Study on relationship of total bilirubin with acute coronary syndrome (ACS) and associated risk factors

Purushotham R., Nitin Gudage, Anand Ambali


Background: Cardiovascular risk factors for ACS are on the rise in people of Indian origin and ACS is now the leading cause of death. More recent evidence suggests that bilirubin is a potent physiological antioxidant that may provide important protection against atherosclerosis and inflammation. Substantial evidence has documented that the development of CAD involves lipid oxidation and formation of oxygen radicals as atherosclerosis and inflammation are associated with formation of oxygen and peroxyl radicals. Keep of these points in mind, the present study was undertaken to find relation between Serum Bilirubin and Acute Coronary Syndrome.

Methods: The present descriptive cross-sectional study conducted at A.J Institute of Medical Sciences and Research Centre, Mangaluru from October 2016 to April 2017. A detailed history, general physical examination, systemic examination and investigations was performed on all patients who fulfill the inclusion criterion and age >18yrs, both sexes who are admitted in CCU.

Results: Hypertension had statistically significant correlation with ACS. All risk factors were more associated with STEMI compared to unstable angina or NSTEMI. On Correlation of LDL and Total leucocyte count with bilirubin both were statistically significant when compared to bilirubin levels.

Conclusions: The study showed an inverse correlation of bilirubin with ACS, which in shows fact that bilirubin acts as an antioxidant and has cardioprotective action and patients with ACS have lower levels of bilirubin. This can use as a factor for screening individuals who have high risk for ACS and preventive strategies applied in them before the onset of overt ACS.



Acute coronary syndrome, Hypertension, Risk factor, Serum bilirubin

Full Text:



Gupta R, Joshi P, Mohan V, Reddy KS, Yusuf S. Epidemiological and causation of coronary heart disease and stroke in India. Heart. 2008;94:16-26.

World Health Organisation. The world health report-reducing risks, promoting healthy life. Geneva, Switzerland;2002. Available at www.who .int/whr/2002/en/whr02_en.pdf.

Leeder S, Raymond S, Greenberg H, Liu H, Esson K. A race against time: the challenge of cardiovascular disease in developing economies. Columbia University New York. 2004. Available at

Grech ED, Ramsdale DR. Acute coronary syndrome: unstable angina and non-ST segment elevation myocardial infarction. BMJ. 2003;326:1259-61.

Gupta M, Singh N, Verma S. South Asians and cardiovascular risk: what clinicians should know? Circulation. 2006;113:e924-9.

Mackman N. Triggers, targets and treatments for thrombosis. Nature. 2008;451:914-8.

Wang XL, Rain water DL, Vande Berg JF, Mitchel BD, Mahaney MC. Genetic contribution to plasma antioxidant activity. Arterioscler Thromb Vasc Biol. 2001;21:1190-5.

Fukagawa NK. Aging: is oxidative stress a marker or is it causal? Proc Soc Exp Biol Med. 1999;222:293-8.

Harrison DG. Endothelial function and oxidant stress. Clin cardiol. 1997;20:11-7.

Marui N, Offermann MK, Swerlick R, Kunsch C, Rosen CA, Ahmad M, et al. Vascular cell adhesion molecule-1(VCAM-1) Gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. J Clin Invest. 1993;92:1866-74.

Alho H, Leinonen J. Total antioxidant activity measured by chemiluminescence methods. Methods Enzymol. 1999;299:3-15.

Trapani L, Segatto M, Incerpi S, Pallottini V. 3-hydroxy 3-Methylglutaryl Coenzyme A reductase regulation by antioxidant compound: new therapeutic tools for hypercholesterolemia? Curr Mol Med. 2011;11:790-7.

Karihtala P, Soini Y. Reactive oxygen species and antioxidant mechanisms in human tissues and their relation to malignancies. APMIS. 2007;115:81-103.

Wei S, Gao C, Wei G, Chen Y, Zhong L, Li X. The level of serum bilirubin associated with coronary lesion types in patients with coronary artery disease. J Cardiovasc Med (Hagerstown). 2012;13:432-8.

Minetti M, Mallozzi C, Di Stasi AM, Pietraforte D. Bilirubin is an effective antioxidant of peroxynitrite-mediated protein oxidation in human blood plasma. Arch Biochem Biophys. 1998;352:165-74.

Baranano DE, Rao M, Ferris CD, Snyder SH. Biliverdin reductase: a major physiologic cytoprotectant. Proc Natl Acad Sci. 2002;99:16093-8.

HO, Oh GS, Lee BS, Rim JS, Kim YM, Chung HT. 3-Hydroxyanthranilic acid, one of L-tryptophan metabolites, inhibits monocyte chemoattractant protein-1 secretion and vascular cell adhesion molecule-1 expression via heme oxygenase-1 induction in human umbilical vein endothelial cells. Atherosclerosis. 2006;187:274-84

Kawamura K, Ishikawa K, Wada Y, Kimura S, Matsumoto H, Kohro T, et al. Bilirubin from heme oxygenase-1 attenuates vascular endothelial activation and dysfunction. Arterioscler ThrombVasc Biol. 2005;25:155-60.

Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN. Bilirubin is an antioxidant of possible physiological importance. Science. 1987;235:1043-6.

Ajay VS, Prabhakaran D. Coronary heart disease in Indians: Implications of the INTERHEART study. Ind J Med Res. 2010;132(5):561.

Ghem C, Sarmento-Leiye RE, De Quadros AS, Rosesetto S, Gottschall CA. Serum bilirubin concentration in patients with an established coronary artery disease. Int Heart J. 2010;51:86-91.

Vitek L, Jirsa M, Brodanová M, Kalab M, Marecek Z, Danzig V, et al. Gilbert syndrome and ischaemic heart disease: a protective effect of elevated bilirubin levels. Atherosclerosis. 2002;160:449-56.

Xavier D, Pais P, Devereaux PJ, Xie C, Prabhakaran D, Reddy KS, et al. Treatment and outcomes of acute coronary syndromes in India (CREATE): a prospective analysis of registry data. The Lancet. 2008;371(9622):1435-42.

O Malley SS, Wu R, Mayne ST, Jatlow PI. Smoking cessation is followed by increases in serum bilirubin, an endogenous antioxidant associated with lower risk of lung cancer and cardiovascular disease. Nicotine Tob Res. 2014;16:1145-9.

Kimm H, Yun JE, Jo J, Jee SH. Low serum bilirubin level as an independent predictor of stroke incidence: a prospective study in Korean men and women. Stroke. 2009;40:3422-7.

Erdogan T, Ciçek Y, Kocaman SA, Canga A, Cetin M, Durakoglugil E, et al. Increased serum bilirubin level is related to good collateral development in patients with chronic total coronary occlusion. Intern Med. 2012;51:249-55.

Robert P. Giugliano, Christopher P. Cannon, and Eugene Braunwald. Non-ST Elevation Acute Coronary Syndromes. In: Douglas L. Mann, Douglas P. Zipes, Peter Libby, Robert Bonow, editors. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine.10th edition. Philadelphia. Elseiver;2014:1155-74.

Sahin O, Kaya MG, Akpek M, Duran M, Uysal OK, Karadavut S, et al. Relation between serum total bilirubin levels and severity of coronary artery disease in patients with non-ST-segment elevation myocardial infarction. Angiology. 2014;65:245-9.

Hopkins PN, Wu LL, Hunt SC, James BC, Vincent GM, Williams RR. Higher serum bilirubin is associated with decreased risk for early familial coronary artery disease. Arterioscler Thromb Vasc Biol. 1996;16:250-5.

Troughton JA, Woodside JV, Young IS, Arveiler D, Amouyel P, Ferrières J, et al. PRIME Study Group. Bilirubin and coronary heart disease risk in the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Eur J Cardiovasc Prev Rehabil. 2007;14:79-84.

Kim KM, Kim BT, Park SB, Cho DY, Je SH, Kim KN. Serum total bilirubin concentration is inversely correlated with Framingham risk score. Arch Med Res. 2012;43:288-93.

Veerendra Kumar Arumalla, Niranjan Gopal, Rao BN. Role of serum bilirubin in coronary artery disease. Int J Med Heal Sci. 2012;2:56-62.

Kharb S. Association of serum concentration of total bilirubin and low-density lipoprotein cholesterol with myocardial infarction. World J Med Sci. 2006;1:93-4.

Song YS, Koo BK, Cho NH, Moon MK. Effect of low serum total bilirubin levels (≤0.32mg/dl) on risk of coronary artery disease in patients with metabolic syndrome. Am J Cardiol. 2014;114:1695-700.

Huang SS, Huang PH, Leu HB, Wu TC, Lin SJ, Chen JW. Serum bilirubin predicts long-term clinical outcomes in patients with cardiac syndrome X. Heart. 2009;96:1227-32.

Jaundice. In: Sherlock Sheila and Dooley James editors. Diseases of the liver and Biiary system, 11th edition Oxford, UK:Blackwell Science;2002:205-7.

Lin JP, Vitek L, Schwertner HA. Serum bilirubin and genes controlling bilirubin concentrations as biomarkers for cardiovascular disease. Clin Chem. 2010;56:1535-43.

Lin JP, O'Donnell CJ, Schwaiger JP, Cupples LA, Lingenhel A, Hunt SC, et al. Association between the UGT1A1*28 Allele, Bilirubin Levels, and Coronary Heart Disease in the Framingham Heart Study. Circulation. 2006;114:1476-81.

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):2556-64.