New Approaches in Detection and Treatment of Familial Hypercholesterolemia.
New Approaches in Detection and Treatment of Familial Hypercholesterolemia.
复制标题
DOI：
10.1007/s11886-015-0665-x
复制
发表时间：
2015-12
影响因子：
3.7
通讯作者：
Hovingh GK
中科院分区：
文献类型：
--
作者：
Hartgers ML;Ray KK;Hovingh GK
家族性高胆固醇血症（FH）是一种常染色体显性遗传疾病，临床上可导致低密度脂蛋白胆固醇（LDL-C）水平升高。因此，FH患者处于心血管疾病（CVD）的高风险中。在编码LDLR、apoB和PCSK 9的基因中发现突变，尽管在这些基因之一中没有突变的情况下不能排除FH。在早期诊断FH至关重要，因为降脂可降低心血管并发症的风险，特别是如果早期开始，但不幸的是FH在很大程度上未被诊断出来。虽然有许多临床标准可用，但许多人认为鉴定上述三种基因中任何一种的致病性突变是建立FH明确诊断的一种方法。应该记住，临床治疗是基于LDL-C水平，而不仅仅是基于是否存在基因突变，因为LDL-C是导致风险的因素。传统上，突变检测是通过双脱氧测序来完成的。然而，新的分子检测方法正在逐步引入。这些基于测序的下一代方法一旦确定其功效和对成本的影响，就有可能在更广泛的范围内应用。他汀类药物是FH患者的一线治疗选择，因为它们已被证明可以降低包括高胆固醇血症在内的一系列疾病的CVD风险（尽管未在FH中进行专门测试）。然而，尽管使用了最大剂量的他汀类药物和其他降脂治疗，仍有相当比例的FH患者未达到LDL-C目标。这强调了对其他疗法的需求，而抑制PCSK 9和CETP是最有前途的新治疗选择之一。在这篇综述中，我们的目的是提供有关FH的定义，诊断，筛选，以及当前和新的治疗方法的最新信息的概述。
Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder that clinically leads to increased low density lipoprotein-cholesterol (LDL-C) levels. As a consequence, FH patients are at high risk for cardiovascular disease (CVD). Mutations are found in genes coding for the LDLR, apoB, and PCSK9, although FH cannot be ruled out in the absence of a mutation in one of these genes. It is pivotal to diagnose FH at an early age, since lipid lowering results in a decreased risk of cardiovascular complications especially if initiated early, but unfortunately FH is largely underdiagnosed. While a number of clinical criteria are available, identification of a pathogenic mutation in any of the three aforementioned genes is seen by many as a way to establish a definitive diagnosis of FH. It should be remembered that clinical treatment is based on LDL-C levels and not solely on presence or absence of genetic mutations as LDL-C is what drives risk. Traditionally, mutation detection has been done by means of dideoxy sequencing. However, novel molecular testing methods are gradually being introduced. These next generation sequencing-based methods are likely to be applied on broader scale once their efficacy and effect on cost are being established. Statins are the first-line therapy of choice for FH patients as they have been proven to reduce CVD risk across a range of conditions including hypercholesterolemia (though not specifically tested in FH). However, in a significant proportion of FH patients LDL-C goals are not met, despite the use of maximal statin doses and additional lipid-lowering therapies. This underlines the need for additional therapies, and inhibition of PCSK9 and CETP is among the most promising new therapeutic options. In this review, we aim to provide an overview of the latest information about the definition, diagnosis, screening, and current and novel therapies for FH.