炎症和血栓形成过程与家族性高胆固醇血症患儿的血管功能障碍有关。

Inflammatory and thrombotic processes are associated with vascular dysfunction in children with familial hypercholesterolemia.

作者信息

Charakida Marietta, Tousoulis Dimitris, Skoumas Ioannis, Pitsavos Christos, Vasiliadou Carmen, Stefanadi Elli, Antoniades Charalambos, Latsios George, Siasos Gerasimos, Stefanadis Christodoulos

机构信息

Cardiology Unit, Hippokration Hospital, Athens University Medical School, Athens, Greece.

出版信息

Atherosclerosis. 2009 Jun;204(2):532-7. doi: 10.1016/j.atherosclerosis.2008.09.025. Epub 2008 Oct 5.

DOI:10.1016/j.atherosclerosis.2008.09.025

PMID:19004443

Abstract

BACKGROUND

Evidence suggests that children with familial hypercholesterolemia (FH) have endothelial dysfunction. Inflammatory and haemostatic abnormalities are associated with advanced atherosclerosis and increased cardiovascular events. However, it is unknown whether these abnormalities present in FH children and contribute to their vascular dysfunction.

METHODS AND RESULTS

We studied 38 children with FH (19 males, 19 females aged 14.8+/-0.9 years mean+/-S.E.) and 41 healthy children (controls; 22 males, 19 females aged 15.4+/-0.7 years). Endothelium-dependent reactive hyperemia (RH%) and endothelium-independent nitrate hyperemia dilatation (NH%) were measured by strain gauge plethysmography. Inflammatory and haemostatic parameters were assessed by ELISA. RH% and NH% were significantly reduced in FH compared to controls (91.3+/-9.3% vs. 120.4+/-10.6% and 53.6+/-3.8% vs. 74.5+/-7.4%, p<0.05 for both). Total cholesterol and lipoprotein (a) were increased in FH children compared to controls (282.3+/-8.8 mg/dl vs. 163.8+/-4.6 mg/dl and 11.0[4.6, 30.7]mg/dl vs. 5.24[2.63, 11.0]mg/dl median [IQR] respectively; p<0.001 for both). Intercellular cell adhesion molecule (ICAM-1) and interleukin 1 beta (IL-1 beta) serum levels were increased in FH compared to controls (p<0.05 and <0.001, respectively). Plasminogen activator inhibitor 1 (PAI-1) levels were also higher in FH children (p<0.001). Multivariate analysis revealed that reactive hyperemia was independently associated with nitrate-dependent reactive hyperemia (beta=0.597(0.199), p<0.01), PAI-1(beta=-6.78(2.65), p<0.05), log IL-1 beta (beta=-102.8 (30.2), p<0.01), age (beta=-5.06 (2.35), p<0.05) and FH status (beta=-25.2(10.6), p<0.05) (R(2) for the model: 0.63, p=0.001).

CONCLUSIONS

Inflammatory and haemostatic abnormalities are present in FH children and contribute to the endothelial dysfunction observed in these children.

摘要

背景

有证据表明，家族性高胆固醇血症（FH）患儿存在内皮功能障碍。炎症和止血异常与晚期动脉粥样硬化及心血管事件增加有关。然而，尚不清楚这些异常是否存在于FH患儿中并导致其血管功能障碍。

方法与结果

我们研究了38例FH患儿（19例男性，19例女性，平均年龄14.8±0.9岁，均值±标准误）和41例健康儿童（对照组；22例男性，19例女性，年龄15.4±0.7岁）。通过应变片体积描记法测量内皮依赖性反应性充血（RH%）和非内皮依赖性硝酸酯充血扩张（NH%）。通过酶联免疫吸附测定法评估炎症和止血参数。与对照组相比，FH患儿的RH%和NH%显著降低（分别为91.3±9.3% 对120.4±10.6%以及53.6±3.8% 对74.5±7.4%，两者p均<0.05）。与对照组相比，FH患儿的总胆固醇和脂蛋白（a）升高（分别为282.3±8.8mg/dl对163.8±4.6mg/dl以及11.0[4.6, 30.7]mg/dl对5.24[2.63, 11.0]mg/dl，中位数[四分位间距]；两者p均<0.001）。与对照组相比，FH患儿血清中的细胞间黏附分子（ICAM-1）和白细胞介素1β（IL-1β）水平升高（分别为p<0.05和<0.001）。FH患儿的纤溶酶原激活物抑制剂1（PAI-1）水平也更高（p<0.001）。多变量分析显示，反应性充血与硝酸酯依赖性反应性充血独立相关（β=0.597(0.199)，p<0.01）、PAI-1（β=-6.78(2.65)，p<0.05）、log IL-1β（β=-102.8(30.2)，p<0.01）、年龄（β=-5.06(2.35) p<0.05）以及FH状态（β=-25.2(10.6)，p<0.05）（该模型的R²：0.63，p=0.001）。