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The Nonlinear Relationship Between Total Bilirubin and Coronary Heart Disease: A Dose-Response Meta-Analysis

Chaoxiu Li1, Wenying Wu2, Yumeng Song1

  • 1Department of Clinical Epidemiology and Center of Evidence-Based Medicine, The First Hospital of China Medical University, Shenyang, China.

Frontiers in Cardiovascular Medicine
|January 24, 2022
PubMed

Insights

Total bilirubin offers a protective effect against coronary heart disease (CHD). This meta-analysis reveals a U-shaped dose-response relationship, indicating optimal protection within a specific bilirubin level range.

Area of Science:

  • Cardiology
  • Biochemistry
  • Epidemiology

Background:

  • The potential cardioprotective role of total bilirubin is suggested by existing evidence.
  • However, the precise dose-response relationship between total bilirubin and coronary heart disease (CHD) risk remains debated.
  • A comprehensive meta-analysis was needed to clarify this association.

Approach:

  • A systematic literature search was conducted across PubMed, Web of Science, Cochrane Library, and Embase up to October 1, 2021.
  • Seven prospective studies, encompassing 170,209 participants (6,342 CHD cases), were included in this meta-analysis.
  • Restricted cubic splines were employed to model the dose-response curve, with statistical analysis performed using Stata 12.0.

Key Points:

  • Compared to the lowest quantile, the third quantile of bilirubin levels showed a protective effect on CHD risk (RR, 0.90; 95% CI, 0.82-0.99).
  • A U-shaped curve characterized the relationship between bilirubin levels (3.42-49 μmol/L) and CHD risk (Plinear < 0.001).
  • The protective effect intensified up to 13 μmol/L, then diminished, with potential adverse effects at higher concentrations.

Conclusions:

  • Elevated total bilirubin levels demonstrate a protective effect against coronary heart disease risk.
  • A significant U-shaped dose-response relationship exists between serum bilirubin concentration and CHD risk.
  • Optimal cardioprotection is observed within a specific range of bilirubin levels, highlighting the complexity of this association.

Keywords:
bilirubincoronary heart diseasedose responsemeta-analysisnonlinear

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