METHODS FOR DETECTING MAJOR ADVERSE CARDIOVASCULAR AND CEREBROVASCULAR EVENTS

• US 20110045514A1
• Filed: 10/10/2008
• Published: 02/24/2011
• Est. Priority Date: 10/10/2007
• Status: Abandoned Application

• Current Assignee: BG Medicine, Inc.
• Original Assignee: BG Medicine, Inc.
• Inventors: Myers, Rene, Muntendam, Pieter, Balasubramanian, Rajalakshmi
• Application Number:
  US12/682,492
• Publication Number:
  US 20110045514A1
• Time in Patent Office: Days
• US Class Current: 435/15
• CPC Class Codes: G01N 2333/7454 Tissue factor (tissue thromboplastin, Factor III)
• CPC Class Codes: G01N 2800/2871 Cerebrovascular disorders, e.g. stroke, cerebral infarct, cerebral haemorrhage, transient ischemic event
• 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 2800/60 Complex ways of combining multiple protein biomarkers for diagnosis
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere
• CPC Class Codes: H01J 49/0009 Calibration of the apparatus

Abstract

The present teachings relate to a method of assessing the probability of a major adverse cardiovascular or cerebrovascular event in a human. The method can include measuring a concentration, in a blood-based sample of a human, of a set of analytes, for example, alpha-fetoprotein, cancer antigen 125, glutathione S-transferase, and tissue factor. The method also can include determining a MACCE index for the set of analytes and identifying the human as having an increased likelihood of a major adverse cardiovascular or cerebrovascular event if the MACCE index is greater than zero, or a decreased likelihood of a major adverse cardiovascular or cerebrovascular event if the MACCE index is less than or equal to zero.

Claims

1. A method of assessing the probability of a major adverse cardiovascular or cerebrovascular event in a human, the method comprising:

measuring a concentration, in a blood-based sample of a human, of a set of analytes comprising alpha-fetoprotein, cancer antigen 125, glutathione S-transferase, and tissue factor;

determining a MACCE index for the set of analytes; and

identifying the human as having an increased likelihood of a major adverse cardiovascular or cerebrovascular event if the MACCE index is greater than zero, or a decreased likelihood of a major adverse cardiovascular or cerebrovascular event if the MACCE index is less than or equal to zero.

4. The method of claim 1, wherein the set of analytes further comprises CD40, fibrinogen, IL-3, IL-8, SGOT, and von Willebrand factor.

5. The method of claim 1, wherein determining a MACCE index for the set of analytes comprises:

standardizing the measured concentration of each analyte to obtain a standardized concentration;

multiplying the standardized concentration of each analyte by an analyte constant to obtain an analyte value; and

summing the analyte value of each analyte to obtain the MACCE index.

6. The method of claim 5, wherein standardizing the measured concentration comprises subtracting from the measured concentration a population average value to obtain a result and then dividing the result by a standard deviation of the population average value.

20. The method of claim 1, wherein the blood-based sample comprises serum or plasma.

2. A method of assessing the probability of a major adverse cardiovascular or cerebrovascular event in a human, the method comprising:

determining, based on a measured concentration of a set of analytes in a blood-based sample of a human, a MACCE index having a value indicative of the likelihood of a major adverse cardiovascular or cerebrovascular event, wherein the set of analytes comprises alpha-fetoprotein, cancer antigen 125, glutathione S-transferase, and tissue factor; and

transmitting, displaying, storing or outputting at least one of the MACCE index, the likelihood of a major adverse cardiovascular or cerebrovascular event, or an equivalent thereof to a user interface device, a computer readable storage medium, or a local or remote computer system.

25. The method of claim 2, wherein the MACCE index, the likelihood of a major adverse cardiovascular or cerebrovascular event, the measured concentration, the predetermined threshold or an equivalent thereof is displayed on a screen or a tangible medium.

26. The method of claim 2, wherein the MACCE index, the likelihood of a major adverse cardiovascular or cerebrovascular event, the measured concentration, the predetermined threshold or an equivalent thereof is transmitted to a person in a medical industry.

27. The method of claim 26, wherein the MACCE index, the likelihood of a major adverse cardiovascular or cerebrovascular event, the measured concentration, the predetermined threshold or an equivalent thereof is transmitted to a medical insurance provider or to a physician.

3. (canceled)

7. A method of assessing the probability of a major adverse cardiovascular or cerebrovascular event in a human, the method comprising:

measuring a concentration, in a blood-based sample of a human, of a set of analytes consisting of alpha-fetoprotein, cancer antigen 125, CD40, fibrinogen, glutathione S-transferase, IL-3, IL-8, SGOT, tissue factor, and von Willebrand factor;

determining a MACCE index for the set of analytes; and

identifying the human as having an increased likelihood of a major adverse cardiovascular or cerebrovascular event if the MACCE index is greater than zero, or a decreased likelihood of a major adverse cardiovascular or cerebrovascular event if the MACCE index is less than or equal to zero.

10. The method of claim 7, wherein determining a MACCE index for the set of analytes comprises:

standardizing the measured concentration of each analyte to obtain a standardized concentration;

multiplying the standardized concentration of each analyte by an analyte constant to obtain an analyte value; and

summing the analyte value of each analyte to obtain the MACCE index.

11. The method of claim 10, wherein standardizing the measured concentration comprises subtracting from the measured concentration a population average value to obtain a result and then dividing the result by a standard deviation of the population average value.

8. (canceled)

9. (canceled)

12. A method of assessing the probability of a major adverse cardiovascular or cerebrovascular event in a human, the method comprising:

measuring a concentration, in a blood-based sample of a human, of at least one analyte of a set of analytes selected from the group consisting of cysteine, von Willebrand factor, IL-8, 16;

0/18;

1 phosphatidylcholine, N-carboxy-alanine, fibrinogen, MMP-2, 18;

0/20;

4 phosphatidylethanolamine, apolipoprotein A1, 16;

0/22;

6 phosphatidylethanolamine, 18;

1/18;

0/18;

0 triacylglycerol, alpha-1 antitrypsin, 18;

2/18;

1/17;

0 triacylglycerol, 20;

1/18;

1/18;

1 triacylglycerol, 16;

0/16;

0 phosphatidylcholine, 20;

4 lysophosphatidylcholine, 16;

0 sphingomyelin, SHBG, 18;

1/17;

1, 16;

0 triacylglycerol, arabinose, and 18;

1/18;

1/17;

0 triacylglycerol; and

identifying the human as having an increased or decreased likelihood of a major adverse cardiovascular or cerebrovascular event based on a comparison of the measured concentration to a predetermined threshold.

16. The method of claim 12, wherein the predetermined threshold for each of the analytes:

cysteine, von Willebrand factor, IL-8, 16;

0/18;

1 phosphatidylcholine, N-carboxy-alanine, fibrinogen, MMP-2, 18;

0/20;

4 phosphatidylethanolamine, 16;

0/22;

6 phosphatidylethanolamine, 18;

1/18;

0/18;

0 triacylglycerol, alpha-1 antitrypsin, 18;

2/18;

1/17;

0 triacylglycerol, 20;

1/18;

1/18;

1 triacylglycerol, 16;

0/16;

0 phosphatidylcholine, 16;

0 sphingomyelin, SHBG, 18;

1/17;

1, 16;

0 triacylglycerol, and 18;

1/18;

1/17;

0 triacylglycerol, is the lower limit of the 4^th quartile in Table 4 for each respective analyte, wherein a measured concentration within the 4^th quartile increases the likelihood of a major adverse cardiovascular or cerebrovascular event.

17. The method of claim 12, wherein the predetermined threshold for each of the analytes:

cysteine, von Willebrand factor, IL-8, 16;

0/18;

1 phosphatidylcholine, N-carboxy-alanine, fibrinogen, MMP-2, 18;

0/20;

4 phosphatidylethanolamine, 16;

0/22;

6 phosphatidylethanolamine, 18;

1/18;

0/18;

0 triacylglycerol, alpha-1 antitrypsin, 18;

2/18;

1/17;

0 triacylglycerol, 20;

1/18;

1/18;

1 triacylglycerol, 16;

0/16;

0 phosphatidylcholine, 16;

0 sphingomyelin, SHBG, 18;

1/17;

1, 16;

0 triacylglycerol, and 18;

1/18;

1/17;

0 triacylglycerol, is the lower limit of the 3^rd and 4^th quartiles in Table 4 for each respective analyte, wherein a measured concentration within the 3^rd and 4^th quartiles increases the likelihood of a major adverse cardiovascular or cerebrovascular event.

18. The method of claim 12, wherein the predetermined threshold for each of the analytes apolipoprotein A1, 20:

4 lysophosphatidylcholine and arabinose is the upper limit of the 1st quartile in Table 4 for each respective analyte, wherein a measured concentration within the 1st quartile increases the likelihood of a major adverse cardiovascular or cerebrovascular event.

19. The method of claim 12, wherein the predetermined threshold for each of the analytes apolipoprotein A1, 20:

4 lysophosphatidylcholine and arabinose is the upper limit of the 1^st and 2nd quartiles in Table 4 for each respective analyte, wherein a measured concentration within the 1st and 2^nd quartiles increases the likelihood of a major adverse cardiovascular or cerebrovascular event.

13. (canceled)

14. A method of assessing the probability of a major adverse cardiovascular or cerebrovascular event in a human, the method comprising:

measuring a concentration, in a blood-based sample of a human, of at least one analyte of a set of analytes selected from the group consisting of 16;

0/18;

1 phosphatidylcholine, 18;

0/20;

4 phosphatidylethanolamine, 16;

0/22;

6 phosphatidylethanolamine, 18;

1/18;

0/18;

0 triacylglycerol, 18;

2/18;

1/17;

0 triacylglycerol, 20;

1/18;

1/18;

1 triacylglycerol, 16;

0/16;

0 phosphatidylcholine, 20;

4 lysophosphatidylcholine, 16;

0 sphingomyelin, 18;

1/17;

1/16;

0 triacylglycerol, and 18;

1/18;

1/17;

0 triacylglycerol; and

identifying the human as having an increased or decreased likelihood of a major adverse cardiovascular or cerebrovascular event based on a comparison of the measured concentration to a predetermined threshold.

15. (canceled)

21-24. -24. (canceled)

28. (canceled)

29. (canceled)