Serum total bilirubin and new-onset hypertension in perimenopausal women: A cross-sectional study

Zhen He, Shengchao Zhang, Chris Thio, Yue Wang, Min Li, Yan Wu, Rongqing Lin, Zhixi Liu, Harold Snieder, Qingying Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
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Objective: Previous studies have shown negative associations between total bilirubin (TBIL) and hypertension. However, the association of TBIL with new-onset hypertension in perimenopausal women is unknown.

Methods: A total of 196 perimenopausal women were included in this cross-sectional study of which 85 had new-onset hypertension. All participants underwent 24-hour ambulatory blood pressure monitoring and a clinical assessment including anthropometrics. Sociodemographic, lifestyle, and menopausal symptoms (modified Kupperman Index [mKI]) were measured by questionnaire. A fasting blood sample was taken to measure a wide range of biomarkers and hormone levels. Restricted cubic spline regression was used to investigate potential nonlinearity. Multivariable logistic and robust linear regression analyses adjusting for minimal sufficient adjustment sets based on directed acyclic graphs were performed to test the association of TBIL with hypertension/blood pressure. We examined mKI-stratified analyses and a TBIL-mKI interaction term to explore potential effect modification by number of menopausal symptoms.

Results: Hypertensive women had significantly lower TBIL levels than did normotensive women (11.15 vs 12.55 μmol/L, P = 0.046). Univariate restricted cubic spline regression showed nonsignificant nonlinearity (P value for nonlinearity, 0.339). Multivariable regression analyses adjusted for minimal sufficient adjustment sets revealed that higher TBIL level was associated with lower odds of hypertension (odds ratio, 0.91 per μmol/L TBIL; 95% confidence interval [CI], 0.84-0.98; P = 0.019). Total bilirubin showed a significant inverse association with average 24-hour diastolic blood pressure (β = -0.36 mm Hg per μmol/L TBIL; 95% CI, -0.62 to -0.10; P = 0.008) but not with 24-hour systolic blood pressure (β = -0.37 mm Hg per μmol/L TBIL; 95% CI, -0.79 to 0.06; P = 0.090). Stratified analyses suggested stronger inverse associations of TBIL with hypertension and 24-hour blood pressure in women with fewer menopausal symptoms (mKI ≤10), although the TBIL-mKI interaction was not significant.

Conclusions: In perimenopause, TBIL was inversely associated with diastolic blood pressure and new-onset hypertension, diagnosed using 24-hour ambulatory blood pressure monitoring.

Original languageEnglish
Pages (from-to)944-951
Number of pages8
Issue number8
Publication statusPublished - 1-Aug-2022


  • Hypertension
  • Perimenopause
  • Total bilirubin

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