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1
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Maguire PB, Parsons ME, Szklanna PB, Zdanyte M, Münzer P, Chatterjee M, Wynne K, Rath D, Comer SP, Hayden M, Ní Áinle F, Gawaz M. Comparative Platelet Releasate Proteomic Profiling of Acute Coronary Syndrome versus Stable Coronary Artery Disease. Front Cardiovasc Med 2020; 7:101. [PMID: 32671099 PMCID: PMC7328343 DOI: 10.3389/fcvm.2020.00101] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 05/12/2020] [Indexed: 01/23/2023] Open
Abstract
Upon activation, platelets release a host of soluble and vesicular signals, collectively termed the “platelet releasate” (PR). The contents of this PR play a significant role in haemostasis, inflammation, and pathologic sequelae. Despite this, proteomic studies investigating the PR in coronary artery disease have not been performed. Here, we undertook a comparative label-free quantitative (LFQ) proteomic profiling of the 1 U/ml thrombin-induced PR from 13 acute coronary syndrome vs. 14 stable angina pectoris patients using a tandem mass spectrometry approach. Data are available via ProteomeXchange with identifier PXD009356. 318 PR proteins were identified across both cohorts with 9 proteins found to be differentially released, including tetranectin (CLEC3B), protein disulfide-isomerase-A3 (PDIA3), coagulation factor V (F5), and fibronectin (FN1). Strikingly, these 9 differential proteins were all associated with the gene ontology cellular component term “extracellular vesicle” and reduced levels of EVs were detected in the corresponding plasma of ST-segment elevation myocardial infarction (STEMI) patients. Network analysis revealed 3 proteins either reduced (F5; FN1) or absent (CLEC3B) in the PR of STEMI patients that are strongly connected to both the clotting cascade and major druggable targets on platelets. This moderated proteomic signature may prove useful for non-invasive risk assessment of the progression of coronary artery disease. These data further contribute to the growing evidence-base of using the platelet releasate as a predictor of pathological state and disease severity.
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Affiliation(s)
- Patricia B Maguire
- Conway SPHERE Research Group, Conway Institute, University College Dublin, Dublin, Ireland.,School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.,UCD Institute for Discovery, University College Dublin, Dublin, Ireland.,Irish Centre for Vascular Biology, Dublin, Ireland
| | - Martin E Parsons
- Conway SPHERE Research Group, Conway Institute, University College Dublin, Dublin, Ireland.,School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
| | - Paulina B Szklanna
- Conway SPHERE Research Group, Conway Institute, University College Dublin, Dublin, Ireland.,School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.,Irish Centre for Vascular Biology, Dublin, Ireland
| | - Monika Zdanyte
- Universitätsklinikum Tübingen, Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Tübingen, Germany
| | - Patrick Münzer
- Universitätsklinikum Tübingen, Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Tübingen, Germany
| | - Madhumita Chatterjee
- Universitätsklinikum Tübingen, Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Tübingen, Germany
| | - Kieran Wynne
- Proteomics Core, Conway Institute, University College Dublin, Dublin, Ireland
| | - Dominik Rath
- Universitätsklinikum Tübingen, Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Tübingen, Germany
| | - Shane P Comer
- Conway SPHERE Research Group, Conway Institute, University College Dublin, Dublin, Ireland.,School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
| | - Melanie Hayden
- Conway SPHERE Research Group, Conway Institute, University College Dublin, Dublin, Ireland.,School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
| | - Fionnuala Ní Áinle
- Conway SPHERE Research Group, Conway Institute, University College Dublin, Dublin, Ireland.,Irish Centre for Vascular Biology, Dublin, Ireland.,School of Medicine, University College Dublin, Dublin, Ireland.,Department of Haematology, Rotunda Hospital, Dublin, Ireland.,Department of Haematology, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Meinrad Gawaz
- Universitätsklinikum Tübingen, Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Tübingen, Germany
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2
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Spiezia L, Al Mamary A, Campello E, Piazza D, Maggiolo S, Dalla Valle F, Napodano M, Simioni P. On-treatment platelet reactivity in peripheral and coronary blood in patients undergoing primary PCI for ST-segment elevation myocardial infarction (STEMI). Scandinavian Journal of Clinical and Laboratory Investigation 2018; 78:281-286. [PMID: 29575927 DOI: 10.1080/00365513.2018.1455220] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Dual antiplatelet therapy is recommended in patients undergoing primary percutaneous coronary intervention (p-PCI) for ST-segment elevation myocardial infarction (STEMI). Pre-analytical variables may influence platelet function analysis results. Our aim was to evaluate the on-treatment platelet reactivity in peripheral artery vs coronary blood in patients with STEMI. We enrolled one hundred and nine patients who consecutively underwent p-PCI at Cardiology Unit of Padua University Hospital between June 2014 and June 2015. Before the procedure, all patients received intravenous aspirin 250 mg and either of the thienopyridines; clopidogrel 600 mg, prasugrel 60 mg or ticagrelor 180 mg. ASPI-test and ADP-test using multiple electrode aggregometry (MEA) were performed in samples collected from both a peripheral artery and the culprit coronary artery. 'Low responders' were patients with an ASPI-test or ADP-test value greater than or equal to a pre-established normal range. No significant differences were observed in ASPI-test values between peripheral (19 (median) [3-49 (10-90 percentiles)] U) vs coronary (12 [1-40] U, p = .06) blood and in ADP-test (40 [14-82] U vs 33 [7-79] U, p =.68) blood. In peripheral blood, fifteen (14%) patients were 'low aspirin' and forty-one (38%) 'low thienopyridines' responders. The prevalence of 'low clopidogrel' responders was higher (45%) than prasugrel (36%) and ticagrelor (33%). Similar results were observed in coronary blood. In patients undergoing p-PCI for STEMI, MEA platelet function observed in coronary arteries was consistent with peripheral artery blood's independently of the antiplatelet drug used. The clinical significance of peripheral and coronary on-aspirin/thienopyridines platelet reactivity needs further clarification.
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Affiliation(s)
- Luca Spiezia
- a Department of Medicine, Thrombotic and Haemorrhagic Diseases Unit , University of Padua , Padua , Italy
| | - Ahmed Al Mamary
- b Department of Cardiac, Thoracic and Vascular Sciences, Cardiology Unit , University of Padua , Padua , Italy
| | - Elena Campello
- a Department of Medicine, Thrombotic and Haemorrhagic Diseases Unit , University of Padua , Padua , Italy
| | - Daniele Piazza
- a Department of Medicine, Thrombotic and Haemorrhagic Diseases Unit , University of Padua , Padua , Italy
| | - Sara Maggiolo
- a Department of Medicine, Thrombotic and Haemorrhagic Diseases Unit , University of Padua , Padua , Italy
| | - Fabio Dalla Valle
- a Department of Medicine, Thrombotic and Haemorrhagic Diseases Unit , University of Padua , Padua , Italy
| | - Massimo Napodano
- b Department of Cardiac, Thoracic and Vascular Sciences, Cardiology Unit , University of Padua , Padua , Italy
| | - Paolo Simioni
- a Department of Medicine, Thrombotic and Haemorrhagic Diseases Unit , University of Padua , Padua , Italy
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3
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Vecchio S, Varani E, Chechi T, Balducelli M, Vecchi G, Aquilina M, Ricci Lucchi G, Dal Monte A, Margheri M. Coronary thrombus in patients undergoing primary PCI for STEMI: Prognostic significance and management. World J Cardiol 2014; 6:381-392. [PMID: 24976910 PMCID: PMC4072828 DOI: 10.4330/wjc.v6.i6.381] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2013] [Revised: 03/26/2014] [Accepted: 04/11/2014] [Indexed: 02/06/2023] Open
Abstract
Acute ST-elevation myocardial infarction (STEMI) usually results from coronary atherosclerotic plaque disruption with superimposed thrombus formation. Detection of coronary thrombi is a poor prognostic indicator, which is mostly proportional to their size and composition. Particularly, intracoronary thrombi impair both epicardial blood flow and myocardial perfusion, by occluding major coronary arteries and causing distal embolization, respectively. Thus, although primary percutaneous coronary intervention is the preferred treatement strategy in STEMI setting, the associated use of adjunctive antithrombotic drugs and/or percutaneous thrombectomy is crucial to optimize therapy of STEMI patients, by improving either angiographical and clinical outcomes. This review article will focus on the prognostic significance of intracoronary thrombi and on current antithrombotic pharmacological and interventional strategies used in the setting of STEMI to manage thrombotic lesions.
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Manjarrez-Gutiérrez G, Ramírez-Campillo R, Borrayo-Sánchez G, Hernández-Rodríguez J. Disturbance of serotonergic neurotransmission in patients with postmyocardial infarction and depression. Metab Brain Dis 2013; 28:15-20. [PMID: 23129293 DOI: 10.1007/s11011-012-9355-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2012] [Accepted: 10/28/2012] [Indexed: 10/27/2022]
Abstract
The objective of this study was to assess the hypothesis that patients who develop depression after myocardial infarction (MI) have a lower level of brain serotonergic neurotransmission through measurement of plasma free fraction of L-tryptophan and intensity-dependence auditory-evoked potentials (IDAEPs). A cross-sectional study was carried out in 74 adults after MI. Thirty-four patients suffered from depression and 40 patients did not demonstrate depressive symptoms. We measured the free fraction, bound and total plasma L-tryptophan, and neutral amino acids as well as recording IDAEPs. Patients who developed depression after MI showed a significantly lower level in the free fraction of L-tryptophan and in the ratios of free fraction of L-tryptophan/total L-tryptophan and free fraction of L-tryptophan/neutral amino acids. It is noteworthy that the slope of the amplitude/stimulus intensity functions (ASF slope) of the N1/P2 component was significantly higher post-MI in depressed patients. Higher ASF slope of the N1/P2 component associated with a low free fraction of L-tryptophan in plasma reflect a low brain serotonergic neurotransmission. These findings suggest an important deterioration of brain serotonergic activity as a pathophysiological mechanism in post-MI patients for the development of clinical depression. Therefore, we propose these biochemical and electrophysiological procedures as noninvasive clinical indicators of brain serotonergic activity in these patients.
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Affiliation(s)
- Gabriel Manjarrez-Gutiérrez
- Laboratorio de Patología Molecular, Unidad de Investigación Biomolecular, Hospital de Cardiología, Centro Médico Nacional Siglo XXI (CMN-SXXI), Instituto Mexicano del Seguro Social (IMSS), Av. Cuauhtémoc 330, México, DF, México.
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Yunoki K, Naruko T, Sugioka K, Inaba M, Itoh A, Haze K, Yoshiyama M, Ueda M. Thrombus Aspiration Therapy and Coronary Thrombus Components in Patients with Acute ST-Elevation Myocardial Infarction. J Atheroscler Thromb 2013; 20:524-37. [DOI: 10.5551/jat.17608] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
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Parguiña AF, Grigorian-Shamagian L, Agra RM, López-Otero D, Rosa I, Alonso J, Teijeira-Fernández E, González-Juanatey JR, García Á. Variations in Platelet Proteins Associated With ST-Elevation Myocardial Infarction. Arterioscler Thromb Vasc Biol 2011; 31:2957-64. [DOI: 10.1161/atvbaha.111.235713] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Objective—
Our aim in this study was to provide novel information on the molecular mechanisms playing a major role in the unwanted platelet activation associated with ST-elevation myocardial infarction (STEMI).
Methods and Results—
We compared the platelet proteome of 11 STEMI patients to a matched control group of 15 stable chronic ischemic cardiopathy patients. In addition, we did a prospective study to follow the STEMI patients over time. Proteins were separated by high-resolution 2D gel electrophoresis, identified by mass spectrometry, and validated by Western blotting. Platelets from STEMI patients on admission displayed 56 protein spot differences (corresponding to 42 unique genes) compared with the control group. The number of differences decreased with time during the patients' follow-up. Interestingly, the adapter protein CrkL and the active form of Src (phosphorylated in Tyr418) were found to be upregulated in platelets from STEMI patients. Major signaling pathways related to the proteins identified include integrin, integrin-linked kinase, and glycoprotein VI (GPVI) signaling. Interestingly, a study on an independent cohort of patients showed a higher degree of activation of GPVI signaling in STEMI patients.
Conclusion—
CrkL, the active form of Src, and GPVI signaling are upregulated in platelets from STEMI patients.
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Affiliation(s)
- Andrés F. Parguiña
- From the Department of Pharmacology, Faculty of Pharmacy (A.F.P., I.R., A.G.) and Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) (A.F.P., I.R., A.G.), Universidade de Santiago de Compostela, Santiago de Compostela, Spain; Cardiology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain (L.G.-S.); Cardiology Department and Coronary Unit (L.G.-S., R.M.A., D.L.-O., E.T.-F., J.R.G.-J.) and Proteomic Unit, Instituto de Investigaciones Sanitarias (J.A.), Hospital
| | - Lilian Grigorian-Shamagian
- From the Department of Pharmacology, Faculty of Pharmacy (A.F.P., I.R., A.G.) and Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) (A.F.P., I.R., A.G.), Universidade de Santiago de Compostela, Santiago de Compostela, Spain; Cardiology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain (L.G.-S.); Cardiology Department and Coronary Unit (L.G.-S., R.M.A., D.L.-O., E.T.-F., J.R.G.-J.) and Proteomic Unit, Instituto de Investigaciones Sanitarias (J.A.), Hospital
| | - Rosa M. Agra
- From the Department of Pharmacology, Faculty of Pharmacy (A.F.P., I.R., A.G.) and Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) (A.F.P., I.R., A.G.), Universidade de Santiago de Compostela, Santiago de Compostela, Spain; Cardiology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain (L.G.-S.); Cardiology Department and Coronary Unit (L.G.-S., R.M.A., D.L.-O., E.T.-F., J.R.G.-J.) and Proteomic Unit, Instituto de Investigaciones Sanitarias (J.A.), Hospital
| | - Diego López-Otero
- From the Department of Pharmacology, Faculty of Pharmacy (A.F.P., I.R., A.G.) and Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) (A.F.P., I.R., A.G.), Universidade de Santiago de Compostela, Santiago de Compostela, Spain; Cardiology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain (L.G.-S.); Cardiology Department and Coronary Unit (L.G.-S., R.M.A., D.L.-O., E.T.-F., J.R.G.-J.) and Proteomic Unit, Instituto de Investigaciones Sanitarias (J.A.), Hospital
| | - Isaac Rosa
- From the Department of Pharmacology, Faculty of Pharmacy (A.F.P., I.R., A.G.) and Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) (A.F.P., I.R., A.G.), Universidade de Santiago de Compostela, Santiago de Compostela, Spain; Cardiology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain (L.G.-S.); Cardiology Department and Coronary Unit (L.G.-S., R.M.A., D.L.-O., E.T.-F., J.R.G.-J.) and Proteomic Unit, Instituto de Investigaciones Sanitarias (J.A.), Hospital
| | - Jana Alonso
- From the Department of Pharmacology, Faculty of Pharmacy (A.F.P., I.R., A.G.) and Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) (A.F.P., I.R., A.G.), Universidade de Santiago de Compostela, Santiago de Compostela, Spain; Cardiology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain (L.G.-S.); Cardiology Department and Coronary Unit (L.G.-S., R.M.A., D.L.-O., E.T.-F., J.R.G.-J.) and Proteomic Unit, Instituto de Investigaciones Sanitarias (J.A.), Hospital
| | - Elvis Teijeira-Fernández
- From the Department of Pharmacology, Faculty of Pharmacy (A.F.P., I.R., A.G.) and Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) (A.F.P., I.R., A.G.), Universidade de Santiago de Compostela, Santiago de Compostela, Spain; Cardiology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain (L.G.-S.); Cardiology Department and Coronary Unit (L.G.-S., R.M.A., D.L.-O., E.T.-F., J.R.G.-J.) and Proteomic Unit, Instituto de Investigaciones Sanitarias (J.A.), Hospital
| | - José Ramón González-Juanatey
- From the Department of Pharmacology, Faculty of Pharmacy (A.F.P., I.R., A.G.) and Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) (A.F.P., I.R., A.G.), Universidade de Santiago de Compostela, Santiago de Compostela, Spain; Cardiology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain (L.G.-S.); Cardiology Department and Coronary Unit (L.G.-S., R.M.A., D.L.-O., E.T.-F., J.R.G.-J.) and Proteomic Unit, Instituto de Investigaciones Sanitarias (J.A.), Hospital
| | - Ángel García
- From the Department of Pharmacology, Faculty of Pharmacy (A.F.P., I.R., A.G.) and Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) (A.F.P., I.R., A.G.), Universidade de Santiago de Compostela, Santiago de Compostela, Spain; Cardiology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain (L.G.-S.); Cardiology Department and Coronary Unit (L.G.-S., R.M.A., D.L.-O., E.T.-F., J.R.G.-J.) and Proteomic Unit, Instituto de Investigaciones Sanitarias (J.A.), Hospital
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7
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Fernández Parguiña A, Grigorian-Shamajian L, Agra RM, Teijeira-Fernández E, Rosa I, Alonso J, Viñuela-Roldán JE, Seoane A, González-Juanatey JR, García Á. Proteins involved in platelet signaling are differentially regulated in acute coronary syndrome: a proteomic study. PLoS One 2010; 5:e13404. [PMID: 20976234 PMCID: PMC2954807 DOI: 10.1371/journal.pone.0013404] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2010] [Accepted: 09/22/2010] [Indexed: 01/08/2023] Open
Abstract
Background Platelets play a fundamental role in pathological events underlying acute coronary syndrome (ACS). Because platelets do not have a nucleus, proteomics constitutes an optimal approach to follow platelet molecular events associated with the onset of the acute episode. Methodology/Principal Findings We performed the first high-resolution two-dimensional gel electrophoresis-based proteome analysis of circulating platelets from patients with non-ST segment elevation ACS (NSTE-ACS). Proteins were identified by mass spectrometry and validations were by western blotting. Forty protein features (corresponding to 22 unique genes) were found to be differentially regulated between NSTE-ACS patients and matched controls with chronic ischemic cardiopathy. The number of differences decreased at day 5 (28) and 6 months after the acute event (5). Interestingly, a systems biology approach demonstrated that 16 of the 22 differentially regulated proteins identified are interconnected as part of a common network related to cell assembly and organization and cell morphology, processes very related to platelet activation. Indeed, 14 of those proteins are either signaling or cytoskeletal, and nine of them are known to participate in platelet activation by αIIbβ3 and/or GPVI receptors. Several of the proteins identified participate in platelet activation through post-translational modifications, as shown here for ILK, Src and Talin. Interestingly, the platelet-secreted glycoprotein SPARC was down-regulated in NSTE-ACS patients compared to stable controls, which is consistent with a secretion process from activated platelets. Conclusions/Significance The present study provides novel information on platelet proteome changes associated with platelet activation in NSTE-ACS, highlighting the presence of proteins involved in platelet signaling. This investigation paves the way for future studies in the search for novel platelet-related biomarkers and drug targets in ACS.
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Affiliation(s)
- Andrés Fernández Parguiña
- Departamento de Farmacoloxía, Facultade de Farmacia, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
| | - Lilian Grigorian-Shamajian
- Servicio de Cardiología y Unidad Coronaria, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
- Servicio de Cardiología, Complejo Hospitalario Universitario de Vigo, Vigo, Spain
| | - Rosa M. Agra
- Servicio de Cardiología y Unidad Coronaria, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
| | - Elvis Teijeira-Fernández
- Servicio de Cardiología y Unidad Coronaria, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
| | - Isaac Rosa
- Departamento de Farmacoloxía, Facultade de Farmacia, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
| | - Jana Alonso
- Laboratorio de Proteómica, Instituto de Investigaciones Sanitarias, Hospital Clínico Universitario, Santiago de Compostela, Spain
| | - Juan E. Viñuela-Roldán
- Laboratorio de Inmunología, Hospital Clínico Universitario, Santiago de Compostela, Spain
| | - Ana Seoane
- Servicio de Cardiología y Unidad Coronaria, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
| | - José Ramón González-Juanatey
- Servicio de Cardiología y Unidad Coronaria, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
| | - Ángel García
- Departamento de Farmacoloxía, Facultade de Farmacia, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
- * E-mail:
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Schwarz AK, Zeymer U. Enoxaparin in patients with primary percutaneous coronary intervention for acute ST segment elevation myocardial infarction. Future Cardiol 2009; 5:43-9. [PMID: 19371202 DOI: 10.2217/14796678.5.1.43] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
The inhibition of thrombin plays a key role as adjunct therapy in the management of patients with primary percutaneous coronary intervention for ST elevation myocardial infarction. Enoxaparin provides a more predictable and constant level of anticoagulation compared with the current standard unfractionated heparin. The available data from smaller studies and prospective registries suggest that enoxaparin is associated with a reduction in the rate of death and nonfatal reinfarction after primary percutaneous coronary intervention without an increase in bleeding complications. Thus, a large randomized trial is warranted to further evaluate the role of enoxaparin in these patients.
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9
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Mehilli J, Ndrepepa G, Kastrati A, Neumann FJ, ten Berg J, Bruskina O, Dotzer F, Seyfarth M, Pache J, Kufner S, Dirschinger J, Berger PB, Schömig A. Sex and effect of abciximab in patients with acute coronary syndromes treated with percutaneous coronary interventions: results from Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 2 trial. Am Heart J 2007; 154:158.e1-7. [PMID: 17584569 DOI: 10.1016/j.ahj.2007.03.050] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2007] [Accepted: 03/21/2007] [Indexed: 10/23/2022]
Abstract
BACKGROUND It is not known whether there exists a sex-dependent difference in the clinical benefit of abciximab in patients with acute coronary syndromes (ACS) undergoing a percutaneous coronary intervention (PCI). METHODS We performed this retrospective analysis of 2022 patients (498 women) with ACS enrolled in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 2 trial and randomized to receive abciximab or placebo during a PCI procedure. The incidence of major adverse cardiac events (MACE) during the 30 days after PCI was the primary end point of the study. RESULTS Among men, the 30-day incidence of MACE was 8.6% in the abciximab group compared with 12.6% in the placebo group, relative risk (RR) 0.69 (95% confidence interval [CI] 0.50-0.94), P = .01. The 30-day incidence of MACE in women was 9.7% in the abciximab group compared with 9.9% in the placebo group, RR 0.98 (95% CI, 0.56-1.72), P = .97. After adjustment for baseline clinical and angiographic characteristics, there was no significant interaction between sex and abciximab (P = .71); adjusted RR was 0.70 (95% CI, 0.34-1.34) in women and 0.60 (95% CI, 0.40-0.90) in men. The incidence of major bleeding was significantly greater in women (3.6%) than in men (0.7%), RR 5.5 (95% CI, 2.54-11.9), P < .001, without any dependence on the form of therapy received. CONCLUSIONS In patients with non-ST elevation ACS undergoing a PCI, the benefit with abciximab is greater in men than in women. This is apparently the result of sex-based differences in risk profile.
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Affiliation(s)
- Julinda Mehilli
- Deutsches Herzzentrum Technische Universität, Munich, Germany.
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10
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de Chantal M, Diodati JG, Nasmith JB, Amyot R, LeBlanc AR, Schampaert E, Pharand C. Progressive epicardial coronary blood flow reduction fails to produce ST-segment depression at normal heart rates. Am J Physiol Heart Circ Physiol 2006; 291:H2889-96. [PMID: 16905602 DOI: 10.1152/ajpheart.00400.2006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
ST-segment depression is commonly seen in patients with acute coronary syndromes. Most authors have attributed it to transient reductions in coronary blood flow due to nonocclusive thrombus formation on a disrupted atherosclerotic plaque and dynamic focal vasospasm at the site of coronary artery stenosis. However, ST-segment depression was never reproduced in classic animal models of coronary stenosis without the presence of tachycardia. We hypothesized that ST-segment depression occurring during acute coronary syndromes is not entirely explained by changes in epicardial coronary artery resistance and thus evaluated the effect of a slow, progressive epicardial coronary artery occlusion on the ECG and regional myocardial blood flow in anesthetized pigs. Slow, progressive occlusion over 72 min (SD 27) of the left anterior descending coronary artery in 20 anesthetized pigs led to a 90% decrease in coronary blood flow and the development of ST-segment elevation associated with homogeneous and transmural myocardial blood flow reductions, confirmed by microspheres and myocardial contrast echocardiography. ST-segment depression was not observed in any ECG lead before the development of ST-segment elevation. At normal heart rates, progressive epicardial stenosis of a coronary artery results in myocardial ischemia associated with homogeneous, transmural reduction in regional myocardial blood flow and ST-segment elevation, without preceding ST-segment depression. Thus, in coronary syndromes with ST-segment depression and predominant subendocardial ischemia, factors other than mere increases in epicardial coronary resistance must be invoked to explain the heterogeneous parietal distribution of flow and associated ECG changes.
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Affiliation(s)
- Marilyn de Chantal
- Research Center, Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, Canada H4J 1C5
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Leal A, Paiva C, Höfer S, Amado J, Gomes L, Oldridge N. Evaluative and Discriminative Properties of the Portuguese MacNew Heart Disease Health-related Quality of Life Questionnaire. Qual Life Res 2005; 14:2335-41. [PMID: 16328913 DOI: 10.1007/s11136-005-7213-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/10/2005] [Indexed: 01/22/2023]
Abstract
The aim of this study was to validate the Portuguese version of the self-administered MacNew Heart Disease Health-related Quality of Life (MacNew) questionnaire in patients after diagnosis of acute coronary syndrome. The MacNew, with a Global score and physical, emotional and social subscales, the Short Form SF-36 (SF-36) and the Hospital Anxiety and Depression Scale (HADS) were completed at baseline by 150 patients and again by 48 clinically stable patients 2-3 weeks later. A cohort of 50 different patients completed the same questionnaires before and after a cardiac rehabilitation program in order to examine responsiveness. Acceptance of the MacNew by the patients was good and the three factor model was substantiated and explained 52.2% of the variance. Internal consistency, intra-class-correlation, and test-retest reliability each exceeded 0.72. The predicted construct validity hypotheses were partially confirmed. The discriminative validity of the MacNew was confirmed with significantly higher MacNew scores for patients with normal left ventricular function, with improved health status, and who were not anxious or depressed. Even though MacNew scores improved significantly following cardiac rehabilitation, the evaluative validity of the MacNew was less robust with small responsiveness statistics. The Portuguese version of the MacNew HRQL questionnaire appears to be a reliable, valid, and moderately responsive instrument to evaluate health-related quality of life after diagnosis of acute coronary syndrome.
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Affiliation(s)
- A Leal
- Cardiac Rehabilitation Unit, Hospital Sto António Porto, Largo Prof Abel Salazar 400, Portugal.
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