An important cardiovascular risk factor and a clinical conundrum

Endocrinology and Metabolism Clinics of North America

Volumn 43, Issue 4, 2014, Pages 949-962

  Koschinsky, Marlys L ^a   Boffa, Michael B ^a  

^a UNIVERSITY OF WINDSOR   (Canada)

Author keywords

Apolipoprotein(a); Atherosclerosis; Coronary heart disease; Genetics; Lipoprotein(a); Oxidized phospholipids; Risk factors; Thrombosis

Indexed keywords

LIPOPROTEIN A;

ALLELE; ARTICLE; ATHEROSCLEROSIS; CARDIOVASCULAR DISEASES; CARDIOVASCULAR RISK; CHEMISTRY; CLINICAL PRACTICE; COPY NUMBER VARIATION; DIAGNOSIS; DIAGNOSTIC USE; DRUG THERAPY; GENETICS; HUMAN; LIPOPROTEIN METABOLISM; LPA GENE; METABOLISM; PROTEIN BLOOD LEVEL; PROTEIN STRUCTURE; RISK FACTOR; SINGLE NUCLEOTIDE POLYMORPHISM; THROMBOSIS;

CARDIOVASCULAR DISEASES; CHEMISTRY; DIAGNOSIS; DIAGNOSTIC USE; DRUG THERAPY; GENETICS; HUMANS; LIPOPROTEIN(A); METABOLISM; RISK FACTORS;

EID: 84964224954     PISSN: 08898529     EISSN: 15584410     Source Type: Journal    
DOI: 10.1016/j.ecl.2014.08.002     Document Type: Review

References (93)

1. Fless GM, ZumMallen ME, Scanu AM. Physicochemical properties of apolipoprotein( a) and lipoprotein(a-) derived from the dissociation of human plasma lipoprotein (a). J Biol Chem 1986;261:8712-8.
2. Koschinsky ML, CôtéGP, Gabel BR, et al. Identification of the cysteine residue in apolipoprotein(a) that mediates extracellular coupling with apolipoprotein B- J Biol Chem 1993;268:19819-25.
3. McLean JW, Tomlinson JE, Kuang WJ, et al. cDNA sequence of human apolipoprotein( a) is homologous to plasminogen. Nature 1987;330:132-7.
4. van der Hoek YY, Wittekoek ME, Beisiegel U, et al. The apolipoprotein(a) kringle IV repeats which differ from the major repeat kringle are present in variablysized isoforms. Hum Mol Genet 1993;2:361-6.
5. Marcovina SM, Albers JJ, Wijsman E, et al. Differences in Lp[a] concentrations and apo[a] polymorphs between black and white Americans. J Lipid Res 1996; 37:2569-85.
6. Lackner C, Cohen JC, Hobbs HH. Molecular definition of the extreme size polymorphism in apolipoprotein(a). Hum Mol Genet 1993;2:933-40.
7. Marcovina SM, Gaur VP, Albers JJ. Biological variability of cholesterol, triglyceride, low-and high-density lipoprotein cholesterol, lipoprotein(a), and apolipoproteins A-I and B. Clin Chem 1994;40:574-8.
8. Utermann G. Genetic architecture and evolution of the lipoprotein(a) trait. Curr Opin Lipidol 1999;10:133-41.
9. Kronenberg F, Utermann G. Lipoprotein(a): resurrected by genetics. J Intern Med 2013;273:6-30.
10. White AL, Guerra B, Lanford RE. Influence of allelic variation on apolipoprotein( a) folding in the endoplasmic reticulum. J Biol Chem 1997;272:5048-55.
11. Brewer HB Jr. Effectiveness of diet and drugs in the treatment of patients with elevated Lp(a) levels. In: Scanu AM, editor. Lipoprotein(a). New York: NY Academic Press, Inc; 1990. p. 211-20.
12. Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, et al. Genetically elevated lipoprotein( a) and increased risk of myocardial infarction. JAMA 2009;301:2331-9.
13. Clarke R, Peden JF, Hopewell JC, et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med 2009;361:2518-28.
14. IBC 50K CAD Consortium. Large-scale gene-centric analysis identifies novel variants for coronary artery disease. PLoS Genet 2011;7:e1002260.
15. Boerwinkle E, Leffert CC, Lin J, et al. Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations. J Clin Invest 1992;90:52-60.
16. DubéJB, Boffa MB, Hegele RA, et al. Lipoprotein(a): more interesting than ever after 50 years. Curr Opin Lipidol 2012;23:133-40.
17. Lanktree MB, Anand SS, Yusuf S, et al. Comprehensive analysis of genomic variation in the LPA locus and its relationship to plasma lipoprotein(a) in South Asians, Chinese, and European Caucasians. Circ Cardiovasc Genet 2010;3:39-46.
18. Luke MM, Kane JP, Liu DM, et al. A polymorphism in the protease-like domain of apolipoprotein(a) is associated with severe coronary artery disease. Arterioscler Thromb Vasc Biol 2007;27:2030-6.
19. Li ZG, Li G, Zhou YL, et al. Lack of association between lipoprotein(a) genetic variants and subsequent cardiovascular events in Chinese Han patients with coronary artery disease after percutaneous coronary intervention. Lipids Health Dis 2013;12:127.
20. Rader DJ, Cain W, Ikewaki K, et al. The inverse association of plasma lipoprotein( a) concentrations with apolipoprotein(a) isoform size is not due to differences in Lp(a) catabolism but to differences in production rate. J Clin Invest 1994;93:2758-63.
21. Cain WJ, Millar JS, Himebauch AS, et al. Lipoprotein [a] is cleared from the plasma primarily by the liver in a process mediated by apolipoprotein [a]. J Lipid Res 2005;46:2681-91.
22. Tam SP, Zhang X, Koschinsky ML. Interaction of a recombinant form of apolipoprotein[ a] with human fibroblasts and with the human hepatoma cell line HepG2. J Lipid Res 1996;37:518-33.
23. Rader DJ, Mann WA, Cain W, et al. The low density lipoprotein receptor is not required for normal catabolism of Lp(a) in humans. J Clin Invest 1995;95: 1403-8.
24. Gonbert S, Malinsky S, Sposito AC, et al. Atorvastatin lowers lipoprotein(a) but not apolipoprotein(a) fragment levels in hypercholesterolemic subjects at high cardiovascular risk. Atherosclerosis 2002;164:305-11.
25. van Wissen S, Smilde TJ, Trip MD, et al. Long term statin treatment reduces lipoprotein( a) concentrations in heterozygous familial hypercholesterolaemia. Heart 2003;89:893-6.
26. Takagi H, Umemoto T. Atorvastatin decreases lipoprotein(a): a meta-analysis of randomized trials. Int J Cardiol 2012;154:183-6.
27. Desai NR, Kohli P, Giugliano RP, et al. 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;128:962-9.
28. McKenney JM, Koren MJ, Kereiakes DJ, et al. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am Coll Cardiol 2012;59:2344-53.
29. Yang XP, Amar MJ, Vaisman B, et al. Scavenger receptor-BI is a receptor for lipoprotein( a). J Lipid Res 2013;54:2450-7.
30. Boffa MB, Koschinsky ML. Update on lipoprotein(a) as a cardiovascular risk factor and mediator. Curr Atheroscler Rep 2013;15:360.
31. Anglês-Cano E, de la Peña Dîaz A, Loyau S. Inhibition of fibrinolysis by lipoprotein( a). Ann N Y Acad Sci 2001;936:261-75.
32. Seimon TA, Nadolski MJ, Liao X, et al. Atherogenic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticulum stress. Cell Metab 2010;12:467-82.
33. Cho T, Jung Y, Koschinsky ML. Apolipoprotein(a), through its strong lysinebinding site in KIV(10'), mediates increased endothelial cell contraction and permeability via a Rho/Rho kinase/MYPT1-dependent pathway. J Biol Chem 2008;283:30503-12.
34. Cho T, Romagnuolo R, Scipione C, et al. Apolipoprotein(a) stimulates nuclear translocation of b-catenin: a novel pathogenic mechanism for lipoprotein(a). Mol Biol Cell 2013;24:210-21.
35. Tsimikas S, Mallat Z, Talmud PJ, et al. Oxidation-specific biomarkers, lipoprotein( a), and risk of fatal and nonfatal coronary events. J Am Coll Cardiol 2010; 56:946-55.
36. Tsimikas S, Bergmark C, Beyer RW, et al. Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes. J Am Coll Cardiol 2003;41:360-70.
37. Bergmark C, Dewan A, Orsoni A, et al. A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma. J Lipid Res 2008;49:2230-9.
38. Leibundgut G, Scipione C, Yin H, et al. Determinants of binding of oxidized phospholipids on apolipoprotein (a) and lipoprotein (a). J Lipid Res 2013;54: 2815-30.
39. Hughes SD, Lou XJ, Ighani S, et al. Lipoprotein(a) vascular accumulation in mice. In vivo analysis of the role of lysine binding sites using recombinant adenovirus. J Clin Invest 1997;100:1493-500.
40. Deshmane SL, Kremlev S, Amini S, et al. Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res 2009;29:313-26.
41. Wiesner P, Tafelmeier M, Chittka D, et al. MCP-1 binds to oxidized LDL and is carried by lipoprotein(a) in human plasma. J Lipid Res 2013;54:1877-83.
42. O'Donoghue ML, Morrow DA, Tsimikas S, et al. Lipoprotein(a) for risk assessment in patients with established coronary artery disease. J Am Coll Cardiol 2014;63:520-7.
43. 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 Thromb Vasc Biol 2013;33:2902-8.
44. 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;129:635-42.
45. Thanassoulis G, Campbell CY, Owens DS, et al. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med 2013;368:503-12.
46. Kamstrup PR, Tybjærg-Hansen A, Nordestgaard BG. Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population. J Am Coll Cardiol 2014;63:470-7.
47. Kamstrup PR, Tybjærg-Hansen A, Nordestgaard BG. Genetic evidence that lipoprotein( a) associates with atherosclerotic stenosis rather than venous thrombosis. Arterioscler Thromb Vasc Biol 2012;32:1732-41.
48. Danik JS, Buring JE, Chasman DI, et al. Lipoprotein(a), polymorphisms in the LPA gene, and incident venous thromboembolism among 21483 women. J Thromb Haemost 2013;11:205-8.
49. Helgadottir A, Gretarsdottir S, Thorleifsson G, et al. Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism. J Am Coll Cardiol 2012;60:722-9.
50. Undas A, Cieśla-Dul M, Drazkiewicz T, et al. Altered fibrin clot properties are associated with residual vein obstruction: effects of lipoprotein(a) and apolipoprotein( a) isoform. Thromb Res 2012;130:e184-7.
51. Rowland CM, Pullinger CR, Luke MM, et al. Lipoprotein (a), LPA Ile4399Met, and fibrin clot properties. Thromb Res 2014;133:863-7.
52. Kardys I, Oemrawsingh RM, Kay IP, et al. Lipoprotein(a), interleukin-10, C-reactive protein, and 8-year outcome after percutaneous coronary intervention. Clin Cardiol 2012;35:482-9.
53. Greif M, Arnoldt T, von Ziegler F, et al. Lipoprotein (a) is independently correlated with coronary artery calcification. Eur J Intern Med 2013;24:75-9.
54. Sung KC, Wild SH, Byrne CD. Lipoprotein (a), metabolic syndrome and coronary calcium score in a large occupational cohort. Nutr Metab Cardiovasc Dis 2013;23:1239-46.
55. Sharma A, Kasim M, Joshi PH, et al. Abnormal lipoprotein(a) levels predict coronary artery calcification in Southeast Asians but not in Caucasians: use of noninvasive imaging for evaluation of an emerging risk factor. J Cardiovasc Transl Res 2011;4:470-6.
56. Erbel R, Lehmann N, Churzidse S, et al. Gender-specific association of coronary artery calcium and lipoprotein parameters: the Heinz Nixdorf recall study. Atherosclerosis 2013;229:531-40.
57. Qasim AN, Martin SS, Mehta NN, et al. Lipoprotein(a) is strongly associated with coronary artery calcification in type-2 diabetic women. Int J Cardiol 2011;150: 17-21.
58. Brown WV, Ballantyne CM, Jones PH, et al. Management of Lp(a). J Clin Lipidol 2010;4:240-7.
59. Hopewell JC, Seedorf U, Farrall M, et al. Impact of lipoprotein(a) levels and apolipoprotein( a) isoform size on risk of coronary heart disease. J Intern Med 2013; 276(3):260-8. http://dx.doi.org/10.1111/joim.12187.
60. Anderson TJ,Grêgoire J,HegeleRA, et al.2012 update of theCanadianCardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol 2013;29:151-67.
61. Virani SS, Brautbar A, Davis BC, et al. Associations between lipoprotein(a) levels and cardiovascular outcomes in black and white subjects: the atherosclerosis risk in communities (ARIC) study. Circulation 2012;125:241-9.
62. Kamstrup PR, Tybjærg-Hansen A, Nordestgaard BG. Extreme lipoprotein(a) levels and improved cardiovascular risk prediction. J Am Coll Cardiol 2013; 61:1146-56.
63. Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J 2010;31:2844-53.
64. Greenland P, Alpert JS, Beller GA, et al. American College of Cardiology Foundation; AmericanHeartAssociation. 2010ACCF/AHAguidelineforassessment of cardiovascular risk in asymptomatic adults. J Am Coll Cardiol 2010;56:e50-103.
65. Kostner KM, März W, Kostner GM. When should we measure lipoprotein (a)? Eur Heart J 2013;34:3268-76.
66. Marcovina SM, Koschinsky ML, Albers JJ, et al. Report of the National Heart, Lung, and Blood Institute workshop on lipoprotein(a) and cardiovascular disease: recent advances and future directions. Clin Chem 2003;49:1785-96.
67. Seman LJ, DeLuca C, Jenner JL, et al. Lipoprotein(a)-cholesterol and coronary heart disease in the Framingham heart study. Clin Chem 1999;45:1039-46.
68. Konerman M, Kulkarni K, Toth PP, et al. Lipoprotein(a) particle concentration and lipoprotein(a) cholesterol assays yield discordant classification of patients into four physiologically discrete groups. J Clin Lipidol 2012;6:368-73.
69. Lamon-Fava S, Marcovina SM, Albers JJ, et al. Lipoprotein(a) levels, apo(a) isoform size, and coronary heart disease risk in the Framingham Offspring Study. J Lipid Res 2011;52:1181-7.
70. Jacobson TA. Lipoprotein(a), cardiovascular disease, and contemporary management. Mayo Clin Proc 2013;88:1294-311.
71. Nicholls SJ, Tang WH, Scoffone H, et al. Lipoprotein(a) levels and long-term cardiovascular risk in the contemporary era of statin therapy. J Lipid Res 2010;51: 3055-61.
72. 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;62:1575-9.
73. Chasman DI, Shiffman D, Zee RY, et al. Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy. Atherosclerosis 2009;203:371-6.
74. 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 Pract Cardiovasc Med 2009;6: 229-39.
75. Leebmann J, Roeseler E, Julius U, et al. Lipoprotein apheresis in patients with maximally tolerated lipid-lowering therapy, lipoprotein(a)-hyperlipoproteinemia, and progressive cardiovascular disease: prospective observational multicenter study. Circulation 2013;128:2567-76.
76. Safarova MS, Ezhov MV, Afanasieva OI, et al. Effect of specific lipoprotein(a) apheresis on coronary atherosclerosis regression assessed by quantitative coronary angiography. Atheroscler Suppl 2013;14:93-9.
77. Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011;365: 2255-67.
78. Besseling J, Hovingh GK, Stroes ES. Antisense oligonucleotides in the treatment of lipid disorders: pitfalls and promises. Neth J Med 2013;71:118-22.
79. Raal FJ, Santos RD, Blom DJ, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet 2010;375:998-1006.
80. Stein EA, Dufour R, Gagne C, et al. Apolipoprotein B synthesis inhibition with mipomersen in heterozygous familial hypercholesterolemia: results of a randomized, double-blind, placebo-controlled trial to assess efficacy and safety as add-on therapy in patients with coronary artery disease. Circulation 2012;126: 2283-92.
81. McGowan MP, Tardif JC, Ceska R, et al. Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy. PLoS One 2012;7:e49006.
82. Thomas GS, Cromwell WC, Ali S, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, reduces atherogenic lipoproteins in patients with severe hypercholesterolemia at high cardiovascular risk: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol 2013;62:2178-84.
83. Visser ME, Wagener G, Baker BF, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial. Eur Heart J 2012;33:1142-9.
84. Merki E, Graham M, Taleb A, et al. Antisense oligonucleotide lowers plasma levels of apolipoprotein (a) and lipoprotein (a) in transgenic mice. J Am Coll Cardiol 2011;57:1611-21.
85. Cannon CP, Shah S, Dansky HM, et al. Safety of anacetrapib in patients with or at high risk for coronary heart disease. N Engl J Med 2010;363:2406-15.
86. Dias CS, Shaywitz AJ, Wasserman SM, et al. Effects of AMG 145 on low-density lipoprotein cholesterol levels: results from 2 randomized, double-blind, placebocontrolled, ascending-dose phase 1 studies in healthy volunteers and hypercholesterolemic subjects on statins. J Am Coll Cardiol 2012;60:1888-98.
87. Raal F, Scott R, Somaratne R, et al. Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/ kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the reduction of LDL-C with PCSK9 Inhibition in heterozygous familial hypercholesterolemia disorder (RUTHERFORD) randomized trial. Circulation 2012;126:2408-17.
88. Sullivan D, Olsson AG, Scott R, et al. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial. JAMA 2012;308:2497-506.
89. Roth EM, McKenney JM, Hanotin C, et al. Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N Engl J Med 2012;367: 1891-900.
90. Cuchel M, Bloedon LT, SzaparyPO, et al. Inhibition ofmicrosomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med 2007;356:148-56.
91. Cuchel M, Meagher EA, du Toit Theron H, et al. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet 2013; 381:40-6.
92. Samaha FF, McKenney J, Bloedon LT, et al. Inhibition of microsomal triglyceride transfer protein alone or with ezetimibe in patients with moderate hypercholesterolemia. Nat Clin Pract Cardiovasc Med 2008;5:497-505.
93. Schultz O, Oberhauser F, Saech J, et al. Effects of inhibition of interleukin-6 signalling on insulin sensitivity and lipoprotein (a) levels in human subjects with rheumatoid diseases. PLoS One 2010;5:e14328.