Body size measures, hemostatic and inflammatory markers and risk of venous thrombosis: The Longitudinal Investigation of Thromboembolism Etiology

• Obesity is a leading risk factor for venous thrombosis (VT), with unknown mechanism.
• Obesity drives a procoagulant, proinflammatory state.
• We observed associations of most body size measures with VT risk.
• Hemostasis and inflammation biomarkers did not substantially mediate associations.
• Physical factors not biochemical effects, are more likely causal for VT in obesity.

ObjectiveObesity is an important venous thrombosis (VT) risk factor but the reasons for this are unclear.Materials and methodsIn a cohort of 20,914 individuals aged 45 and older without prior VT, we calculated the relative risk (RR) of VT over 12.6 years follow-up according to baseline body size measures, and studied whether associations were mediated by biomarkers of hemostasis and inflammation that are related to adiposity.ResultsGreater levels of all body size measures (weight, height, waist, hip circumference, calf circumference, body-mass index, waist-hip ratio, fat mass and fat-free mass) were associated with increased risk of VT, with 4th versus 1st quartile RRs of 1.5–3.0. There were no multiplicative interactions of biomarkers with obesity status. Adjustment for biomarkers associated with VT risk and body size (factors VII and VIII, von Willebrand factor, partial thromboplastin time, D-dimer, C-reactive protein and factor XI) only marginally lowered, or did not impact, the RRs associated with body size measures.ConclusionsGreater body size, by multiple measures, is a risk factor for VT. Associations were not mediated by circulating levels of studied biomarkers suggesting that body size relates to VT because of physical factors associated with blood flow, not the hypercoagulability or inflammation associated with adiposity.