Weight change and blood coagulability and fibrinolysis in healthy obese women

OBJECTIVES: To study the effect of weight loss and subsequent weight mainte nance or weight regain on the activities of FVII and plasminogen activator inhibitor 1 (PAI-1) and the concentration of fibrinogen over 12 months in o bese women consuming a hypoenergetic, low-fat diet with or without orlistat . In addition, the relation between the changes of the activities of PAI-1 and FVII with the changes of other cardiovascular risk factors were examine d. METHODS AND PROCEDURES: Design -a 12-month randomized double-blind weight r eduction trial of placebo and orlistat. Subjects-51 healthy obese women (ag e 44+/-0.7 y, BMI 36.2+/-0.5 kg/m(2), mean+/-s.e.m.) Treatment-the particip ants were on a hypoenergetic diet (-600 kcal daily). The diet was adjusted for actual body weight (-300 kcal) at 6 months. Women were randomized to re ceive either orlistat 120 mg three times daily (n = 25) or placebo three ti mes daily (n = 26) for 12 months according to a double-blind protocol after a 1 month run-in period. Measurements - changes of body weight, body compo sition, haemostatic and other cardiovascular risk factors were measured at 3-6 month intervals. The activity of plasma PAI-1 was measured by a chromog enic method, fibrinogen by the PT-derived method and the activity of FVII b y the one-stage method. RESULTS: The changes in body weight between orlistat and placebo groups wer e not statistically significantly different. Orlistat did not influence hae mostatic factors beyond its effect on weight loss. Therefore, the results o f the orlistat and placebo groups were pooled. The average weight loss at 3 , 6 and 12 months was 7.6, 9.5 and 10.0 kg, respectively (P < 0.001). Betwe en 6 and 12 months, 35% of women regained weight, 24% had stable weight and 41% continued to lose weight. No changes in the mean plasma fibrinogen con centration were observed at any time point during the trial. During the fir st 3 months the activities of PAI-1 and FVII decreased. The decline depende d on the magnitude of weight loss. Between months 6 and 12 the changes of P AI-1 and FVII activities paralleled the changes of body weight. The activit ies rose with weight rebound but remained below the 6-month values if weigh t loss was sustained or continued. The changes of serum insulin were signif icantly correlated with the changes of both PAI-1 and FVII at 6 months and with PAI-1 at 12 months. CONCLUSIONS: The maintenance of modest weight loss is associated with long- term benefits in PAI-1 and FVII in obese women. The change of serum insulin is associated with the changes of PAI-1 activities. Fibrinogen is not affe cted by modest weight loss.