The Importance of the Harmonization and Standardization of Lipoprotein(a) Measurements

See article vol. 32: 580-595

Lipoprotein (a) [Lp(a)] is a unique and complex lipoprotein particle containing apolipoprotein(a) [apo(a)], which is homologous to plasminogen, and it also has a similar lipid and protein composition, such as apolipoprotein B-100, to low-density lipoprotein (LDL)¹⁾. This confers atherosclerotic properties to Lp(a)¹⁾. Currently, Lp(a) in the blood is globally recognized as a causal risk factor for cardiovascular disease^2-4). Lp(a) is attracting further attention as a residual cardiovascular risk factor beyond LDL when the LDL-cholesterol levels are controlled^2-4). Clinical trials using RNA-based drugs to lower Lp(a) in the blood are ongoing as a promising strategy to prevent cardiovascular events⁵⁾.

In this context, the standardization of Lp(a) measurements has been challenging because of the inconsistent results observed between assays^6-9). Recently, efforts have been made to accurately measure Lp(a) using the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)-endorsed mass spectrometry (MS)-based reference measurement procedure (RMP) for apo(a), ensuring SI traceability in line with international laboratory measurement standards⁸⁾. Miida et al. reported the harmonization of Lp(a) measurements across immunoassays using serum panels with Lp(a) levels assigned by the IFCC MS-based PMR¹⁰⁾. Miida et al. showed a large degree of variation among the five types of immunoassays used for the study but demonstrated that the harmonization of Lp(a) could be achieved after converting the Lp(a) levels by the respective immunoassays to the IFCC MS-equivalent levels¹⁰⁾. This report represents a significant step towards resolving the issue of the existing Lp(a) measurements.

When consistent levels of Lp(a) are obtained across assays through harmonization, Lp(a) measurements are expected to become more useful for cardiovascular risk assessment. For instance, some guidelines recommend testing Lp(a) at least once during a person’s lifetime^{2, 3)}. Furthermore, although there is an observation that a linear correlation between the Lp(a) levels and cardiovascular events exists regardless of thresholds⁶⁾, 30 or 50 mg/dL of Lp(a) is thought to be a threshold for elevated Lp(a)^{2, 3)}. These require strictly harmonized Lp(a) measurements.

When the Lp(a) levels are comparable through harmonization, Lp(a) measurements would also be more helpful for both therapeutic assessment and patient management⁵⁾. We are now at such a time as Lp(a)-specific drugs are awaiting clinical use, thus allowing patients to be treated with drugs to lower Lp(a) levels, which should be comparatively monitored in several clinics. Moreover, recorded information and data, including laboratory measurements, are becoming usable at the personal and inter-clinic levels. In this situation, the harmonization and standardization of Lp(a) measurements are considered to be important for the preparation of a new era.

Conflict of Interest

The author declares no conflicts of interest in association with the present study.

Author’s Contribution

K.K. conceptualized and designed the study, wrote the manuscript, and approved the final version of the paper.

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