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Association of bilirubin with coronary artery calcification and cardiovascular events in the general population without known liver disease: the Heinz Nixdorf Recall study

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Abstract

Background

Bilirubin is a product of heme oxygenase and an antioxidant per se. In selected cohorts and patient studies, bilirubin was associated with decreased risk for cardiovascular events. We aimed to determine the association of serum bilirubin with coronary artery calcification (CAC) and incident cardiovascular disease in the unselected general population.

Methods

Participants without prior coronary heart or liver disease were drawn from the population-based Heinz Nixdorf Recall study. CAC was measured from electron beam computed tomography and quantified using the Agatston method. Incident major cardiovascular events (coronary events, stroke, cardiovascular death) were assessed during follow-up. The association of bilirubin with CAC score and incident events was calculated using regression analysis.

Results

A total of 3,553 subjects (mean age 59.4 years, 44 % male) were included. Bilirubin was inversely correlated with CAC in men [estimated % change in (CAC + 1) per each gender-specific standard deviation of bilirubin [95 % confidence interval (CI): −6.1 (−11.6; −1.7) %, p = 0.032] but less so in women [−3.6 (−7.7; 0.2) %, p = 0.065], when adjusting for age only. With adjustment for traditional cardiovascular risk factors, the association was less pronounced [men: −2.5 (−7.5; 2.6) %, p = 0.35, women: −0.2 (−4.1; 3.5) %, p = 0.9]. Likewise, higher bilirubin by one standard deviation was associated with 19 % lower frequency of incident cardiovascular events in age- and gender-adjusted Cox regression analysis [hazard ratio (95 % CI): 0.81 (0.68; 0.96), p = 0.014]; this effect was slightly attenuated after adjustment for traditional cardiovascular risk factors [0.87 (0.73; 1.04), p = 0.13].

Conclusion

Our data from a general population suggest that a potential protective role of bilirubin in the atherosclerosis process is largely secondary to a more beneficial risk factor profile.

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Acknowledgments

This work was supported by the Heinz Nixdorf Foundation Germany, the German Ministry of Education and Science (BMBF), and the German Research Council Assessment (Deutsche Forschungsgemeinschaft, DFG).

Conflict of interest

No conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Cardiology, West German Heart Center, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany

    Amir A. Mahabadi, Stefan Möhlenkamp, Hagen Kälsch, Marcus Bauer & Raimund Erbel

  2. Institute of Medical Informatics, Biometry, and Epidemiology, University of Duisburg-Essen, Essen, Germany

    Nils Lehmann, Susanne Moebus & Karl-Heinz Jöckel

  3. Department of Cardiology, Krankenhaus Bethanien, Moers, Germany

    Stefan Möhlenkamp

  4. Institute of Physiology, Justus-Liebig-University Giessen, Giessen, Germany

    Rainer Schulz

  5. Institute of Pathophysiology, University of Duisburg-Essen, Essen, Germany

    Gerd Heusch

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  1. Amir A. Mahabadi
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  2. Nils Lehmann
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Correspondence to Amir A. Mahabadi.

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Mahabadi, A.A., Lehmann, N., Möhlenkamp, S. et al. Association of bilirubin with coronary artery calcification and cardiovascular events in the general population without known liver disease: the Heinz Nixdorf Recall study. Clin Res Cardiol 103, 647–653 (2014). https://doi.org/10.1007/s00392-014-0697-z

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  • DOI: https://doi.org/10.1007/s00392-014-0697-z

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