Article Data

  • Views 415
  • Dowloads 137

Original Research

Open Access

Total bilirubin and fasting plasma glucose levels are associated with coronary collateral development in elderly patients

  • Ertan Vuruskan1
  • Irfan Veysel Duzen1
  • Mehmet Kaplan1
  • Gokhan Altunbas1
  • Enes Alıc1
  • Fatma Yılmaz Coskun1
  • Murat Sucu1

1Department of Cardiology, Faculty of Medicine, Gaziantep University, 27000 Gaziantep, Turkey

DOI: 10.31083/jomh.2021.085

Submitted: 23 March 2021 Accepted: 26 May 2021

Online publish date: 04 August 2021

*Corresponding Author(s): Ertan Vuruskan E-mail:

PDF (155.52 kB)


Background and objective: We aimed to investigate biochemical factors affecting coronary collateral circulation development in an elderly population aged 75 years and over.

Material and methods: The study group consisted of patients with a prior coronary angiography for stable coronary artery disease (CAD). Patients with total occlusion of at least one vessel were included in the study. Enrolled patients were divided into two groups, good collateral (GC; n = 73) and bad collateral (BC; n = 55), in accordance with the Cohen-Rentop's classification system.

Results: In comparison to the GC group, bilirubin levels were significantly lower (p < 0.001), and fasting plasma glucose (FPG) levels were significantly higher in the BC group (p = 0.026). Low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were significantly lower in the BC group when compared to the GC group (p = 0.002 and p < 0.001, respectively). Backward elimination stepwise logistic regression analysis identified bilirubin and FPG as variables that strongly predicted the presence of a well-developed coronary collateral circulation and a poorly developed coronary collateral circulation, respectively.

Conclusion: Bilirubin and FPG were seemed as the most important factors affecting coronary collateral circulation development in patients with stable CAD who were older than 75 years.


Collateral; Bilirubin; Coronary artery disease; Older patients

Cite and Share

Ertan Vuruskan,Irfan Veysel Duzen,Mehmet Kaplan,Gokhan Altunbas,Enes Alıc,Fatma Yılmaz Coskun,Murat Sucu. Total bilirubin and fasting plasma glucose levels are associated with coronary collateral development in elderly patients. Journal of Men's Health. 2021.doi:10.31083/jomh.2021.085.


[1] GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018; 392: 1736–1788.

[2] Baroldi G, Mantero O, Scomazzoni G. The collaterals of the coronary arteries in normal and pathologic hearts. Circulation Research. 1956; 4: 223–229.

[3] Chalothorn D, Faber JE. Formation and maturation of the native cerebral collateral circulation. Journal of Molecular and Cellular Cardiology. 2010; 49: 251–259.

[4] Takeshita A, Koiwaya Y, Nakamura M, Yamamoto K, Torii S. Immediate appearance of coronary collaterals during ergonovine-induced arterial spasm. Chest. 1982; 82: 319–322.

[5] Małek ŁA, Śpiewak M, Kłopotowski M, Marczak M, Witkowski A. Combined analysis of myocardial function, viability, and stress perfusion in patients with chronic total occlusion in relation to collateral flow. Kardiologia Polska. 2015; 73: 909–915.

[6] Choi JH, Chang SA, Choi JO, Song YB, Hahn JY, Choi SH, et al. Frequency of myocardial infarction and its relationship to angiographic collateral flow in territories supplied by chronically occluded coronary arteries. Circulation. 2013; 127: 703–709.

[7] Banerjee AK, Madan Mohan SK, Ching GW, Singh SP. Functional significance of coronary collateral vessels in patients with previous ’Q’ wave infarction: relation to aneurysm, left ventricular end diastolic pressure and ejection fraction. International Journal of Cardiology. 1993; 38: 263–271.

[8] Celik T, Celik M, Iyisoy A. Coronary collateral circulation. Turk Kardiyoloji Dernegi Arsivi. 2010; 38: 505–514.

[9] İkitimur B. Approach to coronary artery disease in the elderly. Turk Kardiyoloji Dernegi Arsivi. 2017; 45: 32–34.

[10] Task Force Members, Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. European Heart Journal. 2013; 34: 2949–3003.

[11] Pfisterer M. Trial of Invasive versus Medical therapy in Elderly patients Investigators. Long-term outcome in elderly patients with chronic angina managed invasively versus by optimized medical therapy: four-year follow-up of the randomized Trial of Invasive versus Medical therapy in Elderly patients (TIME). Circulation. 2004; 110: 1213–1218.

[12] Cohen M, Rentrop KP. Limitation of myocardial ischemia by collateral circulation during sudden controlled coronary artery occlusion in human subjects: a prospective study. Circulation. 1986; 74: 469–476.

[13] Zimarino M, D’Andreamatteo M, Waksman R, Epstein SE, De Caterina R. The dynamics of the coronary collateral circulation. Nature Reviews. Cardiology. 2014; 11: 191–197.

[14] Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN. Bilirubin is an antioxidant of possible physiological importance. Science. 1987; 235: 1043–1046.

[15] Stocker R, Glazer AN, Ames BN. Antioxidant activity of albumin-bound bilirubin. Proceedings of the National Academy of Sciences of the United States of America. 1987; 84: 5918–5922.

[16] Araujo JA, Zhang M, Yin F. Heme oxygenase-1, oxidation, inflamma-tion, and atherosclerosis. Front Pharmacol. 2012; 3: 119.

[17] Nakagami T, Toyomura K, Kinoshita T, Morisawa S. A beneficial role of bile pigments as an endogenous tissue protector: anti-complement effects of biliverdin and conjugated bilirubin. Biochimica et Biophysica Acta. 1993; 1158: 189–193.

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

[19] Kang SJ, Kim D, Park HE, Chung GE, Choi SH, Choi SY, et al. Elevated serum bilirubin levels are inversely associated with coronary artery atherosclerosis. Atherosclerosis. 2013; 230: 242–248.

[20] Mahabadi AA, Lehmann N, Möhlenkamp S, Kälsch H, Bauer M, Schulz R, 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. Clinical Research in Cardiology. 2014; 103: 647–653.

[21] Zhang ZY, Bian LQ, Kim SJ, Zhou CC, Choi YH. Inverse relation of total serum bilirubin to coronary artery calcification score detected by multidetector computed tomography in males. Clinical Cardiology. 2012; 35: 301–306.

[22] Erdogan D, Gullu H, Yildirim E, Tok D, Kirbas I, Ciftci O, et al. Low serum bilirubin levels are independently and inversely related to impaired flow-mediated vasodilation and increased carotid intima-media thickness in both men and women. Atherosclerosis. 2006; 184: 431–437.

[23] Neuzil J, Stocker R. Free and albumin-bound bilirubin are efficient co-antioxidants for alpha-tocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation. Journal of Biological Chemistry. 1994; 269: 16712–16719.

[24] Lee YB, Lee SE, Jun JE. Change in Serum Bilirubin Level as a Predictor of Incident Metabolic Syndrome. PLoS ONE. 2016; 11: e0168253.

[25] Jung CH, Lee MJ, Kang YM, Hwang JY, Jang JE, Leem J, et al. Higher serum bilirubin level as a predictor factor for the development of diabetes in healthy Korean men: a 4 year prospective study. Metabolism. 2014; 63: 87–93.

[26] Kawamoto R, Ninomiya D, Senzaki K, Kumagi T. Mildly elevated serum total bilirubin is negatively associated with hemoglobin a1c independently of confounding factors among community-dwelling middle-aged and elderly persons. Journal of Circulating Biomarkers. 2017; 6: 184945441772660.

[27] Kundur AR, Santhakumar AB, Bulmer AC, Singh I. Mildly elevated unconjugated bilirubin is associated with reduced platelet activation-related thrombogenesis and inflammation in Gilbert’s syndrome. Platelets. 2017; 28: 779–785.

[28] 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 chronictotal coronary occlusion. Internal Medicine. 2012; 51: 249–255.

[29] Demirbag R, Gur M, Yilmaz R, Kunt AS, Erel O, Andac MH. Influence of oxidative stress on the development of collateral circulation in total coronary occlusions. International Journal of Cardiology. 2007; 116: 14–19.

[30] Nakae I, Fujita M, Miwa K. Age-dependent impairment of coronary collateral development in humans. Heart Vessels. 2000; 15: 176–180.

[31] Shimada T, Takeshita Y, Murohara T, Sasaki K, Egami K, Shintani S, et al. Angiogenesis and vasculogenesis are impaired in the precocious-aging klotho Mouse. Circulation. 2004; 110: 1148–1155.

[32] Kokubun T, Saitoh SI, Miura S, Ishida T, Takeishi Y. Telomerase Plays a Pivotal Role in Collateral Growth Under Ischemia by Suppressing Age-Induced Oxidative Stress, Expression of p53, and Pro-Apoptotic Proteins. International Heart Journal. 2019; 60: 736–745.

[33] Kocaman SA, Sahinarslan A, Biberoglu G, Hasanoglu A, Akyel A, Timurkaynak T, et al. Asymmetric dimethylarginine and coronary collateral vessel development. Coronary Artery Disease. 2008; 19: 469–474.

[34] Förstermann U, Xia N, Li H. Roles of Vascular Oxidative Stress and Nitric Oxide in the Pathogenesis of Atherosclerosis. Circulation Research. 2017; 120: 713–735.

[35] Ganji SB, Kasagani S, Revupalli S, Kavali S, Chidugulla SK. Bilirubin as an indirect measure of laboratory performance of bilirubin determination. Journal of Evolution of Medical and Dental Sciences. 2015; 4: 13149–13155.

[36] Vreman HJ, Verter J, Oh W, Fanaroff AA, Wright LL, Lemons JA, et al. Interlaboratory variability of bilirubin measurements. Clinical Chemistry. 1996; 42: 869–873.

[37] Turhan H, Yasar AS, Erbay AR. Impaired coronary collateral vessel development in patients with metabolic syndrome. Coronary Artery Disease. 2005; 16: 281–285.

[38] Shen Y, Ding FH, Dai Y, Wang XQ, Zhang RY, Lu L, et al. Reduced coronary collateralization in type 2 diabetic patients with chronic total occlusion. Cardiovascular Diabetology. 2018; 17: 26.

[39] Kadi H, Ozyurt H, Ceyhan K, Koc F, Celik A, Burucu T. The Relationship between High-Density Lipoprotein Cholesterol and Coronary Collateral Circulation in Patients with Coronary Artery Disease. Journal of Investigative Medicine. 2012; 60: 808–812.

[40] Bhatt H, Kochar S, Htun WW, Julliard K, Fernaine G. Coronary Collateral Circulation and Cardiovascular Risk Factors. Angiology. 2015; 66: 588–594.

[41] Dincer I, Ongun A, Turhan S, Ozdol C, Ertas F, Erol C. Effect of statin treatment on coronary collateral development in patients with diabetes mellitus. The American Journal of Cardiology. 2006; 97: 772–774.

Abstracted / indexed in

Science Citation Index Expanded Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Social Sciences Citation Index Social Sciences Citation Index contains over 3,400 journals across 58 social sciences disciplines, as well as selected items from 3,500 of the world’s leading scientific and technical journals. More than 9.37 million records and 122 million cited references date back from 1900 to present.

Current Contents - Social & Behavioral Sciences Current Contents - Social & Behavioral Sciences provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in the social and behavioral sciences.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

SCOPUS Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.

DOAJ DOAJ is a community-curated online directory that indexes and provides access to high quality, open access, peer-reviewed journals.

CrossRef Crossref makes research outputs easy to find, cite, link, assess, and reuse. Crossref committed to open scholarly infrastructure and collaboration, this is now announcing a very deliberate path.

Portico Portico is a community-supported preservation archive that safeguards access to e-journals, e-books, and digital collections. Our unique, trusted process ensures that the content we preserve will remain accessible and usable for researchers, scholars, and students in the future.

Submission Turnaround Time