Gastroesophageal reflux disease increases the risk of essential hypertension: results from the Nationwide Readmission Database and Mendelian randomization analysis

Abstract

Background: The link between gastroesophageal reflux disease (GERD) and essential hypertension (EH) and its causal nature remains controversial. Our study examined the connection between GERD and the risk of hypertension and assessed further whether this correlation has a causal relationship.

Methods: First, we utilized the National Readmission Database including 14 422 183 participants to conduct an observational study. Dividing the population into GERD and non-GERD groups, we investigated the correlation between GERD and EH using multivariate logistic regression. Next, bidirectional two-sample Mendelian randomization was adopted. The summary statistics for GERD were obtained from a published genome-wide association study including 78 707 cases and 288 734 controls. We collected summary statistics for hypertension containing 70 651 cases and 223 663 controls from the FinnGen consortium. We assessed causality primarily by the inverse-variance weighted method with validation by four other Mendelian randomization approaches as well as an array of sensitivity analyses.

Results: In the unadjusted model, GERD patients had a higher risk of EH than the non-GERD group, regardless of gender (odds ratio, 1.43; 95% confidence interval: 1.42-1.43; P < .001). Further adjusting for critical confounders did not change this association. For Mendelian randomization, we found that genetically predicted GERD was causally linked to an enhanced risk of EH in inverse-variance weighted technique (odds ratio, 1.52; 95% confidence interval: 1.39-1.67; P = 3.51 × 10-18); conversely, EH did not raise the risk of GERD causally.

Conclusions: GERD is a causal risk factor for EH. Further research is required to probe the mechanism underlying this causal connection.

Keywords: Mendelian randomization; essential hypertension; gastroesophageal reflux disease; national readmission database.