Skip to main content
SpringerLink
Log in

The role of bilirubin and its protective function against coronary heart disease

Rolle des Bilirubins und seiner Schutzfunktion vor koronarer Herzkrankheit

  • Original article
  • Published:
Herz Aims and scope Submit manuscript

Abstract

Background

Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality both in industrialized and developing countries. Atherosclerosis is a chronic inflammatory disease of the arterial wall, which also involves deposition and peroxidation of lipids. Bilirubin, an important endogenous antioxidant, may limit lipid peroxidation and retard the progression of atherosclerosis. Previous studies have reported an inverse relationship between serum bilirubin levels and the risk of coronary artery disease (CAD). Taking into account that atherosclerosis is a complex process that is initiated and accelerated by diverse risk factors, we aimed to test the antiatherosclerotic effects of bilirubin in a population with multiple risk factors for CAD.

Methods

The study included 221 patients who underwent coronary angiography owing to symptoms suggestive of ischemia and/or positive noninvasive stress test results. Of the patients, 76 had normal coronary angiograms and served as the control group. The remaining 145 patients with documented CAD and two or more cardiovascular risk factors constituted the study group. The study group (n=145) was further classified according to the Gensini score as follows: group 1 if Gensini score was 1–19 (minimal CAD, n=82), and group 2 if Gensini score was 20 or higher (significant CAD, n=63). Biochemical assessments including total and direct serum bilirubin levels were carried out using standard methods in automated systems.

Results

All of the cardiovascular risk factors were found significantly more frequently in the study group (groups 1 and 2) than in the control group. Total and direct serum bilirubin levels did not differ significantly between the control group, group 1, and group 2. There was a moderate and significant positive correlation between direct bilirubin levels and the Gensini score (r = 0.158, p = 0.019). There was no significant correlation between total bilirubin levels and the Gensini score.

Conclusion

In conclusion, our findings suggest that in the presence of multiple risk factors, similar concentrations of serum bilirubin may not confer the same level of protection against CAD as in an individual with a more favorable risk profile. The relationship between direct bilirubin levels and the Gensini score is unlikely to be causative, given the established antiatherosclerotic effects of bilirubin.

Zusammenfassung

Hintergrund

Die atherosklerotische Herz-Kreislauf-Erkrankung ist führende Ursache bei Morbidität und Mortalität sowohl in Industrie- als auch in Entwicklungsländern. Atherosklerose ist eine chronisch-entzündliche Erkrankung der Arterienwand, bei der eine Ablagerung und Peroxidation von Lipiden stattfindet. Bilirubin, ein wichtiges endogenes Antioxidans, kann die Lipidperoxidation einschränken und das Fortschreiten der Atherosklerose verzögern. In früheren Studien wurde über ein umgekehrtes Verhältnis zwischen Serumbilirubin und dem Risiko einer koronaren Herzkrankheit (KHK) berichtet. Unter Berücksichtigung dessen, dass die Atherosklerose ein komplexer Vorgang ist, der durch verschiedene Risiken ausgelöst und beschleunigt wird, war es Ziel der Studie, die antiatherosklerotischen Wirkungen von Bilirubin in einer Population mit mehreren Risikofaktoren für KHK zu untersuchen.

Methoden

221 Patienten, bei denen aufgrund ischämieverdächtiger Symptome eine Koronarangiographie erfolgte und/oder ein positives Ergebnis beim nichtinvasiven Belastungstest vorlag, wurden in die Studie aufgenommen. Als Kontrollgruppe dienten 76 Patienten mit normalen Koronarangiogrammen. Die restlichen 145 Patienten mit dokumentierter KHK und 2 oder mehr kardiovaskulären Risikofaktoren bildeten die Studiengruppe. Die Studiengruppe (n = 145) wurde nach dem Gensini-Score aufgeteilt: In der Gruppe I lag der Gensini-Score zwischen 1 und 19 (leichte KHK, n = 82); in Gruppe II lag der Gensini-Score bei 20 oder darüber (signifikante KHK, n = 63). Labortests von biochemischen Parametern, einschließlich Gesamt- und direktem Bilirubin, wurden mittels Standardtestmethoden mit automatisierten Laborsystemen durchgeführt.

Ergebnisse

Alle kardiovaskulären Risikofaktoren traten in der Studiengruppe (Gruppe I und II) im Vergleich zur Kontrollgruppe signifikant häufiger auf. Gesamt- und direktes Bilirubin unterschieden sich nicht signifikant zwischen der Kontrollgruppe, Gruppe I und Gruppe II. Es lag eine mäßige, statistisch signifikante positive Korrelation zwischen direktem Bilirubin und dem Gensini-Score vor (r = 0,158; p = 0,019). Eine signifikante Korrelation zwischen dem Gesamt-Bilirubin-Wert und dem Gensini-Score bestand nicht.

Schlussfolgerung

Die vorliegenden Ergebnisse weisen darauf hin, dass bei mehreren Risikofaktoren ähnliche Bilirubinspiegel im Serum nicht den gleichen Schutz gegen KHK verleihen wie vergleichsweise bei Individuen mit einem günstigeren Risikoprofil. In Anbetracht der antiatherosklerotischen Wirkungen von Bilirubin ist es unwahrscheinlich, dass das Verhältnis zwischen direktem Bilirubin und dem Gensini-Score ursächlich ist.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Gimbrone MA Jr, Topper JN, Nagel T et al (2000) Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann N Y Acad Sci 902:230–239

    Article  PubMed  CAS  Google Scholar 

  2. Stocker R, Yamamoto Y, McDonagh AF et al (1987) Bilirubin is an antioxidant of possible physiological importance. Science 235:1043–1046

    Article  PubMed  CAS  Google Scholar 

  3. Neuzil J, Stocker R (1994) Free and albumin-bound bilirubin are efficient co-antioxidants for alpha-tocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation. J Biol Chem 269:16712–16719

    PubMed  CAS  Google Scholar 

  4. Ollinger R, Yamashita K, Bilban M et al (2007) Bilirubin and biliverdin treatment of atherosclerotic diseases. Cell Cycle 6:39–43

    Article  PubMed  Google Scholar 

  5. Ollinger R, Bilban M, Erat A et al (2005) Bilirubin: a natural inhibitor of vascular smooth muscle cell proliferation. Circulation 112:1030–1039

    Article  PubMed  Google Scholar 

  6. Schwertner HA, Jackson WG, Tolan G (1994) Association of low serum concentration of bilirubin with increased risk of coronary artery disease. Clin Chem 40:18–23

    PubMed  CAS  Google Scholar 

  7. Breimer LH, Wannamethee G, Ebrahim S, Shaper AG (1995) Serum bilirubin and risk of ischemic heart disease in middle-aged British men. Clin Chem 41:1504–1508

    PubMed  CAS  Google Scholar 

  8. Hopkins PN, Wu LL, Hunt SC et al (1996) Higher serum bilirubin is associated with decreased risk for early familial coronary artery disease. Arterioscler Thromb Vasc Biol 16:250–255

    Article  PubMed  CAS  Google Scholar 

  9. Levinson SS (1997) Relationship between bilirubin, apolipoprotein B, and coronary artery disease. Ann Clin Lab Sci 27:185–192

    PubMed  CAS  Google Scholar 

  10. Schwertner HA, Fischer JR Jr (2000) Comparison of various lipid, lipoprotein, and bilirubin combinations as risk factors for predicting coronary artery disease. Atherosclerosis 150:381–387

    Article  PubMed  CAS  Google Scholar 

  11. Vitek L, Jirsa M, Bodanova M et al (2002) Gilbert syndrome and ischemic heart disease: a protective effect of elevated bilirubin levels. Atherosclerosis 160:449–456

    Article  PubMed  CAS  Google Scholar 

  12. Gul M, Uyarel H, Ergelen M et al (2013) Prognostic value of total bilirubin in patients with st-segment elevation acute myocardial infarction undergoing primary coronary intervention. Am J Cardiol 111(2):166–171

    Article  PubMed  CAS  Google Scholar 

  13. Wei S, Gao C, Wei G et al (2012) The level of serum bilirubin associated with coronary lesion types in patients with coronary artery disease. J Cardiovasc Med 13:432–438

    Article  CAS  Google Scholar 

  14. Troughton JA, Woodside JV, Young IS et al (2007) Bilirubin and coronary heart disease risk in the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Eur J Cardiovasc Prev Rehabil 14(1):79–84

    Article  PubMed  Google Scholar 

  15. Gensini GG (1983) A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol 51:606

    Article  PubMed  CAS  Google Scholar 

  16. Lin JP, O’Donnell CJ, Schwaiger JP et al (2006) Association between the UGT1A1*28 allele, bilirubin levels, and coronary heart disease in the Framingham Heart Study. Circulation 114:1476–1481

    Article  PubMed  CAS  Google Scholar 

  17. Schwertner HA (1998) Association of smoking and low serum bilirubin anti-oxidant concentrations. Atherosclerosis 136:383–387

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

On behalf of all authors, the corresponding author states that there are no conflicts of interest.

Author information

Authors and Affiliations

  1. Ufuk University School of Medicine, Mevlana Bulvarı 86-88, Balgat, 06520, Ankara, Turkey

    A. Erkan MD, PhD, B. Ekici, M. Uğurlu, G. İş, R. Şeker, S. Demirtaş & Ş. Korkmaz

Authors
  1. A. Erkan MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Ekici
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Uğurlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. İş
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. Şeker
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Demirtaş
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ş. Korkmaz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Erkan MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Erkan, A., Ekici, B., Uğurlu, M. et al. The role of bilirubin and its protective function against coronary heart disease. Herz 39, 711–715 (2014). https://doi.org/10.1007/s00059-013-3872-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00059-013-3872-5

Keywords

Schlüsselwörter

Search

Navigation