Clinical and analytical evaluation of an immunoturbidimetric heart-type fatty acid-binding protein assay

Abstract

Background. Heart-type fatty acid-binding protein (H-FABP) is a low molecular weight protein involved in the intracellular uptake and buffering of long chain fatty acids in the myocardium. It is an early marker for ACS. We have evaluated the Randox Laboratories immunoturbidimetric assay on a Siemens Advia 1800 analyzer. The assay employs latex particles coated with mouse monoclonal anti-HFABP antibodies to generate turbidity. Methods. We used redundant patient samples and pools to assess precision, functional sensitivity, limit of detection, linearity, recovery of recombinant H-FABP and interference. We evaluated the 99th centile values and compared H-FABP with troponin in samples routinely received from chest pain patient samples. Results. Precision was typically < 10% and 12.5% at all concentrations for within and between batches. The functional sensitivity was 2.4 μg/L. The assay was linear on dilution over the range 2.76–115 μg/L. Recovery of recombinant H-FABP was approximately 20–25%. No interference was seen with haemoglobin concentrations <1.5 g/L, bilirubin < 250 μg/L and triacylglycerol < 5 mmol/L or rheumatoid factor. The 99th centile value in a reference population with eGFR > 60mL/min/1.73m² was 9.1 μg/L with no significant gender difference. H-FABP was measured in routine clinical samples (N = 1310) received for troponin I measurement. Using Siemens TnI > 50 ng/L as an indicator of myocardial damage, the ROC area under curve for H-FABP was 0.82. Conclusions. The immunoturbidimetric H-FABP assay is robustly designed and shows good analytical performance. It is therefore well suited for use in a routine clinical laboratory.     

心型脂肪酸结合蛋白金标记免疫层析法的建立

目的建立胶体金免疫层析检测人心型脂肪酸结合蛋白(H-FABP)的方法。方法采用胶体金标记抗H-FABP单克隆抗体67D3,将其与生物素化的抗H-FABP单抗66E2包被于吸水纤维,将链霉亲合素结合于硝酸纤维素膜,制成免疫层析试条,依据试剂条上出现肉[可见的红色线条判定结果。用其检测93例发病6h内的胸痛患者血浆中的H-FABP,与心肌肌钙蛋白Ⅰ(cTnI)和肌酸激酶MB同工酶(CK-MB)的检测结果比较,评价其诊断急性心肌梗死(AMI)的敏感性和特异性。结果金标记试条检测H-FABP的浓度低限值为16.8ng/ml,检测结果与ELISA方法比较符合率达96.9%,诊断发病3h内和6h内AMI的敏感性分别为64.29%和84.38%,高于cTnI(28.57%、53.13%)和CK-MB(21.43%、56.25%)(P<0.05),特异性无显著性差异。结论本法简便、快速、准确,可用于AMI早期筛查。     

Performance of a semi-quantitative whole blood test for human heart-type fatty acid-binding protein (H-FABP)

OBJECTIVES: We evaluated the accuracy of visually reading the whole blood Rapicheck H-FABP panel test using the quantitative plasma H-FABP concentration as the reference. SUBJECTS AND METHODS: Consecutive patients with chest pain (n = 237) who were suspected of having acute myocardial infarction were recruited. The appearance of an evident test line within 5 min was given a grade of +3 (strongly positive), appearance within 15 min +2 (moderately positive) and the appearance of a weak test line within 15 min +1 (weakly positive). RESULTS AND DISCUSSION: The concordance rates were 91.8% for positive, 70.1% for negative and 80.2% for overall. Plasma H-FABP concentrations were above the cut-off value for 9.2% of negative (0) results. Fifty percent of weakly positive (+1) and 25.0% of moderately positive (+2) results had H-FABP concentrations lower than the cut-off value. All of the strongly positive (+3) were above the cut-off value. These results suggested that the false-positive and false-negative results of Rapicheck H-FABP were caused by over or underestimation in visual reading when the plasma H-FABP concentration was near the cut-off concentration. CONCLUSIONS: Low accuracy of visual reading of Rapicheck H-FABP was due to poor estimation by manual reading around the cut-off value.     

Analytical and clinical evaluation of a new heart-type fatty acid-binding protein automated assay.

BACKGROUND: The accurate and rapid recognition of myocardial injury in patients presenting in the emergency department (ED) with chest pain continues to be a clinical challenge. Heart-type fatty acid-binding protein (H-FABP) appears to be one of the best candidates among the new early cardiac markers studied. METHODS: We evaluated the analytical characteristics of a new quantitative and fully automated H-FABP assay (Randox Laboratories Ltd., Crumlin, UK) and compared its clinical performance with respect to the myoglobin (Myo) assay (Dade Behring, Milan, Italy). A precision study was carried out by testing three levels of quality control (QC) material and two in-house pool (P) samples. To test the accuracy of H-FABP determinations in plasma (lithium-heparin) samples, H-FABP concentrations measured in a set of matched sera and plasma samples were compared. A total of 77 non-consecutive patients (51 males and 26 females; 62+/-16 years) who presented to the ED with chest pain suggesting myocardial ischemia were enrolled. The patients were classified into two groups (acute myocardial infarction, n=22; non-acute myocardial infarction, n=55) on the basis of the discharge diagnosis. RESULTS: The between-day imprecision for three levels of control material and serum pool samples was 6.26%-8.04% (range 2.32-44.03 microg/L) and 9.03%-12.63% (range 11.85-65.13 microg/L), respectively. In the serum vs. plasma study, bias was +0.178 (95% CI -0.033 to +0.389). The best cut-off and the associated diagnostic efficacy were 95 microg/L and 89.47% for Myo and 5.09 microg/L and 98.70% for H-FABP, respectively. CONCLUSIONS: H-FABP determination in patients with ischemic symptoms may be a more reliable early indication of cardiac damage than myoglobin.     

血浆心肌脂肪酸结合蛋白在急性胸痛患者诊断中的意义

目的探讨血浆心肌脂肪酸结合蛋白(H-FABP)在急性胸痛患者中的诊断价值。方法对93例胸痛发作6 h内的患者,采用夹心ELISA法检测血浆H-FABP水平,其中急性心肌梗死(AMI)32例、不稳定型心绞痛(UAP)24例、稳定型心绞痛(SAP)22例,非心源性胸痛(NCCP)15例,并选69例健康体检者为对照组。结果AMI组的H-FABP水平(78.58±52.2 ng/mL)最高,UAP组(12.57±5.80 ng/mL)次之,差异有统计学意义(P<0.01);SAP组(3.52±2.29 ng/mL)、NCCP组(4.09±4.18 ng/mL)与对照组(3.30±1.56 ng/mL)比较差异无统计学意义(P>0.05)。以16.8 ng/mL作为H-FABP诊断AMI的最佳临界值,其诊断AMI敏感性为84.4%,特异性为91.8%。结论血浆H-FABP水平可作为心肌坏死或损伤的早期判断指标,可为急性胸痛患者的诊断提供依据。     

Prognostic impact of the serum heart-type fatty acid-binding protein (H-FABP) levels in patients admitted to the non-surgical intensive care unit

Background

Biomarkers predicting adverse outcomes in non-surgical intensive care patients have not been reported.

Methods and results

Data for 1,006 emergency department patients were prospectively analyzed. The serum heart-type fatty acid-binding protein (s-H-FABP) level was measured within 10 min of admission. The patients were assigned to intensive care (n = 835) or other departments (n = 171). The intensive care patients were divided into survivors (n = 745) and non-survivors (n = 90) according to the in-hospital mortality and assigned to four groups according to the quartiles of s-H-FABP (Q1, Q2, Q3 and Q4). The s-H-FABP levels were significantly higher in the intensive care patients (12.7 [6.1–38.8] ng/ml versus 5.3 [3.1–9.4] ng/ml) and in the non-survivors (44.9 [23.2–87.6] ng/ml versus 11.5 [5.6–32.6] ng/ml). A Kaplan–Meier curve showed a significantly higher survival rate in Q3 than in Q1 and Q2 and in Q4 than in the other groups. The multivariate Cox regression model identified Q3 (HR 4.646, 95 % CI 1.526–14.146) and Q4 (HR 9.483, 95 % CI 3.152–28.525) as independent predictors of 90-day mortality. The sensitivity and specificity of H-FABP for in-hospital mortality were 81.1 and 66.0 % (AUC 0.775) at 20.95 ng/ml. The in-hospitality rate was significantly higher in the high s-H-FABP patients than in the low s-H-FABP patients in each etiology group.

Conclusions

The s-H-FABP level is an effective biomarker for risk stratification in non-surgical intensive care patients.     

Human heart-type cytoplasmic fatty acid-binding protein (H-FABP) for the diagnosis of acute myocardial infarction. Clinical evaluation of H-FABP in comparison with myoglobin and creatine kinase isoenzyme MB.

Heart-type fatty acid-binding protein (H-FABP) is a low molecular weight cytoplasmic protein and present abundantly in the myocardium. When the myocardium is injured, as in the case of myocardial infarction, low molecular weight cytoplasmic proteins including H-FABP are released into the circulation and H-FABP is detectable in a blood sample. We have already developed a direct sandwich-ELISA for quantification of human H-FABP using two distinct types of monoclonal antibodies specific for human H-FABP. In this study we investigated the clinical validity of H-FABP as a biochemical diagnostic marker in the early phase of acute myocardial infarction (AMI). To evaluate the diagnostic usefulness of H-FABP in the early phase of AMI, blood samples were obtained from the following patients within 12 hours after the appearance of symptoms, and serum levels of H-FABP were compared with those of conventional diagnostic markers, such as myoglobin and creatine kinase isoenzyme MB (CK-MB). Blood samples were collected from patients with confirmed AMI (n=140), patients with chest pain who were afterwards not classified as AMI by normal CK-MB levels (non-AMI) (n=49) and normal healthy volunteers (n=75). The serum concentration of H-FABP was quantified with our direct sandwich-ELISA. The concentration of myoglobin mass was measured with a commercial RIA kit. The serum CK-MB activity was determined with an immuno-inhibition assay kit. The overall sensitivity of H-FABP, within 12 hours after the appearance of symptoms, was 92.9%, while it was 88.6% with myoglobin and 18.6% with CK-MB. The overall specificity of H-FABP was 67.3%, while it was 57.1% with myoglobin and 98.0% with CK-MB. The diagnostic efficacy rates with these markers were 86.2% (H-FABP), 80.4% (myoglobin) and 39.2% (CK-MB), respectively. The diagnostic validity of H-FABP was further assessed by receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) of H-FABP was 0.921, which was significantly greater than with myoglobin (AUC: 0.843) and CK-MB (AUC: 0.654). These parameters, such as sensitivity, specificity, diagnostic efficacy and diagnostic accuracy, obtained for patients with chest pain within 3 hours and/or 6 hours after the onset of symptoms were almost the same as those for patients within 12 hours after symptoms. H-FABP is more sensitive than both myoglobin and CK-MB, more specific than myoglobin for detecting AMI within 12 hours after the onset of symptoms, and shows the highest values for both diagnostic efficacy and ROC curve analysis. Thus, H-FABP has great potential as an excellent biochemical cardiac marker for the diagnosis of AMI in the early phase.     

心型脂肪酸结合蛋白在急性心肌梗死早期诊断中的价值

目的探讨血清心型脂肪酸结合蛋白(H-FABP)在急性心肌梗死(AMI)早期诊断中的临床应用价值。方法随机选择110例临床疑似AMI胸痛患者,采用时间分辨免疫荧光测定法(TRIFA)检测患者入院即刻血清中H-FABP含量,并与心肌肌钙蛋白I(cTnI)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、超敏C反应蛋白(hsCRP)和肌红蛋白(MYO)进行比较;对11例患者入院即刻和入院6 h后进行动态分析;以60例体检健康者作对照,绘制各心肌损伤标志物受试者工作特征(ROC)曲线并进行曲线下面积(AUC)比较,分析6种心肌损伤标志物诊断早期AMI的敏感度和特异度。结果 AMI患者入院即刻各心肌损伤标志物的AUC由大到小依次为H-FABP、hsCRP、cTnI、CK-MB、CK和MYO,最佳临界值诊断灵敏度分别为85.0%、78.7%、81.3%、73.8%、72.5%和61.3%,特异度分别为93.3%、95.0%、93.3%、100.0%、100.0%、98.3%。H-FABP的AUC与hsCRP、cTnI比较差异无统计学意义(P>0.05),与CK-MB、CK、MYO比较差异有统计学意义(P<0.05)。H-FABP诊断早期AMI的阳性率达85.0%。结论 H-FABP对于AMI早期诊断具有相对较早的检测窗口期和相对较好的特异度,在时效性、灵敏度和特异度等方面具有综合优势,可作为AMI早期诊断或排除诊断的血清标志物。多项心肌损伤指标联合检测可提高AMI实验室诊断的灵敏度、特异度及准确性。     

Diagnostic accuracy of heart-type fatty acid-binding protein for the early diagnosis of acute myocardial infarction

Objective

The aim of this study was to evaluate the diagnostic efficacy of multiple tests—heart-type fatty acid–binding protein (H-FABP), cardiac troponin I (cTnI), creatine kinase-MB, and myoglobin—for the early detection of acute myocardial infarction among patients who present to the emergency department with chest pain.

Methods

A total of 1128 patients provided a total of 2924 venous blood samples. Patients with chest pain were nonselected and treated according to hospital guidelines. Additional cardiac biomarkers were assayed simultaneously at serial time points using the Cardiac Array (Randox Laboratories Ltd, Crumlin, United Kingdom).

Results

Heart-type fatty acid–binding protein had the greatest sensitivity at 0 to 3 hours (64.3%) and 3 to 6 hours (85.3%) after chest pain onset. The combination of cTnI measurement with H-FABP increased sensitivity to 71.4% at 3 to 6 hours and 88.2% at 3 to 6 hours. Receiver operating characteristic curves demonstrated that H-FABP had the greatest diagnostic ability with area under the curve at 0 to 3 hours of 0.841 and 3 to 6 hours of 0.894. The specificity was also high for the combination of H-FABP with cTnI at these time points. Heart-type fatty acid–binding protein had the highest negative predictive values of all the individual markers: 0 to 3 hours (93%) and 3 to 6 hours (97%). Again, the combined measurement of cTnI with H-FABP increased the negative predictive values to 94% at 0 to 3 hours, 98% at 3 to 6 hours, and 99% at 6 to 12 hours.

Conclusion

Testing both H-FABP and cTnI using the Cardiac Array proved to be both a reliable diagnostic tool for the early diagnosis of myocardial infarction/acute coronary syndrome and also a valuable rule-out test for patients presenting at 3 to 6 hours after chest pain onset.     

2项指标联合检测在慢性心力衰竭诊断中的应用价值

目的探讨心型脂肪酸结合蛋白和同型半胱氨酸联合检测在慢性心力衰竭诊断中的应用价值,并结合相关临床表现,为临床诊治提供依据。方法选择2013年2月至2014年4月确诊为慢性心力衰竭的患者68例作为试验组,同期健康体检人员70例作为对照组,并对心型脂肪酸结合蛋白、同型半胱氨酸水平进行检测。结果与对照组比较,试验组患者的心型脂肪酸结合蛋白和同型半胱氨酸水平均有明显升高,差异有统计学意义(P0.05);试验组单独检测心型脂肪酸结合蛋白和同型半胱氨酸的阳性率分别为86.76%、88.24%,均低于联合检测阳性率(94.12%),差异有统计学意义(P0.05);以临床诊断为金标准,2项指标联合检测结果与临床诊断结果 Kappa一致性分析得出Kappa=0.94。结论心型脂肪酸结合蛋白和同型半胱氨酸对于慢性心力衰竭疾病的辅助诊断具有一定的临床价值,两者联合检测能有效提高阳性检出率,降低漏诊率。     

Critical review and meta-analysis on the combination of heart-type fatty acid binding protein (H-FABP) and troponin for early diagnosis of acute myocardial infarction

An early diagnosis is crucial for effective triage and management of patients with suspected acute myocardial infarction (AMI). Although troponin testing is the cornerstone of diagnosis, the sensitivity of this biomarker is still suboptimal at patient admission. The heart-type fatty acid binding protein (H-FABP) is an early and sensitive biomarker of myocardial ischemia, whose appropriate setting is in combination with troponin testing. We performed a systematic review and meta-analysis of articles that have assessed the combination of troponin and H-FABP in the early diagnosis of AMI. Eight studies, totaling 2735 patients, met the inclusion criteria but none of them used a high-sensitivity troponin immunoassay. The between-study variation was high (98.5%), and attributable to heterogeneity. When considered alone, troponin exhibited a significantly greater pooled area under the curve (AUC) than H-FABP alone (0.820 versus 0.784; p < 0.001). The pooled specificity was also higher for troponin alone than for H-FABP alone (0.94 versus 0.83; p < 0.001), whereas the cumulative sensitivity was lower for troponin than for H-FABP (0.73 versus 0.80; p = 0.02). The combination of both biomarkers exhibited a greater AUC than troponin alone (0.881; p < 0.001), as well as a higher pooled sensitivity (0.91; p < 0.001), which was however counterbalanced by a lower specificity (0.82; p < 0.001). These results attest that the combination of H-FABP with a conventional troponin immunoassay seems advantageous for increasing the sensitivity of the former biomarker, at the expense of a lower specificity. The introduction of H-FABP testing would hence require careful assessment of laboratory data or clinical signs and symptoms for excluding sources of elevation different from AMI. Further studies are needed to assess the diagnostic effectiveness of combining H-FABP with a high-sensitivity troponin immunoassay.     

Development of a simple whole blood panel test for detection of human heart-type fatty acid-binding protein.

OBJECTIVE: For the diagnosis of acute myocardial infarction (AMI), we have developed a rapid and simple whole blood panel test for the detection of human heart-type fatty acid-binding protein (H-FABP) using one-step immunochromatography. METHODS AND RESULTS: We have developed a whole blood panel test for rapid detection of human H-FABP using a one-step immunochromatography technique. The result of this panel test was not affected by the other contents of the blood such as bilirubin, hemoglobin and others. Furthermore, no cross-reactivity of the antibodies was found with other cardiac markers or other tissue-type FABPs. The result of this panel test was similar to the diagnostic cut-off value, 6.2 ng of H-FABP per mL of serum which was evaluated by the enzyme-linked immunosorbent assay (ELISA). CONCLUSION: We have developed a simple one-step immunochromatography technique to detect H-FABP in whole blood sample. Further studies are required to identify the value of this point-of-care testing (POCT) as a diagnostic marker for AMI.     

受试者特征曲线评价心肌型脂肪酸结合蛋白在急性心肌梗死早期诊断中的价值

目的　探讨国内研制的心肌型脂肪酸结合蛋白 (H FABP)在急性心肌梗死 (AMI)早期诊断中的应用价值。方法　应用酶联免疫吸附试验 (ELISA)对 5 3例AMI患者 ,分别于梗死后 2、4h进行血清心肌型脂肪酸结合蛋白H FABP、肌红蛋白 (MYO)、心肌型肌酸激酶同工酶 (CK MB)、肌钙蛋白I(cTnI)检测 ,并同时检测 12 6名健康体检者作对照 ,描绘各自的受试者特征 (ROC)曲线并进行ROC曲线分析。结果　AMI后H FABP、cTnI、CK MB、MYO 2h和 4h的ROC曲线下面积 (AUC)分别为 0 2 8、0 82 1、0 6 87、0 5 5 9和 0 95 1、0 880、0 797、0 75 9;2、4h各心肌标志物的ROC曲线下AUC大小依次为H FABP >cTnI>CK MB >MYO。其 2、4h的最佳截断点时灵敏度分别为 87 76 %、80 2 6 %、6 1 80 %、6 1 80 %和 88 12 %、83 0 8%、81 2 %、75 0 0 % ;特异度分别为 83 0 8%、84 12 %、6 2 5 0 %、4 7 12 %和 91 5 4 %、96 2 4 %、72 86 %、6 8 5 4 %。结论　H FABP较cTnI、CK MB、MYO对早期AMI具有更好的诊断价值 ,有望成为新的AMI早期诊断标志物     

缺血修饰清蛋白和心型脂肪酸结合蛋白检测在不稳定性心绞痛诊断及危险分层中的应用

目的探讨血清缺血修饰清蛋白(IMA)、心型脂肪酸结合蛋白(H-FABP)、B型利钠肽(BNP)、同型半胱氨酸(Hcy)与不稳定性心绞痛(UA)危险分层的关联性,为临床提供评估患者病情的依据。方法选取135例不稳定性心绞痛(UA)患者作为病例组,根据全球急性冠状动脉事件注册(GRACE)危险评分软件,将病例组分为低危组70例、中危组60例及高危组5例;另选取体检健康者145例作为对照组。检测血清IMA、H-FABP、BNP及Hcy水平,将病例组与对照组、病例组各危险分层进行比较。结果将病例组与对照组比较,血清H-FABP、BNP及Hcy水平差异具有统计学意义(P0.05),血清IMA差异无统计学意义(P0.05);病例组内各危险分层IMA、H-FABP、Hcy水平差异均无统计学意义(P0.05);高危组BNP水平高于低危组和中危组,差异有统计学意义(P0.05),中危组与低危组比较差异无统计学意义(P0.05)。结论 H-FABP、BNP及Hcy对临床诊断UA有一定意义,BNP对患者病情危险程度有提示作用。     

The potential role of a turbidimetric heart-type fatty acid-binding protein assay to aid in the interpretation of persistently elevated,non-changing,cardiac troponin I concentrations

BackgroundElevated and non-changing high-sensitivity cardiac troponin (hs-cTn) concentrations may suggest a process other than acute injury, possibly due to chronic condition(s) causing the elevation, an analytical error/interference or the formation of macrocomplexes. Heart-type fatty acid binding protein (H-FABP) might be useful in this setting to identify the etiology of abnormally high and non-changing cTn concentrations which could aid clinical decision making in the hospital setting.MethodsWe analytically validated the H-FABP assay (Randox) on the Abbott ARICHTECTc8000 platform, testing imprecision, linearity, stability, and matrix comparison. Over the 2-month analytical validation; EDTA plasma samples from patients with a hospital visit with persistently elevated and stable cTnI concentrations (Abbott hs-cTnI≥52 ng/L or 2x99th percentile upper limit of normal (ULN = 26 ng/L) with change between results <20%) were collected and frozen (−20 °C). These samples were tested with the H-FABP assay, polyethylene glycol (PEG) precipitation, with the lowest estimated glomerular filtration rate (eGRF) during the hospital visit also obtained from these patients.ResultsThe H-FABP assay was linear, with concentrations stable after 4 freeze/thaw cycles, up to 150 h at room temperature, and comparable between lithium heparin and EDTA plasma. During the validation there were 6 patients with eGFR ≥60 ml/min/1.73m² identified (total population screened n = 917) with high and non-changing hs-cTnI concentrations. All 6 patients had H-FABP<2xULN; with 3 patients having a macrocomplex and a final diagnosis of not ACS.ConclusionTesting of H-FABP in patients with an eGFR≥60 ml/min/1.73m² with persistently high and stable cTn elevations may help to confirm prior cardiac injury or the presence of macrocomplexes as the source of these elevations.     

心型脂肪酸结合蛋白与急性冠脉综合征冠脉病变程度的相关分析

目的:探讨心型脂肪酸结合蛋白(heart-type fatty acid-binding protein,H-FABP)与近期发作急性冠脉综合征(ACS)的患者冠脉病变严重程度的相关性及原因。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21例、不稳定性心绞痛77例。采用双抗体两步夹心ELISA法定量测量待测血清H-FABP;根据美国心脏病协会所规定的冠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H检验分析H-FABP是否大于8.0ng/mL与Gensini积分的相关性,卡方检验分析血H-FABP与狭窄程度、病变支数的相关性,采用一元回归分析方法分析血清H-FABP与患者冠脉病变严重程度的相关程度。结果:H-FABP>8.0ng/mL组与H-FABP<8.0ng/mL组冠脉狭窄程度、累及支数及Gensini积分有明显差异(P<0.001);血清H-FABP与患者冠脉病变严重程度的一元回归分析结果,标准回归系数为0.658,P<0.001;一元线性回归方程,y=13.177 3.597x(y为Gensini积分,x为血中H-FABP浓度)。结论:H-FABP与近期发作ACS的患者冠脉病变严重程度呈正相关。血清H-FABP升高是冠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。     

Analytical performance and clinical efficacy for cardiovascular risk estimation of an Olympus immunoturbidimetric high-sensitivity C-reactive protein assay.

Increased C-reactive protein (CRP) concentration within the reference interval (<10.0 mg/L) is a strong predictor of cardiovascular disease (CVD) in apparently healthy adults. Cutoff points for use of CRP in estimating CVD risk are <1, 1-3 and >3 mg/L for low, average and high relative risk, respectively. For measuring CRP concentrations to assess cardiovascular risk, high-sensitivity CRP (hsCRP) assays have been developed. The aim of this study was to evaluate the analytical performance and clinical efficacy for cardiovascular risk estimation of the Olympus immunoturbidimetric latex CRP assay (sensitive application). The comparative method used was the CardioPhase* hsCRP assay, approved by the Food and Drug Administration for use in CVD risk assessment. The imprecision of the Olympus hsCRP assay in the concentration range 0.2-10.0 mg/L was 0.38-8.16% within runs and 3.75-9.63% between runs. For method comparison studies, 194 fresh serum samples were selected to cover the interval 0.15-10.0 mg/L CRP. Comparison of the Dade Behring and Olympus methods was performed using weighted Deming regression analysis (slope 0.99 mg/L, intercept 0.002 mg/L, S(y,x)=0.02 mg/L, r=0.992) and a Bland-Altman relative difference plot (mean difference -0.002%, SD=0.040%). The agreement between the Dade Behring and Olympus methods for relative risk class assignments was 95.4%. Statistical analysis of the agreement between the two methods for each relative risk class showed that the differences between the methods were not statistically significant (p>0.10). Although previous reports found poor performance of the Olympus CRP tests for use in cardiovascular and peripheral vascular risk estimation, our study proved good analytical performance and clinical efficacy of the Olympus hsCRP assay for this use.     

心脏型脂肪酸结合蛋白持续增高对慢性心力衰竭患者不良结局的预测研究

目的研究慢性心力衰竭(CHF)患者不同疾病阶段心脏型脂肪酸结合蛋白(H-FABP)的变化规律,探讨持续增高的H-FABP早期对其不良结局的预测价值。方法连续分析184例CHF患者(入院时、出院时)和100名正常对照者(正常对照组)血清H-FABP、B型纳尿肽(BNP)水平。依据测定结果进行分组,第1组患者(82例)的H-FABP处于较低水平,第2组患者(102例)的H-FABP持续处于高水平,对两组患者进行随访,观察其不良结局的发生情况。结果正常对照组H-FABP水平为≤0.6 ng/mL,第1组患者H-FABP在其入院及出院时均处于较低水平[3.042±0.914、(2.891±0.890)ng/mL];第2组患者H-FABP入院及出院时均处于较高水平[12.276±3.991、(9.374±3.116)ng/mL]。随访中,共有54例患者发生心血管事件(29.35%,54/184),其中24例因心血管事件而死亡、30例因心血管事件而再次入院。第1组中有10例(12.20%)患者发生心血管事件,第2组中有44例(43.14%)患者发生心血管事件,两组比较差异有统计学意义(P0.01)。Kaplan-Meier曲线显示,相对于第1组而言,第2组无病生存率明显较低(P0.001)。在心血管事件发生前平均27 d H-FABP即出现明显升高,而BNP出现明显升高的时间比心血管事件发生平均早10 d,H-FABP比BNP平均早17 d出现异常。单因素Cox比例风险模型显示年龄、纽约心脏病学会(NYHA)分级、BNP、H-FABP均与心血管事件相关,将其纳入多因素Cox比例风险模型分析,结果显示H-FABP持续高表达是未来发生心血管事件的独立影响因素(OR=5.462,P0.000 1)。结论对CHF患者而言,H-FABP是一种较新的监测指标,能为早期预测患者预后、优化治疗方案提供有效的临床信息。     

心脏型脂肪酸结合蛋白和D-二聚体及高敏肌钙蛋白T在急性冠状动脉综合征早期诊断中的应用

目的 探讨心脏型脂肪酸结合蛋白(human heart-type fatty acid-binding protein,h-FABP)、D-二聚体(D-dimer)及超敏肌钙蛋白T(high-sensitive cardiac troponin T,hs-cTn T)对急性冠脉综合征(acute coronary syndrome,ACS)的早期诊断价值. 方法 收集2014年3月至2015年5月东莞市常平医院急诊科157例胸痛患者、50名健康体检者(健康对照组)的静脉血,分离得血清及血浆.测定所有研究标本的h-FABP、D-二聚体和hs-cTn T.所有实验数据均通过SPSS13.0软件进行统计学处理. 结果 ACS患者中的不稳定性心绞痛(unstable angina,UA)组、非ST段抬高心肌梗死(non-ST-elevation myocardial infarction,NSTEMI)组、ST段抬高心肌梗死(ST-elevation myocardial infarction,STEMI)组血清h-FABP水平、血浆D-二聚体水平、血清hs-cTnT水平均高于非缺血性胸痛(non-ischemic chest pain,NICP)组和健康对照组,差异具有统计学意义(P=0.002).胸痛3h以内组和3～6h组ACS患者血清h-FABP水平均高于健康对照组,差异具有统计学意义(P=0.003).胸痛3～6 h组ACS患者血浆D-二聚体、血清hs-cTn T水平均高于健康对照组,差异具有统计学意义(P=0.005).单独应用h-FABP诊断ACS(胸痛3～6 h)的敏感度为87.07％,特异度为73.62％,准确性为82.03％.h-FABP、D-二聚体及hs-cTn T联合应用诊断ACS(胸痛3～6 h)的敏感度为97.41％,特异度为59.22％,准确性为87.65％. 结论 血清h-FABP是ACS发病早期心肌缺血的敏感指标,优于hs-cTnT和血浆D-二聚体对ACS发病早期的心肌缺血诊断作用.联合检测h-FABP、D-二聚体及hs-cTnT可提高诊断的敏感性和准确性,对指导临床早期诊断ACS有一定价值.