Serum Bilirubin and Risk of First Stroke in Hypertensive Patients

Abstract

Background: Identification of novel risk factors is essential to further lower stroke risk. Data concerning the relation of serum bilirubin levels with the risk of stroke are limited. We sought to evaluate the association between serum bilirubin and the risk of first stroke in hypertensive patients. Methods: Our analyses included a total of 19,906 hypertensive patients from the China Stroke Primary Prevention Trial (CSPPT). In the CSPPT, a total of 20,702 hypertensive patients without major cardiovascular diseases were randomly assigned to a double-blind, daily treatment with either 10mg enalapril and 0·8mg folic acid or 10 mg enalapril alone. The median treatment duration was 4·5 years. Findings: There was a significant inverse association between serum total bilirubin (TBiL) (per-SD increment; HR, 0·90; 95%CI: 0·81-0·99) or direct bilirubin (DBiL) (HR, 0·83; 95%CI: 0·74-0·93) and the risk of first ischemic stroke. Consistently, when TBiL was assessed as tertiles, the adjusted HR for participants in tertile 3 was 0·74 (95%CI: 0·58-0·93), when compared with those in tertile 1. When DBiL was assessed as tertiles, a significantly lower risk of first ischemic stroke was also found in participants in tertile 3 (HR, 0·73; 95%CI: 0·57-0·93) compared with those in tertile 1. However, there was no significant association between serum TBiL (per-SD increment; HR, 1·15; 95%CI: 0·96, 1·38) or DBiL (HR, 1·10; 95%CI: 0·91-1·33) and first hemorrhagic stroke. Interpretation: Our data showed a significant inverse association between serum TBiL or DBiL levels and the risk of first ischemic stroke among Chinese hypertensive adults. Funding: The study was supported by funding from the following: the National Key Research and Development Program, the National Natural Science Foundation of China; the Science and Technology Planning Project of Guangzhou, China; the Science, Technology and Innovation Committee of Shenzhen, China. Declaration of Interest: Dr. Yong Huo reports grants from the National Key Research and Development Program [2016YFC0903103]. Dr. Yimin Cui reports grants from the National Key Research and Development Program [2016YFC0904900]. Dr. Xiping Xu reports grants from the National Key Research and Development Program [2016YFE0205400, 2018ZX09739, 2018ZX09301034003], the Science and Technology Planning Project of Guangzhou, China [201707020010], and the Science, Technology and Innovation Committee of Shenzhen [JSGG20170412155639040, GJHS20170314114526143]. Dr. Xianhui Qin reports grants from the National Natural Science Foundation of China [81730019]. Ethical Approval: Both the CSPPT and the current study were approved by the Ethics Committee of the Institute of Biomedicine, Anhui Medical University, Hefei, China (FWA assurance number: FW1263).