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Bilirubin: from an unimportant waste product to important myocardial infarction predictor


Authors: Jaroslav A. Hubáček 1;  Libor Vítek 2,3
Authors‘ workplace: Centrum experimentální medicíny IKEM, Praha 1;  IV. interní klinika 1. LF UK a VFN v Praze 2;  Ústav lékařské biochemie a laboratorní diagnostiky 1. LF UK a VFN v Praze 3
Published in: Vnitř Lék 2018; 64(12): 1148-1152
Category:

Overview

Bilirubin is the major catabolic product of heme degradation. It has long been regarded as an unimportant waste product. However, within the last twenty-five years, it has been demonstrated to play a very important role in maintaining the body’s redox equilibrium. Disturbances of this equilibrium – increased oxidative stress – are currently considered one of the major risk factors for the development of non-communicable diseases. Although the exact mechanism is not known, a number of human studies have proved a reduced incidence of a number of (especially cardiovascular but also cancer) diseases in individuals with mildly elevated bilirubin concentrations.

Key words:

bilirubin – cardiovascular disease – morbidity – mortality


Sources
  1. Hunter DJ, Reddy KS. Noncommunicable diseases. N Engl J Med 2013; 369(14): 1336–1343. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMra1109345>.
  2. Wu LL. Review of risk factors for cardiovascular diseases. Ann Clin Lab Sci 1999; 29(2): 127–133.
  3. Hubacek JA, Stanek V, Gebauerova M et al. Traditional risk factors of acute coronary syndrome in four different male populations – total cholesterol value does not seem to be relevant risk factor. Physiol Res 2017; 66(Suppl 1): S121-S128.
  4. Tamosiunas A, Luksiene D, Baceviciene M et al. Health factors and risk of all-cause, cardiovascular, and coronary heart disease mortality: findings from the MONICA and HAPIEE studies in Lithuania. PLoS One 2014; 9(12): e114283. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0114283>.
  5. Petursson H, Sigurdsson JA, Bengtsson C et al. Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study. J Eval Clin Pract 2012; 18(1): 159–168. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1365–2753.2011.01767.x>.
  6. Hubáček J. Základy genetické determinace civilizačních onemocnění. Postgrad Med 2018; 20(Supl 1): 6–10.
  7. O‘Donnell CJ, Nabel EG. Genomics of cardiovascular disease. N Engl J Med 2011; 365(22): 2098–2109. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMra1105239>.
  8. Ezzati M, Riboli E. Behavioral and dietary risk factors for noncommunicable diseases. N Engl J Med 2013; 369(10): 954–964. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMra1203528>.
  9. Koene RJ, Prizment AE, Blaes A et al. Shared risk factors in cardiovascular disease and cancer. Circulation 2016; 133(11): 1104–1114. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.115.020406>.
  10. Virchow R. Die Pathologischen Pigmente. In Virchow R, Reinhardt B (eds). Archiv für pathologische Anatomie und Physiologie und Klinische Medicin (Virchow‘s Archiv) 1847; 1:407. Dostupné z DOI: <http://doi.org/10.1007/BF02114470>.
  11. Vitek L, Ostrow JD. Bilirubin chemistry and metabolism; harmful and protective aspects. Curr Pharm Des 2009; 15(25): 2869–2883.
  12. Zucker SD, Horn PS, Sherman KE. Serum bilirubin levels in the U.S. population: gender effect and inverse correlation with colorectal cancer. Hepatology 2004; 40(4): 827–835. Dostupné z DOI: <http://dx.doi.org/10.1002/hep.20407>.
  13. Johnson AD, Kavousi M, Smith AV et al. Genome-wide association meta-analysis for total serum bilirubin levels. Hum Mol Genet 2009; 18(14): 2700–2710. Dostupné z DOI: <http://dx.doi.org/10.1093/hmg/ddp202>.
  14. Stocker R, Yamamoto Y, McDonagh AF et al. Bilirubin is an antioxidant of possible physiological importance. Science 1987; 235(4792): 1043–1046.
  15. Ryter SW, Alam J, Choi AM. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev 2006; 86(2): 583–650. Dostupné z DOI: <http://dx.doi.org/10.1152/physrev.00011.2005>.
  16. Vítek L. Úloha bilirubínu v prevenci kardiovaskulárních a nádorových onemocnění. Čas Lék Česk 2016; 155(2): 10–14.
  17. Vítek L. Bilirubin and atherosclerotic diseases. Physiol Res 2017; 66(Suppl 1): S11-S20.
  18. Vítek L. Vztah bilirubinu k nemocem vyvolaným zvýšeným oxidačním stresem. Vnitř Lék 2013; 59(7): 618–621.
  19. Schwertner HA, Jackson WG, Tolan G. Association of low serum concentration of bilirubin with increased risk of coronary artery disease. Clin Chem 1994; 40(1): 18–23.
  20. Hopkins PN, Wu LL, Hunt SC et al. Higher serum bilirubin is associated with decreased risk for early familial coronary artery disease. Arterioscler Thromb Vasc Biol 1996; 16(2): 250–255.
  21. Kunutsor SK, Bakker SJ, Gansevoort RT et al. Circulating total bilirubin and risk of incident cardiovascular disease in the general population. Arterioscler Thromb Vasc Biol 2015; 35(3): 716–724. Dostupné z DOI: <http://dx.doi.org/10.1161/ATVBAHA.114.304929>.
  22. Kang SJ, Kim D, Park HE et al. Elevated serum bilirubin levels are inversely associated with coronary artery atherosclerosis. Atherosclerosis 2013; 230(2): 242–248. <http://dx.doi.org/10.1016/j.atherosclerosis.2013.06.021>.
  23. Horsfall LJ, Nazareth I, Petersen I. Cardiovascular events as a function of serum bilirubin levels in a large, statin-treated cohort. Circulation 2012; 126(22): 2556–2564. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.112.114066>.
  24. Marconi VC, Duncan MS, So-Armah K et al. Bilirubin is inversely associated with cardiovascular disease among HIV-positive and HIV-negative individuals in VACS (Veterans Aging Cohort Study). J Am Heart Assoc 2018; 7(10): pii: e007792. Dostupné z DOI: <http://dx.doi.org/10.1161/JAHA.117.007792>.
  25. Suh S, Cho YR, Park MK et al. Relationship between serum bilirubin levels and cardiovascular disease. PLoS One 2018; 13(2): e0193041. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0193041>.
  26. Lingenhel A, Kollerits B, Schwaiger JP et al. Serum bilirubin levels, UGT1A1 polymorphisms and risk for coronary artery disease. Exp Gerontol 2008; 43(12): 1102–1107. Dostupné z DOI: <http://dx.doi.org/10.1016/j.exger.2008.08.047>.
  27. Breimer LH, Mikhailidis DP. Is bilirubin a marker of vascular disease and/or cancer and is it a potential therapeutic target? Curr Pharm Des 2011; 17(33): 3644–3655.
  28. Wagner KH, Wallner M, Mölzer C et al. Looking to the horizon: the role of bilirubin in the development and prevention of age-related chronic diseases. Clin Sci (Lond) 2015; 129(1): 1–25. <http://dx.doi.org/10.1042/CS20140566>.
  29. Gazzin S, Vitek L, Watchko J et al. A novel perspective on the biology of bilirubin in health and disease. Trends Mol Med 2016; 22: 758–768.
  30. Oda E. Does serum builirubin prevent cardiovascular disease? J Xiangya Med 2017; 2: 58. Dostupné z DOI: <http://dx.doi.org/10.21037/jxym.2017.07.05>.
  31. Ong KL, Allison MA, Cheung BM et al. The relationship between total bilirubin levels and total mortality in older adults: the United States National Health and Nutrition Examination Survey (NHANES) 1999–2004. PLoS One 2014; 9(4): e94479. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0094479>.
  32. Mahabadi AA, 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 2014; 103(8): 647–653. Dostupné z DOI: <http://dx.doi.org/10.1007/s00392–014–0697-z>.
  33. Kimm H, Yun JE, Jo J et al. Low serum bilirubin level as an independent predictor of stroke incidence: a prospective study in Korean men and women. Stroke 2009; 40(11): 3422–3427. Dostupné z DOI: <http://dx.doi.org/10.1161/STROKEAHA.109.560649>.
  34. Gul M, Kalkan AK, Uyarel H. Serum bilirubin: a friendly or an enemy against cardiovascular diseases? J Crit Care 2014; 29(2): 305–306. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jcrc.2013.11.019>.
  35. Stender S, Frikke-Schmidt R, Nordestgaard BG et al. Genetically elevated bilirubin and risk of ischaemic heart disease: three Mendelian randomization studies and a meta-analysis. J Intern Med 2013; 273(1): 59–68. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1365–2796.2012.02576.x>.
  36. Bian LQ, Li RZ, Zhang ZY et al. Effects of total bilirubin on the prevalence of osteoporosis in postmenopausal women without potential liver disease. J Bone Miner Metab 2013; 31(6): 637–643. Dostupné z DOI: <http://dx.doi.org/10.1007/s00774–013–0452-y>.
  37. Apperley S, Park HY, Holmes DT et al. Serum bilirubin and disease progression in mild COPD. Chest 2015; 148(1): 169–175. Dostupné z DOI: <http://dx.doi.org/10.1378/chest.14–2150>.
  38. Peng F, Deng X, Yu Y et al. Serum bilirubin concentrations and multiple sclerosis. J Clin Neurosci 2011; 18(10): 1355–1359. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jocn.2011.02.023>.
  39. Balta S, Balta I, Mikhailidis DP et al. Bilirubin levels and their association with carotid intima media thickness and high-sensitivity C-reactive protein in patients with psoriasis vulgaris. Am J Clin Dermatol 2014; 15(2): 137–142. Dostupné z DOI: <http://dx.doi.org/10.1007/s40257–014–0069–5>.
  40. Zhao J, Tan S, Liu F et al. Heme oxygenase and ocular disease: a review of the literature. Curr Eye Res 2012; 37(11): 955–960. Dostupné z DOI: <http://dx.doi.org/10.3109/02713683.2012.700753>.
  41. Vitek L, Novotná M, Lenícek M et al. Serum bilirubin levels and UGT1A1 promoter variants in patients with schizophrenia. Psychiatry Res 2010; 178(2): 449–450. Dostupné z DOI: <http://dx.doi.org/10.1016/j.psychres.2009.12.008>.
  42. Gama-Marques J, Tinoco I, Pedro I et al. Unconjugated bilirubin and acute schizophrenia: a probable correlation? Actas Esp Psiquiatr 2017; 45(2): 79–88.
  43. Cao L, Xue L, Luo DM. Lower serum bilirubin concentration in patients with migraine. Int J Clin Exp Med 2015; 8(8): 13398–13402.
  44. Kim TS, Pae CU, Yoon SJ et al. Decreased plasma antioxidants in patients with Alzheimer‘s disease. Int J Geriatr Psychiatry 2006; 21(4): 344–348. Dostupné z DOI: <http://dx.doi.org/10.1002/gps.1469>.
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