Causal Effects of Basal Metabolic Rate on Cardiovascular Disease: A Bidirectional Mendelian Randomization Study.

ABSTRACT

BACKGROUND: Despite the health effects of basal metabolic rate (BMR), the causal effect of BMR on cardiovascular diseases (CVDs) remains undetermined. To elucidate the causal nature, Mendelian randomization (MR) analyses were performed. METHODS AND RESULTS: Summary genome-wide association statistics regarding BMR and 5 CVDs were obtained from European databases. A 2-sample bidirectional MR was performed to assess the causal association between BMR and CVDs. The causal effects were estimated using inverse variance weighting. Simultaneously, multiple sensitivity analyses were performed to validate the robustness and reliability of the results. Our results indicated that genetically predicted BMR was significantly positively associated with the risk of heart failure (odds ratio, 1.53 [95% CI, 1.39-1.67]; P<0.001), atrial fibrillation and flutter (odds ratio, 2.12 [95% CI, 1.87-2.40]; P<0.001), and aortic aneurysm (odds ratio, 1.64 [95% CI, 1.41-1.92]; P<0.001). Genetically predicted BMR may not be causally associated with coronary artery disease and ischemic stroke risk. Furthermore, a significant causal effect of CVDs on BMR was not found in the reverse MR analysis. Multivariable MR was applied to further assess the direct effect of BMR on CVDs. Multivariable MR indicated that a high level of BMR still increased the risk of heart failure and atrial fibrillation and flutter after adjustment independent of possible confounders. However, the P value of aortic aneurysm was not significant. CONCLUSIONS: The present study provides robust evidence that genetically predicted BMR is independently causally associated with heart failure and atrial fibrillation and flutter but not vice versa. These findings have implications for the prevention and treatment of CVDs in clinical practice.