Lipoprotein(a) level as a predictor of cardiovascular disease and small apoliprotein(a) isoforms in dialysis patients: assay-related differences are important.
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.
Longenecker
J Craig
JC
Johns Hopkins University, Baltimore, MD, USA. jlongene@hsc.edu.kw
Coresh
Josef
J
Klag
Michael J
MJ
Powe
Neil R
NR
Fink
Nancy E
NE
Marcovina
Santica M
SM
D001054:Apolipoproteins A / Q000097:blood*; D002318:Cardiovascular Diseases / Q000175:diagnosis*; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry / Q000379:methods; D020033:Protein Isoforms / Q000097:blood; D006435:Renal Dialysis; D012680:Sensitivity and Specificity
D001054:Apolipoproteins A; D017270:Lipoprotein(a); D020033:Protein Isoforms