Objectives: In this study we examined the association between leptin and blood pressure in a population-based study of Danish and Norwegian children and adolescents. Because of the putative bidirectional relationship between leptin and adiposity we formally tested (i) the mediating effect of body mass index in the association between leptin and blood pressure, and (ii) the mediating effect of leptin in the association between body mass index and blood pressure.

Methods: To examine these aims we used a cross-sectional random sample of children and adolescents from Denmark and Norway (n = 1993) who had measures of leptin, anthropometry, blood pressure and other personal and biological risk factors for raised blood pressure available.

Results: Both body mass index and leptin were positively associated with blood pressure (P < 0.001). The association with leptin was stronger in pre- and early-pubertal children compared to late- and post-pubertal adolescents (P < 0.01 for interaction). The association between leptin and blood pressure was almost completely mediated by body mass index, whereas the association between body mass index and blood pressure was modestly mediated by leptin.

Conclusion: Leptin was strongly associated with blood pressure, a relationship that to a large extent was mediated by body mass index. Conversely, the association between body mass index and blood pressure was only modestly mediated by leptin. This indicates that the influence of adiposity on blood pressure is also driven by other biological risk factors beyond leptin. Such factors could include insulin, glucose, and triglycerides although residual confounding also could account for the observed relationships.