# US 10,502,748 B2 · Method of differentiating stable angina pectoris from acute coronary syndrome and diagnostic kit thereof

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- Number: US 10,502,748 B2
- Document ID: US10502748B2
- Status: Granted
- Kind: B2
- Application number: 15/599,419
- Filed: 2017-05-18
- Published: 2018-03-29
- Granted: 2019-12-10
- Earliest claimed: 2016-09-23
- Assignees: Lianwen Qi
- Applicants: Lianwen Qi
- Inventors: Lianwen Qi; Yong Fan; Ping Li; Wei Zhu; Yan Chen
- Web page: https://patentgrep.com/patent/US10502748B2

## CPC

- G01N 33/6893: {related to diseases not provided for elsewhere}
- G01N 30/7206: {interfaced to gas chromatograph (interfaces in general for introducing or extracting samples to be analysed with specially adapted mass spectrometer, see H01J49/04)}
- G01N 33/492: {Determining multiple analytes}
- G01N 33/6815: {containing sulfur, e.g. cysteine, cystine, methionine, homocysteine}
- G01N 33/88: involving prostaglandins {or their receptors}
- G01N 33/92: involving lipids, e.g. cholesterol {, lipoproteins, or their receptors (steroid hormones G01N33/743)}
- G01N 30/7233: {interfaced to liquid or supercritical fluid chromatograph (interfaces in general for introducing or extracting samples to be analysed with specially adapted mass spectrometer, see H01J49/04)}
- G01N 2030/8822: {involving blood}
- G01N 2560/00: Chemical aspects of mass spectrometric analysis of biological material
- G01N 2570/00: Omics, e.g. proteomics, glycomics or lipidomics; Methods of analysis focusing on the entire complement of classes of biological molecules or subsets thereof, i.e. focusing on proteomes, glycomes or lipidomes
- G01N 2800/324: Coronary artery diseases, e.g. angina pectoris, myocardial infarction
- G16H 50/20: for computer-aided diagnosis, e.g. based on medical expert systems
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA

## Abstract

This application discloses a method of differentiating stable angina pectoris from acute coronary syndrome, including: obtaining a blood plasma sample from a patient; measuring a relative concentration of at least one metabolic biomarker in the blood plasma sample, wherein the at least one metabolic biomarker is selected from the group consisting of malic acid, taurine, arachidonic acid, citramalic acid, methionine, and pentadecanoic acid; calculating a value according to the relative concentration of at least one metabolic biomarker; comparing the value with a predefined critical value, if the value is more than the predefined critical value, the patient has the acute coronary syndrome, otherwise, the patient has the stable angina pectoris. The method and a diagnostic kit thereof is capable of differential diagnosis of SA and ACS and it can improve the diagnostic convenience and promote the diagnostic standardization.

## Claims

### Claim 1

A method of differentiating stable angina pectoris from acute coronary syndrome, comprising:
obtaining a blood plasma sample from a patient;
measuring a relative concentration of at least one metabolic biomarker in the blood plasma sample, wherein the at least one metabolic biomarker is selected from the group consisting of malic acid, taurine, arachidonic acid, citramalic acid, methionine, and pentadecanoic acid; wherein, the step of measuring a relative concentration of at least one metabolic biomarker in the blood plasma sample further comprises the following steps: a), adding an internal standard of 2-isopropyl malic acid into the blood plasma to obtain the blood plasma having the internal standard at a concentration of 1 μg/ml; b), preparing the blood plasma having the internal standard into a sample solution, using a solvent; c), dissolving a reference mixture using the solvent to prepare a reference solution, wherein the reference mixture includes 2-isopropyl malic acid and the at least one metabolic biomarker, and the purities of the 2-isopropyl malic acid and the at least one metabolic biomarker are no less than 98%; and d), analyzing the sample solution and the reference solution by UPLC-Q/TOF-MS, measuring a peak area of extracted ion chromatogram of the at least one metabolic biomarker and a peak area of extracted ion chromatogram of the 2-isopropyl malic acid in the sample solution, and using a ratio of the peak area of the extracted ion chromatogram of the at least one metabolic biomarker to the peak area of the extracted ion chromatogram of the 2-isopropyl malic acid as a relative concentration of the at least one metabolic biomarker;
obtaining a differentiating value according to the relative concentration of at least one metabolic biomarker; wherein the differentiating value is a value calculated by a formula; and
comparing the differentiating value with a predefined critical value, if the differentiating value is more than the predefined critical value, the patient has the acute coronary syndrome, otherwise, the patient has the stable angina pectoris, wherein the predefined critical value is determined according to the at least one metabolic biomarker.

### Claim 2 (depends on 1)

The method of claim 1, wherein the at least one metabolic biomarker includes three metabolic biomarkers taurine, arachidonic acid and methionine, wherein the predefined critical value is 0.591.

### Claim 3 (depends on 2)

The method of claim 2, wherein the differentiating value is calculated by the formula of 1/(1+exp[(−6.487+24.535× a relative concentration of taurine+0.064× a relative concentration of arachidonic acid −3.119× a relative concentration of methionine)]).

### Claim 4 (depends on 1)

The method of claim 1, wherein the at least one metabolic biomarker includes six metabolic biomarkers malic acid, taurine, arachidonic acid, citramalic acid, methionine, and pentadecanoic acid, wherein the predefined critical value is 0.572.

### Claim 5 (depends on 4)

The method of claim 4, wherein the differentiating value is calculated by the formula of 1/(1+exp[(−3.893+32.540× a relative concentration of malic acid+0.046× a relative concentration of taurine −3.926× a relative concentration of arachidonic acid+0.045× a relative concentration of citramalic acid+0.028× a relative concentration of methionine −0.022× a relative concentration of pentadecanoic acid)]).

### Claim 6 (depends on 1)

The method of claim 1, wherein the solvent is 20% acetonitrile aqueous solution.