Possibilities of correction of elevated lipoprotein (a) levels

Authors: Yaroustovsky M.B.1, Abramyan M.V.1, Rogal'skaya E.A.1, Komardina E.V.1, Nazarova E.I.1, Grigoryan D.A.2, Podschekoldina O.O.1

Company: 1 Bakoulev National Medical Research Center for Cardiovascular Surgery of Ministry of Health of the Russian Federation, Rublevskoe shosse, 135, Moscow, 121552, Russian Federation;
2 Pirogov Russian National Research Medical University of Ministry of Health of the Russian Federation, ulitsa Ostrovityanova, 1, Moscow, 117997, Russian Federation

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Type:  Reviews


DOI: https://doi.org/10.24022/1997-3187-2019-13-2-129-146

For citation: Yaroustovsky M.B., Abramyan M.V., Rogal'skaya E.A., Komardina E.V., Nazarova E.I., Grigoryan D.A., Podschekoldina O.O. Possibilities of correction of elevated lipoprotein (a) levels. Creative Cardiology. 2019; 13 (2): 129–46 (in Russ.). DOI: 10.24022/1997-3187-2019-13-2-129-146

Received / Accepted:  31.05.2019/05.06.2019

Keywords: atherosclerosis, cholesterol, low density lipoprotein cholesterol, lipoprotein(a), lipoprotein apheresis, H.E.L.P.-apheresis, cascade filtration cascade lipidfiltration, cardiovascular diseases, coronary heart disease

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Abstract

High blood lipoprotein (a) (Lp(a)) could promote atherosclerosis development directly as well as indirectly. Today, blood purification methods remain the most reasonable for reducing hyperlipoproteidemia. This method plays role for primary and/or secondary prevention of complications of the cardiovascular system. Selective lipoprotein apheresis techniques can reduce the level of Lp(a) by 65–75% per procedure. At the same time, these methods are aimed at correcting high levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and fibrinogen. Regular treatment with lipoprotein apheresis can improve the prognosis of the cardiovascular disease, the effectiveness of surgical and medical treatment, and, most importantly, improve the quality of life of patients. In this report, we present the clinical cases of the use of selective lipid apheresis – H.E.L.P-therapy (Heparin-induced Extracorporeal Lipoprotein Precipitation) and cascade lipidfiltration – in patients with type IIa hypercholesterolemia in combination with hyperlipoproteidemia. To date, hyperlipoproteidemia (more than 50 mg/dL) along with progressive cardiovascular disease has been approved as indication for regular lipoprotein apheresis. Apheresis techniques are the most correct in the treatment of elevated levels of Lp(a), but in each case an individual approach is required to determine the protocol of the procedure.

References

  1. Julius U. Current role of lipoprotein apheresis in the treatment of high-risk patients. J. Cardiovasc. Dev. Dis. 2018; 5: 27. DOI: 10.3390/jcdd5020027
  2. Julius U. History of lipidology and lipoprotein apheresis. Atheroscler. Suppl. 2017; 30: 1–8. DOI: 10.1016/j.atherosclerosissup.2017.05.034
  3. Safarova M.S., Ezhov M.V. The Evolution of Viewson Lipoprotein(a): From Biomarker to the Thera-peutic Target. Kardiologiia. 2015; 55 (4): 71–82(in Russ.).
  4. 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
  5. Waldmann E., Parhofer K.G. Lipoprotein apheresis to treat elevated lipoprotein (a). J. Lipid. Res. 2016; 57: 1751–7. DOI: 10.1194/jlr.R056549
  6. Mellwig K.-P., Horstkotte D., van Buuren F. Lipoprotein (a) and coronary heart disease – is there an efficient secondary prevention? Clin. Res. Cardiol. Suppl. 2017; 12: 18–21. DOI: 10.1007/s11789-017-0088-x
  7. Pokrovsky S.N., Afanasieva O.I., Safarova M.S., Balakhonova T.V., Matchin Y.G., Adamova I.Yu. et al. Specific Lp(a) apheresis: A tool to prove lipoprotein(a) atherogenicity. Atheroscler. Suppl. 2017; 30: 166–73. DOI: 10.1016/j.atherosclerosissup.2017.05.004
  8. Jaeger B.R., Richter Y., Nagel D., Heigl F., Vogt A., Roeseler E. et al. Group of Clinical Investigators. Longitudinal cohort study on the effectiveness of lipid apheresis treatment to reduce high lipoprotein(a) levels and prevent major adverse coronary events. Nat. Clin. Pract. Cardiovasc. Med. 2009; 6: 229–39.
  9. Vogt A. Hyperlipoproteinaemia(a) – apheresis and emerging therapies. Clin. Res. Cardiol. Suppl. 2017; 12: 12–7. DOI: 10.1007/s11789-017-0083-2
  10. Roeseler E., Julius U., Heigl F., Spitthoever R., Heutling D., Breitenberger P. et al. Lipoprotein apheresis for lipoprotein(a)-associated cardiovascular disease: prospective 5 years of follow-up and apolipoprotein(a) characterization. Arterioscler. Thromb. Vasc. Biol. 2016; 36 (9): 2019–27. DOI: 10.1161/ATVBAHA.116.307983
  11. Yaroustovsky M.B., Abramyan M.V. Significanceof lipoprotein (a) in the pathogenesis of cardiovas-cular diseases. Creative Cardiology.2019; 13 (1):40–51 (in Russ.)
  12. Boffa M.B. Emerging therapeutic options for lowering of lipoprotein (a): implications for prevention of cardiovascular disease. Curr. Atheroscler. Rep. 2016; 18: 69. DOI: 10.1007/s11883-016-0622-1
  13. Hoover-Plow J., Huang M. Lipoprotein(a) metabolism: potential sites for therapeutic targets. Met. Clinical. Experiment. 2013; 62: 479–91. DOI: 10.1016/j.metabol.2012.07.024
  14. Vogt A. Lipoprotein(a)-apheresis in the light of new drug developments. Atheroscler. Suppl. 2017; 30: 38–43. DOI: 10.1016/j.atherosclerosissup.2017.05.025
  15. Chennamsetty I., Claudel T., Kostner K.M., Baghdasaryan A., Kratky D., Levak-Frank S. et al. Farnesoid X receptor represses hepatic human APOA gene expression. J. Clin. Invest. 2011; 121: 3724–34. DOI: 10.1172/JCI45277
  16. Van Capelleveen J.C., van der Valk F.M., Stroes E.S. Current therapies for lowering lipoprotein (a). J. Lipid. Res. 2016; 57 (9): 1612–8. DOI: 10.1194/jlr.R053066
  17. Howard B.V., Rossouw J.E. Estrogens and cardiovascular disease risk revisited: the Women's Health Initiative. Curr. Opin. Lipidol. 2013; 24: 493–9.
  18. Tsimikas S., Viney N.J., Hughes S.G., Singleton W., Graham M.J., Baker B.F. et al. Antisense therapy targeting apolipoprotein(a): a randomised, double-blind, placebo-controlled phase 1 study. Lancet. 2015; 386: 1472–83. DOI: 10.1016/S0140-6736(15)61252-1
  19. Rader D.J., Kastelein J.J. Lomitapide and mipomersen: two first-in-class drugs for reducing lowdensity lipoprotein cholesterol in patients with homozygous familial hypercholesterolemia. Circulation. 2014; 129 (9): 1022–32. DOI: 10.1161/CIRCULATIONAHA.113. 001292
  20. Waldmann E., Vogt A., Crispin A., Altenhofer J., Riks I., Parhofer K.G. Effect of mipomersen on LDL-cholesterol in patients with severe LDLhypercholesterolaemia and atherosclerosis treated by lipoprotein apheresis (The MICA-Study). Atheroscler. 2017; 259: 20–5. DOI: 10.1016/j.atherosclerosis.2017.02.019
  21. Nicholls S.J., Tang W.H., Scoffone H., Brennan D.M., Hartiala J., Allayee H. et al. Lipoprotein(a) levels and long-term cardiovascular risk in the contemporary era of statin therapy. J. Lipid. Res. 2010; 51 (10): 3055–61. DOI: 10.1194/jlr.M008961
  22. Sahebkar A., Reiner Z., Simental-Mendia L.E., Ferretti G., Cicero A.F. Effect of extended-release niacin on plasma lipoprotein(a) levels: a systematic review and meta-analysis of randomized placebo- controlled trials. Metabolism. 2016; 65 (11): 1664–78. DOI: 10.1016/j.metabol.2016.08.007
  23. HPS2-THRIVE Collaborative Group None, Landray M.J., Haynes R., Hopewell J.C., Parish S., Aung T. et al. Effects of extended-release niacin with laropiprant in high-risk patients. N. Engl. J. Med. 2014; 371: 203–12. DOI: 10.1056/NEJMoa1300955
  24. HPS2-THRIVE Collaborative Group. HPS2- THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment. Eur. Heart J. 2013; 34 (17): 1279–91.
  25. Kastelein J.P., Besseling J., Shah S., Bergeron J., Langslet G., Hovingh G.K. et al. Anacetrapib as lipid-modifying therapy in patients with heterozygous familial hypercholesterolaemia (REALIZE): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet. 2015; 385 (9983): 2153–61.
  26. Shinkai H. Cholesteryl ester transfer-protein modulator and inhibitors and their potential for the treatment of cardiovascular diseases. Vasc. Health. Risk. Manag. 2012; 8: 323–31.
  27. Sjouke B., Langslet G., Ceska R., Nicholls S.J., Nissen S.E., Öhlander M. et al. Eprotirome in patients with familial hypercholesterolaemia (the AKKA trial): a randomized, double-blind, placebo- controlled phase 3 study. Lancet. Diabet. Endocrin. 2014; 2 (6): 455–63. DOI: 10.1016/S2213-8587(14)70006-3
  28. Tancevski I., Ritsch A., Eller Ph. Thyroid hormone analogues to treat dyslipidemia. Clin. Lipid. 2010; 5 (4): 477–80.
  29. Moriarty P.M., Parhofer K.G., Babirak S.P., Cornier M.A., Duell P.B., Hohenstein B. et al. Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial. Eur. Heart. J. 2016; 37 (48): 3588–95. DOI: 10.1093/eurheartj/ehw388
  30. Raal F.J., Giugliano R.P., Sabatine M.S., Koren M.J., Blom D., Seidah N.G. 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): 1086–96. DOI: 10.1194/jlr.P065334.
  31. Grützmacher P., Öhm B., Szymczak S., Dorbath C., Brzoska M., Kleinert C. Primary and secondary prevention of cardiovascular disease in patients with hyperlipoproteinemia (a). Clin. Res. Cardiol. Suppl. 2017; 12: 22–6. DOI: 10.1007/s11789-017-0090-3
  32. Schettler V.J., Neumann C.L., Peter C., Zimmermann T., Julius U., Roeseler E. et al. Impact of the German Lipoprotein Apheresis Registry (DLAR) on therapeutic options to reduce increased Lp(a) levels. Clin. Res. Cardiol. Suppl. 2015; 10: 14–20. DOI: 10.1007/s11789-015-0073-1
  33. Ferreira L., Ramos M.H., Queirós J.A., Madureira A., Silveira J., Oliveria J.C. et al. Lipoprotein apheresis in the treatment of hyperlipoproteinaemia( a) with progressive cardiovascular disease: case report and review. J. Cardiol. Clin. Res. 2017; 5 (4): 1105.
  34. Moriarty P.M., Minchew H.M., Oktona D.C. Treating lipoprotein(a)-hyperproteinemia and progressive cardiovascular disease with lipid-apheresis in North America. JACC. 2018; 71 (11): 1784. DOI: 10.1016/S0735-1097(18)32325-8
  35. Ezhov M.V., Afanasieva O.I., Il'ina L.N., Safarova M.S., Adamova I.Yu., Matchin Y.G. et al. Association of lipoprotein(a) level with short- and long-term outcomes after CABG: The role of lipoprotein apheresis. Atheroscler. Suppl. 2017; 30: 187–92. DOI: 10.1016/j.atherosclerosissup.2017.05.011
  36. Hohenstein B., Julius U., Lansberg P., Jaeger B., Mellwig K.-P., Weiss N. et al. Rationale and design of MultiSELECt: A European Multicenter Study on the Effect of Lipoprotein(a) Elimination by lipoprotein apheresis on Cardiovascular outcomes. Atheroscler. Suppl. 2017; 30: 180–6. DOI: 10.1016/j.atherosclerosissup.2017.05.009
  37. Derfler K., Steiner S., Sinzinger H. Lipoproteinapheresis: Austrian consensus on indication and performance of treatment. Wien. Klin. Wochenschr. 2015; 127 (15–16): 655–63. DOI: 10.1007/s00508-015-0833-4
  38. Stefanutti C., Thompson G.R. Lipoprotein apheresis in the management of familial hypercholesterolaemia: historical perspective and recent advances. Curr. Atheroscler. Rep. 2015; 17 (1): 465. DOI: 10.1007/s11883-014-0465-6
  39. Szczepiorkowski Z.M., Winters J.L., Bandarenko N., Kim H.C., Linenberger M.L., Marques M.B. et al. Apheresis Applications Committee of the American Society for Apheresis. Guidelines on the use of therapeutic apheresis in clinical practice-evidence- based approach from the Apheresis Applications Committee of the American Society for Apheresis. J. Clin. Apher. 2010; 25: 83–177.
  40. Temizhan A., Cetin E.H., Cetin M.S., Tak B.T. Comparison of two lipid apheresis systems in patients with homozygous familial hypercholesterolemia: a single center 3-year experience. JACC. 2018; 71 (11): 1780. DOI: 10.1016/S0735-1097 (18)32321-0
  41. Abramyan M.V., Plyushch M.G., Rogal’skaya E.A.,Nazarova E.I. Blood purification for the treatmentof lipid metabolism disorders in patients with mul-tifocal atherosclerosis. The Bulletin of BakoulevCenter for Cardiovascular Diseases.2017; 18 (S3):118 (in Russ.).
  42. Franchini M., Capuzzo E., Liumbruno G.M. Lipoprotein apheresis for the treatment of elevated circulating levels of lipoprotein(a): a critical literature review. Blood. Transfus. 2016; 14: 413–8. DOI: 10.2450/2015.0163-15
  43. Gross E., Hohenstein B., Julius U. Effects of lipoprotein apheresis on the lipoprotein(a) levels in the long run. Atheroscler. Suppl. 2015; 18: 226–32.
  44. Heigl F., Hettich R., Lotz N., Reeg H., Pflederer T., Osterkorn D. et al. Efficacy, safety, and tolerability of long-term lipoprotein apheresis in patients with LDL- or Lp(a) hyperlipoproteinemia: findings gathered from more than 36,000 treatments at one center in Germany. Atheroscler. Suppl. 2015; 18: 154–62. DOI: 10.1016/j.atherosclerosissup.2015.02.013
  45. Yaroustovsky M.B., Abramyan M.V., Plyushch M.G.,Samsonova N.N., Nazarova E.I., Stupchenko O.S.New medical technologies in cardiovascular surgery.Treatment of atherosclerosis and its complicationsby the method of H.E.L.P.-apheresis. CreativeCardiology.2009; 3 (2): 98–117 (in Russ.).
  46. Susekov A.V., Afanas’eva O.I., Adamova I.Yu.,Lyakishev A.A., Kukharchuk V.V., Pokrovskiy S.N.Use of immunosorption for selective decrease oflipoprotein(a) levels in patients with coronaryatherosclerosis. Kardiologiia. 1992; 32 (11–12):52–6 (in Russ.).
  47. Seidel D., Wieland H. Ein neues verfahren zur selektiven messung und extrakorporalen elimination von low-density lipoproteinen. J. Clin. Chem. Clinical. Biochem. 1982; 20: 684–5.
  48. Agishi T. Technical aspects of double filtration plasmapheresis. Plasma. Ther. Transfus. Technol. 1983; 4: 397–404.
  49. Klingel R., Fassbender T., Fassbender C., Gohlen B. From membrane differential filtration to lipidfiltration: technological progress in low-density lipoprotein apheresis. Ther. Apher. Dial. 2003; 7 (3): 350–8. DOI: 10.1046/j.1526-0968.2003.00062.x
  50. Bisoendial R.J., Boekholdt S.M., Vergeer M., Stroes E.S., Kastelein J.J. C-reactive protein is a mediator of cardiovascular disease. Eur. Heart. J. 2010; 31: 2087–91.
  51. Tishko V.V., Bel’skikh A.N., Tyrenko V.V., Sizov D.N.,Sokolov A.A., Zakharov M.V. et al. Effect of appli-cation of software cascade plasma filtration on lipidmetabolism in patients with lipoprotein (a)-hyper-lipoproteidemy after coronary stenting. Herald ofthe Russian Military Medical Academy.2014; 3 (47):7–11 (in Russ.).

About Authors

  • Mikhail B. Yaroustovsky, Professor, Corresponding Member of Russian Academy of Sciences, Deputy Director, Head of Department, ORCID
  • Marina V. Abramyan, Cand. Med. Sc., Leading Researcher, ORCID
  • Ekaterina A. Rogal’skaya, Cand. Med. Sc., Doctor of Clinical Laboratory Diagnostics, ORCID
  • Ekaterina V. Komardina, Junior Researcher, ORCID
  • Elena I. Nazarova, Transfusiologist, ORCID
  • David A. Grigoryan, Student, ORCID
  • Ol’ga O. Podshchekoldina, Doctor of Clinical Laboratory Diagnostics, ORCID

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery