Predicting risk of major adverse cardiac events

• US 9,886,553 B2
• Filed: 03/06/2013
• Issued: 02/06/2018
• Est. Priority Date: 04/18/2008
• Status: Expired due to Fees

• Current Assignee: Critical Care Diagnostics Inc.
• Original Assignee: Critical Care Diagnostics Inc.
• Inventors: Snider, James V., Heyman, Eugene R.
• Primary Examiner(s): Zeman, Mary K
• Application Number:
  US13/787,137
• Publication Number:
  US 20130244236A1
• Time in Patent Office: 1,798 Days
• Field of Search: 702 19, 702 20
• 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 and hospitalizing the subject, the method comprising:

(a) determining a first level of soluble ST2 in a biological sample comprising serum, blood, or plasma that is obtained from a subject at a first time point (ST2 T0) using an immunoassay comprising a monoclonal antibody that binds specifically to ST2;

(b) determining a second level of soluble ST2 in a biological sample comprising serum, blood, or plasma that is obtained from the subject at a second time point (ST2 T1) using the immunoassay comprising the monoclonal antibody that specifically binds to ST2;

(c) determining a level of a natriuretic peptide (NP) in a biological sample comprising serum, blood, or plasma that is obtained from the subject at the second time point (NP T1) using an immunoassay comprising a monoclonal antibody that specifically binds to the NP;

(d) determining a MACE risk score (MACERS) for a subject utilizing, at least in part, the ratio of ST2 T1 to ST2 T0, in combination with a weighted logarithm of NP T1;

(e) identifying a subject having an elevated MACERS as compared to a reference MACERS as having an increased risk of a MACE within one year; and

(f) hospitalizing the subject identified as having an increased risk of a MACE within one year.

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

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

MACERS=(ST2 T1/ST2 T0)+α

ln(NP T1),

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 N-terminal pro-brain natriuretic peptide (NT-proBNP).

6. The method of claim 1, wherein the first time point is within 1 to 7 days of the 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 reference MACERS is about 3.2.

12. The method of claim 1, wherein the subject has a body mass index (BMI) of 25-29, a BMI of ≧

30, or impaired renal function.

13. The method of claim 1, wherein the biological sample obtained at the first time point and the biological sample obtained at the second time point are obtained from a subject that has been hospitalized after having an acute cardiac event.

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

15. The method of claim 14, wherein the pulmonary disorder is acute infection, chronic obstructive pulmonary disorder, or pulmonary embolism.

16. The method of claim 14, wherein the liver disorder is a liver disorder associated with chemotherapy, alcohol toxicity, or drug toxicity.

17. The method of claim 1, wherein the subject is undiagnosed.

18. The method of claim 1, wherein the subject exhibits one or more non-specific symptoms.

19. The method of claim 1, wherein the immunoassay comprising the monoclonal antibody that binds specifically to ST2 is an enzyme-linked immunosorbent assay.

20. The method of claim 1, wherein the immunoassay comprising the monoclonal antibody that binds specifically to the NP is an enzyme-linked immunosorbent assay.