Relationship of lipoprotein(a) molar concentrations and mass according to lipoprotein(a) thresholds and apolipoprotein(a) isoform size

Sotirios Tsimikas, Sergio Fazio, Nicholas J. Viney, Shuting Xia, Joseph L. Witztum, Santica M. Marcovina

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    Background: Lipoprotein(a) [Lp(a)] is reported as Lp(a) particle mass (mg/dL) or molar concentration of apolipoprotein(a) [apo(a)] (nmol/L), which is considered the gold standard. Values are often converted from one measurement to the other but the validity of this is unknown. Objectives: To quantify the relationship between Lp(a) molar concentration and Lp(a) mass in the context of various Lp(a) level thresholds and apo(a) isoform size. Methods: In all samples, Lp(a) levels in molar concentration and apo(a) isoform size were determined at the Northwest Lipid Metabolism and Diabetes Research Laboratories (NLMDRL). Lp(a) mass levels were determined at the University of California, San Diego (UCSD) (1635 samples), by 5 commercially available assays: Denka 1 and Denka 2 (each 80 samples), 2 turbidimetric assays (2545 and 2673 samples, respectively), and an enzyme-linked immunosorbent assay (2605 samples). The ratios between Lp(a) molar concentration and mass (eg, nmol/L/mg/dL) were calculated and related to apo(a) isoform size. Results: The mean (SD) ratios for NLMDRL/UCSD, NLMDRL/Denka1, and NLMDRL/Denka2 were 2.42 (1.25), 1.64 (0.18), and 2.02 (0.22), respectively. The ratios for NLMDRL/UCSD, NLMDRL/Denka1, and NLMDRL/Denka2 increased by Lp(a) cutoffs, with ratios of 1.82, 1.52, and 1.87, respectively, for Lp(a) < 75 nmol/L and 2.80, 1.89, and 2.24, respectively, for Lp(a) > 125 nmol/L. For the commercial turbidimetric assays and enzyme-linked immunosorbent assay, the ratios ranged from <1 to >5. Conclusions: Lp(a) molar/mass ratios are threshold, method, and isoform dependent. A single factor between assays is not appropriate. These data support the transition of Lp(a) mass assays to molar concentration to improve diagnostic and clinical interpretation of Lp(a)-mediated risk.

    Original languageEnglish (US)
    JournalJournal of Clinical Lipidology
    DOIs
    StateAccepted/In press - Jan 1 2018

    Fingerprint

    Apoprotein(a)
    Lipoprotein(a)
    Protein Isoforms
    Lipid Metabolism
    Research
    Enzyme-Linked Immunosorbent Assay

    Keywords

    • Aortic stenosis
    • Assay
    • Cardiovascular disease
    • Lipoprotein(a)

    ASJC Scopus subject areas

    • Internal Medicine
    • Endocrinology, Diabetes and Metabolism
    • Nutrition and Dietetics
    • Cardiology and Cardiovascular Medicine

    Cite this

    Relationship of lipoprotein(a) molar concentrations and mass according to lipoprotein(a) thresholds and apolipoprotein(a) isoform size. / Tsimikas, Sotirios; Fazio, Sergio; Viney, Nicholas J.; Xia, Shuting; Witztum, Joseph L.; Marcovina, Santica M.

    In: Journal of Clinical Lipidology, 01.01.2018.

    Research output: Contribution to journalArticle

    @article{09e86256ae204c279a82acc9847f7f9e,
    title = "Relationship of lipoprotein(a) molar concentrations and mass according to lipoprotein(a) thresholds and apolipoprotein(a) isoform size",
    abstract = "Background: Lipoprotein(a) [Lp(a)] is reported as Lp(a) particle mass (mg/dL) or molar concentration of apolipoprotein(a) [apo(a)] (nmol/L), which is considered the gold standard. Values are often converted from one measurement to the other but the validity of this is unknown. Objectives: To quantify the relationship between Lp(a) molar concentration and Lp(a) mass in the context of various Lp(a) level thresholds and apo(a) isoform size. Methods: In all samples, Lp(a) levels in molar concentration and apo(a) isoform size were determined at the Northwest Lipid Metabolism and Diabetes Research Laboratories (NLMDRL). Lp(a) mass levels were determined at the University of California, San Diego (UCSD) (1635 samples), by 5 commercially available assays: Denka 1 and Denka 2 (each 80 samples), 2 turbidimetric assays (2545 and 2673 samples, respectively), and an enzyme-linked immunosorbent assay (2605 samples). The ratios between Lp(a) molar concentration and mass (eg, nmol/L/mg/dL) were calculated and related to apo(a) isoform size. Results: The mean (SD) ratios for NLMDRL/UCSD, NLMDRL/Denka1, and NLMDRL/Denka2 were 2.42 (1.25), 1.64 (0.18), and 2.02 (0.22), respectively. The ratios for NLMDRL/UCSD, NLMDRL/Denka1, and NLMDRL/Denka2 increased by Lp(a) cutoffs, with ratios of 1.82, 1.52, and 1.87, respectively, for Lp(a) < 75 nmol/L and 2.80, 1.89, and 2.24, respectively, for Lp(a) > 125 nmol/L. For the commercial turbidimetric assays and enzyme-linked immunosorbent assay, the ratios ranged from <1 to >5. Conclusions: Lp(a) molar/mass ratios are threshold, method, and isoform dependent. A single factor between assays is not appropriate. These data support the transition of Lp(a) mass assays to molar concentration to improve diagnostic and clinical interpretation of Lp(a)-mediated risk.",
    keywords = "Aortic stenosis, Assay, Cardiovascular disease, Lipoprotein(a)",
    author = "Sotirios Tsimikas and Sergio Fazio and Viney, {Nicholas J.} and Shuting Xia and Witztum, {Joseph L.} and Marcovina, {Santica M.}",
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    month = "1",
    day = "1",
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    language = "English (US)",
    journal = "Journal of Clinical Lipidology",
    issn = "1933-2874",
    publisher = "Elsevier BV",

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    T1 - Relationship of lipoprotein(a) molar concentrations and mass according to lipoprotein(a) thresholds and apolipoprotein(a) isoform size

    AU - Tsimikas, Sotirios

    AU - Fazio, Sergio

    AU - Viney, Nicholas J.

    AU - Xia, Shuting

    AU - Witztum, Joseph L.

    AU - Marcovina, Santica M.

    PY - 2018/1/1

    Y1 - 2018/1/1

    N2 - Background: Lipoprotein(a) [Lp(a)] is reported as Lp(a) particle mass (mg/dL) or molar concentration of apolipoprotein(a) [apo(a)] (nmol/L), which is considered the gold standard. Values are often converted from one measurement to the other but the validity of this is unknown. Objectives: To quantify the relationship between Lp(a) molar concentration and Lp(a) mass in the context of various Lp(a) level thresholds and apo(a) isoform size. Methods: In all samples, Lp(a) levels in molar concentration and apo(a) isoform size were determined at the Northwest Lipid Metabolism and Diabetes Research Laboratories (NLMDRL). Lp(a) mass levels were determined at the University of California, San Diego (UCSD) (1635 samples), by 5 commercially available assays: Denka 1 and Denka 2 (each 80 samples), 2 turbidimetric assays (2545 and 2673 samples, respectively), and an enzyme-linked immunosorbent assay (2605 samples). The ratios between Lp(a) molar concentration and mass (eg, nmol/L/mg/dL) were calculated and related to apo(a) isoform size. Results: The mean (SD) ratios for NLMDRL/UCSD, NLMDRL/Denka1, and NLMDRL/Denka2 were 2.42 (1.25), 1.64 (0.18), and 2.02 (0.22), respectively. The ratios for NLMDRL/UCSD, NLMDRL/Denka1, and NLMDRL/Denka2 increased by Lp(a) cutoffs, with ratios of 1.82, 1.52, and 1.87, respectively, for Lp(a) < 75 nmol/L and 2.80, 1.89, and 2.24, respectively, for Lp(a) > 125 nmol/L. For the commercial turbidimetric assays and enzyme-linked immunosorbent assay, the ratios ranged from <1 to >5. Conclusions: Lp(a) molar/mass ratios are threshold, method, and isoform dependent. A single factor between assays is not appropriate. These data support the transition of Lp(a) mass assays to molar concentration to improve diagnostic and clinical interpretation of Lp(a)-mediated risk.

    AB - Background: Lipoprotein(a) [Lp(a)] is reported as Lp(a) particle mass (mg/dL) or molar concentration of apolipoprotein(a) [apo(a)] (nmol/L), which is considered the gold standard. Values are often converted from one measurement to the other but the validity of this is unknown. Objectives: To quantify the relationship between Lp(a) molar concentration and Lp(a) mass in the context of various Lp(a) level thresholds and apo(a) isoform size. Methods: In all samples, Lp(a) levels in molar concentration and apo(a) isoform size were determined at the Northwest Lipid Metabolism and Diabetes Research Laboratories (NLMDRL). Lp(a) mass levels were determined at the University of California, San Diego (UCSD) (1635 samples), by 5 commercially available assays: Denka 1 and Denka 2 (each 80 samples), 2 turbidimetric assays (2545 and 2673 samples, respectively), and an enzyme-linked immunosorbent assay (2605 samples). The ratios between Lp(a) molar concentration and mass (eg, nmol/L/mg/dL) were calculated and related to apo(a) isoform size. Results: The mean (SD) ratios for NLMDRL/UCSD, NLMDRL/Denka1, and NLMDRL/Denka2 were 2.42 (1.25), 1.64 (0.18), and 2.02 (0.22), respectively. The ratios for NLMDRL/UCSD, NLMDRL/Denka1, and NLMDRL/Denka2 increased by Lp(a) cutoffs, with ratios of 1.82, 1.52, and 1.87, respectively, for Lp(a) < 75 nmol/L and 2.80, 1.89, and 2.24, respectively, for Lp(a) > 125 nmol/L. For the commercial turbidimetric assays and enzyme-linked immunosorbent assay, the ratios ranged from <1 to >5. Conclusions: Lp(a) molar/mass ratios are threshold, method, and isoform dependent. A single factor between assays is not appropriate. These data support the transition of Lp(a) mass assays to molar concentration to improve diagnostic and clinical interpretation of Lp(a)-mediated risk.

    KW - Aortic stenosis

    KW - Assay

    KW - Cardiovascular disease

    KW - Lipoprotein(a)

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    DO - 10.1016/j.jacl.2018.07.003

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    JO - Journal of Clinical Lipidology

    JF - Journal of Clinical Lipidology

    SN - 1933-2874

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