Testing
A UK reference-change-value study finds Lp(a) must shift by more than 24-32% between tests to represent a real biological change (Ann Clin Biochem 2025)
Original title: Determination of the biological variation and reference change value of lipoprotein (a)
This study established the biological variation (BV) and reference change value (RCV) of Lp(a) in a UK cohort, recruiting 22 healthy individuals with weekly blood samples over six consecutive weeks, analysed in duplicate on the Sentinel Diagnostics assay via Beckman Coulter AU5800, following the 14 BIVAC quality items. Four participants were excluded for mean Lp(a) below the assay's functional sensitivity; among the remainder, mean Lp(a) ranged from 14 to 241 nmol/L, and the overall within-person biological variation (CVI) was 10.9% (95% CI 9.1-13.0%), yielding an RCV of +31.6%/-24.0%. This CVI estimate was notably lower than Lp(a) estimates from studies before 2003, reflecting improved assay quality, but the authors still conclude that a single Lp(a) measurement has real limitations for prognosticating ASCVD risk or identifying candidates for novel Lp(a) therapies when the result sits near a clinical decision threshold, since only changes exceeding the RCV can be interpreted as true biological change rather than measurement noise.
Original abstract
BackgroundUnderstanding lipoprotein (a) [Lp(a)] measurement variability is essential in establishing its coronary heart disease (CHD) association, and optimizing assessment and management of atherosclerotic cardiovascular disease (ASCVD) risk. We established the components of biological variation (BV) and reference change value (RCV) of Lp(a) in a UK cohort.Method22 healthy individuals were recruited to the study. Blood samples were collected for six consecutive weeks and analysed in duplicate using the Lp(a) assay by Sentinel Diagnostics on the Beckman Coulter AU5800. Outlier, heterogeneity, normality, and trend analysis were performed, followed by CV-ANOVA to determine estimates of BV, adhering to the 14 BIVAC quality items. RCV was calculated based on estimated CVA and CVI.ResultsFour participants were excluded from the analysis as their mean Lp(a) levels fell below the functional sensitivity of the assay. Mean Lp(a) concentration ranged from 14 to 241 nmol/L. The overall estimate of CVI for all participants was 10.9% (95% CI of 9.1 - 13.0%). The RCV for Lp(a) was +31.6%/-24.0%.ConclusionOur study obtained a CVI estimate for Lp(a) that aligned consistently with recent studies adhering to the quality specifications outlined in the BIVAC checklist. The CVI estimate was significantly lower than Lp(a) estimates reported in studies up to 2003. The CVI estimate highlights the limitations of relying solely on a single Lp(a) measurement for prognosticating ASCVD risk and identifying candidates for novel Lp(a) therapies, particularly when the measured value is near clinical decision thresholds.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.