USE OF MULTIPLE RISK PREDICTORS FOR DIAGNOSIS OF CARDIOVASCULAR DISEASE

• US 20140113833A1
• Filed: 10/18/2013
• Published: 04/24/2014
• Est. Priority Date: 10/18/2012
• Status: Abandoned Application

• Current Assignee: Cleveland Clinic Foundation
• Original Assignee: Cleveland Clinic Foundation
• Inventors: Hazen, Stanley L.
• Application Number:
  US14/057,106
• Publication Number:
  US 20140113833A1
• Time in Patent Office: Days
• US Class Current: 506/9
• 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 33/6893 related to diseases not provided for elsewhere

Abstract

Methods and kits for characterizing the risk of developing cardiovascular disease are described. The methods include determining the levels of a plurality of risk predictors selected from the group consisting of B-type natriuretic peptide (BNP), myeloperoxidase (MPO), and high-sensitivity C-reactive protein (hsCRP) predictors in a biological sample from a subject. The levels of the plurality of risk predictors are then compared to corresponding control values to obtain a risk predictor differential for each risk predictor. The plurality of risk predictor differentials are then added to provide a cardiac biomarker score, and the cardiac biomarker score is compared to a reference biomarker score. A positive difference between the cardiac biomarker score and the reference biomarker score indicates the subject has an increased risk of developing cardiovascular disease compared to the risk of a reference population. The methods can be used for risk stratification.

Claims

1. A method of characterizing the risk for developing cardiovascular disease comprising:

determining the levels of a plurality of risk predictors in a biological sample obtained from a subject using an analytic device, wherein the risk predictors are selected from the group consisting of B-type natriuretic peptide (BNP), myeloperoxidase (MPO), and high-sensitivity C-reactive protein (hsCRP);

comparing the levels of the plurality of risk predictors to corresponding control values to obtain a risk predictor differential for each risk predictor;

adding the plurality of risk predictor differentials to provide a cardiac biomarker score; and

comparing the cardiac biomarker score to a reference biomarker score, wherein a positive difference between the cardiac biomarker score and the reference biomarker score indicates the subject has an increased risk of developing cardiovascular disease compared to the risk of a reference population.

2. The method of claim 1, wherein the amount of the positive difference between the cardiac biomarker score and the reference biomarker score correlates with the level of increased risk of developing cardiovascular disease.

3. The method of claim 1, wherein the method of characterizing the risk for developing cardiovascular disease comprises risk stratification, and the risk stratification is obtained by identifying where the subject'"'"'s cardiac biomarker score falls within a risk profile range.

4. The method of claim 1, wherein each risk predictor that exceeds the control value is designated a positive risk predictor having a risk predictor differential of 1 and all other risk predictors are designated as null risk predictors having a risk predictor differential of 0.

5. The method of claim 1, wherein the risk predictors comprise BNP and MPO.

6. The method of claim 1, wherein the risk predictors comprise BNP and hsCRP.

7. The method of claim 1, wherein the risk predictors comprise MPO and hsCRP.

8. The method of claim 1, wherein the risk predictors comprise BNP, MPO, and hsCRP.

9. The method of claim 3, wherein the subject is diabetic and a diabetic risk profile is used.

10. The method of claim 3, wherein the subject is pre-diabetic and a pre-diabetic risk profile is used.

11. The method of claim 1, wherein the step of determining the level of BNP further comprises determining the level of NT-pro-BNP.

12. The method of claim 1, wherein the biological sample is selected from the group consisting of blood, serum, plasma, and urine.

13. The method of claim 1, wherein the cardiovascular disease comprises a major adverse cardiac event.

14. The method of claim 1, wherein the analytic device is an ultraviolet spectrometer or mass spectrometer.

15. The method of claim 1, wherein the biological sample is stored before determining the levels of the plurality of risk predictors.

16. The method of claim 1, wherein one of the risk profile ranges is a high risk profile, and the method further comprises providing cardiovascular therapeutic invention to a subject identified as having a high risk profile.

17. The method of claim 16, wherein the cardiovascular therapeutic intervention is administration of a therapeutic agent.

18. The method of claim 16, wherein the cardiovascular therapeutic intervention is a beneficial cardiovascular life style change.

19. The method of method of claim 1, wherein the method further comprises one or more additional steps selected from

a) determining the subject'"'"'s blood pressure;

b) determining the levels of low density lipoprotein, cholesterol, apolipoprotein A1, apolipoprotein B100, or creatinine in a biological sample from the subject;

c) assessing the subject'"'"'s response to a stress test; and

d) determining the subject'"'"'s atherosclerotic plaque burden;

wherein the results of the additional steps are factored into calculation of the cardiac biomarker score.

20. A kit comprising:

a plurality of reagents selected from the group consisting of;

a reagent capable of detecting B-type natriuretic peptide (BNP),

a reagent capable of detecting myeloperoxidase (MPO), and

a reagent capable of detecting high-sensitivity C-reactive protein (hsCRP);

a plurality of reference values or control samples suitable for use with the selected reagents, and a package holding the reagents.

21. The kit of claim 20, wherein the kit further comprises instructions for using the kit to carry out a method of characterizing the risk for cardiovascular disease for a subject using the reagents and the reference values or control samples.

22. The kit of claim 20, wherein the reagents are antibodies capable of specifically binding to the compound they are capable of detecting.

23. The kit of claim 20, wherein the reagents comprise a reagent capable of detecting B-type natriuretic peptide (BNP), a reagent capable of detecting myeloperoxidase (MPO), and a reagent capable of detecting high-sensitivity C-reactive protein (hsCRP).

24. The kit of claim 20, further comprising at least one additional reagent capable of detecting low density lipoprotein, cholesterol, apolipoprotein A1, apolipoprotein B100, or creatinine.