The 2022 consensus statement of the European Atherosclerosis Society (EAS) on lipoprotein(a) (Lp(a)) recognizes the role of Lp(a) as a relevant genetically determined risk factor and recommends its measurement at least once in an individual’s lifetime. It also strongly urges that Lp(a) test results are expressed as apolipoprotein (a) (apo(a)) amount of substance in molar units and no longer in confounded Lp(a) mass units (mg/dL or mg/L). Therefore, IVD manufacturers should transition to molar units. A prerequisite for this transition is the availability of an Lp(a) Reference Measurement Procedure (RMP) that allows unequivocal molecular detection and quantification of apo(a) in Lp(a). To that end an ISO 17511:2020 compliant LC–MS based and IFCC-endorsed RMP has been established that targets proteotypic peptides of apolipoprotein(a) (apo(a)) in Lp(a). The RMP is laborious and requires highly skilled operators. To guide IVD-manufacturers of immunoassay-based Lp(a) test kits in the transition from mass to molar units, a Designated Comparison Method (DCM) has been developed and evaluated. To assess whether the DCM provides equivalent results compared to the RMP, the procedural designs were compared and the analytical performance of DCM and RMP were first evaluated in a head-to-head comparison. Subsequently, apo(a) was quantified in 153 human clinical serum samples. Both DCM and RMP were calibrated using external native calibrators that produce results traceable to SRM2B. Measurement uncertainty (MU) was checked against predefined allowable MU. The major difference in the design of the DCM for apo(a) is the use of only one enzymatic digestion step. The analytical performance of the DCM and RMP for apo(a) is highly similar. In a direct method comparison, equivalent results were obtained with a median regression slope 0.997 of and a median bias of − 0.2 nmol/L (− 0.2%); the intermediate imprecision of the test results was within total allowable error (TEa) (CVa of 10.2% at 90 nmol/L). The semi-automated, higher throughput, LC–MS-based method for Lp(a) meets the predefined analytical performance specifications and allowable MU and is hence applicable as a higher order Designated Comparison Method, which is ideally suited to guide IVD manufacturers in the transition from Lp(a) mass to molar units.

中文翻译：

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基于 LC-MS 的指定比较方法，其性能与 Lp(a) 参考测量程序相似，可指导摩尔 Lp(a) 标准化

欧洲动脉粥样硬化协会 (EAS) 2022 年关于脂蛋白 (a) (Lp(a)) 的共识声明承认 Lp(a) 作为相关基因决定的危险因素的作用，并建议在个人一生中至少测量一次。它还强烈敦促 Lp(a) 测试结果以摩尔单位的载脂蛋白 (a) (apo(a)) 物质量表示，而不再以混淆的 Lp(a) 质量单位（mg/dL 或 mg/L）表示。因此，IVD 制造商应转向摩尔单位。这一转变的先决条件是 Lp(a) 参考测量程序 (RMP) 的可用性，该程序允许对 Lp(a) 中的 apo(a) 进行明确的分子检测和定量。为此，我们建立了符合 ISO 17511:2020 标准且经 IFCC 认可的基于 LC-MS 的 RMP，其目标是 Lp(a) 中载脂蛋白 (a) (apo(a)) 的蛋白肽。RMP 非常费力，需要高技能的操作员。为了指导基于免疫分析的 Lp(a) 检测试剂盒的 IVD 制造商从质量单位过渡到摩尔单位，我们开发并评估了指定比较方法 (DCM)。为了评估 DCM 是否提供与 RMP 相同的结果，对程序设计进行了比较，并首先在头对头比较中评估了 DCM 和 RMP 的分析性能。随后，对 153 份人类临床血清样本中的 apo(a) 进行了定量。DCM 和 RMP 均使用外部本机校准器进行校准，产生的结果可追溯到 SRM2B。根据预定义的允许 MU 检查测量不确定度 (MU)。apo(a) DCM 设计的主要区别在于仅使用一个酶消化步骤。DCM 和 RMP 对 apo(a) 的分析性能非常相似。在直接方法比较中，获得了等效结果，中位回归斜率为 0.997，中位偏倚为 − 0.2 nmol/L (− 0.2%)；测试结果的中间不精密度在总允许误差（TEa）范围内（90 nmol/L时CVa为10.2%）。Lp(a) 的半自动化、更高通量、基于 LC-MS 的方法满足预定义的分析性能规格和允许的 MU，因此可用作更高阶的指定比较方法，非常适合指导 IVD 制造商从 Lp(a) 质量到摩尔单位的转换。