Conventional and bi-directional genetic evidence on resting heart rate and cardiometabolic traits

Abstract Objectives To examine the direction, strength and causality of the associations of resting heart rate (RHR) with cardiometabolic traits. Methods We assessed the strength of associations between measured RHR and cardiometabolic traits in 506,211 and 372,452 participants from China Kadoorie Biobank (CKB) and UK Biobank (UKB). Mendelian randomization (MR) analyses were used to make causal inferences in 99,228 and 371,508 participants from CKB and UKB, respectively. Results We identified significant, directionally-concordant observational associations between RHR and higher total cholesterol, triglycerides (TG), low-density lipoprotein, C-reactive protein (CRP), glucose, body mass index, waist-hip ratio (WHR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) after the Bonferroni correction. MR analyses showed that 10 beat/min higher genetically-predicted RHR were trans-ethnically associated with a higher DBP (beta 2.059 [95%CI 1.544, 2.574] mmHg in CKB; 2.037 [1.845, 2.229] mmHg in UKB), higher CRP (0.180 [0.057, 0.303] log mg/L in CKB; 0.154 [0.134, 0.174] log mg/L in UKB), higher TG (0.052 [-0.009, 0.113] log mmol/L in CKB; 0.020 [0.010, 0.030] log mmol/L in UKB) and higher WHR (0.218 [-0.033, 0.469] % in CKB; 0.225 [0.111, 0.339] % in UKB). In the opposite direction, higher genetically-predicted SBP, TG, glucose, WHR and lower high-density lipoprotein were associated with elevated RHR. Conclusion Our large-scale analyses provide causal evidence between RHR and cardiometabolic traits, highlighting the importance of monitoring heat rate as a means of alleviating the adverse effect of metabolic disorders.