title: Lipoprotein(a)-cholesterol levels estimated by vertical auto profile correlate poorly with Lp(a) mass in hyperlipidemic subjects: Implications for clinical practice interpretation of Lp(a)-mediated risk.
abstract: Lipoprotein(a) [Lp(a)] is generally measured as total mass of the entire particle or as apolipoprotein(a) particle number.
  
  
  
  The cholesterol content of Lp(a) [Lp(a)-C)] can be estimated by the vertical auto profile (VAP) method. We assessed whether this is an accurate surrogate measurement of Lp(a) mass.
  
  
  
  VAP-Lp(a)-C and VAP-high density lipoprotein cholesterol (HDL-C) estimated by the VAP technique, Lp(a) mass, oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) that primarily reflect OxPL on Lp(a), and HDL-C measured by enzymatic methods were measured in 552 hypercholesterolemic patients at baseline and 24 weeks after therapy with niacin monotherapy (N = 118), ezetimibe/simvastatin monotherapy (n = 155), or ezetimibe/simvastatin (10/20 mg) + niacin (to 2 g) (N = 279) in a randomized, double-blind trial.
  
  
  
  VAP-Lp(a)-C correlated only modestly with Lp(a) mass at baseline (r = 0.56, P < .001) and 24 weeks (r = 0.56, P < .001), explaining only 31% of the association. VAP-Lp(a)-C correlated with HDL-C at baseline (r = 0.34, P < .001) and 24 weeks (r = 0.30, P < .001) and with VAP-HDL-C at baseline (r = 39, P < .001) and 24 weeks (r = 0.33, P < .001). In contrast, Lp(a) mass did not correlate with HDL-C at baseline (r = 0.06, P = .12) and 24 weeks (r = -0.01 P = .91). Lp(a) mass correlated strongly with oxidized phospholipids on apolipoprotein B-100 at baseline (r = 0.81, P < .001) and 24 weeks (r = 0.79, P < .001). VAP-Lp(a)-C levels increased linearly with HDL-C and VAP-HDL-C quartiles (P < .001 for both) but Lp(a) mass did not. Quantitating the percent of cholesterol present on Lp(a) by dividing VAP-Lp(a)-C by Lp(a) mass revealed that 25% of patients had a percentage >100, which is not possible.
  
  
  
  VAP-Lp(a)-C is a poor estimate for Lp(a) mass and likely reflects the content of HDL-C in the overlapping density spectrum of Lp(a) and HDL. These data suggest that patients with prior VAP-Lp(a)-C measurements may have misclassification of Lp(a)-related risk.
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, Sulpizio Cardiovascular Center, University of California, La Jolla, CA, USA.
authors.forename: Calvin
authors.initials: C
authors.lastname: Yeang
authors.affiliation: San Diego Veteran's Administration Medical Center, La Jolla, CA, USA.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Clopton
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, Sulpizio Cardiovascular Center, University of California, La Jolla, CA, USA. Electronic address: stsimikas@ucsd.edu.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tsimikas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D053299:Apolipoprotein B-100 / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000627:therapeutic use; D010743:Phospholipids / Q000097:blood / Q000737:chemistry; D019821:Simvastatin / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D000924:Anticholesteremic Agents; D053299:Apolipoprotein B-100; D008076:Cholesterol, HDL; D017270:Lipoprotein(a); D010743:Phospholipids; D014280:Triglycerides; D009525:Niacin; D019821:Simvastatin; D000069438:Ezetimibe
keywords: HDL-Cholesterol; Lipoprotein(a); Lipoprotein(a)-cholesterol; Niacin; Oxidized phospholipids; VAP