Lipoprotein (a) as a cause of cardiovascular disease: Insights from epidemiology, genetics, and biology

Journal of Lipid Research

Volumn 57, Issue 11, 2016, Pages 1953-1975

  Nordestgaard, Børge G ^a,b   Langsted, Anne ^a,b  

^a GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

Apolipoproteins; Atherosclerosis; Cholesterol; Dyslipidemias; Infammation; Lipids; Low density lipoprotein; Plasminogen; Vascular biology

Indexed keywords

APOLIPOPROTEIN A; APOLIPOPROTEIN B; LIPOPROTEIN A; LOW DENSITY LIPOPROTEIN RECEPTOR;

AORTA VALVE STENOSIS; BLOOD CLOTTING; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CAUSALITY; CHILDBIRTH; COPY NUMBER VARIATION; CORONARY ARTERY ATHEROSCLEROSIS; CORONARY ARTERY OBSTRUCTION; EPIDEMIOLOGICAL DATA; FAMILIAL HYPERCHOLESTEROLEMIA; FIBRINOLYSIS; GENETIC ANALYSIS; GENETIC VARIATION; GENOTYPE; HEART FAILURE; HEART INFARCTION; HUMAN; INFECTION; INJURY; ISCHEMIC HEART DISEASE; KRINGLE DOMAIN; LIPOPROTEIN BLOOD LEVEL; MENDELIAN RANDOMIZATION ANALYSIS; MOLECULAR BIOLOGY; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; THROMBOSIS; VENOUS THROMBOEMBOLISM; WOUND HEALING; AORTIC VALVE STENOSIS; BLOOD; CARDIOVASCULAR DISEASES; GENETIC PREDISPOSITION; GENETICS; MYOCARDIAL INFARCTION; PATHOLOGY; RISK FACTOR;

AORTIC VALVE STENOSIS; CARDIOVASCULAR DISEASES; DNA COPY NUMBER VARIATIONS; GENETIC PREDISPOSITION TO DISEASE; HUMANS; LIPOPROTEIN(A); MYOCARDIAL INFARCTION; RISK FACTORS;

EID: 84994045135     PISSN: 00222275     EISSN: 15397262     Source Type: Journal    
DOI: 10.1194/jlr.R071233     Document Type: Review

References (281)

1. Berg, K. 1963. A new serum type system in man-the LP system. Acta Pathol. Microbiol. Scand. 59: 369-382.
2. Berg, K., and J. Mohr. 1963. Genetics of the LP system. Acta Genet. Stat. Med. 13: 349-360.
3. Mohr, J., and K. Berg. 1963. Genetics of the LP serum types: associations and linkage relations. Acta Genet. Stat. Med. 13: 343-348.
4. McLean, J. W., J. E. Tomlinson, W. J. Kuang, D. L. Eaton, E. Y. Chen, G. M. Fless, A. M. Scanu, and R. M. Lawn. 1987. cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature. 330: 132-137.
5. Lawn, R. M. 1992. Lipoprotein(a) in heart disease. Sci. Am. 266: 54-60.
6. Kamstrup, P. R., A. Tybjaerg-Hansen, R. Steffensen, and B. G. Nordestgaard. 2009. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 301: 2331-2339.
7. Erqou, S., S. Kaptoge, P. L. Perry, A. E. Di, A. Thompson, I. R. White, S. M. Marcovina, R. Collins, S. G. Thompson, and J. Danesh. 2009. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 302: 412-423.
8. Clarke, R., J. F. Peden, J. C. Hopewell, T. Kyriakou, A. Goel, S. C. Heath, S. Parish, S. Barlera, M. G. Franzosi, S. Rust, et al. 2009. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N. Engl. J. Med. 361: 2518-2528.
9. Nordestgaard, B. G., M. J. Chapman, K. Ray, J. Boren, F. Andreotti, G. F. Watts, H. Ginsberg, P. Amarenco, A. Catapano, O. S. Descamps, et al. 2010. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur. Heart J. 31: 2844-2853.
10. Thanassoulis, G., C. Y. Campbell, D. S. Owens, J. G. Smith, A. V. Smith, G. M. Peloso, K. F. Kerr, S. Pechlivanis, M. J. Budoff, T. B. Harris, et al. 2013. Genetic associations with valvular calcification and aortic stenosis. N. Engl. J. Med. 368: 503-512.
11. Kamstrup, P. R., A. Tybjaerg-Hansen, and B. G. Nordestgaard. 2014. Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population. J. Am. Coll. Cardiol. 63: 470-477.
12. Brown, M. S., and J. L. Goldstein. 1987. Plasma lipoproteins: teaching old dogmas new tricks. Nature. 330: 113-114.
13. Utermann, G. 1989. The mysteries of lipoprotein(a). Science. 246: 904-910.
14. Utermann, G. 2001. Lipoprotein(a). In The Metabolic and Molecular Bases of Inherited Disease. 8th edition. C. R. Scriver, A. L. Beaudet, W. S. Sly, et al., editors. McGraw-Hill, New York. 2753-2787.
15. Scanu, A. M., and G. M. Fless. 1990. Lipoprotein (a). Heterogeneity and biological relevance. J. Clin. Invest. 85: 1709-1715.
16. Scanu, A. M. 1990. Lipoprotein(a). Academic Press, Inc., San Diego.
17. Dahlén, G. H. 1994. Lp(a) lipoprotein in cardiovascular disease. Atherosclerosis. 108: 111-126.
18. Rader, D. J., J. M. Hoeg, and H. B. Brewer, Jr. 1994. Quantitation of plasma apolipoproteins in the primary and secondary prevention of coronary artery disease. Ann. Intern. Med. 120: 1012-1025.
19. Howard, G. C., and S. V. Pizzo. 1993. Lipoprotein(a) and its role in atherothrombotic disease. Lab. Invest. 69: 373-386.
20. Mbewu, A. D., and P. N. Durrington. 1990. Lipoprotein (a): structure, properties and possible involvement in thrombogenesis and atherogenesis. Atherosclerosis. 85: 1-14.
21. Nielsen, L. B. 1999. Atherogenecity of lipoprotein(a) and oxidized low density lipoprotein: insight from in vivo studies of arterial wall influx, degradation and efflux. Atherosclerosis. 143: 229-243.
22. Kamstrup, P. R. 2010. Lipoprotein(a) and ischemic heart disease-A causal association? A review. Atherosclerosis. 211: 15-23.
23. Danesh, J., R. Collins, and R. Peto. 2000. Lipoprotein(a) and coronary heart disease. Meta-analysis of prospective studies. Circulation. 102: 1082-1085.
24. Erqou, S., A. Thompson, A. E. Di, D. Saleheen, S. Kaptoge, S. Marcovina, and J. Danesh. 2010. Apolipoprotein(a) isoforms and the risk of vascular disease: systematic review of 40 studies involving 58,000 participants. J. Am. Coll. Cardiol. 55: 2160-2167.
25. Nordestgaard, B. G., and A Tybjaerg-Hansen. 2011. Genetic determinants of LDL, lipoprotein(a), triglyceride-rich lipoproteins and HDL: concordance and discordance with cardiovascular disease risk. Curr. Opin. Lipidol. 22: 113-122.
26. Dubé, J. B., M. B. Boffa, R. A. Hegele, and M. L. Koschinsky. 2012. Lipoprotein(a): more interesting than ever after 50 years. Curr. Opin. Lipidol. 23: 133-140.
27. Kronenberg, F., and G. Utermann. 2013. Lipoprotein(a): resurrected by genetics. J. Intern. Med. 273: 6-30.
28. Kostner, K. M., W. Marz, and G. M. Kostner. 2013. When should we measure lipoprotein (a)? Eur. Heart J. 34: 3268-3276.
29. Jacobson, T. A. 2013. Lipoprotein(a), cardiovascular disease, and contemporary management. Mayo Clin. Proc. 88: 1294-1311.
30. Jansen, H., N. J. Samani, and H. Schunkert. 2014. Mendelian randomization studies in coronary artery disease. Eur. Heart J. 35: 1917-1924.
31. Nave, A. H., K. S. Lange, C. O. Leonards, B. Siegerink, W. Doehner, U. Landmesser, E. Steinhagen-Thiessen, M. Endres, and M. Ebinger. 2015. Lipoprotein (a) as a risk factor for ischemic stroke: a meta-analysis. Atherosclerosis. 242: 496-503.
32. Orho-Melander, M. 2015. Genetics of coronary heart disease: towards causal mechanisms, novel drug targets and more personalized prevention. J. Intern. Med. 278: 433-446.
33. Witztum, J. L., and H. N. Ginsberg. 2016. Lipoprotein (a): coming of age at last. J. Lipid Res. 57: 336-339.
34. Boffa, M. B., and M. L. Koschinsky. 2016. Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease? J. Lipid Res. 57: 745-757.
35. Thanassoulis, G. 2016. Lipoprotein (a) in calcific aortic valve disease: from genomics to novel drug target for aortic stenosis. J. Lipid Res. 57: 917-924.
36. Tsimikas, S. 2016. Lipoprotein(a): novel target and emergence of novel therapies to lower cardiovascular disease risk. Curr. Opin. Endocrinol. Diabetes Obes. 23: 157-164.
37. Stender, S., and A. Tybjaerg-Hansen. 2016. Using human genetics to predict the effects and side-effects of drugs. Curr. Opin. Lipidol. 27: 105-111.
38. Musunuru, K, and S. Kathiresan. 2016. Surprises from genetic analyses of lipid risk factors for atherosclerosis. Circ. Res. 118: 579-585.
39. Schmidt, K., A. Noureen, F. Kronenberg, and G. Utermann. 2016. Structure, function, and genetics of lipoprotein(a). J. Lipid Res. 57: 1339-1359.
40. Kronenberg, F. 2016. Human genetics and the causal role of lipoprotein(a) for various diseases. Cardiovasc. Drugs Ther. 30: 87-100.
41. Rath, M., A. Niendorf, T. Reblin, M. Dietel, H. J. Krebber, and U. Beisiegel. 1989. Detection and quantification of lipoprotein(a) in the arterial wall of 107 coronary bypass patients. Arteriosclerosis. 9: 579-592.
42. Niendorf, A., M. Rath, K. Wolf, S. Peters, H. Arps, U. Beisiegel, and M. Dietel. 1990. Morphological detection and quantification of lipoprotein(a) deposition in atheromatous lesions of human aorta and coronary arteries. Virchows Arch. A Pathol. Anat. Histopathol. 417: 105-111.
43. Cushing, G. L., J. W. Gaubatz, M. L. Nava, B. J. Burdick, T. M. Bocan, J. R. Guyton, D. Weilbaecher, M. E. DeBakey, G. M. Lawrie, and J. D. Morrisett. 1989. Quantitation and localization of apolipo proteins [a] and B in coronary artery bypass vein grafts resected at re-operation. Arteriosclerosis. 9: 593-603.
44. Smith, E. B., and S. Cochran. 1990. Factors influencing the accumulation in fibrous plaques of lipid derived from low density lipoprotein. II. Preferential immobilization of lipoprotein (a) (Lp(a)). Atherosclerosis. 84: 173-181.
45. Hoff, H. F., J. O'Neil, and A. Yashiro. 1993. Partial characterization of lipoproteins containing apo[a] in human atherosclerotic lesions. J. Lipid Res. 34: 789-798.
46. Reblin, T., N. Meyer, C. Labeur, D. Henne-Bruns, and U. Beisiegel. 1995. Extraction of lipoprotein(a), apo B, and apo E from fresh human arterial wall and atherosclerotic plaques. Atherosclerosis. 113: 179-188.
47. Nachman, R. L., D. Gavish, N. Azrolan, and T. B. Clarkson. 1991. Lipoprotein(a) in diet-induced atherosclerosis in nonhuman primates. Arterioscler. Thromb. 11: 32-38.
48. Kreuzer, J., M. B. Lloyd, D. Bok, G. M. Fless, A. M. Scanu, A. J. Lusis, and M. E. Haberland. 1994. Lipoprotein (a) displays increased accumulation compared with low-density lipoprotein in the murine arterial wall. Chem. Phys. Lipids. 67-68: 175-190.
49. Nielsen, L. B., B. G. Nordestgaard, S. Stender, A. Niendorf, and K. Kjeldsen. 1995. Transfer of lipoprotein(a) and LDL into aortic intima in normal and in cholesterol-fed rabbits. Arterioscler. Thromb. Vasc. Biol. 15: 1492-1502.
50. Yeang, C., B. Cotter, and S. Tsimikas. 2016. Experimental animal models evaluating the causal role of lipoprotein(a) in atherosclerosis and aortic stenosis. Cardiovasc. Drugs Ther. 30: 75-85.
51. O'Brien, K. D., D. D. Reichenbach, S. M. Marcovina, J. Kuusisto, C. E. Alpers, and C. M. Otto. 1996. Apolipoproteins B, (a), and E accumulate in the morphologically early lesion of 'degenerative' valvular aortic stenosis. Arterioscler. Thromb. Vasc. Biol. 16: 523-532.
52. Nielsen, L. B., M. L. Gronholdt, T. V. Schroeder, S. Stender, and B. G. Nordestgaard. 1997. In vivo transfer of lipoprotein(a) into human atherosclerotic carotid arterial intima. Arterioscler. Thromb. Vasc. Biol. 17: 905-911.
53. Nielsen, L. B., S. Stender, M. Jauhiainen, and B. G. Nordestgaard. 1996. Preferential influx and decreased fractional loss of lipoprotein(a) in atherosclerotic compared with nonlesioned rabbit aorta. J. Clin. Invest. 98: 563-571.
54. Nordestgaard, B. G., and L. B. Nielsen. 1994. Atherosclerosis and arterial infux of lipoproteins. Curr. Opin. Lipidol. 5: 252-257.
55. Nielsen, L. B., K. Juul, and B. G. Nordestgaard. 1998. Increased degradation of lipoprotein(a) in atherosclerotic compared with nonlesioned aortic intima-inner media of rabbits: in vivo evidence that lipoprotein(a) may contribute to foam cell formation. Arterioscler. Thromb. Vasc. Biol. 18: 641-649.
56. Nielsen, L. B., S. Stender, K. Kjeldsen, and B. G. Nordestgaard. 1996. Specific accumulation of lipoprotein(a) in balloon-injured rabbit aorta in vivo. Circ. Res. 78: 615-626.
57. Nordestgaard, B. G. 1996. The vascular endothelial barrier-selective retention of lipoproteins. Curr. Opin. Lipidol. 7: 269-273.
58. Fless, G. M., and M. L. Snyder. 1994. Polymorphic forms of Lp(a) with different structural and functional properties: cold-induced self-association and binding to fibrin and lysine-Sepharose. Chem. Phys. Lipids. 67-68: 69-79.
59. Bihari-Varga, M., E. Gruber, M. Rotheneder, R Zechner, and G M. Kostner. 1988. Interaction of lipoprotein Lp(a) and low density lipoprotein with glycosaminoglycans from human aorta. Arteriosclerosis. 8: 851-857.
60. Bottalico, L. A., G. A Keesler, G. M. Fless, and I. Tabas. 1993. Cholesterol loading of macrophages leads to marked enhancement of native lipoprotein(a) and apoprotein(a) internalization and degradation. J. Biol. Chem. 268: 8569-8573.
61. Skiba, P. J., G. A. Keesler, and I. Tabas. 1994. Interferon-gamma down-regulates the lipoprotein(a)/apoprotein(a) receptor activity on macrophage foam cells. Evidence for disruption of ligandinduced receptor recycling by interferon-gamma. J. Biol. Chem. 269: 23059-23067.
62. Keesler, G. A., Y Li, P. J. Skiba, G. M. Fless, and I. Tabas. 1994. Macrophage foam cell lipoprotein(a)/apoprotein(a) receptor. Cell-surface localization, dependence of induction on new protein synthesis, and ligand specificity. Arterioscler. Thromb. 14: 1337-1345.
63. Stary, H. C., A. B. Chandler, S. Glagov, J. R. Guyton, W. Insull, Jr., M. E. Rosenfeld, S. A. Schaffer, C. J. Schwartz, W. D. Wagner, and R. W. Wissler. 1994. A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler. Thromb. 14: 840-856.
64. Nordestgaard, B. G., and A. Varbo. 2014. Triglycerides and cardiovascular disease. Lancet. 384: 626-635.
65. Nordestgaard, B. G. 2016. Triglyceriderich lipoproteins and atherosclerotic cardiovascular disease: new insights from epidemiology, genetics, and biology. Circ. Res. 118: 547-563.
66. Schunkert, H., I. R. Konig, S. Kathiresan, M. P. Reilly, T. L. Assimes, H. Holm, M. Preuss, A. F. Stewart, M. Barbalic, C. Gieger, et al. 2011. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat. Genet. 43: 333-338.
67. Kamstrup, P. R., and B. G. Nordestgaard. 2013. Lipoprotein(a) concentrations, isoform size, and risk of type 2 diabetes: a Mendelian randomisation study. Lancet Diabetes Endocrinol. 1: 220-227.
68. Enkhmaa, B., E. Anuurad, and L. Berglund. 2016. Lipoprotein (a): impact by ethnicity and environmental and medical conditions. J. Lipid Res. 57: 1111-1125.
69. Sandholzer, C, D. M. Hallman, N. Saha, G. Sigurdsson, C. Lackner, A Csaszar, E. Boerwinkle, and G. Utermann. 1991. Effects of the apolipoprotein(a) size polymorphism on the lipoprotein(a) concentration in 7 ethnic groups. Hum. Genet. 86: 607-614.
70. Kraft, H. G., A. Lingenhel, R. W. Pang, R Delport, M. Trommsdorff, H. Vermaak, E. D. Janus, and G. Utermann. 1996. Frequency distributions of apolipoprotein(a) kringle IV repeat alleles and their effects on lipoprotein(a) levels in Caucasian, Asian, and African populations: the distribution of null alleles is non-random. Eur. J. Hum. Genet. 4: 74-87.
71. Gaw, A., E. Boerwinkle, J. C. Cohen, and H. H. Hobbs. 1994. Comparative analysis of the apo(a) gene, apo(a) glycoprotein, and plasma concentrations of Lp(a) in three ethnic groups. Evidence for no common "null" allele at the apo(a) locus. J. Clin. Invest. 93: 2526-2534.
72. Matthews, K. A., M. F. Sowers, C. A. Derby, E. Stein, H. MiracleMcMahill, S. L. Crawford, and R. C. Pasternak. 2005. Ethnic differences in cardiovascular risk factor burden among middle-aged women: Study of Women's Health Across the Nation (SWAN). Am. Heart J. 149: 1066-1073.
73. Marcovina, S. M., J. J. Albers, E. Wjsman, Z. Zhang, N. H. Chapman, and H. Kennedy. 1996. Differences in Lp[a] concentrations and apo[a] polymorphs between black and white Americans. J. Lipid Res. 37: 2569-2585.
74. Helmhold, M., J. Bigge, R Muche, J. Mainoo, J. Thiery, D. Seidel, and V. W. Armstrong. 1991. Contribution of the apo[a] phenotype to plasma Lp[a] concentrations shows considerable ethnic variation. J. Lipid Res. 32: 1919-1928.
75. Schultz, J. S., D. C. Schreffler, C. F. Sing, and N. R. Harvie. 1974. The genetics of the Lp antigen. I. Its quantitation and distribution in a sample population. Ann. Hum. Genet. 38: 39-46.
76. Sing, C. F., J. S. Schultz, and D. C. Shreffler. 1974. The genetics of the Lp antigen. II. A family study and proposed models of genetic control. Ann. Hum. Genet. 38: 47-56.
77. Iselius, L., G. Dahlen, U. de Faire, and T. Lundman. 1981. Complex segregation analysis of the Lp(a)/pre-beta 1-lipoprotein trait. Clin. Genet. 20: 147-151.
78. Hasstedt, S. J., D. E. Wilson, C. Q. Edwards, W. N. Cannon, D. Carmelli, and R. R. Williams. 1983. The genetics of quantitative plasma Lp(a): analysis of a large pedigree. Am. J. Med. Genet. 16: 179-188.
79. Morton, N. E., K. Berg, G. Dahlen, R. E. Ferrell, and G. G. Rhoads. 1985. Genetics of the Lp lipoprotein in Japanese-Americans. Genet. Epidemiol. 2: 113-121.
80. Hasstedt, S. J., and R R. Williams. 1986. Three alleles for quantitative Lp(a). Genet. Epidemiol. 3: 53-55.
81. Fless, G. M., M. E. ZumMallen, and A. M. Scanu. 1986. Physicochemical properties of apolipoprotein(a) and lipoprotein(a-) derived from the dissociation of human plasma lipoprotein (a). J. Biol. Chem. 261: 8712-8718.
82. Utermann, G., H. J. Menzel, H. G. Kraft, H. C. Duba, H. G. Kemmler, and C. Seitz. 1987. Lp(a) glycoprotein phenotypes. Inheritance and relation to Lp(a)-lipoprotein concentrations in plasma. J. Clin. Invest. 80: 458-465.
83. Grinstead, G. F., and R. D. Ellefson. 1988. Heterogeneity of lipoprotein Lp(a) and apolipoprotein(a). Clin. Chem. 34: 1036-1040.
84. Utermann, G., C. Duba, and H. J. Menzel. 1988. Genetics of the quantitative Lp(a) lipoprotein trait. II. Inheritance of Lp(a) glycoprotein phenotypes. Hum. Genet. 78: 47-50.
85. Utermann, G., H. G. Kraft, H. J. Menzel, T. Hopferwieser, and C. Seitz. 1988. Genetics of the quantitative Lp(a) lipoprotein trait. I. Relation of LP(a) glycoprotein phenotypes to Lp(a) lipoprotein concentrations in plasma. Hum. Genet. 78: 41-46.
86. Boerwinkle, E., H. J. Menzel, H. G. Kraft, and G. Utermann. 1989. Genetics of the quantitative Lp(a) lipoprotein trait. III. Contribution of Lp(a) glycoprotein phenotypes to normal lipid variation. Hum. Genet. 82: 73-78.
87. Kraft, H. G., C. Sandholzer, H. J. Menzel, and G. Utermann. 1992. Apolipoprotein (a) alleles determine lipoprotein (a) particle density and concentration in plasma. Arterioscler. Thromb. 12: 302-306.
88. Hallman, D. M., E. Boerwinkle, N. Saha, C. Sandholzer, H. J. Menzel, A. Csazar, and G. Utermann. 1991. The apolipoprotein E polymorphism: a comparison of allele frequencies and effects in nine populations. Am. J. Hum. Genet. 49: 338-349.
89. Barlera, S., C. Specchia, M. Farrall, B. D. Chiodini, M. G. Franzosi, S. Rust, F. Green, E. B. Nicolis, J. Peden, G. Assmann, et al. 2007. Multiple QTL influence the serum Lp(a) concentration: a genome-wide linkage screen in the PROCARDIS study. Eur. J. Hum. Genet. 15: 221-227.
90. López, S., A. Buil, J. Ordoñez, J. C. Souto, L. Almasy, M. Lathrop, J. Blangero, F. Blanco-Vaca, J. Fontcuberta, and J. M. Soria. 2008. Genome-wide linkage analysis for identifying quantitative trait loci involved in the regulation of lipoprotein a (Lpa) levels. Eur. J. Hum. Genet. 16: 1372-1379.
91. Ober, C., A. S. Nord, E. E. Thompson, L. Pan, Z. Tan, D. Cusanovich, Y. Sun, R. Nicolae, C. Edelstein, D. H. Schneider, et al. 2009. Genome-wide association study of plasma lipoprotein(a) levels identifies multiple genes on chromosome 6q. J. Lipid Res. 50: 798-806.
92. Zabaneh, D., M. Kumari, M. Sandhu, N. Wareham, N. Wainwright, T. Papamarkou, J. Hopewell, R. Clarke, K Li, J. Palmen, et al. 2011. Meta analysis of candidate gene variants outside the LPA locus with Lp(a) plasma levels in 14,500 participants of six White European cohorts. Atherosclerosis. 217: 447-451.
93. Qi, Q., T. Workalemahu, C. Zhang, F. B. Hu, and L. Qi. 2012. Genetic variants, plasma lipoprotein(a) levels, and risk of cardiovascular morbidity and mortality among two prospective cohorts of type 2 diabetes. Eur. Heart J. 33: 325-334.
94. Mora, S., P. R. Kamstrup, N. Rifai, B. G. Nordestgaard, J. E. Buring, and P. M. Ridker. 2010. Lipoprotein(a) and risk of type 2 diabetes. Clin. Chem. 56: 1252-1260.
95. Ye, Z., P. C. Haycock, D. Gurdasani, C. Pomilla, S. M. Boekholdt, S. Tsimikas, K. T. Khaw, N. J. Wareham, M. S. Sandhu, and N. G. Forouhi. 2014. The association between circulating lipoprotein(a) and type 2 diabetes: is it causal? Diabetes. 63: 332-342.
96. Ding, L., A. Song, M. Dai, M. Xu, W Sun, B. Xu, J. Sun, T Wang, Y Xu, J. Lu, et al. 2015. Serum lipoprotein (a) concentrations are inversely associated with T2D, prediabetes, and insulin resistance in a middle-aged and elderly Chinese population. J. Lipid Res. 56: 920-926.
97. Lamina, C., and F. Kronenberg. 2013. The mysterious lipoprotein(a) is still good for a surprise. Lancet Diabetes Endocrinol. 1: 170-172.
98. Katan, M. B. 1986. Apolipoprotein E isoforms, serum cholesterol, and cancer. Lancet. 1: 507-508.
99. Gray, R., and K. Wheatley. 1991. How to avoid bias when comparing bone marrow transplantation with chemotherapy. Bone Marrow Transplant. 7(Suppl 3): 9-12.
100. Tybjaerg-Hansen, A., B. Agerholm-Larsen, S. E. Humphries, S. Abildgaard, P. Schnohr, and B. G. Nordestgaard. 1997. A common mutation (G-455→ A) in the beta-fibrinogen promoter is an independent predictor of plasma fibrinogen, but not of ischemic heart disease. A study of 9,127 individuals based on the Copenhagen City Heart Study. J. Clin. Invest. 99: 3034-3039.
101. Sandholzer, C, E. Boerwinkle, N. Saha, M. C. Tong, and G. Utermann. 1992. Apolipoprotein(a) phenotypes, Lp(a) concentration and plasma lipid levels in relation to coronary heart disease in a Chinese population: evidence for the role of the apo(a) gene in coronary heart disease. J. Clin. Invest. 89: 1040-1046.
102. Sandholzer, C., N. Saha, J. D. Kark, A. Rees, W. Jaross, H. Dieplinger, F. Hoppichler, E. Boerwinkle, and G. Utermann. 1992. Apo(a) isoforms predict risk for coronary heart disease. A study in six populations. Arterioscler. Thromb. 12: 1214-1226.
103. Smith, G. D., and S. Ebrahim. 2003. 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? Int. J. Epidemiol. 32: 1-22.
104. Smith, G. D., and S. Ebrahim. 2004. Mendelian randomization: prospects, potentials, and limitations. Int. J. Epidemiol. 33: 30-42.
105. Davey Smith, G., S. Ebrahim, S. Lewis, A. L. Hansell, L. J. Palmer, and P. R. Burton. 2005. Genetic epidemiology and public health: hope, hype, and future prospects. Lancet. 366: 1484-1498.
106. Lawlor, D. A., R. M. Harbord, J. A. Sterne, N. Timpson, and G. Davey Smith. 2008. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat. Med. 27: 1133-1163.
107. Palmer, T. M., J. A. Sterne, R. M. Harbord, D. A. Lawlor, N. A. Sheehan, S. Meng, R. Granell, G. Davey Smith, and V. Didelez. 2011 Instrumental variable estimation of causal risk ratios and causal odds ratios in Mendelian randomization analyses. Am. J. Epidemiol. 173: 1392-1403.
108. Davey Smith, G., and G. Hemani. 2014. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum. Mol. Genet. 23: R89-R98.
109. Clarke, R., M. Shipley, S. Lewington, L. Youngman, R. Collins, M. Marmot, and R. Peto. 1999. Underestimation of risk associations due to regression dilution in long-term follow-up of prospective studies. Am. J. Epidemiol. 150: 341-353.
110. MacMahon, S., R. Peto, J. Cutler, R. Collins, P. Sorlie, J. Neaton, R. Abbott, J. Godwin, A. Dyer, and J. Stamler. 1990. Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet. 335: 765-774.
111. Kamstrup, P. R., A. Tybjaerg-Hansen, and B. G. Nordestgaard. 2012 Genetic evidence that lipoprotein(a) associates with atherosclerotic stenosis rather than venous thrombosis. Arterioscler. Thromb. Vasc. Biol. 32: 1732-1741.
112. Langsted, A., A. Varbo, P. R. Kamstrup, and B. G. Nordestgaard. 2015. Elevated lipoprotein(a) does not cause low-grade inflammation despite causal association with aortic valve stenosis and myocardial infarction: a study of 100,578 individuals from the general population. J. Clin. Endocrinol. Metab. 100: 2690-2699.
113. Langsted, A., P. R. Kamstrup, M. Benn, A. Tybjaerg-Hansen, and B. G. Nordestgaard. 2016. High lipoprotein(a) as a possible cause of clinical familial hypercholesterolaemia: a prospective cohort study. Lancet Diabetes Endocrinol. 4: 577-587.
114. Afzal, S., P. Brondum-Jacobsen, S. E. Bojesen, and B. G. Nordestgaard. 2014. Genetically low vitamin D concentrations and increased mortality: Mendelian randomisation analysis in three large cohorts. BMJ. 349: g6330.
115. Thomsen, M., A. Varbo, A. Tybjaerg-Hansen, and B. G. Nordestgaard. 2014. Low nonfasting triglycerides and reduced all-cause mortality: a Mendelian randomization study. Clin. Chem. 60: 737-746.
116. Dahlén, G., C. Ericson, C. Furberg, L. Lundkvist, and K. Svardsudd. 1972. Studies on an extra pre-beta lipoprotein fraction. Acta Med. Scand. Suppl. 531: 1-29.
117. Berg, K., G. Dahlén, and M. H. Frick. 1974. Lp(a) lipoprotein and pre-beta1-lipoprotein in patients with coronary heart disease. Clin. Genet. 6: 230-235.
118. Dahlén, G., K. Berg, T. Gillnas, and C. Ericson. 1975. Lp(a) lipoprotein/pre-beta1-lipoprotein in Swedish middle-aged males and in patients with coronary heart disease. Clin. Genet. 7: 334-341.
119. Rhoads, G. G., N. E. Morton, C. L. Gulbrandsen, and A. Kagan. 1978. Sinking pre-beta lipoprotein and coronary heart disease in Japanese-American men in Hawaii. Am. J. Epidemiol. 108: 350-356.
120. Kostner, G. M., P. Avogaro, G. Cazzolato, E. Marth, G. Bittolo-Bon, and G. B. Qunici. 1981. Lipoprotein Lp(a) and the risk for myocardial infarction. Atherosclerosis. 38: 51-61.
121. Dahlen, G. H., J. R. Guyton, M. Attar, J. A. Farmer, J. A. Kautz, and A. M. Gotto, Jr. 1986. Association of levels of lipoprotein Lp(a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography. Circulation. 74: 758-765.
122. Wiklund, O., B. Angelin, S. O. Olofsson, M. Eriksson, G. Fager, L. Berglund, and G. Bondjers. 1990. Apolipoprotein(a) and ischaemic heart disease in familial hypercholesterolaemia. Lancet. 335: 1360-1363.
123. Rhoads, G. G., G. Dahlén, K. Berg, N. E. Morton, and A. L. Dannenberg. 1986. Lp(a) lipoprotein as a risk factor for myocardial infarction. JAMA. 256: 2540-2544.
124. Durrington, P. N., M. Ishola, L. Hunt, S. Arrol, and D. Bhatnagar. 1988. Apolipoproteins (a), AI, and B and parental history in men with early onset ischaemic heart disease. Lancet. 1: 1070-1073.
125. Seed, M., F. Hoppichler, D. Reaveley, S. McCarthy, G. R. Thompson, E. Boerwinkle, and G. Utermann. 1990. Relation of serum lipoprotein(a) concentration and apolipoprotein(a) phenotype to coronary heart disease in patients with familial hypercholesterolemia. N. Engl. J. Med. 322: 1494-1499.
126. Sandkamp, M., H. Funke, H. Schulte, E. Kohler, and G. Assmann. 1990. Lipoprotein(a) is an independent risk factor for myocardial infarction at a young age. Clin. Chem. 36: 20-23.
127. Kark, J. D., C. Sandholzer, Y. Friedlander, and G. Utermann. 1993. Plasma Lp(a), apolipoprotein(a) isoforms and acute myocardial infarction in men and women: a case-control study in the Jerusalem population. Atherosclerosis. 98: 139-151.
128. Simons, L., Y. Friedlander, J. Simons, and J. McCallum. 1993. Lipoprotein(a) is not associated with coronary heart disease in the elderly: cross-sectional data from the Dubbo study. Atherosclerosis. 99: 87-95.
129. Zhuang, Y. Y., J. J. Wang, and P. Xu. 1993. Increased lipoprotein (a) as an independent risk factor for cardiovascular and cerebrovascular diseases. Chin. Med. J. (Engl.) 106: 597-600.
130. Orth-Gomér, K., M. A. Mittleman, K. Schenck-Gustafsson, S. P. Wamala, M. Eriksson, K. Belkic, R. Kirkeeide, B. Svane, and L. Rydén. 1997. Lipoprotein(a) as a determinant of coronary heart disease in young women. Circulation. 95: 329-334.
131. Rosengren, A., L. Wilhelmsen, E. Eriksson, B. Risberg, and H. Wedel. 1990. Lipoprotein (a) and coronary heart disease: a prospective case-control study in a general population sample of middle aged men. BMJ. 301: 1248-1251.
132. Jauhiainen, M., P. Koskinen, C. Ehnholm, M. H. Frick, M. Manttari, V. Manninen, and J. K. Huttunen. 1991. Lipoprotein (a) and coronary heart disease risk: a nested case-control study of the Helsinki Heart Study participants. Atherosclerosis. 89: 59-67.
133. Coleman, M. P., T. J. Key, D. Y. Wang, C. Hermon, I. S. Fentiman, D. S. Allen, M. Jarvis, M. C. Pike, and T. A. Sanders. 1992. A prospective study of obesity, lipids, apolipoproteins and ischaemic heart disease in women. Atherosclerosis. 92: 177-185.
134. Ridker, P. M., C. H. Hennekens, and M. J. Stampfer. 1993. A prospective study of lipoprotein(a) and the risk of myocardial infarction. JAMA. 270: 2195-2199.
135. Cremer, P., D. Nagel, B. Labrot, H. Mann, R. Muche, H. Elster, and D. Seidel. 1994. Lipoprotein Lp(a) as predictor of myocardial infarction in comparison to fibrinogen, LDL cholesterol and other risk factors: results from the prospective Gottingen Risk Incidence and Prevalence Study (GRIPS). Eur. J. Clin. Invest. 24: 444-453.
136. Alfthan, G., J. Pekkanen, M. Jauhiainen, J. Pitkaniemi, M. Karvonen, J. Tuomilehto, J. T. Salonen, and C. Ehnholm. 1994. Relation of serum homocysteine and lipoprotein(a) concentrations to atherosclerotic disease in a prospective Finnish population based study. Atherosclerosis. 106: 9-19.
137. Wald, N. J., M. Law, H. C. Watt, T. Wu, A. Bailey, A. M. Johnson, W. Y. Craig, T. B. Ledue, and J. E. Haddow. 1994. Apolipoproteins and ischaemic heart disease: implications for screening. Lancet. 343: 75-79.
138. Assmann, G., H. Schulte, and A. von Eckardstein. 1996. Hypertriglyceridemia and elevated lipoprotein(a) are risk factors for major coronary events in middle-aged men. Am. J. Cardiol. 77: 1179-1184.
139. Klausen, I. C., A. Sjol, P. S. Hansen, L. U. Gerdes, L. Moller, L. Lemming, M. Schroll, and O. Faergeman. 1997. Apolipoprotein(a) isoforms and coronary heart disease in men: a nested case-control study. Atherosclerosis. 132: 77-84.
140. Wild, S. H., S. P. Fortmann, and S. M. Marcovina. 1997. A prospective case-control study of lipoprotein(a) levels and apo(a) size and risk of coronary heart disease in Stanford Five-City Project participants. Arterioscler. Thromb. Vasc. Biol. 17: 239-245.
141. Craig, W. Y., L. M. Neveux, G. E. Palomaki, M. M. Cleveland, and J. E. Haddow. 1998. Lipoprotein(a) as a risk factor for ischemic heart disease: metaanalysis of prospective studies. Clin. Chem. 44: 2301-2306.
142. Dahlén, G. 1988. Lipoprotein (a) as a risk factor for atherosclerotic diseases. Arctic Med. Res. 47(Suppl 1): 458-461.
143. Dahlén, G. H., L. Weinehall, H. Stenlund, J. H. Jansson, G. Hallmans, F. Huhtasaari, and S. Wall. 1998. Lipoprotein(a) and cholesterol levels act synergistically and apolipoprotein A-I is protective for the incidence of primary acute myocardial infarction in middle-aged males. An incident case-control study from Sweden. J. Intern. Med. 244: 425-430.
144. Cantin, B., F. Gagnon, S. Moorjani, J. P. Despres, B. Lamarche, P. J. Lupien, and G. R. Dagenais. 1998. Is lipoprotein(a) an indepen-dent risk factor for ischemic heart disease in men? The Quebec Cardiovascular Study. J. Am. Coll. Cardiol. 31: 519-525.
145. Bostom, A. G., L. A. Cupples, J. L. Jenner, J. M. Ordovas, L. J. Seman, P. W. Wilson, E. J. Schaefer, and W. P. Castelli. 1996. Elevated plasma lipoprotein(a) and coronary heart disease in men aged 55 years and younger. A prospective study. JAMA. 276: 544-548.
146. Bostom, A. G., D. R. Gagnon, L. A. Cupples, P. W. Wilson, J. L. Jenner, J. M. Ordovas, E. J. Schaefer, and W. P. Castelli. 1994. A prospective investigation of elevated lipoprotein (a) detected by electrophoresis and cardiovascular disease in women. The Framingham Heart Study. Circulation. 90: 1688-1695.
147. Nguyen, T. T., R. D. Ellefson, D. O. Hodge, K. R. Bailey, T. E. Kottke, and H. S. Abu-Lebdeh. 1997. Predictive value of electrophoretically detected lipoprotein(a) for coronary heart disease and cerebrovascular disease in a community-based cohort of 9936 men and women. Circulation. 96: 1390-1397.
148. Marcovina, S. M., J. J. Albers, B. Gabel, M. L. Koschinsky, and V. P. Gaur. 1995. Effect of the number of apolipoprotein(a) kringle 4 domains on immunochemical measurements of lipoprotein(a). Clin. Chem. 41: 246-255.
149. Tate, J. R., N. Rifai, K. Berg, R. Couderc, F. Dati, G. M. Kostner, I. Sakurabayashi, and A. Steinmetz. 1998. International Federation of Clinical Chemistry standardization project for the measurement of lipoprotein(a). Phase I. Evaluation of the analytical performance of lipoprotein(a) assay systems and commercial calibrators. Clin. Chem. 44: 1629-1640.
150. Marcovina, S. M., M. L. Koschinsky, J. J. Albers, and S. Skarlatos. 2003. Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein(a) and Cardiovascular Disease: recent advances and future directions. Clin. Chem. 49: 1785-1796.
151. Kronenberg, F., E. Trenkwalder, H. Dieplinger, and G. Utermann. 1996. Lipoprotein(a) in stored plasma samples and the ravages of time. Why epidemiological studies might fail. Arterioscler. Thromb. Vasc. Biol. 16: 1568-1572.
152. von Eckardstein, A., H. Schulte, P. Cullen, and G. Assmann. 2001. Lipoprotein(a) further increases the risk of coronary events in men with high global cardiovascular risk. J. Am. Coll. Cardiol. 37: 434-439.
153. Sharrett, A. R., C. M. Ballantyne, S. A. Coady, G. Heiss, P. D. Sorlie, D. Catellier, and W. Patsch. 2001. 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. 104: 1108-1113.
154. Luc, G., J. M. Bard, D. Arveiler, J. Ferrieres, A. Evans, P. Amouyel, J. C. Fruchart, and P. Ducimetiere. 2002. Lipoprotein (a) as a predictor of coronary heart disease: the PRIME Study. Atherosclerosis. 163: 377-384.
155. Ariyo, A. A., C. Thach, and R. Tracy. 2003. Lp(a) lipoprotein, vascular disease, and mortality in the elderly. N. Engl. J. Med. 349: 2108-2115.
156. Rifai, N., J. Ma, F. M. Sacks, P. M. Ridker, W. J. Hernandez, M. J. Stampfer, and S. M. Marcovina. 2004. Apolipoprotein(a) size and lipoprotein(a) concentration and future risk of angina pectoris with evidence of severe coronary atherosclerosis in men: The Physicians' Health Study. Clin. Chem. 50: 1364-1371.
157. Suk Danik, J., N. Rifai, J. E. Buring, and P. M. Ridker. 2006. Lipoprotein(a), measured with an assay independent of apolipoprotein(a) isoform size, and risk of future cardiovascular events among initially healthy women. JAMA. 296: 1363-1370.
158. Kamstrup, P. R., M. Benn, A. Tybjaerg-Hansen, and B. G. Nordestgaard. 2008. Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: the Copenhagen City Heart Study. Circulation. 117: 176-184.
159. Trégouët, D. A., I. R. König, J. Erdmann, A. Munteanu, P. S. Braund, A. S. Hall, A. Grosshennig, P. Linsel-Nitschke, C. Perret, M. DeSuremain, et al. 2009. Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease. Nat. Genet. 41: 283-285.
160. Helgadottir, A., S. Gretarsdottir, G. Thorleifsson, H. Holm, R. S. Patel, T. Gudnason, G. T. Jones, A. M. van Rij, D. J. Eapen, A. F. Baas, et al. 2012. Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism. J. Am. Coll. Cardiol. 60: 722-729.
161. Gazzaruso, C., A. Garzaniti, P. Buscaglia, G. Bonetti, C. Falcone, P. Fratino, G. Finardi, and D. Geroldi. 1998. Apolipoprotein(a) phenotypes and their predictive value for coronary heart disease: identification of an operative cut-off of apolipoprotein(a) polymorphism. J. Cardiovasc. Risk. 5: 37-42.
162. Qin, S., S. Wang, and C. Li. 1995. Apolipoprotein (a) polymorphism in relation to coronary heart disease in Chinese Han nationality [article in Chinese]. Zhonghua Yi Xue Za Zhi. 75: 588-591.
163. Emanuele, E., E. Peros, P. Minoretti, A. D'Angelo, M. N. Piccinni, L. Montagna, and D. Geroldi. 2004. Apolipoprotein(a) size polymorphism is associated with coronary heart disease in polygenic hypercholesterolemia. Nutr. Metab. Cardiovasc. Dis. 14: 193-199.
164. Emanuele, E., E. Peros, P. Minoretti, A. D'Angelo, L. Montagna, C. Falcone, and D. Geroldi. 2004. Significance of apolipoprotein(a) phenotypes in acute coronary syndromes: relation with clinical presentation. Clin. Chim. Acta. 350: 159-165.
165. Emanuele, E., E. Peros, P. Minoretti, C. Falcone, A. D'Angelo, L. Montagna, and D. Geroldi. 2003. Relationship between apolipoprotein(a) size polymorphism and coronary heart disease in overweight subjects. BMC Cardiovasc. Disord. 3: 12.
166. Parlavecchia, M., A. Pancaldi, R. Taramelli, P. Valsania, L. Galli, G Pozza, S. Chierchia, and G. Ruotolo. 1994. Evidence that apolipoprotein(a) phenotype is a risk factor for coronary artery disease in men < 55 years of age. Am. J. Cardiol. 74: 346-351.
167. Martín, S., J. Pedro-Botet, J. Joven, J. M. Simó, M. G. Ladona, M. Pavesi, and J. Rubiés-Prat. 2002. Heterozygous apolipoprotein (a) status and protein expression as a risk factor for premature coronary heart disease. J. Lab. Clin. Med. 139: 181-187.
168. Simó, J. M., J. Joven, E. Vilella, M. Ribas, M. A. Pujana, I. M. Sundaram, J. P. Hammel, and J. L. Hoover-Plow. 2001. Impact of apolipoprotein(a) isoform size heterogeneity on the lysine binding function of lipoprotein(a) in early onset coronary artery disease. Thromb. Haemost. 85: 412-417.
169. Geethanjali, F. S., V. J. Jose, and A. S. Kanagasabapathy. 2002. Lipoprotein (a) phenotypes in south Indian patients with coronary artery disease. Indian Heart J. 54: 50-53.
170. Zeljkovic, A, N. Bogavac-Stanojevic, Z. Jelic-Ivanovic, V. Spasojevic-Kalimanovska, J. Vekic, and S. Spasic. 2009. Combined effects of small apolipoprotein (a) isoforms and small, dense LDL on coronary artery disease risk. Arch. Med. Res. 40: 29-35.
171. Calmarza, P., J. Cordero, V. Santos, and J. C. Vella. 2004. Apolipoprotein(a) isoforms in infarcted men under 60 years old. Clin. Biochem. 37: 911-918.
172. Akanji, A. O. 2000. Apo(a) isoforms do not predict risk for coronary heart disease in a Gulf Arab population. Ann. Clin. Biochem. 37: 360-366.
173. Katsouras, C. S., S. A. Karabina, A. P. Tambaki, J. A. Goudevenos, L. K. Michalis, L. D. Tsironis, C. S. Stroumbis, M. S. Elisaf, D. A Sideris, and A. D. Tselepis. 2001. Serum lipoprotein(a) concentrations and apolipoprotein(a) isoforms: association with the severity of clinical presentation in patients with coronary heart disease. J. Cardiovasc. Risk. 8: 311-317.
174. Gazzaruso, C., A. Garzaniti, C. Falcone, D. Geroldi, G. Finardi, and P. Fratino. 2001. Association of lipoprotein(a) levels and apolipoprotein(a) phenotypes with coronary artery disease in type 2 diabetic patients and in non-diabetic subjects. Diabet. Med. 18: 589-594.
175. Gambhir, J. K., H. Kaur, K. M. Prabhu, J. D. Morrisett, and D. S. Gambhir. 2008. Association between lipoprotein(a) levels, apo(a) isoforms and family history of premature CAD in young Asian Indians. Clin. Biochem. 41: 453-458.
176. Zorio, E., C. Falco, M. A. Arnau, F. Espana, A. Osa, L. A. Ramon, R Castello, L. Almenar, M. A. Palencia, and A. Estelles. 2006. Lipoprotein (a) in young individuals as a marker of the presence of ischemic heart disease and the severity of coronary lesions. Haematologica. 91: 562-565.
177. Kalina, A., A. Csaszar, G. Fust, B. Nagy, C. Szalai, I. Karadi, J. Duba, Z. Prohaszka, L. Horvath, and H. Dieplinger. 2001. The association of serum lipoprotein(a) levels, apolipoprotein(a) size and (TTTTA)(n) polymorphism with coronary heart disease. Clin. Chim. Acta. 309: 45-51.
178. Bigot, E., B. Robert, J. M. Bard, and F. Mainard. 1997. Lipoprotein (a) phenotype distribution in a population of bypass patients and its influence on lipoprotein (a) concentration. Clin. Chim. Acta. 265: 99-111.
179. Paultre, F., T. A. Pearson, H. F. Weil, C. H. Tuck, M. Myerson, J. Rubin, C. K. Francis, H. F. Marx, E. F. Philbin, R. G. Reed, et al. 2000. High levels of Lp(a) with a small apo(a) isoform are associated with coronary artery disease in African American and white men. Arterioscler. Thromb. Vasc. Biol. 20: 2619-2624.
180. Abe, A., A. Noma, Y. J. Lee, and H. Yamaguchi. 1992. Studies on apolipoprotein(a) phenotypes. Part 2. Phenotype frequencies and Lp(a) concentrations in different phenotypes in patients with angiographically defined coronary artery diseases. Atherosclerosis. 96: 9-15.
181. Brazier, L., L. Tiret, G. Luc, D. Arveiler, J. B. Ruidavets, A. Evans, J. Chapman, F. Cambien, and J. Thillet. 1999. Sequence polymorphisms in the apolipoprotein(a) gene and their association with lipoprotein(a) levels and myocardial infarction. The ECTIM Study. Atherosclerosis. 144: 323-333.
182. Holmer, S. R., C. Hengstenberg, H. G. Kraft, B. Mayer, M. Poll, S. Kurzinger, M. Fischer, H. Lowel, G. Klein, G. A. Riegger, et al. 2003. Association of polymorphisms of the apolipoprotein(a) gene with lipoprotein(a) levels and myocardial infarction. Circulation. 107: 696-701.
183. Geethanjali, F. S., K. Luthra, A. Lingenhel, A. S. Kanagasaba-Pathy, J. Jacob, L. M. Srivastava, S. Vasisht, H. G. Kraft, and G. Utermann. 2003. Analysis of the apo(a) size polymorphism in Asian Indian populations: association with Lp(a) concentration and coronary heart disease. Atherosclerosis. 169: 121-130.
184. Lim, E. T., P. Wurtz, A. S. Havulinna, P. Palta, T. Tukiainen, K Rehnstrom, T. Esko, R. Magi, M. Inouye, T. Lappalainen, et al. 2014. Distribution and medical impact of loss-of-function variants in the Finnish founder population. PLoS Genet. 10: e1004494.
185. Kyriakou, T., U. Seedorf, A. Goel, J. C. Hopewell, R. Clarke, H. Watkins, and M. Farrall. 2014. A common LPA null allele associates with lower lipoprotein(a) levels and coronary artery disease risk. Arterioscler. Thromb. Vasc. Biol. 34: 2095-2099.
186. Virani, S. S., A. Brautbar, B. C. Davis, V. Nambi, R. C. Hoogeveen, A. R. Sharrett, J. Coresh, T. H. Mosley, J. D. Morrisett, D. J. Catellier, et al. 2012. Associations between lipoprotein(a) levels and cardiovascular outcomes in black and white subjects: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 125: 241-249.
187. Spence, J. D. 2006. Lipoprotein(a): involved in events, but not burden of atherosclerotic disease? Stroke. 37: 1350-1351.
188. Spence, J. D., and M. Koschinsky. 2012. Mechanisms of lipoprotein(a) pathogenicity: prothrombotic, proatherosclerotic, or both? Arterioscler. Thromb. Vasc. Biol. 32: 1550-1551.
189. Frick, M. H., G. Dahlen, K. Berg, M. Valle, and P. Hekali. 1978. Serum lipids in angiographically assessed coronary atherosclerosis. Chest. 73: 62-65.
190. Tsimikas, S., E. S. Brilakis, E. R. Miller, J. P. McConnell, R. J. Lennon, K. S. Kornman, J. L. Witztum, and P. B. Berger. 2005. Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease. N. Engl. J. Med. 353: 46-57.
191. Klein, J. H., R. A. Hegele, D. G. Hackam, M. L. Koschinsky, M. W. Huff, and J. D. Spence. 2008. Lipoprotein(a) is associated differentially with carotid stenosis, occlusion, and total plaque area. Arterioscler. Thromb. Vasc. Biol. 28: 1851-1856.
192. Volpato, S., G. B. Vigna, M. M. McDermott, M. Cavalieri, C. Maraldi, F. Lauretani, S. Bandinelli, G. Zuliani, J. M. Guralnik, R. Fellin, et al. 2010. Lipoprotein(a), inflammation, and peripheral arterial disease in a community-based sample of older men and women (the InCHIANTI study). Am. J. Cardiol. 105: 1825-1830.
193. Ronald, J., R. Rajagopalan, F. Cerrato, A. S. Nord, T. Hatsukami, T. Kohler, S. Marcovina, P. Heagerty, and G. P. Jarvik. 2011. Genetic variation in LPAL2, LPA, and PLG predicts plasma lipoprotein(a) level and carotid artery disease risk. Stroke. 42: 2-9.
194. Armstrong, V. W., P. Cremer, E. Eberle, A. Manke, F. Schulze, H. Wieland, H. Kreuzer, and D. Seidel. 1986. The association between serum Lp(a) concentrations and angiographically assessed coronary atherosclerosis. Dependence on serum LDL levels. Atherosclerosis. 62: 249-257.
195. Groves, P., A. Rees, A. Bishop, R. Morgan, M. Ruttley, N. Lewis, I. Lane, and R. Hall. 1993. Apolipoprotein (a) concentrations and susceptibility to coronary artery disease in patients with peripheral vascular disease. Br. Heart J. 69: 26-30.
196. Budde, T., C. Fechtrup, E. Bosenberg, C. Vielhauer, A. Enbergs, H. Schulte, G. Assmann, and G. Breithardt. 1994. Plasma Lp(a) levels correlate with number, severity, and length-extension of coronary lesions in male patients undergoing coronary arteriography for clinically suspected coronary atherosclerosis. Arterioscler. Thromb. 14: 1730-1736.
197. Wang, X. L., C. Tam, R. M. McCredie, and D. E. Wilcken. 1994. Determinants of severity of coronary artery disease in Australian men and women. Circulation. 89: 1974-1981.
198. Zenker, G., P. Koltringer, G. Bone, K. Niederkorn, K. Pfeiffer, and G. Jurgens. 1986. Lipoprotein(a) as a strong indicator for cerebrovascular disease. Stroke. 17: 942-945.
199. Cambillau, M., A. Simon, J. Amar, P. Giral, V. Atger, P. Segond, J. Levenson, I. Merli, J. L. Megnien, and M. C. Plainfosse. 1992. Serum Lp(a) as a discriminant marker of early atherosclerotic plaque at three extracoronary sites in hypercholesterolemic men. The PCVMETRA Group. Arterioscler. Thromb. 12: 1346-1352.
200. Brown, S. A., J. D. Morrisett, E. Boerwinkle, R. Hutchinson, and W. Patsch. 1993. The relation of lipoprotein[a] concentrations and apolipoprotein[a] phenotypes with asymptomatic atherosclerosis in subjects of the Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler. Thromb. 13: 1558-1566.
201. Baldassarre, D., E. Tremoli, G. Franceschini, S. Michelagnoli, and C. R. Sirtori. 1996. Plasma lipoprotein(a) is an independent factor associated with carotid wall thickening in severely but not moderately hypercholesterolemic patients. Stroke. 27: 1044-1049.
202. Norrgård, O., K. A. Angquist, and G. Dahlen. 1991. Lp(a) lipoprotein in patients with arterial insufficiency of the lower extremities. Eur. J. Vasc. Surg. 5: 277-282.
203. Mölgaard, J., I. C. Klausen, C. Lassvik, O. Faergeman, L. U. Gerdes, and A. G. Olsson. 1992. Significant association between low-molecular-weight apolipoprotein(a) isoforms and intermittent claudication. Arterioscler. Thromb. 12: 895-901.
204. Widmann, M. D., and B. E. Sumpio. 1993. Lipoprotein (a): a risk factor for peripheral vascular disease. Ann. Vasc. Surg. 7: 446-451.
205. Pedro-Botet, J., M. Senti, T. Auguet, X. Nogues, J. Rubies-Prat, C. Aubo, and F. Vidal-Barraquer. 1993. Apolipoprotein(a) genetic polymorphism and serum lipoprotein(a) concentration in patients with peripheral vascular disease. Atherosclerosis. 104: 87-94.
206. Valentine, R. J., P. A. Grayburn, G. L. Vega, and S. M. Grundy. 1994. Lp(a) lipoprotein is an independent, discriminating risk factor for premature peripheral atherosclerosis among white men. Arch. Intern. Med. 154: 801-806.
207. Schreiner, P. J., J. D. Morrisett, A. R. Sharrett, W. Patsch, H. A. Tyroler, K. Wu, and G. Heiss. 1993. Lipoprotein[a] as a risk factor for preclinical atherosclerosis. Arterioscler. Thromb. 13: 826-833.
208. Denti, L., L. Marchini, G. Pasolini, M. T. Baffoni, F. Ablondi, and G. Valenti. 1995. Lipoprotein Lp(a) and cerebrovascular disease in the elderly: correlations with the severity of extracranial carotid atherosclerosis assessed by ultrasonography. Acta Biomed. Ateneo Parmense. 66: 175-183.
209. Srámek, A., J. H. Reiber, R. Baak-Pablo, A. Sturk, and F. R. Rosendaal. 2003. Lipoprotein(a) and ultrasonographically determined early atherosclerotic changes in the carotid and femoral artery. J. Thromb. Haemost. 1: 374-379.
210. Grebe, M. T., E. Schoene, C. A. Schaefer, R. H. Boedeker, B. Kemkes-Matthes, R. Voss, and H. H. Tillmanns. 2007. Elevated lipoprotein(a) does not promote early atherosclerotic changes of the carotid arteries in young, healthy adults. Atherosclerosis. 190: 194-198.
211. Kivimäki, M., C. G. Magnussen, M. Juonala, M. Kähönen, J. Kettunen, B. M. Loo, T. Lehtimäki, J. Viikari, and O. T. Raitakari. 2011. Conventional and Mendelian randomization analyses suggest no association between lipoprotein(a) and early atherosclerosis: the Young Finns Study. Int. J. Epidemiol. 40: 470-478.
212. Calmarza, P., J. M. Trejo, C. Lapresta, and P. Lopez. 2012. Relationship between lipoprotein(a) concentrations and intimamedia thickness: a healthy population study. Eur. J. Prev. Cardiol. 19: 1290-1295.
213. Bos, S., M. H. Duvekot, A. C. Touw-Blommesteijn, A. J. Verhoeven, M. T. Mulder, G. F. Watts, E. J. Sijbrands, and J. E. Roeters van Lennep. 2015. Lipoprotein (a) levels are not associated with carotid plaques and carotid intima media thickness in statin-treated patients with familial hypercholesterolemia. Atherosclerosis. 242: 226-229.
214. Gotoh, T., T. Kuroda, M. Yamasawa, M. Nishinaga, T. Mitsuhashi, Y. Seino, N. Nagoh, K. Kayaba, S. Yamada, and H. Matsuo. 1995. Correlation between lipoprotein(a) and aortic valve sclerosis assessed by echocardiography (the JMS Cardiac Echo and Cohort Study). Am. J. Cardiol. 76: 928-932.
215. Stewart, B. F., D. Siscovick, B. K. Lind, J. M. Gardin, J. S. Gottdiener, V. E. Smith, D. W. Kitzman, and C. M. Otto. 1997. Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. J. Am. Coll. Cardiol. 29: 630-634.
216. Glader, C. A., L. S. Birgander, S. Soderberg, H. P. Ildgruben, P. Saikku, A. Waldenstrom, and G. H. Dahlen. 2003. Lipoprotein(a), Chlamydia pneumoniae, leptin and tissue plasminogen activator as risk markers for valvular aortic stenosis. Eur. Heart J. 24: 198-208.
217. Bozbas, H., A. Yildirir, I. Atar, B. Pirat, S. Eroglu, A. Aydinalp, B. Ozin, and H. Muderrisoglu. 2007. Effects of serum levels of novel atherosclerotic risk factors on aortic valve calcification. J. Heart Valve Dis. 16: 387-393.
218. Arsenault, B. J., S. M. Boekholdt, M. P. Dube, E. Rheaume, N. J. Wareham, K. T. Khaw, M. S. Sandhu, and J. C. Tardif. 2014. Lipoprotein(a) levels, genotype, and incident aortic valve stenosis: a prospective Mendelian randomization study and replication in a case-control cohort. Circ Cardiovasc Genet. 7: 304-310.
219. Capoulade, R., K. L. Chan, C. Yeang, P. Mathieu, Y. Bosse, J. G. Dumesnil, J. W. Tam, K. K. Teo, A. Mahmut, X. Yang, et al. 2015. Oxidized phospholipids, lipoprotein(a), and progression of calcific aortic valve stenosis. J. Am. Coll. Cardiol. 66: 1236-1246.
220. Vongpromek, R., S. Bos, G. J. Ten Kate, R. Yahya, A. J. Verhoeven, P. J. de Feyter, F. Kronenberg, J. E. Roeters van Lennep, E. J. Sijbrands, and M. T. Mulder. 2015. Lipoprotein(a) levels are associated with aortic valve calcification in asymptomatic patients with familial hypercholesterolaemia. J. Intern. Med. 278: 166-173.
221. Yang, N., G. Zhang, X. Li, and L. Zhou. 2015. Correlation analysis between serum lipoprotein (a) and the incidence of aortic valve sclerosis. Int. J. Clin. Exp. Med. 8: 19318-19324.
222. Hojo, Y., H. Kumakura, H. Kanai, T. Iwasaki, S. Ichikawa, and M. Kurabayashi. 2016. Lipoprotein(a) is a risk factor for aortic and mitral valvular stenosis in peripheral arterial disease. Eur. Heart J. Cardiovasc. Imaging. 17: 492-497.
223. Nsaibia, M. J., A. Mahmut, M. C. Boulanger, B. J. Arsenault, R. Bouchareb, S. Simard, J. L. Witztum, M. A. Clavel, P. Pibarot, Y. Bosse, et al. Autotaxin interacts with lipoprotein(a) and oxidized phospholipids in predicting the risk of calcific aortic valve stenosis in patients with coronary artery disease. J. Intern. Med. Epub ahead of print. May 30, 2016; doi:10.1111/joim.12519.
224. Sofi, F., R. Marcucci, R. Abbate, G. F. Gensini, and D. Prisco. 2007. Lipoprotein (a) and venous thromboembolism in adults: a metaanalysis. Am. J. Med. 120: 728-733.
225. Atsumi, T., M. A. Khamashta, C. Andujar, M. J. Leandro, O. Amengual, P. R. Ames, and G. R. Hughes. 1998. Elevated plasma lipoprotein(a) level and its association with impaired fibrinolysis in patients with antiphospholipid syndrome. J. Rheumatol. 25: 69-73.
226. von Depka, M., U. Nowak-Gottl, R. Eisert, C. Dieterich, M. Barthels, I. Scharrer, A. Ganser, and S. Ehrenforth. 2000. Increased lipoprotein (a) levels as an independent risk factor for venous thromboembolism. Blood. 96: 3364-3368.
227. Marcucci, R., A. A. Liotta, A. P. Cellai, A. Rogolino, A. M. Gori, B. Giusti, D. Poli, S. Fedi, R. Abbate, and D. Prisco. 2003. Increased plasma levels of lipoprotein(a) and the risk of idiopathic and recurrent venous thromboembolism. Am. J. Med. 115: 601-605.
228. März, W., E. Aygören, M. Trommlitz, I. Scharrer, and W. Gross. 1990. Lipoprotein(a): an indicator of risk in thromboembolic disease? [article in German]. Klin. Wochenschr. 68(Suppl 22): 111-112.
229. Van Wersch, J. W. 1994. The behaviour of lipoprotein(a) in patients with various diseases. Scand. J. Clin. Lab. Invest. 54: 559-562.
230. Vormittag, R., T. Vukovich, M. Stain, S. Lehr, E. Minar, and I. Pabinger. 2007. Lipoprotein (a) in patients with spontaneous venous thromboembolism. Thromb. Res. 120: 15-20.
231. Tsai, A. W., M. Cushman, W. D. Rosamond, S. R. Heckbert, J. F. Polak, and A. R. Folsom. 2002. Cardiovascular risk factors and venous thromboembolism incidence: the longitudinal investigation of thromboembolism etiology. Arch. Intern. Med. 162: 1182-1189.
232. Nowak-Göttl, U., O. Debus, M. Findeisen, R. Kassenbohmer, H. G. Koch, H. Pollmann, C. Postler, P. Weber, and H. Vielhaber. 1997. Lipoprotein (a): its role in childhood thromboembolism. Pediatrics. 99: E11.
233. Münchow, N., A. Kosch, R. Schobess, R. Junker, K. Auberger, and U. Nowak-Göttl. 1999. Role of genetic prothrombotic risk factors in childhood caval vein thrombosis. Eur. J. Pediatr. 158(Suppl 3): S109-S112.
234. Nowak-Göttl, U., R. Junker, M. Hartmeier, H. G. Koch, N. Münchow, G. Assmann, and A. von Eckardstein. 1999. Increased lipoprotein(a) is an important risk factor for venous thromboembolism in childhood. Circulation. 100: 743-748.
235. Nowak-Göttl, U., C. Wermes, R. Junker, H. G. Koch, R. Schobess, G. Fleischhack, D. Schwabe, and S. Ehrenforth. 1999. Prospective evaluation of the thrombotic risk in children with acute lymphoblastic leukemia carrying the MTHFR TT 677 genotype, the prothrombin G20210A variant, and further prothrombotic risk factors. Blood. 93: 1595-1599.
236. Heller, C., R. Schobess, K Kurnik, R. Junker, G. Gunther, W. Kreuz, and U. Nowak-Gottl. 2000. Abdominal venous thrombosis in neonates and infants: role of prothrombotic risk factors - a multicentre case-control study. For the Childhood Thrombophilia Study Group. Br. J. Haematol. 111: 534-539.
237. Kosch, A., R. Junker, K Kurnik, R. Schobess, G. Gunther, H. Koch, and U. Nowak-Gottl. 2000. Prothrombotic risk factors in children with spontaneous venous thrombosis and their asymptomatic parents: a family study. Thromb. Res. 99: 531-537.
238. Korte, W., J. Greiner, A. Feldges, and W. F. Riesen. 2001. Increased lipoprotein(a) levels are not a steady prothrombotic defect. Blood. 98: 1993-1994.
239. Nowak-Göttl, U., R. Junker, W. Kreuz, A. von Eckardstein, A Kosch, N. Nohe, R. Schobess, and S. Ehrenforth. 2001. Risk of recurrent venous thrombosis in children with combined prothrombotic risk factors. Blood. 97: 858-862.
240. Gözdaşoǧlu, S., Z. Uysal, M. Ertem, and N. Akar. 2002. Three risk factors-high lipoprotein (a), elevated FVIII, and FV Leiden-in a pediatric Behcet's disease patient with deep vein thrombosis. Thromb. Res. 106: 263.
241. Revel-Vilk, S., A. Chan, M. Bauman, and P. Massicotte. 2003. Prothrombotic conditions in an unselected cohort of children with venous thromboembolic disease. J. Thromb. Haemost. 1: 915-921.
242. Kosch, A., E. Kuwertz-Broking, C. Heller, K Kurnik, R. Schobess, and U. Nowak-Gottl. 2004. Renal venous thrombosis in neonates: prothrombotic risk factors and long-term follow-up. Blood. 104: 1356-1360.
243. Danik, J. S., J. E. Buring, D. I. Chasman, R. Y. Zee, P. M. Ridker, and R. J. Glynn. 2013. Lipoprotein(a), polymorphisms in the LPA gene, and incident venous thromboembolism among 21483 women. J. Thromb. Haemost. 11: 205-208.
244. Sticchi, E., A. Magi, P. R. Kamstrup, R. Marcucci, D. Prisco, I. Martinelli, P. M. Mannucci, R. Abbate, and B. Giusti. 2016. Apolipoprotein(a) kringle-IV type 2 copy number variation is associated with venous thromboembolism. PLoS One. 11: e0149427.
245. Nordestgaard, B. G., and A. Langsted. 2015. How does elevated lipoprotein(a) cause aortic valve stenosis? J. Am. Coll. Cardiol. 66: 1247-1249.
246. Caplice, N. M., C. Panetta, T. E. Peterson, L. S. Kleppe, C. S. Mueske, G. M. Kostner, G. J. Broze, Jr., and R. D. Simari. 2001. Lipoprotein (a) binds and inactivates tissue factor pathway inhibitor: a novel link between lipoproteins and thrombosis. Blood. 98: 2980-2987.
247. Boffa, M. B., S. M. Marcovina, and M. L. Koschinsky 2004. Lipoprotein(a) as a risk factor for atherosclerosis and thrombosis: mechanistic insights from animal models. Clin. Biochem. 37: 333-343.
248. Ishikawa, S., K Kotani, K Kario, K Kayaba, T. Gotoh, Y. Nakamura, and E. Kajii. 2013. Inverse association between serum lipoprotein(a) and cerebral hemorrhage in the Japanese population. Thromb. Res. 131: e54-e58.
249. Anglés-Cano, E., D. A. de la Peña, and S. Loyau. 2001. Inhibition of fibrinolysis by lipoprotein(a). Ann. N. Y. Acad. Sci. 936: 261-275.
250. Undas, A., E. Stepien, W. Tracz, and A. Szczeklik. 2006. Lipoprotein(a) as a modifer of fibrin clot permeability and susceptibility to lysis. J. Thromb. Haemost. 4: 973-975.
251. von Zychlinski, A., T. Kleffmann, M. J. Williams, and S. P. McCormick. 2011. Proteomics of lipoprotein(a) identifies a protein complement associated with response to wounding. J. Proteomics. 74: 2881-2891.
252. van der Valk, F. M., S. Bekkering, J. Kroon, C. Yeang, J. Van den Bossche, J. D. van Buul, A. Ravandi, A. J. Nederveen, H. J. Verberne, C. Scipione, et al. 2016. Oxidized phospholipids on lipoprotein(a) elicit arterial wall inflammation and an inflammatory monocyte response in humans. Circulation. 134: 611-624.
253. Varbo, A., M. Benn, A. Tybjaerg-Hansen, and B. G. Nordestgaard. 2013. Elevated remnant cholesterol causes both low-grade inflammation and ischemic heart disease, whereas elevated low-density lipoprotein cholesterol causes ischemic heart disease without inflammation. Circulation. 128: 1298-1309.
254. Loscalzo, J., M. Weinfeld, G. M. Fless, and A. M. Scanu. 1990. Lipoprotein(a), fibrin binding, and plasminogen activation. Arteriosclerosis. 10: 240-245.
255. Simon, D. I., G. M. Fless, A. M. Scanu, and J. Loscalzo. 1991. Tissue-type plasminogen activator binds to and is inhibited by surface-bound lipoprotein(a) and low-density lipoprotein. Biochemistry. 30: 6671-6677.
256. Rouy, D., P. Grailhe, F. Nigon, J. Chapman, and E. Angles-Cano. 1991 Lipoprotein(a) impairs generation of plasmin by fibrinbound tissue-type plasminogen activator. In vitro studies in a plasma milieu. Arterioscler. Thromb. 11: 629-638.
257. Yano, Y, K Shimokawa, Y. Okada, and A. Noma. 1997. Immunolocalization of lipoprotein(a) in wounded tissues. J. Histochem. Cytochem. 45: 559-568.
258. Hoff, H. F., G. J. Beck, C. I. Skibinski, G. Jurgens, J. O'Neil, J. Kramer, and B. Lytle. 1988. Serum Lp(a) level as a predictor of vein graft stenosis after coronary artery bypass surgery in patients. Circulation. 77: 1238-1244.
259. Cooke, T., R. Sheahan, D. Foley, M. Reilly, G. D'Arcy, W. Jauch, M. Gibney, G. Gearty, P. Crean, and M. Walsh. 1994. Lipoprotein(a) in restenosis after percutaneous transluminal coronary angioplasty and coronary artery disease. Circulation. 89: 1593-1598.
260. Graham, M. J., N. Viney, R. M. Crooke, and S. Tsimikas. 2016. Antisense inhibition of apolipoprotein (a) to lower plasma lipoprotein (a) levels in humans. J. Lipid Res. 57: 340-351.
261. Guo, H. C, M. J. Chapman, E. Bruckert, J. P. Farriaux, and J. L. De Gennes. 1991. Lipoprotein Lp(a) in homozygous familial hypercholesterolemia: density profile, particle heterogeneity and apolipoprotein(a) phenotype. Atherosclerosis. 86: 69-83.
262. Leitersdorf, E., Y. Friedlander, J. M. Bard, J. C. Fruchart, S. Eisenberg, and Y. Stein. 1991. Diverse effect of ethnicity on plasma lipoprotein[a] levels in heterozygote patients with familial hypercholesterolemia. J. Lipid Res. 32: 1513-1519.
263. Mbewu, A. D., D. Bhatnagar, P. N. Durrington, L. Hunt, M. Ishola, S. Arrol, M. Mackness, P. Lockley, and J. P. Miller. 1991. Serum lipoprotein(a) in patients heterozygous for familial hypercholesterolemia, their relatives, and unrelated control populations. Arterioscler. Thromb. 11: 940-946.
264. Soutar, A. K, S. N. McCarthy, M. Seed, and B. L. Knight. 1991. Relationship between apolipoprotein(a) phenotype, lipoprotein(a) concentration in plasma, and low density lipoprotein receptor function in a large kindred with familial hypercholesterolemia due to the pro664 - leu mutation in the LDL receptor gene. J. Clin. Invest. 88: 483-492.
265. Bowden, J. F., P. H. Pritchard, J. S. Hill, and J. J. Frohlich. 1994. Lp(a) concentration and apo(a) isoform size. Relation to the presence of coronary artery disease in familial hypercholesterolemia. Arterioscler. Thromb. 14: 1561-1568.
266. Lingenhel, A., H. G. Kraft, M. Kotze, A. V. Peeters, F. Kronenberg, R Kruse, and G. Utermann. 1998. Concentrations of the atherogenic Lp(a) are elevated in FH. Eur. J. Hum. Genet. 6: 50-60.
267. Ghiselli, G., A. Gaddi, G. Barozzi, A. Ciarrocchi, and G. Descovich. 1992 Plasma lipoprotein(a) concentration in familial hypercholesterolemic patients without coronary artery disease. Metabolism. 41: 833-838.
268. Carmena, R., S. Lussier-Cacan, M. Roy, A. Minnich, A. Lingenhel, F. Kronenberg, and J. Davignon. 1996. Lp(a) levels and atherosclerotic vascular disease in a sample of patients with familial hypercholesterolemia sharing the same gene defect. Arterioscler. Thromb. Vasc. Biol. 16: 129-136.
269. Benn, M., G. F. Watts, A. Tybjaerg-Hansen, and B. G. Nordestgaard. 2012. Familial hypercholesterolemia in the Danish general population: prevalence, coronary artery disease and cholesterol-lowering medication. J. Clin. Endocrinol. Metab. 97: 3956-3964.
270. Nordestgaard, B. G., M. J. Chapman, S. E. Humphries, H. N. Ginsberg, L. Masana, O. S. Descamps, O. Wiklund, R. A. Hegele, F. J. Raal, J. C. Defesche, et al. 2013. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur. Heart J. 34: 3478-3490a.
271. Benn, M., G. F. Watts, A. Tybjaerg-Hansen, and B. G. Nordestgaard. 2016. Mutations causative of familial hypercholesterolaemia: screening of 98 098 individuals from the Copenhagen General Population Study estimated a prevalence of 1 in 217. Eur. Heart J. 37: 1384-1394.
272. Sjouke, B., D. M. Kusters, I. Kindt, J. Besseling, J. C. Defesche, E. J. Sijbrands, J. E. Roeters van Lennep, A. F. Stalenhoef, A. Wiegman, J. de Graaf, et al. 2015. Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: prevalence, genotypephenotype relationship, and clinical outcome. Eur. Heart J. 36: 560-565.
273. Do, R., N. O. Stitziel, H. H. Won, A. B. Jorgensen, S. Duga, M. P. Angelica, A. Kiezun, M. Farrall, A. Goel, O. Zuk, et al. 2015. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature. 518: 102-106.
274. Rader, D. J., W. A. Mann, W. Cain, H. G. Kraft, D. Usher, L. A. Zech, J. M. Hoeg, J. Davignon, P. Lupien, and M. Grossman. 1995. The low density lipoprotein receptor is not required for normal catabolism of Lp(a) in humans. J. Clin. Invest. 95: 1403-1408.
275. Rader, D. J., W. Cain, K. Ikewaki, G. Talley, L. A. Zech, D. Usher, and H. B. Brewer, Jr. 1994. 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. 93: 2758-2763.
276. Kraft, H. G., A. Lingenhel, F. J. Raal, M. Hohenegger, and G. Utermann. 2000. Lipoprotein(a) in homozygous familial hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol. 20: 522-528.
277. Tybjaerg-Hansen, A., H. K. Jensen, M. Benn, R. Steffensen, G. Jensen, and B. G. Nordestgaard. 2005. Phenotype of heterozygotes for low-density lipoprotein receptor mutations identified in different background populations. Arterioscler. Thromb. Vasc. Biol. 25: 211-215.
278. Jansen, A. C., E. S. van Aalst-Cohen, M. W. Tanck, M. D. Trip, P. J. Lansberg, A. H. Liem, H. W. van Lennep, E. J. Sijbrands, and J. J. Kastelein. 2004. The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolaemia: data in 2400 patients. J. Intern. Med. 256: 482-490.
279. Cuchel, M., E. Bruckert, H. N. Ginsberg, F. J. Raal, R. D. Santos, R. A. Hegele, J. A. Kuivenhoven, B. G. Nordestgaard, O. S. Descamps, E. Steinhagen-Thiessen, et al. 2014. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur. Heart J. 35: 2146-2157.
280. Wiegman, A., S. S. Gidding, G. F. Watts, M. J. Chapman, H. N. Ginsberg, M. Cuchel, L. Ose, M. Averna, C. Boileau, J. Boren, et al. 2015. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur. Heart J. 36: 2425-2437.
281. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994. 344: 1383-1389.