The potential of spironolactone to mitigate the risk of nonalcoholic fatty liver disease in hypertensive populations: evidence from a cohort study

OBJECTIVE: While the link between nonalcoholic fatty liver disease (NAFLD) and hypertension is well recognized, the potential protective effects of the widely used antihypertensive medication, spironolactone, on NAFLD risk remain unclear. This study aimed to evaluate the impact of spironolactone on the development of NAFLD in hypertensive patients, shedding light on its potential broader clinical benefits beyond blood pressure control. METHODS: A total of 7241 participants were included. Propensity score matching (1 : 4 ratio) was employed to minimize confounding factors, creating balanced groups of spironolactone users and nonusers. Multivariate Cox regression analysis and Kaplan-Meier survival analysis were used to evaluate the association between spironolactone use and NAFLD risk. Restricted cubic splines (RCS) were applied to assess the dose-response relationship, and subgroup and sensitivity analyses were performed to validate the robustness of the findings. RESULTS: After matching, the study included 4110 participants (822 spironolactone users and 3288 nonusers). Spironolactone use was associated with a significantly lower risk of NAFLD, with a 16.3% reduction in risk compared with nonusers (hazard ratio: 0.821; 95% confidence interval: 0.714-0.944). The RCS analysis revealed that a cumulative spironolactone dose exceeding 635 mg*months was associated with a significant reduction in NAFLD risk. Subgroup and sensitivity analyses confirmed the consistency of these findings across various patient characteristics and conditions. CONCLUSION: This study demonstrates a significant association between spironolactone use and a reduced risk of NAFLD in hypertensive patients, suggesting that it may have potential dual benefits in managing hypertension and protecting liver health.