Predictive value of different bilirubin subtypes for clinical outcomes in patients with acute ischemic stroke receiving thrombolysis therapy

Aims To explore the association of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) levels with, as well as the incremental predictive value of different bilirubin subtypes for, poor outcomes in acute ischemic stroke patients after thrombolysis. Methods We analyzed 588 individuals out of 718 AIS participants, and all patients were followed up at 3 months after thrombolysis. The primary outcome was 3‐month death and major disability (modified Rankin Scale (mRS) score of 3–6). The secondary outcomes were 3‐month mortality (mRS score of 6), moderate‐severe cerebral edema, and symptomatic intracranial hemorrhage (sICH), respectively. Results Elevated DBIL pre‐thrombolysis was associated with an increased risk of primary outcome (OR 3.228; 95% CI 1.595–6.535; p for trend = 0.014) after fully adjustment. Elevated TBIL pre‐thrombolysis showed the similar results (OR 2.185; 95% CI 1.111–4.298; p for trend = 0.047), while IBIL pre‐thrombolysis was not significantly associated with primary outcome (OR 1.895; 95% CI 0.974–3.687; p for trend = 0.090). Multivariable‐adjusted spline regression model showed a positive linear dose‐response relationship between DBIL pre‐thrombolysis and risk of primary outcome (p for linearity = 0.004). Adding DBIL pre‐thrombolysis into conventional model had greater incremental predictive value for primary outcome, with net reclassification improvement (NRI) 95% CI = 0.275 (0.084–0.466) and integrated discrimination improvement (IDI) 95% CI = 0.011 (0.001–0.024). Increased DBIL post‐thrombolysis had an association with primary outcome (OR 2.416; 95%CI 1.184–4.930; p for trend = 0.039), and it also elevated the incremental predictive value for primary outcome, with NRI (95% CI) = 0.259 (0.066–0.453) and IDI (95% CI) = 0.025 (0.008–0.043). Conclusion Increased DBIL pre‐thrombolysis had a stronger association with, as well as greater incremental predictive value for, poor outcomes than TBIL and IBIL did in AIS patients after thrombolysis, which should be understood in the context of retrospective design. The effect of DBIL on targeted populations should be investigated in further researches. Stroke is a systemic disease, with bilirubin metabolism enhanced in liver after stroke, exerting neurotoxicity in ischemia brain. Direct bilirubin (conjugated bilirubin) is superior in predicting the clinical outcomes in acute stroke patients receiving thrombolysis therapy than both total bilirubin and indirect bilirubin (un