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

• Published in: Journal of the American College of Cardiology Vol. 60; no. 8; pp. 722 - 729
• Main Authors: 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
• Format: Journal Article Web Resource
• Language: English
• Published: New York, NY Elsevier Inc 21-08-2012; Elsevier; Elsevier Limited
• 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; 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; coronary artery disease; SVD; TOAST; Trial of Org 10172 in Acute Stroke Treatment; single nucleotide polymorphism; VTE; myocardial infarction; association; odds ratio; cardioembolism; abdominal aortic aneurysm; Lp(a); thrombosis; intracranial aneurysm; SNP; IA; apolipoprotein (a); MI; atherosclerosis; genetic; AAA; CE; OR; CI; effective sample size; CAD; peripheral arterial disease; LAA; IMT; intima-media thickness; small vessel disease; large artery atherosclerosis; n e; PAD; venous thromboembolism; confidence interval; LPA; lipoprotein(a); apolipoprotein(a) gene; ne; Genetic variant; Coronary artery; Deep vein thrombosis; Cardiovascular disease; Systemic; Coronary heart disease; Venous disease; Vascular disease; Apolipoprotein A; Atherosclerosis; Venous thrombosis; Circulatory system; Disseminated; Cardiology; Thromboembolism
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2012.01.078

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.