Gastroesophageal reflux disease influences blood pressure components, lipid profile and cardiovascular diseases: Evidence from a Mendelian randomization study

Background Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder associated with a range of cardiovascular and metabolic complications. However, the relationship between GERD and blood pressure components, lipid profile, and cardiovascular diseases remains unclear. Methods Leveraging genetic variants associated with GERD as instrumental variables, we performed this Mendelian randomization (MR) analyses. Blood pressure components, lipid profile parameters, as well as cardiovascular diseases were considered as outcomes. Furthermore, we conducted reverse MR analysis to explore the association of these factors with the risk of GERD. Results Our MR analysis discovered a potential causal influence of GERD on blood pressure components, with genetically predicted GERD positively associated with systolic blood pressure (beta = 0.053, P = 0.036), diastolic blood pressure (beta = 0.100, P < 0.001), and mean arterial pressure (beta = 0.106, P < 0.001). Additionally, genetically predicted GERD showed a significant impact on lipid profile, leading to increased genetically predicted levels of low-density lipoprotein (LDL) cholesterol (beta = 0.093, P < 0.001), and triglycerides (beta = 0.153, P < 0.001), while having a negative effect on high-density lipoprotein (HDL) cholesterol (beta = -0.115, P = 0.002). Furthermore, our study indicated a noteworthy causal association between genetically predicted GERD and increased risk of myocardial infarction [odds ratio (OR) = 1.272, P = 0.019)] and hypertension (OR = 1.357, P < 0.001). No significant association was found between GERD and pulse pressure, total cholesterol, heart failure, and atrial fibrillation (P > 0.05). Reverse MR analysis indicates that blood pressure components, lipid profile, and cardiovascular diseases do not lead to an increased risk of GERD (all P > 0.05). Furthermore, mediation MR analysis reveals that LDL cholesterol (proportion mediated: 19.99%, 95% CI: 4.49% to 35.50%), HDL cholesterol (proportion mediated: 11.71%, 95% CI: 5.23% to 18.19%), and hypertension (proportion mediated: 35.09%, 95% CI: 24.66% to 45.53%) mediated the effect of GERD on myocardial infarction, while other factors did not participate in this pathway. Conclusions This MR study provides evidence supporting a causal relationship between GERD and alterations in blood pressure components, lipid profile, and increased risk of cardiovascular diseases.