Signal biomarkers

1. A method for predicting, diagnosing, or monitoring in a subject (i) a cardiac disorder, optionally a cardiac disorder is selected from the group consisting of acute coronary syndromes including AMI and angina, heart failure, vulnerable plaque, and vascular disease including atherosclerosis, or (ii) an acute and/or chronic renal disease, injury, or disorder, the method comprising:

(a) measuring the level of EPOsp (erythropoietin signal peptide fragments) and/or CNPsp (C-type natriuretic peptide signal peptide fragments) immunoreactivity, or an EPOsp and/or CNPsp, or an EPOsp and/or a CNPsp fragment in a biological sample from the subject, wherein the measuring optionally is performed within the first forty-eight hours, twenty-four hours, twelve hours, six hours, four hours, two hours, one hour, or 30 minutes of onset of, or clinical presentation with, the cardiac or renal disease or disorder, optionally using an assay selected from mass spectroscopy (including SELDI, ESI, MALDI or FTIC), RIA, ELISA, fluoroimmunoassay, immunofluorometric assay, and immunoradiometric assay; and

(b) comparing the level of said EPOsp (erythropoietin signal peptide fragments) and/or CNPsp (C-type natriuretic peptide signal peptide fragments) immunoreactivity or said EPOsp and/or said CNPsp peptide or fragment with the level from a control,

wherein a measured level of EPOsp and/or CNPsp immunoreactivity, an EPOsp and/or CNPsp, or an EPOsp fragment and/or a CNPsp fragment thereof higher than the control level is indicative of said cardiac disorder.

2. A method according to claim 1 , wherein said method is used to evaluate or monitor a response to treatment of a cardiac or renal disease or disorder afflicting the subject, wherein a change in the measured level of EPOsp and/or CNPsp immunoreactivity, an EPOsp, and/or CNPsp or fragment thereof from the control level is indicative of a response to the treatment.

3. A method according to claim 1 wherein a level of EPOsp and/or CNPsp immunoreactivity, an EPOsp and/or CNPsp, or fragment thereof in the sample (i) in the range 40 to 250 pmol/L, 65 to 200 pmol/L, 70 to 150, or 70 to 130 pmol/L, and/or (ii) 1.5 to 10, 1.5 to 5, or 2 to 3 times higher than the control level, is indicative of an ACS.

4. A method according to claim 1 wherein the acute cardiac disorder is selected from the group consisting of an acute myocardial infarction (AMI) with ST-elevation on presenting ECG, unstable angina, an acute non ST-elevated myocardial infarction; cardiac ischemia, acute cardiac injury, acute cardiac damage resulting from acute drug toxicity, and an acute cardiomyopathy.

5. A method according to claim 1 wherein the biological sample is selected from the group consisting of a blood, venous blood, arterial blood, plasma, serum, saliva, interstitial fluid, urine, and heart tissue sample.

6. A method according to claim 1 for predicting, diagnosing, or monitoring an acute coronary syndrome (ACS), wherein the method further comprises measuring a level of one or more non-EPOsp and/or CNPsp markers of said ACS, and comparing the level(s) against marker levels from a control wherein a deviation in the measured level from the control level, together with a measured level of an EPOsp and/or CNPsp or fragment thereof, which is higher than the control level of an EPOsp and/or CNPsp or fragment thereof, is predictive or diagnostic of the ACS, or can be used to monitor said ACS.

7. A method according to claim 6 wherein the non-EPOsp and/or CNPsp marker(s) is(are) selected from the group consisting of troponin T, troponin I, creatine kinase-MB, myoglobin, ANP, ANP-SP, BNP, NT-BNP, BNP-SP, LDH, aspartate aminotransferase, H-FABP, ischemia modified albumin, endothelin, adrenomedullin, renin, and angiotensin II.

8. A method for measuring a biomarker in a blood or plasma sample from a patient for use in the diagnosis of an acute cardiac syndrome, the improvement comprising measuring the presence or amount of a C-type natriuretic peptide signal peptide fragment or an erythropoietin signal peptide fragment.

9. A method according to claim 8 , wherein the acute cardiac syndrome is selected from the group consisting of acute myocardial infarction, angina, and heart failure.

10. A method according to claim 8 , wherein the method is selected from the group consisting of mass spectroscopy, RIA, ELISA, fluoroimmunoassay, immunofluorometric assay, and immunoradiometric assay.

11. A method according to claim 8 , wherein the erythropoietin signal peptide fragment is MGVHECPAW (SEQ ID NO:2) or SLPLGLPVLG (SEQ ID NO:3)

12. A method according to claim 8 , wherein the C-type natriuretic peptide signal peptide fragment is MHLSQLLACALLL (SEQ ID NO:5) or TLLSLRPSEA (SEQ ID NO:6).

13. A method according to claim 8 , wherein the patient is a human.