Adipocytokine levels mark endothelial function in normotensive individuals

Background: Endothelial dysfunction is an independent risk factor for cardiovascular events. Inflammatory mediators released by the adipose tissue can lead to local insulin resistance and endothelial dysfunction. This study addressed the relationship of adipocytokines with endothelial function and blood pressure. Methods: In 92 newly diagnosed, drug-nave essential hypertensive patients (HT, mean age 49 yrs) without organ damage and 66 normotensive subjects (NT, mean age 47 yrs), by an automated system, we measured endothelium-dependent and -independent vasodilation as brachial artery flow-mediated dilation before and after administration of glyceryl-trinitrate. Retinol binding protein-4 (RBP4) and resistin levels were determined by ELISA and RIA, respectively. Oxidative stress was evaluated by measuring serum malondyaldehyde (MDA). Results: Flow-mediated dilation was significantly (p = 0.03) lower in HT (5.3 +/- 2.6%) than NT (6.1 +/- 3.1%), while response to glyceryl-trinitrate (7.5 +/- 3.7% vs 7.9 +/- 3.4%) was similar. RBP4 (60.6 +/- 25.1 vs 61.3 +/- 25.9 mu g/ml), resistin (18.8 +/- 5.3 vs 19.9 +/- 6.1 ng/ml) and MDA levels (2.39 +/- 1.26 vs 2.08 +/- 1.17 nmol/ml) were not different in HT and NT. RBP4 (r = -0.25; p = 0.04) and resistin levels (r = - 0.29; p = 0.03) were related to flow- mediated dilation in NT, but not in HT (r = - 0.03 and r = - 0.10, respectively). In NT, multivariate analysis including RBP4 and confounders showed that only BMI or waist circumference remained related to flow-mediated dilation. In the multivariate model including resistin and confounders, BMI, age and resistin were significantly related to flow-mediated dilation, while only age significant correlated with this parameter when BMI was replaced by waist circumference. Conclusions: Adipocytokine levels may be independent predictors of endothelial dysfunction in the peripheral circulation of healthy subjects, providing a pathophysiological link between inflammation from adipose tissue and early vascular alterations.