Developing an SI-traceable Lp(a) reference measurement system: a pilgrimage to selective and accurate apo(a) quantification

References

• Berg K. A new serum type system in man–the lp system. Acta Pathol Microbiol Scand. 1963;59:369–382.
   PubMedGoogle Scholar
• Ridker PM, Hennekens CH, Stampfer MJ. A prospective study of lipoprotein(a) and the risk of myocardial infarction. JAMA. 1993; 270(18):2195–2199.
   PubMed Web of Science ®Google Scholar
• Ridker PM, Stampfer MJ, Hennekens CH. Plasma concentration of lipoprotein(a) and the risk of future stroke. JAMA. 1995; 273(16):1269–1273.
   PubMed Web of Science ®Google Scholar
• Ridker PM, Stampfer MJ, Rifai N. Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA. 2001; 285(19):2481–2485.
   PubMed Web of Science ®Google Scholar
• Rifai N, Ma J, Sacks FM, et al. Apolipoprotein(a) size and lipoprotein(a) concentration and future risk of angina pectoris with evidence of severe coronary atherosclerosis in men: the physicians’ health study. Clin Chem. 2004;50(8):1364–1371.
   PubMed Web of Science ®Google Scholar
• Marcovina SM, Albers JJ. Lipoprotein (a) measurements for clinical application. J Lipid Res. 2016; 57(4):526–537.
   PubMed Web of Science ®Google Scholar
• Pearson GJ, Thanassoulis G, Anderson TJ, et al. 2021 Canadian cardiovascular society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in adults. Can J Cardiol. 2021;37(8):1129–1150.
   PubMed Web of Science ®Google Scholar
• Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American college of cardiology/American heart association task force on clinical practice guidelines. Circulation. 2019;139(25):e1046–e1081.
   PubMed Web of Science ®Google Scholar
• Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: executive summary: a report of the American college of cardiology/American heart association task force on clinical practice guidelines. J Am Coll Cardiol. 2019;74(10):1376–1414.
   PubMed Web of Science ®Google Scholar
• Kronenberg F, Mora S, Stroes ESG, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European atherosclerosis society consensus statement. Eur Heart J. 2022;43(39):3925–3946.
   PubMed Web of Science ®Google Scholar
• Authors/Task Force M, Guidelines ESCCfP. Societies ESCNC. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Atherosclerosis. 2019; 290:140–205.
   PubMed Web of Science ®Google Scholar
• Puri R, Mehta V, Duell PB, et al. Evidence for intensive LDL-C lowering for acute coronary syndrome: recommendations from the lipid association of India. J Clin Lipidol. 2022;16(3):261–271.
   PubMed Web of Science ®Google Scholar
• Chinese Society of Cardiology of Chinese Medical A, Cardiovascular Disease P, Rehabilitation Committee of Chinese Association of Rehabilitation M, et al. [Chinese guideline on the primary prevention of cardiovascular diseases]. Zhonghua Xin Xue Guan Bing Za Zhi. 2020; 48(12):1000–1038.
   PubMedGoogle Scholar
• Clarke R, Peden JF, Hopewell JC, et al. Genetic variants associated with lp(a) lipoprotein level and coronary disease. N Engl J Med. 2009;361(26):2518–2528.
   PubMed Web of Science ®Google Scholar
• Burgess S, Ference BA, Staley JR, et al. Association of LPA variants With risk of coronary disease and the implications for lipoprotein(a)-lowering therapies: a Mendelian randomization analysis. JAMA Cardiol. 2018;3(7):619–627.
   PubMed Web of Science ®Google Scholar
• Patel AP, Wang M, Pirruccello JP, et al. Lp(a) (lipoprotein[a]) concentrations and incident atherosclerotic cardiovascular disease: new insights From a large national biobank. Arterioscler Thromb Vasc Biol. 2021;41(1):465–474.
   PubMed Web of Science ®Google Scholar
• Kamstrup PR, Benn M, Tybjaerg-Hansen A, et al. Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: the copenhagen city heart study. Circulation. 2008;117(2):176–184.
   PubMed Web of Science ®Google Scholar
• Nordestgaard BG, Langsted A. Lipoprotein (a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology. J Lipid Res. 2016; 57(11):1953–1975.
   PubMed Web of Science ®Google Scholar
• Rhainds D, Brodeur MR, Tardif JC. Lipoprotein (a): when to measure and how to treat? Curr Atheroscler Rep. 2021; 23(9):51.
   PubMed Web of Science ®Google Scholar
• Cobbaert C, Arentsen JC, Mulder P, et al. Significance of various parameters derived from biological variability of lipoprotein(a), homocysteine, cysteine, and total antioxidant status. Clin Chem. 1997;43(10):1958–1964.
   PubMed Web of Science ®Google Scholar
• Sandberg S, Fraser CG, Horvath AR, et al. Defining analytical performance specifications: consensus statement from the 1st strategic conference of the European federation of clinical chemistry and laboratory medicine. Clin Chem Lab Med. 2015; 53(6):833–835.
   PubMed Web of Science ®Google Scholar
• Langlois MR, Nordestgaard BG, Langsted A, et al. Quantifying atherogenic lipoproteins for lipid-lowering strategies: consensus-based recommendations from EAS and EFLM. Clin Chem Lab Med. 2020;58(4):496–517.
   PubMed Web of Science ®Google Scholar
• Aarsand AKF-CP, Webster C, Coskun A, et al. The EFLM biological variation database. https://biologicalvariation.eu/. EFLM; 2019.
   Google Scholar
• Ricos CA, Cava F, Garcia-Lario JV, et al. Current databases on biologic variation: pros, cons and progress. https://www.westgard.com/biodatabase1.htm. : Scand J Clin Lab Invest 1999; 2014.
   Google Scholar
• Ruhaak LR, Cobbaert CM. Quantifying apolipoprotein(a) in the era of proteoforms and precision medicine. Clin Chim Acta. 2020;511:260–268.
   PubMed Web of Science ®Google Scholar
• Cobbaert CM, Althaus H, Begcevic Brkovic I, et al. Towards an SI-traceable reference measurement system for seven serum apolipoproteins using bottom-up quantitative proteomics: conceptual approach enabled by cross-disciplinary/cross-sector collaboration. Clin Chem. 2021;67(3):478–489.
   PubMed Web of Science ®Google Scholar
• Tsimikas S, Fazio S, Ferdinand KC, et al. NHLBI working group recommendations to reduce lipoprotein(a)-mediated risk of cardiovascular disease and aortic stenosis. J Am Coll Cardiol. 2018;71(2):177–192.
   PubMed Web of Science ®Google Scholar
• Marcovina SM, Albers JJ, Gabel B, et al. Effect of the number of apolipoprotein(a) kringle 4 domains on immunochemical measurements of lipoprotein(a). Clin Chem. 1995;41(2):246–255.
   PubMed Web of Science ®Google Scholar
• Dati F, Tate JR, Marcovina SM, et al. First WHO/IFCC international reference reagent for lipoprotein(a) for immunoassay–lp(a) SRM 2B. Clin Chem Lab Med. 2004;42(6):670–676.
   PubMed Web of Science ®Google Scholar
• Cobbaert C, Deprez L, Ruhaak LR. On the way to a next generation lp(a) reference measurement system based on quantitative protein mass spectrometry and molar units. In Kostner K, Kostner G, Toth P, editors. Lipoprotein(a). Contemporary cardiology. Cham, Switzerland: Humana; 2023.
   Google Scholar
• Clouet-Foraison N, Vaisar T, Marcovina SM. Standardization of analytical methods for the measurement of lipoprotein(a): bridging Past and future initiatives. In: Kostner K, Kostner GM, Toth PP, editors. Lipoprotein(a). Cham: Springer International Publishing; 2023. p. 297–323.
   Google Scholar
• Vesper HW, Thienpont LM. Traceability in laboratory medicine. Clin Chem. 2009; 55(6):1067–1075.
   PubMed Web of Science ®Google Scholar
• ISO. (International Organization for Standardization) 17511. 2020. Requirements for establishing metrological traceability of values assigned to calibrators, trueness control materials and human samples.
   Google Scholar
• Joint Committee for Guides in Metrology, International Vocabulary of Metrology [accessed 15 Jan 2023.
   Google Scholar
• SI. Brochure: The International System of Units [accessed on 12 December 2012]; 2023.
   Google Scholar
• ISO. (International, Organization, for, Standardization) 15195; 2018. Laboratory medicine—Requirements for the competence of calibration laboratories using reference measurement procedures. https://www.iso.org/standard/69824.html.
   Google Scholar
• ISO. (International, Organization, for, Standardization) 15193; 2009. in vitro diagnostic medical devices—measurement of quantities in samples of biological origin—Requirements for content and presentation of reference measurement procedures.
   Google Scholar
• Tsimikas S, Fazio S, Viney NJ, et al. Relationship of lipoprotein(a) molar concentrations and mass according to lipoprotein(a) thresholds and apolipoprotein(a) isoform size. J Clin Lipidol. 2018;12(5):1313–1323.
   PubMed Web of Science ®Google Scholar
• McConnell JP, Guadagno PA, Dayspring TD, et al. Lipoprotein(a) mass: a massively misunderstood metric. J Clin Lipidol. 2014;8(6):550–553.
   PubMed Web of Science ®Google Scholar
• Koschinsky ML, Marcovina SM. Structure-function relationships in apolipoprotein(a): insights into lipoprotein(a) assembly and pathogenicity. Curr Opin Lipidol. 2004; 15(2):167–174.
   PubMed Web of Science ®Google Scholar
• Koschinsky ML, Marcovina SM. Lipoprotein(a): structural implications for pathophysiology. Int J Clin Lab Res. 1997;27(1):14–23.
   PubMedGoogle Scholar
• Enas EA, Varkey B, Dharmarajan TS, et al. Lipoprotein(a): an independent, genetic, and causal factor for cardiovascular disease and acute myocardial infarction. Indian Heart J. 2019;71(2):99–112.
   PubMedGoogle Scholar
• Kronenberg F. Human genetics and the causal role of lipoprotein(a) for various diseases. Cardiovasc Drugs Ther. 2016; 30(1):87–100.
   PubMed Web of Science ®Google Scholar
• Tsimikas S, Brilakis ES, Miller ER, et al. Oxidized phospholipids, lp(a) lipoprotein, and coronary artery disease. N Engl J Med. 2005;353(1):46–57.
   PubMed Web of Science ®Google Scholar
• Subramanian SP, Gundry RL. The known unknowns of apolipoprotein glycosylation in health and disease. iScience. 2022; 25(9):105031.
   PubMed Web of Science ®Google Scholar
• Garner B, Merry AH, Royle L, et al. Structural elucidation of the N- and O-glycans of human apolipoprotein(a): role of o-glycans in conferring protease resistance. J Biol Chem. 2001;276(25):22200–22208.
   PubMed Web of Science ®Google Scholar
• Gries A, Nimpf J, Nimpf M, et al. Free and apo B-associated lpa-specific protein in human serum. Clin Chim Acta. 1987;164(1):93–100.
   PubMed Web of Science ®Google Scholar
• Cauza E, Kletzmaier J, Bodlaj G, et al. Relationship of non-LDL-bound apo(a), urinary apo(a) fragments and plasma lp(a) in patients with impaired renal function. Nephrol Dial Transplant. 2003;18(8):1568–1572.
   PubMed Web of Science ®Google Scholar
• McLean JW, Tomlinson JE, Kuang WJ, et al. cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature. 1987; 330(6144):132–137.
   PubMed Web of Science ®Google Scholar
• Lawn RM, Schwartz K, Patthy L. Convergent evolution of apolipoprotein(a) in primates and hedgehog. Proc Natl Acad Sci U S A. 1997; 94(22):11992–11997.
   PubMed Web of Science ®Google Scholar
• Parson W, Kraft HG, Niederstatter H, et al. A common nonsense mutation in the repetitive kringle IV-2 domain of human apolipoprotein(a) results in a truncated protein and low plasma lp(a). Hum Mutat. 2004;24(6):474–480.
   PubMed Web of Science ®Google Scholar
• Hoff HF, O'Neil J, Smejkal GB, et al. Immunochemically detectable lipid-free apo(a) in plasma and in human atherosclerotic lesions. Chem Phys Lipids. 1994;67-68:271–280.
   PubMed Web of Science ®Google Scholar
• Mooser V, Marcovina SM, White AL, et al. Kringle-containing fragments of apolipoprotein(a) circulate in human plasma and are excreted into the urine. J Clin Invest. 1996;98(10):2414–2424.
   PubMed Web of Science ®Google Scholar
• Fortunato JE, Bassiouny HS, Song RH, et al. Apolipoprotein (a) fragments in relation to human carotid plaque instability. J Vasc Surg. 2000;32(3):555–563.
   PubMed Web of Science ®Google Scholar
• ISO. (International, Organization, for, Standardization), 20914. 2019. Medical laboratories – practical guidance for the estimation of measurement uncertainty.
   Google Scholar
• Lord SJ, St John A, Bossuyt PM, et al. Setting clinical performance specifications to develop and evaluate biomarkers for clinical use. Ann Clin Biochem. 2019;56(5):527–535.
   PubMed Web of Science ®Google Scholar
• White GH. Basics of estimating measurement uncertainty. Clin Biochem Rev. 2008; 29 Suppl 1(Suppl 1):S53–S60.
   PubMedGoogle Scholar
• Jones GRD, Albarede S, Kesseler D, et al. Analytical performance specifications for external quality assessment - definitions and descriptions. Clin Chem Lab Med. 2017;55(7):949–955.
   PubMed Web of Science ®Google Scholar
• Marcovina SM, Clouet-Foraison N, Koschinsky ML, et al. Development of an LC-MS/MS proposed candidate reference method for the standardization of analytical methods to measure lipoprotein(a). Clin Chem. 2021;67(3):490–499.
   PubMed Web of Science ®Google Scholar
• Renee Ruhaak L, van der Laarse A, Cobbaert CM. Apolipoprotein profiling as a personalized approach to the diagnosis and treatment of dyslipidaemia. Ann Clin Biochem. 2019; 56(3):338–356.
   PubMed Web of Science ®Google Scholar
• Harris EK. Proposed goals for analytical precision and accuracy in single-point diagnostic testing. Theoretical basis and comparison with data from college of American pathologists proficiency surveys. Arch Pathol Lab Med. 1988; 112(4):416–420.
   PubMed Web of Science ®Google Scholar
• Clouet-Foraison N, Marcovina SM, Guerra E, et al. Analytical performance specifications for lipoprotein(a), apolipoprotein B-100, and apolipoprotein A-I using the biological variation model in the EuBIVAS population. Clin Chem. 2020;66(5):727–736.
   PubMed Web of Science ®Google Scholar
• Greif M, Arnoldt T, von Ziegler F, et al. Lipoprotein (a) is independently correlated with coronary artery calcification. Eur J Intern Med. 2013; 24(1):75–79.
   PubMed Web of Science ®Google Scholar
• Jurgens G, Hermann A, Aktuna D, et al. Dissociation-enhanced lanthanide fluorescence immunoassay of lipoprotein(a) in serum. Clin Chem. 1992;38(6):853–859.
   PubMed Web of Science ®Google Scholar
• Lequin RM. Enzyme immunoassay (EIA)/enzyme-linked immunosorbent assay (ELISA). Clin Chem. 2005; 51(12):2415–2418.
   PubMed Web of Science ®Google Scholar
• Albers JJ, Hazzard WR. Immunochemical quantification of human plasma lp(a) lipoprotein. Lipids. 1974; 9(1):15–26.
   PubMed Web of Science ®Google Scholar
• Albers JJ, Adolphson JL, Hazzard WR. Radioimmunoassay of human plasma lp(a) lipoprotein. J Lipid Res. 1977; 18(3):331–338.
   PubMed Web of Science ®Google Scholar
• Yeang C, Witztum JL, Tsimikas S. Novel method for quantification of lipoprotein(a)-cholesterol: implications for improving accuracy of LDL-C measurements. J Lipid Res. 2021; 62:100053.
   PubMed Web of Science ®Google Scholar
• Yeang C, Witztum JL, Tsimikas S. LDL-C’ = LDL-C + lp(a)-C: implications of achieved ultra-low LDL-C levels in the proprotein convertase subtilisin/kexin type 9 era of potent LDL-C lowering. Curr Opin Lipidol. 2015; 26(3):169–178.
   PubMed Web of Science ®Google Scholar
• Brown WV, Ballantyne CM, Jones PH, et al. Management of lp(a). J Clin Lipidol. 2010;4(4):240–247.
   PubMed Web of Science ®Google Scholar
• Cegla J, France M, Marcovina SM, et al. Lp(a): when and how to measure it. Ann Clin Biochem. 2021;58(1):16–21.
   PubMed Web of Science ®Google Scholar
• Kronenberg F, Tsimikas S. The challenges of measuring lp(a): a fight against hydra? Atherosclerosis. 2019; 289:181–183.
   PubMed Web of Science ®Google Scholar
• Kronenberg F. Lipoprotein(a) measurement issues: Are we making a Mountain out of a molehill? Atherosclerosis. 2022; 349:123–135.
   PubMed Web of Science ®Google Scholar
• Kang C, Dominguez M, Loyau S, et al. Lp(a) particles mold fibrin-binding properties of apo(a) in size-dependent manner: a study with different-length recombinant apo(a), native lp(a), and monoclonal antibody. Arterioscler Thromb Vasc Biol. 2002;22(7):1232–1238.
   PubMed Web of Science ®Google Scholar
• Utermann G, Menzel HJ, Kraft HG, et al. Lp(a) glycoprotein phenotypes. Inheritance and relation to lp(a)-lipoprotein concentrations in plasma. J Clin Invest. 1987;80(2):458–465.
   PubMed Web of Science ®Google Scholar
• Ruhaak L, Renee RF, Brkovic BZ, Dittrich JUHL, et al. Development of an LC-MRM-MS based candidate reference measurement procedure for standardization of serum apolipoprotein (a) tests. Clin Chem. 2023; 69(3):251–261.
   Google Scholar
• Kostner KM, Kostner GM, Wierzbicki AS. Is lp(a) ready for prime time use in the clinic? A pros-and-cons debate. Atherosclerosis. 2018; 274:16–22.
   PubMed Web of Science ®Google Scholar
• Marcovina SM, Navabi N, Allen S, et al. Development and validation of an isoform-independent monoclonal antibody-based ELISA for measurement of lipoprotein(a). J Lipid Res. 2022;63(8):100239.
   PubMed Web of Science ®Google Scholar
• Hoofnagle AN, Wener MH. The fundamental flaws of immunoassays and potential solutions using tandem mass spectrometry. J Immunol Methods. 2009; 347(1-2):3–11.
   PubMed Web of Science ®Google Scholar
• Siepen JA, Keevil EJ, Knight D, et al. Prediction of missed cleavage sites in tryptic peptides aids protein identification in proteomics. J Proteome Res. 2007;6(1):399–408.
   PubMed Web of Science ®Google Scholar
• Smit NPM, Ruhaak LR, Romijn F, et al. The time has come for quantitative protein mass spectrometry tests that target unmet clinical needs. J Am Soc Mass Spectrom. 2021;32(3):636–647.
   PubMed Web of Science ®Google Scholar
• Smit NPM, Romijn F, van Ham VJJ, et al. Quantitative protein mass-spectrometry requires a standardized pre-analytical phase. Clin Chem Lab Med. 2023;61(1):55–66.
   PubMed Web of Science ®Google Scholar
• Dikaios IA, Angles-Cano E, Ceglarek U, et al. Commutability assessment of candidate reference materials for lipoprotein(a) by comparison of a MS-based candidate reference measurement procedure with immunoassays. Clin Chem Forthcoming. Clin Chem. 2023; 69(3):262–272.
   PubMed Web of Science ®Google Scholar
• Marcovina SM, Albers JJ, Scanu AM, et al. Use of a reference material proposed by the international federation of clinical chemistry and laboratory medicine to evaluate analytical methods for the determination of plasma lipoprotein(a). Clin Chem. 2000;46(12):1956–1967.
   PubMed Web of Science ®Google Scholar
• JCTLM. JCTLM Database: higher-order reference materials, methods and services. [cited 2023 Jan14] Available from: https://www.jctlmdb.org/#/app/home2022.
   Google Scholar
• Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31(23):2844–2853.
   PubMed Web of Science ®Google Scholar
• Piepoli MF, Hoes AW, Agewall S, et al. 2016 European guidelines on cardiovascular disease prevention in clinical practice: the sixth joint task force of the European society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of 10 societies and by invited experts)developed with the special contribution of the European association for cardiovascular prevention & rehabilitation (EACPR). Eur Heart J. 2016;37(29):2315–2381.
   PubMed Web of Science ®Google Scholar
• Cardiovascular disease: risk assessment and reduction, including lipid modification. London: National Institute for Health and Care Excellence (NICE); 2023.
   Google Scholar
• Cegla J, Neely RDG, France M, et al. HEART UK consensus statement on lipoprotein(a): A call to action. Atherosclerosis. 2019;291:62–70.
   PubMed Web of Science ®Google Scholar
• Correction to: 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease Executive summary: a report of the American college of cardiology/American heart association task force on clinical practice guidelines. Circulation. 2020; 141(16):e773.
   PubMed Web of Science ®Google Scholar
• Ponte-Negretti CI, Isea-Perez JE, Lorenzatti AJ, et al. Atherogenic dyslipidemia in Latin America: prevalence, causes and treatment: expert’s position paper made by The Latin American academy for the study of lipids (ALALIP) endorsed by the Inter-American society of cardiology (IASC), the South American society of cardiology (SSC), the Pan-American college of endothelium (PACE), and the international atherosclerosis society (IAS). Int J Cardiol. 2017;243:516–522.
   PubMed Web of Science ®Google Scholar
• Rhee EJ, Kim HC, Kim JH, et al. 2018 Guidelines for the management of dyslipidemia in Korea. J Lipid Atheroscler. 2019;8(2):78–131.
   PubMedGoogle Scholar
• Kinoshita M, Yokote K, Arai H, et al. Japan atherosclerosis society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017. J Atheroscler Thromb. 2018;25(9):846–984.
   PubMed Web of Science ®Google Scholar
• Klug E, et al. South African dyslipidaemia guideline consensus statement. S Afr Med J. 2012; 102(3 Pt 2):178–187.
   PubMed Web of Science ®Google Scholar
• O'Callaghan CJ, Rong P, Goh MY. National guidelines for the management of absolute cardiovascular disease risk. Med J Aust. 2014; 200(8):454, 456.
   PubMed Web of Science ®Google Scholar
• Scharnagl H, Stojakovic T, Dieplinger B, et al. Comparison of lipoprotein (a) serum concentrations measured by six commercially available immunoassays. Atherosclerosis. 2019;289:206–213.
   PubMed Web of Science ®Google Scholar
• Wyness SP, Genzen JR. Performance evaluation of five lipoprotein(a) immunoassays on the roche cobas c501 chemistry analyzer. Pract Lab Med. 2021; 25:e00218.
   PubMedGoogle Scholar
• Lapic I, Segulja D, Dukic K, et al. Analytical validation of 39 clinical chemistry tests and 17 immunoassays on the alinity analytical system. Scand J Clin Lab Invest. 2022; 82(3):199–209.
   PubMed Web of Science ®Google Scholar