Increase in both pro-thrombotic and anti-thrombotic factors in obese premenopausal women: relationship with body fat distribution

Abstract

OBJECTIVE: To examine the relationship of obesity, body fat distribution, and fasting plasma insulin concentrations with the plasma levels of both pro-thrombotic and anti-thrombotic factors in premenopausal women. SUBJECTS: 32 obese women with BMI>28 and 33 age-matched non-obese=women with BMI<25. MEASUREMENTS: (i) plasma concentrations of plasminogen activator inhibitor-1 antigen (PAI-1 Ag), plasminogen activator inhibitor-1 activity (PAI-1 activity), fibrinogen, von Willebrand factor antigen (vWF Ag), von Willebrand factor activity (vWF activity), and factor VII activity as pro-thrombotic factors; (ii) plasma concentrations of tissue plasminogen activator antigen (t-PA Ag), protein C, and antithrombin III as anti-thrombotic factors; (iii) fasting plasma insulin and glucose concentrations, and the lipid pattern (triglycerides, total and HDL-cholesterol) as metabolic parameters. The body fat distribution was evaluated by measuring the waist circumference and the waist-to-hip ratio (WHR). RESULTS: Obese subjects had higher plasma concentrations of all pro-thrombotic factors as compared to non-obese controls (PAI-1 Ag, P<0.001; PAI-1 activity, P<0.05; fibrinogen, P<0.001; vWF Ag, P<0.001; vWF activity, P<0.05; factor VII, P<0.05). The plasma concentrations of PAI-1 Ag and vWF Ag were directly correlated with the waist circumference independently of other metabolic and non-metabolic variables (P<0.05). Obese women were also characterized by higher plasma concentrations of anti-thrombotic factors such as t-PA Ag and protein C as compared to non-obese controls (P<0.001 and P<0.001, respectively), although these factors were not independently correlated with the waist circumference or the WHR. CONCLUSION: Plasma concentrations of the pro-thrombotic factors are increased in obese women as compared to non-obese controls, and plasma levels of PAI-1 Ag and vWF Ag correlate with central fat accumulation specifically. Plasma concentrations of anti-thrombotic factors (namely protein C and t-PA Ag) are also raised in obese women, but they are not correlated with parameters of body fat distribution. The increase in protein C levels may represent a protective response partly counteracting the increase in pro-thrombotic factors in these individuals.