Background

Lipoprotein(a) [Lp(a)] is a pro-atherogenic and pro-thrombotic LDL-like particle recognized as an independent risk factor for cardiovascular disease (CVD). The cholesterol within Lp(a) (Lp(a)-C) contributes to the reported LDL-cholesterol (LDL-C) concentration by nearly all available methods. Accurate LDL-C measurements are critical for identification of genetic dyslipidemias such as familial hypercholesterolemia (FH). FH diagnostic criteria, such as the Dutch Lipid Clinic Network (DLCN) criteria, utilize LDL-C concentration cut-offs to assess the likelihood of FH. Therefore, failure to adjust for Lp(a)-C can impact accurate FH diagnosis and classification, appropriate follow-up testing and treatments, and interpretation of cholesterol-lowering treatment efficacy.

Objective

In this study, we use direct Lp(a)-C measurements to assess the potential misclassification of FH from contributions of Lp(a)-C to reported LDL-C in patient samples submitted for advanced lipoprotein profiling.

Methods

A total of 31,215 samples submitted for lipoprotein profiling were included. LDL-C was measured by beta quantification or calculated by one of three equations. Lp(a)-C was measured by quantitative lipoprotein electrophoresis. DLCN LDL-C cut-offs were applied to LDL-C results before and after accounting for Lp(a)-C contribution.

Results

Lp(a)-C was detected in 8665 (28%) samples. A total of 940 subjects were reclassified to a lower DLCN LDL-C categories; this represents 3% of the total patient series or 11% of subjects with measurable Lp(a)-C.

Conclusion

Lp(a)-C is present in a significant portion of samples submitted for advanced lipid testing and could cause patient misclassification when using FH diagnostic criteria. These misclassifications could trigger inappropriate follow-up, treatment, and cascade testing for suspected FH.

中文翻译：

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测量Lp（a）胆固醇对LDL-C解释的贡献

背景

脂蛋白（a）[Lp（a）]是促动脉粥样硬化和促血栓形成的LDL样颗粒，被认为是心血管疾病（CVD）的独立危险因素。Lp（a）（Lp（a）-C）中的胆固醇通过几乎所有可用方法有助于报告的LDL-胆固醇（LDL-C）浓度。准确的LDL-C测量对于鉴定遗传性血脂异常（如家族性高胆固醇血症（FH））至关重要。FH诊断标准，例如荷兰血脂临床网络（DLCN）标准，利用LDL-C浓度临界值评估FH的可能性。因此，未能针对Lp（a）-C进行调整可能会影响准确的FH诊断和分类，适当的后续测试和治疗以及对降低胆固醇的治疗效果的解释。

目的

在这项研究中，我们使用直接的Lp（a）-C测量来评估潜在的FH分类错误，这是由于Lp（a）-C对高级脂蛋白谱分析患者样品中报告的LDL-C的贡献所致。

方法

总共包括31,215个用于脂蛋白分析的样品。LDL-C通过β定量测量或通过三个方程式之一计算。通过定量脂蛋白电泳测量Lp（a）-C。在考虑Lp（a）-C贡献之前和之后，将DLCN LDL-C临界值应用于LDL-C结果。

结果

在8665（28％）个样品中检测到Lp（a）-C。总共940位受试者被重新分类为较低的DLCN LDL-C类别；这代表了全部患者系列的3％或可测量Lp（a）-C受试者的11％。

结论

Lp（a）-C存在于提交进行高级脂质测试的很大一部分样品中，使用FH诊断标准可能会导致患者分类错误。这些错误分类可能会导致对可疑的FH进行不适当的随访，治疗和级联检测。