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Comparative Study
. 2008 Nov;397(1-2):36-41.
doi: 10.1016/j.cca.2008.07.012. Epub 2008 Jul 18.

Lipoprotein(a) level as a predictor of cardiovascular disease and small apoliprotein(a) isoforms in dialysis patients: assay-related differences are important

J Craig Longenecker  1 , Josef Coresh, Michael J Klag, Neil R Powe, Nancy E Fink, Santica M Marcovina
Affiliations
Comparative Study

Lipoprotein(a) level as a predictor of cardiovascular disease and small apoliprotein(a) isoforms in dialysis patients: assay-related differences are important

J Craig Longenecker et al. Clin Chim Acta. 2008 Nov.

Abstract

Background: Lipoprotein(a) assays sensitive to apolipoprotein(a) size may underestimate associations of lipoprotein(a) with cardiovascular disease (CVD) and low molecular weight (LMW) apolipoprotein(a) isoforms. This study among 629 dialysis patients compares the value of two lipoprotein(a) assays in predicting CVD events and small isoforms.

Methods: Lipoprotein(a) level was measured by an apolipoprotein(a) size-insensitive ELISA and apolipoprotein(a) size-sensitive immunoturbidometric (IT) assay; and apolipoprotein(a) size by Western blot. Positive/negative predictive values (PPV/NPV) for small isoforms were calculated, and CVD events ascertained prospectively.

Results: The ELISA assay predicted CVD more strongly [Relative Hazard, RH=1.8; p=0.045, at the 85th Lipoprotein(a) percentile] than the IT assay (RH=1.3; p=0.37). The PPV for LMW isoforms using the ELISA (Whites, 98%; Blacks, 90%) were much higher than the IT assay (Whites, 75%; Blacks, 68%). Relative to the ELISA assay values, a positive bias in the IT assay values was seen for participants with larger apolipoprotein(a) isoforms, which may explain these findings.

Conclusions: When measured by an apolipoprotein(a) size-insensitive ELISA assay, but not a size-sensitive IT assay, high lipoprotein(a) levels predict both incident CVD and LMW isoforms in dialysis patients. Clinicians ordering lipoprotein(a) levels and research studies of lipoprotein(a) should determine if an apolipoprotein(a)-size related bias is present in the assay they use.

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Figures

Figure 1
Figure 1
potential mechanism of bias in the determination of lipoprotein(a) level using an apolipoprotein(a) size-sensitive assay. Footnote for Figure 1. Illustration of potential mechanism of bias in the determination of lipoprotein(a) concentration using an assay that measures lipoprotein(a) mass. Panel A demonstrates that even if the lipoprotein(a) concentration is the same in the reference sample and test samples, an apolipoprotein(a) size-sensitive lipoprotein(a) mass assay in an individual with LMW isoforms will underestimate the lipoprotein(a) concentration, and overestimate it in an individual with HMW isoforms. On the other hand, as shown in Panel B, the apolipoprotein(a) size-insensitive assay measures concentration accurately, and the signal is not affected or biased by the size of apolipoprotein(a).
Figure 2
Figure 2
ROC Curve for the ELISA and IT assays, in identification of LMW apolipoprotein(a) isoforms.
Figure 3
Figure 3
Ratio of IT assay values to ELISA values, stratified by race and apolipoprotein(a) size category demonstrating a bias in the ratio of the IT assay to the ELISA, according to apolipoprotein size. Footnote for Figure 3. *Non-parametric test for trend for the difference in median ratio across apo(a) groups.
See this image and copyright information in PMC

References

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