Predicting risk of major adverse cardiac events

• US 8,090,562 B2
• Filed: 04/17/2009
• Issued: 01/03/2012
• Est. Priority Date: 04/18/2008
• Status: Active Grant

• Current Assignee: Critical Care Diagnostics Inc.
• Original Assignee: Critical Care Diagnostics Inc.
• Inventors: Snider, James V., Heyman, Eugene R.
• Primary Examiner(s): Smith, Carolyn L.
• Application Number:
  US12/425,956
• Publication Number:
  US 20090264779A1
• Time in Patent Office: 991 Days
• Field of Search: None
• US Class Current: 703/11
• 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 a subject'"'"'s risk of a major adverse cardiac event (MACE) within one year, the method comprising:

determining a first level of soluble Growth Stimulation-Expressed Gene 2 (ST2) in a biological sample obtained from a subject at a first time point (ST2T0), a second level of soluble ST2 in a biological sample obtained from a subject at a second time point (ST2T1), and a level of natriuretic peptide (NP) in a biological sample obtained from a subject at the second time point (NPT1);

determining a MACE risk score (MACERS) for a subject utilizing, at least in part, a ratio of ST2T1 to ST2T0, in combination with a weighted logarithm of NPT1, 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, wherein the logarithm of NPT1 includes a natural logarithm.

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

MACERS=(ST2T1/ST2T0)+α

ln(NPT1),

wherein the coefficient α

is a weighting factor for the variable it acts on.

4. The method of claim 3, wherein the coefficient α

is about 0.33.

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

6. The method of claim 1, wherein the first time point is within 1 to 7 days of an onset of symptoms in the subject.

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

8. The method of claim 1, wherein the MACE 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.

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

10. The method of claim 1, wherein the reference MACERS is a MACERS of a subject or group of subjects having a low risk of a MACE within one year.

11. The method of claim 1, wherein the biological sample obtained at the first time point or the biological sample obtained at the second time point comprises serum, blood, plasma, or urine.

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

13. The method of claim 1, wherein the subject has a body mass index (BMI) of 25 to 29, a BMI of greater than or equal to 30, or impaired renal function.

14. The method of claim 1, wherein a decision to discharge the subject or to continue treating the subject on an inpatient basis is made based in part on the MACERS.

15. The method of claim 1, wherein the biological samples are obtained from a subject that has been hospitalized after having an acute cardiac event.

16. The method of claim 1, wherein the subject has a pulmonary disorder or a liver disorder.

17. The method of claim 16, wherein the pulmonary disorder is acute infection, chronic obstructive pulmonary disease, or pulmonary embolism.

18. The method of claim 16, wherein the liver disorder is a liver disorder associated with chemotherapy, alcohol toxicity, or drug toxicity.