Plasma Levels of Leptin and Risk of Future Incident Venous Thromboembolism

Background Circulating levels of leptin, an adipocyte-derived hormone, are frequently elevated in obesity. Leptin has been reported to upregulate prothrombotic hemostatic factors in vitro and could potentially mediate venous thromboembolism (VTE) risk in obesity. However, whether leptin is associated with VTE remains uncertain. Objective This article investigates the association between plasma leptin and risk of incident VTE, and the potential of leptin to mediate VTE risk in obesity. Methods A population-based nested case-control study with 416 VTE cases and 848 age- and sex-matched controls was derived from the TromsO Study. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for VTE across leptin quartiles. Analyses were performed separately in men and women using sex-specific quartile cut-offs determined in controls. Results In the age-adjusted model, the VTE risk increased across leptin quartiles, particularly in men. Compared with the lowest quartile, the ORs for VTE in the highest quartile were 1.70 (95% CI 1.04-2.79) in men and 1.36 (95% CI 0.85-2.17) in women. However, with additional adjustment for body mass index (BMI), risk estimates were markedly attenuated in men (OR 1.03, 95% CI 0.55-1.93) and women (OR 0.82, 95% CI 0.45-1.48). The ORs for VTE were increased in obese men and women (BMI >= 30kg/m (2) ) and were only marginally affected after adjustment for leptin. Conclusion Our results indicate that the apparent association between plasma leptin levels and VTE risk is confounded by BMI and that leptin is not a relevant mediator for VTE risk in obesity.