Role of Inflammatory Biomarkers in Mediating Causal Effect of Life Course Body Composition on Hypertension

BACKGROUND: The mediating role of inflammatory biomarkers in the causal relationship between body composition and hypertension remains unclear and requires further investigation. METHODS: This study used a combination of retrospective observational analysis and Mendelian randomization approaches. Observational data were derived from 4717 Chinese children and adolescents aged 6 to 18 years who underwent dual-energy X-ray absorptiometry to assess body composition. Mendelian randomization analyses utilized summary statistics from large-scale data sets, including UK Biobank, deCODE2021, International Consortium of Blood Pressure, FinnGen, and other consortia. The inflammatory biomarkers included leptin, insulin, adiponectin, osteocalcin, FGF23 (fibroblast growth factor 23), and PTH (parathyroid hormone). RESULTS: The observational analysis revealed that increased fat mass positively influenced diastolic blood pressure through osteocalcin, while fat-free mass had an inverse effect. Insulin mediated the association between fat mass and systolic blood pressure, diastolic blood pressure, and hypertension, with additional indirect effects observed for PTH (all P<0.05). The Mendelian randomization analyses demonstrated a causal relationship between childhood body mass index and hypertension mediated by insulin (indirect effect: odds ratio, 0.87 [95% CI, 0.78-0.97]) and adiponectin (odds ratio, 1.13 [95% CI, 1.04-1.23]). Adiponectin mediated the effects of fat-free mass (odds ratio, 0.81 [95% CI, 0.71-0.93]) and fat mass (odds ratio, 1.30 [95% CI, 1.11-1.51]) on hypertension. Leptin, adiponectin, and insulin also mediated the causal effects of body composition on systolic blood pressure, diastolic blood pressure, and hypertension. CONCLUSIONS: These findings indicate that body composition influences blood pressure through distinct inflammatory biomarkers. Targeting inflammatory biomarkers may provide tailored strategies for managing body composition and hypertension.