Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
CNS Neurosci Ther. 2022 Feb;28(2):226-236. doi: 10.1111/cns.13759. Epub 2021 Nov 14.
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.
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.
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).
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.
探讨总胆红素(TBIL)、直接胆红素(DBIL)和间接胆红素(IBIL)水平与急性缺血性脑卒中(AIS)患者溶栓后不良结局的关系,以及不同胆红素亚型对不良结局的预测价值。
我们对 718 名 AIS 患者中的 588 名患者进行了分析,所有患者均在溶栓后 3 个月进行随访。主要结局为 3 个月时的死亡和主要残疾(改良 Rankin 量表(mRS)评分 3-6 分)。次要结局分别为 3 个月时的死亡率(mRS 评分 6 分)、中重度脑水肿和症状性颅内出血(sICH)。
溶栓前 DBIL 升高与主要结局的风险增加相关(OR 3.228;95%CI 1.595-6.535;趋势检验 p 值=0.014),经充分校正后仍有此结果。溶栓前 TBIL 升高也显示出类似的结果(OR 2.185;95%CI 1.111-4.298;趋势检验 p 值=0.047),而溶栓前 IBIL 与主要结局无显著相关性(OR 1.895;95%CI 0.974-3.687;趋势检验 p 值=0.090)。多变量校正的样条回归模型显示,溶栓前 DBIL 与主要结局风险之间存在正线性剂量反应关系(p 值线性检验=0.004)。将 DBIL 纳入常规模型后,对主要结局的预测具有更大的增量预测价值,净重新分类改善(NRI)95%CI=0.275(0.084-0.466),综合判别改善(IDI)95%CI=0.011(0.001-0.024)。溶栓后 DBIL 升高与主要结局相关(OR 2.416;95%CI 1.184-4.930;趋势检验 p 值=0.039),并提高了对主要结局的增量预测价值,NRI(95%CI)=0.259(0.066-0.453),IDI(95%CI)=0.025(0.008-0.043)。
与 TBIL 和 IBIL 相比,溶栓前 DBIL 与 AIS 患者溶栓后不良结局的相关性更强,对不良结局的预测价值更高,但应结合回顾性设计来理解。应在进一步的研究中调查 DBIL 对目标人群的影响。