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The J-shape Association between Total Bilirubin and Stroke in Older Patients with Obstructive Sleep Apnea Syndrome: A Multicenter Study

  • Original Research
  • Published:
The journal of nutrition, health & aging

Abstract

Objectives

To explore the relationship between total bilirubin (TBil) and stroke risk in older patients with obstructive sleep apnea syndrome (OSAS).

Methods

A total of 1,007 patients with OSAS without stroke history aged ≥ 60 years and with complete serum TBil records were enrolled in this study. The median follow-up was 42 months. Participants were divided into four groups based on the quartile of the baseline serum TBil concentration. Multivariate Cox proportional hazards analysis and restricted cubic spline (RCS) were used to investigate the association of TBil with the incidence of new-onset stroke.

Results

The PRIMARY part: the third quantile TBil level group had the lowest prevalence of stroke among the four groups. The RCS functions depicted a J-type curve relationship between TBil (3.3–33.3 µmol/L) and stroke (nonlinear P < 0.05). When the TBil level was in the range of 3.3 to 11.5 µmol/L, the possible protective influence of bilirubin against stroke in patients with OSAS enhanced with an increasing TBil level. However, when the TBil level exceeded 11.5 µmol/L and gradually increased, the effect of TBil on stroke risk became more and more pronounced. The SECONDARY part: for every 1 µmol/L increase in TBil levels in the range of 11.5 to 33.3 µmol/L, the risk of stroke in patients with OSAS increased by 16.2% (P < 0.001). In addition, there was a higher risk in women with OSAS (hazard ratio (HR)=1.292, 95% confidence interval (95%CI): 1.093–1.528; P = 0.003). Moreover, an increased TBil level alone was significantly associated with stroke in subjects aged < 75 years (HR: 1.190, 95%CI: 1.069–1.324), patients with mild-to-moderate OSAS (HR: 1.215, 95%CI: 1.083–1.364), and individuals without atrial fibrillation (AF) (HR: 1.179, 95%CI: 1.083–1.285) within a TBil level in the range of 11.5 to 33.3 µmol/L.

Conclusions

Both lower and higher bilirubin levels may increase the risk of stroke in older persons with OSAS, and there was a J-type dose-response relationship. The risk of stroke was lowest when the TBil level was approximately 11.5 µmol/L.

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Acknowledgments: Not applicable.

Funding

Funding: This study was supported by Military Health Care Project (23BJZ27 and 22BJZ52), Military experimental animal special research project (SYDW_KY[2021]04), and Military Equipment Construction Application Research Project (LB20211A010013). The funders had no direct role in the design, data collection, analysis, interpretation, or writing of the manuscript.

Author information

Author notes

  1. Yinghui Gao, Libo Zhao and Kailiang Li contributed equally to this work.

Authors and Affiliations

  1. Sleep Center, Peking University International Hospital, Beijing, 102206, China

    Yinghui Gao

  2. Cardiology Department of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China

    Libo Zhao, J. Li, Z. Zhao & Li Fan

  3. Health Service Department of the Guard Bureau of the General Office of the Central Committee of the Communist Party of China, Beijing, 100031, China

    Kailiang Li

  4. Department of Nursing, West China Hospital, Sichuan University, Chengdu, 610041, China

    X. Su

  5. Institute of Geriatrics, Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatric Diseases, Second Medical Center, Chinese People’s Liberation Army General Hospital, Beijing, 100853, China

    X. Li

  6. College of Nursing, Peking University, Beijing, 100083, China

    H. Wang

  7. Medicine school, Yan’an University, Yan’an, 716000, China

    Z. He & F. Fang

  8. Cardiology Department of Guangdong Provincial People’s Hospital, Guangzhou, 510080, China

    W. Xu

  9. Department of Pulmonary and Critical Care Medicine of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China

    Xiaoshun Qian & Lin Liu

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  1. Yinghui Gao
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Contributions

Author contributions: LL, XsQ and LF contributed to the research design, data interpretation, and critically revised the manuscript. HhW, FfF and ZjH contributed to the data acquisition. XfS, JhL and ZZ collected the data and the samples. LbZ, YhG and KlL contributed to data interpretation and wrote the manuscript. WhX and XhL contributed to design and make the RCS figures. All authors gave final approval and agreed to be accountable for all aspects of this work.

Corresponding authors

Correspondence to Xiaoshun Qian, Li Fan or Lin Liu.

Ethics declarations

Ethics statement: The studies involving human participants were reviewed and approved by the Ethics Committee of Chinese PLA General Hospital (S2020-397-02).

Conflict of interest statement: The authors declare that the study was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Gao, Y., Zhao, L., Li, K. et al. The J-shape Association between Total Bilirubin and Stroke in Older Patients with Obstructive Sleep Apnea Syndrome: A Multicenter Study. J Nutr Health Aging 27, 692–700 (2023). https://doi.org/10.1007/s12603-023-1965-2

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