Measuring lipoprotein(a) concentrations: what and how do we measure and where do we go from here?
Authors:
Vladimír Soška 1,2; Ondřej Kyselák 1,3
Authors‘ workplace:
Oddělení klinické biochemie FN U sv. Anny v Brně
1; II. interní klinika LF MU a FN U sv. Anny v Brně
2; Katedra laboratorních metod LF MU, Brno
3
Published in:
AtheroRev 2023; 8(3): 172-176
Category:
Reviews
Overview
Lipoprotein(a) is an atypical lipoprotein whose level in the blood is genetically determined. According to current knowledge, it is an independent risk factor for atherosclerotic cardiovascular disease and for aortic valvular stenosis. Currently, there is no specific therapy available to reduce its blood concentration, but RNA-interference-based therapy is in advanced clinical trials. The management of patients with high Lp(a) levels will require that a reliable method of measuring its concentration in the blood is available. Currently used methods that measure Lp(a) concentration in mass units cannot be reliable, mainly because of the very high variability of the Lp(a) particle. To improve the quality of diagnosis, standardization of measurements with a transition to measuring the molar concentration of Lp(a) and with a follow-up to a suitable international standard is necessary.
Keywords:
apolipoprotein(a) – LDL-cholesterol – lipoprotein(a) – measurement standardization
Sources
- 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. Dostupné z DOI: <https://doi: 10.1093/eurheartj/ehac361>.
- Berg K. A NEW SERUM TYPE SYSTEM IN MAN--THE LP SYSTEM. Acta Pathol Microbiol Scand 1963:59:369–82. Dostupné z DOI: <https://doi: 10.1111/j.1699–0463.1963.tb01808.x>.
- McLean JW, Tomlinson JE, Kuang WJ et al. cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature 1987; 330(6144): 132–137. Dostupné z DOI: <https://doi: 10.1111/j.1699–0463.1963.tb01808.x>.
- Koschinsky ML, Beisiegel U, Henne-Bruns D et al. Apolipoprotein(a) size heterogeneity is related to variable number of repeat sequences in its mRNA. Biochemistry 1990; 29(3): 640–644. Dostupné z DOI: <https://doi: 10.1021/bi00455a007>.
- Ruhaak LR, Cobbaert CM. Quantifying apolipoprotein(a) in the era of proteoforms and precision medicine. Clin Chim Acta 2020; 511: 260–268. Dostupné z DOI: <https://doi: 10.1016/j.cca.2020.10.010>.
- Kraft HG, Lingenhel A, Kochl S et al. Apolipoprotein(a) kringle IV repeat number predicts risk for coronary heart disease. Arterioscler Thromb Vasc Biol 1996; 16(6): 713–719. Dostupné z DOI: <https://doi: 10.1161/01.atv.16.6.713>.
- Enkhmaa B, Petersen KS, Kris-Etherton PM et al. Diet and Lp(a): Does Dietary Change Modify Residual Cardiovascular Risk Conferred by Lp(a)? Nutrients 2020; 12(7). Dostupné z DOI: <https://doi: 10.3390/nu12072024>.
- Boffa MB, Koschinsky ML. Oxidized phospholipids as a unifying theory for lipoprotein(a) and cardiovascular disease. Nat Rev Cardiol 2019; 16(5): 305–318. Dostupné z DOI: <https://doi: 10.1038/s41569–018–0153–2>.
- McConnell JP, Guadagno PA, Dayspring TD et al. Lipoprotein(a) mass: a massively misunderstood metric. J Clin Lipidol 2014; 8(6): 550–553. Dostupné z DOI: <https://doi: 10.1016/j.jacl.2014.08.003>.
- 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.
- Cegla J, Neely RDG, France M et al. Corrigendum to „HEART UK consensus statement on Lipoprotein(a): A call to action“ [Atherosclerosis 2019; 291: 62–70. doi: 10.1016/j.atherosclerosis.2019.10.011]. Atherosclerosis 2020; 296: 48. PMID: 32018073.
- Marcovina SM, Albers JJ. Lipoprotein (a) measurements for clinical application. J Lipid Res 2016; 57(4): 526–537. Dostupné z DOI: <https://doi: 10.1194/jlr.R061648>.
- Saleheen D, Haycock PC, Zhao W et al. Apolipoprotein(a) isoform size, lipoprotein(a) concentration, and coronary artery disease: a mendelian randomisation analysis. Lancet Diabetes Endocrinol 2017; 5(7): 524–533. Dostupné z DOI: <https://doi: 10.1016/S2213–8587(17)30088–8>.
- Marcovina SM, Moriarty PM, Koschinsky ML et al. JCL roundtable-Lipoprotein(a): The emerging risk factor. J Clin Lipidol 2018; 12(6): 1335–1345. Dostupné z DOI: <https://doi: 10.1016/j.jacl.2018.11.003>.
- 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. Dostupné z DOI: <https://doi: 10.1093/clinchem/hvaa324>.
- 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. Dostupné z DOI: <https://doi: 10.1016/j.atherosclerosis.2019.08.015>.
- 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. Dostupné z DOI: <https://doi: 10.1093/clinchem/hvaa239>.
- Kostner GM, Ibovnik A, Holzer H et al. Preparation of a stable fresh frozen primary lipoprotein[a] (Lp[a]) standard. J Lipid Res 1999; 40(12): 2255–2263. PMID: 10588951.
- Demacker PN, Veerkamp MJ, Bredie SJ et al. Comparison of the measurement of lipids and lipoproteins versus assay of apolipoprotein B for estimation of coronary heart disease risk: a study in familial combined hyperlipidemia. Atherosclerosis 2000; 153(2): 483–490. Dostupné z DOI: <https://doi: 10.1016/s0021–9150(00)00432–9>.
- 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. Dostupné z DOI: <https://doi: 10.1016/j.jlr.2021.100053>.
- Langsted A, Kamstrup PR, Benn M et al. High lipoprotein(a) as a possible cause of clinical familial hypercholesterolaemia: a prospective cohort study. Lancet Diabetes Endocrinol 2016; 4(7): 577–587. Dostupné z DOI: <https://doi: 10.1016/S2213–8587(16)30042–0>.
- Chan DC, Pang J, Hooper AJ et al. Effect of Lipoprotein(a) on the Diagnosis of Familial Hypercholesterolemia: Does It Make a Difference in the Clinic? Clin Chem 2019; 65(10): 1258–1266. Dostupné z DOI: <https://doi: 10.1373/clinchem.2019.306738>.
- Hopewell JC, Parish S, Offer A et al. Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study. Eur Heart J 2013; 34(13): 982–992. Dostupné z DOI: <https://doi: doi: 10.1093/eurheartj/ehs344>.
Labels
Angiology Diabetology Internal medicine Cardiology General practitioner for adultsArticle was published in
Athero Review
2023 Issue 3
Most read in this issue
- Measuring lipoprotein(a) concentrations: what and how do we measure and where do we go from here?
- New treatment possibilities of homozygous familial hypercholesterolemia
- Anti-obesity drug with exceptional benefit for preventive cardiology: current results of the SELECT trial
- 2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance