Methods of diagnosis and risk stratification of adverse events in post myocardial infarction patients using pro-adrenomedullin

Abstract

The invention provides methods for the diagnosis and risk stratification of adverse events in post-myocardial infarction patients by means of proADM, whereby a determination of the marker pro-adrenomedullin or partial sequence or a fragment thereof or contained in a marker combination (panel, cluster) is carried out on a post-myocardial infarction patient. The invention also provides a diagnostic device and a kit for the performance of the method of the method of the invention.

What is claimed is: 
     
         1 . A method for the in vitro diagnosis and/or risk stratification of an adverse event in post-myocardial infarction patients, comprising the step of determining the level of pro-adrenomedullin or partial peptides or fragments thereof from a post-myocardial infarction patient, wherein a significantly elevated level of pro-adrenomedullin correlates with a greater risk of an adverse event in said post-myocardial infarction patient. 
     
     
         2 . The method according to  claim 1 , wherein the fragment of pro-adrenomedullin is MR-proADM (SEQ ID No. 2). 
     
     
         3 . The method according to  claim 1 , wherein said adverse event is at least one of myocardial infarction, heart failure and death. 
     
     
         4 . The method of  claim 1  further comprising the step of determining the level of at least one marker selected from the group consisting of BNP, proBNP, NT-proBNP or a partial sequence thereof in each case, from said post-myocardial infarction patient. 
     
     
         5 . The method according to  claim 1  further comprising the step of determining at least one marker selected from the group consisting of inflammatory markers, cardiovascular markers, neurohormonal markers or ischemic markers from said post-myocardial infarction patient. 
     
     
         6 . The method according to  claim 5 , wherein said inflammatory marker is at least one marker selected form the group consisting of C-reactive protein (CRP), procalcitonin (1-116, 3-116), cytokines, interleukins, and adhesion molecules. 
     
     
         7 . The method according to  claim 6  wherein said cytokine is TNF alpha (tumor necrosis factor-alpha); said interleukin is IL-6, or said adhesion molecule is VCAM or ICAM. 
     
     
         8 . The method according to  claim 5 , wherein said cardiovascular marker is at least one marker selected from the group consisting creatine kinase, myeloperoxidase, myoglobin, natriuretic proteins, cardial troponin, CRP, and circulation-regulating (pro)hormones. 
     
     
         9 . The method according to  claim 8  wherein said natriuretic protein is selected from the group consisting of ANP, ANF, proANP, NT-proANP, BNP, proBNP, NT-proBNP and partial sequences thereof in each case. 
     
     
         10 . The method according to  claim 8  wherein said circulation-regulating (pro)hormone is selected from the group consisting of pro-gastrin-releasing peptide (proGRP), pro-endothelin-1, pro-leptin, pro-neuropeptide-Y, pro-somatostatin, pro-neuropeptide-YY, pro-opiomelanocortin and partial sequence thereof in each case. 
     
     
         11 . The method according to  claim 5 , wherein said ischemic marker is at least one marker selected from the group consisting of troponin I and T, and CK-MB. 
     
     
         12 . The method according to  claim 5 , wherein said neurohormonal marker is at least one natriuretic protein. 
     
     
         13 . The method according to  claim 12 , wherein said at least one natrriuretic protein is selected from the group consisting of ANP, ANF, proANP, NT-proANP, BNP, proBNP (NT-proBNP) and partial sequences thereof in each case. 
     
     
         14 . The method according to  claim 4  wherein parallel or simultaneous determinations of the markers are carried out. 
     
     
         15 . The method according to  claim 5  wherein parallel or simultaneous determinations of the markers are carried out. 
     
     
         16 . The method according to  claim 1 , wherein the determination is made in at least one specimen from said post-myocardial infarction patient. 
     
     
         17 . The method of  claim 16  wherein said specimen is a blood specimen. 
     
     
         18 . A kit for the in vitro diagnosis and/or risk stratification of an adverse event in post-myocardial infarction patients, containing detection reagents for the determination of the marker pro-adrenomedullin or partial peptides or fragments thereof or contained in a marker combination, whereby the marker combination can contain additional markers as well as an auxiliary agent.