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Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism

Helgadottir, Anna; Gretarsdottir, Solveig; Thorleifsson, Gudmar; Holm, Hilma; Patel, Riyaz S.; Gudnason, Thorarinn; Jones, Gregory T.; van Rij, Andre M.; Eapen, Danny J. and Baas, Annette F., et al. (2012) In Journal of the American College of Cardiology 60(8). p.722-729
Abstract
Objectives 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. Background 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. Methods 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 (ne = 4,572); venous thromboembolism (ne =... (More)
Objectives 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. Background 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. Methods 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 (ne = 4,572); venous thromboembolism (ne = 4,607); intracranial aneurysm (ne = 1,328); CAD (n(e) = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). Results LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 X 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 x 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 x 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 x 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 x 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). Conclusions LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes. (J Am Coll Cardiol 2012; 60: 722-9) (C) 2012 by the American College of Cardiology Foundation (Less)
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keywords
association, atherosclerosis, genetic, lipoprotein(a), thrombosis
in
Journal of the American College of Cardiology
volume
60
issue
8
pages
722 - 729
publisher
Elsevier USA
external identifiers
  • wos:000307463800004
  • scopus:84865125773
ISSN
0735-1097
DOI
10.1016/j.jacc.2012.01.078
language
English
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yes
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17a9f062-dc3e-4135-95b2-d6f60c1d0114 (old id 3055823)
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2012-10-05 07:15:30
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2017-10-22 03:03:25
@article{17a9f062-dc3e-4135-95b2-d6f60c1d0114,
  abstract     = {Objectives 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. Background 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. Methods 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 (ne = 4,572); venous thromboembolism (ne = 4,607); intracranial aneurysm (ne = 1,328); CAD (n(e) = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). Results LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 X 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 x 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 x 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 x 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 x 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). Conclusions LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes. (J Am Coll Cardiol 2012; 60: 722-9) (C) 2012 by the American College of Cardiology Foundation},
  author       = {Helgadottir, Anna and Gretarsdottir, Solveig and Thorleifsson, Gudmar and Holm, Hilma and Patel, Riyaz S. and Gudnason, Thorarinn and Jones, Gregory T. and van Rij, Andre M. and Eapen, Danny J. and Baas, Annette F. and Tregouet, David-Alexandre and Morange, Pierre-Emmanuel and Emmerich, Joseph and Lindblad, Bengt and Gottsäter, Anders and Kiemeny, Lambertus A. and Lindholt, Jes S. and Sakalihasan, Natzi and Ferrell, Robert E. and Carey, David J. and Elmore, James R. and Tsao, Philip S. and Grarup, Niels and Jorgensen, Torben and Witte, Daniel R. and Hansen, Torben and Pedersen, Oluf and Pola, Roberto and Gaetani, Eleonora and Magnadottir, Hulda B. and Wijmenga, Cisca and Tromp, Gerard and Ronkainen, Antti and Ruigrok, Ynte M. and Blankensteijn, Jan D. and Mueller, Thomas and Wells, Philip S. and Corral, Javier and Manuel Soria, Jose and Carlos Souto, Juan and Peden, John F. and Jalilzadeh, Shapour and Mayosi, Bongani M. and Keavney, Bernard and Strawbridge, Rona J. and Sabater-Lleal, Maria and Gertow, Karl and Baldassarre, Damiano and Nyyssonen, Kristiina and Rauramaa, Rainer and Smit, Andries J. and Mannarino, Elmo and Giral, Philippe and Tremoli, Elena and de Faire, Ulf and Humphries, Steve E. and Hamsten, Anders and Haraldsdottir, Vilhelmina and Olafsson, Isleifur and Magnusson, Magnus K. and Samani, Nilesh J. and Levey, Allan I. and Markus, Hugh S. and Kostulas, Konstantinos and Dichgans, Martin and Berger, Klaus and Kuhlenbaeumer, Gregor and Ringelstein, E. Bernd and Stoll, Monika and Seedorf, Udo and Rothwell, Peter M. and Powell, Janet T. and Kuivaniemi, Helena and Onundarson, Pall T. and Valdimarsson, Einar and Matthiasson, Stefan E. and Gudbjartsson, Daniel F. and Thorgeirsson, Guomundur and Quyyumi, Arshed A. and Watkins, Hugh and Farrall, Martin and Thorsteinsdottir, Unnur and Stefansson, Kari},
  issn         = {0735-1097},
  keyword      = {association,atherosclerosis,genetic,lipoprotein(a),thrombosis},
  language     = {eng},
  number       = {8},
  pages        = {722--729},
  publisher    = {Elsevier USA},
  series       = {Journal of the American College of Cardiology},
  title        = {Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism},
  url          = {http://dx.doi.org/10.1016/j.jacc.2012.01.078},
  volume       = {60},
  year         = {2012},
}