载脂蛋白(a)对家族性高胆固醇血症诊断的影响：临床意义有区别吗？
Effect of Lipoprotein(a) on the Diagnosis of Familial Hypercholesterolemia: Does It Make a Difference in the Clinic?
机构信息
School of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia.
Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital and Fiona Stanley Hospital Network, Perth, Western Australia, Australia.
出版信息
Clin Chem. 2019 Oct;65(10):1258-1266. doi: 10.1373/clinchem.2019.306738. Epub 2019 Jul 15.
BACKGROUND
Diagnostic tools for familial hypercholesterolemia (FH) rely on estimation of LDL cholesterol concentration. However, routine measurement or calculation of LDL cholesterol concentration using the Friedewald equation contains a cholesterol contribution from lipoprotein(a) [Lp(a)]. We investigated whether Lp(a) influences the phenotypic diagnosis of FH by commonly used clinical criteria.
METHODS
A cohort of 907 adult index patients attending a clinic were studied. The Dutch Lipid Clinic Network (DLCN) and Simon Broome (SB) diagnostic criteria were estimated before and after adjusting LDL cholesterol concentration for the cholesterol content (30%) of Lp(a). Diagnostic reclassification rates and area under the ROC (AUROC) curves in predicting an FH mutation were also compared.
RESULTS
Seventy-four patients defined by DLCN criteria (8.2%) and 207 patients defined by SB criteria (22.8%) were reclassified to "unlikely" FH after adjusting LDL cholesterol for Lp(a) cholesterol. The proportion of FH patients defined by DLCN (probable/definite) and SB (possible/definite) criteria decreased significantly in patients with increased Lp(a) (>0.5 g/L; n = 330) after Lp(a) cholesterol adjustment ( < 0.01). The overall reclassification rate was significantly higher in patients with Lp(a) concentration >1.0 g/L ( < 0.001). The AUROC curve for LDL cholesterol concentration ≥191 mg/dL (≥5.0 mmol/L), DLCN criteria, and SB criteria in predicting an FH mutation increased significantly after adjustment ( < 0.001). There was no significant difference in AUROC curve before and after Lp(a) cholesterol adjustment at an LDL cholesterol concentration ≥251 mg/dL (≥6.5 mmol/L).
CONCLUSIONS
Adjusting LDL cholesterol concentration for Lp(a) cholesterol improves the diagnostic accuracy of DLCN and SB criteria, especially with Lp(a) >1.0 g/L and LDL cholesterol <251 mg/dL (<6.5 mmol/L). Lp(a) should be measured in all patients suspected of having FH.
背景
家族性高胆固醇血症（FH）的诊断工具依赖于 LDL 胆固醇浓度的估计。然而，使用 Friedewald 方程常规测量或计算 LDL 胆固醇浓度时，其中包含脂蛋白(a)[Lp(a)]的胆固醇贡献。我们研究了 Lp(a)是否会影响常用临床标准对 FH 的表型诊断。
方法
研究了 907 名成年指数患者的队列。在调整 LDL 胆固醇浓度以反映 Lp(a)胆固醇（30%）之前和之后，估计了荷兰脂质诊所网络（DLCN）和西蒙布鲁姆（SB）诊断标准。还比较了预测 FH 突变的重新分类率和 ROC 曲线下面积（AUROC）。
结果
在调整 LDL 胆固醇浓度以反映 Lp(a)胆固醇后，根据 DLCN 标准（8.2%）定义的 74 名患者和根据 SB 标准（22.8%）定义的 207 名患者被重新归类为“不太可能”FH。在调整 Lp(a)胆固醇后，Lp(a)浓度增加（>0.5 g/L；n = 330）的患者中，根据 DLCN（可能/确定）和 SB（可能/确定）标准定义的 FH 患者比例显著下降（<0.01）。在 Lp(a)浓度>1.0 g/L（<0.001）的患者中，总体重新分类率显著更高。在调整后，LDL 胆固醇浓度≥191mg/dL（≥5.0mmol/L）、DLCN 标准和 SB 标准的 AUROC 曲线预测 FH 突变的 AUC 曲线显著增加（<0.001）。在 LDL 胆固醇浓度≥251mg/dL（≥6.5mmol/L）时，调整 Lp(a)胆固醇前后的 AUROC 曲线无显著差异。
结论
调整 LDL 胆固醇浓度以反映 Lp(a)胆固醇可提高 DLCN 和 SB 标准的诊断准确性，尤其是在 Lp(a)>1.0 g/L 和 LDL 胆固醇<251mg/dL（<6.5mmol/L）时。应在所有疑似 FH 的患者中测量 Lp(a)。
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