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

Abstract

Objective Obesity is an important venous thrombosis (VT) risk factor but the reasons for this are unclear. Materials and Methods In 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. Results Greater 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 (factor VIII, von Willebrand factor, partial thromboplastin time, D-dimer and factor XI) only marginally lowered, or did not impact, the RRs associated with body size measures. Conclusions Greater 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.

Involvement of inflammatory markers in pathogenesis of venous thromboembolism

“…CRP levels have been directly proportional to the thrombotic load, the extension and volume of thrombus [25]. While some studies did not show a link between CRP levels and a future venous thrombotic event, others demonstrated a significant correlation between high levels of CRP and further development of thromboembolism [1,2,15,24].…”

“…While some studies did not show a link between CRP levels and a future venous thrombotic event, others demonstrated a significant correlation between high levels of CRP and further development of thromboembolism [1,2,15,24]. Although previous studies showed that at the moment of diagnosis there are high levels of CRP, it was proven that plasma CRP levels have no utility in infirming or confirming this diagnosis in patients with clinical suspicion of deep vein thrombosis [1,2,18,25]. Nevertheless, CRP plays a role in assessing the mortality risk and early complications [24,25].…”

“…Although previous studies showed that at the moment of diagnosis there are high levels of CRP, it was proven that plasma CRP levels have no utility in infirming or confirming this diagnosis in patients with clinical suspicion of deep vein thrombosis [1,2,18,25]. Nevertheless, CRP plays a role in assessing the mortality risk and early complications [24,25].…”

“…TNF seems to play a primordial role not only in the mediation of early inflammatory response and in the extravasation of neutrophils, but also in the late inflammatory response. TNF is also an important mediator that determines ICAM (intercellular adhesion molecule)-1 expression on the surface of endothelial cells and facilitates neutrophil, monocyte and lymphocyte adhesion at the inflammation site [24,25].…”

“…Activated macrophages produce IL-1beta as an important mediator of the inflammatory process, but also a procoagulant factor, involved in cell proliferation, differentiation, apoptosis and expression of tissue factor in endothelial and monocytic cells [24,25]. IL-10 levels were high in the vein wall at the time of venous thrombosis, being produced especially by monocytes and, at a lesser extent, by lymphocytes.…”