Effects of body mass index and blood pressure on atrioventricular block: Two-sample mendelian randomization

BACKGROUND Observational studies have suggested associations between some atherogenic risk factors and atrioventricular OBJECTIVE The purpose of this study was to investigate the causal effects of several cardiometabolic exposures on AV block and evaluate the role of coronary artery disease (CAD) as a mediator on the causal pathway by mendelian randomization analysis. METHODS Two-sample bidirectional mendelian randomization was performed to assess the causal effects of cardiometabolic traits on AV block and examine causality inversely. The exposures of interest included body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, fasting insulin, low-density lipoprotein, high-density lipoprotein, and triglyceride. Multivariable mendelian randomization was then conducted to disentangle the effect of each significant exposure. Mediation effect of CAD on the causal pathways were estimated by two-step, two-sample mendelian randomization. RESULTS Genetically predicted elevation of BMI (odds ratio [OR] 1.40; 95% confidence interval [CI] 1.10-1.78; P = .006), SBP (OR 1.02; 95% CI 1.00-1.03; P = .015), and DBP (OR 1.04; 95% CI 1.01-1.07; P = .005) were significantly associated with increased AV block risk. Effects of the other exposures were insignificant. There were no reverse causal effects. Multivariable mendelian randomization showed causal effects of increased BMI, SBP, and DBP on AV block after mutual adjustment. CAD mediated 14.20% (8.82%, 16.46%), 26.32% (25.00%, 26.47,%) and 12.20% (7.69%, 15.94%) of AV block risk from BMI, SBP CONCLUSION Elevated BMI, SBP, and DBP exhibited causal effects on AV block. The impacts were partly mediated by CAD.