Direct Bilirubin, but not Indirect Bilirubin, is Associated with Short-term Adverse Events in HFpEF
- Authors: Wang S.1, Chen Y.2, Ma H.3, Wang Y.4, Luo M.5, Xie X.6, Yang Q.7, Lin K.1, Lin M.1, Lin L.1, Chen P.1, Zheng Q.1, Sun F.1
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Affiliations:
- , Fuqing City Hospital Affiliated to Fujian Medical University
- Department of Ultrasound, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University
- , Ningde People's Hospital
- Department of Management, Fujian Yirong Information Technology Corporation
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
- Department of Cardiology, Fujian Provincial Hospital
- Department of Internal Medicine, Jinshan Branch of Fujian Provincial Hospital
- Issue: Vol 24, No 4 (2024)
- Pages: 321-330
- Section: Life Sciences
- URL: https://j-morphology.com/1566-5232/article/view/644038
- DOI: https://doi.org/10.2174/0115665232273115240102043640
- ID: 644038
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Abstract
Objective:Abnormal live function tests have been identified as independent risk factors for ominous prognosis in patients with heart failure. However, most of the previous studies have failed to determine the contribution of direct bilirubin (DBIL) and indirect bilirubin (IBIL) separately. Hence, we aimed to explore whether DBIL or IBIL is correlated with the prognosis of heart failure with preserved ejection fraction (HFpEF).
Methods:A total of 19837 patients were hospitalized for HFpEF between January 2012 and January 2022 in Fuqing City Hospital affiliated with Fujian Medical University. The primary endpoint was in-hospital all-cause mortality. Secondary endpoints included in-hospital cardiovascular mortality and 30-day re-admission for heart failure.
Results:Univariable analysis indicated that patients with elevated DBIL or IBIL were exposed to a higher risk of mortality and re-admission. However, in multivariable models, both ln-transformed DBIL and TBIL, but not IBIL, were independent risk factors for in-hospital all-cause mortality [hazard ratio (HR)=1.796, 95% confidential interval (CI)=1.477-2.183, P<0.001; HR=1.854, 95% CI=1.461-2.352, P<0.001; HR=1.161, 95% CI=0.959-1.407, P=0.126] and in-hospital cardiovascular mortality (HR=1.831, 95% CI=1.345-2.492, P<0.001; HR=1.899, 95% CI=1.300-2.773, P=0.001; HR=1.145, 95% CI=0.841-1.561, P=0.389). Only DBIL remained independently associated with 30-day readmission for heart failure (HR=1.361, 95% CI=1.036-1.787, P=0.027). Adding ln-transformed DBIL to model 1 increased its discriminatory capacity (C-statistic: 0.851 to 0.869, respectively), whereas adding ln-transformed IBIL yielded little increment (C-statistic: 0.851 to 0.852, respectively).
Conclusion:DBIL, but not IBIL, was associated with short-term ominous prognosis in patients with HFpEF. Hence, DBIL may be the superior predictor for prognosis in HFpEF.
About the authors
Sunying Wang
, Fuqing City Hospital Affiliated to Fujian Medical University
Email: info@benthamscience.net
Yan Chen
Department of Ultrasound, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University
Email: info@benthamscience.net
Hanghao Ma
, Ningde People's Hospital
Email: info@benthamscience.net
Yuwei Wang
Department of Management, Fujian Yirong Information Technology Corporation
Email: info@benthamscience.net
Manqing Luo
Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
Email: info@benthamscience.net
Xianwei Xie
Department of Cardiology, Fujian Provincial Hospital
Email: info@benthamscience.net
Qingyong Yang
Department of Internal Medicine, Jinshan Branch of Fujian Provincial Hospital
Email: info@benthamscience.net
Kaijin Lin
, Fuqing City Hospital Affiliated to Fujian Medical University
Email: info@benthamscience.net
Meihua Lin
, Fuqing City Hospital Affiliated to Fujian Medical University
Email: info@benthamscience.net
Lin Lin
, Fuqing City Hospital Affiliated to Fujian Medical University
Email: info@benthamscience.net
Ping Chen
, Fuqing City Hospital Affiliated to Fujian Medical University
Email: info@benthamscience.net
Qiaowen Zheng
, Fuqing City Hospital Affiliated to Fujian Medical University
Email: info@benthamscience.net
Fuqing Sun
, Fuqing City Hospital Affiliated to Fujian Medical University
Author for correspondence.
Email: info@benthamscience.net
References
- Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2016; 37(27): 2129-200. doi: 10.1093/eurheartj/ehw128 PMID: 27206819
- Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 2006; 355(3): 251-9. doi: 10.1056/NEJMoa052256 PMID: 16855265
- Suzuki K, Claggett B, Minamisawa M, et al. Liver function and prognosis, and influence of sacubitril/valsartan in patients with heart failure with reduced ejection fraction. Eur J Heart Fail 2020; 22(9): 1662-71. doi: 10.1002/ejhf.1853 PMID: 32407608
- Samsky MD, Dunning A, DeVore AD, et al. Liver function tests in patients with acute heart failure and associated outcomes: Insights from ASCEND‐HF. Eur J Heart Fail 2016; 18(4): 424-32. doi: 10.1002/ejhf.440 PMID: 26707029
- Yokoyama M, Watanabe T, Otaki Y, et al. Associatowion of the aspartate aminotransferase to alanine aminotransferase ratio with bnp level and cardiovascular mortality in the general population: The yamagata study 10-year foll-Up. Dis Markers 2016; 2016: 1-9. doi: 10.1155/2016/4857917 PMID: 27872510
- Allen LA, Felker GM, Pocock S, et al. Liver function abnormalities and outcome in patients with chronic heart failure: Data from the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program. Eur J Heart Fail 2009; 11(2): 170-7. doi: 10.1093/eurjhf/hfn031 PMID: 19168515
- Liang W, He X, Wu D, et al. Prognostic implication of liver function tests in heart failure with preserved ejection fraction without chronic hepatic diseases: Insight from TOPCAT trial. Front Cardiovasc Med 2021; 8: 618816. doi: 10.3389/fcvm.2021.618816 PMID: 34055924
- Prenner SB, Kumar A, Zhao L, et al. Effect of serum albumin levels in patients with heart failure with preserved ejection fraction (from the TOPCAT Trial). Am J Cardiol 2020; 125(4): 575-82. doi: 10.1016/j.amjcard.2019.11.006 PMID: 31843232
- Sundaram V, Fang JC. Gastrointestinal and liver issues in heart failure. Circulation 2016; 133(17): 1696-703. doi: 10.1161/CIRCULATIONAHA.115.020894 PMID: 27143152
- Çağlı K, Başar FN, Tok D, Turak O, Başar O. How to interpret liver function tests in heart failure patients? Turk J Gastroenterol 2020; 26(3): 197-203. doi: 10.5152/tjg.2015.0086 PMID: 26006191
- Wang S, Wang Y, Luo M, et al. MELD-XI score is associated with short-term adverse events in patients with heart failure with preserved ejection. Front Cardiovasc Med 2021; 8: 650191. doi: 10.3389/fcvm.2021.650191 PMID: 34113661
- McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021; 42(36): 3599-726. doi: 10.1093/eurheartj/ehab368 PMID: 34447992
- Wu AH, Levy WC, Welch KB, et al. Association between bilirubin and mode of death in severe systolic heart failure. Am J Cardiol 2013; 111(8): 1192-7. doi: 10.1016/j.amjcard.2012.12.048 PMID: 23351460
- Shiomura R, Kobayashi N, Shirakabe A, et al. Systolic blood pressure and cardiac mortality related to serum total bilirubin levels at admission in patients with acute heart failure. Heart Vessels 2021; 36(1): 69-75. doi: 10.1007/s00380-020-01666-1 PMID: 32671462
- Zheng H, Li Y, Xie N. Association of serum total bilirubin levels with diastolic dysfunction in heart failure with preserved ejection fraction. Biol Res 2014; 47(1): 7. doi: 10.1186/0717-6287-47-7 PMID: 25027460
- van Deursen VM, Edwards C, Cotter G, et al. Liver function, in-hospital, and post-discharge clinical outcome in patients with acute heart failure-results from the relaxin for the treatment of patients with acute heart failure study. J Card Fail 2014; 20(6): 407-13. doi: 10.1016/j.cardfail.2014.03.003 PMID: 24642379
- Guan B, Yang M, Shen X, et al. Genetically determined serum bilirubin level and the risk of heart failure: A mendelian randomization study. Front Genet 2023; 14: 1067146. doi: 10.3389/fgene.2023.1067146 PMID: 36713081
- Okada A, Sugano Y, Nagai T, et al. Usefulness of the direct and/or total bilirubin to predict adverse outcomes in patients with acute decompensated heart failure. Am J Cardiol 2017; 119(12): 2035-41. doi: 10.1016/j.amjcard.2017.03.033 PMID: 28456315
- Durante-Mangoni E, Parrella A, Pafundi PC, et al. Liver histopathological findings in advanced heart failure: A reappraisal of cardiac cirrhosis concept. Intern Emerg Med 2019; 14(6): 931-40. doi: 10.1007/s11739-019-02033-3 PMID: 30689135
- Kato T, Niizuma S, Inuzuka Y, et al. Analysis of liver metabolism in a rat model of heart failure. Int J Cardiol 2012; 161(3): 130-6. doi: 10.1016/j.ijcard.2011.07.056 PMID: 21839528
- Yoshihisa A, Sato Y, Yokokawa T, et al. Liver fibrosis score predicts mortality in heart failure patients with preserved ejection fraction. ESC Heart Fail 2018; 5(2): 262-70. doi: 10.1002/ehf2.12222 PMID: 28967709
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