Use of biomarker in preparation of test kit for prognostic risk warning method for patients with acute st-segment elevation myocardial infarction

Abstract

The present application discloses a use of a biomarker in the preparation of a test kit for a prognostic risk warning method for patients with acute ST-segment elevation myocardial infarction. The biomarker comprises an HBP protein. By means of monitoring changes in HBP protein levels, the present application can effectively evaluate whether a patient with acute ST-segment elevation myocardial infarction will experience an adverse prognosis within 30 days after PCI, thereby enabling early identification of high-risk patients and timely clinical intervention, improving treatment response speed and effectiveness, reducing the incidence of adverse cardiovascular events, and ultimately improving patient prognosis.

Description

Application of a biomarker in the preparation of a kit for a prognostic risk prediction method for patients with acute ST-segment elevation myocardial infarction Technical Field

[0001] This application belongs to the field of medical biology technology, and in particular 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 involving the application of HBP protein in the prognostic risk warning of patients with acute ST-segment elevation myocardial infarction. Background Technology

[0002] Acute myocardial infarction (AMI) is a critical and life-threatening disease caused by coronary atherosclerosis, resulting in the rupture of atherosclerotic plaques, thrombosis, and acute occlusion of the culprit vessel, leading to myocardial ischemia and necrosis. It is one of the leading causes of death and disability among cardiovascular diseases. This disease is highly prevalent and poses significant risks. In the past decade, the country has actively promoted the construction of chest pain centers, raising public awareness of myocardial infarction and improving the treatment capacity for AMI, greatly improving prognosis. However, AMI patients still have a high rate of poor prognosis, including re-infarction, acute heart failure, cardiogenic shock, stroke, and other major cardiovascular events (MACCE). Studies have found that poor prognosis in 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 decreased cardiac function. Inflammation plays a crucial role in ventricular remodeling. The more pronounced the inflammatory response and ventricular remodeling after acute myocardial infarction, the more likely one is to develop malignant cardiovascular events such as acute heart failure, cardiogenic shock, cardiac rupture, and stroke.

[0003] Neutrophils are the first cells to reach the infarct area in the inflammatory response following acute myocardial infarction. Tamura et al. confirmed that the neutrophil count in WBCs is correlated with the left ventricular end-systolic diameter and left ventricular end-diastolic diameter.

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

[0005] When HBP is rapidly secreted into the bloodstream, it has a chemotactic effect on monocytes. The inflammatory response caused by HBP-activated and chemotacted monocytes plays an important role in the formation and progression of atherosclerotic cardiovascular disease (ASCVD).

[0006] Hemorrhage-induced blood flow (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 well-established in previous studies. This indicates a close link between HBP and ASCVD. For patients with acute ST-segment elevation myocardial infarction (STEMI), even with emergency PCI, they still face a high risk of poor prognosis post-procedure. Patients with acute myocardial infarction have a persistent risk of recurrence and death within one year of discharge, especially in the first month after discharge, accounting for 30% of 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 patients.

[0007] Although previous studies have shown a strong correlation between hemoglobin (HBP) levels in STEMI patients and poor prognosis during hospitalization, with high HBP levels indicating a poorer outcome, this association has not been widely validated. Furthermore, the correlation between in-hospital HBP levels and adverse events within one month of discharge for myocardial infarction patients has never been confirmed. Therefore, identifying a biomarker that can accurately identify individuals with poor prognoses in the early stages of acute myocardial infarction is crucial. This would facilitate early identification and intensive treatment of high-risk patients, thereby improving long-term survival and short- and long-term outcomes for myocardial infarction patients. Summary of the Invention

[0008] In view of this, this application proposes 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. The aim is to effectively predict the possible deterioration of STEMI patients by utilizing HBP levels, ensuring timely clinical intervention, and ultimately improving the prognosis of these high-risk patients.

[0009] In a first aspect, this application provides 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, wherein the biomarker includes HBP protein.

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

[0011] By adopting the above technical solution, this application provides 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. By monitoring changes in HBP protein levels, the possibility of patient condition deterioration can be effectively assessed, thereby achieving early identification and timely clinical intervention for high-risk patients, and achieving the technical effects of improving treatment response speed and effectiveness, reducing the incidence of adverse cardiovascular events, and improving patient prognosis.

[0012] As an inflammatory marker previously primarily used to assess bacterial infection and sepsis, hemoglobin (HBP) was used for the first time in this study to assess myocardial injury in STEMI patients, representing the largest sample size to date in a prognostic study of myocardial infarction. This study is the first to demonstrate that HBP can be used independently for prognostic assessment in STEMI patients, both in terms of adverse events during hospitalization and short-term adverse events after discharge. Furthermore, it reveals for the first time a close association between elevated HBP levels and the occurrence of heart failure after myocardial infarction, indicating that HBP can serve as an effective tool for predicting the occurrence of heart failure after myocardial infarction. The researchers in this application found that HBP levels on days 1, 2, and 3 after percutaneous coronary intervention (PCI) in STEMI patients were an independent risk factor for heart failure events one month post-PCI. Further research showed that HBP levels on day 3 after PCI in STEMI patients have good discriminatory value in predicting the occurrence of heart failure events one month after discharge.

[0013] In summary, this application provides a novel method for assessing prognostic risk in patients with acute ST-segment elevation myocardial infarction (STEMI) by monitoring changes in HBP protein levels. This technique enables clinicians to effectively assess the likelihood of patient deterioration, particularly for those who remain at high risk after percutaneous coronary intervention (PCI). It allows for early identification and timely clinical intervention, thereby improving treatment response and effectiveness, reducing the incidence of adverse cardiovascular events, and ultimately improving patient prognosis. Furthermore, this study not only establishes HBP as an independent biomarker for prognostic assessment in STEMI patients for the first time but also reveals a close association between elevated HBP levels and the occurrence of post-infarction heart failure, indicating the potential value of HBP in predicting post-infarction heart failure. In particular, HBP levels on day 3 after PCI were found to effectively differentiate the risk of heart failure events within one month, providing valuable reference information for clinical practice.

[0014] The prognostic risk warning method includes, after percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI), sequentially detecting the concentrations of the biomarkers in the plasma of these patients at 24 hours, 48 ​​hours, and 72 hours to determine whether there is a risk of poor prognosis after PCI in these patients. The poor prognosis includes the occurrence of one of the following cardiovascular events: re-infarction, acute heart failure, cardiogenic shock, and stroke.

[0015] By adopting the above-mentioned technical solution, this application can effectively assess the prognostic risk of patients after PCI, identify high-risk patients who may have poor prognosis in a timely manner, and provide clinicians with scientific basis to take corresponding preventive and intervention measures, improve treatment effects, reduce the incidence of adverse cardiovascular events, and ultimately improve the prognosis of patients.

[0016] If the concentration of HBP protein in the plasma of a patient with acute ST-segment elevation myocardial infarction is greater than 19.6 ng / mL within 72 hours, the patient is considered to have a poor prognosis within 30 days after discharge from the hospital after undergoing emergency PCI.

[0017] The biomarkers also include hs-CRP.

[0018] By adopting the above-mentioned technical solution, this application can further enhance the accuracy of prognostic risk assessment for patients with acute ST-segment elevation myocardial infarction (STEMI). When HBP is used in combination with hs-CRP, especially on day 3 after STEMI patients undergo emergency PCI (pPCI), the predictive ability of HBP levels for heart failure events is improved in statistical analysis, thereby providing clinicians with more accurate prognostic information, helping to achieve early identification and timely intervention of high-risk patients, and improving patient treatment outcomes 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 can be used as an early warning indicator in the prognostic risk of patients with acute ST-segment elevation myocardial infarction.

[0021] Optionally, the prognostic risks include one or a combination of risks of re-infarction, acute heart failure, cardiogenic shock, and stroke.

[0022] Optionally, the kit can be used to detect changes in HBP concentration in patients with acute ST-segment elevation myocardial infarction by detecting ex vivo samples from the patients.

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

[0024] Optionally, the application of the biomarker in prognostic risk prediction for patients with acute ST-segment elevation myocardial infarction is carried out as follows:

[0025] S1. Sample Collection: Plasma samples from patients with acute ST-segment elevation myocardial infarction were collected using test tubes containing sodium citrate anticoagulant; the ratio of sodium citrate anticoagulant to plasma sample was 1:9.

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

[0027] S3. Detection Instruments and Methods: The Jet-iStar 3000 fully automated immunoassay analyzer (manufactured by Zhonghan Shengtai Biotechnology Co., Ltd., located in Zhejiang, China) was used to detect HBP levels. The instrument uses dry fluorescence immunoassay for detection.

[0028] S4. Operating procedure: Take 50 microliters (μl) of the plasma sample processed in step S2 and add it to the Jet-iStar 3000 fully automated 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 technical solution, this application can effectively assess the prognostic risk of patients with acute ST-segment elevation myocardial infarction who undergo emergency PCI treatment within 30 days after discharge, thereby enabling early identification and timely clinical intervention of high-risk patients, improving treatment response speed and effectiveness, reducing the incidence of adverse cardiovascular events, and ultimately improving patient prognosis.

[0030] Secondly, this application provides a kit for a prognostic risk warning method for patients with acute ST-segment elevation myocardial infarction, the kit comprising reagents for extracting HBP protein and / or reagents for detecting HBP protein.

[0031] By employing the above-described technical solution, this kit enables clinical laboratories to rapidly and accurately determine 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 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, ultimately 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 an application of a biomarker, HBP, in the preparation of a kit for predicting prognostic risk in patients with acute ST-segment elevation myocardial infarction (STEMI) by monitoring changes in HBP protein levels. This technique enables clinicians to effectively assess the likelihood of patient deterioration, particularly for those at high risk after percutaneous coronary intervention (PCI), allowing for early identification and timely clinical intervention. This improves treatment response and effectiveness, reduces the incidence of adverse cardiovascular events, and ultimately improves patient prognosis. Furthermore, this study not only establishes HBP as an independent biomarker for prognostic assessment in STEMI patients for the first time but also reveals a close association between elevated HBP levels and the occurrence of heart failure after myocardial infarction, indicating the potential value of HBP in predicting post-heart failure. In particular, HBP levels on day 3 after PCI were found to effectively differentiate the risk of heart failure events within one month, providing 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 undergo emergency PCI treatment within 30 days after discharge, thereby enabling early identification and timely clinical intervention of high-risk patients, improving treatment response speed and effectiveness, reducing the incidence of adverse cardiovascular events, and ultimately improving patient prognosis. Attached Figure Description

[0035] Figure 1 shows the HBP fluctuations before and after pPCI in STEMI patients in this application.

[0036] Figure 2 shows the ROC curve analysis of STEMI patients;

[0037] Figure 3 shows the dose-response relationship between HBP and adverse hospital outcomes.

[0038] Figure 4 shows the dose-response relationship between HBP and adverse outcomes 30 days after discharge.

[0039] Figure 5 shows the Kaplan-Meier survival curves;

[0040] Figure 6 shows the correlation between peak HBP levels and echocardiographic LVEF in STEMI patients before PCI and on days 1, 2, and 3 after PCI, and one month after PCI.

[0041] Figure 7 shows the ROC curve analysis. Detailed Implementation

[0042] To make the objectives, technical solutions, and advantages of this application clearer, the following detailed description is provided in conjunction with embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.

[0043] The solution of this application will be described below with reference to the following specific embodiments. Unless otherwise specified, the raw materials used in the following embodiments are all from commercially available products, and the devices or equipment used are all purchased from conventional market sales channels.

[0044] The selection criteria are as follows:

[0045] Patients eligible to enroll in 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 older;

[0048] (3) Based on the generally accepted definition of myocardial infarction*, the diagnosis is spontaneous AMI;

[0049] Spontaneous acute myocardial infarction (AMI) is defined as clinical evidence of myocardial necrosis consistent with myocardial ischemia resulting from a major coronary event. In these cases, spontaneous AMI must be diagnosed according to the following criteria:

[0050] An elevated and / or decreased cardiac enzyme (cardiac troponin, cTn, or CK-MB) was detected, with at least one value exceeding the 99th percentile of the upper limit of normal (URL) or the local laboratory's diagnostic threshold for MI, and at least one of the following pieces of evidence of myocardial ischemia was present:

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

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

[0053] (3) The presence of newly appearing pathological Q waves or left bundle branch block on ECG (*If the patient’s spontaneous MI is secondary to another medical condition, such as anemia, hypotension or arrhythmia, or if the spontaneous MI is thought to be caused by coronary artery spasm and the coronary arteries are normal, the patient is not eligible.

[0054] Patients who presented with clinical manifestations associated with Takotsubo cardiomyopathy did not meet the inclusion criteria (this MI visit refers to the time during which the patient visited the emergency room / emergency department (ER / ED), was admitted to the intensive care unit / cardiovascular care unit (CCU), or was treated in a hospital ward, etc.).

[0055] The exclusion criteria are as follows:

[0056] Patients meeting any of the following criteria are not eligible for enrollment in this study:

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

[0058] (2) Had cardiogenic shock within 24 hours prior to enrollment;

[0059] (3) Persistent clinical heart failure prior to enrollment;

[0060] (4) Stroke or transient ischemic attack occurred within one month prior to enrollment;

[0061] (5) Before enrollment, the researchers assessed that the patient had serious infections, trauma, hematological diseases, surgery, or other diseases that might interfere with HBP measurement.

[0062] The subjects of the study are as follows:

[0063] This study lasted 125 days, 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 with Shanghai Jiao Tong University School of Medicine between August 2023 and April 2024 were included in this study. 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 one month prior to admission, and 15 patients with severe infections were excluded. Ultimately, 215 STEMI patients were included in this study.

[0065] Experimental testing:

[0066] Part 1: Quantitative Detection of HBP

[0067] The test was performed using plasma samples anticoagulated with sodium citrate (1:9).

[0068] During plasma separation, care must be taken to avoid aspirating any leukocytes to prevent the release of high levels of hemoglobin (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 after 18 minutes of incubation using a dry fluorescence immunoassay.

[0069] The statistical analyses relating to this application include the following:

[0070] (1) For continuous variables that conform to a normal distribution, the mean ± standard deviation is used; for continuous variables that do not conform to a normal distribution, the median (25th percentile, 75th percentile) is used.

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

[0072] (3) Correlation analysis was performed using Pearson or Spearman correlation analysis and scatter plots were drawn.

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

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

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

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

[0077] (7) Use 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) to analyze data and create graphs.

[0078] Part Two: Overall participant information is as follows:

[0079] (1) See Table 1 for general information on the participants in this study;

[0080] Table 1 - Overall Information on Participants

[0081] HBP fluctuations before and after pPCI in STEMI patients:

[0082] Figure 1 shows the fluctuations in HBP before and after pPCI in STEMI patients.

[0083] Figure 1 Results analysis: STEMI patients had significantly elevated HBP levels before pPCI, at 43.43 (28.60, 71.96) ng / mL;

[0084] The HBP levels on days 1, 2, and 3 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.

[0085] In summary, the HBP levels of STEMI patients were higher than normal before and 72 hours after pPCI.

[0086] Compared with the preoperative level, the HBP level decreased significantly after pPCI, and the result was statistically significant (p<0.001).

[0087] (2) Predictive value of HBP for in-hospital adverse events in STEMI patients:

[0088] The results of univariate and multivariate logistic regression (Table 2) show that the HBP levels on postoperative days 1, 2, and 3, as well as the peak HBP level, are independent risk factors for the occurrence of in-hospital adverse events in STEMI patients.

[0089] Table 2. Logistic univariate and multivariate analyses of the predictive value of HBP for in-hospital events.

[0090] Δ1HBP is calculated as the level assessed before PCI minus the HBP level on day 1 after PCI.

[0091] Δ2HBP is calculated as the level assessed before PCI minus the HBP level on day 2 after PCI.

[0092] Δ3HBP is calculated as the level assessed before PCI minus the HBP level on day 3 after PCI.

[0093] Model 1 corrects for age and gender;

[0094] Model 2 adjusted for age, sex, baseline BMI, smoking, history of hypertension, history of diabetes, history of dyslipidemia, Killip classification, WBC, hsCRP, and LVEF.

[0095] As shown in Figure 2, the ROC curve analysis of STEMI patients showed that the HBP level on the first day after PCI had a good distinguishing value for in-hospital adverse events.

[0096] A cutoff 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.

[0097] In addition, the HBP level on day 3 after pPCI in STEMI patients also showed good value in differentiating in-hospital adverse events.

[0098] A cutoff level >29.12 ng / mL had a sensitivity of 78.0% and a specificity of 61.9% in predicting in-hospital adverse events.

[0099] (3) Further explore the dose-response relationship between HBP and adverse hospital outcomes, as shown in Figure 3.

[0100] Figure 3 Results Analysis: The inventors found that on the 3rd day after surgery, the risk of in-hospital adverse events was not significant when the HBP level in STEMI patients was less than 19.6 ng / mL, but the risk of in-hospital adverse events increased significantly with increasing HBP level when the HBP level was greater than 19.6 ng / mL.

[0101] (4) The predictive value of HBP for adverse events 30 days after discharge in STEMI patients;

[0102] Univariate and multivariate Cox regression results showed that the HBP levels on postoperative days 1, 2, and 3, as well as the peak HBP level, were independent risk factors for adverse events in STEMI patients at 30-day follow-up (independent of hsCRP, LVEF, etc.).

[0103] Table 3 shows the Cox univariate and multivariate analyses of the predictive value of HBP for adverse events in STEMI patients over 30 days.

[0104] Table 3 - Cox univariate and multivariate analysis of the predictive value of HBP for adverse events in STEMI patients over 30 days.

[0105] Δ1HBP is calculated as the level assessed before pPCI minus the HBP level on day 1 after pPCI.

[0106] Δ2HBP is calculated as the level assessed before pPCI minus the HBP level on day 2 after pPCI.

[0107] Δ3HBP is calculated as the level assessed before pPCI minus the HBP level on day 3 after pPCI.

[0108] Model 1 corrects for age and gender;

[0109] Model 2 adjusted for age, sex, baseline BMI, smoking, history of hypertension, history of diabetes, history of dyslipidemia, Killip classification, WBC, hsCRP, and LVEF.

[0110] (5) Further explore the dose-response relationship between HBP and adverse outcomes 30 days after discharge, as shown in Figure 4;

[0111] Figure 4 shows the results analysis: On postoperative day 2, HBP levels in STEMI patients were less than 21.80 ng / mL. The risk of adverse events at 30 days was not significant. However, after HBP levels exceeded 21.80 ng / mL, the risk of adverse events at 30 days increased with increasing HBP levels.

[0112] For STEMI patients, if the HBP level is less than 19.63 ng / mL on the 3rd postoperative day, the risk of adverse events at 30 days is not significant. However, if the HBP level is greater than 19.63 ng / mL, the risk of adverse events at 30 days increases with increasing HBP level.

[0113] (6) The Kaplan-Meier survival curves are shown in Figure 5;

[0114] Figure 5 shows the results analysis: In STEMI patients, the highest quartile of HBP levels on postoperative days 2 and 3 had a 12-fold increased incidence of adverse events at 30 days compared to the lowest quartile. No statistically significant difference in HBP levels was observed between preoperative and postoperative day 1. HBP is expected to become an effective tool for assessing the long-term prognosis of myocardial infarction patients after discharge.

[0115] (7) Correlation between HBP and left ventricular ejection fraction:

[0116] Figure 6 shows the correlation between peak HBP levels before and on days 1, 2, and 3 after pPCI in STEMI patients and LVEF on echocardiography one month after pPCI.

[0117] Figure 6 Results Analysis: The HBP level and peak HBP on the first day after surgery in STEMI patients were negatively correlated with the ejection fraction at 1 month follow-up after pPCI (r = -0.22, p = 0.017);

[0118] The HBP level on the second day after surgery (r = -0.35, p = 0.0003) and the peak HBP (r = -0.23, p = 0.021) were negatively correlated with LVEF at 1 month follow-up after pPCI.

[0119] In addition, univariate linear regression results showed (see Table 4) that the HBP levels and peak HBP on days 1 and 2 after STEMI were negatively correlated with LVEF at 1 month follow-up after pPCI.

[0120] Table 4. Univariate linear regression analysis of the relationship between HBP levels and peak values ​​during hospitalization and left ventricular ejection fraction at 1 day and 1 month after pPCI in STEMI patients.

[0121] Δ1HBP is calculated as the level assessed before pPCI minus the HBP level on day 1 after pPCI.

[0122] Δ2HBP is calculated as the level assessed before pPCI minus the HBP level on day 2 after pPCI.

[0123] Δ3HBP is calculated as the level assessed before pPCI minus the HBP level on day 3 after pPCI.

[0124] The predictive value of HBP for heart failure events after myocardial infarction in STEMI patients

[0125] Cox regression results (see Table 5) showed that HBP levels on days 1, 2, and 3 post-procedure were independent risk factors for heart failure events during PCI follow-up in STEMI patients.

[0126] Table 5. Cox univariate analysis of the predictive value of HBP for the occurrence of heart failure events 30 days after discharge in STEMI patients.

[0127] (8) In addition, the ROC curve analysis is shown in Figure 7;

[0128] Figure 7 shows the results analysis: HBP levels on day 3 after pPCI in STEMI patients showed good discriminatory value for heart failure events. The 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.

[0129] (9) Predictive value of HBP combined with hs-CRP for heart failure events

[0130] As shown in Table 6, when used in combination with hs-CRP, the HBP level on day 3 after pPCI in STEMI patients improved the prediction of heart failure events in the c-statistic analysis.

[0131] Table 6 - Accuracy of cTnI, hs-CRP, and HBP in predicting the risk of heart failure in STEMI patients.

[0132] In summary, the applicant found that HBP levels in STEMI patients were higher than normal before and within 72 hours after pPCI. Specifically, HBP levels gradually decreased between 24 and 72 hours after pPCI, showing a significant reduction compared to pre-procedure levels. Plasma HBP levels can be used to assess independent risk factors for adverse prognostic events both in-hospital and 30 days post-discharge.

[0133] Furthermore, HBP was negatively correlated with cardiac function levels one month after pPCI in STEMI patients; higher HBP levels were associated with poorer cardiac function and were an independent risk factor for heart failure events following myocardial infarction within 30 days.

[0134] In STEMI patients, HBP levels on day 3 after pPCI, combined with hs-CRP, improved the predictive value for heart failure events one month post-procedure.

[0135] As an inflammatory marker, hemoglobin (HBP) research has previously focused primarily on bacterial infections and sepsis. Currently, few scholars, both domestically and internationally, have applied HBP to assess myocardial injury in patients with acute myocardial infarction. This study is the first to explore the dynamic trends of HBP levels in STEMI patients before and within 72 hours after pPCI, and its relationship with myocardial infarction prognosis. It also represents the largest sample size of HBP research related to STEMI to date. This study is the first to demonstrate that HBP can be used independently for prognostic assessment of STEMI patients, including both in-hospital adverse events and recent adverse outcomes. Furthermore, it is the first to discover a close correlation between elevated HBP levels and the occurrence of heart failure after myocardial infarction, suggesting that HBP can serve as an effective predictor of heart failure after myocardial infarction.

[0136] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Any modifications, equivalent substitutions, and improvements made within the principles of this application should be included within the protection scope of this application.

Claims

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

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

3. Use according to claim 1, characterized in that, The kit is used to detect changes in HBP concentration in patients with acute ST-segment elevation myocardial infarction.

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

5. Use according to claim 4, characterized in that, The prognostic risks include one or a combination of risks of re-infarction, acute heart failure, cardiogenic shock, and stroke.

6. Use according to claim 3, characterized in that, The kit is used to detect changes in HBP concentration in patients with acute ST-segment elevation myocardial infarction by detecting ex vivo samples from the patients.

7. Use according to claim 6, characterized in that, The ex vivo sample was plasma.

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