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Meta-Analysis
. 2012 Aug 21;60(8):722-9.
doi: 10.1016/j.jacc.2012.01.078.

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

Anna Helgadottir  1 Solveig GretarsdottirGudmar ThorleifssonHilma HolmRiyaz S PatelThorarinn GudnasonGregory T JonesAndre M van RijDanny J EapenAnnette F BaasDavid-Alexandre TregouetPierre-Emmanuel MorangeJoseph EmmerichBengt LindbladAnders GottsäterLambertus A KiemenyJes S LindholtNatzi SakalihasanRobert E FerrellDavid J CareyJames R ElmorePhilip S TsaoNiels GrarupTorben JørgensenDaniel R WitteTorben HansenOluf PedersenRoberto PolaEleonora GaetaniHulda B MagnadottirCisca WijmengaGerard TrompAntti RonkainenYnte M RuigrokJan D BlankensteijnThomas MuellerPhilip S WellsJavier CorralJose Manuel SoriaJuan Carlos SoutoJohn F PedenShapour JalilzadehBongani M MayosiBernard KeavneyRona J StrawbridgeMaria Sabater-LlealKarl GertowDamiano BaldassarreKristiina NyyssönenRainer RauramaaAndries J SmitElmo MannarinoPhilippe GiralElena TremoliUlf de FaireSteve E HumphriesAnders HamstenVilhelmina HaraldsdottirIsleifur OlafssonMagnus K MagnussonNilesh J SamaniAllan I LeveyHugh S MarkusKonstantinos KostulasMartin DichgansKlaus BergerGregor KuhlenbäumerE Bernd RingelsteinMonika StollUdo SeedorfPeter M RothwellJanet T PowellHelena KuivaniemiPall T OnundarsonEinar ValdimarssonStefan E MatthiassonDaniel F GudbjartssonGuðmundur ThorgeirssonArshed A QuyyumiHugh WatkinsMartin FarrallUnnur ThorsteinsdottirKari Stefansson
Affiliations
Meta-Analysis

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

Anna Helgadottir et al. J Am Coll Cardiol. .

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 (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 × 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.

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