Usefulness of the Direct and/or Total Bilirubin to Predict Adverse Outcomes in Patients With Acute Decompensated Heart Failure

Okada, Atsushi; Sugano, Yasuo; Nagai, Toshiyuki; Honda, Yasuyuki; Iwakami, Naotsugu; Nakano, Hiroki; Takashio, Seiji; Honda, Satoshi; Asaumi, Yasuhide; Aiba, Takeshi; Noguchi, Teruo; Kusano, Kengo; Yasuda, Satoshi; Anzai, Toshihisa; Kawakami, Shoji; Yamamoto, Yoshiya; Yamamoto, Masahiro; Motokawa, Tetsufumi; Hamatani, Yasuhiro; Shibata, Tatsuhiro; Homma, Takehiro; Chinen, Daigo; Yamane, Takafumi; Yoshida, Chinatsu; Ogura, Sachiko; Maruta, Akiko; Sumita, Yoko

doi:10.1016/j.amjcard.2017.03.033

Cited by 21 publications

(15 citation statements)

References 25 publications

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“…In another study, 22 DB was reported to be associated with increased incidence of coronary heart disease in a dose-response manner in Chinese patients. Likewise, other 2 studies also demonstrated that elevated DB could predict adverse events of acute compensated heart failure 23 and idiopathic pulmonary arterial hypertension. 24 These findings together with ours suggest that it is important to distinguish DB from IDB, 25 as DB is probably a risk factor in cardiac-pulmonary disease.…”

Section: Discussionmentioning

confidence: 90%

Relation of Direct, Indirect, and Total bilirubin to Adverse Long-term Outcomes Among Patients With Acute Coronary Syndrome

Dong

Deng

et al. 2019

The American Journal of Cardiology

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Bilirubin is known as an antioxidant. However, there have been controversies over whether bilirubin is protective against cardiovascular disease or not. In addition, no study has examined the association between subtypes of total bilirubin (direct bilirubin [DB] and indirect bilirubin [IDB]) and long-term outcomes of acute coronary syndrome (ACS) patients. We included 533 consecutive patients with ACS. All the patients were followed up for the composite end point of cardiac death, revascularization, and acute heart failure. At a median follow-up of 2.4 years, Kaplan-Meier curve demonstrated that higher serum DB levels were significantly associated with major adverse cardiac events (MACE) (p <0.05). However, total bilirubin (TB) and IDB were not associated with MACE by Kaplan-Meier analysis. Cox analysis showed that high TB and DB were associated with increased risk of MACE in ACS even after adjustment of cardiovascular risk factors. The receiver operating characteristic curve illustrated that DB had a predictive value of MACE in ACS. In conclusion, we firstly reported that high TB and DB but not IDB were associated with increased risk of MACE in Chinese ACS, and the prognostic value of DB was superior to that of TB or IDB.

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Section: Discussionmentioning

confidence: 90%

Relation of Direct, Indirect, and Total bilirubin to Adverse Long-term Outcomes Among Patients With Acute Coronary Syndrome

Dong

Deng

et al. 2019

The American Journal of Cardiology

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“…Direct hyperbilirubinemia is increasingly recognized as an indirect marker of right heart dynamics and a prognostic indicator for HF. 18 , 19 It is observed in patients with clinical signs of increased right-sided pressure, and is commonly accompanied by other parameters of HF severity, like increased plasma renin activity and decreased total cholesterol. The lack of an independent association between B12 level and clinical right HF, but a significant relationship to mildly increased direct bilirubin levels, indicate that a possible ongoing occult liver injury due to subclinical hepatic congestion is the main determinant of B12 elevation in these patients.…”

Section: Discussionmentioning

confidence: 99%

Elevated levels of vitamin B12 in chronic stable heart failure: a marker for subclinical liver damage and impaired prognosis

Argan

Ural

Karaüzüm

et al. 2018

TCRM

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BackgroundElevated vitamin B12 is a sign for liver damage, but its significance in chronic stable heart failure (HF) is less known. The present study investigated the clinical correlates and prognostic significance of vitamin B12 levels in stable systolic HF.MethodsA total of 129 consecutive patients with HF and 50 control subjects were enrolled. Data regarding demographics, clinical signs, therapeutic and conventional echocardiographic measurements were recorded for all patients. Right-sided HF was defined as the presence of at least one of the typical symptoms (ankle swelling) or specific signs (jugular venous distention or abdominojugular reflux) of right HF. Cox proportional hazards regression analyses were performed to determine the independent prognostic determinants of mortality.ResultsBaseline B12 levels in HF patients (n=129) with and without right sided HF were significantly higher compared to healthy controls (n=50): Median 311 pg/mL and 235 pg/mL vs 198 pg/mL, respectively (P=0.005). Folic acid levels were similar between the study groups. Age, ejection fraction, left atrial size, estimated glomerular filtration rate, and direct and indirect bilirubin levels were significantly correlated to serum B12 level in univariate analysis. In multivariate analysis, independent correlates of B12 were direct bilirubin (R=0.51, P<0.001) and age (R=0.19, P=0.028). Patients with HF were followed-up for a median period of 32 months. Median B12 levels were significantly higher in patients who subsequently died (n=35) compared to survivors, but folic acid was not different between the two groups. ROC analysis showed that B12 values ≥270 pg/mL had 80% sensitivity and 58% specificity for predicting all-cause mortality (area under the curve=0.672, 95% CI=0.562−0.781; P=0.003). However, in Cox regression analysis, only left atrial diameter, level of direct bilirubin, and the presence of abdominojugular reflux were independent predictors of death.ConclusionIncreased B12 in stable HF patients is associated with increased direct bilirubin due to right HF, indicating a cardiohepatic syndrome, but neither B12 nor folic acid are independently associated with mortality.

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“…The validation cohort for our study was the NaDEF study: an ongoing, prospective, single‐centre acute HF registry conducted at the National Cerebral and Cardiovascular Center in Osaka, Japan (West Japan), that began from January 2013. The objectives and detailed design are provided on the University Hospital Medical Information Network (UMIN000017024) …”

Section: Methodsmentioning

confidence: 99%

“…The objectives and detailed design are provided on the University Hospital Medical Information Network (UMIN000017024). 16,17…”

Section: Study Populationmentioning

confidence: 99%

Performance of the MAGGIC heart failure risk score and its modification with the addition of discharge natriuretic peptides

et al. 2018

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AimsPredictive models for heart failure patients are widely used in the clinical practice to stratify patients' mortality and enable clinicians to tailor and intensify their approach. However, such models have not been validated internationally. In addition, biomarkers are now frequently measured to obtain prognostic information, and the implications of this practice are not known. In this study, we aimed to validate the model performance of the Meta‐analysis Global Group in Chronic Heart Failure (MAGGIC) score in a Japanese acute heart failure registry and further explore the incremental prognostic value of discharge B‐type natriuretic peptide (BNP) level.Methods and ResultsIn this study, we evaluated the registered data of 2215 consecutive acute HF patients (with 694 119 person‐years follow‐up) from a prospective multicentre registry (the West Tokyo Heart Failure) conducted in Japan from April 2006 to August 2016. The mean age was 73.0 ± 13.0, and 61.2% were male. The MAGGIC score demonstrated modest discrimination (c‐index = 0.71, 95% confidence interval 0.67–0.74) and good calibration (R 2 value = 0.97); there was constant overestimation for 1 year mortality. However, when the BNP level was added to the original MAGGIC variables, the model demonstrated good discrimination (c‐index = 0.74, 95% confidence interval 0.70–0.78) with adequate calibration (R 2 value = 0.91). The modified MAGGIC BNP score was externally validated in a separate Japanese registry (NaDEF) and demonstrated moderate discrimination (c‐index = 0.69, 95% confidence interval 0.65–0.73) and calibration (R 2 value = 0.85).ConclusionThe original MAGGIC score performed modestly in Japanese patients, but the addition of discharge BNP level enhanced model performance. The addition of objective biomarkers may result in effective modification of preexisting internationally recognized risk models and aid in multinational comparisons of heart failure patients' outcomes.

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Usefulness of the Direct and/or Total Bilirubin to Predict Adverse Outcomes in Patients With Acute Decompensated Heart Failure

Cited by 21 publications

References 25 publications

Relation of Direct, Indirect, and Total bilirubin to Adverse Long-term Outcomes Among Patients With Acute Coronary Syndrome

Relation of Direct, Indirect, and Total bilirubin to Adverse Long-term Outcomes Among Patients With Acute Coronary Syndrome

Elevated levels of vitamin B12 in chronic stable heart failure: a marker for subclinical liver damage and impaired prognosis

Performance of the MAGGIC heart failure risk score and its modification with the addition of discharge natriuretic peptides

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