Karásek D, Vaverková H, Hutyra M, Halenka M, Novotnyý D, Budíková M, Slavík L
III. interní klinika Lékarské fakulty UP a FN, Olomouc.
Vnitr Lek. 2003 Aug;49(8):623-9.
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 dysfunction 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. ultrasound--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 indicated that members of families with familial combined hyperlipidemia represent a high-risk group from the standpoint of early manifestation of arteriosclerosis.
家族性混合性高脂血症是最常见的家族性高脂血症，具有动脉粥样硬化早期表现的高风险。内皮功能障碍是动脉粥样硬化发展的第一步。我们研究的目的是检测家族性混合性高脂血症家族中高脂血症成员及其血脂正常的一级亲属的内皮功能障碍相关指标，并将其与健康个体进行比较。该研究纳入了受影响家族的非吸烟成员（先证者和一级亲属），他们在研究开始时未患有动脉粥样硬化和/或高血压的临床表现。该队列分为高脂血症个体（N = 25）和血脂正常个体（N = 21）。两组均与按年龄和性别匹配的健康个体对照组（两组，每组N = 17）进行比较。检测了以下内皮功能障碍指标：1. 超声——肱动脉血流介导的扩张；2. 体液指标——血管性血友病因子、纤溶酶原激活物抑制剂-1和血管黏附分子（血管细胞黏附分子-1、细胞间黏附分子-1）的血清水平。家族性混合性高脂血症家族的成员表现出内皮功能障碍的症状。与健康对照组相比，高脂血症个体的内皮功能障碍更为明显。他们的肱动脉血流介导的扩张明显更低（3.6±3.3%对6.6±2.8%，P < 0.01），血管性血友病因子水平更高（152.8%±79.1%对110.4%±24.8%，P < 0.05），纤溶酶原激活物抑制剂-1水平更高（94.6±30.8 ng/ml对60.4±38.0 ng/ml，P < 0.01），血管黏附分子：血管细胞黏附分子-1水平更高（927.0±167.7 ng/ml对814.7±171.1 ng/ml，P < 0.05），细胞间黏附分子-1水平更高（601.7±89.5 ng/ml对544.8±59.8 ng/ml，P < 0.05）。血脂正常个体仅表现出肱动脉血流介导的扩张明显更低（5.6±2.6%对7.5±2.8%，P < 0.05）和血管性血友病因子水平更高（136.8±40.32%对104.1±24.9%，P < 0.05）。纤溶酶原激活物抑制剂-1和血管黏附分子水平未发现显著差异。结果表明，从动脉粥样硬化早期表现的角度来看，家族性混合性高脂血症家族的成员是高危人群。
