Harmonization of Lipoprotein(a) Immunoassays with the IFCC- Endorsed Reference Measurement Procedure Validated in Patient Samples and Multiple Routine testing as A Second Step Towards Apolipoprotein Standardization
Abstract
AIM: Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease (CVD); however, the goal of resolving its measurement issues remains unachieved. Expanding on the "first step" by Miida et al., this study evaluated the feasibility of harmonizing Lp(a) measurements using an IFCC endorsed mass spectrometry-based reference measurement procedure (MS-RMP)-assigned serum panel across a broader range of reagents and CVD patient sample types. METHODS: Eleven immunoassays were evaluated using 536 serum samples (including 416 patients with CVD). Mass-to-molar (nmol/L) conversion equations were derived using the IFCC-MS-RMP-assigned CDC serum panels. For high-concentration samples (170-600 nmol/L), the accuracy was validated through a direct comparison with isoform-insensitive MS-RMP and physiological saline test results. RESULTS: All reagents showed a strong correlation (rs＞0.967) with the MS-RMP in the CDC panel. Inter-reagent differences in patient samples, up to 5.3-fold in mass units, were significantly reduced after molar conversion. High-concentration samples showed a good correlation (rs = 0.904) between MS-RMP and the current immunoassay (Roche), elucidating the bias characteristics relative to the isoform-independent reference method. Furthermore, the measurements were acceptable (within 5% error) up to 3-fold physiological saline, whereas reagent-specific variability increased at higher dilution ratios and in samples with extremely high analyte concentrations. CONCLUSION: Expanding on previous findings, the implementation of a serum panel assigned by the IFCC-MS-RMP significantly strengthens the harmonization of Lp(a) measurements. Precise validation using MS-RMP as a benchmark, even in the high-concentration range, provides a robust foundation for international standardization and the establishment of common clinical decision values.
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BibTeX
@article{yamashita2026harmonization,
title = {{Harmonization of Lipoprotein(a) Immunoassays with the IFCC- Endorsed Reference Measurement Procedure Validated in Patient Samples and Multiple Routine testing as A Second Step Towards Apolipoprotein Standardization}},
author = {Keita Yamashita and Mitsuru Wakita and Noriyasu Niizeki and Satomi Ito and Yui Ito and Asako Sato and Hitomi Miura and Hiroshi Yoshida and Takahiro Masaki and Kazuyuki Matsushita and Kenji Kawasaki and Takao Kimura and Kiyomi Nakajima and Masami Murakami and Masato Maekawa and Hubert W Vesper and Christa M Cobbaert and Takashi Miida and for the JSLM, JSCC, JCCLS and JACRI joint Working Group on Japan research project on the global standardization/harmonization of Lipoprotein (a) measurement},
journal = {Journal of Atherosclerosis and Thrombosis},
year = {2026},
month = sep,
doi = {10.5551/jat.66345},
url = {https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_66345/_article},
note = {CC BY-NC-SA},
}
RIS
TY - JOUR
TI - Harmonization of Lipoprotein(a) Immunoassays with the IFCC- Endorsed Reference Measurement Procedure Validated in Patient Samples and Multiple Routine testing as A Second Step Towards Apolipoprotein Standardization
AU - Keita Yamashita
AU - Mitsuru Wakita
AU - Noriyasu Niizeki
AU - Satomi Ito
AU - Yui Ito
AU - Asako Sato
AU - Hitomi Miura
AU - Hiroshi Yoshida
AU - Takahiro Masaki
AU - Kazuyuki Matsushita
AU - Kenji Kawasaki
AU - Takao Kimura
AU - Kiyomi Nakajima
AU - Masami Murakami
AU - Masato Maekawa
AU - Hubert W Vesper
AU - Christa M Cobbaert
AU - Takashi Miida
AU - for the JSLM, JSCC, JCCLS and JACRI joint Working Group on Japan research project on the global standardization/harmonization of Lipoprotein (a) measurement
PY - 2026
DA - 2026/09/18
JO - Journal of Atherosclerosis and Thrombosis
DO - 10.5551/jat.66345
UR - https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_66345/_article
AB - AIM: Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease (CVD); however, the goal of resolving its measurement issues remains unachieved. Expanding on the "first step" by Miida et al., this study evaluated the feasibility of harmonizing Lp(a) measurements using an IFCC endorsed mass spectrometry-based reference measurement procedure (MS-RMP)-assigned serum panel across a broader range of reagents and CVD patient sample types. METHODS: Eleven immunoassays were evaluated using 536 serum samples (including 416 patients with CVD). Mass-to-molar (nmol/L) conversion equations were derived using the IFCC-MS-RMP-assigned CDC serum panels. For high-concentration samples (170-600 nmol/L), the accuracy was validated through a direct comparison with isoform-insensitive MS-RMP and physiological saline test results. RESULTS: All reagents showed a strong correlation (rs＞0.967) with the MS-RMP in the CDC panel. Inter-reagent differences in patient samples, up to 5.3-fold in mass units, were significantly reduced after molar conversion. High-concentration samples showed a good correlation (rs = 0.904) between MS-RMP and the current immunoassay (Roche), elucidating the bias characteristics relative to the isoform-independent reference method. Furthermore, the measurements were acceptable (within 5% error) up to 3-fold physiological saline, whereas reagent-specific variability increased at higher dilution ratios and in samples with extremely high analyte concentrations. CONCLUSION: Expanding on previous findings, the implementation of a serum panel assigned by the IFCC-MS-RMP significantly strengthens the harmonization of Lp(a) measurements. Precise validation using MS-RMP as a benchmark, even in the high-concentration range, provides a robust foundation for international standardization and the establishment of common clinical decision values.
SN - 1880-3873
SN - 1340-3478
ER -