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

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.

• Authors: J Craig Longenecker, Josef Coresh, Michael J Klag, Neil R Powe, Nancy E Fink, Santica M Marcovina
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 397 Issue 1-2 Pg. 36-41 (Nov 2008) ISSN: 0009-8981 [Print] Netherlands
• PMID: 18692032 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Apolipoproteins A
• Lipoprotein(a)
• Protein Isoforms

Topics

• Apolipoproteins A (blood)
• Cardiovascular Diseases (diagnosis)
• Electrophoresis, Polyacrylamide Gel (methods)
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Lipoprotein(a) (blood)
• Male
• Middle Aged
• Nephelometry and Turbidimetry (methods)
• Protein Isoforms (blood)
• Renal Dialysis
• Sensitivity and Specificity