Direct Bilirubin, but not Indirect Bilirubin, is Associated with Short-term Adverse Events in HFpEF

Page: [321 - 330] Pages: 10

  • * (Excluding Mailing and Handling)

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, P0.001; 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, P0.001; 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.

Graphical Abstract

[1]
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.
[http://dx.doi.org/10.1093/eurheartj/ehw128] [PMID: 27206819]
[2]
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.
[http://dx.doi.org/10.1056/NEJMoa052256] [PMID: 16855265]
[3]
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.
[http://dx.doi.org/10.1002/ejhf.1853] [PMID: 32407608]
[4]
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.
[http://dx.doi.org/10.1002/ejhf.440] [PMID: 26707029]
[5]
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.
[http://dx.doi.org/10.1155/2016/4857917] [PMID: 27872510]
[6]
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.
[http://dx.doi.org/10.1093/eurjhf/hfn031] [PMID: 19168515]
[7]
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.
[http://dx.doi.org/10.3389/fcvm.2021.618816] [PMID: 34055924]
[8]
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.
[http://dx.doi.org/10.1016/j.amjcard.2019.11.006] [PMID: 31843232]
[9]
Sundaram V, Fang JC. Gastrointestinal and liver issues in heart failure. Circulation 2016; 133(17): 1696-703.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.020894] [PMID: 27143152]
[10]
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.
[http://dx.doi.org/10.5152/tjg.2015.0086] [PMID: 26006191]
[11]
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.
[http://dx.doi.org/10.3389/fcvm.2021.650191] [PMID: 34113661]
[12]
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.
[http://dx.doi.org/10.1093/eurheartj/ehab368] [PMID: 34447992]
[13]
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.
[http://dx.doi.org/10.1016/j.amjcard.2012.12.048] [PMID: 23351460]
[14]
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.
[http://dx.doi.org/10.1007/s00380-020-01666-1] [PMID: 32671462]
[15]
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.
[http://dx.doi.org/10.1186/0717-6287-47-7] [PMID: 25027460]
[16]
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.
[http://dx.doi.org/10.1016/j.cardfail.2014.03.003] [PMID: 24642379]
[17]
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.
[http://dx.doi.org/10.3389/fgene.2023.1067146] [PMID: 36713081]
[18]
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.
[http://dx.doi.org/10.1016/j.amjcard.2017.03.033] [PMID: 28456315]
[19]
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.
[http://dx.doi.org/10.1007/s11739-019-02033-3] [PMID: 30689135]
[20]
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.
[http://dx.doi.org/10.1016/j.ijcard.2011.07.056] [PMID: 21839528]
[21]
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.
[http://dx.doi.org/10.1002/ehf2.12222] [PMID: 28967709]