Exploring the silent connection: unveiling the intricate relationship between gastroesophageal reflux disease and...

Gastroesophageal reflux disease (GERD) and Sleep Apnea Syndrome (SAS) are two prevalent medical conditions that significantly affect health and quality of life. GERD involves stomach content reflux into the esophagus, while SAS causes recurrent upper airway obstruction during sleep. Despite recent studies hinting at a link, the precise relationship and causality between GERD and SAS remain unclear. Our research uses bidirectional Mendelian randomization to explore this intricate relationship. Additionally, given SAS's high prevalence in cardiovascular patients (40-80%, as highlighted by the American Heart Association), we also investigated its potential association with various cardiovascular diseases to gain new insights into prevention and treatment.

This study employed genetic data from large-scale genome-wide association studies (GWAS) on GERD (129,080 cases, 473,524 controls) and SAS (25,008 cases, 391,473 controls) for two-sample Mendelian randomization (MR) analysis to estimate the causal effects of GERD on the risk of SAS. All SNPs were selected using a strict clump window (r² = 0.001 and kb = 10,000). We initially applied the inverse variance weighted (IVW) method and measured horizontal pleiotropy using MR-Egger, weighted median, and weighted mode methods. I² index and Cochran Q statistics were used for sensitivity analysis. Funnel plot symmetry of IVW MR estimates versus 1/standard error (1/SEIV) was examined to exclude SNPs potentially causing heterogeneity. Additionally, to exclude reverse causality, bidirectional MR was employed to investigate whether genetic susceptibility to SAS causally influenced the risk of GERD.

GERD was associated with an elevated risk of SAS, demonstrating an odds ratio (OR) of 1.750 (95% CI 1.590-1.930; P < 0.001). Conversely, there was no compelling evidence to indicate a causal link between SAS and the risk of developing GERD, with an OR of 1.000 (95% CI 0.989-1.011; P = 0.964). In addition to the primary findings, our study also revealed significant risks associated with SAS for several cardiovascular conditions, including coronary heart disease, atrial fibrillation, coronary artery disease, heart failure, intracerebral hemorrhage, and ischemic stroke.

We discovered compelling evidence indicating an elevated risk of SAS in individuals with GERD, but no significant evidence supporting an increased risk of GERD in those with SAS. Future investigations into SAS risk should take into account the potential therapeutic targeting of GERD. PPI and histamine antagonists can effectively reduce reflux and airway secretions, preventing airway damage and collapse. Furthermore, it is necessary to investigate the underlying mechanisms by which GERD affects SAS. For example, the inflammatory stimulation caused by gastric acid and pepsin in refluxed fluid, as well as the increased tension of bronchial smooth muscle caused by vagus nerve reflex. Thus, early preventive measures can be implemented for potential complications related to SAS.