Use of a biomarker in the preparation of a kit for a prognostic risk warning method for patients with acute ST-segment elevation myocardial infarction

Abstract

The present application discloses the use of a biomarker in the preparation of a kit for a prognostic risk warning method for patients with acute ST-segment elevation myocardial infarction. The biomarker includes HBP protein. By monitoring the change in the level of HBP protein, the present application can effectively evaluate whether a patient with acute ST-segment elevation myocardial infarction will have a poor prognosis within 30 days after PCI, so as to achieve early identification of high-risk patients and timely clinical intervention, improve the treatment response speed and effect, reduce the incidence of adverse cardiovascular events, and ultimately improve the prognosis of patients.

Description

Technical Field

[0001] This application belongs to the technical field of medical biology, and particularly relates to the application of a biomarker in the preparation of a kit for a prognostic risk warning method for patients with acute ST-segment elevation myocardial infarction and the kit thereof, specifically to the application of HBP protein in the prognostic risk warning of 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, where atherosclerotic plaque rupture and thrombosis lead to acute occlusion of the culprit vessel involved, resulting in myocardial ischemia and necrosis. It is one of the main diseases causing death and disability in cardiovascular diseases. Such diseases are highly prevalent and harmful. In the past decade or so, the country has actively carried out the construction of chest pain centers, improving people's awareness of myocardial infarction and the treatment ability for AMI, and greatly improving the prognosis. However, AMI patients still have a relatively high incidence of poor prognosis, including major cardiovascular events (MACCE) such as re-infarction, acute heart failure, cardiogenic shock, and stroke. Studies have found that 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. 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 occur acute heart failure, cardiogenic shock, cardiac rupture, stroke and other malignant cardiovascular events.

[0003] Neutrophils are the first to reach the infarcted area in the inflammatory response after acute myocardial infarction. Tamura et al. confirmed that the neutrophil count in white blood cells (WBC) is related to the left ventricular end-systolic diameter and left ventricular end-diastolic diameter.

[0004] In recent years, a novel inflammatory factor, heparin binding protein (HBP), has been discovered. It is synthesized and stored in corresponding positions by neutrophils. Once neutrophils are activated, a large amount of HBP is released, and it participates in various inflammatory processes as a pro-inflammatory mediator.

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

[0006] HBP has been proven to be able 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 indicates 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 relatively high risk of poor prognosis after the operation. Acute myocardial infarction patients continue to have a risk of recurrence and death within 1 year after discharge, especially within the first month after discharge, with the highest risk, accounting for 30% of the total MACCE. Therefore, early identification of high-risk patients after myocardial infarction and timely treatment and early intervention can help reduce the poor prognosis of these high-risk myocardial infarction patients.

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

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

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

[0010] The HBP is heparin-binding protein (HBP), also known as azurocidin or cationic antimicrobial protein of 37KDa (CAP37), which is a secreted granule protein located in the secretory vesicles and azurophilic granules of neutrophils (PMN). The sequence of HBP is publicly available, for example, obtained with the NCBI accession number NP001691 REGION: 27..248.

[0011] By adopting the above technical solution, the present application provides an application of a biomarker in preparing a kit for a prognostic risk warning method for patients with acute ST-segment elevation myocardial infarction. By monitoring the change in the level of HBP protein, the possibility of the deterioration of the patient's condition can be effectively evaluated, so as to realize the early identification of high-risk patients and timely clinical intervention, achieving the technical effects of improving the treatment response speed and effect, reducing the incidence of adverse cardiovascular events, and improving the prognosis of patients.

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

[0013] In summary, the present application provides a new method for evaluating prognostic risk in patients with acute ST-segment elevation myocardial infarction (STEMI) by monitoring the change in the level of HBP protein. This technical solution enables clinicians to effectively evaluate the possibility of the deterioration of the patient's condition, especially for those patients who still have a high risk after receiving percutaneous coronary intervention (PCI), enabling early identification and timely clinical intervention, thereby improving the treatment response speed and effect, reducing the incidence of adverse cardiovascular events, and ultimately improving the prognosis of patients. In addition, this study not only first used HBP as an independent biomarker that can be used for the prognostic evaluation of STEMI patients, but also revealed the close association between an elevated HBP level 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 3rd day after PCI was found to be able to better distinguish the risk of heart failure events within one month, providing valuable reference information for clinical practice.

[0014] The described prognosis risk warning method includes, after percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction, successively detecting the concentrations of the biomarker in the plasma of the patients with acute ST-segment elevation myocardial infarction at 24 hours, 48 hours, and 72 hours later, to determine whether there is a risk of poor prognosis after percutaneous coronary intervention in the patients with acute ST-segment elevation myocardial infarction; the poor prognosis includes one of the following cardiovascular events: reinfarction, acute heart failure, cardiogenic shock, and stroke.

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

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

[0017] The biomarker also includes hs-CRP.

[0018] By adopting the above technical solution, the present application can further enhance the evaluation accuracy of the prognosis risk of patients with acute ST-segment elevation myocardial infarction (STEMI). When HBP and hs-CRP are used in combination, especially on the 3rd day after emergency PCI (pPCI) treatment of STEMI patients, the predictive ability of HBP level in the statistical analysis for heart failure events has been improved, thus providing more accurate prognosis information for clinicians, helping to achieve early identification and timely intervention of high-risk patients, and improving the treatment effect and prognosis of patients.

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

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

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

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

[0023] Optionally, the in vitro sample is plasma.

[0024] Optionally, the biomarker is used in early warning of prognostic risk in patients with acute ST-segment elevation myocardial infarction by the following method:

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

[0026] S2. Sample handling: During plasma separation, care should be taken to avoid aspirating any leukocytes, as leukocytes can release high levels of HBP, which may interfere with 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). The instrument uses a dry-type fluorescent immunoassay.

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

[0029] By adopting the above-mentioned technical solution, 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 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 employing the aforementioned technical solution, the kit enables clinical laboratories to quickly and accurately measure HBP protein concentrations in patients, thereby helping to assess their risk of poor prognosis within 30 days after PCI. This standardized kit not only simplifies the testing process and improves efficiency, but also ensures the consistency and reliability of test results, providing clinicians with a powerful tool for early identification and timely intervention of high-risk patients, thereby improving treatment outcomes and prognosis.

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

[0033] 1. This application provides a biomarker for use 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 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 assess the prognostic risk of patients with acute ST-segment elevation myocardial infarction who receive emergency PCI 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 patient prognosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 This is a graph showing 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 a dose-response diagram of HBP and adverse in-hospital outcomes;

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

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

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

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

[0042] To make the objectives, technical solutions and advantages of this application more clear and understandable, the following further elaborates on this application in combination with embodiments. It should be understood that the specific embodiments described herein are merely used to explain this application and are not used to limit this application.

[0043] The following elaborates on the solution of this application in combination with the following specific embodiments. Unless otherwise specified, the raw materials used in the following embodiments are all from ordinary commercially available 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 to be included in this study must meet all of the following criteria:

[0046] (1) Written informed consent must be obtained before any evaluation;

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

[0048] (3) Diagnosed with spontaneous AMI according to the recognized definition of myocardial infarction*;

[0049] Spontaneous AMI is defined as: the presence of evidence of myocardial necrosis in a clinical setting, consistent with myocardial ischemia caused by a major coronary artery event. In these cases, spontaneous AMI must be diagnosed according to the following criteria:

[0050] An increase and / or decrease in myocardial enzymes (cardiac troponin, cTn or CK-MB) is detected, and at least one test value exceeds the 99th percentile of the upper limit of normal (URL) or the MI diagnostic threshold of the local laboratory, and at least one of the following evidences of myocardial ischemia is present:

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

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

[0053] (3) The presence of newly emerged pathological Q waves or left bundle branch block in the ECG (*If the patient's spontaneous MI is secondary to another medical condition, such as anemia, hypotension or arrhythmia, or if it is considered to be caused by coronary artery vasospasm and the coronary arteries are normal in the patient with spontaneous MI, they do not meet the eligibility criteria;

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

[0055] The exclusion criteria were as follows:

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

[0057] (1) 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, there were serious infections, trauma, blood system diseases, surgical operations, and 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 patients with STEMI who were admitted to Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, between August 2023 and April 2024 were enrolled. Five patients with a history of heart failure, 15 patients who developed cardiogenic shock within 24 hours of admission, one patient who had a stroke within the month before admission, and 15 patients with severe infection were excluded. A total of 215 patients with STEMI were included in this study.

[0065] Experimental testing:

[0066] Part I: Quantitative detection of HBP:

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

[0068] When separating plasma, care was taken not to aspirate any leukocytes to prevent them from releasing high levels of HBP. A 50 μl plasma sample was analyzed using a Jet-iStar 3000 fully automated immunoassay analyzer (Zhonghan Shengtai Biotechnology Co., Ltd., Zhejiang, China). HBP levels were measured by dry-type fluorescent immunoassay after 18 min of incubation.

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

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

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

[0072] (3) Pearson or Spearman correlation analysis was used for correlation analysis and scatter plots were drawn.

[0073] (4) Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were constructed to interpret each cut-off level of HBP.

[0074] (4) Cox regression analysis was used for related risk factor analysis, and the hazard ratio (HR) and 95% confidence interval (CI) were calculated.

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

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

[0077] (7) R (Bell Labs Version 4.0.0), GraphPad Prism 8.0.2 (GraphPad Software, San Diego, California, USA), and IBM SPSS (Statistics for Windows Version 22.0, IBM, Chicago, Illinois, USA) were used to analyze the data and draw graphs.

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

[0079] (1) In this study, the overall information of the participants can be seen in Table 1.

[0080] Table 1 - Table of the overall information of the participants

[0081]

[0082]

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

[0084] Fluctuation of HBP before and after pPCI in STEMI patients is as Figure 1 shown.

[0085] Figure 1 Result analysis: The level of HBP before pPCI in STEMI patients was significantly increased, being 43.43 (28.60, 71.96) ng / mL.

[0086] The HBP levels on the 1st, 2nd, and 3rd 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 summary, the HBP levels in STEMI patients before and within 72 hours after pPCI were both higher than the normal range.

[0088] Compared with before the operation, the HBP level decreased significantly after pPCI, and the result was statistically significant (p < 0.001).

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

[0090] The results of univariate and multivariate logistic regression showed (Table 2), and it can be seen from the detection data provided in Table 2 that the HBP levels on the 1st, 2nd, and 3rd days after the operation in STEMI patients, as well as the peak HBP level, were all independent risk factors for the occurrence 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 evaluated before PCI minus the HBP level on the 1st day after PCI;

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

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

[0097] Model 1 adjusted for age and gender;

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

[0099] ROC curve analysis showed that Figure 2 the HBP level on the 1st day after PCI in STEMI patients had a good discriminatory value for in-hospital adverse events in patients.

[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. The area under the curve was 0.78.

[0101] In addition, the HBP level on the 3rd day after pPCI in STEMI patients also has a good discriminatory value for in-hospital adverse events.

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

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

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

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

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

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

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

[0109] Uncorrected HR (CI) P Model 1 HR (% 95CI) P Model 2 HR (% 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 the 1st day after surgery 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 2nd day after surgery 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 the 3rd day after surgery 1.009(1.002～1.015) 0.011 1.009(1.002～1.015) 0.012 1.013(1.003～1.024) 0.012 HBP peak 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 is calculated as the level evaluated before pPCI minus the HBP level on the 1st day after pPCI;

[0111] Δ2HBP is calculated as the level evaluated before pPCI minus the HBP level on the 2nd day after pPCI;

[0112] Δ3HBP is calculated as the level evaluated before pPCI minus the HBP level on the 3rd day after pPCI;

[0113] Model 1 adjusts for age and gender;

[0114] Model 2 adjusts for age, gender, baseline BMI, smoking, history of hypertension, history of diabetes, history of dyslipidemia, KILLIP classification, WBC, hsCRP, and LVEF.

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

[0116] Figure 4 Result analysis: The HBP level of STEMI patients on the second day after surgery was less than 21.80 ng / mL. The risk of 30-day adverse events was not significant. After it was greater than 21.80 ng / mL, the risk of 30-day adverse events in patients increased with the increase of the HBP level.

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

[0118] (6) The Kaplan-Meier survival curve is as Figure 5 shown;

[0119] Figure 5 Result analysis: For STEMI patients in the highest quartile of HBP level on the second and third days after surgery, the incidence of 30-day adverse events was 12 times higher than that of patients in the lowest quartile. There was no statistically significant difference in the HBP level before surgery and on the first day after surgery. HBP is expected to become an effective evaluation tool for the long-term prognosis of myocardial infarction patients after discharge.

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

[0121] The correlation between the HBP level of STEMI patients before pPCI and on the first, second, and third days after surgery and the peak HBP level and the LVEF of echocardiogram one month after pPCI is as Figure 6 shown.

[0122] Figure 6 Result analysis: The HBP level on the first day after surgery and the peak HBP level of STEMI patients were negatively correlated with the ejection fraction at one-month follow-up 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 one-month follow-up after pPCI.

[0124] In addition, the results of univariate linear regression showed (see Table 4) that the HBP level on the first and second days after surgery and the peak HBP level of STEMI patients were negatively correlated with the LVEF at one-month follow-up after pPCI.

[0125] Table 4. Univariate linear regression analysis of the relationship between HBP levels and peak values 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 in STEMI patients on days 1, 2, and 3 after surgery 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 levels on day 3 after pPCI in STEMI patients were highly discriminatory for heart failure events. A cutoff 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 the c-statistic analysis.

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

[0140]

[0141]

[0142] In summary, the applicant found that the HBP levels in STEMI patients were higher than the normal values both before and within 72 hours after pPCI. Among them, before pPCI and 24 - 72 hours after pPCI, the HBP gradually decreased and was significantly lower than that before pPCI. The plasma HBP level can be used to evaluate the independent risk factors for adverse events during hospitalization and within 30 days after discharge.

[0143] In addition, HBP was negatively correlated with the cardiac function level of STEMI patients 1 month after pPCI. The higher the HBP level, the worse the cardiac function, which was an independent risk factor for heart failure events after myocardial infarction within 30 days.

[0144] The HBP level on the 3rd day after pPCI in STEMI patients combined with hs - CRP improved the predictive value for heart failure events within 1 month after the operation.

[0145] As an inflammatory marker, HBP has been mostly focused on the research of bacterial infection and sepsis in the past. Currently, few scholars at home and abroad have applied HBP to the assessment of myocardial injury in patients with acute myocardial infarction. This study first explored the dynamic change trend of HBP levels in STEMI patients before and within 72 hours after pPCI, and its relationship with the prognosis of myocardial infarction. It is also the largest sample size of HBP research related to STEMI so far. This study first showed that HBP can be independently used for the prognosis assessment of STEMI patients, whether it is in - hospital adverse events or recent poor prognosis, and first found that the increase in HBP level is closely related to the occurrence of heart failure after myocardial infarction, and can be used as an effective prediction tool for heart failure after myocardial infarction.

[0146] The above are only the preferred embodiments of this application and are not intended to limit this application. Any modifications, equivalent replacements, and improvements made within the principles of this application shall be included in the protection scope of this application.

Claims

1. Use of a reagent for detecting HBP protein in a plasma sample on the 3rd day after emergency percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction in the preparation of a kit for a prognostic risk warning method within 30 days after emergency percutaneous coronary intervention in such patients with acute ST-segment elevation myocardial infarction, characterized in that when the concentration of the HBP protein in the plasma of a patient with acute ST-segment elevation myocardial infarction on the 3rd day after emergency percutaneous coronary intervention is greater than 19.63 ng / ml, it is determined that there is a risk of poor prognosis within 30 days after discharge in the patient with acute ST-segment elevation myocardial infarction who has received emergency percutaneous coronary intervention.

2. The application according to claim 1, wherein It also includes a reagent for detecting hs-CRP.

3. The application according to claim 1, wherein The kit is used for detecting the change in HBP concentration in patients with acute ST-segment elevation myocardial infarction.

4. The application according to claim 3, wherein The change in HBP concentration is used as a warning indicator in the prognostic risk of patients with acute ST-segment elevation myocardial infarction.

5. The application according to claim 4, characterized in that, The prognostic risk includes one or a combined risk of re-infarction, acute heart failure, cardiogenic shock, and stroke.

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