心肌型脂肪酸结合蛋白(H-FABP)在诊断早期AMI中的临床应用

目的探讨血清心肌型脂肪酸结合蛋白（H—FABP）在早期急性心肌梗死（AMI）诊断中的价值。方法选择疑似急性冠脉综合征患者102例,采用酶联免疫吸附法（Elisa）测定AMI发病3h内,4～6h、7～12h时血清中H—FABP浓度,并与心肌肌钙蛋白I（cTnI）、肌酸激酶同工酶（CK—MB）的检测结果进行比较,分析三种心肌损伤标志物在诊断不同发病时间段AMI的敏感性和特异性。结果在AMI发病3h内,H—FABP的诊断敏感性（66．7％）优于cTnI和CK—MB（P〈0．05）;在发病4～6h内,H—FABP的敏感性（94．4％）高于cTnI（61．1％）和CK—MB（50．0％）,差异有统计学意义（P〈0．05）。结论在AMI发病6h内,H—FABP是最敏感的心脏标志物,尤以发病3h内敏感。     

A superior early myocardial infarction marker. Human heart-type fatty acid-binding protein

Human heart-type fatty acid-binding protein (FABP) has a high potential as an early marker for myocardial infarction (MI) being more specific than myoglobin. FABP is a low molecular mass cytoplasmic protein (15 kDa) that is released early after the onset of ischemia and it may be useful for rapid confirmation or exclusion of acute myocardial infarction (AMI). Immunochemically assayed FABP, cardiac troponin I (cTnI) and enzymatically assayed creatine phosphokinase (CPK) were determined serially in plasma and serum samples from 218 patients presenting with chest pain and suspected MI. In the 94 patients with confirmed MI, FABP rose to a maximum level (577.6 +/- 43.8 microg/L) 3 hours after the onset of symptoms and returned to normal within 30 hours. The FABP level peaked 7-9 hours earlier than CPK (2288 +/- 131 U/L) and cTnI (357.1 +/- 23.9 microg/L). CPK took 50-70 hours to return to normal level and cTnI returned to normal level over 70 hours. The areas under the receiver operating characteristic (ROC) curves for FABP were calculated as 0.871 at admission and 0.995 one hour after admission, whereas for CPK the areas were 0.711 and 0.856 and for cTnI the areas were 0.677 and 0.845, indicating that the FABP test gave a better diagnostic classification at the early stage being reached by cTnI (0.995) only 8 hours after admission. For FABP, both sensitivity and negative predictive value (NPV) increased quickly to 100% for samples monitored just one hour after admission. By using only two samples, one at admission and one 1 hour post admission, sequential FABP monitoring can reliably diagnose AMI patients 1 hour after admission and 100% of non-AMI patients can be excluded with no false negative results. The late markers cTnI and CPK have the similar diagnostic performance only 7 hours later. Thus measurement of FABP in plasma or serum allows the earliest immunochemical confirmation or exclusion of AMI.     

Human heart-type fatty acid-binding protein for on-site diagnosis of early acute myocardial infarction

Human heart-type fatty acid-binding protein (H-FABP) has a high potential as an early marker for acute myocardial infarction (AMI) being more sensitive than current routine cardiac markers. Seventy-four patients presenting to hospital with a median symptom onset of 2.2 h (IQR 1.5-2.9 h) were enrolled in this study and 54 (73%) had AMI. At presentation, H-FABP gave the highest sensitivity of 83.3% (95% CI: 70.7-92.1) and troponin I (cTnI) gave the highest specificity of 50.0% (95% CI: 27.2-72.8). This study demonstrated that H-FABP immunotest gave a better diagnostic classification at the early stage. Also, AMI was identified significantly earlier by H-FABP than cTnI (17 vs. 6 patients, p<0.05).     

Diagnostic and prognostic value of heart-type fatty acid-binding protein (H-FABP), an early biochemical marker of myocardial injury

Heart-type fatty acid-binding protein (H-FABP) is a 132 amino acids soluble protein, with general characteristics resembling myoglobin. Because of its low molecular weight (15 kd) and cytoplasmic location, it constitutes a biologic marker readily released into the circulation after myocardial injury. Despite the development of various immunoassays to measure H-FABP, few are currently easy to perform, quantitative and applicable in emergency. Most studies have shown the diagnostic sensitivity of H-FABP (i.e. its ability to detect the presence of a myocardial infarction) to be high, above that of myoglobin in patients presenting within 3 to 6 h of after the onset of chest pain. This superiority is attributable to an earlier and more rapid rise in H-FABP than in myoglobin. After thrombolysis, the serum concentrations of H-FABP peak at approximately 4 h after the onset of chest pain, and return to normal values within 24 h. Because of this rapid return of its blood concentration to baseline, H-FABP can contribute to an early biologic diagnosis of post-thrombolysis reperfusion and re-infarction. In absence of renal insufficiency, H-FABP also provides a reliable estimate of infarct size associated with ST segment elevation. When myocardial injury occurs after cardiac surgery, the second peak in H-FABP concentration precedes that of myoglobin, CK-MB or troponins. In addition, H-FABP peaks earlier and is more sensitive than troponins in the detection of subtle myocardial injury in patients presenting with acute coronary syndrome without ST segment elevation, and in patients with severe heart failure, thus offering early prognostic information. Limitations of H-FABP include a limited cardio-specificity, a narrow diagnostic window (20 to 30 h), and a nearly exclusive renal elimination.     

The role of heart-type fatty acid-binding protein in the diagnosis of acute coronary syndrome

BACKGROUND:

Heart-type fatty acid-binding protein (H-FABP) is a membrane-bound protein that facilitates transport of fatty acids from the blood into the heart. It is currently being used outside the United States for the early diagnosis of myocardial infarction (MI). However, previous studies have shown inconsistent correlation of H-FABP with standard cardiac biomarkers.

METHODS:

Fifty patients admitted with ST segment elevation MI (n=25), non-ST segment elevation MI (n=15) or unstable angina (n=10) were evaluated. The CardioDetect med cardiac infarction test (rennesens GmbH, Germany) was used to measure both qualitative and quantitative H-FABP.

RESULTS:

Of the 40 patients with acute MI, the initial troponin assay was positive in 35 patients (88%), the qualitative H-FABP assay was positive in 23 patients (58%) and the quantitative H-FABP assay was positive in 15 patients (38%) (P=0.001). No patient with MI had a positive H-FABP assay with a negative initial troponin assay.

CONCLUSION:

In the present study, the results of both the qualitative and quantitative H-FABP assays neither appeared earlier nor provided increased sensitivity compared with troponin in diagnosing acute MI. Accordingly, the use of H-FABP as a diagnostic tool for MI is limited.     

Prognostic value of a qualitative test for heart-type fatty acid-binding protein in patients with acute coronary syndrome

Heart-type fatty acid-binding protein (h-FABP) is a novel diagnostic marker for myocardial infarction, but its prognostic value has not been established in patients with acute coronary syndrome (ACS). We sought to determine the value of qualitative analysis of h-FABP for predicting 30-day adverse events in patients with ACS. A retrospective observational study was conducted on patients at a community hospital, and 130 patients admitted through the emergency room (ER) for ACS were identified among 12,077 patients who presented to the ER between January and June 2003. Of these 130 patients, 90 (mean age, 66.8 years, 67 males) who had ACS were eligible for this study. Qualitative tests for serum h-FABP and troponin T (cTnT) were performed on presentation. Follow-up information on adverse events within 30 days after admission, defined as cardiac death or recurrent ACS, was obtained from the medical records. The qualitative tests for h-FABP and troponin T were positive in 62.2% and 36.7%, respectively. The cumulative adverse event rate at 30 days was 14.8% in the h-FABP-positive group and 3.2% in the negative group. The adjusted relative risk of a positive h-FABP test for adverse events was 44.98 (95% CI: 1.48 to 1,364.88). A positive h-FABP test was an independent predictor of adverse events within 30 days in these patients.     

心型脂肪酸结合蛋白、肌钙蛋白I与急性冠脉综合征冠状动脉病变程度的相关分析

目的探讨心型脂肪酸结合蛋白(H-FABP)、肌钙蛋白I(cTnI)与近期发作急性冠脉综合征(ACS)的患者冠状动脉病变严重程度的相关性及原因分析。方法ACS患者于发作12h内入院,1周内行冠脉造影者98例入选,其中急性心肌梗死(AMI)21例、不稳定型心绞痛(UAP)77例。采用双抗体夹心ELISA法定量测量待测血清H-FABP、cTnI;根据美国心脏病协会所规定的冠状动脉血管图像记分分段评价标准,对病变狭窄程度进行分度、累及血管支数计算,采用Gensini积分系统,对冠脉血管病变狭窄程度、病变部位、范围进行定量评定;用卡方检验分析血H-FABP、cTnI与狭窄程度、病变支数的相关性;采用二元回归分析方法分析血清H-FABP、cTnI与患者冠状动脉病变严重程度的相关性。结果H-FABP≥8.0mg/L组与H-FABP<8.0mg/L组冠状动脉狭窄程度、累及支数及Gensini积分有明显差异(P<0.01);cTnI≥1.0mg/L组与cTnI<1.0mg/L组冠状动脉狭窄程度、累及支数及Gensini积分有明显差异(P<0.01);血清H-FABP、cTnI与患者冠状动脉病变严重程度的二元线性回归方程:Y=15.664 2.833x1 1.034x2(Y为Gensini积分,x1血中H-FABP浓度,x2为cTnI浓度);标准回归系数r为0.518和0.253(P<0.01)。结论H-FABP、cTnI与近期发作ACS的患者冠状动脉病变严重程度呈正相关,H-FABP与冠脉病变程度相关程度更高。血清H-FABP、cTnI升高是冠状动脉病变急性加重的直接结果,临床可根据血清H-FABP升高推断冠脉病变的危险度并采取积极的治疗措施。     

心型脂肪酸结合蛋白、肌钙蛋白Ⅰ与急性冠脉综合征冠状动脉病变程度的相关分析

目的探讨心型脂肪酸结合蛋白（H-FABP）、肌钙蛋白Ⅰ（cTnⅠ）与近期发作急性冠脉综合征（ACS）的患者冠状动脉病变严重程度的相关性及原因分析。方法ACS患者于发作12h内入院，1周内行冠脉造影者98例入选，其中急性心肌梗死（AMI）21例、不稳定型心绞痛（UAP）77例。采用双抗体夹心ELISA法定量测量待测血清H-FABP、cTnⅠ；根据关国心脏病协会所规定的冠状动脉血管图像记分分段评价标准，对病变狭窄程度进行分度、累及血管支数计算，采用Gensini积分系统，对冠脉血管病变狭窄程度、病变部位、范围进行定量评定；用卡方检验分析血H-FABP、cTnⅠ与狭窄程度、病变支数的相关性；采用二元回归分析方法分析血清H-FABP、cTnⅠ与患者冠状动脉病变严重程度的相关性。结果H-FABP≥8、0mg／L组与H-FABP〈8．0mg／L组冠状动脉狭窄程度、累及支数及Gensini积分有明显差异（P〈0．01）；cTnⅠ≥1、0mg／L组与cTnⅠ〈1．0mg／L组冠状动脉狭窄程度、累及支数及Gensini积分有明显差异（P〈0．01）；血清H-FABP、cTnⅠ与患者冠状动脉病变严重程度的二元线性回归方程：Y=15．664＋2．833x1＋1．034 x2（Y为Gensini积分，x1血中H-FABP浓度，x2为cTnⅠ浓度）；标准回归系数r为0．518和0．253（P〈0．01）。结论H-FABP、cTnⅠ与近期发作ACS的患者冠状动脉病变严重程度呈正相关，H-FABP与冠脉病变程度相关程度更高。血清H-FABP、cTnⅠ升高是冠状动脉病变急性加重的直接结果，临床可根据血清H-FABP升高推断冠脉病变的危险度并采取积极的治疗措施。     

心型脂肪酸结合蛋白对急性心肌梗死的早期诊断价值

目的 探讨心型脂肪酸结合蛋白（H-FABP）对急性心肌梗死（AMI）的早期诊断价值.方法 采用固相夹心酶联免疫法（ELISA）测定64例AMI患者血浆肌钙蛋白T（cTnT）、肌酸激酶同工酶（CK-MB）、肌红蛋白（MYO）和H-FABP浓度;同时选取53例患者作为对照组.H-FABP采用两种检测方法：固相夹心酶联免疫法和胶乳比浊法免疫测定（LTIA）.结果 cTnT、CK-MB、MYO、H-FABP（by ELISA）、H-FABP（by LTIA）和ECG（心电图）诊断AMI的敏感性分别为39.1%、59.4%、64.1%、68.7%、70.3%和54.7%,特异性为98.1%、71.7%、81.1%、77.4%、90.6%和92.5%.结论 对AMI患者的诊断,H-FABP （by LTIA）优于cTnT、CK-MB、MYO、H-FABP （by ELISA）和ECG.     

心肌型脂肪酸结合蛋白在急性心肌梗死早期诊断中的应用

目的　评定脂肪酸结合蛋白 (H FABP)在急性心肌梗死 (AMI)早期诊断中的应用。　方法　采用自行开发的H FABP酶联免疫吸附试验一步夹心法对 12 6名健康体检者和 5 3例AMI患者血清H FABP进行检测 ,同时测定肌红蛋白 (MYO)、肌酸激酶同工酶 (CK MB)、肌钙蛋白I(cTnI) ,并对AMI进行动态观察 ,对早期诊断的敏感性、特异性、时效性等进行分析。　结果　H FABP在AMI后 (1 84± 0 6 4 )h血浆浓度即开始升高 ,比CK MB、cTnI早 (P <0 0 1) ;时间浓度动态曲线与MYO相似 ,与CK MB、cTnI相比曲线前移。AMI后 2h的敏感性和特异性分别为 76 4 7%、80 4 1% ;4h的敏感性和特异性分别为 89 16 %、91 2 6 %。　结论　AMI后 2、4hH FABP检测对AMI早期诊断具有较高的敏感性和特异性 ,可望成为重要的早期和排除诊断的血清心肌标志物的手段之一。     

Heart-type fatty acid-binding protein (H-FABP) as an early diagnostic biomarker in patients with acute chest pain

Background

Heart-type fatty acid-binding protein (H-FABP) is an emerging biomarker, which was found to be sensitive for the early diagnosis of acute myocardial infarction (AMI). We prospectively investigated the usefulness of H-FABP determination for the evaluation of acute chest pain in patients arriving at the emergency department.

Methods

Fifty-four patients presenting with acute ischemic chest pain were evaluated. H-FABP was estimated at admission using latex-enhanced immunoturbidimetric assay. Serial cardiac troponin I (cTnI), creatinine kinase-MB (CK-MB) determination, ischemia workup with stress testing, and/or coronary angiogram (CAG) were performed according to standard protocols.

Results

The sensitivity and specificity of H-FABP was 89.7% and 68%, for cTnI it was 62.1% and 100%, and for CK-MB it was 44.8% and 92%, respectively for diagnosis of AMI. The sensitivity of H-FABP was found to be far superior to initial cTnI and CK-MB, for those seen within 6 h (100% vs. 46.1%, 33% respectively). On further evaluation of patients with positive H-FABP and negative cTnI, 71.4% of the patients had significant lesion on CAG, indicating ischemic cause of H-FABP elevation. Six patients with normal cTnI and CK-MB with high H-FABP had ST elevation on subsequent ECGs and were taken for primary angioplasty.

Conclusion

H-FABP is a highly sensitive biomarker for the early diagnosis of AMI. H-FABP as early marker and cTnI as late marker would be the ideal combination to cover the complete diagnostic window for AMI. Detection of myocardial injury by H-FABP may also be applied in patients with unstable angina. H-FABP can also be used as a marker for early detection of STEMI before the ECG changes become apparent.     

急性心肌梗死心肌型脂肪酸结合蛋白的动态变化

目的　了解心肌型脂肪酸结合蛋白在急性心肌梗死 (AMI)后血清浓度变化特征 ,探讨其对AMI的潜在价值。方法　采用酶联免疫吸附实验一步夹心法对 12 6例健康体检者和 5 3例AMI患者进行血清心肌型脂肪酸结合蛋白(H FABP)检测 ,其中AMI患者分为再灌注组和非再灌注组 ,同时测定肌红蛋白、心肌型肌酸激酶同工酶、肌钙蛋白I,以各自的诊断参考值为基值作标准化比值时间曲线进行动态分析。结果　AMI后 2hH FABP和肌红蛋白血清浓度明显升高 ,峰值时间及恢复时间较肌酸激酶同工酶和肌钙蛋白I前移 ,脂肪酸结合蛋白、肌钙蛋白I峰值标准化比值显著高于肌红蛋白、肌酸激酶同工酶 ,再灌注组的H FABP较非再灌注组曲线前移和峰值增高更为显著。结论　H FABP将是一种可为临床提供多种有用信息 ,有重要临床价值的AMI心肌标志物     

心脏型脂肪酸结合蛋白诊断急性心肌梗死早期指标的可行性研究

目的：测定急性心肌梗死（AMI）患者、冠心病患者及正常人血清中心脏型脂肪酸结合蛋白（h-FABP)的水平，以检测其作为AMI早期诊断指标的有效性，为早期诊断AMI提供特异而敏感的生化指标。方法：（1）从心脏组织中利用RT－PCR方法克隆h-FABP基因，并转入E.coli中表达。（2）制备抗h-FABP的单抗和多抗；（3）利用ELISA方法，测定不同血清中h-FABP的浓度，结果：（1）h-FABP在E.coli中高水平表达，并经纯化得到了人的h-FABP；（2）制备了抗h-FBAP的单抗及多抗，并通过纯化得到了特异于h-FABP的IgG;(3)AMI患者血清中的h-FABP浓度明显高于冠心病患者和正常人，并且在发病后2h开始升高，在5－6h内达到最高值，在12－24h内恢复到正常水平，结论：h-FABP对于早期诊断AMI具有较高的敏感性和特异性，是早期诊断AMI的理想生化指标。     

心肌脂肪酸结合蛋白对早期急性心肌梗死的诊断

目的研究血浆心肌脂肪酸结合蛋白(HFABP)在早期急性心肌梗死(AMI)诊断中的价值。方法选择93例发病6h内的胸痛患者,其中AMI组32例,非AMI组61例[含不稳定型心绞痛(UAP)24例,稳定型心绞痛(SAP)者22例,非心源性胸痛者15例];正常对照组选择69例正常人。采用双抗体夹心酶联免疫一步法检测正常人和患者发病0～3h或3～6h血浆的HFABP含量,并与心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶(CKMB)和肌红蛋白(MYO)的检测结果进行比较,分析4种生化标志物诊断发病3h内和6h内AMI的敏感性、特异性和准确性。结果在0～3h、0～6h时间段,HFABP诊断AMI的敏感性(64.29%、84.38%)显著高于cTnI(28.57%、53.13%)和CKMB(21.43%、56.25%),与MYO(71.43%、78.13%)比较差异无统计学意义;在诊断特异性上,4种生化标志物差异无统计学意义;在诊断准确性上,HFABP的ROC曲线下面积(0.979、0.958)显著高于cTnI(0.800、0.878)、CKMB(0.575、0.782)和MYO(0.796、0.882)。结论HFABP对于诊断早期AMI具有较高的敏感性和良好的特异性,其诊断准确性优于cTnI、CKMB、MYO。     

心型脂肪酸结合蛋白在急性冠脉综合征中的临床应用

心型脂肪酸结合蛋白是近几年国内外研究较多的一种新型心脏生化标志物,其心肌特异性强,在心肌细胞受损后可早期快速大量释放入外周血中,对于急性心肌损伤的早期诊断及预后判断均有很大的临床意义。本文就心型脂肪酸结合蛋白在急性冠脉综合征中的临床应用前景做一综述。     

心型脂肪酸结合蛋白在急性冠脉综合征患者中的变化及其临床意义

目的探讨心型脂肪酸结合蛋白(H-FABP)在急性冠脉综合征(ACS)患者中的变化及其临床意义。方法冠心病患者110例并行冠脉造影证实,其中急性心肌梗死(AMI)35例、不稳定型心绞痛(UAP)45例,稳定型心绞痛30例。采用双抗体夹心ELISA法定量测量待测血清HFABP、Myo、cTn和CK-MB浓度,根据美国心脏病协会所规定的冠状动脉血管图像记分分段评价标准,对病变狭窄程度进行分度,累及血管支数计算;用卡方检验分析血HFABP、Myo和cTnI以及CK-MB与患者冠状动脉狭窄程度、病变支数的相关性。结果 AMI患者H-FABP、CK-MB、MYO、cTnI较健康体检者、稳定型心绞痛和不稳定型心绞痛患者显著增高(P<0.01),UAP患者H-FABP也较SAP患者升高(P<0.01),无论是胸痛发生3小时前还是3小时之后,H-FABP的阳性率均比Myo和CK-MB以及cTnI敏感性更高(P<0.01)。在ACS患者H-FABP无论在发病3小时之前还是之后均较Myo和cTnI以及CK-MB更早出现(P<0.05)。ACS患者H-FABP的水平与冠脉狭窄程度及病变支数明显相关,即双支病变和多支病变高于单支病变,重度狭窄高于中度和轻度狭窄病变(P<0.05)。ACS患者的心脏射血分数(EF值)小于40%的H-FABP水平要高于EF大于40%的H-FABP水平(P<0.05)。结论 H-FABP对ACS的诊断较Myo、CK-MB和cTnI更敏感。H-FABP、Myo、cTnI以及CK-MB的联合检测与ACS的患者冠状动脉病变严重程度呈正相关,H-FABP与冠脉病变程度相关程度更高。血清H-FABP、Myo、cTnI以及CK-MB升高是冠状动脉病变加重的结果。