Research Institute of the McGill University Health Centre, Royal Victoria Hospital, Montreal, QC, Canada.
Departments of Medicine and Biochemistry, Schulich School of Medicine and Robarts Research Institute, Western University, London, ON, Canada.
Clin Chem. 2018 Feb;64(2):355-362. doi: 10.1373/clinchem.2017.279422. Epub 2017 Oct 16.
Familial hypercholesterolemia (FH) is the most frequent genetic disorder seen clinically and is characterized by increased LDL cholesterol (LDL-C) (>95th percentile), family history of increased LDL-C, premature atherosclerotic cardiovascular disease (ASCVD) in the patient or in first-degree relatives, presence of tendinous xanthomas or premature corneal arcus, or presence of a pathogenic mutation in the , , or genes. A diagnosis of FH has important clinical implications with respect to lifelong risk of ASCVD and requirement for intensive pharmacological therapy. The concentration of baseline LDL-C (untreated) is essential for the diagnosis of FH but is often not available because the individual is already on statin therapy.
To validate a new algorithm to impute baseline LDL-C, we examined 1297 patients. The baseline LDL-C was compared with the imputed baseline obtained within 18 months of the initiation of therapy. We compared the percent reduction in LDL-C on treatment from baseline with the published percent reductions.
After eliminating individuals with missing data, nonstandard doses of statins, or medications other than statins or ezetimibe, we provide data on 951 patients. The mean ± SE baseline LDL-C was 243.0 (2.2) mg/dL [6.28 (0.06) mmol/L], and the mean ± SE imputed baseline LDL-C was 244.2 (2.6) mg/dL [6.31 (0.07) mmol/L] ( = 0.48). There was no difference in response according to the patient's sex or in percent reduction between observed and expected for individual doses or types of statin or ezetimibe.
We provide a validated estimation of baseline LDL-C for patients with FH that may help clinicians in making a diagnosis.
家族性高胆固醇血症（FH）是临床上最常见的遗传性疾病，其特征是 LDL 胆固醇（LDL-C）升高（>95 百分位），家族 LDL-C 升高史，患者或一级亲属中存在早发动脉粥样硬化性心血管疾病（ASCVD），存在肌腱黄色瘤或早发性角膜弓，或存在 、 或 基因的致病性突变。FH 的诊断对 ASCVD 的终身风险和强化药物治疗的需求具有重要的临床意义。基线 LDL-C（未经治疗）的浓度对于 FH 的诊断至关重要，但由于个体已经接受他汀类药物治疗，因此通常无法获得。
为了验证一种新的基线 LDL-C 估算算法，我们检查了 1297 名患者。将基线 LDL-C 与治疗开始后 18 个月内获得的估算基线 LDL-C 进行比较。我们比较了治疗后从基线 LDL-C 的降低百分比与已发表的降低百分比。
在消除了数据缺失、他汀类药物剂量不标准或除他汀类药物或依折麦布以外的其他药物的个体后，我们提供了 951 名患者的数据。平均±SE 基线 LDL-C 为 243.0（2.2）mg/dL[6.28（0.06）mmol/L]，平均±SE 估算基线 LDL-C 为 244.2（2.6）mg/dL[6.31（0.07）mmol/L]（=0.48）。根据患者的性别或观察到的与预期的反应没有差异，也没有根据个体剂量或他汀类药物或依折麦布的类型进行差异。
我们提供了 FH 患者基线 LDL-C 的验证估计值，这可能有助于临床医生进行诊断。
