#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

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


Authors: Vladimír Bláha
Authors‘ workplace: III. interní gerontometabolická klinika LF UK a FN Hradec Králové
Published in: Vnitř Lék 2018; 64(12): 1160-1168
Category:

Overview

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.

Key words:

alirocumab – atherosclerosis – cardiovascular disease – evolocumab – hypercholesterolaemia – lipoprotein(a) – lipoprotein apheresis


Sources
  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>.
  2. Berg K. A new serum type system in man: the Lp system. Acta Pathol Microbiol Scand 1963; 59: 369–382.
  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>.
  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>.
  5. Kamstrup PR, Benn M, Tybjærg-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>.
  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>.
  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>.
  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>.
  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>.
  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>.
  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>.
  12. Kamstrup PR, Tybjærg-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>.
  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>.
  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>.
  15. Kamstrup PR, Tybjærg-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>.
  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>.
  17. Kamstrup PR, Tybjærg-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>.
  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>.
  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>.
  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>.
  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>.
  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>.
  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>.
  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>.
  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>.
  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>.
  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>.
  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].
  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>.
  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>.
  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>.
  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>.
  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>.
  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>.
  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>.
Labels
Diabetology Endocrinology Internal medicine
Topics Journals
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#