Application of biomarker in preparation of kit for prognosis risk early warning method of patient with acute ST segment elevation type myocardial infarction

Abstract

The invention discloses an application of a biomarker in preparation of a kit for a prognosis risk early warning method of an acute ST segment elevation type myocardial infarction patient. The biomarker comprises an HBP (Hepatitis Binding Protein). By monitoring the change of the HBP protein level, whether a patient suffering from the acute ST segment elevation type myocardial infarction has poor prognosis within 30 days after a PCI operation can be effectively evaluated, so that early recognition and timely clinical intervention on high-risk patients are realized, the treatment response speed and effect are improved, the occurrence rate of adverse cardiovascular events is reduced, and the treatment effect of the patient suffering from the acute ST segment elevation type myocardial infarction is improved. And the prognosis of the patient is finally improved.

Description

Technical Field

[0001] The present application belongs to the field of medical biology technology, and in particular, relates to the use of a biomarker in the preparation of a kit for a method for early warning of prognosis risk in patients with acute ST-segment elevation myocardial infarction and the kit, and specifically relates to the use of HBP protein in early warning of prognosis risk in patients with acute ST-segment elevation myocardial infarction. Background Art

[0002] Acute myocardial infarction (AMI) is an acute and critical disease based on coronary atherosclerotic lesions. Atherosclerotic plaques rupture and thrombosis lead to acute occlusion of the affected culprit blood vessels, resulting in myocardial ischemia and necrosis. It is one of the main causes of death and disability among cardiovascular diseases. This type of disease is highly prevalent and harmful. In the past decade, the country has actively carried out the construction of chest pain centers, which has improved people's understanding of myocardial infarction and the ability to treat AMI, greatly improving the prognosis. However, AMI patients still have a high incidence of poor prognosis, including major cardiovascular events (MACCE) such as reinfarction, acute heart failure, cardiogenic shock, and stroke. Studies have found that the poor prognosis of AMI is closely related to ventricular remodeling. A series of ventricular remodeling processes can occur immediately after acute myocardial infarction, causing changes in cardiac structure and reduced cardiac function. The inflammatory response plays a key role in the process of ventricular remodeling. The more obvious the inflammatory response and ventricular remodeling after acute myocardial infarction, the more likely it is to have acute heart failure, cardiogenic shock, heart rupture, stroke and other malignant cardiovascular events.

[0003] In the inflammatory response after acute myocardial infarction, neutrophils are the first to arrive at the infarct area. Tamura et al. confirmed that the neutrophil count in WBC is correlated with the left ventricular end-systolic diameter and left ventricular end-diastolic diameter.

[0004] In recent years, a new type of inflammatory factor, heparin binding protein (HBP), has been discovered. It is synthesized by neutrophils and stored in corresponding locations. Once neutrophils are activated, they release a large amount of HBP, which participates in various inflammatory processes as an inflammatory mediator.

[0005] When HBP is rapidly secreted into the blood, it has the effect of chemotactic monocytes. Monocytes activated and chemotactic by HBP cause inflammatory responses, which play an important role in the formation and progression of atherosclerotic cardiovascular disease (ASCVD).

[0006] HBP has been shown to induce and promote the massive release of inflammatory mediators such as tumor necrosis factor-α (TNF-α) and interleukin 1 (IL-1), and the correlation between TNF-α, IL-1 and ASCVD has been fully confirmed by previous studies. This shows that there is a close connection between HBP and ASCVD. For patients with acute ST-segment elevation myocardial infarction (STEMI), even if they receive emergency PCI treatment, they still face a high risk of poor prognosis after surgery. Patients with acute myocardial infarction continue to have a risk of recurrence and death within 1 year after discharge, especially within the first month after discharge, when the risk is highest, accounting for 30% of the total MACCE. Therefore, early identification of high-risk patients after myocardial infarction, timely treatment and early intervention will help reduce the adverse prognosis of these high-risk myocardial infarction patients.

[0007] Although studies have shown that HBP concentrations in STEMI patients are closely related to their poor prognosis during hospitalization, and high levels of HBP indicate a poor prognosis, this association has not been widely verified, and whether HBP levels during hospitalization are related to adverse events within 1 month after discharge from myocardial infarction has never been confirmed. In view of this, it is crucial to find a biomarker that can accurately identify individuals with poor prognosis in the early stages of acute myocardial infarction, because this will help to achieve early identification and intensive treatment of patients at high risk of myocardial infarction, thereby improving the long-term survival rate of patients with myocardial infarction and improving the short- and long-term prognosis of patients with myocardial infarction. Summary of the invention

[0008] In view of this, the present application proposes the use of a biomarker in the preparation of a kit for the preparation of a prognostic risk warning method for patients with acute ST-segment elevation myocardial infarction, aiming to use HBP levels to effectively predict the possible deterioration of the condition of STEMI patients, ensure that clinical intervention measures can be taken in a timely manner, and ultimately achieve the purpose of improving the prognosis of such high-risk patients.

[0009] In a first aspect, the present application provides a use of a biomarker in the preparation of a kit for a method for early warning of prognosis risk in patients with acute ST-segment elevation myocardial infarction, wherein the biomarker includes HBP protein.

[0010] The HBP is heparin-binding protein (HBP), also known as azurocidin or 37KDa cationic antimicrobial protein (CAP37), which is a secretory granule protein located in the secretory vesicles and azuroic granules of neutrophils (PMN). The sequence of HBP is publicly available, for example, obtained under NCBI accession number NP001691REGION:27..248.

[0011] By adopting the above-mentioned technical scheme, the present application provides an application of a biomarker in the preparation of a kit for the preparation of a prognostic risk warning method for patients with acute ST-segment elevation myocardial infarction. By monitoring the changes in HBP protein levels, the possibility of worsening of the patient's condition can be effectively assessed, thereby achieving early identification of high-risk patients and timely clinical intervention, achieving the technical effect of improving the speed and effect of treatment response, reducing the incidence of adverse cardiovascular events and improving patient prognosis.

[0012] As an inflammatory marker previously used mainly to evaluate bacterial infection and sepsis, HBP was used for the first time in this study to evaluate myocardial injury in STEMI patients, and it is currently the largest sample size related to the prognosis of myocardial infarction. This study demonstrated for the first time that HBP can be used independently for the prognosis evaluation of STEMI patients, both in terms of adverse events during hospitalization and in the near term after discharge, and for the first time revealed the close association between elevated HBP levels and the occurrence of heart failure after myocardial infarction, indicating that HBP can be used as an effective tool to predict the occurrence of heart failure after myocardial infarction. The researchers of this application found that HBP levels on the 1st, 2nd, and 3rd days after STEMI patients underwent percutaneous coronary intervention (PCI) were independent risk factors for the risk of heart failure events within one month after PCI. Further studies have shown that the HBP level on the 3rd day after PCI in STEMI patients has a good discriminatory value for the occurrence of heart failure events in patients one month after discharge.

[0013] In summary, the present application provides a new method for assessing the prognostic risk in patients with acute ST-segment elevation myocardial infarction (STEMI) by monitoring changes in HBP protein levels. This technical solution enables clinicians to effectively assess the possibility of worsening of the patient's condition, especially for those patients who are still at high risk after percutaneous coronary intervention (PCI), and can achieve early identification and timely clinical intervention, thereby improving the response speed and effect of treatment, reducing the incidence of adverse cardiovascular events, and ultimately improving the patient's prognosis. In addition, this study not only used HBP as an independent marker for the prognosis assessment of STEMI patients for the first time, but also revealed the close association between elevated HBP levels and the occurrence of heart failure after myocardial infarction, indicating that HBP has potential value in predicting the occurrence of heart failure after myocardial infarction. In particular, the HBP level on the third day after PCI was found to be able to better distinguish the risk of heart failure events within one month, which provides valuable reference information for clinical practice.

[0014] The prognosis risk warning method includes detecting the concentration of the biomarker in the plasma of the patient with acute ST-segment elevation myocardial infarction 24 hours, 48 ​​hours and 72 hours after percutaneous coronary intervention, to determine whether the patient with acute ST-segment elevation myocardial infarction has a poor prognosis risk after percutaneous coronary intervention; the poor prognosis includes the occurrence of one of the following cardiovascular events: reinfarction, acute heart failure, cardiogenic shock and stroke.

[0015] By adopting the above-mentioned technical scheme, the present application can effectively evaluate the prognostic risk of patients after PCI, promptly identify high-risk patients who may have a poor prognosis, and provide a scientific basis for clinicians to take corresponding preventive and intervention measures, improve treatment effects, reduce the incidence of adverse cardiovascular events, and ultimately improve patient prognosis.

[0016] When the HBP protein concentration in the plasma of patients with acute ST-segment elevation myocardial infarction is detected to be greater than 19.6 ng / mL within 72 hours, it is determined that the patients with acute ST-segment elevation myocardial infarction who receive emergency PCI treatment have a poor prognosis risk within 30 days after discharge.

[0017] The biomarkers also include hs-CRP.

[0018] By adopting the above technical solution, this application can further enhance the accuracy of assessing the prognostic risk of patients with acute ST-segment elevation myocardial infarction (STEMI). When HBP is used in combination with hs-CRP, especially on the third day after STEMI patients received emergency PCI (pPCI) treatment, the predictive ability of HBP levels for heart failure events in statistical analysis is improved, thereby providing clinicians with more accurate prognostic information, helping to achieve early identification and timely intervention of high-risk patients, and improving patients' treatment effects and prognosis.

[0019] Optionally, the kit is used to detect changes in HBP concentration in patients with acute ST-segment elevation myocardial infarction.

[0020] Optionally, the change in HBP concentration serves as a warning indicator for the prognostic risk of patients with acute ST-segment elevation myocardial infarction.

[0021] Optionally, the prognostic risk includes one or a combined risk of reinfarction, acute heart failure, cardiogenic shock and stroke.

[0022] Optionally, the kit is used to detect changes in HBP concentration in patients with acute ST-segment elevation myocardial infarction by detecting in vitro samples of the patients.

[0023] Optionally, the ex vivo sample is plasma.

[0024] Optionally, the biomarker is used in early warning of the prognosis risk of patients with acute ST-segment elevation myocardial infarction, and the method is as follows:

[0025] S1. Sample collection: Use a test tube containing sodium citrate anticoagulant to collect plasma specimens from patients with acute ST-segment elevation myocardial infarction; the ratio of the sodium citrate anticoagulant to the plasma specimen is 1:9;

[0026] S2. Sample handling: During the separation of plasma, care should be taken to avoid aspirating any leukocytes, as leukocytes can release high levels of HBP, which may interfere with the test results.

[0027] S3. Detection instruments and methods: HBP levels were detected using the Jet-iStar 3000 fully automatic immunoassay analyzer (manufactured by Zhonghan Shengtai Biotechnology Co., Ltd., located in Zhejiang, China), which uses a dry fluorescent immunoassay;

[0028] S4. Operation procedure: Take 50 μl of the processed plasma sample in step S2 and add it to the Jet-iStar 3000 fully automatic immunoassay analyzer in step S3. Incubate for 18 minutes, after which the instrument will automatically detect and report the level of HBP.

[0029] By adopting the above-mentioned technical scheme, the present application can effectively evaluate the prognostic risk of patients with acute ST-segment elevation myocardial infarction who receive emergency PCI treatment within 30 days after discharge, thereby achieving early identification and timely clinical intervention of high-risk patients, improving the speed and effectiveness of treatment response, reducing the incidence of adverse cardiovascular events, and ultimately improving the patient's prognosis.

[0030] In a second aspect, the present application provides a kit for a method for early warning of prognosis risk in patients with acute ST-segment elevation myocardial infarction, wherein the kit comprises a reagent for extracting HBP protein and / or a reagent for detecting HBP protein.

[0031] By adopting the above technical solutions, the kit can support clinical laboratories to quickly and accurately measure the concentration of HBP protein in patients, thereby helping to assess the risk of poor prognosis within 30 days after PCI. This standardized kit not only simplifies the testing process and improves the testing efficiency, but also ensures the consistency and reliability of the test results, providing clinicians with a powerful tool to achieve early identification and timely intervention of high-risk patients, thereby improving the treatment effect and prognosis of patients.

[0032] In summary, the present application includes at least one of the following beneficial technical effects:

[0033] 1. This application provides a biomarker for use in a kit for preparing a prognostic risk warning method for patients with acute ST-segment elevation myocardial infarction by monitoring changes in HBP protein levels. This technical solution enables clinicians to effectively assess the possibility of worsening of the patient's condition, especially for those patients who are still at high risk after percutaneous coronary intervention (PCI), and can achieve early identification and timely clinical intervention, thereby improving the response speed and effect of treatment, reducing the incidence of adverse cardiovascular events, and ultimately improving the patient's prognosis. In addition, this study not only used HBP as an independent marker for the prognosis assessment of STEMI patients for the first time, but also revealed a close association between elevated HBP levels and the occurrence of heart failure after myocardial infarction, indicating that HBP has potential value in predicting the occurrence of heart failure after myocardial infarction. In particular, the HBP level on the third day after PCI was found to be able to better distinguish the risk of heart failure events within one month, which provides valuable reference information for clinical practice.

[0034] 2. This application can effectively evaluate the prognostic risk of patients with acute ST-segment elevation myocardial infarction who receive emergency PCI treatment within 30 days after discharge, thereby achieving early identification and timely clinical intervention of high-risk patients, improving the speed and effectiveness of treatment response, reducing the incidence of adverse cardiovascular events, and ultimately improving the prognosis of patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 This is a graph of HBP fluctuations before and after pPCI in STEMI patients in this application;

[0036] Figure 2 This is the ROC curve analysis diagram for STEMI patients;

[0037] Figure 3 This is the dose-response relationship diagram between HBP and adverse in-hospital outcomes;

[0038] Figure 4 This is the dose-response relationship between HBP and adverse outcomes 30 days after discharge;

[0039] Figure 5 It is the Kaplan-Meier survival curve;

[0040] Figure 6 This is the correlation diagram between the peak HBP level before PCI and on the 1st, 2nd, and 3rd days after PCI and the echocardiographic LVEF of STEMI patients 1 month after PCI;

[0041] Figure 7 This is the ROC curve analysis diagram. DETAILED DESCRIPTION

[0042] In order to make the purpose, technical solution and advantages of the present application more clear, the present application is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described here are only used to explain the present application and are not used to limit the present application.

[0043] The scheme of the present application is described below in conjunction with the following specific examples. Unless otherwise specified, the raw materials used in the following examples are all from common commercial products, and the devices or equipment used are all purchased from conventional market sales channels.

[0044] The inclusion criteria are as follows:

[0045] Patients eligible for this study must meet all of the following criteria:

[0046] (1) Written informed consent must be obtained before any assessment is conducted;

[0047] (2) Male or female patients aged 18 or above;

[0048] (3) diagnosed as spontaneous AMI according to the generally accepted definition of myocardial infarction*;

[0049] Spontaneous AMI is defined as a clinical setting in which there is evidence of myocardial necrosis consistent with myocardial ischemia resulting from a major coronary event. In these circumstances, the following criteria must be followed to diagnose spontaneous AMI:

[0050] Elevated and / or decreased cardiac enzymes (cardiac troponin, cTn, or CK-MB) were detected, with at least one value exceeding the 99th percentile of the upper limit of normal (URL) or the local laboratory's MI diagnostic cutoff value, and at least one of the following evidence of myocardial ischemia:

[0051] (1) Ischemic discomfort or other ischemic symptoms;

[0052] (2) ECG features of STEMI, including new or presumed new significant ST-T changes;

[0053] (3) the presence of new pathological Q waves or left bundle branch block on ECG (*Patients whose spontaneous MI was secondary to another medical illness, such as anemia, hypotension, or arrhythmia, or whose spontaneous MI was thought to be caused by coronary vasospasm and whose coronary arteries were normal, were not eligible;

[0054] Patients who had clinical manifestations related to Takotsubo cardiomyopathy also did not meet the inclusion criteria (this MI visit refers to the time when the patient visited the emergency room / emergency department (ER / ED), was admitted to the intensive care unit / cardiovascular care unit (CCU) or hospital ward, etc., for treatment of this MI).

[0055] The exclusion criteria were as follows:

[0056] Patients who met any of the following criteria were not eligible for this study:

[0057] (1) Have a known history of chronic heart failure;

[0058] (2) cardiogenic shock occurred within 24 hours before enrollment;

[0059] (3) persistent clinical heart failure before enrollment;

[0060] (4) stroke or transient ischemic attack within one month before enrollment;

[0061] (5) Before enrollment, the patient had severe infection, trauma, blood system disease, surgical operation, or other diseases that the researchers assessed might interfere with HBP measurement.

[0062] The research subjects are as follows:

[0063] This study lasted 125 days and was approved by the Ethics Committee of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (2018-183), and informed consent was obtained from the participants.

[0064] A total of 251 STEMI patients who visited Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from August 2023 to April 2024 were included. Five patients with a history of heart failure, 15 patients with cardiogenic shock within 24 hours of admission, one patient with stroke within one month before admission, and 15 patients with severe infection were excluded. Finally, 215 STEMI patients were included in this study.

[0065] Experimental testing:

[0066] Part I: HBP quantitative detection:

[0067] Sodium citrate anticoagulated (1:9) plasma specimens were used for testing.

[0068] When separating plasma, be careful not to inhale any leukocytes to prevent them from releasing high levels of HBP. A 50 μl plasma sample was tested using a Jet-iStar3000 fully automatic immunoassay analyzer (Zhonghan Shengtai Biotechnology Co., Ltd., Zhejiang, China), and the HBP level was measured after incubation for 18 min (dry fluorescent immunoassay).

[0069] The statistical analysis related to this application includes the following:

[0070] (1) Continuous variables that conform to normal distribution were expressed as mean ± standard deviation, and continuous variables that do not conform to normal distribution were expressed as median (25% quantile, 75% quantile).

[0071] (2) Categorical variables were expressed as frequency (percentage).

[0072] (3) Correlation analysis was performed using Pearson or Spearman correlation analysis and a scatter plot was drawn;

[0073] (4) construct receiver operating characteristic (ROC) curves and area under the curve (AUC) to illustrate various cutoff levels of HBP;

[0074] (4) Cox regression analysis was used to analyze relevant risk factors and calculate the hazard ratio (HR) and 95% confidence interval (CI).

[0075] (5) Kaplan-Meier survival analysis was performed.

[0076] (6) P < 0.05 was considered statistically significant.

[0077] (7) Data were analyzed and graphs were drawn using R (Bell Laboratories version 4.0.0), GraphPad Prism 8.0.2 (GraphPad Software, San Diego, CA, USA), and IBM SPSS (Statistics for Windows Version 22.0, IBM, Chicago, IL, USA).

[0078] Part II: The overall information of the participants is as follows:

[0079] (1) The overall information of the participants in this study is shown in Table 1;

[0080] Table 1 - Participant general information

[0081]

[0082]

[0083] HBP fluctuations before and after pPCI in STEMI patients:

[0084] HBP fluctuations before and after pPCI in STEMI patients Figure 1 shown.

[0085] Figure 1 Results and analysis: The HBP level of STEMI patients before pPCI was significantly increased, reaching 43.43 (28.60, 71.96) ng / mL;

[0086] The HBP levels at 1, 2, and 3 days after pPCI were 21.24 (11.10, 45.21) ng / mL, 21.86 (13.49, 45.84) ng / mL, and 19.54 (12.34, 32.28) ng / mL, respectively.

[0087] In conclusion, the HBP levels of STEMI patients before and 72 hours after pPCI were higher than the normal range.

[0088] Compared with preoperative level, HBP level decreased significantly after pPCI, and the results were statistically significant (p<0.001).

[0089] (2) The predictive value of HBP for in-hospital adverse events in STEMI patients:

[0090] The results of univariate and multivariate logistic regression showed (Table 2). From the test data provided in Table 2, it can be seen that the HBP levels of STEMI patients on the 1st, 2nd, and 3rd days after surgery, as well as the peak HBP level, are independent risk factors for the risk of in-hospital adverse events in STEMI patients.

[0091] Table 2. Logistic univariate and multivariate analysis of the predictive value of HBP for in-hospital events

[0092]

[0093]

[0094] Δ1HBP was calculated as the level assessed before PCI minus the HBP level on day 1 after PCI;

[0095] Δ2HBP was calculated as the level assessed before PCI minus the HBP level on day 2 after PCI;

[0096] Δ3HBP was calculated as the level assessed before PCI minus the HBP level on day 3 after PCI;

[0097] Model 1 adjusted for age and sex;

[0098] Model 2 was adjusted for age, sex, baseline BMI, smoking, history of hypertension, history of diabetes, history of dyslipidemia, KILLIP grade, WBC, hsCRP, and LVEF.

[0099] ROC curve analysis Figure 2 As shown in the results, HBP level on the first day after PCI in STEMI patients has a good value in distinguishing patients' in-hospital adverse events.

[0100] The cut-off level >33.36 ng / mL had a sensitivity of 72.4% and a specificity of 79.2% in predicting in-hospital adverse events, with an area under the curve of 0.78.

[0101] In addition, the HBP level on the third day after pPCI in STEMI patients also has a good value in distinguishing patients' in-hospital adverse events.

[0102] The cut-off level >29.12 ng / mL had 78.0% sensitivity and 61.9% specificity in predicting in-hospital adverse events.

[0103] (3) Further explore the dose-response relationship between HBP and adverse in-hospital outcomes, such as Figure 3 shown.

[0104] Figure 3 Result analysis: The inventors found that when the HBP level of STEMI patients was less than 19.6 ng / mL on the third day after surgery, the risk of in-hospital adverse events was not significant. When the HBP level was greater than 19.6 ng / mL, the risk of in-hospital adverse events increased significantly with the increase of HBP level.

[0105] (4) The predictive value of HBP for adverse events in STEMI patients within 30 days after discharge;

[0106] The results of univariate and multivariate COX regression showed that HBP levels on the 1st, 2nd, and 3rd days after surgery, as well as HBP peak levels, were independent risk factors for the risk of adverse events in STEMI patients during the 30-day follow-up (independent of hsCRP, LVEF, etc.).

[0107] The COX univariate and multivariate analysis of the predictive value of HBP for 30-day adverse events in STEMI patients is shown in Table 3.

[0108] Table 3-COX univariate and multivariate analysis of the predictive value of HBP for 30-day adverse events in STEMI patients

[0109] Unadjusted HR (CI) P Model 1HR (%95CI) P Model 2HR (%95CI) P Preoperative HBP 1.003(0.997～1.010) 0.304 1.005(0.998～1.011) 0.178 1.023(0.997～1.044) 0.350 HBP on postoperative day 1 1.007(1.001～1.013) 0.024 1.005(0.999～1.011) 0.130 1.009(1.001～1.018) 0.035 HBP on the second postoperative day 1.006(1.002～1.011) 0.007 1.007(1.002～1.012) 0.006 1.008(1.001～1.015) 0.018 HBP on postoperative day 3 1.009(1.002～1.015) 0.011 1.009(1.002～1.015) 0.012 1.013(1.003～1.024) 0.012 Peak HBP 1.005(1.001～1.009) 0.016 1.005(1.001～1.009) 0.016 1.008(1.003～1.013) 0.002 Δ1HBP 1.005(0.998～1.011) 0.194 1.007(1.000～1.014) 0.050 1.121(0.969～1.297) 0.123 Δ2HBP 1.005(0.997～1.013) 0.216 1.007(0.998～1.016) 0.152 1.149(0.841～1.569) 0.384 Δ3HBP 1.004(0.995～1.014) 0.375 1.007(0.996～1.019) 0.222 1.209(0.996～1.447) 0.380

[0110] Δ1HBP was calculated as the level assessed before pPCI minus the HBP level on day 1 after pPCI;

[0111] Δ2HBP was calculated as the level assessed before pPCI minus the HBP level on day 2 after pPCI;

[0112] Δ3HBP was calculated as the level assessed before pPCI minus the HBP level on day 3 after pPCI;

[0113] Model 1 adjusted for age and sex;

[0114] Model 2 was adjusted for age, sex, baseline BMI, smoking, history of hypertension, history of diabetes, history of dyslipidemia, KILLIP grade, WBC, hsCRP, and LVEF.

[0115] (5) Further explore the dose-response relationship between HBP and adverse outcomes 30 days after discharge, such as Figure 4 As shown;

[0116] Figure 4 Results: The HBP level of STEMI patients was less than 21.80 ng / mL on the second day after surgery. The risk of adverse events within 30 days was not significant. When the HBP level was greater than 21.80 ng / mL, the risk of adverse events within 30 days increased with the increase of HBP level.

[0117] When the HBP level of STEMI patients was less than 19.63 ng / mL on the third day after surgery, the risk of 30-day adverse events was not significant. When the HBP level was greater than 19.63 ng / mL, the risk of 30-day adverse events increased with the increase of HBP level.

[0118] (6) Kaplan-Meier survival curve Figure 5 As shown;

[0119] Figure 5 Results: The incidence of adverse events in STEMI patients with the highest quartile of HBP on the second and third days after surgery was 12 times higher than that in the lowest quartile, and there was no statistical difference in HBP levels before and after surgery. HBP is expected to become an effective assessment tool for the long-term prognosis of patients with myocardial infarction after discharge.

[0120] (7) Correlation between HBP and left ventricular ejection fraction:

[0121] Correlation between HBP peak level before pPCI and 1, 2, 3 days after pPCI and LVEF on echocardiography 1 month after pPCI in STEMI patients Figure 6 shown.

[0122] Figure 6 Results: The HBP level and HBP peak value on the first day after STEMI surgery were negatively correlated with the ejection fraction at 1 month after pPCI (r=-0.22, p=0.017);

[0123] The HBP level on the second day after surgery (r=-0.35, p=0.0003) and the peak HBP level (r=-0.23, p=0.021) were negatively correlated with the LVEF at 1 month after pPCI.

[0124] In addition, the results of univariate linear regression showed (see Table 4) that the HBP levels and HBP peak values ​​on the 1st and 2nd days after STEMI surgery were negatively correlated with LVEF at 1 month after pPCI.

[0125] Table 4. Univariate linear regression analysis of the relationship between HBP level and peak value during hospitalization and left ventricular ejection fraction 1 day and 1 month after pPCI in STEMI patients

[0126]

[0127]

[0128] Δ1HBP was calculated as the level assessed before pPCI minus the HBP level on day 1 after pPCI;

[0129] Δ2HBP was calculated as the level assessed before pPCI minus the HBP level on day 2 after pPCI;

[0130] Δ3HBP was calculated as the level assessed before pPCI minus the HBP level on day 3 after pPCI;

[0131] The predictive value of HBP in the occurrence of heart failure in patients with STEMI after myocardial infarction

[0132] The results of COX regression showed (see Table 5) that HBP levels on the 1st, 2nd, and 3rd days after surgery in STEMI patients were independent risk factors for the risk of heart failure events during follow-up after PCI.

[0133] Table 5. COX univariate analysis of the predictive value of HBP for the occurrence of heart failure in STEMI patients within 30 days after discharge

[0134]

[0135] (8) In addition, ROC curve analysis Figure 7 As shown;

[0136] Figure 7 Results: HBP level on the third day after pPCI in STEMI patients had a good value in distinguishing heart failure events. The cut-off level of 20.69 ng / mL had a sensitivity of 58.8% and a specificity of 85.0% in predicting in-hospital adverse events, with an AUC of 0.75.

[0137] (9) The predictive value of HBP combined with hs-CRP for heart failure events

[0138] As shown in Table 6 , when used in combination with hs-CRP, HBP levels on day 3 after pPCI in STEMI patients provided improved prediction of incident HF in c-statistical analysis.

[0139] Table 6-Accuracy of cTnI, hs-CRP and HBP in predicting the risk of heart failure in STEMI patients

[0140]

[0141]

[0142] In summary, the applicant found that the HBP levels of STEMI patients were higher than normal before and within 72 hours after pPCI. Before and 24-72 hours after pPCI, HBP gradually decreased, significantly lower than before the operation. The plasma HBP level can be used to evaluate the independent risk factor for adverse events in the hospital and 30 days after discharge.

[0143] In addition, HBP was negatively correlated with the cardiac function level of STEMI patients one month after pPCI. The higher the HBP level, the worse the cardiac function. It is an independent risk factor for heart failure events after myocardial infarction within 30 days.

[0144] The HBP level combined with hs-CRP on the third day after pPCI in STEMI patients improved the predictive value of heart failure events one month after surgery.

[0145] As an inflammatory marker, HBP has previously focused on research on bacterial infection and sepsis. At present, few scholars at home and abroad have applied HBP to the assessment of myocardial injury in patients with acute myocardial infarction. This study explored for the first time the dynamic changes in HBP levels within 72 hours before and after pPCI in STEMI patients, and its relationship with the prognosis of myocardial infarction. It is also the largest HBP research related to STEMI with a large sample size. This study showed for the first time that HBP can be used independently to assess the prognosis of STEMI patients, whether it is in-hospital adverse events or short-term adverse prognosis. It was also the first time that it was found that increased HBP levels were closely related to the occurrence of heart failure after myocardial infarction, and can be used as an effective predictive tool for heart failure after myocardial infarction.

[0146] The above description is only a preferred embodiment of the present application and is not intended to limit the present application. Any modifications, equivalent substitutions and improvements made within the principles of the present application should be included in the protection scope of the present application.

Claims

1. Use of a biomarker in the preparation of a kit for a method for early warning of prognosis risk in patients with acute ST-segment elevation myocardial infarction, characterized in that: The biomarkers include HBP protein.

2. The use according to claim 1, characterized in that: The biomarkers also include hs-CRP.

3. The use according to claim 1, characterized in that: The kit is used to detect the change of HBP concentration in patients with acute ST-segment elevation myocardial infarction.

4. The use according to claim 3, characterized in that: The HBP concentration change serves as a warning indicator for the prognostic risk of patients with acute ST-segment elevation myocardial infarction.

5. The use according to claim 4, characterized in that: The prognostic risks include one or a combination of risks of reinfarction, acute heart failure, cardiogenic shock and stroke.

6. The use according to claim 3, characterized in that: The kit is used for detecting the change of HBP concentration in patients with acute ST-segment elevation myocardial infarction by detecting the in vitro samples of the patients.

7. The use according to claim 6, characterized in that: The ex vivo sample is plasma.

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