Vnitr Lek 2018, 64(12):1160-1168

Lipoprotein(a) - the cardiovascular risk factor: significance and therapeutic possibilities

Vladimír Blaha
III. interní gerontometabolická klinika LF UK a FN Hradec Králové

About 20 % of the population has raised Lp(a) concentrations and evidence suggests that high levels of Lp(a) are an independent cardiovascular risk factor. Both the European Society of Cardiology and the European Atherosclerosis Society recommend measuring Lp(a) values in intermediate to high-risk patients for risk stratification, as well as in patients already under statin treatment and with recurrent clinical events as a residual risk factor that calls for lipid-lowering therapy intensification. Strategies used to lower Lp(a) concentrations have either been partially disappointing in the past or lack cardiovascular outcome data. Therefore, Lp(a) has often been considered as a nonmodifiable cardiovascular risk factor. New and consistent data retrieved from the PCSK9 inhibitor trials now suggest that Lp(a) can be decreased effectively by roughly 30 %, while emerging data from apo(a) antisense therapy trials suggest that selective and potent Lp(a) reduction is a feasible treatment approach in the future. The impact of such decreases on the occurrence of cardiovascular outcomes, independent from LDL-C, could, if established, herald Lp(a) in the treatment of atherosclerosis.

Keywords: alirocumab; atherosclerosis; cardiovascular disease; evolocumab; hypercholesterolaemia; lipoprotein(a); lipoprotein apheresis

Received: November 2, 2018; Accepted: November 15, 2018; Published: December 1, 2018  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Blaha V. Lipoprotein(a) - the cardiovascular risk factor: significance and therapeutic possibilities. Vnitr Lek. 2018;64(12):1160-1168.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Mozaffarian D, Benjamin EJ, Go AS et al. [American Heart Association Statistics Committee and Stroke Statistics Subcommittee]. Heart disease and stroke statistics - 2015 update: a report from the American Heart Association. Circulation 2015; 131(4): e29-e322. Dostupné z DOI: <http://doi:10.1161/CIR.0000000000000152>. Go to original source... Go to PubMed...
    2. Berg K. A new serum type system in man: the Lp system. Acta Pathol Microbiol Scand 1963; 59: 369-382. Go to original source... Go to PubMed...
    3. Kronenberg F. Human genetics and the causal role of lipoprotein(a) for various diseases. Cardiovasc Drugs Ther 2016; 30(1): 87-100. Dostupné z DOI: <http://dx.doi.org/10.1007/s10557-016-6648-3>. Go to original source... Go to PubMed...
    4. 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. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehq386>. Go to original source... Go to PubMed...
    5. 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. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.107.715698>. Go to original source... Go to PubMed...
    6. Laschkolnig A, Kollerits B, Lamina C et al. Lipoprotein(a) concentrations, apolipoprotein(a) phenotypes, and peripheral arterial disease in three independent cohorts. Cardiovasc Res 2014; 103(1): 28-36. Dostupné z DOI: <http://dx.doi.org/10.1093/cvr/cvu107>. Go to original source... Go to PubMed...
    7. [Emerging Risk Factors Collaboration]. Erqou S, Kaptoge S, Perry PL et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA 2009; 302(4): 412-423. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2009.1063>. Go to original source... Go to PubMed...
    8. Schmidt K, Noureen A, Kronenberg F et al. Structure, function, and genetics of lipoprotein(a). J Lipid Res 2016; 57(8): 1339-1359. Dostupné z DOI: <http://dx.doi.org/10.1194/jlr.R067314>. Go to original source... Go to PubMed...
    9. Tsimikas S. A Test in Context: Lipoprotein(a): Diagnosis, Prognosis, Controversies, and Emerging Therapies. JACC 2017: 69(6): 692-711. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2016.11.042>. Go to original source... Go to PubMed...
    10. van der Valk FM, Bekkering S, Kroon J et al. Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans. Circulation 2016; 134(8): 611-624. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.116.020838>. Go to original source... Go to PubMed...
    11. Kamstrup PR, Tybjaerg-Hansen A, Nordestgaard BG. Genetic evidence that lipoprotein(a) associates with atherosclerotic stenosis rather than venous thrombosis. Arterioscler Thromb Vasc Biol 2012; 32(7): 1732-1741. Dostupné z DOI: <http://dx.doi.org/10.1161/ATVBAHA.112.248765>. Go to original source... Go to PubMed...
    12. Kamstrup PR, Tybjaerg-Hansen A, Nordestgaard BG. Extreme lipoprotein(a) levels and improved cardiovascular risk prediction. J Am Coll Cardiol 2013; 61(11): 1146-1156. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2012.12.023>. Go to original source... Go to PubMed...
    13. Clarke R, Peden JF, Hopewell JC et al. [PROCARDIS Consortium]. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med 2009; 361(26): 2518-2528. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa0902604>. Go to original source... Go to PubMed...
    14. Kyriakou T, Seedorf U, Goel A et al. [PROCARDIS Consortium]. A common LPA null allele associates with lower lipoprotein(a) levels and coronary artery disease risk. Arterioscler Thromb Vasc Biol 2014; 34(9): 2095-2099. Dostupné z DOI: <http://dx.doi.org/10.1161/ATVBAHA.114.303462>. Go to original source... Go to PubMed...
    15. Kamstrup PR, Tybjaerg-Hansen A, Steffensen R et al. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA 2009; 301(22): 2331-2339. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2009.801>. Go to original source... Go to PubMed...
    16. Catapano AL, Graham I, De Backer G et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J 2016; 37(39): 2999-3058. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehw272>. Go to original source... Go to PubMed...
    17. Kamstrup PR, Tybjaerg-Hansen A, Nordestgaard BG. Extreme lipoprotein(a) levels and improved cardiovascular risk prediction. J Am Coll Cardiol 2013; 61(11): 1146-1156. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2012.12.023>. Go to original source... Go to PubMed...
    18. Khera AV, Everett BM, Caulfield MP et al. Lipoprotein(a) concentrations, rosuvastatin therapy, and residual vascular risk: an analysis from the JUPITER Trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin). Circulation 2014; 129(6): 635-642. Dostupné z DOI: http://dx.doi.org/10.1161/CIRCULATIONAHA.113.004406>. Go to original source... Go to PubMed...
    19. Albers JJ, Slee A, O'brien KD et al. Relationship of apolipoproteins A-1 and B, and lipoprotein(a) to cardiovascular outcomes: the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes). J Am Coll Cardiol 2013; 62(17): 1575-1579. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2013.06.051>. Go to original source... Go to PubMed...
    20. Nestel PJ, Barnes EH, Tonkin AM et al. Plasma lipoprotein(a) concentration predicts future coronary and cardiovascular events in patients with stable coronary heart disease. Arterioscler Tromb Vasc Biol 2013; 33(12): 2902-2908. Dostupné z DOI: <http://dx.doi.org/10.1161/ATVBAHA.113.302479>. Go to original source... Go to PubMed...
    21. Yeang C, Hung MY, Byun YS et al. Effect of therapeutic interventions on oxidized phospholipids on apolipoprotein b100 and lipoprotein(a). J Clin Lipidol 2016; 10(3): 594-603. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacl.2016.01.005>. Go to original source... Go to PubMed...
    22. Landray MJ, Haynes R, Hopewell JC et al. [HPS2-THRIVE Collaborative Group]. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med 2014; 371(3): 203-212. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1300955>. Go to original source... Go to PubMed...
    23. Kronenberg F, Utermann G. Lipoprotein(a): resurrected by genetics. J Intern Med 2013; 273(1): 6-30. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1365-2796.2012.02592.x>. Go to original source... Go to PubMed...
    24. Raal FJ, Giugliano RP, Sabatine MS et al. Reduction in lipoprotein(a) with pcsk9 monoclonal antibody evolocumab (amg 145): a pooled analysis of more than 1,300 patients in 4 phase ii trials. J Am Coll Cardiol 2014; 63(13): 1278-1288. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2014.01.006>. Go to original source... Go to PubMed...
    25. Gaudet D, Kereiakes DJ, McKenney JM et al. Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9 antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 mg every two weeks dosing from phase 2 trials). Am J Cardiol 2014; 114(5): 711-715. Dostupné z DOI: <http://dx.doi.org/10.1016/j.amjcard.2014.05.060>. Go to original source... Go to PubMed...
    26. Raal FJ, Giugliano RP, Sabatine MS et al. PCSK9 inhibition-mediated reduction in Lp(a) with evolocumab: An analysis of 10 clinical trials and the LDL receptor's role. J Lipid Res 2016; 57(6): 1086-1096. Dostupné z DOI: <http://dx.doi.org/10.1194/jlr.P065334>. Go to original source... Go to PubMed...
    27. Sabatine MS, Giugliano RP, Keech AC et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017; 376(18): 1713-1722. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1615664>. Go to original source... Go to PubMed...
    28. Graham MJ, Viney N, Crooke RM et al. Antisense inhibition of apolipoprotein (a) to lower plasma lipoprotein(a) levels in humans. J Lipid Res 2016; 57(3): 340-351. Dostupné z DOI: <http://dx.doi.org/10.1194/jlr.R052258>. Erratum in ERRATUM. [J Lipid Res. 2016]. Go to original source... Go to PubMed...
    29. Santos RD, Raal FJ, Catapano AL et al. Mipomersen, an antisense oligonucleotide to apolipoprotein b-100, reduces lipoprotein(a) in various populations with hypercholesterolemia: results of 4 phase III trials. Arterioscl Thromb Vasc Biol 2015; 35(3): 689-699. Dostupné z DOI: <http://dx.doi.org/10.1161/ATVBAHA.114.304549>. Go to original source... Go to PubMed...
    30. Tsimikas S, Viney NJ, Hughes SG et al. Antisense therapy targeting apolipoprotein(a): a randomised, double-blind, placebo-controlled phase 1 study. Lancet 2015; 386(10002): 1472-1483. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140-6736(15)61252-1>. Go to original source... Go to PubMed...
    31. Viney NJ, Capelleveen JCV, Geary RS et al. Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials. Lancet 2016; 388(10057): 2239-2253. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140-6736(16)31009-1>. Go to original source... Go to PubMed...
    32. Jaeger BR, Richter Y, Nagel D et al. Longitudinal cohort study on the effectiveness of lipid apheresis treatment to reduce high lipoprotein(a) levels and prevent major adverse coronary events. Nat Clin Prac Cardiovasc Med 2009; 6(3): 229-239. Dostupné z DOI: <http://dx.doi.org/10.1038/ncpcardio1456>. Go to original source... Go to PubMed...
    33. Roeseler E, Julius U, Heigl F et al. Lipoprotein apheresis for lipoprotein(a)-associated cardiovascular disease: prospective 5 years of follow-up and apolipoprotein(a) characterization. Arterioscl Thromb Vasc Biol 2016; 36(9): 2019-2027. Dostupné z DOI: <http://dx.doi.org/10.1161/ATVBAHA.116.307983>. Go to original source... Go to PubMed...
    34. Heigl F, Hettich R, Lotz N et al. Clinical benefit of long-term lipoprotein apheresis in patients with severe hypercholesterolemia or Lp(a)-hyperlipoproteinemia with progressive cardiovascular disease. Clin Res Cardiol Suppl 2015; 10: 8-13. Dostupné z DOI: <http://dx.doi.org/10.1007/s11789-015-0071-3>. Go to original source... Go to PubMed...
    35. Safarova MS, Ezhov MV, Afanasieva OI et al. Effect of specific lipoprotein(a) apheresis on coronary atherosclerosis regression assessed by quantitative coronary angiography. Atheroscl Suppl 2013; 14(1): 93-99. Dostupné z DOI: <http://dx.doi.org/10.1016/j.atherosclerosissup.2012.10.015>. Go to original source... Go to PubMed...

    Return to the content


    Vnitřní lékařství

    Madam, Sir,
    please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
    Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

    I declare:

    1. that I have met the above instruction
    2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited

    No
    Yes

    If your statement is not true, please be aware
    that brings the risk of danger to their health or the health of others.