Use of IGFBP-7 in the assessment of heart failure

Patent metadata

Field	Value
Publication number	US-10996229-B2
Application number	US-201916598361-A
Country	US
Kind code	B2
Filing date	Oct 10, 2019
Priority date	Jan 25, 2007
Publication date	May 4, 2021
Grant date	May 4, 2021

Abstract

Disclosed is a method for assessing heart failure in vitro including the steps of measuring in a sample the concentration of the marker IGFBP-7, of optionally measuring in the sample the concentration of one or more other marker(s) of heart failure, and of assessing heart failure by comparing the concentration determined in for IGFBP-7 and the concentration(s) determined for the optionally one or more other marker to the concentration of this marker or these markers as established in a reference population. Also disclosed are the use of IGFBP-7 as a marker protein in the assessment of heart failure, a marker combination comprising IGFBP-7 and a kit for measuring IGFBP-7.

First claim

What is claimed is:

1. A method of diagnosing and treating heart failure in an individual at risk for heart failure, the method comprising the steps of:
contacting, in vitro, a portion of a serum, plasma, or whole blood sample from the individual with an antibody or fragment thereof having specific binding affinity for marker insulin like growth factor binding protein 7 (IGFBP-7), thereby forming a complex between the antibody or fragment thereof and the marker IGFBP-7 present in the sample, the antibody having a detectable label;
separating the complex formed in said step of contacting from antibody or fragment thereof not comprising the complex;
quantifying a signal from the detectable label of the antibody or fragment thereof comprising the complex formed in said step of contacting, the signal being proportional to an amount of the marker IGFBP-7 present in the sample of the individual, whereby a concentration of the marker IGFBP-7 within the sample of the individual is based on the quantified signal calculated;
comparing the calculated concentration value of the marker IGFBP-7 within the sample of the individual determined in said step of quantifying to a reference concentration of the marker IGFBP-7;
providing a diagnosis of heart failure in the individual when the calculated concentration value of the marker IGFBP-7 is greater than the reference concentration of the marker IGFBP-7; and
treating the diagnosed individual with one or more of an angiotensin-converting enzyme (ACE) inhibitor, a beta-blocker, an angiotensin II (AT II) inhibitor, an aldosterone antagonist, and an endothelin-1 blocking agent.

2. The method according to claim 1 , wherein said step of contacting comprises a sandwich immunoassay.

3. The method according to claim 1 , further comprising the steps of:
contacting, in vitro, a portion of a sample from an individual with an antibody or fragment thereof having specific binding affinity for one of a natriuretic peptide marker, a cardiac troponin marker, and a marker of inflammation;
calculating a concentration of the one of the natriuretic peptide marker, the cardiac troponin marker, and the marker of inflammation within the sample based on said step of contacting; and
comparing the concentration of the one of the natriuretic peptide marker, the cardiac troponin marker, and the marker of inflammation determined in said step of calculating to a corresponding reference concentration of the one of the natriuretic peptide marker, the cardiac troponin marker, and the marker of inflammation, respectively,
wherein said step of providing comprises providing a diagnosis of heart failure when the calculated concentration of the marker IGFBP-7 determined in said step of calculating is greater than the reference concentration of the marker IGFBP-7 and the calculated concentration of the one of the natriuretic peptide marker, the cardiac troponin marker, and the marker of inflammation determined in said step of calculating is greater than the corresponding reference concentration for the one of the natriuretic peptide marker, the cardiac troponin marker, and the marker of inflammation determined in said step of calculating, respectively.

4. The method according to claim 3 , wherein the natriuretic peptide marker is NT-proBNP.

5. The method according to claim 3 , wherein the cardiac troponin marker is troponin T.

6. The method according to claim 1 , wherein the reference concentration of the marker IGFBP-7 is established in a control sample.

7. The method according to claim 6 , further comprising the steps of:
contacting, in vitro, a portion of the control sample with the antibody or fragment thereof having specific binding affinity for the marker IGFBP-7; and
calculating the reference concentration of the marker IGFBP-7 within the control sample based on said step of contacting.

8. The method according to claim 7 , wherein the control sample comprises a body fluid.

9. The method according to claim 8 , wherein the body fluid is selected from the group consisting of plasma, whole blood, and serum.

10. The method according to claim 1 , wherein the reference concentration comprises a cut-off value of the marker IGFBP-7 in a reference population.

11. The method according to claim 1 , wherein the reference concentration comprises a reference range of the marker IGFBP-7 in a reference population.

12. The method according to claim 11 , wherein the diagnosis of heart failure is provided when the calculated concentration of the marker IGFBP-7 is greater than a ninetieth (90 th ) percentile of the reference range.

13. The method according to claim 1 , wherein said step of quantifying comprises calculating the concentration of IGFBP-7 in the control sample having a specificity of at least 95%, the specificity calculated from an unaffected subgroup of samples.

14. The method according to claim 1 , wherein said step of providing comprises providing a diagnosis of heart failure when the concentration of IGFBP-7 determined in the sample from the individual is at least 1.5 times greater than the reference concentration of IGFBP-7.

15. The method according to claim 1 , wherein said step of providing the diagnosis is performed by a computing device.

16. The method according to claim 1 , wherein said step of quantifying the signal is performed by a computing device.

Assignees

• Roche Diagnostics Operations Inc
• Governing Council Univ Toronto

Inventors

• Wienhues-Thelen Ursula-Henrike
• Hess Georg
• Huedig Hendrik
• Von Der Eltz Herbert
• Emili Andrew
• Gramolini Anthony
• Liu Peter
• Maclennan David
• Fong Vincent
• Isserlin Ruth
• Kislinger Thomas
• Block Dirk

Classifications

• G01N2800/56

  Staging of a disease; Further complications associated with the disease · CPC title

• G01N2333/4737

  C-reactive protein · CPC title

• G01N2800/325

  Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure · CPC title

• G01N2333/4727

  Calcium binding proteins, e.g. calmodulin · CPC title

• G01N2333/4745

  Insulin-like growth factor binding protein · CPC title