title: 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.affiliation: Johns Hopkins University, Baltimore, MD, USA. jlongene@hsc.edu.kw
authors.forename: J Craig
authors.initials: JC
authors.lastname: Longenecker
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Klag
authors.forename: Neil R
authors.initials: NR
authors.lastname: Powe
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Fink
authors.forename: Santica M
authors.initials: SM
authors.lastname: Marcovina
mesh_terms: 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
chemical_list: D001054:Apolipoproteins A; D017270:Lipoprotein(a); D020033:Protein Isoforms