Nghiên cứu biến đổi nồng độ h FABP huyết thanh ở bệnh nhân nhồi máu cơ tim cấp có ST chênh lên TT TIENG ANH

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENCE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES - NGUYEN THANH PHONG STUDY ON THE CHANGES IN SERUM H-FABP LEVELS IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION Speciality: Cardiology Medicine Code: 62.72.01.41 ABSTRACT OF MEDICAL PHD THESIS Hanoi – 2022 THE THESIS WAS DONE IN 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES Supervisor: Ass Prof PhD Pham Nguyen Son Ass Prof PhD Nguyen Hong Son Reviewer: This thesis will be presented at Institute Council at: 108 Institute of Clinical Medical and Pharmaceutical Sciences The thesis can be found at: National Library of Vietnam Library of 108 Institute of Clinical Medical and Pharmaceutical Sciences Central Institute for Medical Science Infomation and Tecnology INTRODUCTION Myocardial infarction in general and acute ST-segment elevation myocardial infarction (STEMI) are among the leading causes of death in developed and developing countries It is estimated that in the United States more than 1.6 million patients are hospitalized each year for acute myocardial infarction (AMI), of which about 30% are due to STEMI, and there are approximately 200,000 to 300,000 deaths annually In Vietnam, the number of patients with AMI tends to increase very rapidly in recent years and is becoming a health issue of great concern Early diagnosis and early treatment of AMI play a decisive role in saving patients' lives and are closely related to short-term as well as long-term complications after AMI Many cardiovascular markers have been studied and widely applied in clinical guidelines, however, Troponin or hs-Troponin as well as other cardiac enzyme markers such as: Myoglobin, CK-MB, LDH, AST all have limited sensitive and specific value In the current new cardiovascular markers, Heart-type fatty acid binding protein (H-FABP) has been receiving much attention from researchers Many studies demonstrating that H-FABP has higher sensitive and specific value than current cardiovascular markers in the early diagnosis of acute coronary syndromes and STEMI In addition, many studies have shown that H-FABP levels are closely related to clinical status, degree of coronary artery damage, risk stratification scales, and has an important role important in the prognosis of shortterm and long-term cardiovascular events in patients with ACS or AMI Currently, domestic and international studies mainly focus on the group of patients with ACS and Non-STEMI, so we conduct a study on the topic: “Study on changes in serum H-FABP level in patients with acute myocardial infarction with ST-segment elevation” with the goal of: Investigation of clinical, laboratory characteristics, concentration changes and diagnostic value of serum H-FABP in patients with ST elevation myocardial infarction Evaluating the relationship between HFABP concentration and some clinical and laboratory characteristics, cardiovascular events and mortality in 30 days of patients with ST-segment elevation myocardial infarction NEW CONTRIBUTIONS OF THE THESIS The thesis has proved the role of early diagnosis of H-FABP, compared with other cardiovascular markers such as CKMB, hsTroponin in STEMI There is an association between H-FABP with clinical, laboratory and major cardiovascular events after 30-day follow-up of STEMI The results help to have more new marker together with current markers to increase the value of early diagnosis STEMI as well as combine with currently applied prognostic scales to help predict the disease status during hospital stay and after discharge to personalize access, care, monitoring and treatment LAYOUT OF THESIS The thesis has 129 pages, including pages of introduction, 33 pages of overview, 21 pages of objects and methods, 34 pages of research results, 36 pages of discussion, pages of conclusion and page of proposals There are 59 results tables, 20 charts, 14 figures and 151 references (18 Vietnamese and 133 English) Chapter OVERVIEW 1.1 Overview of acute myocardial infarction and ST-segment elevation myocardial infarction 1.1.1 Causes of ST-elevation myocardial infarction 1.1.2 Definition and history of acute myocardial infarction AMI is necrosis of an myocardial area, a consequence of myocardial ischemia AMI is characterized by complete occlusion of one or more coronary arteries, causing sudden myocardial ischemia and necrosis of the myocardium perfused by that branch According to the fourth global definition ESC/ACCF/AHA/WHF in 2018: AMI is defined as acute myocardial injury accompanied by clinical evidence of myocardial ischemia, meaning as elevation and/or decrease in troponin levels with at least one value higher than the 99th percentile referenced above, accompanied by at least one of the following: - Symptoms of myocardial ischemia - New ischemic type electrocardiogram changes - A pathological Q wave recorded - A new imaging evidence of dysfunctional myocardium or regional dyskinesia in a setting consistent with ischemia - Coronary thromboembolism was noted during coronary angiography or autopsies STEMI is diagnosed when there is an ECG ST-segment elevation change and an increase and/or decrease in cardiac troponin values with at least one value above the 99th percentile upper term 1.1.3 Diagnosis of ST-elevation myocardial infarction 1.1.3.1 Clinical 1.1.3.2 Laboratory and imaging findings - Electrocardiogram - Cardiac enzyme tests - Echocardiography - Coronary angiography 1.1.4 Some of new biomarkers having a highly diagnostic and prognotic value in of AMI and STEMI 1.1.4.1 Troponin and hs-Troponin (high-sensitive cardiac Troponin) 1.1.4.2 BNP and NT-proBNP 1.1.5 Risk stratification in patients with AMI and STEMI 1.1.5.1 TIMI score scale 1.1.5.2 GRACE Score Scale 1.2 Overview of FABP and H-FABP 1.2.1 Fatty acid-binding protein (FABP) 1.2.2 Heart - Fatty acid-binding protein (H-FABP) 1.2.2.1 Distribution H-FABP also known as FABP3, has been isolated from many types of tissues, concentrated mainly in the heart, some other tissues such as skeletal muscle, brain, renal cortex, lung, testis, aorta, adrenal gland , mammary glands, placenta, ovaries and adipose tissue 1.2.2.2 Structure 1.2.2.3 Biological role Similar to other FABPs, H-FABP is involved in active fatty acid metabolism, it transports fatty acids from cell membranes to mitochondria for oxidation These FABPs are thought to be involved in the uptake, intracellular metabolism and/or transport of long-chain fatty acids H-FABP also has a regulatory effect on cell growth and proliferation, and suppresses the growth of mammary epithelial cells H-FABP is abundant in the myocardium and is rapidly released from cardiomyocytes into the circulation after cell damage begins Serum HFABP levels have been suggested as an early biochemical marker of AMI and a sensitive marker for the detection and assessment of myocardial damage in patients with heart failure 1.2.3 Myocardial ischemia and release of H-FABP Release mechanism and kinetics of H-FABP When the heart muscle is ischemic, the heart muscle cells are not supplied with enough oxygen, accompanied by a stagnation of waste products in the metabolism If this process is prolonged, it will cause the plasma membrane to be destroyed, leading to the escape of intracellular substances through the myocardial interstitium into the microvasculature and lymph Fig.1.12 H-FABP under physiological conditions and myocardial injury * Source: Richard R (2020) Table 1.5 H-FABP kinetics and cardiac biomarkers Molecular Appear Back to Peaked Meaning weight In blood normal Markers (hours) (kDa) (hours) (hours) Rise very H-FABP 15 0.5 - 12 – 1,5 soon Myoglobin 18 1-3 5-8 – 1,5 Early rise Troponin I 22 3-6 14 - 18 - 10 Late rise Troponin T 37 3-6 10 - 48 10 - 15 Late rise CK-MB 86 3-8 - 24 2-3 Late rise * Source: Jan G (2014) 1.3 Several studies of H-FABP in the diagnosis and prognosis of AMI and STEMI 1.3.1 Some foreign studies Research by Orak M et al (2010) showed that the sensitivity and specificity of H-FABP in diagnosing ACS within 0-6 hours from symptom onset was 98% and 71% higher than that of CK-MB has a sensitivity of 86%, a specificity of 52% and TnI 77% and 20% A meta-analysis from studies comparing hs-Troponin and H-FABP values by author Daniel M F (2019) Overall, hs-TnT was more sensitive to H-FABP but less specific For patients admitted within hours of symptom onset, the sensitivity of H-FABP was quite similar to that of hs-TnT, 19-63% versus 25-55%, respectively While the specificity of H-FABP was higher than that of hs-TnT (70 - 99% vs 57 86%), conversely, the AUC of hs-TnT was higher than that of H-FABP (0.67 - 92 vs 0.69 - 0.85) Kilcullen N et al conducted an analysis of the prognostic value of H-FABP based on building single and multivariate regression models, Cox regression models to calculate the risk rate of occurrence of these events over time in group of ACS Univariate regression model for each quartile group H-FABP, adjusted HR for each group: Q1 HR = 1.0, Q2 HR = 2.32 (95% CI 1.25 - 4.30, p = 0.007), Q3 HR = 3.17 (95% CI 1.73 - 5.82, p < 0.001) and Q4 HR = 4.88 (95% CI 2.67 - 8.93, p < 0.001) Multivariable logistic regression model using factors in GRACE scale, combining hs-CRP and Troponin I, mortality in 12 months of followup, adjusted HR for each quartile group H-FABP: Q1 HR = 1.0, Q2 HR = 2.58 (95% CI 1.37 - 4.85, p = 0.003), Q3 HR = 3.77 (95% CI 2.01 7.07, p 0.014 ng/ml + Concentration of H-FABP: select the cut-off point based on the ROC curve in the diagnosis of STEMI on the basis of our research results The cases in which the diagnosis was doubtful were confirmed by testing with diagnostic markers such as CKMB, hs-TnT after hours of admission 2.2.4.4 Standards for echocardiography 2.2.4.5 Criteria for assessment of coronary artery injury - Classification of coronary artery lesions according to the American Heart Association ACC/AHA: divided into types A, B1, B2, C - Assess severity of coronary artery injury by Gensini index: Damage severity = ∑ (Number of lesions x corresponding coefficient) 2.2.4.6 TIMI, GRACE scores for STEMI and cardiovascular events and risk stratification The TIMI and GRACE scores were calculated based on clinical and subclinical symptoms at the time of admission, divided into levels: low, medium and high risk, respectively Criteria for cardiovascular events during hospital stay and during follow-up 2.3 Data processing Data are collected based on pre-built research medical records; entered using Microsoft Excel 2016 software Data processing using SPSS 20.0 medical statistical software; draw ROC and Kaplan-Meier charts using Medcal 20.0 software 10 - Average GRACE score 166.00 ± 31.17 Risk classification: low (48 – 125 points) 8.9%, moderate (126 – 154 points) 31.5% and high (> 155 points) 59.6% - The main events during hospital stay included, heart failure accounted for the highest rate 47.3%, arrhythmia accounted for 14.4% Recorded 14 deaths, accounting for 9.6% - During the 30-day follow-up period after acute MI, the rate of recurrence of chest pain on admission was 4.5%, and hospitalization for severe heart failure 0.8% 3.1.3 Levels of H-FABP in STEMI Chart 3.4 H-FABP concentration of study subjects - H-FABP concentration, ST elevation MI group 60.71 ± 45.82 ng/ml, control group 2.75 ± 1.52 ng/ml (p < 0.01) Table 3.17 Levels of H-FABP in STEMI by time of admission H-FABP (ng/ml) Test p Study group Median IQR X ± SD 15,40 55,04 ± 44,67 48,18 ≤3h 79,55 39,22 70,44 ± 42,77 72,61 >3–6h 100,45 23,71 74,47 ± 51,49 78,41 > – 12 h 120,23 < 0,05* 15,65 64,27 ± 51,58 56,90 > 12 – 24 h 99,46 36,15 ± 31,42 38,29 5,67 - 64,21 > 24 – 36 h * Kruskal Wallis test 3.1.4 H-FABP value in the diagnosis of STEMI, compared with other cardiovascular markers 11 3.1.4.1 H-FABP value in the diagnosis of STEMI Table 3.20 AUC area and H-FABP cut-off point in diagnosis STEMI H-FABP (ng/ml) AUC 0,945 Cut-off point 5,57 5,70 5,79 5,88 6,00 6,13 6,27 95% CI 0,917 - 0,973 Se (%) 89,0 88,4 88,4 88,4 88,4 87,7 87,0 p < 0,01 Sp (%) J index 93,2 0,82 93,2 0,82 93,8 0,82 94,5 0,83 95,2 0,84 95,2 0,83 95,9 0,83 - The ROC curve of H-FABP is above the standard curve, the area under the curve AUC = 0.945; 95% CI: 0.917 - 0.973; p < 0.01 - Based on the highest value of Youden J index, we determined the cut-off point of HFABP in the diagnosis of STEMI is 6.00 ng/ml * Comparison of diagnostic value of H-FABP with CK-MB and HsTnT in general diagnosis of STEMI Table 3.21 AUC area, sensitivity, and specificity of H-FABP compared with Hs-TnT, CK-MB in the diagnosis of STEMI Test AUC 95% CI p Se (%) Sp (%) H-FABP (ng/ml) 0,945 0,917 - 0,973 < 0,01 88,4 95,2 Hs-TnT (ng/ml) 0,961 0,931 - 0,991 < 0,01 95,9 80,8 CK-MB (U/I) 0,866 0,826 - 0,906 < 0,01 70,5 76,7 12 3.1.4.2 H-FABP value in the diagnosis of STEMI by time of patient admission * Group of hospitalized patients ≤ hours and > 3-6 hours Table 3.22-23 Values of H-FABP and Hs-TnT, CK-MB in the diagnosis of STEMI in the hospitalization group hours and > - hours Subjects Tests AUC 95% CI p Se (%) Sp (%) Admission ≤ hours (n = 186) HHsCKFABP TnT MB (ng/ml) (ng/ml) (U/I) Admission > 3- hours (n = 185) HHsCKFABP TnT MB (ng/ml) (ng/ml) (U/I) 0,956 0,909 – 1,000 < 0,01 92,5 95,2 0,979 0,951 – 1,000 < 0,01 94,9 95,2 0,898 0,8070,990 < 0,01 90,0 80,8 0,740 0,6670,812 < 0,01 42,5 76,7 0,978 0,935 1,000 < 0,01 97,4 80,8 0,874 0,803– 0,946 < 0,01 71,8 76,7 Table 3.24-25 Values of H-FABP and Hs-TnT, CK-MB in the diagnosis of STEMI in the hospitalization group > - 12 hours and > 12 hours Subjects Tests AUC 95% CI p Se (%) Sp (%) Admission > -12 hours (n = 171) HHs-TnT CKFABP (ng/ml) MB (ng/ml) (U/I) 0,962 0,971 0,923 0,908 – 0,915 - 0,862 1,000 1,000 0,984 < 0,01 < 0,01 < 0,01 92,0 96,0 76,0 95,2 80,8 76,7 Admission > 12 hours (n = 188) HHs-TnT CKFABP (ng/ml) MB (ng/ml) (U/I) 0,891 1,00 0,945 0,821 - 1,000 - 0,892 0,962 1,000 0,998 < 0,01 < 0,01 < 0,01 76,2 100 92,9 95,2 80,8 76,7 13 3.2 The relationship between HFABP concentration and some clinical, subclinical characteristics, cardiovascular events and mortality in 30 days of patients with STEMI 3.2.1 Association of H-FABP with some clinical and subclinical characteristics Table 3.26 Levels of H-FABP with the degree of acute heart failure according to Killip Tests H-FABP (ng/ml) p Killip Median IQR X ± SD I (n = 45) II (n = 77) III (n = 13) IV (n = 11) 41,72±40,54 63,60±43,28 87,71±47,58 86,17±53,93 23,10 62,35 87,33 80,45 5,56-76,88 24,61-89,96 44,09-125,18 45,97-134,98 < 0,05 Table 3.29 H-FABP concentration with the number of damaged coronary artery branches Tests H-FABP (ng/ml) p Median IQR X ± SD Branches 41,22 3,49-81,59 branch (n = 29) 48,70±48,68 60,12 20,55-79,60 < branches (n = 78) 58,44±42,74 0,05 37,113 branches and/or 74,04±47,57 71,64 120,41 LM (n = 39) Table 3.31-32 H-FABP concentration with coronary injury grade According to the Gensini scale and type ACC/AHA Tests H-FABP (ng/ml) p Median IQR X ± SD Coronary injury Low 46,65±39,27 30,14 7,18-89,70 > Gensini Medium 55,84±44,99 58,60 14,8-80,45 0,05 Scale High 72,30±47,33 62,39 45,09-111,61 Type A 26,47±29,37 14,81 1,92-58,15 Type B1 51,35±44,07 42,09 7,21-78,96 < AHA/ACC Type B2 76,38±45,65 75,36 41,19-115,10 0,01 Type C 78,87±42,54 72,45 48,53-110,78 14 - Results of H-FABP concentration increased gradually according to the risk level of the TIMI scale (p > 0.05) and GRACE (p < 0.01) 3.2.2 Association of H-FABP with cardiovascular events during hospital stay and during 30-day follow-up after STEMI 3.2.2.1 HFABP and hospital stay events Figure 3.14 H-FABP between the event group and the group without cardiovascular events during hospital stay - The concentration of H-FABP in subjects experiencing cardiovascular events after MI during hospital stay was 73.10 ± 46.08 ng/ml, significantly higher than subjects without events 40.20 ± 37, 55 ng/ml (p < 0.01) Table 3.36 AUC of H-FABP in predicting mortality in patients with STEMI Tests AUC 95% CI p 0,659 0,53 - 0,79 > 0,05 CK-MB (U/l) 0,52 - 0,83 Hs-TnT (ng/ml) 0,677 < 0,05 0,64 - 0,93 NT-proBNP (pg/ml) 0,788 < 0,01 0,648 0,46 - 0,83 > 0,05 Hs-CRP (mg/ L) 0,63 - 0,83 H-FABP (ng/ml) 0,729 < 0,01 - The cut-off point in the prognosis of STEMI with H-FABP: 62.75 ng/ml, NT-proBNP: 1541.65 pg/ml; Hs-TnT: 4.99 ng/ml 15 Table 3.37 Prognostic ability of STEMI of H-FABP and some cardiovascular markers Events Tests Study subjects (n=146) Death Non(n=14) death (n = 132) 77 13 55 OR p 95% CI H-FABP (ng/ml) ≤ 62,75 > 62,75 NTproBNP (pg/ml) Hs-TnT (ng/ml) ≤1541,65 >1541,65 12 88 44 18,20 2,31– 143,25 12,00 2,57-55,98 ≤ 4,99 > 4,99 117 15 5,85 1,79-19,18 < 0,01* < 0,01* < 0,01 Table 3.39 AUC area of H-FABP combined with markers and TIMI, GRACE scores in predicting mortality in patients with STEMI H-FABP and markers, scales H-FABP + CKMB H-FABP + Hs-TnT H-FABP + NT- proBNP H-FABP + Hs-CRP H-FABP + TIMI H-FABP + GRACE AUC 95% CI p 0,746 0,758 0,856 0,801 0,784 0,821 0,64 – 0,85 0,64 – 0,88 0,76 – 0,95 0,66 – 0,94 0,67 – 0,89 0,73 – 0,91 < 0,01 < 0,01 < 0,01 < 0,01 < 0,01 < 0,01 3.2.2.2 HFABP and 30-day follow-up events after STEMI - The group of patients with cardiovascular events during the 30-day follow-up had H-FABP concentration at the time of admission was 103.14 ± 37.29 ng/ml; significantly higher than the group without events (p < 0.01) 16 Table 3.41 Cox regression model predicts cardiovascular events during 30-day follow-up after STEMI MI recurrence HR 95% CI p Test ≤ 62,75 H-FABP 8,66 1,04 - 72,97 < 0,05 (ng/ml) > 62,75 - Cox regression model, H-FABP > 62.75 ng/ml is valuable in predicting cardiovascular events in 30 days after STEMI with HR = 8.66; 95% CI: 1.04 - 72.97, p < 0.05 Figure 3.16 Kaplan-Meier curve for cardiovascular events stratified by H-FABP at admission during 30-day follow-up Chapter DISCUSSION 4.1 Clinical, laboratory and variable characteristics of serum HFABP levels in patients with STEMI 4.1.1 General characteristics of research subjects The higher the age of patients with AMI, the worse the prognosis because elderly patients often arrive late and have multiple coronary artery lesions The mean age of the STEMI group was 60.64 ± 14.08 years old, there was no difference compared with the control group (p > 0.05) The age group from 40 - 79 accounts for the majority with 84.3%, of which the age group from 60 - 79 accounts for 47.3%, from 40 - 59 accounts for 37.0%, other age groups only account for a small proportion 4.1.2 Some clinical and sub-clinical characteristics of research subjects 4.1.2.1 Clinical features 17 In our study, patients were admitted to the hospital and early intervention before ≤ hours accounted for the majority, of which the highest rate was before hours (27.4%), followed by 3-6 hours (26.7%) Patients admitted at the time of 6-12h, 12-24h and >24h accounted for 17.1%, 13% and 15.8% respectively The rate of hospital admission before 12 o'clock in our study was higher than that of Nguyen Thi Thanh Trung (2014) According to our research results, the majority of Killip II with 52.7%, Killip I with 30.8%, the rate of Killip IV only accounted for a small percentage with 7.6% The degree of heart failure varies from study to study, but Killip grades I and II usually account for a higher proportion than the other classes The difference in the rate of Killip grading between our study and some other authors can be explained by the difference in study subjects with risk factors, time of hospitalization, time of diagnosis Early treatment, initial treatment and degree of myocardial damage These are factors affecting the clinical condition of patients on admission 4.1.2.2 Sub-clinical findings In our study, lesions of branches accounted for the highest rate of 53.4% and there were 26.7% lesions of branches and/or common trunk of coronary artery, while lesions of branch accounted for 19.9% The difference between the number of damaged coronary branches in AMI is due to the characteristics of the study subjects, the elderly patient groups, many risk factors, often complex lesions, more branches than the rest of the subjects The most common culprit artery was the anterior left anterior descending (LAD) 62.4%, followed by the right coronary artery (RCA) 25.3% and the left circumflex artery (LCx) 12.3% Our results are also consistent with that of author Bui Long (2018), lesions are common in the LAD(41.85%), then the RCA (38.32%), at least the LCx (15.42%) The common cause of injury on these arteries is that the LAD and the RCA are the two main branches of the coronary arteries that feed the myocardium, so the injury rate is high 4.1.2.3 Cardiovascular risk stratification of patients with STEMI according to TIMI, GRACE scores and cardiovascular events during hospital stay The average TIMI and GRACE scores before intervention were 6.49 ± 2.01 points and 166.00 ± 31.17 points, respectively Most of the study subjects were in the moderate to high risk group Our results are higher 18 than the mean scores of TIMI and GRACE in subjects with STEMI of author Correia L.C L (2014) 3.7 ± 2.3 points and 116 ± 36 points, respectively This can be easily explained, on specific research subjects, with patients with different risk factors, clinical and sub-clinical manifestations, there will be fluctuations in the mean score of each point scale However, within the scope of the study, we not analyze in-depth the prognostic value of these two scales, the value of these two scales will be mentioned with the prognostic value of H-FABP in the content of this study below 4.1.3 Serum H-FABP levels in patients with STEMI The results of our study, the average concentration of H-FABP in STEMI subjects increased to 60.71 ± 45.82 ng/ml; median 56.85 ng/ml, IQR 19.05 - 89.70 ng/ml, higher with control group, p < 0.01 The concentration of H-FABP in STEMI subjects based on the time of admission, H-FABP tended to increase from the group of early admission < hours to the group of to hours, the highest group of -12 hours; then the trend gradually decreased in later hospitalized subjects; decreased sharply in the 24-36 hour hospitalization group Research by author Liu Y on 55 subjects with ACS who were admitted to the hospital early, tested negative for Troponin T for the first time, H-FABP and hs-TnT tests were continued at 6, 12, 24 and 48 hours The author noted that the concentration of H-FABP peaked after hours, decreased slightly (12.82%) after 12 hours and decreased significantly by about 79% after 48 hours Meanwhile, hs-TnT peaked after 12 hours, decreased by 50% after 48 hours 4.1.4 Diagnostic value of H-FABP in patients with acute STEMI 4.1.4.1 General diagnostic value of H-FABP and diagnostic cut-off * H-FABP value Through ROC curve analysis, the cut-off point of H-FABP in our study is 6.0 ng/ml, the area under the curve (AUC) of H-FABP is 0.945, which has very good value in diagnosing for STEMI * Compare H-FABP values with hs-TnT and CKMB Based on the area under curve AUC, in the subjects of STEMI, HsTnT had the highest diagnostic value with AUC 0.961, followed by HFABP with AUC 0.945, the lowest is CK-MB with AUC 0.866 Comparing Se, Sp, H-FABP has Se lower than Hs-TnT (88.4% vs 95.9%) but has higher Sp (95.2% vs 80.8%), CKMB has low Se and Sp, 70.5% and 76.7% respectively 19 Table 4.2 Diagnostic value of H-FABP compared with hsTroponin Studies Authors n A MI STE MI H-FABP NSTE MI AU C Se Sp Hs-TnT AU C Se Sp Cappelli 0,3 0,8 0,5 67 26 20 0,84 1,0 0,81 ni* Kagawa 0,8 0,1 0,8 0,7 114 47 26 21 0,59 0,89 * 9 103 0,7 0,9 0,7 Reiter* 166 166 0,84 0,8 0,94 * Short quotes via research author Kevin Liou Through the results of Table 4.2, except for the study of Cappellini with a relatively small sample size (67 patients) with H-FABP having higher diagnostic value than Hs-TnT Meanwhile, the studies of Kagawa and Reiter with larger sample sizes, both recorded a higher diagnostic value of hs-TnT than that of H-FABP 4.1.4.2 Diagnostic value of H-FABP in STEMI according to the time of admission to the study subjects * Group of patients hospitalized < hours after symptom onset In our study, in the group hospitalized for ≤ hours and > - hours, based on AUC, Se, Sp, H-FABP had a much higher diagnostic value than Hs-TnT and CKMB Specifically, the group ≤ hours had AUC, Se and Sp of H-FABP 0.956, 92.5%, 95.2%, respectively; group > - hours, then H-FABP has AUC, Se; Sp respectively are: 0.979; 94.9%; 95.2% A study by Giao Thi Thoa (2018) on MI patients hospitalized < hours had a higher AUC of H-FABP of 0.93 than that of Hs-TnT (0.91), MYO (0.86) and CK- MB (0.83) Mitsunobu Kitamura (2013) studied on 85 patients with ACS, averaged admission 165 minutes, AUC of HFABP was 0.880 higher than Hs-TnT, TnT and CKMB * Group of patients hospitalized – 12 hours and > 12 hours after onset In subjects hospitalized - 12 hours, H-FABP still had high diagnostic value with AUC 0.962 After 12 h, the AUC of H-FABP 20 markedly decreased by 0.891 Along with the decrease in AUC, the Se of H-FABP also decreased from 92.0% to 76.2% In contrast, the AUC and Se diagnostic values of Hs-TnT and CKMB were elevated at both time points In which Hs-TnT has the highest AUC and Se, but lower than H-FABP in terms of Sp specificity Compared at the time points in Willemsen's study (2015) on ACS subjects, the diagnostic value of H-FABP, Se and Sp was higher than that of Hs-TnT at the time points -3, 3-6 and 6-12 hours At 12-24 hours, the Se value of H-FABP decreased, lower than that of Hs-TnT, but Sp was still higher Research by McMahon (2012), Se and Sp of HFABP in the diagnosis gradually increased with time of hospital admission, AUC increased from 0.84 on the group of admission < hours to 0.97 on the group hospitalized from 12 - 24 hours AUC, Se and Sp of H-FABP remained high at 12-24 hours However, the author also noted that, at 12-24 hours, the Se of H-FABP did not increase as clearly as the previous time points and Sp tended to decrease gradually 4.2 Association of H-FABP with some clinical and laboratory features, TIMI risk score, GRACE, mortality prognosis and 30 days of follow-up after STEMI 4.2.1 Association of H-FABP with cardiovascular events and mortality during hospital stay after STEMI * H-FABP with in-hospital cardiovascular events According to our study results, the concentration of H-FABP in the group with cardiovascular events was significantly higher than in the group without events (p < 0.01) Similarly, in the study of the author ShaheenaBanu (2015), in-hospital fatal STEMI patients had a H-FABP concentration of 109.55 ± 108.49 ng/ml, higher than the non-fatal group * H-FABP with prognosis of in-hospital mortality According to our study results, H-FABP has a high value in predicting in-hospital mortality with AUC = 0.750, 95% CI: 0.63 - 0.87, p < 0.01 When combining H-FABP with other cardiovascular markers or TIMI, GRACE scores; The prognostic value increased markedly with AUC 0.746 - 0.856, p < 0.01 Similar to the study results of author Niamh Kilcullen and colleagues, univariate regression model by 21 quartile group H-FABP in predicting in-hospital mortality, adjusted HR for each group: Q1 HR = 1.0; Q2: HR = 2.32 (95% CI 1.25 - 4.30; p = 0.007), Q3 HR = 3.17 (95% CI 1.73 - 5.82; p 114.07 ng/ml in hospital admissions, the risk of mortality was higher 14.72 times, higher than other factors such as NT- proBNP and Killip 4.2.2.2 Association of H-FABP with 30-day follow-up events after SREMI During the 30-day follow-up period, 06 cases of chest pain recurrence and 01 case of severe heart failure required hospitalization The concentration of H-FABP in the rehospitalization group was significantly higher than in the group of patients without events (p < 0.01) H-FABP > 62.75 ng/ml is valuable in predicting cardiovascular events in 30 days after STEMI with HR = 8.66; 95% CI: 1.04 - 72.97, p < 0.05 In the OPUS-TIMI 16 trial O'Donoghue M study, H-FABP was tested on 2,287 ACS patients, the follow-up period was 10 months, the results showed that patients with elevated H-FABP had an increased risk of mortality (HR = 4.1, 95% CI 2.6 – 6.5), recurrent MI (HR = 1.6; 95% CI 1.0 – 2.5), decompensated heart failure (HR = 2.6, CI 95 % 1.9 – 3.5) Author Viswanathan K (2010) on 1,080 ACS patients, the lowest follow-up time was 12 months (median 18 months), event rate 22 96/995 (10.1%), H-FABP concentration was an independent predictor of death or re-myocardial infarction, after adjusting for multivariate analysis Patients with H-FABP concentration > 6.48 μg/l had a higher rate of events than the group ≤ 6.48 μg/l (HR = 2.62; 95% CI 1.30 – 5.28, p = 0.007) Our study also has certain limitations: - Our study only evaluated the H-FABP value at the time of admission, not at many time points to clarify the kinetic changes and the H-FABP value at the time points after MI - The time to follow up cardiovascular events of the study subjects after STEMI is not long, so the long-term prognostic role of H-FABP has not been clarified CONCLUSION Through the study, surveying serum H-FABP levels in 146 patients with STEMI and 146 subjects hospitalized with chest pain not due to cardiovascular disease, we draw the following conclusions: Clinical, sub-clinical characteristics, concentration changes and diagnostic value of serum H-FABP in patients with STEMI: - The mean age of the group of STEMI is: 60.64 ± 14.08 years old The male/female ratio is 2.65/1 The time of admission after symptom onset to hours was 27.4%, from to hours was 26.7% and after 24 hours was 15.8% - Acute heart failure at the time of admission, Killip I accounted for 30.8%, Killip II 52.7% and Killip IV only 7.6% - Injury to branches of coronary artery accounted for 48.6%, branches and or with LM 33.6% Classification of coronary artery lesions according to ACC/AHA: type B1 is 46.6%, type B2 is 27.4% - The mean TIMI, GRACE scores before intervention of patients with STEMI are 6.49 ± 2.01 points and 166.00 ± 31.17 points, respectively - During the hospital stay, there were 14 deaths, accounting for 9.6% During the 30-day follow-up period after STEMI, the rate of chest pain recurrence and hospitalization was 4.5%, severe heart failure hospitalization 0.8% - The average concentration of H-FABP in patients with STEMI was 60.71 ± 45.82 ng/ml, higher than in the control group (p < 0.01) 23 - The concentration of H-FABP increased gradually from the group admitted ≤ 12 hours after symptom onset, the highest in the group of hospitalization from -12 hours and gradually decreased in the hospitalized group at the following time points - The cutoff point of H-FABP concentration in the diagnosis of STEMI was 6.00 ng/ml with AUC = 0.945, 95% CI: 0.917 - 0.973, p < 0.01, Se 88.4%, Sp 95 ,2% - The diagnostic value of H-FABP based on AUC, in the group of patients with STEMI admitted to hospital ≤ hours has the highest value in diagnosis, higher than hs-TnT and CKMB In contrast, the group hospitalized after hours had the highest diagnostic value of HsTnT, higher than H-FABP and CKMB However, H-FABP consistently had a higher diagnostic specificity than hs-TnT and CKMB at all time points of admission The relationship between H-FABP concentration and some clinical, sub-clinical characteristics, cardiovascular events and mortality in 30 days of patients with STEMI - The concentration of H-FABP increased gradually according to the level of acute heart failure according to Killip at the time of admission (p < 0.05) - The concentration of H-FABP increased the highest in the group of branches lesions with/or without the left main coronary artery (LM), followed by branches lesions (p < 0.05) The concentration of HFABP increased gradually according to the coronary injury subtype according to ACC/AHA (p < 0.05) and according to the degree of coronary artery injury according to the Gensini scale (p > 0.05) - The concentration of H-FABP increased gradually according to the risk level of the GRACE scale (p < 0.01) and TIMI (p > 0.05) - During the hospital stay, the group with cardiovascular events had a higher concentration of H-FABP at admission than the group without cardiovascular events (p < 0.01) In which, the group of death and heart failure was significantly higher than the group with other events (p < 0.05) - Patients with an increased H-FABP level above the predictive event cut-off point of 62.75 ng/ml, the risk of in-hospital mortality was higher than the group without an increase, with OR = 18.2, 95% CI 2.31 – 143.2, p < 0.01 Combining H-FABP with routine cardiovascular markers or with TIMI and GRACE scores both increased the AUC 24 value in predicting mortality during hospital stay with AUC = 0.7460.856, p < 0.01 - Follow-up 30 days after MI, the group experiencing events in 30 days had higher H-FABP levels at hospital admission than the group without events (p < 0.01) Patients with H-FABP concentration at admission > 62.75 ng/ml will have a higher risk of events with HR = 8.66, 95% CI: 1.04 - 72.97, p < 05 RECOMMENDATIONS - Since H-FABP has a high sensitivity and specificity for diagnosis in patients with acute ST-segment elevation myocardial infarction (MI) who are hospitalized before hours, H-FABP should be considered in conjunction with current cardiovascular markers in Early diagnosis of patients with ST-segment elevation acute MI - Elevated H-FABP levels at the time of admission have prognostic significance, so the combination of H-FABP with other cardiac enzymes and currently used prognostic scales should be considered to increase the prognostic value and predictive of events 30 days after myocardial infarction in patients with STEMI ... group hospitalized after hours had the highest diagnostic value of HsTnT, higher than H- FABP and CKMB However, H- FABP consistently had a higher diagnostic specificity than hs-TnT and CKMB at all time... the subjects of STEMI, HsTnT had the highest diagnostic value with AUC 0.961, followed by HFABP with AUC 0.945, the lowest is CK-MB with AUC 0.866 Comparing Se, Sp, H- FABP has Se lower than Hs-TnT... - The diagnostic value of H- FABP based on AUC, in the group of patients with STEMI admitted to hospital ≤ hours has the highest value in diagnosis, higher than hs-TnT and CKMB In contrast, the