Researchers have found evidence suggesting that gastroesophageal reflux disease (GERD) may be causally linked to an increased risk of atrial fibrillation.
In a recent study, published in the journal Frontiers in Cardiovascular Medicine, the researchers analyzed data from two large European genome-wide association studies, which included a respective 602,604 patients (129,080 of whom had GERD and 473,524 of whom didn't have the condition) and just over 1 million patients (60,620 of whom had atrial fibrillation and 970,216 of whom didn't have the condition). The researchers used 76 single-nucleotide polymorphisms (SNPs) as genetic markers in their Mendelian randomization analyses after removing outliers and potential pleiotropic SNPs. By using these genetic variants as instrumental variables, the Mendelian randomization approach allowed the researchers to minimize the impact of potential confounding factors and reverse causality.
The researchers revealed a statistically significant causal relationship between GERD and an increased risk of atrial fibrillation. The odds ratio for developing atrial fibrillation was found to be 1.165 (95% confidence interval = 1.102–1.231, P = 7.637 × 10-8) in patients with genetically predicted GERD compared with those without genetically predicted GERD. The causal estimates were examined using the inverse-variance weighted method, and additional statistical methods—including MR-Egger, simple mode, weighted mode, MR Pleiotropy Residual Sum, and weighted median—were used in the sensitivity analyses.
The findings were consistent across multiple sensitivity analyses, which aimed to assess the robustness of the causal estimates. The researchers also found no evidence of pleiotropy, suggesting that the genetic variants used in the study were likely to influence atrial fibrillation risk primarily through their effect on GERD.
While the exact biological mechanisms underlying the observed relationship remained to be elucidated, the researchers propose that proinflammatory cytokines released as a result of esophageal injuries in patients with GERD may create a favorable environment for the development of atrial fibrillation. Additionally, GERD-induced autonomic nervous system dysfunction may also contribute to an increased risk of atrial fibrillation.
The researchers indicated that early treatment of GERD could potentially reduce the risk of developing atrial fibrillation. However, they emphasized that further research, including large-scale intervention trials and prospective cohort studies, may be needed to confirm these results and guide the development of preventive and therapeutic strategies.
The authors declared no competing interests.