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Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism.

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Authors
Helgadottir, Anna
Gretarsdottir, Solveig
Thorleifsson, Gudmar
Holm, Hilma
Patel, Riyaz S
Gudnason, Thorarinn
Jones, Gregory T
van Rij, Andre M
Eapen, Danny J
Baas, Annette F
Tregouet, David-Alexandre
Morange, Pierre-Emmanuel
Emmerich, Joseph
Lindblad, Bengt
Gottsäter, Anders
Kiemeny, Lambertus A
Lindholt, Jes S
Sakalihasan, Natzi
Ferrell, Robert E
Carey, David J
Elmore, James R
Tsao, Philip S
Grarup, Niels
Jørgensen, Torben
Witte, Daniel R
Hansen, Torben
Pedersen, Oluf
Pola, Roberto
Gaetani, Eleonora
Magnadottir, Hulda B
Wijmenga, Cisca
Tromp, Gerard
Ronkainen, Antti
Ruigrok, Ynte M
Blankensteijn, Jan D
Mueller, Thomas
Wells, Philip S
Corral, Javier
Soria, Jose Manuel
Souto, Juan Carlos
Peden, John F
Jalilzadeh, Shapour
Mayosi, Bongani M
Keavney, Bernard
Strawbridge, Rona J
Sabater-Lleal, Maria
Gertow, Karl
Baldassarre, Damiano
Nyyssönen, Kristiina
Rauramaa, Rainer
Smit, Andries J
Mannarino, Elmo
Giral, Philippe
Tremoli, Elena
de Faire, Ulf
Humphries, Steve E
Hamsten, Anders
Haraldsdottir, Vilhelmina
Olafsson, Isleifur
Magnusson, Magnus K
Samani, Nilesh J
Levey, Allan I
Markus, Hugh S
Kostulas, Konstantinos
Dichgans, Martin
Berger, Klaus
Kuhlenbäumer, Gregor
Ringelstein, E Bernd
Stoll, Monika
Seedorf, Udo
Rothwell, Peter M
Powell, Janet T
Kuivaniemi, Helena
Onundarson, Pall T
Valdimarsson, Einar
Matthiasson, Stefan E
Gudbjartsson, Daniel F
Thorgeirsson, Guðmundur
Quyyumi, Arshed A
Watkins, Hugh
Farrall, Martin
Thorsteinsdottir, Unnur
Stefansson, Kari
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Issue Date
2012-08-21

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Citation
J. Am. Coll. Cardiol. 2012, 60(8):722-9
Abstract
The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis. The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST [Trial of Org 10172 in Acute Stroke Treatment] subtypes) (effective sample size [n(e)] = 9,396); peripheral arterial disease (n(e) = 5,215); abdominal aortic aneurysm (n(e) = 4,572); venous thromboembolism (n(e) = 4,607); intracranial aneurysm (n(e) = 1,328); CAD (n(e) = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 × 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 × 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 × 10(-5)), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 × 10(-12)). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (-1.58 years/allele; p = 8.2 × 10(-8)) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15). LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes.
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Additional Links
http://dx.doi.org/10.1016/j.jacc.2012.01.078
http://www.sciencedirect.com/science/article/pii/S0735109712019638#
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Archived with thanks to Journal of the American College of Cardiology
ae974a485f413a2113503eed53cd6c53
10.1016/j.jacc.2012.01.078
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English Journal Articles (Peer Reviewed)

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