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The relationship between hypertension, glucose metabolism, fibrinogen and plasminogen activator inhibitor of endothelial cell type (PAI-1) was studied under conditions in which the influence of obesity and adipose tissue distribution (waist/hip ratio) were controlled. Twenty-two non-obese, middle-aged men with normal blood pressure (n = 11) and untreated mild hypertension (n = 11), respectively, participated in the study. Cholesterol, triglyceride and insulin levels were higher in hypertensive men than in the control group. Glucose disposal was studied as an indicator of insulin sensitivity using the euglycaemic clamp technique. The insulin effect tended to be less marked in men with hypertension. PAI-1 was higher in hypertensive men compared to the controls. A strong positive correlation was observed between PAI-1 and insulin levels as well as blood pressure. PAI-1 and fibrinogen levels correlated negatively with the rate of glucose disposal. Thus, even in these non-obese and mildly hypertensive individuals, an enhanced metabolic risk factor profile for cardiovascular disease was found. The metabolic aberrations were related to elevated fibrinogen and PAI-1 levels which, in turn, increase the risk of thrombus formation.

Insulin resistance and hyperinsulinaemia may play an important role in both the development of hypertension and its accompanying metabolic aberrations. In order to investigate this possibility, nine non-obese, non-diabetic, non-smoking, middle-aged men with untreated hypertension were treated with metformin 850 mg b.i.d. for 6 weeks as a pilot study and within-patient comparison. Metformin decreased total and LDL-cholesterol (P less than 0.01), triglyceride (P less than 0.01), fasting plasma insulin (P less than 0.01) and C-peptide levels (P less than 0.02). Glucose disposal, an indicator of insulin action measured by means of the euglycaemic clamp technique, increased (P less than 0.001). Tissue plasminogen activator (t-PA) activity increased (P less than 0.02), and t-PA antigen decreased (P less than 0.01), whereas plasminogen activator inhibitor (PAI-1) and fibrinogen were unaffected by metformin treatment. Body weight remained unchanged. Withdrawal of metformin was associated with the return of both blood pressure and metabolism towards the initial levels. In conclusion, metformin treatment increased insulin action, lowered blood pressure, improved the metabolic risk factor profile and tended to increase the fibrinolytic activity in these mildly hypertensive subjects. These results support the view that insulin resistance plays a role in hypertension, and may open up a new field for the alleviation of abnormalities associated with cardiovascular disease.

Hypopituitary patients on routine replacement therapy except growth hormone (GH) have an increased risk of death from cardiovascular diseases compared with healthy subjects. Untreated GH deficiency might explain the premature death from vascular disease. Plasminogen activator inhibitor (PAI-1) activity, fibrinogen, insulin, blood lipid, and blood pressure levels were studied in 20 GH-deficient adults (10 men, 10 women) 50±ll years old with routine hormone replacement therapy (except GH) and compared with 20 healthy control subjects matched for sex, age, and body mass index. GH-deficient subjects had a higher waist-to-hip circumference ratio (P<.001), H ypopituitary patients on routine replacement therapy except growth hormone (GH) have an increased risk of death from cardiovascular diseases compared with healthy subjects.1 The cause of death from vascular disorders is unclear, although untreated GH deficiency may play an important role. Recently, hypopituitary patients with untreated GH deficiency were found to have more atheromatous plaques in the carotid and femoral arteries compared with healthy age-and weight-matched control subjects. 2This observation gives further support for a possible association between hypopituitarism and premature atherosclerosis.The importance of GH for the regulation of plasma lipids is not yet fully documented, and the results are somewhat conflicting. However, data suggest that GHdeficient adults have an increased low-density lipoprotein (LDL) to high-density lipoprotein (HDL) cholesterol ratio and that treatment with recombinant human GH reduces LDL and increases HDL cholesterol. Furthermore, body fat is increased in GH-deficient patients, which might raise the risk of cardiovascular diseases/ Obesity, and in particular abdominal fat distribution, is associated with increased concentrations of fibrinogen and plasminogen activator inhibitor (PAI-1) activity. 5 -6 Fibrinogen has been shown to be an independent risk factor for stroke as well as myocardial infarction, 7 and PAI-1 activity has been associated with increased risk for recurrent myocardial infarction. 8To further elucidate the "risk profile" for cardiovascular disorders in adults with GH deficiency, we studied fibrinogen concentration as well as PAI-1 activity in