DIAGNOSIS OF CARDIOVASCULAR DISEASE

• US 20100009356A1
• Filed: 05/01/2007
• Published: 01/14/2010
• Est. Priority Date: 05/01/2006
• Status: Active Grant

• Current Assignee: Critical Care Diagnostics Inc.
• Original Assignee: Critical Care Diagnostics Inc.
• Inventors: Jacobson, Sven, Snider, James V.
• Granted Patent: US 10,203,339 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: G01N 2333/7155 for interleukins [IL]
• CPC Class Codes: G01N 2800/226 Thrombotic disorders, i.e. thrombo-embolism irrespective of location/organ involved, e.g. renal vein thrombosis, venous thrombosis
• CPC Class Codes: G01N 2800/32 Cardiovascular disorders
• CPC Class Codes: G01N 2800/325 Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/6869 Interleukin
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

This invention relates to methods for the detection of cardiovascular disease, e.g., acute coronary syndrome, heart failure and/or pulmonary embolism, in high body mass index (BMI) individuals, e.g., with a BMI of 25-29, or 30 or above, and those with impaired renal function.

Claims

1. A kit for diagnosing cardiovascular disease (CVD), the kit comprising antibodies that specifically bind to ST2, BNP, and D-dimer, or nucleic acid probes that specifically bind to nucleic acids encoding ST2, BNP, and D-dimer, and instructions for use in a method of diagnosing heart failure (HF) or a pulmonary embolism (PE) in a subject who has one or both of (i) a body mass index (BMI) of greater than or equal to 25, or (ii) impaired renal function.

15. The kit of claim 1, wherein a subject has impaired renal function if they have a GFR or less than 50 ml/minute.

27. The kit of claim 1, wherein the CVD is heart failure (HF) or pulmonary embolism (PE).

28. The kit of claim 1, wherein the BNP level, D-dimer level, and ST2 level are detected in a biological sample comprising blood, plasma, or serum.

29. The kit of claim 1, wherein the subject has a BMI of greater than or equal to 30.

30. The kit of claim 1, wherein the subject has a BMI of 25 to 29.

2. A method of diagnosing cardiovascular disease (CVD) in a subject who has one or both of (i) a body mass index (BMI) of greater than or equal to 25, or (ii) impaired renal function, the method comprising:

one or both of;

(A) determining the subject'"'"'s BMI, and if the subject'"'"'s BMI is equal to or greater than 25, selecting the subject;

or

(B) evaluating the subject'"'"'s renal function, and if the subject has impaired renal function, selecting the subject; and

determining levels of BNP, D-dimers, and ST2 in a biological sample from the subject;

wherein the subject'"'"'s BNP level, D-dimer level, and ST2 level indicates whether the subject has CVD.

3. The method of claim 2, wherein the CVD is heart failure (HF) or pulmonary embolism (PE).

4. The method of claim 2, wherein the BNP level, D-dimer level, and ST2 level are detected in a biological sample comprising blood, plasma, or serum.

5. The method of claim 2, wherein if the subject'"'"'s BNP level is less than 500 pg/mL, and the D-dimer level is less than 500 μ

g/L, then the relationship of the ST2 level to a reference level of ST2 indicates whether the subject has HF.

6. The method of claim 2, wherein if the subject'"'"'s BNP level is less than 100 pg/mL, and the D-dimer level is 500-4000 μ

g/L, then the relationship of the ST2 level to a reference level of ST2 indicates whether the subject has PE.

7. The method of claim 5, wherein the reference level of ST2 represents a level in a subject who does not have HF.

8. The method of claim 5, wherein the reference level of ST2 is about 0.2 to 0.3 ng/ml of serum, and values above that level indicate the presence of HF.

9. The method of claim 6, wherein the reference level of ST2 represents a level in a subject who does not have PE.

10. The method of claim 6, wherein the reference level of ST2 is about 0.2 to 0.3 ng/ml of serum, and values above that level indicate the presence of PE.

11. The method of claim 2, wherein the subject'"'"'s BNP level is 100-500 pg/mL.

12. The method of claim 2, further comprising determining a level in the subject of one or more other biomarkers.

13. The method of claim 12, wherein the other biomarkers are selected from the group consisting of NT-pro ANP, ANP, troponin, CRP, creatinine, Blood Urea Nitrogen (BUN), liver function enzymes, albumin, and bacterial endotoxin.

14. The method of claim 2, wherein determining whether the subject has impaired renal function comprises determining glomerular filtration rate (GFR) and/or serum creatinine level, and the subject has impaired renal function if they have a GFR or serum creatinine level shown in the following table:

16. The method of claim 2, wherein the subject has a BMI of greater than or equal to 30.

17. The method of claim 2, wherein the subject has a BMI of 25 to 29.

18. A method of diagnosing cardiovascular disease (CVD) in a subject who has impaired renal function, the method comprising:

evaluating the subject'"'"'s renal function, and if the subject has impaired renal function, selecting the subject; and

determining an ST2 level in a biological sample from the subject;

wherein the relationship of the ST2 level to a reference level of ST2 indicates whether the subject has CVD.

19. The method of claim 18, wherein the reference level of ST2 represents a level in a subject who does not have CVD.

20. The method of claim 18, wherein the reference level of ST2 is about 0.2 to 03 ng/ml of serum, and values above that level indicate the presence of CVD.

21. The method of claim 18, wherein the reference level of ST2 represents a level in a subject who does not have CVD.

22. The method of claim 18, wherein the CVD is heart failure (HF) or pulmonary embolism (PE).

23. The method of claim 18, wherein the biological sample comprises blood, plasma, or serum.

24. The method of claim 18, further comprising determining a level in the subject of one or more other biomarkers.

25. The method of claim 24, wherein the other biomarkers are selected from the group consisting of BNP, D-Dimer, NT-proANP, and ANP troponin, CRP, creatinine, Blood Urea Nitrogen (BUN), liver function enzymes, albumin, and bacterial endotoxin.

26. The method of claim 18, wherein determining whether the subject has impaired renal function comprises determining glomerular filtration rate (GFR) and/or serum creatinine level, and the subject has impaired renal function if they have a GFR or serum creatinine level shown in the following table: