Causal Effects of Basal Metabolic Rate on Cardiovascular Disease: A Bidirectional Mendelian Randomization Study
Causal Effects of Basal Metabolic Rate on Cardiovascular Disease: A Bidirectional Mendelian Randomization Study
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DOI：
10.1161/jaha.123.031447
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发表时间：
2023-12
期刊：
影响因子：
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通讯作者：
Peng Zhao;Feiyuan Han;Xinyu Liang;Li Meng;Bo Yu;Xinxin Liu;Jinwei Tian
中科院分区：
文献类型：
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作者：
Peng Zhao;Feiyuan Han;Xinyu Liang;Li Meng;Bo Yu;Xinxin Liu;Jinwei Tian
背景 尽管基础代谢率 (BMR) 对健康有影响，但 BMR 对心血管疾病 (CVD) 的因果影响仍不确定。为了阐明因果性质，进行了孟德尔随机化 (MR) 分析。方法和结果从欧洲数据库获得有关 BMR 和 5 种 CVD 的全基因组关联统计数据摘要。进行 2 个样本的双向 MR 来评估 BMR 与 CVD 之间的因果关系。使用逆方差加权来估计因果效应。同时，进行了多项敏感性分析，以验证结果的稳健性和可靠性。我们的结果表明，基因预测的 BMR 与心力衰竭（比值比，1.53 [95% CI，1.39–1.67]；P<0.001）、心房颤动和扑动（比值比，2.12 [95% CI，1.87–2.40]；P<0.001）和主动脉瘤风险显着正相关。 （比值比，1.64 [95% CI，1.41–1.92]；P<0.001）。基因预测的 BMR 可能与冠状动脉疾病和缺血性中风风险没有因果关系。此外，在反向 MR 分析中未发现 CVD 对 BMR 的显着因果影响。应用多变量 MR 进一步评估 BMR 对 CVD 的直接影响。多变量 MR 表明，在调整后，高水平的 BMR 仍然会增加心力衰竭、心房颤动和心房扑动的风险，而与可能的混杂因素无关。然而，主动脉瘤的P值并不显着。结论 本研究提供了强有力的证据，表明基因预测的 BMR 与心力衰竭、心房颤动和心房扑动独立因果相关，但反之则不然。这些发现对临床实践中心血管疾病的预防和治疗具有重要意义。
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.