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.