Comparison of lipoprotein (a) serum concentrations measured by six commercially available immunoassays
Hubert Scharnagl1, Tatjana Stojakovic1, Benjamin Dieplinger2
1Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
Insights
Commercial assays for Lipoprotein (a) [Lp(a)] show significant, concentration-dependent biases. Harmonization efforts are crucial for accurate cardiovascular disease risk assessment.
Area of Science:
- Clinical Chemistry
- Cardiovascular Diagnostics
- Biomarker Quantification
Background:
- Lipoprotein (a) [Lp(a)] is a causal risk factor for cardiovascular disease (CVD).
- Accurate Lp(a) measurement is essential for clinical risk assessment.
- Existing quantification methods require evaluation.
Purpose of the Study:
- To compare the performance of commercially available immunochemical assays for Lp(a).
- To identify discrepancies in Lp(a) measurements across different assays and concentrations.
Main Methods:
- Six different commercial Lp(a) assays (mg/dl and nmol/l) were evaluated using 144 serum samples.
- Assays were calibrated using manufacturer-provided materials.
- Apolipoprotein (a) phenotyping was performed using SDS-agarose gel electrophoresis and immunoblotting.
Main Results:
- High correlation (r > 0.90) was observed between most assays.
- Assays showed significant divergence from reference values, with biases ranging from -8% to +22%.
- Discrepancies were concentration-dependent and non-linear, with some assays overestimating Lp(a) at higher levels.
Conclusions:
- Commercial Lp(a) assays exhibit variable calibration and significant, non-linear biases.
- Observed biases are not fully explained by apolipoprotein (a) phenotypes.
- International harmonization of Lp(a) assays is necessary for reliable clinical use.
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.
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