Myeloperoxidase, a risk indicator for cardiovascular disease

• US 9,164,095 B2
• Filed: 12/20/2005
• Issued: 10/20/2015
• Est. Priority Date: 01/02/2001
• Status: Expired due to Fees

• Current Assignee: Cleveland Clinic Foundation
• Original Assignee: Cleveland Clinic Foundation
• Inventors: Hazen, Stanley, Zhang, Renliang
• Primary Examiner(s): Kolker, Daniel E
• Assistant Examiner(s): ROGERS, JAMES L
• Application Number:
  US11/313,012
• Publication Number:
  US 20060105408A1
• Time in Patent Office: 3,591 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/616 by carboxylic acids, e.g. acetylsalicylic acid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12N 1/28 aliphatic
• CPC Class Codes: C12Q 1/28 involving peroxidase
• CPC Class Codes: C12Y 111/01007 Peroxidase (1.11.1.7), i.e. horseradish-peroxidase
• CPC Class Codes: G01N 2333/908 acting on hydrogen peroxide as acceptor (1.11)
• CPC Class Codes: G01N 2800/32 Cardiovascular disorders
• CPC Class Codes: G01N 2800/324 Coronary artery diseases, e.g. angina pectoris, myocardial infarction
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• 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 33/573 for enzymes or isoenzymes
• CPC Class Codes: G16H 10/40 for data related to laboratory analysis, e.g. patient specimen analysis
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment
• CPC Class Codes: G16Z 99/00 Subject matter not provided for in other main groups of this subclass
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

Diagnostic tests for characterizing an individual'"'"'s risk of developing or having a cardiovascular disease. In one embodiment the present diagnostic test comprises determining the level of myeloperoxidase (MPO) activity in a bodily sample obtained from the individual or test subject. In another embodiment, the diagnostic test comprises determining the level of MPO mass in a bodily sample obtained from the test subject. In another embodiment, the diagnostic test comprises determining the level of one or more select MPO-generated oxidation products in a bodily sample obtained from the test subject. The select MPO-generated oxidation products are dityrosine, nitrotyrosine, methionine sulphoxide or an MPO-generated lipid peroxidation products. Levels of MPO activity, MPO mass, or the select MPO-generated oxidation product in bodily samples from the test subject are then compared to a predetermined value that is derived from measurements of MPO activity, MPO mass, or the select MPO-generated oxidation product in comparable bodily samples obtained from healthy controls. Such comparison characterizes the test subject'"'"'s risk of developing CVD.

Claims

1. A method for administering a lipid lowering agent to a human patient based on elevated levels of protein-bound nitrotyrosine, comprising:

(a) performing an enzyme linked immunosorbent assay (ELISA) comprising contacting a bodily serum or plasma sample with a monoclonal anti-nitrotyrosine antibody;

(b) selecting a patient whose nitrotyrosine levels are greater than a predetermined value from comparable samples from an apparently healthy control population; and

(c) administering a lipid lowering agent to the selected human patient.

2. The method of claim 1, wherein the predetermined value is a single representative value or a range of representative values in comparable bodily samples from the general population or a select population of apparently healthy subjects.

3. The method of claim 1, wherein the predetermined value comprises ranges divided into a plurality of groups, and said comparing step comprises determining into which group the patient'"'"'s level of risk predictor falls.

4. The method of claim 1, wherein the patient is a non-diabetic, non-hypertensive, non-smoker.

5. The method of claim 1, wherein said bodily sample comprises plasma.

6. The method of claim 1, wherein said bodily sample comprises serum.

7. A method for administering a lipid lowering agent to a human patient based on elevated levels of protein-bound nitrotyrosine, comprising:

(a) performing an enzyme linked immunosorbent assay (ELISA) comprising contacting a bodily serum or plasma sample with a monoclonal anti-nitrotyrosine antibody; and

(b) administering a lipid lowering agent to the human patient.

8. The method of claim 7, wherein said bodily sample is a serum sample.

9. The method of claim 7, wherein said bodily sample is a plasma sample.