Direct Bilirubin: A New Risk Factor of Adverse Outcome in Idiopathic Pulmonary Arterial Hypertension

Background: Previous studies have shown that elevated total bilirubin was associated with advanced heart failure, yet no study has ascertained the predictive value of direct serum bilirubin (DBIL) in idiopathic pulmonary arterial hypertension (IPAH). This study aimed to investigate the predictive value of both baseline and follow-up DBIL in patients with IPAH.

Methods: Serum DBIL was measured in 404 IPAH patients at enrollment. Almost 92% patients received specific drugs after diagnosis confirmed. Serum DBIL was repeated in 237 patients after a mean of 8.3months treatment. Survival rate among normal DBIL group and abnormal DBIL group was compared using the Kaplan-Meier method. The prognostic value of baseline variables was tested by Cox regression models.

Results: During median follow-up period of 40months, 153 patients died. Baseline DBIL levels were significantly higher in non-survivors compared with survivors (p<0.001). DBIL levels in survivors decreased significantly during PAH therapy, whereas there was almost no decrease in non-survivors. Patients with abnormal DBIL at baseline or during therapy had a significantly lower survival rates than those with normal DBIL group, according to Kaplan-Meier survival analysis (p=0.002 and p<0.0001, respectively). According to multivariate analyses, baseline DBIL was an independent risk factor of mortality in IPAH.

Conclusions: Serum DBIL could predict severity and outcomes of IPAH: in particular, no obvious decrease in DBIL during PAH-specific drug therapy is strongly associated with worse prognosis in IPAH.