Predictive analysis for myocardial infarction

Patent metadata

Field	Value
Publication number	US-10597722-B2
Application number	US-201816007853-A
Country	US
Kind code	B2
Filing date	Jun 13, 2018
Priority date	May 28, 2014
Publication date	Mar 24, 2020
Grant date	Mar 24, 2020

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 individual at increased risk of experiencing a myocardial infarction (MI), comprising:
treating a human individual having increased risk of experiencing an MI with a treatment regimen to decrease risk of thrombus formation, the human individual having no detectable necrosis of cardiomyocytes, and identified as having increased risk of experiencing MI by
(i) having an expression level of mRNA transcripts of genes HBEGF, NR4A2, NR4A3, NFKBIA, SYTL3, SULF1, and RNASE1 that is elevated compared to a control or standard derived from a healthy human individual or population of healthy human individuals; or
(ii) having an expression level of mRNA transcripts of genes NR4A2, NR4A3, NFKBIA, SYTL3, SULF1, and RNASE1, that is elevated compared to the control or standard from a diseased human individual or population of diseased human individuals with known but stable cardiovascular disease.

2. The method of claim 1 , wherein the treatment regimen comprises a drug therapy effective to decrease risk of thrombus formation or a surgical intervention effective to decrease risk of thrombus formation on the human individual.

3. The method of claim 2 , wherein the drug therapy comprises antiplatelet agents, anticoagulants, statins, or fibrinolytic agents, or a combination thereof.

4. The method of claim 2 , wherein the surgical intervention comprises enhanced external counterpulsation, surgical revascularization, angioplasty, coronary artery bypass surgery, emergent or urgent coronary artery bypass grafting, or percutaneous coronary intervention, or a combination thereof.

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

6. The method of claim 1 , wherein the human individual is negative for ST segment elevation on an ECG.

7. The method of claim 1 , wherein the human individual exhibits 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.

8. The method of claim 1 , wherein the human individual has been identified as being at risk of myocardial infarction (MI) by a method comprising:
(a) detecting an expression level of mRNA transcripts of genes HBEGF, NR4A2, NR4A3, NFKBIA, SYTL3, SULF1, and RNASE1 in a blood sample isolated from the individual;
(b) determining a weighted expression level of the mRNA transcripts detected in the blood sample as compared to the control or standard derived from the healthy human individual or population of healthy human individuals, or from the diseased human individual or population of diseased human individuals with known but stable cardiovascular disease, wherein
(i) the weighted expression level of the mRNA transcripts of genes HBEGF, NR4A2, NR4A3, NFKBIA, SYTL3, SULF1, and RNASE1 are compared to the control or standard derived from the healthy human individual or population of healthy human individuals; or
(ii) the weighted expression level of the mRNA transcripts of genes NR4A2, NR4A3, NFKBIA, SYTL3, SULF1, and RNASE1 are compared to the control or standard from the diseased human individual or population of diseased human individuals with known but stable cardiovascular disease is associated with an increased risk of experiencing a MI; and

(c) calculating a risk score based upon an increase in the weighted expression level of the mRNA transcripts, wherein the human individual is identified as having increased risk of experiencing MI if the risk score is greater than a reference risk score.

9. The method of claim 8 , wherein the detecting of the expression levels of mRNA transcripts comprises nucleic acid amplification.

10. The method of claim 8 , wherein the blood sample comprises whole blood or blood plasma.

11. A method of treating a human individual at risk of myocardial infarction that has no detectable necrosis of cardiomyocytes comprising:
(a) identifying a human individual having no detectible necrosis of cardiomyocytes as being at risk of myocardial infarction (MI), based on an increased expression level of a gene expression product of a gene selected from: HBEGF, NR4A2, NR4A3, NFKBIA, SYTL3, SULF1, and/or RNASE1 in a sample obtained from the human individual as compared to: (i) a control or standard derived from a healthy human individual or population of healthy human individuals, or (ii) a control or standard derived from a diseased human individual, or population of diseased human individuals with known but stable cardiovascular disease; and
(b) administering to the human individual at risk of MI a drug therapy effective to decrease risk of thrombus formation or performing a surgical intervention to decrease risk of thrombus formation.

12. The method of claim 11 , wherein the identifying the human individual as being at risk of myocardial infarction (MI) comprises:
(a) detecting expression levels of mRNA transcripts of genes HBEGF, NR4A2, NR4A3, NFKBIA, SYTL3, SULF1, and RNASE1 in the sample isolated from the human individual;
(b) determining a weighted expression level of the mRNA transcripts detected in the sample as compared to the control or standard derived from the healthy human individual or population of healthy human individuals, or from the diseased human individual or population of diseased human individuals with known but stable cardiovascular disease, wherein
(i) 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 the healthy human individual or population of healthy human individuals; or
(ii) 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 the diseased human individual or population of diseased human individuals with known but stable cardiovascular disease is associated with an increased risk of experiencing a MI; and

(c) calculating a risk score based upon an increase in the weighted expression levels of the mRNA transcripts, wherein the human individual is identified as having increased risk of experiencing MI if the risk score is greater than a reference risk score.

13. The method of claim 12 , wherein the detecting of the expression levels of mRNA transcripts comprises nucleic acid amplification.

14. The method of claim 11 , wherein the surgical intervention comprises enhanced external counterpulsation, surgical revascularization, angioplasty, coronary artery bypass surgery, emergent or urgent coronary artery bypass grafting, or percutaneous coronary intervention, or a combination thereof.

15. The method of claim 11 , wherein the drug therapy comprises antiplatelet agents, anticoagulants, statins, or fibrinolytic agents, or a combination thereof.

16. The method of claim 11 , wherein the human individual is negative for pathognomonic electrocardiographic changes, has a negative stress test, negative CT angiography, negative traditional cardiac catheterization, or a combination thereof.

17. The method of claim 11 , wherein the human individual is negative for ST segment elevation on an ECG.

18. The method of claim 11 , wherein the human individual exhibits a symptom selected from the group consisting of chest pain or discomfort; pain in the arms, neck, jaw, shoulder o

Assignees

• Scripps Health
• Ortho Clinical Diagnostics Inc

Inventors

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

Classifications

• C12Q1/6883 Primary

  for diseases caused by alterations of genetic material · CPC title

• G16B25/00

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

• C12Q2600/158

  Expression markers · CPC title

• G16B25/10

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

• G16B25/20

  Polymerase chain reaction [PCR]; Primer or probe design; Probe optimisation · CPC title