Observational and Genetic Evidence for Bidirectional Effects Between Red Blood Cell Traits and Diastolic Blood Pressure

Zhen He, Zekai Chen, Martin de Borst, Qingying Zhang, International Consortium Of Blood Pressure, Harold Snieder*, C. H. L. Thio*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Downloads (Pure)


Background: Previous studies have found associations of red blood cell traits (hemoglobin and red blood cell count, RBC) with blood pressure; whether these associations are causal is unknown.

Methods: We performed cross-sectional analyses in the Lifelines Cohort Study (n=167,785). Additionally, we performed bidirectional two sample Mendelian randomization (MR) analyses to explore the causal effect of the two traits on systolic (SBP) and diastolic blood pressure (DBP), using genetic instrumental variables regarding hemoglobin and RBC identified in UK Biobank (n=350,475) and International Consortium of Blood Pressure studies for SBP and DBP (n= 757,601).

Results: In cross-sectional analyses we observed positive associations with hypertension and blood pressure for both hemoglobin (OR=1.18, 95% CI: 1.16 to 1.20 for hypertension; B=0.11, 95% CI: 0.11 to 0.12 for SBP; B=0.11, 95% CI: 0.10 to 0.11 for DBP, all per SD) and RBC (OR=1.14, 95% CI: 1.12 to 1.16 for hypertension; B=0.11, 95% CI: 0.10 to 0.12 for SBP; B=0.08, 95% CI: 0.08 to 0.09 for DBP, all per SD). MR analyses suggested that higher hemoglobin and RBC cause higher DBP (inverse variance weighted [IVW] B=0.11, 95% CI: 0.07 to 0.16 for hemoglobin; B=0.07, 95% CI: 0.04 to 0.10 for RBC, all per SD). Reverse MR analyses (all per SD) suggested causal effects of DBP on both hemoglobin (B=0.06, 95% CI: 0.03 to 0.09) and RBC (B=0.08, 95% CI: 0.04 to 0.11). No significant effects on SBP were found.

Conclusions: Our results suggest bidirectional causal relationships of hemoglobin and RBC with DBP, but not with SBP.
Original languageEnglish
Pages (from-to)551-560
Number of pages10
JournalAmerican Journal of Hypertension
Issue number10
Early online date11-Jul-2023
Publication statusPublished - Oct-2023


  • blood pressure
  • hemoglobin
  • hypertension
  • Mendelian randomization
  • red blood cell count

Cite this