阅读说明：本技术 基于血清代谢组学改变建立的预测冠心病斑块不稳定性临床模型 (Clinical model for predicting coronary heart disease plaque instability based on serum metabonomics change ) 是由 姜华丽 王善花 李恒 陈本发 于 2020-01-02 设计创作，主要内容包括：本发明涉及生物化学领域,具体涉及基于血清代谢组学改变建立的预测冠心病斑块不稳定性临床模型。一种用于诊断急性冠脉综合征的特异性代谢物,包括甜菜碱、乙酰肉碱、1-十七碳酰-甘油-3-磷酰胆碱、异十一酸中的一种或多种；一种用于计算急性冠脉综合征患者血清中斑块稳定性的临床模型,所述模型为logit(P＝VP vs.SP)＝0.029*甜菜碱+0.051*射血分数-6.137。该模型敏感性高达70.6％,特异性高达80％。利用本发明的诊断模型计算冠脉综合征高危患者的斑块的稳定性,可为临床冠脉综合征斑块的鉴定及早期积极的干预及治疗提供治疗策略。(The invention relates to the field of biochemistry, in particular to a clinical model for predicting coronary heart disease plaque instability, which is established based on serum metabonomics change. A specific metabolite for diagnosing acute coronary syndrome, comprising one or more of betaine, acetyl-carnitine, 1-heptadecacarbonyl-glycerol-3-phosphorylcholine, isoundecanoic acid; a clinical model for calculating plaque stability in serum of a patient with acute coronary syndrome, said model being logit (P ═ VP vs. sp) ═ 0.029 betaine +0.051 ejection fraction-6.137. The sensitivity of the model is as high as 70.6%, and the specificity is as high as 80%. The diagnosis model of the invention is used for calculating the stability of the plaque of the coronary syndrome high-risk patient, and can provide a treatment strategy for the identification of the clinical coronary syndrome plaque and the early active intervention and treatment.)

1. A specific metabolite for use in the diagnosis of acute coronary syndrome comprising one or more of betaine, acetyl-carnitine, 1-heptadecacarbonyl-glycerol-3-phosphorylcholine, isoundecanoic acid.

2. The specific metabolite for diagnosing acute coronary syndrome according to claim 1, comprising any two of said metabolites.

3. The specific metabolite for diagnosing acute coronary syndrome according to claim 1, comprising any three of said metabolites.

4. The specific metabolite for diagnosing acute coronary syndrome according to claim 1, comprising any four of said metabolites.

5. A method for qualitatively or quantitatively analyzing the specific metabolites for diagnosing acute coronary syndrome according to any one of claims 1 to 4, wherein the metabolites are qualitatively or quantitatively analyzed using a liquid chromatography-mass spectrometer.

6. A test kit for diagnosing acute coronary syndrome, comprising a standard of the specific metabolites according to any one of claims 1 to 4, wherein the standard is a chemical monomer or mixture of each specific metabolite.

7. A clinical model for calculating plaque stability in serum of a patient with acute coronary syndrome, wherein said model is logit (P ═ VP vs. sp) ═ 0.029 betaine +0.051 ejection fraction-6.137.

Technical Field

The invention relates to the field of biochemistry, in particular to a clinical model for predicting coronary heart disease plaque instability, which is established based on serum metabonomics change.

Background Art 5

Coronary Artery Disease (CAD) is one of the metabolic diseases that can lead to death from the most severe cardiovascular events. Acute Coronary Syndrome (ACS) is a severe type of coronary heart disease. ACS is often associated with unstable atherosclerotic plaque rupture, coronary thrombosis, acute myocardial ischemia. Clinically, ACS can be classified as Acute Myocardial Infarction (AMI) and Unstable Angina (UA). Early detection of Vulnerable Plaques (VPs) is crucial to timely and effective inhibition of myocardial necrosis and heart failure.

Research has shown that atherosclerosis is a chronic inflammatory arterial disease, resulting from impaired lipid metabolism and an imbalance in immune responses. Although some biomarkers detected in the peripheral or coronary circulation have been reported to be associated with plaque inflammation, they may be useful in predicting the onset and progression of ACS. However, most studies on biomarkers are retrospective, and their predictive value remains uncertain. Therefore, it remains a significant challenge to explore new biomarkers that can predict vulnerable plaques that induce cardiovascular events. Metabolomics is a relatively new discipline. It is believed to be capable of identifying and quantifying various low molecular weight metabolites or endogenous metabolites under physiological or pathological conditions. Metabolomics has been widely used for the diagnosis of a variety of metabolic diseases, such as gastritis, liver fibrosis, diabetes and different types of cancer. Meanwhile, the application of metabonomics in cardiovascular diseases such as hyperlipidemia, atherosclerosis and hypertension is also gradually paid attention. However, the changes in metabolomics in ACS metabolomics have not been studied extensively, nor are they known. Furthermore, the risk stratification of serum metabolic markers in acute coronary syndrome and stable coronary heart disease requires further exploration.

Coronary atherosclerotic heart disease is a heart disease caused by myocardial ischemia, hypoxia or necrosis due to stenosis or obstruction of a blood vessel cavity caused by atherosclerotic lesions generated in coronary vessels, and is often referred to as "coronary heart disease". The number of coronary heart diseases in China is as high as 2.9 hundred million, and more than 350 million people die of coronary artery events every year. Unstable atherosclerotic plaques and thrombosis secondary to plaque rupture are the main causes of the development and progression of Acute Coronary Syndrome (ACS). Therefore, the method for early predicting the stability of the coronary atherosclerotic plaque has important clinical significance for clinical intervention of the coronary heart disease and prevention of occurrence and development of ACS. However, the current method for diagnosing coronary artery unstable plaque is mainly realized by combining Coronary Angiography (CAG) with coronary artery intravascular ultrasound (IVUS), and the problems are mainly as follows: (1) both CAG and IVUS are invasive tests with a certain proportion of heart related risks that patients with poor body base are intolerant; (2) both CAG and IVUS examinations require the injection of an iodine contrast agent into the coronary arteries under X-ray, and both examinations cannot be performed on patients with severe cardiac and renal insufficiency, or patients allergic to iodine agents. (3) The radial artery may be damaged after CAG and IVUS examination, the radial artery is blocked after the patient carries out the two examinations, and sequela such as upper limb numbness, pain and the like can be left in the patient; (4) after CAG and IVUS examination, pressurization hemostasis is needed at the radial artery puncture site, swelling and pain can occur on the upper limb of a patient on the examination side after operation, and pain of the patient is increased; (5) CAG and IVUS examinations must be performed in hospital, increasing hospital administrative burden and patient economic cost; (6) the CAG and IVUS inspection cost is higher, and the cost is about 16000 yuan in the sum of the two inspections, thereby greatly increasing the burden of social and national medical expenses.

Disclosure of Invention

In order to solve the above problems, the present invention provides a specific metabolite and plaque stability diagnostic model for diagnosing acute coronary syndrome, which comprises the following specific steps:

a specific metabolite for diagnosing acute coronary syndrome comprises one or more of betaine, acetyl carnitine, 1-heptadecacarbonyl-glycerol-3-phosphorylcholine, and isoundecanoic acid.

Further, any two of the metabolites are included.

Further, any three of the metabolites are included.

Further, any four of the metabolites are included.

A method for qualitatively or quantitatively analyzing the specific metabolites for diagnosing acute coronary syndrome described above using a liquid chromatography-mass spectrometer for qualitatively or quantitatively analyzing the metabolites.

A detection kit for diagnosing acute coronary syndrome comprises the standard substance of the specific metabolite, wherein the standard substance is a chemical monomer or a mixture of the specific metabolites.

A clinical model for calculating plaque stability in serum of a patient with acute coronary syndrome, said model being logit (P ═ VP vs. sp) ═ 0.029 betaine +0.051 ejection fraction-6.137.

Furthermore, the invention applies the method of logistic regression and the area under ROC curve, the model will bring in all clinical indexes affecting plaque stability, then backward stepwise eliminates the indexes with least significant regression one by one until the evaluation value of the model is the highest, screens out the clinical model (logit (P) ═ VPvs. SP) ═ 0.029 ═ betaine +0.051 ejection fraction-6.137) for diagnosing the sensitivity and specificity of unstable plaque of coronary artery, the sensitivity of the model is up to 70.6%, and the specificity is up to 80%. The model is used for calculating the stability of the plaque of the coronary syndrome high-risk patient, and a treatment strategy is provided for the identification of the clinical coronary syndrome plaque and early active intervention and treatment. The model of the invention has the following advantages:

1. non-invasive examination methods, no trauma and complications, and easier patient acceptance;

2. the hospital is not needed, the operation and the implementation are easy, and the clinic can be finished;

3. the medicine is not affected by other diseases, and can be realized by all patients suspected of coronary heart disease acute coronary syndrome;

4. the accuracy and specificity of diagnosing unstable coronary artery plaques are high;

5. the cost is relatively low, and the economic burden of the patient is reduced;

6. excessive medical examination is avoided, and medical resources are saved;

the invention provides a non-invasive clinical model for diagnosing unstable coronary artery plaques, which can be realized by a method of extracting venous blood without hospitalization, radial artery puncture and contrast tube insertion, avoids the traditional operation risk caused by CAG and IVUS, avoids the pain of swelling and pain at the puncture site of a patient after CAG and IVUS operation, does not need to inject an iodine contrast agent into a coronary artery blood tube, can judge the stability of the coronary artery plaques by a mode of extracting venous blood for all patients suspected of coronary heart diseases, saves the hospitalization time of the patients and lightens the economic burden of the patients. The specificity and the sensitivity of the non-invasive clinical model for diagnosing the unstable coronary artery plaque can reach 70 to 80 percent, and the specificity and the sensitivity are high and can be repeated, so that the method is a quick, economic and efficient method for identifying the unstable coronary artery atherosclerotic plaque.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.

FIG. 1 is a representative mass spectrometric analysis of SPs and VPs patients in example 1, wherein A is a representative mass spectrometric analysis of SPs patients and A is a representative profile analysis of VPs patients;

FIG. 2 is the analysis of serum metabolite P L S-DA in HCs (A), SPs (B), VPs (C) of example 1;

FIG. 3 shows the expression (A-D) and area under the curve (F-H) of the non-targeted four metabolites in VPs and SPs groups in example 1;

FIG. 4 shows the expression (A-C) and area under the curve (D-F) of the VPs and SPs groups for the three metabolites targeted in example 1;

FIG. 5 is a graph showing the diagnostic efficacy of betaine, acetyl-carnitine and 1-heptadecacarbonyl-glycerol-3-phosphocholine in example 1 in ACS group and HCs group (A), VPs group and HCs group (B), SPs group and HCs group (C), VPs group and SPs group (D);

FIG. 6 is a graph of the diagnostic efficacy of the combined betaine and ejection fraction model in plaque stability of example 2.

Detailed Description

The technical solutions of the present invention will be described clearly and completely with reference to specific embodiments, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.