Hypopituitary patients have increased mortality from vascular disease, and in these patients, early markers of atherosclerosis [increased carotid artery intima-media thickness (IMT) and reduced distensibility] are more prevalent. As GH replacement can reverse some risk factors of atherosclerosis, the present study examined the effect of GH treatment on morphological and functional changes in the carotid and brachial arteries of GH-deficient (GHD) adults. Eleven GHD hypopituitary men (24-49 yr old) were treated with recombinant human GH (0.018 U/kg BW x day) for 18 months. IMT of the common carotid artery (CCA) and the carotid bifurcation (CB), and flow-mediated endothelium-dependent dilation (EDD) of the brachial artery were measured by B mode ultrasound before and at 3, 6, 12, and 18 months of treatment, and values were compared with those in 12 age-matched control men. Serum concentrations of lipids, lipoprotein(a), insulin-like growth factor I (IGF-I), and IGF-binding protein-3 (IGFBP-3) were also measured. In GHD men before treatment the IMTs of the CCA [mean(SD), 0.67(0.05) mm] and CB [0.75(0.04) mm] were significantly greater (P < 0.001) than those in control men [0.52(0.07) and 0.65(0.07) mm, respectively]. GH treatment normalized the IMT of the CCA by 6 months [0.53(0.04) mm] and that of the CB by 3 months [0.68(0.05) mm]. The IMT of the carotid artery (CCA and CB) was negatively correlated with serum IGF-I (r = -0.53; P < 0.0001). There was a significant improvement in flow-mediated EDD of the brachial artery at 3 months, which was sustained at 6 and 18 months of GH treatment (P < 0.05). GH treatment increased high density lipoprotein cholesterol at 3 and 6 months, but did not reduce total or low density lipoprotein cholesterol and was without effect on lipoprotein(a). There was no correlation between plasma lipids and changes in IMT or EDD of the arteries examined. In conclusion, GH treatment of hypopituitary GHD men reverses early morphological and functional atherosclerotic changes in major arteries and, if maintained, may reduce vascular morbidity and mortality. GH seems to act via IGF-I, which is known to have important effects on endothelial cell function.

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Increased blood and plasma viscosity has been described in patients with coronary and peripheral arterial disease. However, the relation of viscosity to the extent of arterial wall deterioration--the most important determinant of clinical manifestation and prognosis of the disease--is not well known. Therefore, the authors studied plasma viscosity as one of the major determinants of blood viscosity in patients with different stages of arterial disease of lower limbs (according to Fontaine) and its relation to the presence of some risk factors of atherosclerosis. The study encompassed four groups of subjects: 19 healthy volunteers (group A), 18 patients with intermittent claudication up to 200 m (stage II; group B), 15 patients with critical ischemia of lower limbs (stage III and IV; group C), and 16 patients with recanalization procedures on peripheral arteries. Venous blood samples were collected from an antecubital vein without stasis for the determination of plasma viscosity (with a rotational capillary microviscometer, PAAR), fibrinogen, total cholesterol, alpha-2-macroglobulin, and glucose concentrations. In patients with recanalization procedure local plasma viscosity was also determined from blood samples taken from a vein on the dorsum of the foot. Plasma viscosity was most significantly elevated in the patients with critical ischemia (1.78 mPa.sec) and was significantly higher than in the claudicants (1.68 mPa.sec), and the claudicants also had significantly higher viscosity than the controls (1.58 mPa.sec). In patients in whom a recanalization procedure was performed, no differences in systemic and local plasma viscosity were detected, neither before nor after recanalization of the diseased artery. In all groups plasma viscosity was correlated with fibrinogen concentration (r=0.70, P < 0.01) and total cholesterol concentration (r=0.24, P < 0.05), but in group C (critical ischemia) plasma viscosity was most closely linked to the concentration of alpha-2-macroglobulin (r=0.78, P < 0.01). These results indicate that in patients with peripheral arterial disease plasma viscosity increases with the progression of the atherosclerotic process and is correlated with the clinical stages of the disease.

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Abstract. Z Ï iz Ïek B, Poredos Ï P (University Medical Centre, Ljubljana, Slovenia). Insulin resistance adds to endothelial dysfunction in hypertensive patients and in normotensive offspring of subjects with essential hypertension. J Intern Med 2001; 249: 189±197.Objectives. To evaluate whether endotheliumdependent (nitric oxide-mediated) dilation of the brachial artery (BA) is impaired in patients being treated for essential hypertension (EH), and whether this abnormality can be detected in normotensive offspring of subjects with EH (familial trait, FT); and to investigate the interrelationship between¯ow-mediated vasodilation (FMD) and hyperinsulinaemia/insulin resistance. Design. Cross-sectional study. Setting. Angiology department at a teaching hospital. Subjects. The study encompassed 172 subjects, of whom 46 were treated hypertonics aged 40±55 (49) years, and 44 age-matched, normotensive volunteers as controls. We also investigated 41 normotonics with FT aged 20±30 (25) years and 41 age-and sex-matched controls without FT. Main outcome measures. Using high-resolution ultrasound, BA diameters at rest, during reactive hyperaemia (endothelium-dependent dilation) and after sublingual glyceryl trinitrate (GTN) application (endothelium-independent dilation) were measured. Results. In hypertonics FMD was signi®cantly lower than in controls [2.4 (2.9) vs. 7.4 (2.5)%; P < 0.00005], as was GTN-induced dilation [12.1 (4.3) vs. 16.1 (4.6)%; P 0.0007]. In subjects with FT, FMD was also decreased compared with the control group [5.8 (4.1) vs. 10.0 (3.0)%; P < 0.00005]. The response to GTN was comparable in both groups of young subjects. FMD was negatively related to insulin concentration in all subjects studied (P < 0.00005). Conclusions. In treated patients with EH,¯ow-mediated dilation of the BA as well as endotheliumindependent dilation are decreased. In individuals with FT the endothelial function of the peripheral arteries is also altered in the absence of elevated blood pressure. Endothelial dysfunction is related to hyperinsulinaemia/insulin resistance, which could be one of the pathogenetic determinants of EH and its complications.