PREDICTING RISK OF MAJOR ADVERSE CARDIAC EVENTS

• US 20090264779A1
• Filed: 04/17/2009
• Published: 10/22/2009
• Est. Priority Date: 04/18/2008
• Status: Active Grant

• Current Assignee: Critical Care Diagnostics Inc.
• Original Assignee: Critical Care Diagnostics Inc.
• Inventors: Heyman, Eugene R., Snider, James V.
• Granted Patent: US 8,090,562 B2
• Time in Patent Office: Days
• US Class Current: 600/508
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2333/58 Atrial natriuretic factor complex; Atriopeptin; Atrial natriuretic peptide [ANP]; Brain natriuretic peptide [BNP, proBNP]; Cardionatrin; Cardiodilatin
• CPC Class Codes: G01N 2333/7155 for interleukins [IL]
• CPC Class Codes: G01N 2800/32 Cardiovascular disorders
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• CPC Class Codes: G01N 33/6869 Interleukin
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment

Abstract

Measurement of circulating ST2 and natriuretic peptide (e.g., NT-proBNP) concentrations is useful for the prognostic evaluation of subjects, in particular for the prediction of adverse clinical outcomes, e.g., mortality, transplantation, and heart failure.

Claims

1. A method for evaluating the risk of a major adverse cardiac event (MACE) for a subject within one year, the method comprising:

determining a MACE risk score (MACERS) for a subject based upon, at least in part, the ratio of a second level of Growth Stimulation-Expressed Gene 2 (ST2) in the subject at a second time (ST2 T0) to a first level of ST2 in the subject at a first time (ST2 T1), in combination with a weighted logarithm of a level of a natriuretic peptide (NP) in the subject at the second time (NP T1), and

comparing the MACERS to a reference MACERS;

wherein the MACERS in comparison with the reference MACERS is indicative of the subject'"'"'s risk of a MACE within one year.

2. The method of claim 1, further comprising:

obtaining a first level of ST2 in the subject at a first time point, to determine ST2 T0;

obtaining a second level of ST2 in the subject at a second time point, to determine ST2 T1; and

obtaining a level of an natriuretic peptide (NP) in the subject at the second time point, to determine NP T1.

3. The method of claim 1, wherein the logarithm of NP T1 includes a natural logarithm.

4. The method of claim 1, wherein the MACERS is determined using the following formula:

MACERS=(ST2T1/ST2T0)+α

ln(NPT1),

wherein the coefficient alpha is a weighting factor for the variable it acts on.

5. The method of claim 4, wherein the coefficient alpha is about 0.33.

6. The method of claim 1, wherein the NP is brain-type natriuretic peptide (NT-proBNP).

7. The method of claim 1, wherein the first time point is within 1-7 days of the onset of symptoms.

8. The method of claim 1, wherein the second time point is 2-14 days after the first time point.

9. The method of claim 1, wherein the adverse event is selected from the group consisting of recurrence of an initial cardiac event;

angina;

decompensation of heart failure;

admission for cardiovascular disease (CVD);

mortality due to CVD; and

transplant.

10. The method of claim 1, wherein the subject has been diagnosed with heart failure.

11. The method of claim 1, wherein the reference MACERS represents a score corresponding to a low risk of an adverse event within one year.

12. The method of claim 1, wherein the sample comprises serum, blood, plasma, urine, or body tissue.

13. The method of claim 1, wherein the reference MACERS is about 3.2, and a score that is greater than or equal to the reference score indicates that the subject has an elevated risk of an adverse event within one year, compared to a subject with a score below the reference level.

14. The method of claim 1, wherein the subject has a BMI of 25-29, a BMI of ≧

30, or renal insufficiency.

15. The method of claim 1, wherein a decision to discharge or continue to treat on an inpatient basis is made based on the MACERS.