Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level, and relative body weight in normal and obese subjects

This study was undertaken to obtain further information on the mechanism by which blood fibrinolytic activity, a balance between plasminogen activators and inhibitors, is lowered in obese subjects. Fasting blood samples were collected from 35 subjects, aged 15 to 45 years, with normal glucose tolerance and a Body Mass Index (BMI) varying widely between 16 and 45 (normal, 19 to 25). Euglobulin Fibrinolytic Activity (EFA) did not correlate with the level of tissue type plasminogen activator (t-PA) related antigen but exhibited a negative correlation with the level of PA inhibitor ( r = −.609, P < 0.01). EFA was negatively and PA inhibitor positively correlated with both BMI ( r = −.381, P < 0.02 and .664, P < 0.01, respectively) and plasma insulin level ( r = .410, P < 0.02 and .521, P < 0.01, respectively). Stepwise analysis showed that these correlations were independent. As expected, plasma insulin was correlated with BMI ( r = .512, P < 0.01) and triglyceride level ( r = .38, P < 0.02), total cholesterol with age ( r = .379, P < 0.02). Ten obese subjects were submitted to a 24-hour fast. While body weight did not change appreciably, plasma insulin decreased from 22.3 ± 2.2 to 16.3 ± 1.1 μU/ml, EFA increased from 3.6 ± .8 to 4.9 ± .67 mm, and PA inhibitor decreased from 4.52 ± .76 to 3.44 ± .63 IU/mL. All these differences were significant. T-PA-related antigen did not change. These results suggest that PA inhibitor plays a major role in the regulation of fibrinolysis in healthy subjects and that high plasma insulin levels may be responsible for low fibrinolysis through high levels of PA inhibitor in obese subjects.