Relationship Between Serum Indirect Bilirubin Levels and Cardiovascular Events and All-Cause Mortality in Maintenance Hemodialysis Patients

Overview

Journal Ther Clin Risk Manag

Publisher Dove Medical Press

Date 2022 Dec 13

PMID 36510597

Authors

Yu Chen

Peilei Zhao

Weifeng Fan

Jianying Niu

Affiliations

Soon will be listed here.

Abstract

Purpose: Unconjugated bilirubin is one of the most endogenous antioxidant substances. Mildly elevated total bilirubin concentrations may protect against cardiovascular disease and total death. However, most studies only focused on the association between serum total bilirubin and the risk of cardiovascular disease and total death. This study aimed to investigate the relationship between serum indirect bilirubin (IBIL) and the cardiovascular events in maintenance hemodialysis patients.

Patients And Methods : This retrospective cohort study included 284 maintenance hemodialysis patients. Patients were divided into two groups according to the median IBIL level: high IBIL group (IBIL ≥3.0 μmol/L) and low IBIL group (IBIL <3.0 μmol/L). All demographic and laboratory data were recorded at baseline. The endpoint was cardiovascular events and all-cause mortality.

Results: During the median follow-up time of 62 months, 96 patients developed cardiovascular disease. There were 134 deaths. In Kaplan-Meier analysis curves, the risk of cardiovascular events in the low IBIL group was significantly higher than high IBIL group ( < 0.001). In multivariate Cox regression analysis, the risk of cardiovascular events in high IBIL group was 0.484 times (95% CI 0.278-0.844, = 0.010) the risk in low IBIL group. However, there was no significant association between serum IBIL level and all-cause mortality ( = 0.269).

Conclusion: Our findings suggest that lower circulating IBIL levels were associated with the increased risk of cardiovascular events in maintenance hemodialysis patients.

Citing Articles

The U-shaped association between serum direct bilirubin and incident mild cognitive impairment in hemodialysis patients: a multicenter study.

Yang Y, Li Q, Zhang Q, Yuan J, Zha Y BMC Psychiatry. 2024; 24(1):744.

PMID: 39468523 PMC: 11520874. DOI: 10.1186/s12888-024-06189-x.

Correlation analysis between left ventricular global longitudinal strain and major adverse cardiovascular event occurrence in patients with end-stage renal disease.

Xie J, Long X, Xie J, Yang D, Yang J, Mao X Int Urol Nephrol. 2024; 56(9):3031-3037.

PMID: 38630429 DOI: 10.1007/s11255-024-04046-0.

References

Bulmer A, Bakrania B, Du Toit E, Boon A, Clark P, Powell L . Bilirubin acts as a multipotent guardian of cardiovascular integrity: more than just a radical idea. Am J Physiol Heart Circ Physiol. 2018; 315(3):H429-H447. DOI: 10.1152/ajpheart.00417.2017. View

Li J, Liu D, Liu Z . Serum Total Bilirubin and Progression of Chronic Kidney Disease and Mortality: A Systematic Review and Meta-Analysis. Front Med (Lausanne). 2021; 7:549. PMC: 7868400. DOI: 10.3389/fmed.2020.00549. View

de Jager D, Grootendorst D, Jager K, van Dijk P, Tomas L, Ansell D . Cardiovascular and noncardiovascular mortality among patients starting dialysis. JAMA. 2009; 302(16):1782-9. DOI: 10.1001/jama.2009.1488. View

Ndisang J, Jadhav A . Upregulating the heme oxygenase system suppresses left ventricular hypertrophy in adult spontaneously hypertensive rats for 3 months. J Card Fail. 2009; 15(7):616-28. DOI: 10.1016/j.cardfail.2009.02.003. View

Tanaka S, Ninomiya T, Masutani K, Nagata M, Tsuchimoto A, Tsuruya K . Prognostic impact of serum bilirubin level on long-term renal survival in IgA nephropathy. Clin Exp Nephrol. 2015; 19(6):1062-70. DOI: 10.1007/s10157-015-1096-0. View

Yao H, Shen D, Zhao X, Wang X, Sun T, Zhang J . Prognostic value of total bilirubin in patients with angina pectoris undergoing percutaneous coronary intervention. Int J Clin Exp Med. 2015; 8(9):15930-9. PMC: 4658985. View

Chung S, Yang T, Shin H, Jin H, Seo J, Jang J . Initial Total Bilirubin and Clinical Outcome in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention With Drug-Eluting Stents. Circ J. 2016; 80(6):1437-44. DOI: 10.1253/circj.CJ-15-1397. View

Querido S, Branco P, Silva Sousa H, Adragao T, Goncalves P, Gaspar M . Hypervolemia, hypoalbuminemia and mitral calcification as markers of cardiovascular risk in peritoneal dialysis patients. Rev Port Cardiol. 2017; 36(9):599-604. DOI: 10.1016/j.repc.2016.12.014. View

Chen S, Lin C, Hsu H, Shu J, Liang Y, Hsu P . Serum bilirubin improves the risk predictions of cardiovascular and total death in diabetic patients. Clin Chim Acta. 2018; 488:1-6. DOI: 10.1016/j.cca.2018.10.028. View

10.

Su H, Kao C, Lin Y, Lin Y, Kao C, Chen H . Relationship between serum total bilirubin levels and mortality in uremia patients undergoing long-term hemodialysis: A nationwide cohort study. Atherosclerosis. 2017; 265:155-161. DOI: 10.1016/j.atherosclerosis.2017.09.001. View

11.

Choi Y, Lee S, Spiller W, Jung K, Lee J, Kimm H . Causal Associations Between Serum Bilirubin Levels and Decreased Stroke Risk: A Two-Sample Mendelian Randomization Study. Arterioscler Thromb Vasc Biol. 2019; 40(2):437-445. PMC: 6975519. DOI: 10.1161/ATVBAHA.119.313055. View

12.

Cozzolino M, Mangano M, Stucchi A, Ciceri P, Conte F, Galassi A . Cardiovascular disease in dialysis patients. Nephrol Dial Transplant. 2018; 33(suppl_3):iii28-iii34. PMC: 6168816. DOI: 10.1093/ndt/gfy174. View

13.

Tsujikawa H, Tanaka S, Hara M, Kawai Y, Matsukuma Y, Torisu K . Association of Lower Serum Bilirubin With Loss of Residual Kidney Function in Peritoneal Dialysis Patients. Ther Apher Dial. 2019; 24(2):202-207. DOI: 10.1111/1744-9987.12865. View

14.

Zulus B, Grunbacher G, Kleber M, Marz W, Renner W . The UGT1A1*28 gene variant predicts long-term mortality in patients undergoing coronary angiography. Clin Chem Lab Med. 2017; 56(4):560-564. DOI: 10.1515/cclm-2017-0692. View

15.

Ho Y, Chen T, Huang T, Chen Y, Tarng D . Bilirubin Links and Gene Polymorphisms to Predict Cardiovascular Outcome in Patients Receiving Maintenance Hemodialysis. Antioxidants (Basel). 2021; 10(9). PMC: 8470468. DOI: 10.3390/antiox10091403. View

16.

Stenvinkel P, Heimburger O, Paultre F, Diczfalusy U, Wang T, Berglund L . Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int. 1999; 55(5):1899-911. DOI: 10.1046/j.1523-1755.1999.00422.x. View

17.

Ben-Amotz R, Bonagura J, Velayutham M, Hamlin R, Burns P, Adin C . Intraperitoneal bilirubin administration decreases infarct area in a rat coronary ischemia/reperfusion model. Front Physiol. 2014; 5:53. PMC: 3927123. DOI: 10.3389/fphys.2014.00053. View

18.

Li C, Wu W, Song Y, Xu S, Wu X . The Nonlinear Relationship Between Total Bilirubin and Coronary Heart Disease: A Dose-Response Meta-Analysis. Front Cardiovasc Med. 2022; 8:761520. PMC: 8766987. DOI: 10.3389/fcvm.2021.761520. View

19.

Lan Y, Liu H, Liu J, Zhao H, Wang H . The Relationship Between Serum Bilirubin Levels and Peripheral Arterial Disease and Gender Difference in Patients With Hypertension: BEST Study. Angiology. 2020; 71(4):340-348. DOI: 10.1177/0003319719900734. View

20.

Tian M, Song W, Li Q, Shen Y, Hu Y, Yuan J . [Association of low serum indirect bilirubin level with all-cause mortality in maintenance hemodialysis patients]. Zhonghua Yi Xue Za Zhi. 2019; 99(28):2203-2207. DOI: 10.3760/cma.j.issn.0376-2491.2019.28.010. View