Fibrinolysis

Plasminogen activator inhibitor (PAI)-1, the fast-acting tissue plasminogen activator (t-PA) inhibitor, is the major regulator of fibrinolytic activity in plasma. Increased PAI-1 activity acts in a thrombogenic direction. Elevated PAI-1 activity has been associated with coronary artery disease (84,85), increased risk of myocardial infarction in young patients (86), recurrent myocardial infarction (87), and deep vein thrombosis (88). High PAI-1 activity has previously been found in patients with hypertension, insulin resistance, and abdominal obesity (89-91). In addition, we have recently shown that elevated PAI-1 activity in GH-deficient adults as compared with healthy controls matched for age, sex, and body mass index (58).

Previous population-based studies have shown that fibrinogen is an independent risk factor for stroke as well as myocardial infarction, and is at least as important as blood lipids and blood pressure (92,93). Obesity has been associated with both increased fibrinogen levels and increased PAI-1 activity (90,91,94-96). Also the fibrinogen levels were higher in the GH-deficient group (58): Although patients and controls were matched for BMI, we observed both higher fibrinogen levels and PAI-1 activity in the GH-defi-cient patients, suggesting that other factors, in addition to obesity per se, are of importance. Both the elevated fibrinogen levels and PAI-1 activity may be linked to the abdominal and visceral obesity, indicated by a high waist to hip ration in these patients (58).

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