Bilirubin as a prognostic marker in patients with pulmonary arterial hypertension

Takeda, Yasuko; Takeda, Yutaka; Tomimoto, Shigehiro; Tani, Tohru; Narita, Hitomi; Kimura, Genjiro

doi:10.1186/1471-2466-10-22

Cited by 79 publications

(62 citation statements)

References 15 publications

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“…Alkaline phosphatase and ferritin were elevated in subjects with SCD with PH and were risk factors for death in the univariate and multivariate analyses, confirming previous findings from echocardiography (4). Another previously identified risk factor, direct bilirubin, reflects an association observed in precapillary PH without SCD (52). Increasing age is reported with an increased risk of PH in previous studies (2, 4), but mortality was not explained by old age among patients with PH in our study.…”

Section: Discussionsupporting

confidence: 80%

Hemodynamic Predictors of Mortality in Adults with Sickle Cell Disease

Mehari

Alam

Tian

et al. 2013

Am J Respir Crit Care Med

118

178

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Background: Pulmonary hypertension (PH) in adults with sickle cell disease (SCD) is associated with early mortality, but no prior studies have evaluated quantitative relationships of mortality to physiological measures of pre-and postcapillary PH. Objectives: To identify risk factors associated with mortality and to estimate the expected survival in a cohort of patients with SCD with PH documented by right heart catheterization. Methods: Nine-year follow-up data (median, 4.7 yr) from the National Institutes of Health SCD PH screening study are reported. A total of 529 adults with SCD were screened by echocardiography between 2001 and 2010 with no exclusion criteria. Hemodynamic data were collected from 84 patients. PH was defined as mean pulmonary artery pressure (PAP) > 25 mm Hg. Survival rates were estimated by the Kaplan-Meier method, and mortality risk factors were analyzed by the Cox proportional hazards regression. Measurements and Main Results: Specific hemodynamic variables were independently related to mortality: mean PAP (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.05-2.45 per 10 mm Hg increase; P ¼ 0.027), diastolic PAP (HR, 1.83; 95% CI, 1.09-3.08 per 10 mm Hg increase; P ¼ 0.022), diastolic PAP 2 pulmonary capillary wedge pressure (HR, 2.19; 95% CI, 1.23-3.89 per 10 mm Hg increase; P ¼ 0.008), transpulmonary gradient (HR, 1.78; 95% CI, 1.14-2.79 per 10 mm Hg increase; P ¼ 0.011), and pulmonary vascular resistance (HR, 1.44; 95% CI, 1.09-1.89 per Wood unit increase; P ¼ 0.009) as risk factors for mortality.

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Section: Discussionsupporting

confidence: 80%

Hemodynamic Predictors of Mortality in Adults with Sickle Cell Disease

Mehari

Alam

Tian

et al. 2013

Am J Respir Crit Care Med

118

178

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“…In a study by Takeda et al (18), it was found that total bilirubin was a prognostic marker in patients with PAH, while S-LDH was not (18); in the present study, however, S-LDH was found to be a more effective prognostic marker than total bilirubin. This difference may have been due to the fact that the study by Takeda et al (18) included patients with connective tissue disease-associated PAH in addition to patients with IPAH, and because fewer patients were recruited by Takeda et al (18) compared with the number of patients in the present study (37 vs. 173). The present study also demonstrated that S-LDH was a more effective predictor of mortality than NT-proBNP in patients with IPAH.…”

Section: Discussioncontrasting

confidence: 45%

High levels of serum lactate dehydrogenase correlate with the severity and mortality of idiopathic pulmonary arterial hypertension

Liu

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Liver dysfunction reflects the status of heart failure, and previous studies have demonstrated that serum lactate dehydrogenase (S-LDH) levels are increased in patients exhibiting heart failure and liver dysfunction. Right heart failure is a main characteristic of idiopathic pulmonary arterial hypertension (IPAH). The aim of the present study was to assess the prognostic significance of S-LDH levels in patients with IPAH. S-LDH levels were determined in 173 patients with IPAH, and these patients were subclassified into two groups according to a defined upper reference limit of S-LDH (250 IU/l). Right heart catheterization was performed in all patients. A total of 53 patients were found to have elevated S-LDH to ≥250 IU/l. In a mean follow-up period of 31.2±17.9 months, 57 patients succumbed. In the group with lower S-LDH levels (S-LDH <250 IU/l), 16.7% of the patients succumbed, compared with 69.8% of patients in the group with higher S-LDH levels (S-LDH ≥250 IU/l). The Kaplan-Meier survival curves demonstrated that patients with higher S-LDH levels had a significantly lower survival rate than did those with lower S-LDH levels (log-rank test, P<0.001). Cox proportional hazard analyses identified reduced body mass index, reduced cardiac index, elevated World Health Organization functional class, higher S-LDH and an absence of PAH-targeted therapy as significant predictors of adverse outcomes. In conclusion, elevated S-LDH is a risk factor for mortality in patients with IPAH.

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“…The association between bilirubin and the rate of mortality or incidence of stroke was different between genders (22). In addition, other groups have suggested that hyperbilirubinemia is linked to pulmonary arterial hypertension and chronic heart failure (23,24). Therefore, the purpose of this study was to investigate whether or not the serum bilirubin level is independently associated with baPWV in established CAD.…”

Section: Introductionmentioning

confidence: 92%

Association of Arterial Stiffness with Serum Bilirubin Levels in Established Coronary Artery Disease

et al. 2012

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Objective Elevated serum bilirubin concentrations protect from atherosclerotic diseases, however it is not clear whether or not higher serum bilirubin concentrations have the same effect in coronary artery disease (CAD). The brachial-ankle pulse wave velocity (baPWV) is a reproducible method to assess arterial stiffness. This study was aimed to investigate the relationship between serum total bilirubin (TB) and baPWV in patients with established CAD. Methods We enrolled 638 patients (390 men, 248 women) with established CAD. TB was divided into tertiles. Simple and multiple linear regression analyses were used to assess the correlation between baPWV and TB. Results The mean baPWV tended to decrease in men according to TB tertiles: Tertile 1=2,126.0, Tertile 2= 1,832.5, and Tertile 3=1,692.5 cm/s. Likewise, the mean baPWV tended to decrease in women according to TB tertiles: Tertile 1=1,920.8, Tertile 2=1,829.0, and Tertile 3=1,701.3 cm/s. Univariate analysis showed that age, BMI, TB, ALT, GGT, Cho, SBP, DBP, UA, and TC were significantly associated with baPWV in men. In women, age, BMI, current smoker, Cho, SBP, DBP, UA, TC, TG, HDL-C, and LDL-C were significantly associated with baPWV. BMI, LnSBP, UA, TB, LnCho, and LnTC were correlated with baPWV in men in the multivariate model. However, only LnSBP, UA, and LnHDL-C were correlated with baPWV in women. TB was found to be a significant determinant for decreased baPWV only in men (β=-0.136; p<0.001). Conclusion Our findings show that the level of total serum bilirubin is negatively correlated with arterial stiffness in men with established CAD.

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Bilirubin as a prognostic marker in patients with pulmonary arterial hypertension

Cited by 79 publications

References 15 publications

Hemodynamic Predictors of Mortality in Adults with Sickle Cell Disease

Hemodynamic Predictors of Mortality in Adults with Sickle Cell Disease

High levels of serum lactate dehydrogenase correlate with the severity and mortality of idiopathic pulmonary arterial hypertension

Association of Arterial Stiffness with Serum Bilirubin Levels in Established Coronary Artery Disease

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