Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study
| Autor: | Robert N. Doughty, Marcus E. Kleber, Ulrich Laufs, Aroon D. Hingorani, Vinicius Tragante, Joachim Thiery, Eva Ringdal Pedersen, Sarah Triem, Andreas Leiherer, Alexandra Filips, Kenan Direk, Alexandre F.R. Stewart, Petra A. Lenzini, W.H. Wilson Tang, Thimoteus Speer, Roelof A.J. Smit, Hooman Allayee, Eric Boerwinkle, Ioannis Petrakis, George Thanassoulis, Christoph Sinning, Domenico Girelli, Heinrich V. Groesdonk, Yan Gong, Lutz P. Breitling, A. Mark Richards, Vicky A. Cameron, Benjamin D. Horne, Ruth McPherson, Gard Frodahl Tveitevåg Svingen, Dietrich Rothenbacher, Christopher Labos, Jaana Hartiala, Louise Pilote, Imo E. Hoefer, Christie M. Ballantyne, Ute Mons, Wolfgang Koenig, Bernhard K. Krämer, Stephen Zewinger, Vei-Vei Lee, Danilo Fliser, Ragnar O. Vilmundarson, Stefan Blankenberg, Julie A. Johnson, Riyaz S. Patel, Mira Klug, Christian Werner, Efthymia Vlachopoulou, H Brenner, Daniel Kofink, Michael V. Holmes, James C. Engert, Christopher P. Nelson, Agneta Siegbahn, Axel Mündlein, J. Wouter Jukema, Marek Sanak, Marcin P. Kaczor, Peter S. Braund, Markus Scholz, Niclas Eriksson, Markku S. Nieminen, Christoph Waldeyer, Salim S. Virani, Winfried März, Raymond O McCubrey, Stanley L. Hazen, Heinz Drexel, Yi-An Ko, Nicola Martinelli, Renate B. Schnabel, Hubert Scharnagl, Oliviero Olivieri, Wojciech Szczeklik, Grethe S. Tell, Nilesh J. Samani, Gustav Smith, James M. Brophy, Ottar Nygård, Naveed Sattar, Juha Sinisalo, Richard T. Jennings, Tatjana Stojakovic, Stella Trompet, Emil Hagström, Axel Åkerblom, John A. Spertus, Claes Held, Gerard Pasterkamp, Frank Beutner, Folkert W. Asselbergs, Anna P. Pilbrow, Rhonda M. Cooper-DeHoff, Arshed A. Quyyumi, Christoph H. Saely, Lars Wallentin, Sharon Cresci, Igor Karp, Amand F. Schmidt, Peter Bogaty, Reijo Laaksonen, Graciela E. Delgado, Karl J. Lackner |
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| Přispěvatelé: | Transplantation Laboratory, Medicum, University of Helsinki, Department of Medicine, Clinicum, University Management, Doctoral Programme in Clinical Research |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
Endocrinology Diabetes and Metabolism Coronary Disease Disease 030204 cardiovascular system & hematology Cardiovascular System Cohort Studies 0302 clinical medicine Endocrinology Risk Factors Risk of mortality Medicine 030212 general & internal medicine Myocardial infarction lipoprotein(a) concentrations LPA genetic variants mortality coronary heart disease education.field_of_study Framingham Risk Score biology Lipoprotein(a) Middle Aged Prognosis 3. Good health Europe Survival Rate Diabetes and Metabolism Cardiovascular Diseases Female Cohort study medicine.medical_specialty Population education Polymorphism Single Nucleotide Article 03 medical and health sciences Internal medicine Internal Medicine Journal Article Humans Genetic Association Studies business.industry medicine.disease Blood pressure 3121 General medicine internal medicine and other clinical medicine biology.protein 3111 Biomedicine business Biomarkers |
| Zdroj: | The Lancet Diabetes & Endocrinology, 5(7), 534. Elsevier BV The Lancet Diabetes & Endocrinology The Lancet Diabetes and Endocrinology, 5(7), 534-543 |
| ISSN: | 2213-8587 |
| Popis: | Background: \ud \ud Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear.\ud \ud Methods: \ud \ud We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts.\ud \ud Findings: \ud \ud The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies.\ud \ud Interpretation: \ud \ud In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established.\ud \ud Funding: \ud \ud Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny. |
| Databáze: | OpenAIRE |
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