Heart-Type Fatty Acid Binding Protein, Cardiovascular Outcomes, and Death: Findings From the German CKD Cohort Study.

RATIONALE & OBJECTIVE: Heart-type fatty acid binding protein (H-FABP) is a biomarker that has been shown to provide long-term prognostic information in patients with coronary artery disease independently of high-sensitivity troponin T (hs-TNT). We examined the independent associations of H-FABP with cardiovascular outcomes in patients with chronic kidney disease (CKD). STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 4,951 patients enrolled in the German Chronic Kidney Disease (GCKD) study with an estimated glomerular filtration rate of 30-60 mL/min/1.73 m2 or overt proteinuria (urinary albumin-creatinine ratio > 300 mg/g or equivalent). EXPOSURE: Serum levels of H-FABP and hs-TNT were measured at study entry. OUTCOME: Noncardiovascular (non-CV) death, CV death, combined major adverse CV events (MACE), and hospitalization for congestive heart failure (CHF). ANALYTICAL APPROACH: Hazard ratios (HRs) for associations of H-FABP and hs-TNT with outcomes were estimated using Cox regression analyses adjusted for established risk factors. RESULTS: During a maximum follow-up of 6.5 years, 579 non-CV deaths, 190 CV deaths, 522 MACE, and 381 CHF hospitalizations were observed. In Cox regression analyses adjusted for established risk factors, H-FABP was associated with all 4 outcomes, albeit with lower HRs than those found for hs-TNT. After further adjustment for hs-TNT levels, H-FABP was found to be associated with non-CV death (HR, 1.57 [95% CI, 1.14-2.18]) and MACE (HR, 1.40 [95% CI, 1.02-1.92]) but with neither CV death (HR, 1.64 [95% CI, 0.90-2.99]) nor CHF hospitalizations (HR, 1.02 [95% CI, 0.70-1.49]). LIMITATIONS: Single-point measurements of H-FABP and hs-TNT. Uncertain generalizability to non-European populations. CONCLUSIONS: In this large cohort of patients with CKD, H-FABP was associated with non-CV death and MACE, even after adjustment for hs-TNT. Whether measurement of H-FABP improves cardiovascular disease risk prediction in these patients warrants further studies.

Skin Ultrastructure and the Changes of HIF-2α, H-FABP Expression in the Myocardium of Electric Shock Death Rats / 法医学杂志

Objective To observe the skin ultrastructure change of electric shock death rats and to test the expression changes of hypoxia-inducible factor-2α （HIF-2α） and heart type-fatty acid-binding protein （H-FABP） of myocardial cells, in order to provide basis for forensic identification of electric shock death. Methods The electric shock model of rats was established. The 72 rats were randomly divided into control group, electric shock death group and postmortem electric shock group. Each group was divided into three subgroups, immediate （0 min）, 30 min and 60 min after death. The skin changes of rats were observed by HE staining, the changes of skin ultrastructure were observed by scanning electron microscopy, and the expression of HIF-2α and H-FABP in rats myocardium was tested by immunohistochemical staining. Results The skin in the electric shock death group and postmortem electric shock group had no significant difference through the naked eye or by HE staining. Under the scanning electron microscope, a large number of cellular debris, cells with unclear boundaries, withered cracks, circular or elliptical holes scattered on the cell surface and irregular edges were observed. A large number of spherical foreign body particles were observed. Compared with the control group, the expression of HIF-2α in all electric shock death subgroups increased, reaching the peak immediately after death. In the postmortem electric shock group, HIF-2α expression only increased immediately after death, but was lower than that of electric shock death group （P<0.05）. Compared with the control group, the expression of H-FABP in all subgroups of electric shock death group and postmortem electric shock group significantly decreased. The expression of H-FABP in all subgroups of electric shock death group was lower than that of the postmortem electric shock group （P<0.05）. Conclusion Electric shock can increase HIF-2α expression and decrease H-FABP expression in the myocardium, which may be of forensic significance for the determination of electric shock death and identification of antemortem and postmortem electric shock.

Heart-type fatty acid binding protein predicts cardiovascular events in patients with stable coronary artery disease: a prospective cohort study.

BACKGROUND: Heart-type fatty acid binding protein (H-FABP) has been reported to be a prognostic predictor for cardiovascular outcome in acute coronary syndrome (ACS). However, its prognostic utility in patients with stable coronary artery disease (CAD) has not been well established. The aim of this study was to assess the association between H-FABP with the severity of coronary disease and cardiovascular events (CVEs) in patients with stable CAD. METHODS: A total of 4,370 angiography-proven CAD patients were consecutively enrolled. The severity of CAD was assessed by Gensini Score (GS) and the numbers of diseased vessels. The CVEs included cardiovascular death, myocardial infarction, stroke and coronary revascularization. Cox regression analysis with adjusted hazard ratios (HRs) and Kaplan-Meier analysis were used to evaluate the relation of H-FABP to CVEs in this cohort. RESULTS: During a median follow-up of 51 months, 353 CVEs occurred. Overall, patients in the highest levels of H-FABP group had increased rate of multi-vessel stenosis and higher GS compared with those in the lowest group (P<0.05, respectively). Moreover, H-FABP levels were significantly higher in patients with events compared to those without (P<0.001). In Cox regression analysis, elevated H-FABP levels were found to be independently associated with a high risk of CVEs [adjusted HRs: 1.453; 95% confidence intervals (CIs): 1.040-2.029, P=0.028], especially with cardiovascular death (adjusted HRs: 2.865; 95% CI: 1.315-6.243, P=0.008). CONCLUSIONS: Our results demonstrated that H-FABP was also a useful predictor for CVEs in patients with stable CAD, which needed to be verified by further studies.

Heart-type fatty acid-binding protein (H-FABP), pentraxin-3 (PTX-3) and thrombomodulin in bovine traumatic pericarditis.

The aim of this study was to evaluate the biomarkers of cardiac damage such as heart-type fatty acid-binding protein (H-FABP), pentraxin-3 (PTX-3), and thrombomodulin (TM) for the detection and prognosis of bovine traumatic pericarditis (TP). Spontaneous TP was diagnosed on the basis of history, clinical signs, complete blood count, glutaraldehyde test, ultrasonography, and pericardiocentesis findings. H-FABP, PTX-3 and TM levels in serum were compared between 25 Holstein cows diagnosed with spontaneous TP and 10 healthy control cows using bovine-specific ELISA kits. Serum H-FABP in cattle with TP was significantly (P < 0.05) higher than in the control group and positively correlated with cardiac troponin-I (cTnI), creatine kinase myocardial band (CK-MB), PTX-3 and TM (r = 0.683, 0.342, 0.448 and 0.424, respectively; P < 0.05). The serum levels of PTX-3 (P < 0.05) and TM (P < 0.05) in cattle with TP were significantly higher than in the control group. Cardiac damage biomarkers H-FABP, PTX-3 and TM may be useful in the diagnosis of bovine TP.

New Cardiovascular Biomarkers in Ischemic Heart Disease-GDF-15, A Probable Predictor for Ejection Fraction.

BACKGROUND: Various biomarkers have been associated with coronary artery disease (CAD) and ischemic heart failure. The aim of this study was to investigate the correlation of serum levels of soluble urokinase-type plasminogen activator receptor (suPAR), growth differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), and soluble suppression of tumorigenicity 2 (sST2) with left ventricular ejection fraction (EF) in CAD patients and controls. METHODS AND RESULTS: CAD patients were divided into three groups according to their EF as measured by the biplane Simpson method (53-84%, 31-52%, ≤30%). Overall, 361 subjects were analyzed. In total, 155 CAD patients had an EF of 53-84%, 71 patients had an EF of 31-52%, and 23 patients had an EF of ≤30% as compared to 112 healthy controls (age 51.3 ± 9.0 years, 44.6% female). Mean ages according to EF were 62.1 ± 10.9, 65.2 ± 10.1, and 66.6 ± 8.2 years, respectively, with females representing 29.0, 29.6, and 13.0%. suPAR, GDF-15, H-FABP, and sST2 values were significantly higher in CAD patients and showed an exponential increase with decreasing EF. In a multiple logistic regression model, GDF-15 (p = 0.009), and NT-brain natriuretic peptide (p = 0.003) were independently associated with EF. CONCLUSION: Biomarkers such as suPAR, GDF-15, H-FABP, and sST2 are increased in CAD patients, especially in highly impaired EF. Besides NT-proBNP as a well-known marker for risk prediction, GDF-15 may be an additional tool for diagnosis and clinical follow-up.

Troponin T and Heart Type Fatty Acid Binding Protein (h-Fabp) as Biomarkers in Patients Presenting with Chest Pain.

Acute coronary syndrome (ACS) is a term for a range of clinical signs and symptoms suggestive of myocardial ischemia. It results in functional and structural changes and ultimately releasing protein from injured cardiomyocytes. These cardiac markers play a major role in diagnosis and prognosis of ACS. This study aims to assess the efficacy of heart type fatty acid binding protein (h-FABP) as a marker for ACS along with the routinely used hs-TropT. In our observational study, plasma h-FABP (cut-off 6.32 ng/ml) and routinely done hs-Trop T (cutoff 0.1 and 0.014 ng/ml) were estimated by immunometric laboratory assays in 88 patients with acute chest pain. Based on the clinical and laboratory test findings the patients were grouped into ACS (n = 41) and non-ACS (n = 47). The diagnostic sensitivity, specificity, NPV, PPV and ROC curve at 95 % CI were determined. Sensitivity of hs-TropT (0.1 ng/ml), hs-TropT (0.014 ng/ml) and h-FABP were 53, 86 and 78 % respectively and specificity for the same were 98, 73 and 70 % respectively. Sensitivity, specificity and NPV calculated for a cut-off combination of hs-TropT 0.014 ng/ml and h-FABP was 100, 51 and 100 % respectively. These results were substantiated by ROC analysis. Measurement of plasma h-FABP and hs-TropT together on admission appears to be more precise predictor of ACS rather than either hs-Trop T or h-FABP.

Suspected acute coronary syndrome in the emergency room: Limited added value of heart type fatty acid binding protein point of care or ELISA tests: The FAME-ER (Fatty Acid binding protein in Myocardial infarction Evaluation in the Emergency Room) study.

BACKGROUND: Timely recognition of acute coronary syndrome remains a challenge as many biomarkers, including troponin, remain negative in the first hours following the onset of chest pain. We assessed the diagnostic accuracy of heart-type fatty acid binding protein (H-FABP), a cardiac biomarker with potential value immediately post symptom onset. METHODS AND RESULTS: Prospective monocentre diagnostic accuracy study of H-FABP bedside point of care (CardioDetect®) and ELISA tests in acute coronary syndrome suspected patients presenting within 24 hours of symptom onset to the emergency department, in addition to clinical findings, electrocardiography and the currently recommended biomarker high sensitivity troponin-T (hs-cTnT). The final diagnosis of acute coronary syndrome was adjudicated by two independent cardiologists, blinded to H-FABP results. Acute coronary syndrome was diagnosed in 149 (32.9%) of 453 unselected patients with suspected acute coronary syndrome (56% men, mean age 62.6 years). Negative predictive values were similar for H-FABP point of care and ELISA tests (79% vs. 78% respectively), but inferior to initial hs-cTnT (negative predictive value 86%). The addition of H-FABP point of care results to hs-cTnT increased the negative predictive value to 89%. In a multivariable logistic regression model, H-FABP point of care and ELISA tests yielded relevant diagnostic information in addition to clinical findings and ECG (likelihood ratio test p<0.001) and increased area under the receiver operating characteristics curve (AUC; 0.82 vs. 0.84 and 0.84). This added value attenuated, however, after inclusion of hs-cTnT in the diagnostic model (AUC 0.88). CONCLUSIONS: In patients suspected of acute coronary syndrome presenting to the emergency department, H-FABP testing improves diagnostic accuracy in addition to clinical findings and electrocardiography. H-FABP, however, has no additional diagnostic value when hs-cTnT measurements are also available.

Correlation between Heart-type Fatty Acid-binding Protein Gene Polymorphism and mRNA Expression with Intramuscular Fat in Baicheng-oil Chicken.

This study aims to determine the polymorphism and mRNA expression pattern of the heart-type fatty acid-binding protein (H-FABP) gene and their association with intramuscular fat (IMF) content in the breast and leg muscles of Baicheng oil chicken (BOC). A total of 720 chickens, including 240 black Baicheng oil chicken (BBOC), 240 silky Baicheng oil chicken (SBOC), and 240 white Baicheng oil chicken (WBOC) were raised. Three genotypes of H-FABP gene second extron following AA, AB, and BB were detected by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) strategy. The G939A site created AA genotype and G956A site created BB genotype. The content of IMF in AA genotype in breast muscle of BBOC was significantly higher than that of AB (p = 0.0176) and the genotype in leg muscle of WBOC was significantly higher than that of AB (p = 0.0145). The G939A site could be taken as genetic marker for higher IMF content selecting for breast muscle of BBOC and leg muscle of WBOC. The relative mRNA expression of H-FABP was measured by real-time PCR at 30, 60, 90, and 120 d. The IMF content significantly increased with age in both muscles. The mRNA expression level of H-FABP significantly decreased with age in both muscles of the three types of chickens. Moreover, a significant negative correlation between H-FABP abundance and IMF content in the leg muscles of WBOC (p = 0.035) was observed. The mRNA expression of H-FABP negatively correlated with the IMF content in both breast and leg muscles of BOC sat slaughter time.

Verification of an immunoturbidimetric assay for heart-type fatty acid-binding protein (H-FABP) on a clinical chemistry platform and establishment of the upper reference limit.

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is an early biomarker of cardiac injury. Randox Laboratories developed an immunoturbidimetric H-FABP assay for non-proprietary automated clinical chemistry analysers that could be useful in the emergency department. We verified the analytical performances claimed by Randox Laboratories on Roche Cobas 6000 clinical chemistry platform in use in our laboratory, and we defined our own 99th percentile upper reference limit for H-FABP. METHODS: For the verification of method performances, we used pools of spared patient samples from routine and two levels of quality control material, while samples for the reference value study were collected from 545 blood donors. Following CLSI guidelines we verified limit of blank (LOB), limit of detection (LOD), limit of quantitation (LOQ), repeatability and within-laboratory precision, trueness, linearity, and the stability of H-FABP in EDTA over 24h. RESULTS AND DISCUSSION: The LOQ (3.19 µg/L) was verified with a CV% of 10.4. The precision was verified for the low (mean 5.88 µg/L, CV=6.7%), the medium (mean 45.28 µg/L, CV=3.0%), and the high concentration (mean 88.81 µg/L, CV=4.0%). The trueness was verified as well as the linearity over the indicated measurement interval of 0.747-120 µg/L. The H-FABP in EDTA samples is stable throughout 24h both at room temperature and at 4 °C. The H-FABP 99th percentile upper reference limit for all subjects (3.60 µg/L, 95% CI 3.51-3.77) is more appropriate than gender-specific ones that are not statistically different.

The study of heart-type fatty acid binding protein in the PCI therapy for patients with acute myocardial infarction / 中华急诊医学杂志

Objective To observe the change and clinical significance of the heart type fatty acid binding protein (H-FABP) in ST Segment Elevation Myocardial Infarction (STEMI) after percutaneous coronary intervention (PCI).Methods Of 178 STEMI patients were recruited and were separated as ST segment drop group (137) and ST segment non-drop group (41).All the patients received H-FABP and cTnI tests,and re-tested H-FABP on 1 h,6 h,12 h and 24 h after the PCI,and re-tested cTnI on 12 h and 24 h after the PCI.Also,the ST segment drop amplitude (ΣSTR) was measured 2 h after the PCI.Results The demographics of both groups were similar.In both groups,the H-FABP on 6 h after PCI was significantly higher than the value measured prior to PCI.In the ST segment drop group,the H-FABP was reduced to normal value on 24 h after PCI,while it was not in the ST segment non-drop group.Conclusions The H-FABP elevation is associated with the severity of coronary lesions in ST segment elevation myocardial infarction,and the PCI may be involved in the H-FABP changes.ΣSTR≥50％ and normal HFABP may be used as index for judgment of myocardial injury and myocardial reperfusion.

The Impact of Chronic Liver Diseases on the Level of Heart-Type Fatty Acid-Binding Protein (H-FABP) Concentrations.

OBJECTIVES: Heart-type fatty acid binding-protein (H-FABP) has been reported to be a potential novel biochemical marker for the early diagnosis of acute myocardial infarction (AMI). The presence of H-FABP in the liver has not been reported. The aim of this study was to compare the effect of chronic liver diseases on the level of H-FABP concentrations. METHODS: The effects of chronic liver diseases including infective hepatitis and cirrhosis on the concentration of H-FABP was studied in a small group of patients (n=10, mean age ±SD = 58.33 ± 7.19 years). The serum concentrations of the following markers were measured: H-FABP, alanine aminotransferase (ALT) and bilirubin and compared with a reference control group (20 healthy blood donors, mean age ±SD = 63.8 ±8.01). RESULTS: The serum concentrations of these markers in the control group as compared to patients with chronic liver disease were as follows (mean ± SD): H-FABP = 6.86 ±2.21 µg/L versus 6.44 ±3.06 µg/L (p = NS); ALT = 29.8 ±14.7 U/L versus ALT = 198.67 ±122.89 U/L (p < 0.0005) and bilirubin = 9.6 ±4.0 µmol/L versus bilirubin = 100.89 ±87.85 µmol/L (p < 0.0001). CONCLUSION: These data illustrate clearly that there is no significant interference with the normal concentration of H-FABP in the presence of liver diseases, despite the significant elevation of liver enzymes and proteins. These data may support a useful role of H-FABP for the diagnosis of myocardial injury in patients with liver diseases.

Effects of Tanshinone ⅡA on Arrhythmia and Levels of Ischemia Modified Albumin and Heart Type Fatty Acid Binding Protein in Rats with Myocardial Ischemia-reperfusion Injury / 中药新药与临床药理

Objective To observe the effect of tanshinoneⅡA (TⅡA) on arrhythmia and levels of ischemia modified albumin (IMA) and heart type-fatty acid binding protein (H-FABP) in rats with myocardial ischemia-reperfusion injury.Methods Forty Wistar rats were equally randomized into 5 groups:pseudo-operation group (normal saline),model group (normal saline),and high-,middle-and low-dose TⅡA groups (in the dose of 20,10 and 5 mg?kg-1?d-1 respectively).The rats were treated for 7 days,and received operation 2 hours after the last medication.Rats in pseudo-operation group received threading without ligation,while animal model of myocardial ischemia-reperfusion injury was established by ligating the left-anterior coronary artery for 15 minutes and then loosening for 30 minutes.During the operation,electrocardiogram was traced continuously to observe the arrhythmia.HE staining was used to observe the pathological changes of myocardium.Levels of IMA and H-FABP in myocardium were determined by enzyme-linked immunosorbent assay (ELISA).Results Ischemic changes of the myocardium and arrhythmia occurred,myocardial IMA level increased and H-FABP level decreased in the model rats.TanshinoneⅡA obviously attenuated arrhythmia caused by ischemia-reperfusion injury (P