Our data suggest that forearm endothelial dysfunction is a marker of future cardiovascular events in patients with essential hypertension.

OBJECTIVE -To test whether weight loss may improve endothelial dysfunction in human obesity, we recruited 28 healthy obese subjects, aged 30 -46 years, with BMI 30 -43 kg/m 2 .RESEARCH DESIGN AND METHODS -Endothelium-dependent and -independent vasodilation were investigated by intra-arterial infusion of increasing doses of acetylcholine (ACh; 7.5, 15, and 30 g ⅐ ml Ϫ1 ⅐ min Ϫ1 ) and sodium nitroprusside (0.8, 1.6, and 3.2 g ⅐ ml Ϫ1⅐ min Ϫ1 ). Insulin resistance was estimated by homeostasis model assessment (HOMA). Weight loss was obtained by caloric restriction and physical activity.RESULTS -We observed a significant reduction in BMI (from 33.1 Ϯ 4.2 to 27.5 Ϯ 4.5 kg/m 2 , Ϫ16.9%, P Ͻ 0.0001) and in waist circumference (from 108.2 Ϯ 12.1 to 96.8 Ϯ 12.9 cm, Ϫ10.5%, P Ͻ 0.0001). Weight loss was also associated with a significant increase in AChstimulated forearm blood flow (FBF), from 7.4 Ϯ 2.8 to 12.9 Ϯ 3.4 ml ⅐ 100 ml Ϫ1 of tissue ⅐ min Ϫ1 kg/m 2 (P Ͻ 0.0001). Multivariate regression analysis demonstrated that the only independent predictor of FBF was HOMA, accounting for 44.5% of the variation, whereas the addition of BMI explained another 2.3% of the variation.CONCLUSIONS -Our data demonstrate that energy-restricted diet associated with physical activity induce a significant and clinically relevant improvement in ACh-stimulated vasodilation in obese healthy subjects. Diabetes Care 26:1673-1678, 2003W e recently reported that obesity and abdominal fat distribution are inversely related to endothelium-dependent vasodilation. We have also demonstrated that indexes of insulin sensitivity, which are linearly related to BMI and waist-to-hip ratio (WHR), predict the depressed acetylcholine (ACh)-stimulated forearm blood flow (FBF) in obese subjects (1). These findings are of considerable clinical importance because endothelial dysfunction is considered the early manifestation of the atherosclerotic process (2-4). Impaired endotheliumdependent vasodilation, caused by insulin resistance (IR), may be the mechanism by which obesity confers increased risk for cardiovascular morbidity and mortality. In fact, IR represents a major underlying abnormality driving coronary and extracoronary atherosclerosis and cardiovascular diseases, which are the principal worldwide causes of morbidity and mortality (5). Our previous observations (1) led us to hypothesize that weight loss might be useful in both improving endothelial dysfunction and reducing the risk of subsequent cardiovascular events. This hypothesis is also supported by recent evidence showing that both coronary (6,7) and forearm (8) endothelial dysfunction predict long-term atherosclerotic disease progression and cardiovascular event rates. Endothelial dysfunction associated with obesity is a very important medical problem in light of the evidence that the prevalence of obesity has significantly increased over the last few decades in developed and developing countries (9,10), becoming a major global public health problem (10). Many adverse clinical features associated wi...

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Present data demonstrate that the increase in LVM prevalent in human essential hypertension is directly associated with serum GH levels and inversely related to circulating IGF-1.