Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
Atherosclerosis. 2019 Oct;289:206-213. doi: 10.1016/j.atherosclerosis.2019.08.015. Epub 2019 Aug 27.
BACKGROUND AND AIMS: Lipoprotein (a) [Lp(a)] is an established causal risk factor for cardiovascular disease (CVD), independently of low-density lipoproteins (LDL) and other risk factors. The recognition of Lp(a) as an atherogenic molecule has raised the demand for reliable quantification methods in the clinical laboratory. The aim of this work is to compare commercial immunochemical assays. METHODS: We measured Lp(a) serum concentrations using six different assays, providing Lp(a) in mg/dl (Denka Seiken, Abbott Quantia, Beckman, Diasys 21FS, and Siemens N Latex) or in nmol/l (Roche TinaQuant, Diasys 21 FS) in 144 serum samples covering the clinically relevant range of Lp(a) concentrations. All assays relied on five-point calibrations using calibrators provided by the manufacturers. Apolipoprotein(a) phenotyping was performed by sodium dodecyl sulfate-agarose gel electrophoresis (SDS-agarose) followed by immunoblotting. RESULTS: Most bivariate correlation coefficients were greater than 0.90. Compared to an established IFCC-proposed reference material, the results of the different assays diverged from the target values (43.3 mg/dl or 96.6 nmol/l) by -8% (Siemens N Latex) and +22% (Abbott Quantia). Stratification of the samples into five groups with increasing Lp(a) concentrations and difference plots showed that the differences among assays were concentration-dependent. Some assays overestimated Lp(a) at high concentrations compared to the Denka Seiken assay. CONCLUSIONS: Current commercial immunological assays for measuring Lp(a) concentrations are differently calibrated. Their biases differ significantly across the clinically relevant concentration range in a non-linear manner. This is not conclusively explained by apolipoprotein (a) phenotypes. Further international efforts to harmonize assays for Lp(a) are needed.
背景与目的:脂蛋白(a)[Lp(a)]是心血管疾病(CVD)的既定因果风险因素,独立于低密度脂蛋白(LDL)和其他风险因素。将 Lp(a) 视为动脉粥样硬化分子,这提高了临床实验室对可靠定量方法的需求。本研究旨在比较商业免疫化学测定法。
方法:我们使用六种不同的测定法测量了 144 份血清样本中的 Lp(a)血清浓度,这些样本涵盖了 Lp(a)浓度的临床相关范围,提供了 mg/dl(日本和光 Denka Seiken、雅培 Abbott Quantia、贝克曼 Beckman、德赛 Diasys 21FS 和西门子 Siemens N Latex)或 nmol/l(罗氏 Roche TinaQuant、德赛 Diasys 21FS)的 Lp(a)浓度。所有测定法均依赖于制造商提供的五点校准品进行五点校准。载脂蛋白(a)表型分析采用十二烷基硫酸钠-琼脂糖凝胶电泳(SDS-agarose)进行,随后进行免疫印迹。
结果:大多数双变量相关系数大于 0.90。与既定的 IFCC 建议的参考物质相比,不同测定法的结果与目标值(43.3 mg/dl 或 96.6 nmol/l)相差-8%(西门子 Siemens N Latex)和+22%(雅培 Abbott Quantia)。将样本分为五个浓度递增组,并绘制差异图,结果显示测定法之间的差异与浓度有关。与 Denka Seiken 测定法相比,一些测定法在高浓度下高估了 Lp(a)。
结论:目前用于测量 Lp(a)浓度的商业免疫测定法具有不同的校准方式。它们在非线性方式下,在临床相关浓度范围内的偏差差异显著。这不能完全用载脂蛋白(a)表型来解释。需要进一步开展国际努力,以实现 Lp(a)测定法的协调。
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