WO2008145689A1 - H-fabp utilisée comme prédicteur précoce de l'infarctus du myocarde - Google Patents
H-fabp utilisée comme prédicteur précoce de l'infarctus du myocarde Download PDFInfo
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- WO2008145689A1 WO2008145689A1 PCT/EP2008/056603 EP2008056603W WO2008145689A1 WO 2008145689 A1 WO2008145689 A1 WO 2008145689A1 EP 2008056603 W EP2008056603 W EP 2008056603W WO 2008145689 A1 WO2008145689 A1 WO 2008145689A1
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- fabp
- myoglobin
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- myocardial infarction
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/32—Cardiovascular disorders
- G01N2800/324—Coronary artery diseases, e.g. angina pectoris, myocardial infarction
Definitions
- H-FABP Heart-type fatty acid binding protein
- a variant as referred to in accordance with the present invention shall have an amino acid sequence which differs due to at least one amino acid substitution, deletion and/or addition wherein the amino acid sequence of the variant is still, preferably, at least 50%, 60%, 70%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% identical with the amino sequence of the specific Troponin.
- Variants may be allelic variants or any other species specific homologs, paralogs, or orthologs.
- the variants referred to herein include fragments of the specific cardiac Troponins or the aforementioned types of variants as long as these fragments have the essential immunological and biological properties as referred to above. Such fragments may be, e.g., degradation products of the Troponins. Further included are variants which differ due to posttranslational modifications such as phosphorylation or myristylation.
- the Troponin level in a subject who suffers from acute coronary syndrome and has a cardiac Troponin level which is detectable, but lower than the level that is considered as being indicative for a myocardial infarction (as defined in this application) ranges from 0.002 to 0.1 ng/ml (equal or larger than 0.002, but lower than 0.1 ng/ml).
- variants referred to above may be allelic variants or any other species specific homo logs, paralogs, or orthologs.
- variants referred to herein include fragments of the specific H-FABP and myoglobin polypeptides, respectively or the aforementioned types of variants as long as these fragments have the essential immunological and biological properties as referred to above.
- fragments may be, e.g., degradation products of the H-FABP and myoglobin polypeptides, respectively.
- variants which differ due to posttranslational modifications such as phosphorylation or myristylation.
- the value of the determined amount may be compared to values corresponding to suitable references which are stored in a database by a computer program.
- the computer program may further evaluate the result of the comparison, i.e. automatically provide the desired assessment in a suitable output format. Based on the comparison of the amount(s) determined in step a) to suitable reference amount(s), it is possible to diagnose MI in said subject. It is to be understood that an amount of H-FABP as determined in step (a) of the methods of the presents invention is compared in step (b) to a reference amount for H-FABP as specified elsewhere in this application and that an amount of myoglobin is compared to a reference amount for myoglobin.
- kit refers to a collection of the aforementioned means, preferably, provided separately or within a single container.
- the kit may in addition comprise means for determining the amount of a cardiac Troponin.
- the kit may additionally comprise a user's manual for interpreting the results of any measurement(s) with respect to diagnosing MI in a subject as defined in the present invention.
- a user's manual may include information about what determined amounts corresponds to what kind of diagnosis. This is outlined in detail elsewhere in this specification. Additionally, such user's manual may provide instructions about correctly using the components of the kit for determining the amount of the respective biomarkers.
- FIG. 2 Receiver operating characteristic (ROC) curve for myoglobin.
- ROC curve analysis was done to determine diagnostic accuracy by calculation of diagnostic sensitivity vs. (1 -specificity) for a given diagnostic parameter (myoglobin) according clinical outcome (Non-Myocardial Infarction (M ⁇ )-Converter vs. Myocardial Infarction (M ⁇ )-Converter). Included in this ROC curve are the data obtained for patients with stable coronary heart disease and ACS (see Examples). The cut-off score for the clinical outcome MI is 61 ng/ml myoglobin.
- ROC-AUC Receiver operating characteristic-area under curve; C. O. cut-off).
- a Troponin T level of larger than 0.1 ng/ml in a sample that was obtained at least 6 hours after the onset of symptoms was considered as being indicative for the recent occurence MI (Mi-converter), otherwise UAP was diagnosed (Non-MI-converter).
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Abstract
L'invention concerne un procédé qui permet de diagnostiquer l'infarctus du myocarde chez un sujet souffrant d'un syndrome coronaire aigu et possédant un niveau de troponine cardiaque détectable, mais inférieur au niveau considéré comme indicatif d'un infarctus du myocarde. L'invention se rapporte en outre à un procédé qui permet d'identifier un sujet comme étant susceptible de subir une intervention cardiaque, le sujet souffrant d'un syndrome coronaire aigu et possédant un niveau de troponine cardiaque détectable, mais inférieur au niveau considéré comme indicatif d'un infarctus du myocarde. Les procédés de l'invention reposent sur une mesure de la H-FABP et, facultativement, de la myoglobine dans un échantillon dudit sujet, et sur une comparaison entre la quantité de H-FABP et, facultativement, de la myoglobine, et des quantités de référence. L'invention se rapporte également à des trousses ou dispositifs destinés à la mise en oeuvre de l'invention.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2010509821A JP2010528306A (ja) | 2007-05-29 | 2008-05-29 | 心筋梗塞の早期予測因子としてのｈ−ｆａｂｐ |
| EP08760194A EP2167975A1 (fr) | 2007-05-29 | 2008-05-29 | H-fabp utilisée comme prédicteur précoce de l'infarctus du myocarde |
| US12/623,495 US8062857B1 (en) | 2007-05-29 | 2009-11-23 | H-FABP as early predictor of myocardial infarction |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP07109141.7 | 2007-05-29 | ||
| EP07109141A EP1998178A1 (fr) | 2007-05-29 | 2007-05-29 | H-FABP en tant que prédicateur précoce d'infarctus du myocarde |
| EP07116337.2 | 2007-09-13 | ||
| EP07116337 | 2007-09-13 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US12/623,495 Continuation US8062857B1 (en) | 2007-05-29 | 2009-11-23 | H-FABP as early predictor of myocardial infarction |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2008145689A1 true WO2008145689A1 (fr) | 2008-12-04 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2008/056603 WO2008145689A1 (fr) | 2007-05-29 | 2008-05-29 | H-fabp utilisée comme prédicteur précoce de l'infarctus du myocarde |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP2167975A1 (fr) |
| JP (1) | JP2010528306A (fr) |
| WO (1) | WO2008145689A1 (fr) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011064358A1 (fr) | 2009-11-27 | 2011-06-03 | Roche Diagnostics Gmbh | Procédé pour diagnostiquer et contrôler une ischémie cardiaque chez des patients avec une douleur aiguë da la poitrine et sans infarctus du myocarde |
| WO2012028713A1 (fr) | 2010-09-02 | 2012-03-08 | Roche Diagnostics Gmbh | Méthode de diagnostic et de surveillance de l'état pathophysiologique cardiaque chez un sujet subissant ou ayant subi une intervention coronarienne percutanée (pci) |
| EP2687853A1 (fr) * | 2012-06-22 | 2014-01-22 | Randox Laboratories Ltd. | Combinaison d'exclusion précoce de l'infarctus aigu du myocarde |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL245091B (en) * | 2016-04-13 | 2020-02-27 | Novamed Ltd | Single stage cardiac test device |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6099469A (en) * | 1998-06-02 | 2000-08-08 | Armstrong; E. Glenn | Reflex algorithm for early and cost effective diagnosis of myocardial infractions suitable for automated diagnostic platforms |
| US6443889B1 (en) * | 2000-02-10 | 2002-09-03 | Torgny Groth | Provision of decision support for acute myocardial infarction |
| US20050014198A1 (en) * | 2002-07-11 | 2005-01-20 | Leong Ng | Assays and kits for detecting and monitoring heart disease |
-
2008
- 2008-05-29 WO PCT/EP2008/056603 patent/WO2008145689A1/fr active Search and Examination
- 2008-05-29 EP EP08760194A patent/EP2167975A1/fr not_active Withdrawn
- 2008-05-29 JP JP2010509821A patent/JP2010528306A/ja active Pending
Non-Patent Citations (8)
| Title |
|---|
| ISHII JUNNICHI ET AL: "Prognostic value of serum concentration of heart-type fatty acid-binding protein relative to cardiac troponin T on admission in the early hours of acute coronary syndrome", CLINICAL CHEMISTRY, vol. 51, no. 8, August 2005 (2005-08-01), pages 1397 - 1404, XP002454289, ISSN: 0009-9147 * |
| LEFÈVRE G ET AL: "[Multicenter evaluation of h-FABP semi-quantitative assay (Cardio Detect) in central laboratory: the point in acute myocardial infarction diagnosis]", ANNALES DE BIOLOGIE CLINIQUE 2007 JUL-AUG, vol. 65, no. 4, July 2007 (2007-07-01), pages 377 - 384, XP009090494, ISSN: 0003-3898 * |
| MORROW DAVID A ET AL: "Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction: Results from a randomized trial", JAMA (JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION), vol. 286, no. 19, 21 November 2001 (2001-11-21), pages 2405 - 2412, XP002454292, ISSN: 0098-7484 * |
| SEINO YOSHIHIKO ET AL: "Use of a whole blood rapid panel test for heart-type fatty acid-binding protein in patients with acute chest pain: Comparison with rapid troponin T and myoglobin tests.", AMERICAN JOURNAL OF MEDICINE, vol. 115, no. 3, 15 August 2003 (2003-08-15), pages 185 - 190, XP002454291, ISSN: 0002-9343 * |
| SUZUKI MASARU ET AL: "Prognostic value of a qualitative test for heart-type fatty acid-binding protein in patients with acute coronary syndrome.", INTERNATIONAL HEART JOURNAL JUL 2005, vol. 46, no. 4, July 2005 (2005-07-01), pages 601 - 606, XP002454290, ISSN: 1349-2365 * |
| TANAKA K ET AL: "SERUM AND URINARY HUMAN HEART FATTY ACID-BINDING PROTEIN IN ACUTE MYOCARDIAL INFARCTION", CLINICAL BIOCHEMISTRY, PERGAMON PRESS, vol. 24, 1991, pages 195 - 201, XP009006054, ISSN: 0009-9120 * |
| WATANABE TOSHIO ET AL: "Development of a simple whole blood panel test for detection of human heart-type fatty acid-binding protein", CLINICAL BIOCHEMISTRY, PERGAMON PRESS, vol. 34, no. 4, June 2001 (2001-06-01), pages 257 - 263, XP002256862, ISSN: 0009-9120 * |
| WILL K ET AL: "ONE-STEP ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA) FOR PLASMA FATTY ACID-BINDING PROTEIN", ANNALS OF CLINICAL BIOCHEMISTRY, BRITISH MEDICAL ASSOCIATION, LONDON, GB, vol. 34, no. 3, 1997, pages 263 - 268, XP008023075, ISSN: 0004-5632 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011064358A1 (fr) | 2009-11-27 | 2011-06-03 | Roche Diagnostics Gmbh | Procédé pour diagnostiquer et contrôler une ischémie cardiaque chez des patients avec une douleur aiguë da la poitrine et sans infarctus du myocarde |
| US8663941B2 (en) | 2009-11-27 | 2014-03-04 | Roche Diagnostics Operations, Inc. | Method for diagnosing and monitoring cardiac ischemia in patients with acute chest pain and without myocardial infarction |
| WO2012028713A1 (fr) | 2010-09-02 | 2012-03-08 | Roche Diagnostics Gmbh | Méthode de diagnostic et de surveillance de l'état pathophysiologique cardiaque chez un sujet subissant ou ayant subi une intervention coronarienne percutanée (pci) |
| EP2687853A1 (fr) * | 2012-06-22 | 2014-01-22 | Randox Laboratories Ltd. | Combinaison d'exclusion précoce de l'infarctus aigu du myocarde |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2167975A1 (fr) | 2010-03-31 |
| JP2010528306A (ja) | 2010-08-19 |
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