Department of Cardiology and Atrial fibrillation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
Hum Mol Genet. 2022 Dec 16;31(24):4275-4285. doi: 10.1093/hmg/ddac162.
Observational studies have reported that gastroesophageal reflux disease (GERD) is a risk factor for cardiovascular diseases (CVD); however, the causal inferences between them remain unknown. We conducted a Mendelian randomization (MR) study to estimate the causal associations between GERD and 10 CVD outcomes, as well as 14 cardiovascular risk factors. We used summary statistics from genome-wide association studies for GERD and the FinnGen consortium for CVD. We further investigated whether GERD correlated with cardiovascular risk factors and performed multivariable MR and mediation analyses to estimate the mediating effects of these risk factors on GERD-CVD progression. Sensitivity analyses and replication analyses were also performed. Our results indicated that GERD was positively associated with seven CVD outcomes with odds ratios of 1.26 [95% confidence interval (CI), 1.15, 1.37] for coronary artery disease, 1.41 (95% CI, 1.28, 1.57) for myocardial infarction, 1.34 (95% CI, 1.19, 1.51) for atrial fibrillation, 1.34 (95% CI, 1.21, 1.50) for heart failure, 1.30 (95% CI, 1.18, 1.43) for any stroke, 1.19 (95% CI, 1.06, 1.34) for ischemic stroke and 1.29 (95% CI, 1.16, 1.44) for venous thromboembolism. Furthermore, GERD was associated with nine cardiovascular risk factors and major depressive disorder demonstrated significant mediation effects on the causal pathway linking GERD and any stroke. This study demonstrates that GERD is associated with seven CVD outcomes and nine cardiovascular risk factors. Importantly, GERD treatment may help prevent common CVD events.
观察性研究报告称，胃食管反流病（GERD）是心血管疾病（CVD）的危险因素；然而，它们之间的因果关系尚不清楚。我们进行了一项孟德尔随机化（MR）研究，以估计 GERD 与 10 种 CVD 结局以及 14 种心血管风险因素之间的因果关联。我们使用 GERD 的全基因组关联研究和 FinnGen 联盟的 CVD 汇总统计数据。我们进一步研究了 GERD 是否与心血管风险因素相关，并进行了多变量 MR 和中介分析，以估计这些风险因素对 GERD-CVD 进展的中介作用。还进行了敏感性分析和复制分析。我们的研究结果表明，GERD 与七种 CVD 结局呈正相关，冠心病的比值比（OR）为 1.26（95%置信区间[CI]，1.15，1.37），心肌梗死为 1.41（95%CI，1.28，1.57），心房颤动为 1.34（95%CI，1.19，1.51），心力衰竭为 1.34（95%CI，1.21，1.50），任何类型的中风为 1.30（95%CI，1.18，1.43），缺血性中风为 1.19（95%CI，1.06，1.34），静脉血栓栓塞为 1.29（95%CI，1.16，1.44）。此外，GERD 与九个心血管风险因素相关，而重度抑郁症则在 GERD 与任何类型中风的因果关系中表现出显著的中介作用。这项研究表明，GERD 与七种 CVD 结局和九个心血管风险因素相关。重要的是，GERD 的治疗可能有助于预防常见的 CVD 事件。
