Diagnostic method of cardiovascular disease

• US 9,354,222 B2
• Filed: 02/20/2014
• Issued: 05/31/2016
• Est. Priority Date: 01/14/2014
• Status: Active Grant

• Current Assignee: Korea Advanced Institute of Science and Technology
• Original Assignee: Korea Advanced Institute of Science and Technology
• Inventors: Jung, Byung Hwa, Choi, Jong Min
• Primary Examiner(s): Wallenhorst, Maureen
• Application Number:
  US14/185,300
• Publication Number:
  US 20150198582A1
• Time in Patent Office: 831 Days
• Field of Search: 436/63, 436/71, 436/161, 436/173, 422/430, 435/29
• US Class Current: 1/1
• CPC Class Codes: G01N 2800/324 Coronary artery diseases, e.g. angina pectoris, myocardial infarction
• CPC Class Codes: G01N 30/72 Mass spectrometers mass spectrometers per se H01J49/00
• CPC Class Codes: G01N 33/492 Determining multiple analytes
• CPC Class Codes: G01N 33/92 involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

Biological metabolites LysoPC (18:0), LysoPC (20:3), fatty acid (16:1), fatty acid (18:0), fatty acid (18:1), fatty acid (18:2) and fatty acid (22:6) according to the present disclosure allow for simple and accurate diagnosis of a cardiovascular disease since their level in the blood of a subject increases or decreases if the subject has a cardiovascular disease such as myocardial infarction or angina. In addition, whereas the existing biomarkers can diagnose only whether myocardial infarction occurs or not, the biological metabolites according to the present disclosure can diagnose not only myocardial infarction but also unstable angina occurring prior to the onset of myocardial infarction stage by stage.

Claims

1. A method for diagnosing a cardiovascular disease in a subject, comprising:

obtaining a plasma sample from a patient subject from a normal subject by centrifugation of venous blood sample taken from the patient subject and the normal subject and incubating said plasma sample for a period of time;

deproteinizing the plasma sample by pretreating with methanol;

measuring a level of one or more biological metabolites selected from the group consisting of lysophosphatidylcholine (LysoPC) (18;

0), LysoPC (20;

3), fatty acid (16;

1), fatty acid (18;

0), fatty acid (18;

1), fatty acid (18;

2) and fatty acid (22;

6) in said plasma sample;

wherein the measuring the level of one or more biological metabolites comprises separating the biological metabolites by an ultra-high performance liquid chromatography system and detecting said metabolites using a mass spectrometer;

comparing the level of the biological metabolites in the plasma sample of the patient subject with the level of the biological metabolites in the plasma sample of the normal subject;

wherein the level of the biological metabolites in the plasma samples is a measurable concentration of said biological metabolites in the plasma samples;

wherein the comparing the level of the biological metabolites further comprises diagnosing that the subject has a cardiovascular disease if the level of at least one of LysoPC (20;

3), fatty acid (16;

1), fatty acid (18;

1), fatty acid (18;

2) and fatty acid (22;

6) in the plasma sample of the patient subject is higher as compared to the level in the plasma sample of the normal subject;

wherein the comparing the level of the biological metabolites further comprises diagnosing that the subject has a cardiovascular disease if the level of at least one of LysoPC (18;

0) and fatty acid (18;

0) in the plasma sample of the patient subject is lower as compared to the level in the plasma sample of the normal subject; and

identifying a progress of myocardial infarction and unstable angina occurring prior to an onset of the myocardial infarction in the patient subject based on the level of the biological metabolites in the plasma sample of the patient subject.

2. The method for diagnosing a cardiovascular disease in a subject according to claim 1 further comprising comparing the level of all of said biological metabolites in the plasma samples at the same time.