Predictive analysis for myocardial infarction

Patent metadata

Field	Value
Publication number	US-10041120-B2
Application number	US-201514714063-A
Country	US
Kind code	B2
Filing date	May 15, 2015
Priority date	May 28, 2014
Publication date	Aug 7, 2018
Grant date	Aug 7, 2018

Abstract

Compositions, systems and methods for the diagnosing the risk of acute myocardial infarction are provided. The methods described herein relate to the use of biomarkers, such as gene expression profiles, and analytical tools for providing information to a health care provider or the patient, that is relevant to the cardiovascular health of the patient.

First claim

What is claimed is:

1. A method of treating a human at risk of myocardial infarction (MI) but having no detectable necrosis of cardiomyocytes, the method comprising:
(A) obtaining a blood sample of a human having no detectable necrosis of cardiomyocytes and exhibiting a symptom selected from the group consisting of chest pain or discomfort; pain in the arms, neck, jaw, shoulder or back accompanying chest pain; nausea; fatigue; shortness of breath; sweating; dizziness; and any combination thereof;
(B) detecting an expression level of mRNA transcripts of genes HBEGF, NR4A2, NR4A3, NFKBIA, SYTL3, SULF1, and RNASE1 in the blood sample;
(C) determining a weighted expression level of the mRNA transcripts detected in the blood sample as compared to a control or standard derived from a healthy human individual or population of healthy human individuals, or from a diseased human individual or population of diseased human individuals with known but stable cardiovascular disease, wherein
(1) the weighted expression levels of the mRNA transcripts of genes HBEGF, NR4A2, NR4A3, NFKBIA, SYTL3, SULF1, and RNASE1 are compared to the control or standard derived from a healthy human individual or population of healthy human individuals; or
(2) the weighted expression levels of the mRNA transcripts of genes NR4A2, NR4A3, NFKBIA, SYTL3, SULF1, and RNASE1 are compared to the control or standard from a diseased human individual or population of diseased human individuals with known but stable cardiovascular disease; and

(D) calculating a risk score based upon an increase in the weighted expression levels of the mRNA transcripts;
(E) identifying the human as at risk of an MI if the risk score is greater than a reference risk score; and
(F) treating the human identified as at risk of MI by:
(1) administering a drug therapy selected from the group consisting of antiplatelet agents, anticoagulants, statins, fibrinolytic agents, and combinations thereof;
(2) performing enhanced external counterpulsation (EECP), surgical revascularization, angioplasty, coronary artery bypass surgery, emergent or urgent coronary artery bypass grafting (CABG), or percutaneous coronary intervention (PCI) on the human; or
(3) any combinations thereof.

2. The method of claim 1 , wherein the human is negative for pathognomonic electrocardiographic changes, has a negative stress test, negative CT angiography, negative traditional cardiac catheterization, or a combination thereof.

3. The method of claim 2 , wherein the human is negative for ST segment elevation on an ECG.

4. The method of claim 1 , further comprising detecting expression levels mRNA transcripts of one or more genes selected from the group consisting of: EFEMP1, NLRP3, THBS1, MCAM, RGS1, GABPB1, CXCL2, CCL20, EDN1, CCL3, MGP, VWF, CREM, FN1, PHACTR1, and VPS8.

5. The method of claim 1 , wherein the human has chest pain.

6. The method of claim 1 , wherein the myocardial infarction is non-ST-segment elevation myocardial infarction (NSTEMI).

7. The method of claim 1 , wherein the detecting an expression level of mRNA transcripts comprises nucleic acid amplification.

8. The method of claim 1 , wherein the detecting an expression level of mRNA transcripts comprises polymerase chain reaction (PCR).

Assignees

• Scripps Health
• Ortho Clinical Diagnostics Inc

Inventors

• Topol Eric J
• Muse Evan
• Connelly Mark
• Jatkoe Timothy
• Wang Haiying

Classifications

• G16B25/00

  ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression · CPC title

• C12Q1/6883 Primary

  for diseases caused by alterations of genetic material · CPC title

• C12Q2600/158

  Expression markers · CPC title

• G06F19/20

  Physics · mapped topic

• G16B25/10

  Gene or protein expression profiling; Expression-ratio estimation or normalisation · CPC title