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

BACKGROUND: Previous studies have found associations of red blood cell (RBC) traits (hemoglobin and RBC count) 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 2 sample Mendelian randomization (MR) analyses to explore the causal effect of the 2 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 (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.16–1.20 for hypertension; B = 0.11, 95% CI: 0.11–0.12 for SBP; B = 0.11, 95% CI: 0.10–0.11 for DBP, all per SD) and RBC (OR = 1.14, 95% CI: 1.12–1.16 for hypertension; B = 0.11, 95% CI: 0.10–0.12 for SBP; B = 0.08, 95% CI: 0.08–0.09 for DBP, all per SD). MR analyses suggested that higher hemoglobin and RBC cause higher DBP (inverse-variance weighted B = 0.11, 95% CI: 0.07–0.16 for hemoglobin; B = 0.07, 95% CI: 0.04–0.10 for RBC, all per SD). Reverse MR analyses (all per SD) suggested causal effects of DBP on both hemoglobin (B = 0.06, 95% CI: 0.03–0.09) and RBC (B = 0.08, 95% CI: 0.04–0.11). No significant effects on SBP were found. CONCLUSIONS: Our results suggest bidirectional causal relationships of hemoglobin and RBC with DBP, but not with SBP.