Obesity, Visceral Adipose Tissue, and Essential Hypertension: Evidence From a Mendelian Randomization Study and Mediation Analysis

Abstract

This study aims to investigate the causal relationship between obesity and essential hypertension, and evaluate the mediation effect of visceral adipose tissue (VAT) by Mendelian randomization (MR) analysis. We included body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), WC adjusted for BMI (WCadjbmi), and WHR adjusted for BMI (WHRadjbmi) as obesity-related anthropometric traits. In the bidirectional MR analyses, we found that higher BMI (OR, 1.638; p = 3.97 × 10⁻¹⁹), WC (OR, 1.702; p = 1.45 × 10⁻¹²), and WHR (OR, 1.863; p = 1.84 × 10⁻⁸) were significantly associated with increased risk of essential hypertension, while no evidence of reverse causality was observed. Then, in the two-step MR analyses, all five anthropometric traits had a positive and significant association with VAT mass, especially WC (OR, 2.315; p = 1.00 × 10⁻²¹⁰). Meanwhile, higher predicted VAT mass was significantly associated with increased risk of essential hypertension (OR, 1.713; p = 1.18 × 10⁻³⁸). Furthermore, the mediation analyses revealed that VAT had a significant mediation effect on the causal relationship between obesity-related anthropometric traits and essential hypertension, and mediated proportions in BMI, WC, and WHR were 77.8%, 80.1%, and 41.4%, respectively. Finally, the sensitivity analyses using two other datasets showed a similar result. In conclusion, our results showed that BMI, WC, and WHR have a positive and significant association with increased risk of essential hypertension. Moreover, VAT has a significant mediation effect on the causal relationship between obesity-related anthropometric traits and essential hypertension. Our study provided important statistical evidence suggesting that VAT may play a crucial meditation role in the occurrence and development of obesity-related hypertension.