146313, 2011 Patents & Royalties. Frye:WO: Pyrazolopyrimidine Compounds for the Treatment of Cancer. WO Patent 2011146313, 2011, Pyrazolopyrimidine Compounds for the Treatment of Cancer. WO Patent 2011146313, 2011 Patents & Royalties. Graham:University of Colorado: This author has provisional patent considerations for iMer, This author has provisional patent considerations for iMer Patents & Royalties.

MUC1 Expression Is Essential For Establishment Of Acute Myeloid Leukemia In Vivo

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3787-3787
Author(s):  
Dina Stroopinsky ◽  
Hasan Rajabi ◽  
Jacalyn Rosenblatt ◽  
Heidi Mills ◽  
Turner Kufe ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Injection Site ◽  
Flow Cytometric Analysis ◽  
Survivin Expression ◽  
Leukemia Cells ◽  
Mouse Bone Marrow ◽  
Control Groups ◽  
Hematopoietic Stem ◽  
And Control

Abstract Introduction MUC1 is an oncoprotein aberrantly expressed on AML cells that interacts with multiple transcription factors, such as NFK-B and the β-catenin/TCF4 complex, that regulate cell survival and proliferation and are linked to malignant transformation. We have demonstrated that inhibition of MUC1 results in AML cell death and differentiation. We have also demonstrated that MUC1 is strongly expressed by leukemia initiating cells but not normal hematopoietic stem cells. In a xenogeneic murine model with primary AML cells, transplantation of the subset of cells expressing high levels of MUC1 results in a high level of efficiency of disease engraftment. Conversely, treatment with a MUC1 inhibitor prevents leukemia engraftment and is capable of eradicating the established disease. In the present study, we sought to better elucidate the effect of MUC1 on AML pathogenesis. Methods and Results To study the significance of MUC1-C expression on engraftment of AML in vivo, MUC1-C was silenced in MOLM-14 AML cells using lentiviral shRNA hairpin against MUC1-C. Following the infection, these cells were shown to have significantly decreased MUC1-C expression at both mRNA and protein levels. As a control, wild type MOLM-14 (wt) cells and MOLM -14 cells infected with control shRNA (control) were analyzed. MUC1-C silenced MOLM-14, wt and control cells were transplanted (10x103 cells/ mouse) into sub-lethally irradiated NSG mice in cohort of 8 mice/group using retro orbital injections. The animals were sacrificed at day 14 following injection and analyzed for leukemia establishment. The mice inoculated with wt and control cells developed large tumors at the injection site. Furthermore, flow cytometric analysis of the mice bone marrow revealed mean involvement of 54% and 48% with human CD45+ leukemia cells for the wt and control MOLM-14 AML cells respectively. Infiltration with leukemia cells was observed in all recipient mice (8/8) in the two control groups. Remarkably, 8 mice that were inoculated with MUC1-C silenced MOLM-14 cells showed no symptoms of leukemia and had no tumors at the injection site. Bone marrow analysis of these mice revealed mean AML involvement of 6% of the bone marrow cells that was significantly lower than that observed in the wt and the control groups p=.003 and p=.01 respectively. The MUC1 oncoprotein facilitates the nuclear translocation of active β-catenin necessary for downstream signaling including the regulation of cyclin D1, Myc and survivin expression. In the present model, we demonstrated that MUC1-C/β-catenin colocalized in the nucleus of MOLM-14 cells using immunoflourescence (IF) staining. A significant decrease in colocolization of MUC1-C/β-catenin complex in the nucleus of the MUC1-C silenced MOLM-14 cells as opposed to control MOLM-14 cells. Intriguingly the silencing of MUC1 resulted in the down-regulation of mRNA and protein expression of survivin, a factor shown to regulate leukemia stem cell activity. These observations suggest that the loss of AML engraftment of MUC1 silenced MOLM-14 cells in mouse bone marrow depends on survivin, a downstream target of β-catenin/TCF4 pathways. Conclusions The results demonstrate that MUC1 is essential for establishment of AML in vivo. Silencing of MUC1 markedly diminishes the engraftment capacity of AML cells. MUC1-C colocalizes with activated β-catenin in the nucleus. Silencing of MUC1 down modulates expression of survivin, which is critical for the support of leukemia initiating cells. MUC1 a novel therapeutic target for AML and a clinical trial of a MUC1 inhibitor is being planned for patients with recurrent AML. Disclosures: Kufe: Genus Oncology: Consultancy, Equity Ownership.

Abstract 205: Risk of Intracranial Hemorrhage with Protease-activated Receptor-1 Antagonists

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Meng Lee ◽  
Jeffrey L Saver ◽  
Keun-Sik Hong ◽  
Hsiu-Chuan Wu ◽  
Bruce Ovbiagele
Keyword(s):  
Acute Coronary Syndrome ◽  
Vascular Disease ◽  
Intracranial Hemorrhage ◽  
Active Treatment ◽  
Control Groups ◽  
Risk Of Death ◽  
Coronary Syndrome ◽  
History Of ◽  
Protease Activated Receptor 1 ◽  
And Control

Background: Recent clinical trial data suggest that protease-activated receptor-1 (PAR-1) antagonists may increase the risk of intracranial hemorrhage (ICH). Our objective was to investigate the qualitative and quantitative risk of ICH in patients receiving PAR-1 antagonist therapy. Methods: Pubmed and EMBASE from 1966 to May 2012 were searched to identify relevant studies. We included randomized controlled trials that included a comparison of PAR-1 antagonist with placebo, and in which the total number of patients and ICH events were reported separately for active treatment and control groups. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using random-effects models. Between-study heterogeneity was assessed using the I 2 statistic. Results: In 9 PAR-1 antagonist trials with 42, 000 patients with a history of thrombotic vascular disease or acute coronary syndrome, PAR-1 antagonist treatment was associated with increased risk of ICH (0.59% vs. 0.30%; RR 1.98, 95% CI 1.46 to 2.68, P < 0.00001) (Figure). There was no heterogeneity across trials (P=0.84, I 2 =0%), PAR-1 antagonist agent (P=0.52), treatment duration (P=0.38), or trial-qualifying event (P=0.59). Risk of death from any cause or a cardiovascular cause did not differ between active treatment and control groups. Conclusion: This meta-analysis showed that patients with a history of thrombotic vascular disease or acute coronary syndrome treated with PAR-1 antagonists are at higher risk of experiencing ICH, a dreaded form of stroke, associated with high mortality and greater loss of health over a survivor’s lifetime than ischemic stroke.

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