Vishwanath Raghu, Hemphill Linda C
Genzyme Rare Diseases Medical Affairs, Cambridge, MA, USA.
Cardiology Department, Massachusetts General Hospital, Yawkey Center, Suite 5800, 55 Fruit Street, Boston, MA 02114, USA.
J Clin Lipidol. 2014 Jan-Feb;8(1):18-28. doi: 10.1016/j.jacl.2013.11.002. Epub 2013 Nov 8.
Familial hypercholesterolemia (FH), an autosomal-dominant inherited disorder, can occur in either the heterozygous (HeFH) or homozygous (HoFH) state, and is characterized by high levels of serum low-density lipoprotein cholesterol (LDL-C). Although potent statins and maximally tolerated lipid-lowering therapy (LLT) have greatly reduced the risk of premature coronary heart disease (CHD) and death, all patients with HoFH and many with severe HeFH remain far from treatment goals and are thus at risk of cardiovascular disease. LDL apheresis is the treatment of choice for these patients but remains underutilized. No formal studies or epidemiologic data have estimated the prevalence of HoFH. An HeFH prevalence of 1:500 and a simplified Hardy-Weinberg equilibrium model was used to determine the probability of finding HoFH as 1:1 million in the general population. A US population of approximately 314.8 million was used to determine the number of cases of HoFH and HeFH. The following key parameters were used to estimate the prevalence of severe HeFH: baseline pretreatment LDL-C level and distribution of patients with FH, posttreatment LDL-C level and distribution after maximally tolerated LLT, and baseline percentage of patients with HeFH who have CHD. We assumed an HeFH prevalence of 1:500 and used statistics for a Gaussian distribution after the posttreatment means and standard deviations of LDL-C levels in patients with HeFH receiving maximally tolerated LLT, as has been documented by data from clinical trials and cross-sectional studies. These estimates do not include the statin-intolerant population. The objective of this analysis was to determine the prevalence of the US population with severe HeFH with or without CHD who still will be eligible for LDL apheresis despite maximally tolerated LLT. We estimated that there are 315 US patients with HoFH and 650,000 with HeFH. The estimated prevalence of the severe HeFH population eligible for apheresis is approximately 1:20,000 (range, 1:11,700-1:62,500). This estimate suggests that, based on the efficacy of maximally tolerated LLT and CHD status, approximately 15,000 (approximately 2.4%) of the 625,000 patients with HeFH who are maximally treated will still be eligible for LDL apheresis.
家族性高胆固醇血症（FH）是一种常染色体显性遗传性疾病，可呈杂合子（HeFH）或纯合子（HoFH）状态，其特征是血清低密度脂蛋白胆固醇（LDL-C）水平升高。尽管强效他汀类药物和最大耐受量降脂治疗（LLT）已大幅降低了早发性冠心病（CHD）和死亡风险，但所有HoFH患者以及许多重度HeFH患者仍远未达到治疗目标，因此仍有心血管疾病风险。低密度脂蛋白去除术是这些患者的首选治疗方法，但仍未得到充分利用。尚无正式研究或流行病学数据估计HoFH的患病率。利用HeFH患病率为1:500以及简化的哈迪-温伯格平衡模型，确定在一般人群中发现HoFH的概率为1:100万。以约3.148亿美国人口来确定HoFH和HeFH的病例数。以下关键参数用于估计重度HeFH的患病率：基线治疗前LDL-C水平及FH患者分布、最大耐受量LLT治疗后的LDL-C水平及分布，以及HeFH合并CHD患者的基线百分比。我们假定HeFH患病率为1:500，并根据接受最大耐受量LLT的HeFH患者治疗后LDL-C水平的均值和标准差，采用高斯分布统计数据，临床试验和横断面研究的数据已证实了这一点。这些估计未包括不耐受他汀类药物的人群。本分析的目的是确定美国重度HeFH患者（无论是否合并CHD）的患病率，这些患者尽管接受了最大耐受量LLT，但仍有资格接受低密度脂蛋白去除术。我们估计美国有315例HoFH患者和65万例HeFH患者。符合去除术条件的重度HeFH人群的估计患病率约为1:20,000（范围为1:11,700至1:62,500）。这一估计表明，基于最大耐受量LLT的疗效和CHD状态，在接受最大治疗的62.5万例HeFH患者中，约15,000例（约2.4%）仍有资格接受低密度脂蛋白去除术。
