title: Population and assay thresholds for the predictive value of lipoprotein (a) for coronary artery disease: the EPIC-Norfolk Prospective Population Study.
abstract: Variable agreement exists between different lipoprotein (a) [Lp(a)] measurement methods, but their clinical relevance remains unclear. The predictive value of Lp(a) measured by two different assays [Randox and University of California, San Diego (UCSD)] was determined in 623 coronary artery disease (CAD) cases and 948 controls in a case-control study within the EPIC-Norfolk Prospective Population Study. Participants were divided into sex-specific quintiles, and by Lp(a) <50 versus ∼50 mg/dl, which represents the 80th percentile in northern European subjects. Randox and UCSD Lp(a) levels were strongly correlated; Spearman's correlation coefficients for men, women, and sexes combined were 0.905, 0.915, and 0.909, respectively (P< 0.001 for each). The >80th percentile cutoff values, however, were 36 mg/dl and 24 mg/dl for the Randox and UCSD assays, respectively. Despite this, Lp(a) levels were significantly associated with CAD risk, with odds ratios of 2.18 (1.58-3.01) and 2.35 (1.70-3.26) for people in the top versus bottom Lp(a) quintile for the Randox and UCSD assays, respectively. This study demonstrates that CAD risk is present at lower Lp(a) levels than the currently suggested optimal Lp(a) level of <50 mg/dl. Appropriate thresholds may need to be population and assay specific until Lp(a) assays are standardized and Lp(a) thresholds are evaluated broadly across all populations at risk for CVD and aortic stenosis.
authors.affiliation: Department of Vascular Medicine Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Rutger
authors.initials: R
authors.lastname: Verbeek
authors.affiliation: Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: S Matthijs
authors.initials: SM
authors.lastname: Boekholdt
authors.affiliation: Department of Vascular Medicine Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Stoekenbroek
authors.affiliation: Department of Vascular Medicine Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.affiliation: Division of Endocrinology, Department of Medicine, University of California, San Diego, La Jolla, CA.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.affiliation: Medical Research Council Epidemiology Unit, Cambridge, United Kingdom.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Manjinder S
authors.initials: MS
authors.lastname: Sandhu
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.affiliation: Vascular Medicine Program, Sulpizio Cardiovascular Center, University of California, San Diego, La Jolla, CA stsimikas@ucsd.edu.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tsimikas
mesh_terms: D000368:Aged; D001774:Blood Chemical Analysis / Q000379:methods* / Q000592:standards*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012016:Reference Values
chemical_list: D017270:Lipoprotein(a)
keywords: aortic stenosis; atherosclerosis; risk factor
references.citation: Clin Chem. 2000 Dec;46(12):1956-67
references.pmid: 11106328
references.citation: Biomark Med. 2011 Oct;5(5):673-94
references.pmid: 22003918
references.citation: Circulation. 2004 Jun 29;109(25):3164-70
references.pmid: 15184281
references.citation: Clin Chem Lab Med. 2004;42(6):670-6
references.pmid: 15259385
references.citation: Circulation. 2004 Sep 14;110(11):1406-12
references.pmid: 15353498
references.citation: Am J Med. 2004 Sep 15;117(6):390-7
references.pmid: 15380495
references.citation: Atherosclerosis. 1981 Jan-Feb;38(1-2):51-61
references.pmid: 7470205
references.citation: Arterioscler Thromb. 1992 Mar;12(3):302-6
references.pmid: 1532126
references.citation: J Clin Invest. 1992 Jul;90(1):52-60
references.pmid: 1386087
references.citation: Clin Chem. 1995 Feb;41(2):246-55
references.pmid: 7533064
references.citation: Clin Chem. 1996 Mar;42(3):436-9
references.pmid: 8598109
references.citation: Br J Cancer. 1999 Jul;80 Suppl 1:95-103
references.pmid: 10466767
references.citation: Arterioscler Thromb Vasc Biol. 2007 Sep;27(9):2030-6
references.pmid: 17569884
references.citation: Circulation. 2008 Jan 15;117(2):176-84
references.pmid: 18086931
references.citation: Atherosclerosis. 2009 Apr;203(2):371-6
references.pmid: 18775538
references.citation: JAMA. 2009 Jul 22;302(4):412-23
references.pmid: 19622820
references.citation: N Engl J Med. 2009 Dec 24;361(26):2518-28
references.pmid: 20032323
references.citation: J Am Coll Cardiol. 2010 May 11;55(19):2160-7
references.pmid: 20447543
references.citation: J Am Coll Cardiol. 2010 Sep 14;56(12):946-55
references.pmid: 20828647
references.citation: Eur Heart J. 2010 Dec;31(23):2844-53
references.pmid: 20965889
references.citation: J Clin Lipidol. 2010 Jul-Aug;4(4):240-7
references.pmid: 21122656
references.citation: N Engl J Med. 2010 Dec 16;363(25):2406-15
references.pmid: 21082868
references.citation: J Lipid Res. 2011 Jun;52(6):1181-7
references.pmid: 21478162
references.citation: J Am Coll Cardiol. 2012 Aug 21;60(8):716-21
references.pmid: 22898069
references.citation: Arterioscler Thromb Vasc Biol. 2012 Dec;32(12):3058-65
references.pmid: 23065826
references.citation: J Intern Med. 2013 Jan;273(1):6-30
references.pmid: 22998429
references.citation: J Am Coll Cardiol. 2013 Mar 19;61(11):1146-56
references.pmid: 23375930
references.citation: Metabolism. 2013 Apr;62(4):479-91
references.pmid: 23040268
references.citation: J Lipid Res. 2013 Oct;54(10):2815-30
references.pmid: 23828779
references.citation: J Am Coll Cardiol. 2013 Oct 22;62(17):1575-9
references.pmid: 23973688
references.citation: Arterioscler Thromb Vasc Biol. 2013 Dec;33(12):2902-8
references.pmid: 24092750
references.citation: J Am Coll Cardiol. 2014 Apr 8;63(13):1278-88
references.pmid: 24509273
references.citation: Am J Cardiol. 2014 Sep 1;114(5):711-5
references.pmid: 25060413
references.citation: J Am Coll Cardiol. 2014 Sep 2;64(9):851-60
references.pmid: 25169167
references.citation: Arterioscler Thromb Vasc Biol. 2015 Mar;35(3):689-99
references.pmid: 25614280
references.citation: Arterioscler Thromb Vasc Biol. 2015 Apr;35(4):996-1001
references.pmid: 25810300
references.citation: Lancet. 2015 Oct 10;386(10002):1472-83
references.pmid: 26210642
references.citation: Clin Chem. 2003 Nov;49(11):1785-96
references.pmid: 14578310