Application of sTREM2 as marker in vulnerable plaque diagnosis model and reagent

Abstract

According to the application of the serological biomarker in preparation of the vulnerable plaque diagnostic kit, the serological biomarker comprises sTREM2. Human peripheral blood serum is collected, and the concentration of soluble myeloid cell triggered receptor 2 (sTREM2) in the serum is determined by using an enzyme-linked immunosorbent assay (ELISA) kit or an equivalent immunoassay method, so that early discovery and (dynamic) monitoring of vulnerable plaques are realized. Through verification, the sTREM2 is suitable for being used as a diagnosis and prediction marker of vulnerable plaque related diseases, and guidance is provided for further clinical diagnosis (such as OCT / IVUS) and treatment.

Description

TECHNICAL FIELD

[0001] The present application relates to the application of a biomarker in auxiliary diagnosis, in particular to the application of a marker in auxiliary diagnosis of the possibility of occurrence of unstable (vulnerable) plaque, and a kit. BACKGROUND

[0002] Unstable (vulnerable) plaque is the pathological basis of various critical and acute diseases. The rupture of vulnerable plaque forms thrombus or embolus, causing acute occlusion of blood vessels, leading to ischemic necrosis of target organs, which is the core link of diseases such as acute myocardial infarction, acute ischemic stroke, acute limb ischemia or mesenteric arterial embolism. This kind of disease has high disability and mortality, seriously endangers human health, and increases the social burden of disease. Therefore, early identification, discovery and intervention of vulnerable / unstable plaque have important clinical and economic significance for preventing and treating vascular-related acute events and improving patient prognosis.

[0003] Currently, the early assessment of vulnerable plaque / unstable plaque in clinic is mainly through imaging detection, so that high-risk patients can receive accurate and reliable treatment before symptoms occur. Imaging detection includes non-invasive methods and invasive methods (intraluminal imaging techniques). Non-invasive methods include CT angiography (CTA), high-resolution magnetic resonance imaging (HR-MR) and positron emission tomography / computed tomography (PET / CT). CTA can show the outline of the vascular lumen, but cannot show the internal structure of the lumen, and is not good at analyzing and comparing the composition of the plaque, so it can only be used as a preliminary screening diagnosis; MRI can quantify plaque burden and provide information about plaque composition, including lipid content, calcification and thrombus, and can distinguish between calcified plaque and lipid plaque. However, whether the high-risk plaque identified by MRI is vulnerable plaque lacks clinical verification, and MRI is expensive and time-consuming, and is not suitable for patients with metal implants. PET / CT can provide detailed information about plaque inflammation and microcalcification, but this examination is too expensive and involves radiation exposure, so it is rarely used in clinical practice. Intraluminal imaging techniques are the most commonly used invasive methods, including coronary angiography, including near-infrared spectroscopy (NIRS), intravascular ultrasound (IVUS), optical coherence tomography (OCT) and other techniques. IVUS and OCT have become important tools for daily coronary plaque assessment and interventional treatment decision-making in the catheter laboratory. NIRS can only provide information about the composition of superficial lipid plaques, and it is difficult to assess the characteristics of deep lipid plaques, and it cannot show the condition of the vascular wall; IVUS can quantitatively analyze the composition and morphology of atherosclerotic plaques, but it cannot provide information about the thin fibrous cap of vulnerable plaques; Compared with IVUS, OCT has higher resolution and can accurately identify plaque composition and related plaque characteristics, especially identifying plaque composition related to vulnerability and performing qualitative and quantitative analysis. However, OCT also has limitations, such as high imaging requirements, weak penetration, and poor display of deep lipid necrotic cores and calcification. In addition to their own limitations, invasive methods are all invasive and expensive, making it difficult to continuously monitor the development of vulnerable plaques, which greatly limits their widespread use in clinical practice.

[0004] Therefore, in combination with the characteristics of vulnerable plaques and imaging methods, the current imaging methods mainly have the following deficiencies: 1. Imaging evaluation only focuses on local plaques, while atherosclerosis is a systemic and systematic disease, and it is difficult to evaluate the overall risk; 2. Imaging provides anatomic features at a single time point, while the development of vulnerable plaques is a dynamic biological process, and imaging cannot achieve low-cost dynamic monitoring; 3. Whether non-invasive or invasive imaging methods, they all face the problems of radiation, contrast agent risk and economic cost, especially invasive intraluminal imaging, which is difficult to be used as a universal tool for early screening, evaluation and dynamic monitoring of vulnerable plaques in the population. Therefore, finding a convenient, economical and repeatable serum biomarker of vulnerable plaques has always been a research hotspot in the field of pan-vascular diseases. SUMMARY

[0005] An object of the present application is to provide an application of a serum biomarker in a vulnerable plaque diagnosis model, which is beneficial for efficient early screening.

[0006] Another object of the present application is to provide an application of a serum biomarker in an early risk screening model of acute coronary syndrome.

[0007] Still another object of the present application is to provide an application of a kit in a vulnerable plaque diagnosis model, which is used as an auxiliary means before imaging evaluation to achieve low-cost dynamic monitoring.

[0008] Still another object of the present application is to provide a diagnosis model of vulnerable plaques.

[0009] The present application establishes a serum metabolic marker with high sensitivity and specificity, which is suitable for early screening and auxiliary diagnosis of vulnerable plaques in combination with the technical means of imaging, by systematically collecting metabolite data in the serum of patients on the basis of a large sample size.

[0010] The present application realizes early detection and (dynamic) monitoring of coronary vulnerable plaques by collecting human peripheral blood serum, and determining the concentration of soluble myeloid cell trigger receptor 2 (sTREM2) in the serum by using an enzyme-linked immunosorbent assay (ELISA) kit or an equivalent immunological analysis method.

[0011] Based on clinical research data, the AUC of sTREM2 in predicting vulnerable plaques is 0.778, and the 95% confidence interval is 0.730-0.846, which has statistical significance (P<0.0001) with OCT or IVUS defined vulnerable plaques as the standard; the Cutoff value of sTREM2 in predicting vulnerable plaques is 947.24 pg / ml, and the sensitivity is 63.7% and the specificity is 82.5%

[0012] The serological marker provided by the application is complementary to the existing imaging method, realizes the whole-process management of serological preliminary screening (finding high-risk individuals) + imaging detailed examination (locating responsible lesions) + serological monitoring (evaluating treatment response), realizes early warning and dynamic prevention and treatment of pan-vascular diseases (such as coronary heart disease, acute myocardial infarction, acute ischemic stroke and acute peripheral arterial occlusion), and has extremely important clinical value.

[0013] The application mainly relates to a detection method of a biomarker for assisting in diagnosing unstable (vulnerable) plaques and application thereof. sTREM2 is a novel biomarker. By detecting the change in the level thereof in circulation, the sTREM2 can be used for early screening, auxiliary diagnosis and dynamic monitoring of unstable (vulnerable) plaques, so as to predict and evaluate the risk of occurrence of serious clinical events such as acute myocardial infarction, acute ischemic stroke and acute peripheral vascular embolism.

[0014] The application of the serological marker provided by the application in a vulnerable plaque diagnosis model is beneficial to early warning and dynamic prevention and treatment.

[0015] The serological marker provided by the application is used for serological detection of vulnerable plaques, for example, is used for a diagnosis model and early risk screening.

[0016] The application of the marker in constructing an acute pan-vascular disease prediction model provides a basis for formulating an early prevention scheme for a patient.

[0017] The application of the marker in constructing an acute pan-vascular disease prediction model provides a basis for further imaging diagnosis, and accelerates the efficiency and detection cost of diagnosis.

[0018] A detection device synchronously or asynchronously detects and obtains the content information of sTREM2 in peripheral blood, provides objective information for the risk of vulnerable plaques, provides a basis for imaging evaluation in clinic, and provides prediction information for the risk of disease occurrence.

[0019] A system for disease risk prediction comprises the following units:

[0020] A data acquisition unit acquires the content information of sTREM2 in a sample;

[0021] An analysis unit analyzes the result detected by the data acquisition unit as an input item; and

[0022] An evaluation unit outputs the information of the risk of vulnerable plaques of an individual corresponding to the sample, and provides further diagnosis and treatment suggestions.

[0023] The system of the application further comprises a detection unit, and information of the detection unit is obtained by using a kit. The instrument synchronously or asynchronously detects and obtains content information of sTREM2 in the sample.

[0024] Compared with the existing imaging examination means in the art, the detection of the serum biological marker has more advantages, such as:

[0025] 1. Atherosclerosis is a systemic and systematic disease, and the circulating biological marker can comprehensively and integrally reflect the inflammatory state of the body, and has guiding significance for overall risk assessment.

[0026] 2. The development of vulnerable plaque is a dynamic biological process, and the serological detection is convenient and repeatable, and is very suitable for dynamic monitoring of high-risk patients, and realizes long-term management from early risk warning of the disease to post-treatment monitoring.

[0027] 3. The vulnerable plaque defined by imaging is mainly “morphological vulnerability” (such as thin fiber cap and large lipid core), and it is difficult to penetrate the appearance to evaluate the “biological vulnerability” of the plaque (such as the level and number of activated macrophages), so the detection of the biological marker can complement the imaging detection, and realize more accurate risk stratification. That is, sTREM2 can be combined with other existing biological markers, advanced imaging examination and invasive evaluation methods to form a multi-modal diagnostic method. This comprehensive method can improve the accuracy of diagnosis, enhance the risk stratification ability, and provide early personalized management strategies.

[0028] The currently reported serum biological markers valuable for predicting vulnerable plaques include C-reactive protein (CRP), interleukin family (such as IL-1β and IL-6), and matrix metalloproteinase family (MMPs, such as MMP-9). Compared with the above biological markers, the sTREM2 provided by the application has higher specificity: unlike traditional inflammatory markers such as CRP and IL-6, these markers can be produced by various inflammatory cells or endothelial cells in circulation, while sTREM2 is mainly produced by macrophages in atherosclerotic plaques, and can more specifically reflect the inflammatory state of atherosclerotic plaques and the activation of macrophages, thereby more accurately indicating the stability of the plaque.

[0029] The change of sTREM2 level can be related to the activity and severity of atherosclerotic lesions, and as the lesions progress, more sTREM2 can be released from TREM2-positive macrophages in the plaques into the blood circulation. Therefore, sTREM2 can not only be used as a diagnostic and predictive marker of the disease, but also can be used for monitoring the development process of the disease and evaluating the treatment effect, thereby providing guidance for clinical treatment. Through peripheral blood sTREM2 level to predict vulnerable plaques and realize the dynamic management of the disease, the method is fast, economical, safe, and has good repeatability, and has good clinical application prospect.

[0030] The vulnerable plaque biomarker provided by the application can be used for early diagnosis and dynamic monitoring of vulnerable plaques through a non-invasive, low-cost, safe and green, and repeatable method, and can not only prevent and treat acute myocardial infarction early, reduce MACE events, but also can be used for efficacy evaluation after treatment, and has important clinical significance for long-term management and improvement of prognosis of patients.

[0031] The high expression or low expression referred to in the application is determined by ROC curve analysis of two groups of vulnerable plaques and non-vulnerable plaques, and then the cutoff value is determined to define "high" or "low". BRIEF DESCRIPTION OF DRAWINGS

[0032] Figure 1 A is a statistical chart of serum sTREM2 concentration detection results of the non-vulnerable plaque group (non-VP) and the vulnerable plaque group (VP), and B is an ROC curve chart of sTREM2 as a biomarker for predicting vulnerable plaques;

[0033] Figure 2 A is the proportion of vulnerable plaques defined by IVUS / OCT examination in the low-level sTREM2 group and the high-level sTREM2 group, B is the correlation analysis of sTREM2 level and IVUS-defined vulnerable plaques / non-vulnerable plaques;

[0034] Figure 3 A is a statistical chart of serum sTREM2 concentration detection results of the non-coronary heart disease group (control), the stable angina pectoris group (stable) and the acute coronary syndrome group (ACS), and B is an ROC curve chart of sTREM2 as a biomarker for predicting acute coronary syndrome; DETAILED DESCRIPTION

[0035] The technical solutions of the present application are described in detail below with reference to the drawings. The embodiments of the present application are only used to illustrate the technical solutions of the present application and not to limit the present application. Although the present application has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solutions of the present application can be modified or replaced equivalently without departing from the spirit and scope of the technical solutions of the present application, and all of them should be covered in the scope of claims of the present application.

[0036] Example 1 Verification of the correlation between serum sTREM2 level and vulnerable plaque

[0037] Soluble TREM2 (sTREM2) is a derivative of TREM2 protein. TREM2 on the cell membrane is cut by specific enzymes, and its extracellular domain is released into the extracellular space or body fluid (such as cerebrospinal fluid and blood), which is the main source of sTREM2. The level of sTREM2 reflects the activation state and number of myeloid cells expressing TREM2. Therefore, detecting the level of sTREM2 in circulation can indirectly measure the degree of immune activity in the body, especially the inflammatory activation state of myeloid cells (such as macrophages). Given that macrophages and inflammatory reactions run throughout atherosclerosis and play an important role in the formation of vulnerable atherosclerotic plaques, it is of great significance to verify the relationship between sTREM2 and vulnerable plaque formation, such as sTREM2 has the potential to become a new biomarker for monitoring vulnerable plaques.

[0038] Study population: A total of 322 patients with coronary heart disease evaluated by intraluminal imaging were included.

[0039] Inclusion criteria: 1) Patients aged ≥18 years; 2) Patients receiving interventional surgery for the first time; 3) Predicted survival period >1 year; 4) Signed informed consent. Exclusion criteria: 1) Patients aged <18 years; 2) Severe liver and kidney dysfunction; 3) History of severe cardiovascular disease; 4) Severe active infection or chronic inflammation; 5) Obesity (BMI>30kg / m2); 6) Severe nervous system disease; 7) Pregnancy or lactation; 8) Poor compliance.

[0040] Characteristics of vulnerable plaques under the guidance of intraluminal imaging: thin fibrous cap atherosclerotic plaque (fibrous cap thickness <65um, arc >180°), or plaque burden >70%, accompanied by larger lipid pools (lipid pool / plaque area >20%) or plaque rupture, dissection, thrombus, or obvious macrophage infiltration, punctate calcification, neovascularization, etc.

[0041] The study includes:

[0042] 1) Collect and analyze the baseline levels of patients in each group;

[0043] 2) Screening of patients who have undergone intravascular imaging (IVUS and OCT) information, according to the intravascular imaging analysis results are divided into vulnerable / non-vulnerable plaque group and baseline analysis;

[0044] 3) ELISA method for detecting serum sTREM2 levels, and analyzing the difference between vulnerable plaque group and non-vulnerable plaque group;

[0045] 4) ROC curve analysis of serum sTREM2 for the diagnostic prediction value of vulnerable plaque, to evaluate its sensitivity and specificity as a biomarker of vulnerable plaque.

[0046] The experimental steps include:

[0047] 1) Peripheral blood plasma preparation: according to the principle of informed consent, patients take blood 5ml in the morning on an empty stomach, heparin anticoagulation tube anticoagulation. After centrifugation of whole blood at 2000 rpm for 20 min, the upper plasma was collected and stored at -80℃. The sample should be prevented from hemolysis during preparation.

[0048] 2) sTREM2 determination: the protein expression level of sTREM2 in plasma sample was detected by enzyme-linked immunosorbent assay, and the specific detection method was carried out according to the steps shown in the product instruction.

[0049] 3) Statistical analysis: all data were analyzed by spss 27.0 software. Continuous variables were expressed as mean ± standard deviation if they met normal distribution, and t test was used; if they did not meet normal distribution, median and interquartile range were used, and rank sum test was used. The number of cases and percentage were used to express the classification variables, and chi-square test was used. ROC curve was used to evaluate the diagnostic value of sTREM2 as a biomarker of vulnerable plaque.

[0050] The experimental results of sTREM2 as a biomarker for the prediction value of vulnerable plaque (VP) are as follows:

[0051] Screening of patients who have undergone intravascular imaging (IVUS and OCT) information, according to the examination results, the patients were divided into non-vulnerable (non-VP) plaque group and vulnerable plaque (VP) group, and the plasma sTREM2 protein level was detected, the results showed that the peripheral blood sTREM2 protein level of vulnerable plaque patients was significantly higher than that of non-vulnerable plaque patients (p<0.001) Figure 1 A).

[0052] ROC curve analysis as Figure 1As shown in B, the AUC of sTREM2 as a vulnerable plaque biomarker was 0.788, with a 95% confidence interval of 0.730-0.846, indicating that sTREM2 had good predictive value for vulnerable plaques, and the Cutoff value of sTREM2 for predicting vulnerable plaques was 947.24 pg / ml, with a diagnostic sensitivity of 63.7% and a specificity of 82.5%.

[0053] Example 2 Verification of the correlation between serum sTREM2 levels and IVUS image features

[0054] Currently, the early assessment of vulnerable plaques / unstable plaques in the clinic is mainly through imaging detection, among which intraluminal imaging techniques such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are the main means for clinical evaluation of high-risk plaques, and play an important role in the evaluation and treatment decision of coronary vulnerable plaques. The features of plaques evaluated by IVUS include plaque burden, positive vascular remodeling, size of lipid core, presence or absence of punctate calcification, calcification, calcification arc, presence or absence of thrombus and ruptured plaque; The features of plaques evaluated by OCT include fiber cap thickness, lipid core arc, calcification, presence or absence of plaque rupture, plaque erosion, local thrombus, hematoma and macrophage infiltration, etc. Although the above two techniques have unique advantages in evaluating plaque characteristics, they are both invasive and expensive, which greatly limits their widespread use in clinical practice. Given the high expression of sTREM2 in peripheral blood of patients with vulnerable plaques, it is of great significance to verify the consistency of sTREM2 with IVUS / OCT image examination results. For example, detecting serum sTREM2 levels can be used as a screening method to identify high-risk individuals, providing a basis for further improving IVUS / OCT examination, and significantly improving clinical detection efficiency.

[0055] Study population: A total of 322 patients with coronary heart disease evaluated by intraluminal imaging were included, among which 234 patients were evaluated for plaque properties using IVUS, and 88 patients were evaluated for plaque properties using OCT.

[0056] Inclusion criteria: 1) Patients aged ≥18 years; 2) Patients receiving interventional surgery for the first time; 3) Predicted survival period >1 year; 4) Signed informed consent. Exclusion criteria: 1) Patients aged <18 years; 2) Severe liver and kidney dysfunction; 3) History of severe cardiovascular disease; 4) Severe active infection or chronic inflammation; 5) Obesity (BMI >30 kg / m 2 ); 6) Severe nervous system disease; 7) Pregnancy or lactation; 8) Poor compliance.

[0057] Characteristics of vulnerable plaque under intraluminal imaging guidance: thin fibrous cap atheroma (fibrous cap thickness <65 um, arc >180°), or plaque burden >70% with larger lipid pool (lipid pool / plaque area >20%) or plaque rupture, dissection, thrombus, or significant macrophage infiltration, punctate calcification, neovascularization, etc.

[0058] The research content includes:

[0059] 1) Collect and analyze the baseline level of patients;

[0060] 2) Detect the level of serum sTREM2 by ELISA method, and take the cutoff value of sTREM2 for predicting vulnerable plaque as 947.24 pg / ml as the boundary value, and divide it into low level sTREM2 group (low, ≤947.24 pg / ml) and high level sTREM2 group (high, >947.24 pg / ml);

[0061] 3) Analyze the proportion of vulnerable plaque and plaque characteristics of patients in two groups, and verify the correlation between serum sTREM2 level and IVUS / OCT image characteristics.

[0062] The experimental steps include:

[0063] 1) Preparation of peripheral blood plasma: according to the principle of informed consent, 5 ml of blood was collected in the morning on an empty stomach, and heparin anticoagulation tube was used for anticoagulation. After centrifugation of whole blood at 2000 rpm for 20 min, the upper plasma was collected and stored at -80℃. Hemolysis should be prevented during sample preparation.

[0064] 2) sTREM2 determination: the protein expression level of sTREM2 in plasma samples was detected by enzyme-linked immunosorbent assay, and the specific detection method was carried out according to the steps shown in the product instruction.

[0065] 3) Statistical analysis: data were analyzed by spss 27.0 software. Continuous variables were expressed as mean ± standard deviation if they met normal distribution, and t test was used; if they did not meet normal distribution, median and interquartile range were used, and rank sum test was used. The number of cases and percentage were used to express the classification variables, and chi-square test was used; the correlation analysis between classification variables and continuous variables was carried out by R language software, and point two column correlation was used for analysis.

[0066] The correlation verification results of serum sTREM2 level and IVUS image characteristics are as follows:

[0067] Patients were divided into low level sTREM2 group and high level sTREM2 group according to the cutoff value of sTREM2 predicting vulnerable plaque. Statistical analysis results show that, using IVUS to evaluate plaque characteristics, the proportion of vulnerable plaque is higher, the plaque burden is heavier, the proportion of lipid core is higher, the proportion of punctate calcification is higher, and the calcification arc is larger in the high level sTREM2 group than in the low level sTREM2 group (Table 1, Figure 2 A).

[0068] Using point-two column correlation analysis, the correlation between sTREM2 and IVUS image results (vulnerable plaque is defined as 1, and non-vulnerable plaque is defined as 0) is analyzed. The results show that the correlation coefficient r is 0.469, and the 95% CI is 0.363-0.563, indicating that there is a moderate correlation between the two, and it has significant statistical significance (P<0.001). Figure 2 B).

[0069] Therefore, detecting serum sTREM2 level can be used as a screening method to find high-risk individuals, providing a basis for further improving IVUS examination, and significantly improving clinical detection efficiency.

[0070] Table 1 Difference and statistical results of vulnerable plaque characteristics defined by IVUS examination

[0071]

[0072] Example 3 Verification of sTREM2 for risk prediction of acute coronary syndrome (ACS)

[0073] Acute coronary syndrome is one of the important causes of cardiovascular death. The formation of vulnerable plaque is the core link of the occurrence and development of acute coronary syndrome. The inflammatory response mediated by macrophage infiltration is an important pathological feature of vulnerable plaque. The level of sTREM2 reflects the activation state and number of TREM2-expressing myeloid cells. Therefore, detecting the level of sTREM2 in circulation can indirectly measure the degree of immune activity in the body, especially the inflammatory activation state of myeloid cells (such as macrophages). Given the important role of macrophages and inflammatory response in the formation of vulnerable plaque, it is of great significance to verify the relationship between sTREM2 and acute coronary syndrome, such as: sTREM2 has the potential to become a new biomarker for early prediction of acute coronary syndrome, which is of great significance for early intervention of patients, reduction of adverse cardiovascular events, and improvement of patient prognosis.

[0074] Study population: A total of 392 patients from the coronary heart disease sample bank were included.

[0075] Inclusion criteria: 1) Patients aged ≥18 years; 2) Patients receiving interventional surgery for the first time; 3) Predicted survival period >1 year; 4) Signed informed consent. Exclusion criteria: 1) Patients aged <18 years; 2) Severe liver and kidney dysfunction; 3) History of severe cardiovascular disease; 4) Severe active infection or chronic inflammation; 5) Obesity (BMI >30 kg / m 2 ); 6) Severe nervous system disease; 7) Pregnancy or lactation; 8) Poor compliance.

[0076] The research content includes:

[0077] 1) Collect and analyze the baseline levels of patients in each group;

[0078] 2) According to the patient's medical history, laboratory examination and electrocardiogram, the patients are divided into non-coronary heart disease group (control), stable coronary heart disease group (stable) and acute coronary syndrome group (acs);

[0079] 3) ELISA method is used to detect the level of serum sTREM2, and analyze the difference between each group;

[0080] 4) ROC curve analysis of serum sTREM2 for the diagnostic prediction value of acute coronary syndrome, to evaluate its sensitivity and specificity as an early biomarker of acute coronary syndrome.

[0081] The experimental steps include:

[0082] 1) Peripheral blood plasma preparation: according to the principle of informed consent, 5ml of blood is collected in the morning on an empty stomach, and heparin anticoagulation tube is used for anticoagulation. After centrifugation of whole blood at 2000 rpm for 20 min, the upper plasma is collected and stored at -80℃. Hemolysis should be prevented during sample preparation.

[0083] 2) sTREM2 determination: the protein expression level of sTREM2 in plasma samples is detected by enzyme-linked immunosorbent assay, and the specific detection method is carried out according to the steps shown in the product instruction.

[0084] 3) Statistical analysis: all data are analyzed by spss 27.0 software. Continuous variables are expressed as mean ± standard deviation if they meet normal distribution, and t test is used; if they do not meet normal distribution, they are expressed as median and interquartile range, and rank sum test is used. Classification variables are expressed as number and percentage, and chi-square test is used. ROC curve is used to evaluate the predictive value of sTREM2 for early diagnosis of acute coronary syndrome.

[0085] The experimental results of sTREM2 as a biomarker for predicting the value of acute coronary syndrome are as follows:

[0086] Patients were divided into non-coronary heart disease group (control), stable coronary heart disease group (stable) and acute coronary syndrome group (acs), and the plasma sTREM2 protein level was detected. The results showed that the peripheral blood sTREM2 protein level of acute coronary syndrome patients was significantly higher than that of stable coronary heart disease group and non-coronary heart disease group (p<0.001) Figure 3 A).

[0087] ROC curve analysis as shown in Figure 3 B, the AUC of sTREM2 as an acute coronary syndrome biomarker was 0.714, and the 95% confidence interval was 0.657-0.771, indicating that sTREM2 had good predictive value for ACS, and the Cutoff value of sTREM2 for predicting ACS was 799.78 pg / ml, with a sensitivity of 78% and a specificity of 62.1%.

Claims

1. The application of a serum biomarker in the preparation of a diagnostic kit for vulnerable plaques, characterized in that... The serum biomarkers mentioned include sTREM2.

2. The application according to claim 1, characterized in that... The kit is used to detect the level of sTREM2 in peripheral blood, which serves as a basis for determining the appropriate level for imaging examinations.

3. The application of a serum biomarker in constructing a diagnostic model for vulnerable plaques, characterized in that... The serum biomarkers mentioned include sTREM2.

4. The application according to claim 3, characterized in that... The sTREM2 mentioned above includes information on its content in peripheral blood.

5. The application according to claim 3, characterized in that... The information on the content of sTREM2 in peripheral blood is used as a basis for determining the implementation of imaging examinations.

6. The application according to claim 3, characterized in that... The information output by the vulnerable plaque diagnostic model provides early warning for acute cardiovascular and cerebrovascular diseases and acute peripheral vascular diseases.

7. The application according to claim 6, characterized in that... Provides early warning for acute coronary syndrome.

8. A system for predicting disease risk, characterized in that, Includes the following units: The data acquisition unit acquires information on the sTREM2 content in the sample; The analysis unit takes the results detected by the data acquisition unit as input and analyzes them. as well as The assessment unit outputs information on the risk of developing vulnerable plaques for the individual corresponding to the sample, and provides further diagnostic and treatment recommendations.

9. The system according to claim 8, characterized in that, It also includes a detection unit, whose information is obtained from testing using a kit.

10. A detection device, characterized in that, The content of sTREM2 as described in claim 1 was detected.

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