Testing
A common lab method for estimating Lp(a) cholesterol correlates poorly with actual Lp(a) mass, risking misclassified risk, a study of 552 patients (J Clin Lipidol 2016)
Original 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
This study compared Lp(a) cholesterol estimated by the vertical auto profile (VAP) method against directly measured Lp(a) mass in 552 hypercholesterolaemic patients treated with niacin (n=118), ezetimibe/simvastatin (n=155), or the combination (n=279) in a randomised, double-blind trial, at baseline and 24 weeks. VAP-estimated Lp(a) cholesterol correlated only modestly with Lp(a) mass at baseline and 24 weeks (r=0.56 both, P<.001), explaining just 31% of the association, and correlated instead with HDL cholesterol (r=0.34 and 0.30, P<.001), while true Lp(a) mass did not correlate with HDL cholesterol at either time point. Lp(a) mass correlated strongly with oxidized phospholipids on apoB-100 (r=0.81 and 0.79, P<.001), while VAP-Lp(a) cholesterol rose linearly with HDL cholesterol quartiles (P<.001) but Lp(a) mass did not; 25% of patients had an implausible VAP-Lp(a)-cholesterol-to-mass ratio exceeding 100%. The findings show VAP-estimated Lp(a) cholesterol is a poor surrogate for Lp(a) mass, likely reflecting overlapping HDL density, and may have led to misclassified Lp(a)-related risk in patients relying on this method.
Original abstract
Background: Lipoprotein(a) [Lp(a)] is generally measured as total mass of the entire particle or as apolipoprotein(a) particle number.
Objective: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.