School of Medicine, University of Western Australia, Perth, Western Australia, Australia.
Department of Clinical Biochemistry, PathWest Laboratory Medicine, Royal Perth Hospital and Fiona Stanley Hospital Network, Perth, Western Australia, Australia.
J Clin Endocrinol Metab. 2018 Apr 1;103(4):1704-1714. doi: 10.1210/jc.2017-02622.
The gold standard for diagnosing familial hypercholesterolemia (FH) is identification of a causative pathogenic mutation. However, genetic testing is expensive and not widely available.
To compare the validity of the Dutch Lipid Clinic Network (DLCN), Simon Broome (SB), Make Early Diagnosis to Prevent Early Deaths (MEDPED), and American Heart Association (AHA) criteria in predicting an FH-causing mutation.
DESIGN, SETTING, AND PATIENTS: An adult cohort of unrelated patients referred to a lipid clinic for genetic testing.
Odds ratio (OR), area under the curve (AUC), sensitivity, and specificity.
A pathogenic FH-causing mutation was detected in 30% of 885 patients tested. Elevated low-density lipoprotein (LDL) cholesterol and personal or family history of tendon xanthomata were independent predictors of a mutation (OR range 5.3 to 16.1, P < 0.001). Prediction of a mutation for the DLCN and SB definite and MEDPED criteria (ORs 9.4, 11.7, and 10.5, respectively) was higher than with the AHA criteria (OR 4.67). The balance of sensitivity and specificity was in decreasing order DLCN definite (Youden Index 0.487), MEDPED (0.457), SB definite (0.274), and AHA criteria (0.253), AUC being significantly higher with DLCN definite and MEDPED than other criteria (P < 0.05). Pretreatment LDL cholesterol and tendon xanthomata had the highest AUC in predicting a mutation.
The DLCN, SB, and MEDPED criteria are valid predictors of an FH-causing mutation in patients referred to a lipid clinic, but concordance between these phenotypic criteria is only moderate. Use of pretreatment LDL cholesterol and tendon xanthomata alone may be particularly useful for deciding who should be genetically tested for FH.
诊断家族性高胆固醇血症（FH）的金标准是确定致病突变。然而，基因检测费用昂贵且尚未广泛普及。
比较荷兰血脂诊所网络（DLCN）、Simon Broome（SB）、早期诊断以预防早逝（MEDPED）和美国心脏协会（AHA）标准在预测 FH 致病突变方面的准确性。
设计、地点和患者：一组无关联的成年患者，因遗传检测而被转诊至血脂诊所。
比值比（OR）、曲线下面积（AUC）、敏感性和特异性。
在 885 名接受检测的患者中，有 30%检测出致病性 FH 致病突变。升高的低密度脂蛋白（LDL）胆固醇和个人或家族的肌腱黄色瘤病史是突变的独立预测因素（OR 范围为 5.3 至 16.1，P<0.001）。DLCN 明确和 SB 明确以及 MEDPED 标准（OR 分别为 9.4、11.7 和 10.5）对突变的预测高于 AHA 标准（OR 4.67）。敏感性和特异性的平衡顺序为 DLCN 明确（约登指数为 0.487）、MEDPED（0.457）、SB 明确（0.274）和 AHA 标准（0.253），DLCN 明确和 MEDPED 的 AUC 显著高于其他标准（P<0.05）。治疗前 LDL 胆固醇和肌腱黄色瘤对预测突变的 AUC 最高。
DLCN、SB 和 MEDPED 标准是血脂诊所患者 FH 致病突变的有效预测指标，但这些表型标准之间的一致性仅为中等。单独使用治疗前 LDL 胆固醇和肌腱黄色瘤可能特别有助于决定谁应接受 FH 的基因检测。
