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

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• 作者：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-Alex ; re Tregouet ; Pierre-Emmanuel Morange ; Joseph Emmerich ; Bengt Lindblad ; Anders Gotts?ter ; Lambertus A. Kiemeny ; Jes S. Lindholt ; Natzi Sakalihasan ; Robert E. Ferrell ; David J. Carey ; et al.
• 关键词：association ; atherosclerosis ; genetic ; lipoprotein(a) ; thrombosis
• 刊名：Journal of the American College of Cardiology
• 出版年：2012
• 出版时间：21 August, 2012
• 年：2012
• 卷：60
• 期：8
• 页码：722-729
• 全文大小：538 K

文摘

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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 (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).

Results

LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 ¡Á 10^-4), peripheral artery disease (OR: 1.47; p = 2.9 ¡Á 10^-14), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 ¡Á 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 ¡Á 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 ¡Á 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.