Northwest Lipid Metabolism and Diabetes Research Laboratories, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA.
Laboratory Medicine, Ospedale San Raffaele, Milan, Italy.
Clin Chem. 2020 May 1;66(5):727-736. doi: 10.1093/clinchem/hvaa054.
With increased interest in lipoprotein(a) (Lp[a]) concentration as a target for risk reduction and growing clinical evidence of its impact on cardiovascular disease (CVD) risk, rigorous analytical performance specifications (APS) and accuracy targets for Lp(a) are required. We investigated the biological variation (BV) of Lp(a), and 2 other major biomarkers of CVD, apolipoprotein A-I (apoA-I) and apolipoprotein B-100 (apoB), in the European Biological Variation Study population.
Serum samples were drawn from 91 healthy individuals for 10 consecutive weeks at 6 European laboratories and analyzed in duplicate on a Roche Cobas 8000 c702. Outlier, homogeneity, and trend analysis were performed, followed by CV-ANOVA to determine BV estimates and their 95% CIs. These estimates were used to calculate APS and reference change values. For Lp(a), BV estimates were determined on normalized concentration quintiles.
Within-subject BV estimates were significantly different between sexes for Lp(a) and between women aged <50 and >50 years for apoA-I and apoB. Lp(a) APS was constant across concentration quintiles and, overall, lower than APS based on currently published data, whereas results were similar for apoA-I and apoB.
Using a fully Biological Variation Data Critical Appraisal Checklist (BIVAC)-compliant protocol, our study data confirm BV estimates of Lp(a) listed in the European Federation of Clinical Chemistry and Laboratory Medicine database and reinforce concerns expressed in recent articles regarding the suitability of older APS recommendations for Lp(a) measurements. Given the heterogeneity of Lp(a), more BIVAC-compliant studies on large numbers of individuals of different ethnic groups would be desirable.
随着人们对脂蛋白 (a) (Lp[a]) 浓度作为降低风险目标的兴趣增加，以及越来越多的临床证据表明其对心血管疾病 (CVD) 风险的影响，需要严格的分析性能规范 (APS) 和 Lp(a) 的准确性目标。我们调查了欧洲生物学变异研究人群中脂蛋白 (a) 以及另外两种主要 CVD 生物标志物载脂蛋白 A-I (apoA-I) 和载脂蛋白 B-100 (apoB) 的生物学变异 (BV)。
从欧洲 6 家实验室的 91 名健康个体中抽取血清样本，连续 10 周每周抽取 1 次，并在罗氏 Cobas 8000 c702 上进行双份分析。进行离群值、同质性和趋势分析，然后进行 CV-ANOVA 以确定 BV 估计值及其 95%CI。这些估计值用于计算 APS 和参考变化值。对于 Lp(a)，BV 估计值是基于归一化浓度五分位数确定的。
Lp(a)的个体内 BV 估计值在性别之间存在显著差异，apoA-I 和 apoB 的个体内 BV 估计值在<50 岁和>50 岁的女性之间存在显著差异。Lp(a)的 APS 在浓度五分位数之间保持不变，总体上低于目前发表的数据的 APS，而 apoA-I 和 apoB 的结果相似。
使用完全符合生物学变异数据关键评估清单 (BIVAC) 的方案，我们的研究数据证实了欧洲临床化学和实验室医学联合会数据库中列出的 Lp(a)的 BV 估计值，并加强了最近几篇文章中对 Lp(a)测量的旧 APS 建议的适用性的关注。鉴于 Lp(a)的异质性，对于不同种族的大量个体进行更多符合 BIVAC 的研究将是理想的。
