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. 2024 Feb;38(1):191-197.
doi: 10.1007/s10557-022-07407-y. Epub 2022 Nov 26.

Quantification of LDL-Cholesterol Corrected for Molar Concentration of Lipoprotein(a)

Robert S Rosenson  1 , J Antonio G López  2 , Maria Laura Monsalvo  2 , You Wu  2 , Huei Wang  2 , Santica M Marcovina  3
Affiliations

Quantification of LDL-Cholesterol Corrected for Molar Concentration of Lipoprotein(a)

Robert S Rosenson et al. Cardiovasc Drugs Ther. 2024 Feb.

Abstract

Purpose: Cholesterol in lipoprotein(a) [Lp(a)-C] is commonly estimated as 30% of the measured Lp(a) mass. However, difficulties in the accurate measurement of Lp(a) mass, along with the inaccuracy of the 30% assumption, produce erroneous values when LDL-C is corrected for Lp(a) [LDL-CLp(a)corr]. Our aim was to develop a new formula for LDL-CLp(a)corr to reduce this error.

Methods: We developed a new formula to calculate Lp(a)-C from the molar measurement of Lp(a), which is Lp(a) nmol/L × 0.077 = Lp(a)-C mg/dL. The calculated Lp(a)-C is subtracted from LDL-C to obtain LDL-CLp(a)corr. The results obtained with our novel formula versus the conventional formula were compared in 440 samples from 239 participants enrolled in the BANTING study.

Results: With the conventional formula, approximately 7% of samples with low LDL-C resulted in negative LDL-CLp(a)corr values. With the new formula, no negative LDL-CLp(a)corr values occurred. Among groups with the highest Lp(a)/apoB ratio (p < 0.001) and smaller apolipoprotein(a) isoform size (p < 0.006), LDL-CLp(a)corr was significantly underestimated by the conventional formula, which may result in the undertreatment of some patients.

Conclusion: The new formula provides more reliable estimates of LDL-CLp(a)corr than the conventional formula.

Trial registration: ClinicalTrials.gov NCT02739984.

Keywords: Apo(a) isoform; Apolipoprotein B; Cardiovascular risk; LDL-cholesterol; Lipoprotein(a); Methods.

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Conflict of interest statement

RSR reports research support from Amgen, Arrowhead, Lilly, Novartis, NIH, and Regeneron; consulting/advisory roles for Amgen, Arrowhead, CRISPR Therapeutics, Lilly, Novartis, Precision BioSciences, Regeneron, and Ultragenyx; speaking (non-promotional) roles with Amgen, Kowa; stock holdings with MediMergent; and royalties from Wolters Kluwer. RSR and SMM are co-inventors in a patent application on the method described in this article (EFS ID: 43877461, application number 63248837 filed on September 27, 2021). JAGL, MLM, YW, and HW are employees and stockholders of Amgen Inc. SMM reports consulting roles for Roche, Denka, and Novartis and research support from Amgen through Medpace.

Figures

Fig. 1
Fig. 1
Conventional estimate versus Rosenson-Marcovina formula: dot plot with regression line and boxplot of reflexive LDL-C deciles for the overall population. LDL-C, low-density lipoprotein cholesterol; LDL-CLp(a)corr, lipoprotein(a)-corrected low-density lipoprotein cholesterol; SD, standard deviation
See this image and copyright information in PMC

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