荷兰阿姆斯特丹大学医学中心John J.P. Kastelein课题组，近日公布了他们对家族性高胆固醇血症儿童服用他汀类药物20年随访的结果。该项研究成果发表在2019年10月17日出版的《新英格兰医学杂志》上。

家族性高胆固醇血症的特点是低密度脂蛋白胆固醇（LDL）水平严重升高和过早发生心血管疾病。儿童服用他汀类药物的短期疗效良好，但关于其心血管疾病风险变化的长期随访却很少。

研究组对他汀类药物治疗的儿童进行了长达20年的随访研究。共有214名家族性高胆固醇血症患者（98%经基因确认）和他们的95名健康兄弟姐妹接受了随访。这些患者均参加过之前关于普伐他汀治疗2年的效果和安全性的安慰剂对照试验。所有参与者均填写调查问卷，提供血样，并测量颈动脉内膜中层厚度。

随访结果表明，患者的平均LDL水平从237.3 mg/dL降至160.7 mg/dL（6.13 mmol/L降至4.16 mmol/L），下降了32%；37名（20%）患者达到了治疗目标，即LDL水平低于100 mg/dL。在整个随访期间，家族性高胆固醇血症患者的颈动脉内膜中层厚度的平均进展为0.0056 mm，而健康兄弟姐妹为0.0057 mm。家族性高胆固醇血症患者39岁时心血管事件和心血管原因所致死亡的累积发生率分别为1%和0%，均显著低于其同样患病的父母（26%和7%）。

总之，家族性高胆固醇血症患者从儿童期开始进行他汀类药物治疗可减缓颈动脉内膜中层厚度的进展，降低成年期心血管疾病的风险。

附：英文原文

Title: 20-Year Follow-up of Statins in Children with Familial Hypercholesterolemia

Author: Ilse K. Luirink, Albert Wiegman, D. Meeike Kusters, Michel H. Hof, Jaap W. Groothoff, Eric de Groot, John J.P. Kastelein, Barbara A. Hutten

Issue&Volume: 2019-10-16

Abstract: 

BACKGROUND
Familial hypercholesterolemia is characterized by severely elevated low-density lipoprotein (LDL) cholesterol levels and premature cardiovascular disease. The short-term efficacy of statin therapy in children is well established, but longer follow-up studies evaluating changes in the risk of cardiovascular disease are scarce.

METHODS
We report a 20-year follow-up study of statin therapy in children. A total of 214 patients with familial hypercholesterolemia (genetically confirmed in 98% of the patients), who were previously participants in a placebo-controlled trial evaluating the 2-year efficacy and safety of pravastatin, were invited for follow-up, together with their 95 unaffected siblings. Participants completed a questionnaire, provided blood samples, and underwent measurements of carotid intima–media thickness. The incidence of cardiovascular disease among the patients with familial hypercholesterolemia was compared with that among their 156 affected parents.

RESULTS
Of the original cohort, 184 of 214 patients with familial hypercholesterolemia (86%) and 77 of 95 siblings (81%) were seen in follow-up; among the 214 patients, data on cardiovascular events and on death from cardiovascular causes were available for 203 (95%) and 214 (100%), respectively. The mean LDL cholesterol level in the patients had decreased from 237.3 to 160.7 mg per deciliter (from 6.13 to 4.16 mmol per liter) — a decrease of 32% from the baseline level; treatment goals (LDL cholesterol <100 mg per deciliter [2.59 mmol per liter]) were achieved in 37 patients (20%). Mean progression of carotid intima–media thickness over the entire follow-up period was 0.0056 mm per year in patients with familial hypercholesterolemia and 0.0057 mm per year in siblings (mean difference adjusted for sex, −0.0001 mm per year; 95% confidence interval, −0.0010 to 0.0008). The cumulative incidence of cardiovascular events and of death from cardiovascular causes at 39 years of age was lower among the patients with familial hypercholesterolemia than among their affected parents (1% vs. 26% and 0% vs. 7%, respectively).

CONCLUSIONS
In this study, initiation of statin therapy during childhood in patients with familial hypercholesterolemia slowed the progression of carotid intima–media thickness and reduced the risk of cardiovascular disease in adulthood. 

DOI: NJ201910173811608

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1816454