Methods of diagnosing acute cardiac disorders using BNP-SP
The invention provides methods for predicting, diagnosing or monitoring acute cardiac disorders, cardiac transplant rejection, or distinguishing acute cardiac disorders from pulmonary disorders, by measuring BNP signal peptide levels in a sample taken from a subject shortly after onset of, or presentation with the disorder or transplant rejection.
1. A method for predicting, diagnosing or monitoring an acute cardiac disorder in a subject, the method comprising:
a. determining the level of BNP-SP (17-26) (SEQ ID NO:19) in a biological sample obtained from the subject; and
b. comparing the level of BNP-SP (17-26) (SEQ ID NO:19) in the sample with the level of BNP-SP (17-26) (SEQ ID NO:19) in a control,
wherein a level of BNP-SP (17-26) (SEQ ID NO:19) in the sample that is higher than the control level is indicative of an acute cardiac disorder.
2. A method according to claim 1 , wherein said method is used to evaluate or monitor a response to treatment of an acute cardiac disorder, wherein a change in the measured level of BNP-SP (17-26) (SEQ ID NO:19) from the control level is indicative of a response to the treatment.
3. A method according to claim 1 , wherein said method is carried out on a sample taken within two hours of onset of the acute cardiac disorder.
4. A method according to claim 1 , wherein said method is carried out on a sample taken within two hours of presentation with acute cardiac disorder.
5. A method according to claim 1 , wherein said method is carried out on a sample taken within one hour of onset of the acute cardiac disorder.
6. A method according to claim 1 , wherein said method is carried out on a sample taken within one hour of presentation with acute cardiac disorder.
7. A method according to claim 1 , wherein said method is carried out on a sample taken within thirty minutes of onset of the acute cardiac disorder.
8. A method according to claim 1 , wherein said method is carried out on a sample taken within thirty minutes of presentation with acute cardiac disorder.
9. A method according to claim 1 , wherein repeat BNP-SP (17-26) (SEQ ID NO:19) level evaluations are carried out on separate samples from the subject.
10. A method according to claim 9 , wherein two to four BNP-SP (17-26) (SEQ ID NO:19) level evaluations are carried out.
11. A method according to claim 9 , wherein one or two BNP-SP (17-26) (SEQ ID NO:19) level evaluations are carried out on a sample taken within the first hour of onset or presentation of an acute cardiac disorder, and one or two BNP-SP (17-26) (SEQ ID NO:19) level evaluations are carried out (a) on a sample taken within two to four hours of onset or presentation of an acute cardiac disorder, or (b) on a sample taken within two to four hours the taking of a sample for initial evaluation of BNP-SP (17-26) (SEQ ID NO:19) level.
12. A method according to claim 11 , wherein a repeat BNP-SP (17-26) (SEQ ID NO:19) level evaluation is made within two to three hours of onset or clinical presentation, or initial measurement.
13. A method according to claim 1 wherein a sample level of BNP-SP (17-26) (SEQ ID NO:19) in the range of any of 20to 300 pmol/L, 25 to 250 pmol/L, 20 to 180 pmol/L, 30 to 180 pmol/L, 35 to 150 pmol/L, 40 to 130 pmol/L, 40 to 120 pmol/L, 40 to 90 pmol/L, 45 to 80 pmol/L, 45 to 160 pmol/L, and 50 to 100 pmol/L, 50 to 200 pmol/L is indicative of an acute cardiac disorder.
14. A method according to claim 1 , wherein a sample level of BNP-SP (17-26) (SEQ ID NO:19) in the range of 20 to 300 pmol/L.
15. A method according to claim 1 , wherein a sample level of BNP-SP (17-26) (SEQ ID NO:19) in the range of 30 to 180 pmol/L.
16. A method according to claim 1 , wherein a sample level of BNP-SP (17-26) (SEQ ID NO:19) in the range of 40 to 120 pmol/L.
17. A method according to claim 1 , wherein a level of BNP-SP (17-26) (SEQ ID NO:19) in the sample which is four to ten times higher than the control level is indicative of acute cardiac disorder.
18. A method according to claim 17 wherein a level of BNP-SP (17-26) (SEQ ID NO:19) in the sample of from five to eight times higher than the control level is indicative of acute cardiac disorder.
19. A method according to claim 1 , wherein the acute cardiac disorder is unstable angina.
20. A method according to claim 1 , wherein the acute cardiac disorder is an acute myocardial infarction.
21. A method according to claim 20 , wherein the acute myocardial infarction is an acute myocardial infarction with ST-elevation on presenting ECG.
22. A method according to claim 20 , wherein the acute cardiac disorder is non-ST elevated myocardial infarction.
23. A method as claimed in claim 1 , wherein the acute cardiac disorder is acute cardiac ischemia.
24. A method according to claim 19 , wherein the acute cardiac disorder is an acute cardiac injury, acute cardiac damage resulting from acute drug toxicity, an acute cardiomyopathy or a cardiac transplant rejection episode.
25. A method according to claim 1 , wherein the biological sample is blood.
26. A method according to claim 1 , wherein the biological sample is plasma.
27. A method according to claim 1 , wherein the evaluation is carried out by immunoassay.
28. A method according to claim 27 , wherein the immunoassay is a competitive binding assay, a non-competitive assay, a sandwich assay, a fluoroimmunoassay, an immunofluorometric assay, an immunoradiometric assay, a luminescence assay or a chemiluniescence assay.
29. A method according to claim 27 , wherein the immunoassay is a quantitative immunoassay.
30. A method according to claim 27 , wherein the immunoassay comprises a monoclonal antibody, a polyclonal antibody, a chimeric antibody, a bispecific antibody, a humanized antibody, or a binding fragment or fragments thereof.
31. A method according to claim 30 , wherein the antibody or binding fragment is coupled to a solid phase.
32. A method according to claim 1 , wherein the BNP-SP (17-26) (SEQ ID NO:19) BNP SP fragment level is evaluated by mass spectroscopy.
33. The method according to claim 32 , wherein the mass spectroscopy is SELDI, ESI, MALDI or FTICR.
34. A method according to claim 1 , which further comprises measuring the level of one or more non-BNP-SP markers associated with said acute cardiac disorder.
35. A method as claimed in claim 34 wherein the non-BNP-SP marker is selected from the group consisting of troponin, troponin T, troponin I, creatine kinase-MB, myoglobin, BNP, NT-BNP, and H-FABP.