Familial Combined Hyperlipidemia is the most frequent familial hyperlipidemia with a high risk a early manifestation of arteriosclerosis. Endothelial dysfunction is the first step in the development of arteriosclerosis. The aim of our investigation was to examine selected markers of endothelial dyscunction in hyperlipidemic members of families with familial combined hyperlipidemia and their normolipidemia first-line relatives and to compare them with healthy individuals. The study includes non-smoking members of the affected families (probands and first-line relatives), who have not suffered from clinical manifestations of arteriosclerosis and/or hypertension during the start of the study. The cohort was divided into hyperlipidemic individuals (N = 25) and normolipidemic individuals (N = 21). Both groups were compared with control groups of healthy individuals (two groups, N = 17 each), who were adjusted by age and sex. The following markers of endothelial dysfunction were examined: 1. utrasound – flow mediated dilatation of brachial artery and 2. humoral – serum levels of von Willebrand factor, inhibitor of activator of plasminogen- 1 and vasoadhesive molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule- 1). The members of families with familial combined hyperlipidemia displayed symptoms of endothelial dysfunction. In comparison with healthy controls the endothelial dysfunction was more expressed in hyperlipidemic individuals. They displayed a significantly lower flow-mediated dilatation of brachial artery (3.6 ± 3.3 % versus 6.6 ± 2.8 %, P < 0,01), higher levels of von Willebrand factor (152.8 % ± 79.1 % versus 110.4 % ± 24.8 %, P < 0.05), inhibitor of activator of plasminogen- 1 (94.6 ± 30.8 ng/ml versus 60.4 ± 38.0 ng/ml, P < 0.01) and vasoadhesive molecules: vascular cell adhesion molecule-1 (927.0 ± 167.7 ng/ml versus 814.7 ± 171.1 ng/ml, P < 0.05), intercellular adhesion molecule-1 (601.7 ± 89.5 ng/ml versus 544.8 ± 59.8 ng/ml, P < 0.05). The normolipidemic individuals displayed only a significantly lower flow-mediated dilatation of brachial artery (5.6 ±2.6 % versus 7.5 ± 2.8 %, P < 0.05) and higher levels of von Willebrand factor (136.8 ± 40.32 % versus 104.1 ± 24.9 %, P < 0.05. No significant difference was found in the levels of inhibitor of activator of plasminogen-1 and vasoadhesive molecules. The results indicate that members of families with familial combined hyperlipidemia represent a high-risk group from the standpoint of early manifestation of arteriosclerosis.

        Key words: Familial combined hyperlipidemia – Endothelial dysfunction - Flow mediated dilatation - von Willebrand factor - Inhibitor of plasminogen activator - Adhesive molecules