Lp(a): When and How to Measure It

Overview

Journal Ann Clin Biochem

Specialty Biochemistry

Date 2020 Oct 12

PMID 33040574

Citations 32

Authors

Jaimini Cegla

Michael France

Santica M Marcovina

R Dermot G Neely

Affiliations

Soon will be listed here.

Abstract

Lipoprotein(a) has long been regarded as a risk factor for cardiovascular disease; however, its routine use in clinical practice has been hampered by difficulties inherent in the measurement of this complex lipoprotein. The major challenges relate to its size heterogeneity and related issues including (1) use of appropriate calibrators (2) standardization of calibration protocols (3) traceability and (4) reporting units. In the UK, results from the current EQA schemes for lipoprotein(a) suggest that there is considerable work required to standardize lipoprotein(a) measurement. This is becoming increasingly pertinent with the increasing recognition of lipoprotein(a) as an independent risk factor for cardiovascular disease in international guidelines and the emergence of novel antisense therapies to effectively reduce lipoprotein(a). This article raises awareness of the importance of measurement of lipoprotein(a) for the assessment of cardiovascular disease risk and gives guidance to clinical laboratories regarding choice of appropriate assays.

Citing Articles

Interaction Between Lipoprotein(a) and Other Lipid Molecules: A Review of the Current Literature.

Sheashaa H, Mousa H, Abbas M, Farina J, Awad K, Pereyra M Biomolecules. 2025; 15(2).

PMID: 40001465 PMC: 11853184. DOI: 10.3390/biom15020162.

Lipoprotein(a) as a Causal Risk Factor for Cardiovascular Disease.

Doherty S, Hernandez S, Rikhi R, Mirzai S, De Los Reyes C, McIntosh S Curr Cardiovasc Risk Rep. 2025; 19(1):8.

PMID: 39980866 PMC: 11836235. DOI: 10.1007/s12170-025-00760-1.

Prevalence of Lp(a) in a real-world Portuguese cohort: implications for cardiovascular risk assessment.

Saraiva M, Garcez J, da Silva B, Ferreira I, Oliveira J, Palma I Lipids Health Dis. 2025; 24(1):16.

PMID: 39827353 PMC: 11742203. DOI: 10.1186/s12944-025-02433-9.

Increasing provider awareness of Lp(a) testing for patients at risk for cardiovascular disease: A comparative study.

Eid W, Sapp E, Conroy C, Bessinger C, Moody C, Yadav R Am J Prev Cardiol. 2024; 21:100895.

PMID: 39720768 PMC: 11666892. DOI: 10.1016/j.ajpc.2024.100895.

Lipoprotein(a) and the risk of type I cardiorenal syndrome in patients with coronary artery disease: A retrospective clinical study.

Jiang Z, Ma H, Meng J, Zhu D, Lu Y Int J Cardiol Heart Vasc. 2024; 56:101568.

PMID: 39720339 PMC: 11667174. DOI: 10.1016/j.ijcha.2024.101568.

References

Albers J, Adolphson J, Hazzard W . Radioimmunoassay of human plasma Lp(a) lipoprotein. J Lipid Res. 1977; 18(3):331-8. View

Tsimikas S . A Test in Context: Lipoprotein(a): Diagnosis, Prognosis, Controversies, and Emerging Therapies. J Am Coll Cardiol. 2017; 69(6):692-711. DOI: 10.1016/j.jacc.2016.11.042. View

Kronenberg F, Utermann G . Lipoprotein(a): resurrected by genetics. J Intern Med. 2012; 273(1):6-30. DOI: 10.1111/j.1365-2796.2012.02592.x. View

Nguyen T, ELLEFSON R, Hodge D, Bailey K, Kottke T, Abu-Lebdeh H . Predictive value of electrophoretically detected lipoprotein(a) for coronary heart disease and cerebrovascular disease in a community-based cohort of 9936 men and women. Circulation. 1997; 96(5):1390-7. DOI: 10.1161/01.cir.96.5.1390. View

Rifai N, Ma J, Sacks F, Ridker P, Hernandez W, Stampfer M . 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):1364-71. DOI: 10.1373/clinchem.2003.030031. View

Scharnagl H, Stojakovic T, Dieplinger B, Dieplinger H, Erhart G, Kostner G . Comparison of lipoprotein (a) serum concentrations measured by six commercially available immunoassays. Atherosclerosis. 2019; 289:206-213. DOI: 10.1016/j.atherosclerosis.2019.08.015. View

Sandholzer C, Saha N, Kark J, Rees A, Jaross W, Dieplinger H . Apo(a) isoforms predict risk for coronary heart disease. A study in six populations. Arterioscler Thromb. 1992; 12(10):1214-26. DOI: 10.1161/01.atv.12.10.1214. View

Marcovina S, Koschinsky M, Albers J, Skarlatos S . Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein(a) and Cardiovascular Disease: recent advances and future directions. Clin Chem. 2003; 49(11):1785-96. DOI: 10.1373/clinchem.2003.023689. View

Boffa M, Koschinsky M . Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease?. J Lipid Res. 2015; 57(5):745-57. PMC: 4847635. DOI: 10.1194/jlr.R060582. View

10.

Dahlen G, FRICK M, Berg K, Valle M, WILJASALO M . Further studies of Lp(a) lipoprotein/pre- beta1-lipoprotein in patients with coronary heart disease. Clin Genet. 1975; 8(3):183-9. DOI: 10.1111/j.1399-0004.1975.tb01492.x. View

11.

Marcovina S, Albers J, Gabel B, Koschinsky M, Gaur V . Effect of the number of apolipoprotein(a) kringle 4 domains on immunochemical measurements of lipoprotein(a). Clin Chem. 1995; 41(2):246-55. View

12.

Ridker P, Hennekens C, Stampfer M . A prospective study of lipoprotein(a) and the risk of myocardial infarction. JAMA. 1993; 270(18):2195-9. View

13.

Kraft H, Lingenhel A, Pang R, Delport R, Trommsdorff M, Vermaak H . Frequency distributions of apolipoprotein(a) kringle IV repeat alleles and their effects on lipoprotein(a) levels in Caucasian, Asian, and African populations: the distribution of null alleles is non-random. Eur J Hum Genet. 1996; 4(2):74-87. DOI: 10.1159/000472175. View

14.

Enkhmaa B, Anuurad E, Berglund L . Lipoprotein (a): impact by ethnicity and environmental and medical conditions. J Lipid Res. 2015; 57(7):1111-25. PMC: 4918859. DOI: 10.1194/jlr.R051904. View

15.

Kamstrup P, Tybjaerg-Hansen A, Nordestgaard B . Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population. J Am Coll Cardiol. 2013; 63(5):470-7. DOI: 10.1016/j.jacc.2013.09.038. View

16.

Tsimikas S, Fazio S, Viney N, Xia S, Witztum J, Marcovina S . 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. DOI: 10.1016/j.jacl.2018.07.003. View

17.

Wieringa G . Lipoprotein(a): what's in a measure?. Ann Clin Biochem. 2000; 37 ( Pt 5):571-80. DOI: 10.1258/0004563001899799. View

18.

Erqou S, Kaptoge S, Perry P, Di Angelantonio E, Thompson A, White I . Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009; 302(4):412-23. PMC: 3272390. DOI: 10.1001/jama.2009.1063. View

19.

Mackness M, Hughes E . Variability in the measurement of lipoprotein(a) in the British Isles. Ann Clin Biochem. 2009; 46(Pt 4):311-5. DOI: 10.1258/acb.2009.08166. View

20.

Marcovina S, Albers J, Scanu A, Kennedy H, Giaculli F, Berg K . 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):1956-67. View