Assessing the Accuracy of Estimated Lipoprotein(a) Cholesterol and Lipoprotein(a)-Free Low-Density Lipoprotein Cholesterol

Weili Zheng, Michael Chilazi, Jihwan Park, Vasanth Sathiyakumar, Leslie J. Donato, Jeffrey W. Meeusen, Mariana Lazo, Eliseo Guallar, Krishnaji R. Kulkarni, Allan S. Jaffe, Raul D. Santos, Peter P. Toth, Steven R. Jones, Seth S. Martin

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Accurate measurement of the cholesterol within lipoprotein(a) (Lp[a]-C) and its contribution to low-density lipo-protein cholesterol (LDL-C) has important implications for risk assessment, diagnosis, and treatment of atherosclerotic cardiovascular disease, as well as in familial hypercholesterolemia. A method for estimating Lp(a)-C from particle number using fixed conversion factors has been proposed (Lp[a]-C from particle number divided by 2.4 for Lp(a) mass, multiplied by 30% for Lp[a]-C). The accuracy of this method, which theoretically can isolate “Lp(a)-free LDL-C,” has not been validated. METHODS AND RESULTS: In 177 875 patients from the VLDbL (Very Large Database of Lipids), we compared estimated Lp(a)-C and Lp(a)-free LDL-C with measured values and quantified absolute and percent error. We compared findings with an analo-gous data set from the Mayo Clinic Laboratory. Error in estimated Lp(a)-C and Lp(a)-free LDL-C increased with higher Lp(a)-C values. Median error for estimated Lp(a)-C <10 mg/dL was −1.9 mg/dL (interquartile range, −4.0 to 0.2); this error increased lin-early, overestimating by +30.8 mg/dL (interquartile range, 26.1– 36.5) for estimated Lp(a)-C ≥50 mg/dL. This error relationship persisted after stratification by overall high-density lipoprotein cholesterol and high-density lipoprotein cholesterol subtypes. Similar findings were observed in the Mayo cohort. Absolute error for Lp(a)-free LDL-C was +2.4 (interquartile range, −0.6 to 5.3) for Lp(a)-C<10 mg/dL and −31.8 (interquartile range, −37.8 to −26.5) mg/dL for Lp(a)-C≥50 mg/dL. CONCLUSIONS: Lp(a)-C estimations using fixed conversion factors overestimated Lp(a)-C and subsequently underestimated Lp(a)-free LDL-C, especially at clinically relevant Lp(a) values. Application of inaccurate Lp(a)-C estimations to correct LDL-C may lead to undertreatment of high-risk patients.

Original languageEnglish (US)
Article numbere023136
JournalJournal of the American Heart Association
Issue number2
StatePublished - Jan 18 2022


  • LDL-C
  • Lipoprotein(a)

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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