Rodenburg Jessica, Vissers Maud N, Wiegman Albert, van Trotsenburg A S Paul, van der Graaf Anouk, de Groot Eric, Wijburg Frits A, Kastelein John J P, Hutten Barbara A
Academic Medical Centre, Department of Vascular Medicine, University of Amsterdam, The Netherlands.
Circulation. 2007 Aug 7;116(6):664-8. doi: 10.1161/CIRCULATIONAHA.106.671016. Epub 2007 Jul 30.
We previously demonstrated in a randomized placebo-controlled trial that 2-year pravastatin treatment induced a significant regression of carotid intima-media thickness (IMT) in 8- to 18-year-old children with familial hypercholesterolemia. Subsequently, we continued to follow up these children to explore the relation between the age of statin initiation and carotid IMT after follow-up on statin treatment. We also examined safety aspects of statin therapy during this long-term follow-up.
All 214 children who initially participated in the previous placebo-controlled study were eligible for the follow-up study. After completion of the placebo-controlled study, all children continued treatment with pravastatin 20 or 40 mg, depending on their age. Blood samples were taken on a regular basis for lipids and safety parameters, and a carotid IMT measurement was performed after an average treatment period of 4.5 years. Follow-up data for 186 children were available for the statistical analyses. Multivariate analyses revealed that age at statin initiation was an independent predictor for carotid IMT after follow-up with adjustment for carotid IMT at initiation of statin treatment, sex, and duration of treatment. Early initiation of statin treatment was associated with a subsequently smaller IMT. Furthermore, no serious laboratory adverse events were reported during follow-up, and statin treatment had no untoward effects on sexual maturation.
These data indicate that early initiation of statin treatment delays the progression of carotid IMT in adolescents and young adults. The present study shows for the first time that early initiation of statin therapy in children with familial hypercholesterolemia might be beneficial in the prevention of atherosclerosis in adolescence.
我们先前在一项随机安慰剂对照试验中证明，对8至18岁的家族性高胆固醇血症儿童进行为期2年的普伐他汀治疗可使颈动脉内膜中层厚度（IMT）显著消退。随后，我们继续对这些儿童进行随访，以探讨他汀类药物起始治疗年龄与他汀类药物治疗随访后颈动脉IMT之间的关系。我们还在这一长期随访过程中检查了他汀类药物治疗的安全性。
所有最初参与先前安慰剂对照研究的214名儿童均符合随访研究条件。在安慰剂对照研究完成后，所有儿童根据年龄继续接受20或40mg普伐他汀治疗。定期采集血样检测血脂和安全参数，并在平均治疗4.5年后进行颈动脉IMT测量。186名儿童的随访数据可用于统计分析。多变量分析显示，在对他汀类药物治疗起始时的颈动脉IMT、性别和治疗持续时间进行校正后，他汀类药物起始治疗时的年龄是随访后颈动脉IMT的独立预测因素。早期开始他汀类药物治疗与随后较小的IMT相关。此外，随访期间未报告严重的实验室不良事件，他汀类药物治疗对性成熟没有不良影响。
这些数据表明，早期开始他汀类药物治疗可延缓青少年和青年成人颈动脉IMT的进展。本研究首次表明，对家族性高胆固醇血症儿童早期开始他汀类药物治疗可能有利于预防青少年动脉粥样硬化。
