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Increased H-FABP concentrations in nonalcoholic fatty liver disease

Possible marker for subclinical myocardial damage and subclinical atherosclerosis

Erhöhte H-FABP-Konzentrationen bei nichtalkoholbedingter Steatosis hepatis

Ein möglicher Marker für subklinische Myokardschädigung und subklinische Atherosklerose

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Abstract

Aim

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder which is reported as the hepatic manifestation of metabolic syndrome with an increased risk of cardiovascular events. Patients with NAFLD are also at risk of future cardiac events independently of metabolic syndrome. The aim of this study was to examine serum concentrations of heart type fatty acid binding protein (H-FABP) in NAFLD and to investigate its correlations with metabolic parameters and subclinical atherosclerosis.

Patients and methods

A total of 34 patients with NAFLD and 35 healthy subjects were enrolled in the study. NAFLD patients had elevated liver enzymes and steatosis graded on ultrasonography. Healthy subjects had normal liver enzymes and no steatosis on ultrasonography. H-FABP levels were measured using an enzyme linked immunosorbent assay (ELISA) method and correlations with metabolic parameters and subclinical atherosclerosis were examined. Subclinical atherosclerosis was determined with carotid artery intima–media thickness (CIMT) which was measured by high resolution B mode ultrasonography.

Results

H-FABP levels were elevated in patients with NAFLD (16.3 ± 4.0 ng/ml) when compared with healthy controls (13.8 ± 2.1 ng/ml; p  < 0.001). NAFLD patients had significantly higher CIMT than the controls had (0.64 ± 0.17 mm vs. 0.43 ± 0.14 mm, p = 0.009). The H-FABP concentrations were significantly positively correlated with body mass index (r = 0.255, p = 0.042), fasting blood glucose level (r = 0.300, p = 0.013), CIMT (r = 0.335, p = 0.043), and homeostasis model assessment-estimated insulin resistance (HOMA-IR; r = 0.156, p = 0.306). In multiple linear regression analysis, H-FABP levels were only independently associated with CIMT (p = 0.04)

Conclusion

Serum H-FABP concentrations increase in patients with NAFLD. Our results may not only suggest that H-FABP is a marker of subclinical myocardial damage in patients with NAFLD but also of subclinical atherosclerosis, independent of metabolic syndrome and cardiac risk factors.

Zusammenfassung

Ziel

Die nichtalkoholbedingte Steatosis hepatis (NAFLD) ist die häufigste Lebererkrankung, die als hepatische Manifestation eines metabolischen Syndroms mit erhöhtem Risiko für kardiovaskuläre Ereignisse angegeben wird. Auch unabhängig von einem metabolischen Syndrom haben NAFLD-Patienten ein erhöhtes Risiko für kardiale Ereignisse. Ziel der Studie war es, die Serumkonzentrationen von H-FABP (herzspezifisches fettsäurebindendes Protein, „heart type fatty acid binding protein“) bei NAFLD-Patienten zu bestimmen und auf mögliche Korrelationen mit metabolischen Parametern sowie einer subklinischen Atherosklerose hin zu untersuchen.

Patienten und Methoden

In die Studie aufgenommen wurden 34 NAFLD-Patienten und 35 gesunden Probanden. NAFLD-Patienten hatten erhöhte Leberenzyme und eine sonographisch graduierte Steatosis hepatis, die Probanden normwertige Leberenzyme und keine sonographisch nachzuweisende Steatosis. H-FABP wurde mit einer ELISA(„enzyme-linked immunosorbent assay“)-Methode ermittelt und auf mögliche Korrelationen mit metabolischen Parametern sowie subklinischer Atherosklerose untersucht. Über die sonographische Messung der Intimadicke der A. carotis („carotid artery intima media thickness“, CIMT) im hochauflösenden B-Modus wurde die subklinische Atherosklerose bestimmt.

Ergebnisse

H-FABP-Serumkonzentrationen waren bei NAFLD-Patienten im Vergleich mit gesunden Probanden erhöht (16,3±4,0 vs. 13,8±2,1 ng/ml; p<0,001). CIMT-Werte waren bei NAFLD-Patienten höher als bei den Kontrollen 0,64±0,17 vs. 0,43±0,14 mm, p=0,009). Signifikante positive Korrelationen bestanden zwischen H-FABP-Serumkonzentrationen und BMI (r=0,255, p=0,042), Nüchternglukosekonzentrationen (r=0,300, p=0,013), CIMT (r=0,335, p=0,043) und HOMAR-IR („homeostasis model assessment-estimated insulin resistance“, r=0,156, p=0,306). In der multiplen Regressionsanalyse bestand ein unabhängiger Zusammenhang nur zwischen H-FABP-Konzentrationen und CIMT (p=0,04).

Fazit

H-FABP-Serumkonzentrationen sind bei NAFLD-Patienten erhöht. Unsere Ergebnisse könnten darauf hinweisen, dass H-FABP bei diesen Patienten nicht nur ein Marker für subklinische Myokardschädigungen ist, sondern auch für eine subklinische Atherosklerose − unabhängig von einem metabolischen Syndrom und kardialen Risikofaktoren.

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Abbreviations

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

CIMT:

Carotid artery intima–media thickness

H-FABP:

Heart type fatty acid binding protein

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

GGT:

Gama glutamyl transferase

BMI:

Body mass index

HOMA-IR:

Homeostasis model assessment-estimated insulin resistance

ELISA:

Enzyme linked immunosorbent assay

LDL:

Low-density lipoprotein

HDL:

High-density lipoprotein

TnT:

Troponin-T

NR:

Normal range

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Conflict of interest

On behalf of all authors, the corresponding author states that there are no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Financial support

No financial support was received for the study.

Ethics adherence

The study was approved by the ethics review committee of our hospital.

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Authors and Affiliations

  1. Department of Gastroenterology, Akdeniz University School of Medicine, Antalya, Turkey

    Ö. Başar M.D. & Y. Tuna

  2. Department of Gastroenterology, Ankara Education and Research Hospital, Ankara, Turkey

    E. Akbal, S. Köklü & E. Koçak

  3. Department of Cardiology, Akdeniz University School of Medicine, Antalya, Turkey

    N. Başar

  4. Department of Cardiology, Türkiye Yüksek İhtisas Education and Research Hospital, Ankara, Turkey

    D. Tok

  5. Department of General Surgery, Pamukkale University School of Medicine, Denizli, Turkey

    H. Erbiş

  6. Department of Biochemistry, Ankara Education and Research Hospital, Ankara, Turkey

    M. Şenes

  7. Department of Gastroenterology, Dişkapı Yıldırım Beyazıt Education and Research Hospital, Karargahtepe mahallesi Çamaltı sokak, 41/3, 06120, Ankara, Keçiören, Turkey

    Ö. Başar M.D.

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  1. Ö. Başar M.D.
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Başar, Ö., Akbal, E., Köklü, S. et al. Increased H-FABP concentrations in nonalcoholic fatty liver disease. Herz 38, 417–422 (2013). https://doi.org/10.1007/s00059-012-3714-x

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