Evidence map›Paper›PMID 33517366›Full record

ArticleClinical chemistry2021

Development of an LC-MS/MS Proposed Candidate Reference Method for the Standardization of Analytical Methods to Measure Lipoprotein(a).

Santica M Marcovina, Noémie Clouet-Foraison, Marlys L Koschinsky, Mark S Lowenthal, Allen Orquillas, Michael B Boffa, Andrew N Hoofnagle, Tomáš Vaisar

Open access · bronzeAbstract read
In one paragraph

Article in Clinical chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 64 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Cardiovascular disease lipids and lipoproteins biomarker standardization.Critical reviews in clinical laboratory sciences · 2025
    Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Lipoprotein(a): Just an Innocent Bystander in Arterial Hypertension?International journal of molecular sciences · 2023
    Review
  17. Lipoprotein (a), Inflammation, and Atherosclerosis.Journal of clinical medicine · 2023
    Article
  18. The ins and outs of lipoprotein(a) assay methods.Archives of medical sciences. Atherosclerotic diseases · 2023
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Santica M MarcovinaDivision of Metabolism, Endocrinology, and Nutrition, Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle, WA, USA.
Noémie Clouet-ForaisonDivision of Metabolism, Endocrinology, and Nutrition, Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle, WA, USA.
Marlys L KoschinskyDepartment of Physiology & Pharmacology, Robarts Research Institute, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
Mark S LowenthalNational Institute of Standards and Technology (NIST), Gaithersburg, MD, USA.
Allen OrquillasDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Michael B BoffaDepartment of Biochemistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
Andrew N HoofnagleDivision of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA, USA.
Tomáš VaisarDivision of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA, USA.
University of Washington · USWestern University · CANational Institute of Standards and Technology · US

Funding

Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · PI Sakeneh Zraika · 1986 to 2026
$41.4M
HDL composition/function and cardiovascular risk in youths with diabetesR01HL144558 · NHLBI · UNIVERSITY OF WASHINGTON · PI VAISAR, TOMAS · 2019 to 2022
$2.8M
Quantifying proteins in plasma to democratize personalized medicine for patients with type 1 diabetesU01DK121289 · NIDDK · UNIVERSITY OF WASHINGTON · PI HOOFNAGLE, ANDREW N · 2019 to 2021
$1.9M
HDL and cardiovascular risk in chronic kidney diseaseR01HL111375 · NHLBI · UNIVERSITY OF WASHINGTON · PI HOOFNAGLE, ANDREW N · 2012 to 2015
$1.5M
NHLBI NIH HHS R01 HL111375NHLBI NIH HHS R01 HL144558NIDDK NIH HHS P30 DK017047NIDDK NIH HHS U01 DK121289
6 · The paper itself

Abstract

backgroundUse of lipoprotein(a) concentrations for identification of individuals at high risk of cardiovascular diseases is hampered by the size polymorphism of apolipoprotein(a), which strongly impacts immunochemical methods, resulting in discordant values. The availability of a reference method with accurate values expressed in SI units is essential for implementing a strategy for assay standardization.

methodA targeted LC-MS/MS method for the quantification of apolipoprotein(a) was developed based on selected proteotypic peptides quantified by isotope dilution. To achieve accurate measurements, a reference material constituted of a human recombinant apolipoprotein(a) was used for calibration. Its concentration was assigned using an amino acid analysis reference method directly traceable to SI units through an unbroken traceability chain. Digestion time-course, repeatability, intermediate precision, parallelism, and comparability to the designated gold standard method for lipoprotein(a) quantification, a monoclonal antibody-based ELISA, were assessed.

resultsA digestion protocol providing comparable kinetics of digestion was established, robust quantification peptides were selected, and their stability was ascertained. Method intermediate imprecision was below 10% and linearity was validated in the 20-400 nmol/L range. Parallelism of responses and equivalency between the recombinant and endogenous apo(a) were established. Deming regression analysis comparing the results obtained by the LC-MS/MS method and those obtained by the gold standard ELISA yielded y = 0.98*ELISA +3.18 (n = 64).

conclusionsOur method for the absolute quantification of lipoprotein(a) in plasma has the required attributes to be proposed as a candidate reference method with the potential to be used for the standardization of lipoprotein(a) assays.

Indexed as

CalibrationChromatography, LiquidHumansLipoprotein(a)Reference StandardsReproducibility of ResultsTandem Mass SpectrometryLipoprotein(a)apolipoprotein(a)Lipoprotein(a)reference methodstandardization

Identifiers

PMID33517366
PMCPMC7935757
OpenAlexW3128300220

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.