Response of fractional synthesis rate (FSR) of fibrinogen, concentration of D-dimer and fibrinolytic balance to physical activity-based intervention in obese children.

Author(s): Balagopal P, George D, Sweeten S, Mann KJ, Yarandi H, Mauras N, Vaughan DE

Affiliation(s): Nemours Childrens Clinic, Jacksonville, FL 32207, USA. bbalagop@nemours.org

Publication date & source: 2008-08, J Thromb Haemost., 6(8):1296-303. Epub 2008 May 26.

Publication type: Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

BACKGROUND: Physical activity-induced reduction in obesity-related hyperfibrinogenemia in children has been reported. The underlying mechanisms remain elusive. Further, the effect of such interventions on fibrinolysis in children is scarce. OBJECTIVES: To investigate in obese children, before and after a physical activity-based intervention: (i) the mechanistic role of fractional synthesis rate (FSR) of fibrinogen in the reduction of hyperfibrinogenemia; and (ii) the changes in fibrinolytic factors. METHODS: Subjects included 21 (age > 14 < 18 years; Tanner stage, IV-V) children (15 obese, BMI >95%tile for age and sex and six lean, BMI <85%tile). After baseline measurements of FSR of fibrinogen, and concentrations of fibrinogen, D-dimer, PAI-1 and t-PA in all children, studies were repeated after a 3-month randomized controlled physical activity-based lifestyle intervention in obese children only. RESULTS: FSR of fibrinogen was higher (P = 0.002) in the obese (vs. lean) group, which was reduced (P = 0.001) after intervention. This almost completely accounted for the reduction in obesity-related hyperfibrinogenemia. High levels of D-dimer decreased (P = 0.001) after intervention, whereas fibrinolysis was not enhanced. CONCLUSIONS: The direct reduction in the FSR of fibrinogen and the remarkable correlation between the magnitudes of reduction in fibrinogen FSR and concentration signify a mechanistic role for FSR in the regulation of physical activity-induced reversal of hyperfibrinogenemia in obese children. The congruent reductions in the FSR of fibrinogen and the concentrations of fibrinogen and D-dimer in response to intervention despite depressed fibrinolysis suggest an overall improvement in the hypercoagulable state in obese children with physical activity-based lifestyle intervention.