Methods of diagnosis and risk stratification of adverse events in post myocardial infarction patients using pro-adrenomedullin
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.
1. A method for the in vitro diagnosis or risk stratification of an adverse event in post-myocardial infarction patients, comprising
a) determining the level of MR-proADM (SEQ ID NO: 2) in at least one blood specimen from a post-myocardial infarction patient using an immunoassay and an antibody specific for MR-proADM (SEQ ID NO: 2), and
b) diagnosing or stratifying the risk of an adverse event in said post-myocardial infarction patient based on the result in a), wherein a level of MR-proADM (SEQ ID NO: 2) of greater than 0.73 nmol/L in said specimen correlates with a greater risk of death of or heart failure in said post-myocardial infarction patient.
2. The method of claim 1 , wherein a level of MR-proADM (SEQ ID NO: 2) of greater than 1.04 nmol/L in said specimen correlates with a greater risk of death of said post-myocardial infarction patient.
3. The method of claim 1 further comprising the step of determining the level of NT-proBNP in at least one blood specimen from said post-myocardial infarction patient using an immunoassay, wherein a level of NT-proBNP of greater than 914 pmol/L in said specimen correlates with a greater risk of death of or heart failure in said post-myocardial infarction patient.
4. The method according to claim 1 , wherein said adverse event is at least one of myocardial infarction, heart failure and death.
5. 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, and NT-proBNP, from said post-myocardial infarction patient, wherein a significantly elevated level of said marker, in comparison with post-myocardial infarction patients without adverse events independently correlates with a greater risk of an adverse event in said post-myocardial infarction patient.
6. The method according to claim 5 wherein parallel or simultaneous determinations of the markers are carried out.
7. The method of claim 5 wherein said marker is NT-proBNP.
8. 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 and ischemic markers from said post-myocardial infarction patient.
9. The method according to claim 8 , 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.
10. The method according to claim 9 wherein said cytokine is TNF alpha (tumor necrosis factor-alpha); said interleukin is IL-6, or said adhesion molecule is VCAM or ICAM.
11. The method according to claim 8 , 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.
12. The method according to claim 11 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.
13. The method according to claim 8 , wherein said ischemic marker is at least one marker selected from the group consisting of troponin I and T, and CK-MB.
14. The method according to claim 8 , wherein said marker is at least one natriuretic protein.
15. The method according to claim 14 , wherein said at least one natriuretic protein is selected from the group consisting of ANP, ANF, proANP, NT-proANP, BNP, proBNP and NT-proBNP.
16. The method according to claim 8 wherein parallel or simultaneous determinations of the markers are carried out.
17. The method according to claim 1 , wherein the determination is made in at least one specimen from said post-myocardial infarction patient.
18. The method of claim 17 wherein said specimen is a blood specimen.