Narverud Ingunn, Retterstøl Kjetil, Iversen Per Ole, Halvorsen Bente, Ueland Thor, Ulven Stine M, Ose Leiv, Aukrust Pål, Veierød Marit B, Holven Kirsten B
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1046, Blindern, 0317 Oslo, Norway; Lipid Clinic, Oslo University Hospital Rikshospitalet, P.O. Box 4950, Nydalen, 0424 Oslo, Norway.
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1046, Blindern, 0317 Oslo, Norway; Department of Haematology, Oslo University Hospital, P.O. Box 4950, Nydalen, 0424 Oslo, Norway.
Atherosclerosis. 2014 Aug;235(2):299-309. doi: 10.1016/j.atherosclerosis.2014.05.917. Epub 2014 May 20.
Atherosclerosis is a multi-step process, where lipids, inflammatory and hemostatic mediators orchestrate plaque formation and progression, which subsequently may lead to myocardial infarction and ischemic stroke. Familial hypercholesterolemia (FH) is associated with increased risk of premature atherosclerosis due to the genetically determined elevated low density lipoprotein (LDL)-cholesterol seen in these individuals. Children with FH are suitable to investigate the isolated effect of elevated LDL-cholesterol on early markers of atherosclerosis. The aim of the present paper was to review the literature to summarize the findings of atherosclerotic markers in children with FH to better understand how elevated LDL-cholesterol per se promotes atherogenesis.
We conducted a systematic literature search from the years 1990-2013, resulting in identification of 903 articles. In order to investigate whether intima-media thickness (IMT) is different in children with and without FH, we conducted a meta-analysis of the studies comparing FH children with a control group.
37 original articles were included. Among these, 24 reported subclinical measurements, whereas other articles reported measurements of atherogenic lipids (n = 9), inflammatory markers (n = 10), hemostatic markers (n = 6) and other surrogate markers of atherosclerosis (n = 7). In the meta-analysis (n = 8), IMT was significantly thicker in children with FH than in control children (weighted mean difference 0.06, 95% confidence interval [0.01, 0.11]).
Elevated LDL-cholesterol distinguishes children with and without FH, but these groups of children also differ in several other ways. In particular, children with FH display a variety of changes reflecting both the lipid and the inflammatory arm of atherosclerosis. The IMT-meta-analysis result strengthens the evidence of early atherosclerotic development in children with FH. In a clinical perspective, early diagnosing and treatment of children with FH is of high importance to attenuate development of the potential ongoing early atherosclerotic process in these individuals.
动脉粥样硬化是一个多步骤过程，其中脂质、炎症和止血介质共同作用于斑块的形成和进展，随后可能导致心肌梗死和缺血性中风。家族性高胆固醇血症（FH）与过早发生动脉粥样硬化的风险增加相关，因为这些个体中基因决定的低密度脂蛋白（LDL）胆固醇水平升高。FH患儿适合用于研究LDL胆固醇升高对动脉粥样硬化早期标志物的单独影响。本文的目的是回顾文献，总结FH患儿动脉粥样硬化标志物的研究结果，以更好地理解LDL胆固醇升高本身如何促进动脉粥样硬化的发生。
我们对1990年至2013年期间的文献进行了系统检索，共识别出903篇文章。为了研究有FH和无FH儿童的内膜中层厚度（IMT）是否存在差异，我们对比较FH患儿与对照组的研究进行了荟萃分析。
纳入37篇原创文章。其中，24篇报告了亚临床测量结果，其他文章报告了致动脉粥样硬化脂质（n = 9）、炎症标志物（n = 10）、止血标志物（n = 6）和其他动脉粥样硬化替代标志物（n = 7）的测量结果。在荟萃分析（n = 8）中，FH患儿的IMT显著厚于对照儿童（加权平均差0.06，95%置信区间[0.01, 0.11]）。
LDL胆固醇升高区分了有FH和无FH的儿童，但这两组儿童在其他几个方面也存在差异。特别是，FH患儿表现出多种反映动脉粥样硬化脂质和炎症方面的变化。IMT荟萃分析结果加强了FH患儿早期动脉粥样硬化发展的证据。从临床角度来看，早期诊断和治疗FH患儿对于减缓这些个体潜在的正在进行的早期动脉粥样硬化进程的发展至关重要。
