Raal Frederick J, Sjouke Barbara, Hovingh G Kees, Isaac Barton F
Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, Netherlands.
Atherosclerosis. 2016 May;248:238-44. doi: 10.1016/j.atherosclerosis.2016.03.009. Epub 2016 Mar 11.
Homozygous familial hypercholesterolaemia (HoFH) is a rare disorder usually caused by mutations in both alleles of the low-density lipoprotein receptor gene (LDLR). Premature death, often before the age of 20 years, was a common fate for patients with HoFH prior to the introduction of statins in 1990 and the use of lipoprotein apheresis. Consequently, HoFH has been widely considered a condition exclusive to a population comprising very young patients with extremely high LDL cholesterol (LDL-C) levels. However, recent epidemiologic and genetic studies have shown that the HoFH patient population is far more diverse in terms of age, LDL-C levels, and genetic aetiology than previously realised. We set out to investigate the clinical characteristics regarding age and LDL-C ranges of patients with HoFH.
We analysed the data from 3 recent international studies comprising a total of 167 HoFH patients. The age of the patients ranged from 1 to 75 years, and a large proportion of the patients, both treated and untreated, exhibited LDL-C levels well below the recommended clinical diagnostic threshold for HoFH. LDL-C levels ranged from 4.4 mmol/L to 27.2 mmol/L (170-1052 mg/dL) for untreated patients, and from 2.6 mmol/L to 20.3 mmol/L (101-785 mg/dL) for treated patients. When patients were stratified according to LDLR functionality, a similarly wide range of age and LDL-C values was observed regardless of LDLR mutation status.
These results demonstrate that HoFH is not restricted to very young patients or those with extremely high LDL-C levels.
纯合子家族性高胆固醇血症（HoFH）是一种罕见疾病，通常由低密度脂蛋白受体基因（LDLR）的两个等位基因发生突变引起。在1990年他汀类药物问世和脂蛋白分离术应用之前，HoFH患者往往在20岁之前就过早死亡，这是他们的常见命运。因此，HoFH一直被广泛认为是一种仅见于非常年轻且低密度脂蛋白胆固醇（LDL-C）水平极高的患者群体的疾病。然而，最近的流行病学和遗传学研究表明，HoFH患者群体在年龄、LDL-C水平和遗传病因方面比之前认识到的要更加多样化。我们着手研究HoFH患者年龄和LDL-C范围的临床特征。
我们分析了来自3项近期国际研究的数据，这些研究共纳入167例HoFH患者。患者年龄范围为1至75岁，并且很大一部分患者，无论是否接受治疗，其LDL-C水平均远低于HoFH推荐的临床诊断阈值。未治疗患者的LDL-C水平范围为4.4 mmol/L至27.2 mmol/L（170 - 1052 mg/dL），治疗患者的LDL-C水平范围为2.6 mmol/L至20.3 mmol/L（101 - 785 mg/dL）。当根据LDLR功能对患者进行分层时，无论LDLR突变状态如何，均观察到年龄和LDL-C值范围同样广泛。
这些结果表明HoFH并不局限于非常年轻的患者或LDL-C水平极高的患者。
