Determinants of endothelial dysfunction and carotid intima???media thickness in combined hyperlipidemia

Abstract

Early functional and morphological changes in the course of the atherosclerotic process are manifested as endothelial dysfunction and increased intima-media thickness (IMT) of the arterial wall. These are both associated with various atherosclerotic risk factors. We investigated whether the same factors are associated with functional and morphological changes of the arterial wall in men with combined hyperlipidemia. Flow-mediated dilatation (FMD) of the brachial artery and carotid IMT were measured in 72 male patients aged 46+/-5 years with combined hyperlipidemia. Serum lipoproteins, fibrinolytic and coagulation parameters, blood glucose, proinflammatory cytokines and C-reactive protein were also measured. Tumor necrosis factor-alpha, interleukin 6 and apolipoprotein (apo) B were found to be independent predictors of FMD, explaining 87% of FMD variability in multivariate analysis. On the other hand, total tissue factor pathway inhibitor and apo B were independent predictors of increased carotid IMT, explaining 82% of the variation in carotid IMT. Apo B, which is a marker for the presence of the atherogenic lipoproteins, is associated with both functional and morphological changes of the artery wall. In addition, in asymptomatic overweight middle-aged men with combined hyperlipidemia, functional changes are associated with proinflammatory cytokines, while morphological changes are associated with coagulation parameters.