Department of Vascular Medicine, Academic Medical Centre, The Netherlands.
StOEH, Foundation for Identification of Persons with Inherited Hypercholesterolemia, Amsterdam, The Netherlands.
Atherosclerosis. 2014 Mar;233(1):219-23. doi: 10.1016/j.atherosclerosis.2013.12.020. Epub 2014 Jan 11.
Some recently emerged lipid-lowering therapies are currently restricted to patients with homozygous familial hypercholesterolemia (HoFH), and studies are underway to also assess these therapies in patients with 'severe heterozygous FH (HeFH)'. However, no uniform definition of 'severe HeFH' exists, although untreated low-density lipoprotein cholesterol (LDL-C) levels above 8 mmol/L (309 mg/dl) have been historically used to define this phenotype. Our aim was to define severe HeFH, to establish its prevalence and CVD risk, and to study the relative contribution of classical risk factors to CVD risk in HeFH patients.
We analysed a cohort of 14,283 patients with molecularly defined HeFH, identified by the national FH screening programme in the Netherlands. Age and gender specific percentiles of untreated LDL-C were determined. The percentile corresponding to an LDL-C level of 8 mmol/L (309 mg/dL) in men aged 36-40 years (90(th) percentile) was selected as the cut-off value for severe HeFH. By applying this percentile-criterion to the whole cohort, 11% of the HeFH patients could be considered as having severe HeFH. Combined with an estimated HeFH prevalence of 1:300 in the Netherlands, this would translate into a prevalence of approximately 1:3,000 for severe HeFH. CVD risk was significantly increased in severe HeFH patients compared to non-severe HeFH patients (adjusted hazard ratio: 1.25 [95% CI: 1.05-1.51], p = 0.015). In line, male gender, increased age, increased BMI, smoking, hypertension, diabetes, high LDL-C and low high-density lipoprotein cholesterol were independent CVD risk factors in HeFH per se.
We changed the commonly used static LDL-C level of 8 mmol/L for the identification of severe HeFH into an age and gender corrected percentile. This definition would theoretically result in a prevalence of 1:3,000 for severe HeFH. Patients with severe HeFH are at increased CVD risk compared to non-severe HeFH patients, which underscores the need for more aggressive LDL-C lowering these patients.
一些新出现的降脂治疗方法目前仅限于纯合子家族性高胆固醇血症（HoFH）患者，目前正在进行研究以评估这些疗法在“严重杂合子 FH（HeFH）”患者中的疗效。然而，目前尚无“严重 HeFH”的统一定义，尽管未经治疗的低密度脂蛋白胆固醇（LDL-C）水平超过 8mmol/L（309mg/dl）曾被用于定义该表型。我们的目的是定义严重 HeFH，确定其患病率和心血管疾病（CVD）风险，并研究经典危险因素对 HeFH 患者 CVD 风险的相对贡献。
我们分析了荷兰全国 FH 筛查计划中确定的 14283 例分子定义的 HeFH 患者队列。确定了未经治疗的 LDL-C 的年龄和性别特异性百分位数。选择男性 36-40 岁人群中 LDL-C 水平为 8mmol/L（309mg/dL）对应的百分位数（第 90 个百分位数）作为严重 HeFH 的截断值。通过将此百分位标准应用于整个队列，可将 11%的 HeFH 患者归类为严重 HeFH。结合荷兰估计的 HeFH 患病率为 1:300，这意味着严重 HeFH 的患病率约为 1:3000。与非严重 HeFH 患者相比，严重 HeFH 患者的 CVD 风险显著增加（校正后的危险比：1.25[95%CI：1.05-1.51]，p=0.015）。同样，男性、年龄增加、BMI 增加、吸烟、高血压、糖尿病、高 LDL-C 和低高密度脂蛋白胆固醇都是 HeFH 本身的独立 CVD 危险因素。
我们将常用于识别严重 HeFH 的 8mmol/L 静态 LDL-C 水平改为年龄和性别校正的百分位数。根据这一定义，严重 HeFH 的理论患病率为 1:3000。与非严重 HeFH 患者相比，严重 HeFH 患者的 CVD 风险增加，这突出表明这些患者需要更积极地降低 LDL-C。
