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, p<0.01). Total serum cholesterol did not differ between controls and obese patients,
whereas plasma triglycerides were higher in the latter group. Basal TFPI antigen plasma
levels were similar in obese and controls (83.8 ± 5.0 versus 77.7 ± 3.5 ng/mL, p=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.
Keywords:
TFPI - obesity - hyperinsulinemia - lipids - heparin
