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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)722-729
Number of pages8
JournalJournal of the American College of Cardiology
Volume60
Issue number8
DOIs
Publication statusPublished - Aug 21 2012

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Keywords

  • association
  • atherosclerosis
  • genetic
  • lipoprotein(a)
  • thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Helgadottir, A., Gretarsdottir, S., Thorleifsson, G., Holm, H., Patel, R. S., Gudnason, T., Jones, G. T., Van Rij, A. M., Eapen, D. J., Baas, A. F., Tregouet, D. A., Morange, P. E., Emmerich, J., Lindblad, B., Gottster, A., Kiemeny, L. A., Lindholt, J. S., Sakalihasan, N., Ferrell, R. E., ... Stefansson, K. (2012). Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism. Journal of the American College of Cardiology, 60(8), 722-729. https://doi.org/10.1016/j.jacc.2012.01.078