FATTY ACID BINDING PROTEIN – THE DISCOVERY

• Diagnostic potential as biomarker for heart injury discovered in 1988 by
Professor Jan Glatz, Maastricht, Netherlands (note*1)
• Small cytoplasmic protein (15 kDa) (*1)
• Transports fatty acids from cell membrane to mitochondria for oxidation (*1)
• 20 times more specific to cardiac muscle than Myoglobin (*2)
• 10-fold lower in skeletal muscle than heart muscle, and the amounts in the
kidney, liver and small intestine are even lower again  (*3,*4)

FATTY ACID BINDING PROTEIN – THE RELEASE KINETICS

Early release mechanism of protein after MI (*2)

• Low normal plasma value
• Early release due to cytoplasmic location
• Extremely stable protein
• Detectable as early as 30 minutes after ischemic episode (*5)
• Rapid increase from base levels to clinical cut-off value, even
faster than Myoglobin (*4)

FATTY ACID BINDING PROTEIN – THE DIAGNOSTIC VALUE

H-FABP – A highly accurate early ischemic marker

H-FABP has the highest accuracy of all markers 0-12 hours post pain (*2)

“Combining H-FABP and cTnT….provided a significant improvement in sensitivity for patients presenting within 4 and 12 hours”  (*6)

“Using the combination approach consistently improved the NPV, negative likelihood ratio, and the risk ratio” (*6)

Multi-marker measurement of H-FABP and cTnl is 20% more sensitive than Troponin alone (*2)

Multi-analyte negative predictive value (NPV) enables early MI rule out

98% Negative Predictive Value (NPV) at 3-6 hours (*2)

Enables earlier exclusion of MI (*2)

More accurate risk stratification of low-medium risk chest pain patients (*2)

FATTY ACID BINDING PROTEIN – THE PROGNOSTIC VALUE

Fatty Acid Binding Protein – Presence equals increased risk

Elevated Fatty Acid Binding Protein is a significant predictor of death or MI up to 1 year (*7)

Fatty Acid Binding Protein provides additional prognostic information, independent of Troponin T, ECG and clinical examination (*7)

Increased H-FABP concentrators confers increased risk

“Patients with H-FABP concentrations >6.48ug/L had significantly increased risk of adverse events” (*8)

“Among Troponin negative patients, the cut-off of 6.48ug/L identified patients at very high risk of adverse outcomes independent of patient age and serum Creatinine” (*8)

H-FABP predicts mortality after ACS

Raised concentrations of H-FABP are strongly predictive of mortality after ACS (*9)

H-FABP allows identification of high risk patients across the full range of Tnl concentrations (*9)

Negative test result for both Tnl and H-FABP was associated with 0% mortality at 6 months (*9)

H-FABP – Prognostic value across the ACS spectrum

“This demonstrated the additive value of H-FABP, particularly for ACS subtypes such as Unstable Angina, traditionally considered to be associated with a low long-term risk” (*9)

H-FABP – COMPARISONS WITH TROPONIN

H-FABP – As accurate as high sensitivity Troponin

Benefits evident, even when used in addition to a high sensitivity Troponin assay (Siemens Tnl-Ultra) that meets the ACC/ESC guidelines (*8)

H-FABP – VALUE IN PULMONARY EMBOLISM

Only H-FABP significantly predicts 30 day mortality

“H-FABP was the only significant 30-day mortality predictor in univariate hazard ratio analysis” (*10)

H-FABP – VALUE IN CHRONIC HEART FAILURE

H-FABP is more effective than Troponin T at risk stratification in a heart failure population

H-FABP – OTHER AREAS OF ONGOING RESEARCH

Similar to Troponin, H-FABP levels can be raised in patients with renal insufficiency.

Neurodegenerative Diseases – emerging evidence suggests that H-FABP may have a role in differentiating between Alzheimer’s Disease, Dementia with Lewey-Bodies and Creutzfeld Jacobs Disease (*12)

Post-mortem detection of MI (*13)

REFERENCES

1.  Glatz JFC, van Bilsen M, Paulussen RJA, Veerkamp J, van der Vusse GJ, Reneman RS. Release of fatty acid-binding protein from isolated rat heart subjected to ischemia and reperfusion or the calcium paradox. Biochim Biophys Acta.1988;961:148-52

2.   Data on file

3.  Ghani F, Wu A, Graff L, Petry C, Armstrong G, Prigent F, Brown M. Role of heart-type fatty acid-binding protein in early detection of acute myocardial infarction. Clin. Chem. 2000; 46: 718-719

4.  Pelsers MM, Hermens WT, Glatz JF. Fatty acid-binding proteins as plasma markers of tissue injury. Clin. Chem. Acta. 2005; 352(1-2):15-35.

5.  Kleine AH, Glatz JF, van Nieuwenhoven FA. van der Vasse GJ. Release of heart type fatty acid binding protein into plasma after acute myocardial infarction in man. Mol Cell Biochem.1992;116:155-162.

6.  McCann CJ, Glover BM, Menown IB, Moore MJ, McEneny J, Owens CG, Smith B, Sharpe PC, Young IS, Adgey JA. Novel biomarkers in early diagnosis of acute myocardial infarction compared with cardiac troponin T. Eur. Heart J. 2008;29(23):2843-50.

7.  McCann CJ, Glover BM, Menown IB, Moore MJ, McEneny J, Owens CG, Smith B, Sharpe PC, Young IS, Adgey JA. Prognostic value of a multimarker approach for patients presenting to hospital with acute chest pain. Am. J. Cardiol. 2009:103(1):22-8.

8.  Viswanathan K, Kilcullen N, Morrell C, Thistlethwaite SJ, Sivananthan MU, Hassan TB, Barth JH, Hall AS. heart-type fatty-acid binding-protein (H-FABP) predicts long-term mortality and re-infarction in consecutive patients with suspected acute coronary syndrome who are troponin negative. J. Am. Coll. Cardiol. 2010;55(23): 2590-8

9.  Kilcullen N, Viswanathan K, Das R, Morrell C, Farrin A, Barth JH, Hall AS; EMMACE-2 Investigators. Heart-type fatty acid-binding protein predicts long-term mortality after acute coronary syndrome and identifies high-risk patients across the range of troponin values. J. Am. Coll. Cardiol. 2007;50(21):2061-7.

10. Kaczyñska A, Pelsers MM, Bochowicz A, Kostrubiec M, Glatz JF, Pruszczyk P. Plasma heart-type fatty acid binding protein is superior to troponin and myoglobin for rapid risk stratification in acute pulmonary embolism. Clin Chim Acta. 2006;371(1-2):117-23.

11. Niizeki T, Takeishi Y, Arimoto T, Takabatake N, Nozaki N, Hirono O, Watanabe T, Nitobe J, Harada M, Suzuki S, Koyama Y, Kitahara T, Sasaki T, Kubota I. Heart-type fatty acid-binding protein is more sensitive than troponin T to detect the ongoing myocardial damage in chronic heart failure patients. J. Card. Fail. 2007 Mar;13(2):120-7.

12. Mollenhauer B, Steinacker P, Bahn E, Bibl M, Brechlin P, Schlossmacher MG, Locascio JJ, Wiltfang J, Kretzschmar HA, Poser S, Trenkwalder C, Otto M. Serum heart-type fatty acid-binding protein and cerebrospinal fluid tau: marker candidates for dementia with Lewy bodies. Neurodegener. Dis. 2007;4(5):366-75.

13. Lescuyer P, Allard L, Zimmermann-Ivol CG, Burgess JA, Hughes-Frutiger

S, Burkhard PR, Sanchez JC, Hochstrasser DF. Identification of post-

mortem cerebrospinal fluid proteins as potential biomarkers of ischemia

and neurodegeneration. Proteomics. 2004;4(8):2234-41.

Contact Randox Laboratories for any specific questions relating to Fatty Acid Binding Protein.