Ischemic biomarker heart-type fatty acid binding protein (hFABP) in acute heart failure - diagnostic and prognostic insights compared to NT-proBNP and troponin I

Ursula Hoffmann, Florian Espeter, Christel Weiß, Parviz Ahmad-Nejad, Siegfried Lang, Martina Brueckmann, Ibrahim Akin, Michael Neumaier, Martin Borggrefe, Michael Behnes, Ursula Hoffmann, Florian Espeter, Christel Weiß, Parviz Ahmad-Nejad, Siegfried Lang, Martina Brueckmann, Ibrahim Akin, Michael Neumaier, Martin Borggrefe, Michael Behnes

Abstract

Background: To evaluate diagnostic and long-term prognostic values of hFABP compared to NT-proBNP and troponin I (TnI) in patients presenting to the emergency department (ED) suspected of acute heart failure (AHF).

Methods: 401 patients with acute dyspnea or peripheral edema, 122 suffering from AHF, were prospectively enrolled and followed up to 5 years. hFABP combined with NT-proBNP versus NT-proBNP alone was tested for AHF diagnosis. Prognostic value of hFABP versus TnI was evaluated in models predicting all-cause mortality (ACM) and AHF related rehospitalization (AHF-RH) at 1 and 5 years, including 11 conventional risk factors plus NT-proBNP.

Results: Additional hFABP measurements improved diagnostic specificity and positive predictive value (PPV) of sole NT-proBNP testing at the cutoff <300 ng/l to "rule out" AHF. Highest hFABP levels (4th quartile) were associated with increased ACM (hazard ratios (HR): 2.1-2.5; p = 0.04) and AHF-RH risk at 5 years (HR 2.8-8.3, p = 0.001). ACM was better characterized in prognostic models including TnI, whereas AHF-RH was better characterized in prognostic models including hFABP. Cox analyses revealed a 2 % increase of ACM risk and 3-7 % increase of AHF-RH risk at 5 years by each unit increase of hFABP of 10 ng/ml.

Conclusions: Combining hFABP plus NT-proBNP (<300 ng/l) only improves diagnostic specificity and PPV to rule out AHF. hFABP may improve prognosis for long-term AHF-RH, whereas TnI may improve prognosis for ACM.

Trial registration: ClinicalTrials.gov identifier: NCT00143793 .

Figures

Fig. 1
Fig. 1
hFABP levels were significantly higher in patients suffering from acute heart failure (AHF) (n = 122) compared to those without (n = 279) (p = 0.0001). Data are presented as medians with 25th and 75th percentiles (boxes) and 5th and 95th percentiles (whiskers)
Fig. 2
Fig. 2
hFABP levels were significantly higher in patients of functional NYHA class III/IV (n = 128) compared to those of NYHA class I/II (n = 70) (p = 0.01) (left) and higher in patients of structural AHA/ACC stage C/D (n = 215) compared to those of stage A/B (n = 132) (p = 0.0001) (right). Data are presented as medians with 25th and 75th percentiles (boxes) and 5th and 95th percentiles (whiskers)
Fig. 3
Fig. 3
Kaplan-Meier curves evaluated by quartiles of hFABP after 1 (left panel) and 5 (right panel) years of follow-up in the total study cohort (n = 401). Increasing hFABP levels were significantly associated with long term all-cause mortality (a, top) and AHF related rehospitalization (b, bottom). Hazard Ratios (HR) were calculated for each risk group according to hFABP quartiles
Fig. 4
Fig. 4
Performance of models for all-cause mortality (top) and AHF-related rehopitalization (bottom) at 1 and 5 years in all patients (n = 401)
Fig. 5
Fig. 5
Performance of models for all-cause mortality (top) and AHF-related rehopitalization (bottom) at 1 and 5 years in AHF patients (n = 122)

References

    1. Offner GD, Brecher P, Sawlivich WB, Costello CE, Troxler RF. Characterization and amino acid sequence of a fatty acid-binding protein from human heart. Biochem J. 1988;252(1):191–8. doi: 10.1042/bj2520191.
    1. Glatz JF, van der Vusse GJ. Nomenclature of fatty acid-binding proteins. Mol Cell Biochem. 1990;98(1–2):231–5. doi: 10.1007/BF00231389.
    1. Fournier NC, Richard MA. Role of fatty acid-binding protein in cardiac fatty acid oxidation. Mol Cell Biochem. 1990;98(1–2):149–59.
    1. Alhadi HA, Fox KA. Do we need additional markers of myocyte necrosis: the potential value of heart fatty-acid-binding protein. QJM. 2004;97(4):187–98. doi: 10.1093/qjmed/hch037.
    1. Smathers RL, Petersen DR. The human fatty acid-binding protein family: evolutionary divergences and functions. Hum Genomics. 2011;5(3):170–91. doi: 10.1186/1479-7364-5-3-170.
    1. Jones RM, Prasad MR, Das DK. Modulation of fatty acid-binding capacity of heart fatty acid-binding protein by oxygen-derived free radicals. Mol Cell Biochem. 1990;98(1–2):161–6.
    1. Samanta A, Das DK, Jones R, George A, Prasad MR. Free radical scavenging by myocardial fatty acid binding protein. Free Radic Res Commun. 1989;7(2):73–82. doi: 10.3109/10715768909087926.
    1. Otaki Y, Watanabe T, Takahashi H, Hirayama A, Narumi T, Kadowaki S, et al. Association of heart-type fatty acid-binding protein with cardiovascular risk factors and all-cause mortality in the general population: the Takahata study. PLoS One. 2014;9(5):e94834. doi: 10.1371/journal.pone.0094834.
    1. Wolfrum C, Borrmann CM, Borchers T, Spener F. Fatty acids and hypolipidemic drugs regulate peroxisome proliferator-activated receptors alpha–and gamma-mediated gene expression via liver fatty acid binding protein: a signaling path to the nucleus. Proc Natl Acad Sci U S A. 2001;98(5):2323–8. doi: 10.1073/pnas.051619898.
    1. Azzazy HM, Pelsers MM, Christenson RH. Unbound free fatty acids and heart-type fatty acid-binding protein: diagnostic assays and clinical applications. Clin Chem. 2006;52(1):19–29. doi: 10.1373/clinchem.2005.056143.
    1. Colli A, Josa M, Pomar JL, Mestres CA, Gherli T. Heart fatty acid binding protein in the diagnosis of myocardial infarction: where do we stand today? Cardiology. 2007;108(1):4–10. doi: 10.1159/000095594.
    1. van der Vusse GJ, Glatz JF, Stam HC. Myocardial fatty acid homeostasis. Mol Cell Biochem. 1989;88(1–2):1–6. doi: 10.1007/BF00223416.
    1. Storch J, McDermott L. Structural and functional analysis of fatty acid-binding proteins. J Lipid Res. 2009;50(Suppl):S126–31.
    1. Storch J, Thumser AE. Tissue-specific functions in the fatty acid-binding protein family. J Biol Chem. 2010;285(43):32679–83. doi: 10.1074/jbc.R110.135210.
    1. Dekker MS, Mosterd A, Van’tHof AW, Hoes AW. Novel biochemical markers in suspected acute coronary syndrome: systematic review and critical appraisal. Heart. 2010;96(13):1001–10. doi: 10.1136/hrt.2009.189886.
    1. Bruins Slot MH, Reitsma JB, Rutten FH, Hoes AW, van der Heijden GJ. Heart-type fatty acid-binding protein in the early diagnosis of acute myocardial infarction: a systematic review and meta-analysis. Heart. 2010;96(24):1957–63. doi: 10.1136/hrt.2010.208272.
    1. Kim KS, Lee HJ, Kim K, Jo YH, Kim TY, Lee JH, et al. Heart-type fatty acid binding protein as an adjunct to cardiac troponin-I for the diagnosis of myocardial infarction. J Korean Med Sci. 2011;26(1):47–52. doi: 10.3346/jkms.2011.26.1.47.
    1. Lippi G, Mattiuzzi C, Cervellin G. 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. Clin Biochem. 2013;46(1–2):26–30. doi: 10.1016/j.clinbiochem.2012.10.016.
    1. McMahon CG, Lamont JV, Curtin E, McConnell RI, Crockard M, Kurth MJ, et al. Diagnostic accuracy of heart-type fatty acid-binding protein for the early diagnosis of acute myocardial infarction. Am J Emerg Med. 2012;30(2):267–74. doi: 10.1016/j.ajem.2010.11.022.
    1. Reiter M, Twerenbold R, Reichlin T, Mueller M, Hoeller R, Moehring B, et al. Heart-type fatty acid-binding protein in the early diagnosis of acute myocardial infarction. Heart. 2013;99(10):708–14. doi: 10.1136/heartjnl-2012-303325.
    1. Kilcullen N, Viswanathan K, Das R, Morrell C, Farrin A, Barth JH, et al. 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. doi: 10.1016/j.jacc.2007.08.021.
    1. Viswanathan K, Kilcullen N, Morrell C, Thistlethwaite SJ, Sivananthan MU, Hassan TB, et al. Heart-type fatty acid-binding protein 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. doi: 10.1016/j.jacc.2009.12.062.
    1. Hlatky MA, Greenland P, Arnett DK, Ballantyne CM, Criqui MH, Elkind MS, et al. Criteria for evaluation of novel markers of cardiovascular risk: a scientific statement from the American Heart Association. Circulation. 2009;119(17):2408–16. doi: 10.1161/CIRCULATIONAHA.109.192278.
    1. Thygesen K, Mair J, Mueller C, Huber K, Weber M, Plebani M, et al. Recommendations for the use of natriuretic peptides in acute cardiac care: a position statement from the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care. Eur Heart J. 2012;33(16):2001–6. doi: 10.1093/eurheartj/ehq509.
    1. Sun YP, Wang WD, Ma SC, Wang LY, Qiao LY, Zhang LP. [Changes of heart-type fatty acid-binding protein in children with chronic heart failure and its significance] Zhongguo Dang Dai Er Ke Za Zhi. 2013;15(2):99–101.
    1. Liu M, Zhou M, Bao Y, Xu Z, Li H, Zhang H, et al. Circulating adipocyte fatty acid-binding protein levels are independently associated with heart failure. Clin Sci (Lond) 2013;124(2):115–22. doi: 10.1042/CS20120004.
    1. Djousse L, Bartz TM, Ix JH, Kochar J, Kizer JR, Gottdiener JS, et al. Fatty acid-binding protein 4 and incident heart failure: the Cardiovascular Health Study. Eur J Heart Fail. 2013;15(4):394–9. doi: 10.1093/eurjhf/hfs196.
    1. Wang WD, Sun YP, Cui XQ. [Serum levels of fatty acid-binding protein and brain natriuretic peptide in children with pneumonia complicated by acute congestive heart failure] Zhongguo Dang Dai Er Ke Za Zhi. 2008;10(3):304–6.
    1. Behnes M, Brueckmann M, Ahmad-Nejad P, Lang S, Wolpert C, Elmas E, et al. Diagnostic performance and cost effectiveness of measurements of plasma N-terminal pro brain natriuretic peptide in patients presenting with acute dyspnea or peripheral edema. Int J Cardiol. 2009;135(2):165–74. doi: 10.1016/j.ijcard.2008.03.045.
    1. Behnes M, Lang S, Breithardt OA, Kaden JJ, Haghi D, Ahmad-Nejad P, et al. Association of NT-proBNP with severity of heart valve disease in a medical patient population presenting with acute dyspnea or peripheral edema. J Heart Valve Dis. 2008;17(5):557–65.
    1. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012;33(14):1787–847. doi: 10.1093/eurheartj/ehs104.
    1. Swedberg K, Cleland J, Dargie H, Drexler H, Follath F, Komajda M, et al. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J. 2005;26(11):1115–40. doi: 10.1093/eurheartj/ehi204.
    1. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, et al. 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;119(14):e391–479. doi: 10.1161/CIRCULATIONAHA.109.192065.
    1. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr. 2009;10(2):165–93. doi: 10.1093/ejechocard/jep007.
    1. hFABP ELISA EA-0305; available online at: .
    1. Pelsers MM, Hermens WT, Glatz JF. Fatty acid-binding proteins as plasma markers of tissue injury. Clin Chim Acta. 2005;352(1–2):15–35. doi: 10.1016/j.cccn.2004.09.001.
    1. Apple FS, Collinson PO, Biomarkers ITFoCAoC Analytical characteristics of high-sensitivity cardiac troponin assays. Clin Chem. 2012;58(1):54–61. doi: 10.1373/clinchem.2011.165795.
    1. Hanley JA, McNeil BJ. A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology. 1983;148(3):839–43. doi: 10.1148/radiology.148.3.6878708.
    1. Bayes-Genis A, de Antonio M, Vila J, Penafiel J, Galan A, Barallat J, et al. Head-to-head comparison of 2 myocardial fibrosis biomarkers for long-term heart failure risk stratification: ST2 versus galectin-3. J Am Coll Cardiol. 2014;63(2):158–66. doi: 10.1016/j.jacc.2013.07.087.
    1. Cook NR. Use and misuse of the receiver operating characteristic curve in risk prediction. Circulation. 2007;115(7):928–35. doi: 10.1161/CIRCULATIONAHA.106.672402.
    1. Cook NR. Methods for evaluating novel biomarkers–a new paradigm. Int J Clin Pract. 2010;64(13):1723–7. doi: 10.1111/j.1742-1241.2010.02469.x.
    1. Pencina MJ, D’Agostino RB, Sr, D’Agostino RB, Jr, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27(2):157–72. doi: 10.1002/sim.2929.
    1. Niizeki T, Takeishi Y, Arimoto T, Nozaki N, Hirono O, Watanabe T, et al. Persistently increased serum concentration of heart-type fatty acid-binding protein predicts adverse clinical outcomes in patients with chronic heart failure. Circ J. 2008;72(1):109–14. doi: 10.1253/circj.72.109.
    1. Niizeki T, Takeishi Y, Arimoto T, Okuyama H, Takabatake N, Tachibana H, et al. Serum heart-type fatty acid binding protein predicts cardiac events in elderly patients with chronic heart failure. J Cardiol. 2005;46(1):9–15.
    1. Niizeki T, Takeishi Y, Arimoto T, Takabatake N, Nozaki N, Hirono O, et al. 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;13(2):120–7. doi: 10.1016/j.cardfail.2006.10.014.
    1. Kociol RD, Pang PS, Gheorghiade M, Fonarow GC, O'Connor CM, Felker GM. Troponin elevation in heart failure prevalence, mechanisms, and clinical implications. J Am Coll Cardiol. 2010;56(14):1071–8. doi: 10.1016/j.jacc.2010.06.016.
    1. Butler J, Kalogeropoulos A. Hospital strategies to reduce heart failure readmissions: where is the evidence? J Am Coll Cardiol. 2012;60(7):615–7. doi: 10.1016/j.jacc.2012.03.066.
    1. Kalogeropoulos AP, Georgiopoulou VV, Butler J. Clinical adoption of prognostic biomarkers: the case for heart failure. Prog Cardiovasc Dis. 2012;55(1):3–13. doi: 10.1016/j.pcad.2012.05.004.
    1. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics–2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2–220. doi: 10.1161/CIR.0b013e31823ac046.
    1. Behnes M, Brueckmann M, Lang S, Espeter F, Weiss C, Neumaier M, et al. Diagnostic and prognostic value of osteopontin in patients with acute congestive heart failure. Eur J Heart Fail. 2013;15(12):1390–400. doi: 10.1093/eurjhf/hft112.
    1. Behnes M, Brueckmann M, Lang S, Weiss C, Ahmad-Nejad P, Neumaier M, et al. Connective tissue growth factor (CTGF/CCN2): diagnostic and prognostic value in acute heart failure. Clin Res Cardiol. 2014;103(2):107–16. doi: 10.1007/s00392-013-0626-6.

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