LOWER ANDROGENICITY IS ASSOCIATED WITH HIGHER PLASMA-LEVELS OF PROTHROMBOTIC FACTORS IRRESPECTIVE OF AGE, OBESITY BODY-FAT DISTRIBUTION, AND RELATED METABOLIC PARAMETERS IN MEN

The purpose of this study was to examine the relationships between and rogenic status and plasma levels of both prothrombotic and antithrombo tic factors in men, irrespective of obesity, body fat distribution, an d metabolic parameters. Sixty-four apparently healthy men, 40 with a b ody mass index (BMI) greater than 25 kg/m(2) (overweight and obese [OO ]) and 24 non-obese controls with a BMI less than 25, were selected an d evaluated for (1) plasma concentrations of plasminogen activator inh ibitor-1 (PAI-1) antigen, PAI-1 activity, fibrinogen, von Willebrand f actor (vWF) antigen, vWF activity, and factor VII (FVII) as the prothr ombotic factors; (2) plasma levels of tissue plasminogen activator (TP A) antigen, protein C, and antithrombin III as the antithrombotic fact ors: (3) fasting plasma concentrations of insulin and glucose and the lipid pattern (triglycerides [TG] and total and high-density lipoprote in [HDL], cholesterol) as the metabolic parameters; and (4) free testo sterone (FT), dehydroepiandrosterone sulfate (DHEAS), and sex hormone- binding globulin (SHBG) serum levels as the parameters of androgenicit y. Body fat distribution was evaluated by the waist to hip ratio (WHR) . In OO and non-obese subjects taken together, plasma levels of PAI-1 antigen, fibrinogen, and FVII were inversely associated with FT (r = . 255, P < .05, r = -3.14, P < .05, and r = -.278, P < .05, respectively ), and the negative relationships of both fibrinogen and FVII with FT were maintained after stepwise multiple regression analysis. Plasma co ncentrations of PAI-1 antigen and PAI-1 activity were also negatively correlated with SHBG (r = -.315, P < .05 and r = -.362, P < .01, respe ctively), and these associations held irrespective of the other parame ters investigated. None of the antithrombotic and fibrinolytic factors were independently related to serum androgen levels. Subjects with a BMI higher than 25 kg/m(2) had higher plasma concentrations of PAI-1 a ntigen, PAI-1 activity, and fibrinogen as compared with non-obese cont rols (P < .001, P < .001, and P < .01, respectively). In addition, in OO and control subjects as a whole, multiple stepwise regression analy sis showed that the associations of BMI with PAI-1 activity, fibrinoge n, vWF antigen, and vWF activity were independent of any other metabol ic and hormonal parameters. Plasma concentrations of PAI-1 antigen, PA I-1 activity, and fibrinogen were also directly correlated with WHR in all subjects taken together, irrespective of the other parameters inv estigated. Evaluation of antithrombotic factors showed that OO subject s had higher TPA plasma concentrations than non-obese controls (P < .0 01), whereas protein C and antithrombin III did not differ in the two groups. TPA was also directly correlated with BMI (r = .415, P < .001) and WHR (r = .393, P < .001) in all subjects. The results of this stu dy indicate that (1) men with lower FT serum levels have higher fibrin ogen and FVII plasma concentrations, and those with lower SHBG serum l evels also have higher levels of PAI-1 antigen and activity; (2) irres pective of other factors, obesity per se may account for higher concen trations of PAI-1, fibrinogen, and vWF; (3) plasma levels of PAI-1 (an tigen and activity) and fibrinogen correlate independently with WHR; a nd (4) among the investigated antithrombotic factors (TPA antigen, pro tein C, antithrombin III), only TPA antigen plasma concentrations are higher in men with abdominal obesity. Thus, because of the increase in several prothrombotic factors, men with central obesity, particularly those with lower androgenicity, seem to be at greater risk for corona ry heart disease (CHD). Aparently, this risk is not counteracted by a parallel increase in plasma concentrations of antithrombotic factors. Copyright (C) 1997 by W.B. Saunders Company.