Diagnostic Value in Acute Coronary Syndrome

The early release mechanism of H-FABP following myocardial ischemia (i.e. detectable within 30 minutes), means that it is a highly effective biomarker in the diagnosis and management of patients with suspected Acute Coronary Syndrome (ACS), especially when used in combination with Troponin (TnT or TnI).

Although H-FABP has been studied as a cardiac biomarker since the early 1990s, early progress in clinical studies was hampered by the lack of monoclonal antibodies and high quality (quantitative) assays. However, gradual improvements in H-FABP antibodies and assays over recent years has meant that the true clinical value of the biomarker has now become clear.

“Novel Biomarkers in early diagnosis of acute myocardial infarction compared with cardiac troponin” 1

McCann CJ, Glover BM, Menown IB, Moore MJ, McEneny J, Owens CG, Smith B, Sharpe PC, Young IS, Adgey JA. Eur Heart J. 2008 Dec;29(23):2843-50

“Measurement of H-FABP in patients with acute ischaemic-type chest pain at the time of admission is useful, and complements the measurement of cTnT”

McCann’s study (EHJ 2008) in the European Heart Journal in 2008 prospectively evaluated 664 chest pain patients presenting to two coronary units in the UK. They demonstrated that assessment of H-FABP within the first 4 hours of symptom onset was superior to TnT (4th gen) for the detection of AMI, and is a useful additional biomarker for patients with acute chest pain. In addition, they also found that the combination of H-FABP and TnT together offered the best diagnostic sensitivity at all timepoints (i.e.12h).

H-FABP: A highly sensitive early biomarker for diagnosis of AMI

Fig 1: Sensitivities for diagnosis of AMI for H-FABP, TnT or the combination of either biomarker.

McCann also found that median concentration levels of H-FABP differed significantly between AMI and non-AMI patients, which wasn’t the case for all the candidate biomarkers evaluated in the study.

Biomarker No acute MI, median (IQR) Acute MI, median (IQR) P<value
GP-BB (ng/mL) 7.0 (4.1-11.5) 9.3(5.5-14.8) 0.001
NT – proBNP(ng/L) 201 (80-524) 576 (166-2080) <0.001
D-dimer (ug/mL) 0.38 (0.24-0.64) 0.51 (0.30-1.10) <0.001
hsCRP (mg/L) 2.5 (1.2-7.0) 3.5 (1.7-11.4) 0.015
H-FABP (ng/mL) 3.9 (1.7-7.9) 15.6 (5.4-52.0) <0.001
MPO (ng/mL) 248 (147-415) 280 (153-447) 0.178
MMP-9 (ng/mL) 1084 (714-1167) 1152 (807-1689) 0.046
PAPP-A (ng/mL) 5.0(1.7-11.0) 6.7 (2.6-12.4) 0.044
sCD40L (pg/mL) 176 (11-623) 187 (104-342) 0.548
Fig 2: Differences in concentrations of H-FABP between AMI and non-AMI patients

“Diagnostic accuracy of H-FABP for the early diagnosis of AMI” 2

McMahon CG, Lamont JV, Curtin E, McConnell RI, Crockard M, Kurth MJ, Crean P, Fitzgerald SP. Am J Emerg Med. 2012 Feb;30(2):267-74.

McMahon’s study (AJEM 2012) prospectively evaluated 1128 chest pain patients presenting to an inner-city hospital’s emergency department in Dublin, Ireland. They evaluated TnI, CK-MB, Myoglobin and H-FABP at a range of time points after chest pain onset, and found that the optimum combination for the diagnosis of AMI (across all timepoints) was, again, Troponin and H-FABP together. This was superior to a strategy of Troponin alone, and any other combinations involving CK-MB and/or Myoglobin. In addition, they found that this dual marker strategy offered a very high negative predictive value (NPV) of 98% for the exclusion of AMI at just 3-6 hours after chest pain onset.

Troponin and H-FABP: the optimum biomarker strategy for early diagnosis of AMI

Fig 3: Sensitivity for AMI for biomarker combinations across time from symptom onset

“A FABP-ulous ‘rule out’ strategy? H-FABP and Troponin for rapid exclusion of AMI” 3

Body R, McDowell G, Carley S, Wibberley C, Ferguson J, Mackway-Jones K. Resuscitation. 2011 Aug;82(8):1041-6.

“Early diagnostic value for AMI independent of cTnI”

Body’s study (Res 2011) evaluated 705 patients presenting with suspected cardiac chest pain (within the last 24 hours, median 3.5 hours) to an emergency department (ED) in the UK, and collected blood samples at a single timepoint – on presentation to the ED.

They evaluated both Troponin alone and a commonly used strategy of Troponin, CK-MB and Myoglobin (via a point of care instrument). They also evaluated the utility of H-FABP as part of a panel of candidate cardiac biomarkers. The study found that H-FABP had a significantly higher Area Under Curve (AUC) than any of the other biomarkers, even Troponin, based on this single sample upon presentation.

Multivariate analysis identified that TnI and H-FABP was the optimal biomarker combination, with a sensitivity of 96.9% and NPV of 98.8. They also found that the combination of TnI and H-FABP was better than the triple marker panel (TnI, CKMB & Myoglobin) across all the diagnostic measures of sensitivity, specificity, NPV and PPV.

Troponin and H-FABP: the optimum biomarker strategy for diagnosis of AMI on presentation to the ED

Fig 4: Performance of biomarker combinations for diagnosis of AMI on presentation

“H-FABP Offers Similar Diagnostic Performance to High-Sensitivity Troponin T in Emergency Room Patients Presenting with Chest Pain” 4

Circ J. 2011;75(12):2813-20.

“Many more false positive hsTnT tests than false-positive H-FABP tests occurred in patients with non-ACS”

Inoue’s study (Circ J 2011) compared the diagnostic performance of H-FABP to the latest (5th) generation of Troponin T, hsTnT, in a multicentre study of 432 chest pain patients across several Japanese emergency departments. They aimed to evaluate whether H-FABP could further improve the sensitivity of hsTnT, as well as assisting in the interpretation of positive hsTnT due to non-ACS causes (e.g. heart failure, myocarditis).

They found that, based on samples taken at presentation, although hsTnT offers excellent sensitivity for AMI diagnosis, it is highly prone to false positives due to non-ACS elevations. H-FABP offers similarly excellent sensitivity, but with the added benefit of reduced false positives, especially in patients presenting to hospital in the early hours after chest pain onset (e.g. <3h).

H-FABP is additive to high sensitivity Troponin on presentation to the ED

Fig 5: Receiver operating characteristic curves showing diagnostic performance of the 2 cardiac biomarker assays on blood samples of the overall cohort, obtained at presentation for the diagnosis of acute coronary syndrome. H-FABP and hsTnT.

“Combining H-FABP and high sensitivity Troponin in the Emergency Department” 5

Body R, Carley S, Burrows G, Pemberton P, Mackway-Jones K. Abstract presented at International College of Emergency Medicine, Dublin, Ireland, June 2012

“Combination of H-FABP, hsTnT & ECG had a sensitivity of 99.1% and NPV of 99.7% at presentation”

In a poster presented at the recent International College of Emergency Medicine conference (Dublin, June 2012), Body (ICEM 2012) demonstrated that using a combination of ECG, hsTnT and H-FABP was a highly effective way of ruling-out AMI based on a single blood sample upon presentation to the ED (across 1,171 patients). This combination provided a sensitivity of 99.1% and a NPV of 99.7%, offering the potential to exclude AMI in 48.8% of all patients in the study.

Furthermore, after adjusting for hsTnT and ECG, H-FABP was also found to be independently predictive of both AMI (odds ratio 5.1, 95% CI 3.2-8.2) and MACE (odds ratio 2.8, CI 1.9-4.2) within the next 30 days.

The combination of ECG, hsTnT & H-FABP is the most effective strategy for early rule-out of AMI

Protocol Diagnostic cut-offs Sensitivity Specificity PPV NPV
H-FABP & hsTnT & ECG 95th centile = 2.5 ng/ml 99th centile = 14ng/l ECG negative 99.1% 59.3% 35% 99.7%
Table 6: Diagnostic efficacy for AMI of the combination of ECG, hsTnT & H-FABP, based on a single sample at presentation

When these results are compared to two recent publications evaluating alternative biomarker strategies, it is clear that hsTnT and H-FABP (along with ECG) is the optimum combination for the early assessment of patients with suspected AMI.

Percentage of symtomatic patients excludable for AMI according to diagnostic protocol
9.8% 27.7% 48.8%
ASPECT Study 6 (n=3582) 11 Manchester Study 7 hsTnT (n=703)12 Manchester & Stockport 5 Study (n=1171)10
TnI, CK-MB & Myo at 0h + 2h Plus ECG & TIMI scoring hsTnT at 0h using assay LoD as cut-off (3ng/l) hsTnT, H-FABP & ECG at 0h
9.8% of patients excluded forAMI at 2h 27.7% of patients excluded for AMI at 0h 48.8% of patients excluded for AMI at 0h
Figure 7: Percentage of symptomatic patients excludable for AMI according to diagnostic protocol
Prognostic Value in Acute Coronary Syndrome

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