Endothelial Cell-Associated Tissue Factor Pathway Inhibitor (TFPI) Antigen in Severe Nondiabetic Obese Patients: Effect of Hyperinsulinemia

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Abstract
It has been suggested that the extrinsic coagulation system plays a crucial role in the initiation of blood coagulation in atherosclerotic disease and that TFPI, the inhibitor of the factor VIIa/tissue factor complex, bound to the endothelial cells, could prevent in vivo blood clotting. Because obesity has a role in the pathogenesis of atherosclerotic cardiovascular disease, we measured TFPI antigen plasma levels (ng/mL) by ELISA at baseline and 5 minutes after an IV bolus of 20 IU/kg body weight of unfractionated commercial mucous heparin in 12 obese patients with a mean body mass index (BMI) of 41.4 ± 1.4 kg/m2 and 14 normal-weight control subjects (BMI 23.1 ± 1.3 kg/m2). All subjects were submitted to an OGTT. The obese patients displayed a normal glucose tolerance. However, they had a different glucoseinduced hyperinsulinemia (14.9 ± 2.0 versus 7.8 ± 0.8 mU/L, pp=N.S.). In contrast, after heparin a significantly lower rise in TFPI antigen plasma levels was observed in obese patients (319.3 ± 37.9 ng/mL) as compared to controls (511.2 ± 43.4 ng/mL) (p<0.003). Moreover, a significant inverse correlation was found between the heparin-stimulated TFPI antigen plasma levels and both BMI and basal plasma insulin concentrations. Thus, the link between insulin level and endothelial cell-associated TFPI could at least partially explain why obese patients are more prone to develop cardiovascular disorders.

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