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Based on genetic evidence provided by studies conducted over the last two decades, <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>p(a) is currently considered to be the strongest genetic risk factor for coronary heart disease (<jats:styled-content style=\"fixed-case\">CHD<\/jats:styled-content>). The copy number variation of kringle <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> in the <jats:italic><jats:styled-content style=\"fixed-case\">LPA<\/jats:styled-content><\/jats:italic> gene has been strongly associated with both <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>p(a) levels in plasma and risk of <jats:styled-content style=\"fixed-case\">CHD<\/jats:styled-content>, thereby fulfilling the main criterion for causality in a <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>endelian randomization approach. Alleles with a low kringle <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> copy number that together have a population frequency of 25\u201335% are associated with a doubling of the relative risk for outcomes, which is exceptional in the field of complex genetic phenotypes. The recently identified binding of oxidized phospholipids to <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>p(a) is considered as one of the possible mechanisms that may explain the pathogenicity of <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>p(a). Drugs that have been shown to lower <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>p(a) have pleiotropic effects on other <jats:styled-content style=\"fixed-case\">CHD<\/jats:styled-content> risk factors, and an improvement of cardiovascular endpoints is up to now lacking. However, it has been established in a proof of principle study that lowering of very high <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>p(a) by apheresis in high\u2010risk patients with already maximally reduced low\u2010density lipoprotein cholesterol levels can dramatically reduce major coronary events.<\/jats:p>","DOI":"10.1111\/j.1365-2796.2012.02592.x","type":"journal-article","created":{"date-parts":[[2013,4,12]],"date-time":"2013-04-12T13:53:01Z","timestamp":1365774781000},"page":"6-30","source":"Crossref","is-referenced-by-count":497,"title":["Lipoprotein(a): resurrected by genetics"],"prefix":"10.1111","volume":"273","author":[{"given":"F.","family":"Kronenberg","sequence":"first","affiliation":[{"name":"Division of Genetic Epidemiology Department of Medical Genetics, Molecular and Clinical Pharmacology Innsbruck Medical University Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Utermann","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Department of Medical Genetics, Molecular and Clinical Pharmacology Innsbruck Medical University Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,11,12]]},"reference":[{"key":"e_1_2_18_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1699-0463.1963.tb01808.x"},{"key":"e_1_2_18_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2530631"},{"key":"e_1_2_18_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(91)90007-P"},{"key":"e_1_2_18_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1993.03510180065035"},{"key":"e_1_2_18_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.1063"},{"key":"e_1_2_18_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.10.080"},{"key":"e_1_2_18_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.801"},{"key":"e_1_2_18_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.314"},{"key":"e_1_2_18_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0902604"},{"key":"e_1_2_18_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq386"},{"key":"e_1_2_18_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/330132a0"},{"key":"e_1_2_18_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.22.11992"},{"key":"e_1_2_18_14_1","doi-asserted-by":"crossref","first-page":"5957","DOI":"10.1016\/S0021-9258(18)83643-2","article-title":"Rhesus monkey apolipoprotein(a). 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