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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, 2012-08, Vol.60 (8), p.722-729 [Peer Reviewed Journal]

American College of Cardiology Foundation ;2012 American College of Cardiology Foundation ;2015 INIST-CNRS ;Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. ;Copyright Elsevier Limited Aug 21, 2012 ;ISSN: 0735-1097 ;ISSN: 1558-3597 ;EISSN: 1558-3597 ;DOI: 10.1016/j.jacc.2012.01.078 ;PMID: 22898070 ;CODEN: JACCDI

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Title:
Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism
Author: Helgadottir, Anna, MD, PhD ; Gretarsdottir, Solveig, PhD ; Thorleifsson, Gudmar, PhD ; Holm, Hilma, MD ; Patel, Riyaz S., MD ; Gudnason, Thorarinn, MD, PhD ; Jones, Gregory T., PhD ; van Rij, Andre M., MD ; Eapen, Danny J., MD ; Baas, Annette F., PhD ; Tregouet, David-Alexandre, PhD ; Morange, Pierre-Emmanuel, MD ; Emmerich, Joseph, MD, PhD ; Lindblad, Bengt, MD, PhD ; Gottsäter, Anders, MD, PhD ; Kiemeny, Lambertus A., PhD ; Lindholt, Jes S., MD, PhD ; Sakalihasan, Natzi, MD, PhD ; Ferrell, Robert E., PhD ; Carey, David J., PhD ; Elmore, James R., MD ; Tsao, Philip S., PhD ; Grarup, Niels, MD, PhD ; Jørgensen, Torben, MD, DMSci ; Witte, Daniel R., MD, PhD ; Hansen, Torben, MD, PhD ; Pedersen, Oluf, MD, DMSci ; Pola, Roberto, MD, PhD ; Gaetani, Eleonora, MD ; Magnadottir, Hulda B., MD ; Wijmenga, Cisca, PhD ; Tromp, Gerard, PhD ; Ronkainen, Antti, MD, PhD ; Ruigrok, Ynte M., MD ; Blankensteijn, Jan D ; Mueller, Thomas, MD ; Wells, Philip S., MD ; Corral, Javier, PhD ; Soria, Jose Manuel, PhD ; Souto, Juan Carlos, MD, PhD ; Peden, John F., PhD ; Jalilzadeh, Shapour, MD, PhD ; Mayosi, Bongani M., DPhil ; Keavney, Bernard, MD ; Strawbridge, Rona J., PhD ; Sabater-Lleal, Maria, PhD ; Gertow, Karl, PhD ; Baldassarre, Damiano, PhD ; Nyyssönen, Kristiina, PhD ; Rauramaa, Rainer, MD, PhD ; Smit, Andries J., MD, PhD ; Mannarino, Elmo, MD ; Giral, Philippe, MD ; Tremoli, Elena, PhD ; de Faire, Ulf, MD, PhD ; Humphries, Steve E., PhD ; Hamsten, Anders, MD, PhD ; Haraldsdottir, Vilhelmina, MD ; Olafsson, Isleifur, MD, PhD ; Magnusson, Magnus K., MD ; Samani, Nilesh J., MD ; Levey, Allan I., MD, PhD ; Markus, Hugh S., MD ; Kostulas, Konstantinos, MD, PhD ; Dichgans, Martin, MD ; Berger, Klaus, MD ; Kuhlenbäumer, Gregor, MD ; Ringelstein, E. Bernd, MD ; Stoll, Monika, PhD ; Seedorf, Udo, PhD ; Rothwell, Peter M., MD, PhD ; Powell, Janet T., MD ; Kuivaniemi, Helena, MD, PhD ; Onundarson, Pall T., MD ; Valdimarsson, Einar, MD ; Matthiasson, Stefan E., MD, PhD ; Gudbjartsson, Daniel F., PhD ; Thorgeirsson, Guðmundur, MD, PhD ; Quyyumi, Arshed A., MD ; Watkins, Hugh, MD, PhD ; Farrall, Martin, MD ; Thorsteinsdottir, Unnur, PhD ; Stefansson, Kari, MD, PhD
Subjects: African Americans - genetics ; Age ; Age of Onset ; Angiography ; Aortic Aneurysm, Abdominal - genetics ; Apolipoproteins ; Apolipoproteins A - genetics ; association ; Atherosclerosis ; Atherosclerosis (general aspects, experimental research) ; Atherosclerosis - genetics ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood pressure ; Brain Ischemia - genetics ; Cardiac and Cardiovascular Systems ; Cardiology. Vascular system ; Cardiovascular ; Cardiovascular disease ; Carotid Intima-Media Thickness ; Chirurgie ; Clinical Medicine ; Confidence intervals ; Coronary Artery Disease - genetics ; Coronary heart disease ; Coronary vessels ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Drug therapy ; European Continental Ancestry Group/genetics ; genetic ; Genetic Predisposition to Disease ; Heart ; Human health sciences ; Humans ; Internal Medicine ; Intracranial Aneurysm - genetics ; Kardiologi ; Klinisk medicin ; Linear Models ; lipoprotein(a) ; Logistic Models ; Medical and Health Sciences ; Medical imaging ; Medical sciences ; Medicin och hälsovetenskap ; Methods ; Myocardial Infarction - genetics ; Odds Ratio ; Peripheral Arterial Disease - genetics ; Polymorphism, Single Nucleotide ; Risk Factors ; Sciences de la santé humaine ; Severity of Illness Index ; Stroke ; Stroke - genetics ; Studies ; Surgery ; Thrombosis ; Values ; Venous Thromboembolism - genetics ; Whites - genetics
Is Part Of: Journal of the American College of Cardiology, 2012-08, Vol.60 (8), p.722-729
Description: 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 [ ne ] = 9,396); peripheral arterial disease ( ne = 5,215); abdominal aortic aneurysm ( ne = 4,572); venous thromboembolism ( ne = 4,607); intracranial aneurysm ( ne = 1,328); CAD ( ne = 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 × 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). Conclusions LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes.
Publisher: New York, NY: Elsevier Inc
Language: English
Identifier: ISSN: 0735-1097
ISSN: 1558-3597
EISSN: 1558-3597
DOI: 10.1016/j.jacc.2012.01.078
PMID: 22898070
CODEN: JACCDI
Source: GFMER Free Medical Journals
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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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