Obesity, plasma metabolites, and hypertension: A mediation Mendelian randomization study based on STROBE-MR guidelines

Studies have shown the association between obesity and hypertension. Plasma metabolites may have a potential association between the 2. Plasma metabolites mediate the relationship between obesity indicators and hypertension were explored through Mendelian randomization analysis. The inverse variance weighted method was employed as the primary analytical technique, supplemented by Mendelian randomization-Egger, simple mode, weighted median, and weighted mode analysis. Sensitivity analyses were conducted to ensure the robustness of our findings. Furthermore, mediation analysis was utilized to elucidate potential mediating effects of plasma metabolites and obesity. The inverse variance weighted results indicated that obesity indicators served as risk factors for hypertension [odds ratio (OR) = 1.197-1.823; P < .001]. In exploring the associations between plasma metabolites and hypertension, 94 significant causal relationships were identified; among these, "propionylglycine levels" (OR = 0.936; P < .001) emerged as protective factor while "margarate (17:0) levels" was identified as risk factor (OR = 1.098; P < .001). Further mediation analyses suggested the possibility of 19 pairs of mediating effects via plasma metabolites as mediator; notably, "phosphate to asparagine ratio" could reduce the risk effect of obesity on hypertension (1.588%). Sensitivity analyses confirmed the reliability of these results. This study revealed the complex causal relationships between obesity indicators, plasma metabolites, and hypertension, and confirmed the potential mediating role of plasma metabolites between obesity indicators and hypertension. These findings provided new perspectives for the prevention and treatment of hypertension.