1887
Volume 2014, Issue 1
  • ISSN: 2305-7823
  • EISSN:

Abstract

It is increasingly recognised that lipoprotein(a) [Lp(a)], an inherited, genetically-determined form of LDL-cholesterol, is an independent cardiovascular risk factor and predictor of adverse cardiovascular outcomes. Lp(a) is felt to increase cardiovascular risk via its pro-thrombotic effect and by enhancing intimal lipoprotein deposition. Lipoprotein apheresis is currently the most effective treatment for raised Lp(a). There is a growing body of evidence suggesting that aggressively lowering raised Lp(a) may improve cardiovascular and clinical outcomes, although much more research is required in this field.

Angina which is refractory to conventional medical therapy and revascularisation, is extremely challenging to manage. Treatment options for such patients remain very limited. We describe the case of a patient with refractory angina and raised lipoprotein(a) in whom aggressive reduction of Lp(a) with lipoprotein apheresis successfully ameliorated the progression of coronary stenosis and provided effective and durable relief of angina symptoms. In our centre, we are currently conducting a prospective, randomised controlled cross-over study of patients with refractory angina and raised Lp(a), randomised to undergoing lipoprotein apheresis or ‘sham’ apheresis with assessment of myocardial perfusion, carotid atherosclerosis, endothelial vascular function, thrombogenesis, oxidised phospholipids and their antibodies, exercise capacity, angina symptoms and quality of life at the beginning and end of treatment.

Loading

Article metrics loading...

/content/journals/10.5339/gcsp.2014.3
2014-06-01
2024-04-24
Loading full text...

Full text loading...

/deliver/fulltext/gcsp/2014/1/gcsp.2014.3.html?itemId=/content/journals/10.5339/gcsp.2014.3&mimeType=html&fmt=ahah

References

  1. Berg K. A new serum type system in man: the Lp system. Acta Pathol Microbiol Scand. 1963; 59::369382.
    [Google Scholar]
  2. Cremer P, Nagel D, Labrot B, Mann H, Muche R, Elster H, Seidel D. Lipoprotein Lp(a) as a predictor of myocardial infarction in comparison to fibrinogen, LDL cholesterol and other risk factors: results from the Prospective Gottingen Risk Incidence and Prevalance Study (GRIPS). Eur J Clin Invest. 1994; 24:7:444453.
    [Google Scholar]
  3. Danesh J, Collins R, Peto R. Lipoprotein(a) and coronary heart disease. Meta-analysis of prospective studies. Circulation. 2000; 102:10:10821085.
    [Google Scholar]
  4. Nordestgaard BG, Chapman MJ, Ray K, Bore J, Andreotti F, Watts GF, Ginsberg H. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010; 31::28442853.
    [Google Scholar]
  5. Cremer P, Nagel D, Labrot B, Mann H, Muche R, Elster H, Seidel D. Lipoprotein Lp(a) as predictor of myocardial infarction in comparison to fibrinogen, LDL cholesterol and other risk factors: results from the prospective Göttingen Risk Incidence and Prevalence Study (GRIPS). Eur J Clin Invest. 1994; 24::444453.
    [Google Scholar]
  6. Bennet A, Di Angelantonio E, Erqou S, Eiriksdottir G, Sigurdsson G, Woodward M, Rumley A, Lowe GD, Danesh J, Gudnason V. Lipoprotein(a) levels and risk of future coronary heart disease: large scale prospective data. Arch Intern Med. 2008; 168::598608.
    [Google Scholar]
  7. Emerging Risk Factors Collaboration , Erqou S, Kaptoge S, Perry PL, Di Angelantonio E, Thompson A, White IR, Marcovina SM, Collins R, Thompson SG, Danesh J. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke and non-vascular mortality. JAMA. 2009; 302::412423.
    [Google Scholar]
  8. Kamstrup PR, Benn M, Tybjaerg-Hansen A, Nordestgaard BG. Extreme lipoprotein(a) levels and the risk of myocardial infarction in the general population: the Copenhagen City Heart Study. Circulation. 2008; 117::176184.
    [Google Scholar]
  9. Enas EA, Senthilkumar A, Chacko V, Puthumana N. Dyslipidemia among Indo-Asians: strategies for identification and management. Brit J Diabetes Vasc Dis. 2005; 5::8190.
    [Google Scholar]
  10. Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D, Patsch W, Atherosclerosis Risk in Communities Study Group . Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: The Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2001; 104:10:11081113.
    [Google Scholar]
  11. Brown SA, Hutchinson R, Morrisett J, Boerwinkle E, Davis CE, Gotto AM Jr, Patsch W. Plasma lipid, lipoprotein cholesterol, and apoprotein distributions in selected US communities. The Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb. 1993; 13:8:11391158.
    [Google Scholar]
  12. Enas EA, Chacko V, Senthilkumar A, Puthumana N, Mohan V. Elevated lipoprotein(a)—a genetic risk factor for premature vascular disease in people with and without standard risk factors: a review. Dis Mon. 2006; 52::550.
    [Google Scholar]
  13. Cobbaert C, Kesteloot H. Serum lipoprotein(a) levels in racially different populations. Am J Epidemiol. 1992; 136:4:441449.
    [Google Scholar]
  14. Anand SS, Yusuf S, Vuksan V, Devanesen S, Teo KK, Montague PA, Kelemen L, Yi C, Lonn E, Gerstein H, Hegele RA, McQueen M. Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the Study of Health Assessment and Risk in Ethnic groups (SHARE). Lancet 2000; 356:9226:279284.
    [Google Scholar]
  15. Nielson LB. Atherogenicity of lipoprotein(a) and oxidised low density lipoprotein: an insight from in-vivo studies of arterial wall influx, degradation and efflux. Atherosclerosis 1999; 143::229243.
    [Google Scholar]
  16. Lundstam U, Hurt-Camejo E, Olsson G, Sartipy P, Camejo G, Wiklund O. Proteoglycans contribution to association of Lp(a) and LDL with smooth muscle cell extracellular matrix. Arterioscler Thromb Vasc Biol. 1999; 19::11621167.
    [Google Scholar]
  17. Bdeir K, Cane W, Canziani G, Chaiken I, Weisel J, Koschinsky ML, Lawn RM, Bannerman PG, Sachais BS, Kuo A, Hancock MA, Tomaszewski J, Raghunath PN, Ganz T, Higazi AA, Cines DB. Defensin promotes the binding of lipoprotein(a) to vascular matrix. Blood 1999; 94::20072019.
    [Google Scholar]
  18. Bergmark C, Dewan A, Orsoni A, Merki E, Miller ER, Shin MJ, Binder CJ, Hörkkö S, Krauss RM, Chapman MJ, Witztum JL, Tsimikas S. A novel function of lipoprotein(a) as a preferential carrier of oxidised phospholipids in human plasma. J Lipid Res. 2008; 49::22302239.
    [Google Scholar]
  19. Tsimikas S, Mallat Z, Talmud PJ, Kastelein JJ, Wareham NJ, Sandhu MS, Miller ER, Benessiano J, Tedgui A, Witztum JL, Khaw KT, Boekholdt SM. Oxidation-specific biomarkers, lipoprotein(a) and risk of fatal and non-fatal coronary events. J Am Coll Cardiol. 2010; 56::946955.
    [Google Scholar]
  20. Rouy D, Grailhe P, Nigon F, Chapman J, Angles-Cano E. Lipoprotein(a) impairs generation of plasmin by fibrin-bound tissue-type plasminogen activator. In vitro studies in a plasma milieu. Arterioscler Thromb. 1991; 11::629638.
    [Google Scholar]
  21. Caplice NM, Panetta C, Peterson TE, Kleppe LS, Mueske CS, Kostner GM, Broze GJ Jr, Simari RD. Lipoprotein(a) binds and inactivates tissue factor pathway inhibitor: a novel link between lipoproteins and thrombosis. Blood 2001; 98::29802987.
    [Google Scholar]
  22. Clarke R, Peden JF, Hopewell JC, Kyriakou T, Goel A, Heath SC, Parish S, Barlera S, Franzosi MG, Rust S, Bennett D, Silveira A, Malarstig A, Green FR, Lathrop M, Gigante B, Leander K, de Faire U, Seedorf U, Hamsten A, Collins R, Watkins H, Farrall M, PROCARDIS Consortium . Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med. 2009; 361:26:25182528.
    [Google Scholar]
  23. Bambauer R, Olbricht CJ, Schoeppe E. Low-density lipoprotein apheresis for prevention and regression of atherosclerosis: clinical results. Ther Apher. 1997; 1::242248.
    [Google Scholar]
  24. Bohl S, Kassner U, Eckardt R, Utz W, Mueller-Nordhorn J, Busjahn A, Thomas HP, Abdel-Aty H, Klingel R, Marcovina S, Dietz R, Steinhagen-Thiessen E, Schulz-Menger J, Vogt A. Single lipoprotein apheresis session improves cardiac microvascular function in patients with elevated lipoprotein(a): detection by stress/rest perfusion magnetic resonance imaging. Ther Apher Dial. 2009; 13::129137.
    [Google Scholar]
  25. Chapman MJ, Redfern JS, McGovern ME, Giral P. Niacin and fibrates in atherogenic dyslipidemia: pharmacotherapy to reduce cardiovascular risk. Pharmacol Ther. 2010; 126::314345.
    [Google Scholar]
  26. Pan J, Lin M, Kesala RL, Van J, Charles MA. Niacin treatment of the atherogenic lipid profile and Lp(a) in diabetes. Diabetes Obes Metab. 2002; 4:4:255261.
    [Google Scholar]
  27. 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; 34:17:12791291.
    [Google Scholar]
  28. Borberg H. Comparison of different Lp(a) elimination techniques: A retrospective evaluation. Transfus Apher Sci. 2009; 41::6165.
    [Google Scholar]
  29. Stefanutti C, Vivenzio A, Di Giacomo S, Mazzarella B, Ferraro PM, Abbolito S. Treatment of symptomatic hyperLp(a) lipidaemia with LDL-apheresis vs. usual care. Transfus Apher Sci. 2010; 42:1:2126.
    [Google Scholar]
  30. Mellwig KP, Baller D, Gleichmann U, Moll D, Betker S, Weise R, Notohamiprodjo G. Improvement of coronary vasodilatation capacity through single LDL apheresis. Atherosclerosis 1998; 139:1:173178.
    [Google Scholar]
  31. Sachais BS, Katz J, Ross J, Rader DJ. Long term effects of LDL apheresis in patients with severe hypercholesterolaemia. J Clin Apher. 2005; 20:4:252255.
    [Google Scholar]
  32. Otto C, Geiss HC, Laubach E, Schwandt P. Effects of direct adsorption of lipoprotein apheresis on lipoproteins, low-density lipoprotein subtypes and hemorheology in hypercholesterolemic patients with coronary artery disease. Ther Apher. 2002; 6:2:130135.
    [Google Scholar]
  33. Thompson GR, Catapano A, Saheb S, Atassi-Dumont M, Barbir M, Eriksson M, Paulweber B, Sijbrands E, Stalenhoef AF, Parhofer KG. Severe hypercholesterolaemia; therapeutic goals and eligibility criteria for LDL apheresis in Europe. Curr Opin Lipidol. 2010; 21:6:492498.
    [Google Scholar]
  34. Merki E, Graham M, Taleb A, Leibundgut G, Yang X, Miller ER, Fu W, Mullick AE, Lee R, Willeit P, Crooke RM, Witztum JL, Tsimikas S. Antisense oligonucleotide lowers plasma levels of apolipoprotein(a) and lipoprotein (a) in transgenic mice. J Am Coll Cardiol. 2011; 57:15:16111621.
    [Google Scholar]
  35. Desai NR, Kohli P, Giugliano RP, O'Donoghue ML, Somaratne R, Zhou J, Hoffman EB, Huang F, Rogers WJ, Wasserman SM, Scott R, Sabatine MS. AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type 9, significantly reduces lipoprotein(a) in hypercholesterolemic patients receiving statin therapy: an analysis from the LDL-C Assessment with Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined With Statin Therapy (LAPLACE)-Thrombolysis in Myocardial Infarction (TIMI) 57 Trial. Circulation. 2013; 128:9:962969.
    [Google Scholar]
  36. Maher V, Brown G, Marcovina S, Hillger L, Zhao X, Albers J. Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein(a). JAMA 1995; 274:22:17711774.
    [Google Scholar]
  37. Jaeger BR, Richter Y, Nagel D, Heigl F, Vogt A, Roeseler E, Parhofer K, Ramlow W, Koch M, Utermann G, Labarrere CA, Seidel D, Group of Clinical Investigators . Longitudinal cohort study on the effectiveness of apheresis treatment to reduce high lipoprotein(a) levels and prevent major adverse coronary events. Nat Clin Pract Cardiovasc Med. 2009; 6:3:229239.
    [Google Scholar]
  38. Safarova MS, Ezhov MV, Afanasieva OI, Matchin YG, Atanesyan RV, Adamova IY, Utkina EA, Konovalov GA, Pokrovsky SN. Effect of specific lipoprotein(a) apheresis on coronary atherosclerosis regression assessed by quantitative coronary angiography. Atheroscler Suppl. 2013; 14:1:9399.
    [Google Scholar]
  39. Kim MC, Kini A, Sharma SK. Refractory angina pectoris. Mechanism and therapeutic options. J Am Coll Cardiol. 2002; 39:6:923934.
    [Google Scholar]
  40. Mannheimer C, Camici P, Chester MR, Collins A, DeJongste M, Eliasson T, Follath F, Hellemans I, Herlitz J, Lüscher T, Pasic M, Thelle D. The problem of chronic refractory angina; report from the ESC joint study group on the treatment of refractory angina. Eur Heart J. 2002; 23:5:355370.
    [Google Scholar]
  41. DeJongste MJL, Tio RA, Foreman RD. Chronic therapeutically refractory angina pectoris. Heart 2004; 90::225230.
    [Google Scholar]
  42. Weiner L, Cox W. Influence of stellate ganglion block on angina pectoris and the post-exercise electrocardiogram. Am J Med Sci. 1966; 252::289295.
    [Google Scholar]
  43. Mulcahy D, Knight C, Stables R, Fox K. Lasers, burns, cuts, tingles and pumps: a consideration of alternative treatments for intractable angina. Br Heart J. 1994; 71::406407.
    [Google Scholar]
  44. Andersen C, Hole P. Long-term home treatment with epidural analgesia does not affect later spinal cord stimulation in patients with otherwise intractable angina pectoris. Clin J Pain. 1998; 14:4:315319.
    [Google Scholar]
  45. Arora RR, Chou TM, Jain D, Fleishman B, Crawford L, McKiernan T, Nesto RW. The multicenter study of enhanced external counterpulsation (MUST-EECP): effect of EECP on exercise-induced myocardial ischaemia and angina episodes. J Am Coll Cardiol. 1999; 33:7:18331840.
    [Google Scholar]
  46. Lauer B, Junghans U, Stahl F, Kluge R, Oesterle SN, Schuler G. Catheter- based percutaneous myocardial laser revascularisation in patients with end-stage coronary artery disease. J Am Coll Cardiol. 1999; 34:6:16631670.
    [Google Scholar]
  47. Ibrahim M, Ussen B, Pottle A, Barbir M. Low-density lipoprotein apheresis is effective in reducing lipoprotein(a) levels and in improving symptoms in a patient with refractory angina secondary to accelerated coronary artery disease. J Clin Lipidol. 2012; 6:2:192194.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.5339/gcsp.2014.3
Loading
/content/journals/10.5339/gcsp.2014.3
Loading

Data & Media loading...

  • Article Type: Review Article
Keyword(s): Ischaemic heart diseaseLipoprotein ApheresisLipoprotein(a) and Refractory angina
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error