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
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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. / Zewinger, Stephen; Kleber, Marcus E; Tragante, Vinicius; McCubrey, Raymond O; Schmidt, Amand F; Direk, Kenan; Laufs, Ulrich; Werner, Christian; Koenig, Wolfgang; Rothenbacher, Dietrich; Mons, Ute; Breitling, Lutz P; Brenner, Herrmann; Jennings, Richard T; Petrakis, Ioannis; Triem, Sarah; Klug, Mira; Filips, Alexandra; Blankenberg, Stefan; Waldeyer, Christoph; Sinning, Christoph; Schnabel, Renate B; Lackner, Karl J; Vlachopoulou, Efthymia; Nygård, Ottar; Svingen, Gard Frodahl Tveitevåg; Pedersen, Eva Ringdal; Tell, Grethe S; Sinisalo, Juha; Nieminen, Markku S; Laaksonen, Reijo; Trompet, Stella; Smit, Roelof A J; Sattar, Naveed; Jukema, J Wouter; Groesdonk, Heinrich V; Delgado, Graciela; Stojakovic, Tatjana; Pilbrow, Anna P; Cameron, Vicky A; Richards, A Mark; Doughty, Robert N; Gong, Yan; Cooper-DeHoff, Rhonda; Johnson, Julie; Scholz, Markus; Beutner, Frank; Thiery, Joachim; Smith, J Gustav; Vilmundarson, Ragnar O; McPherson, Ruth; Stewart, Alexandre F R; Cresci, Sharon; Lenzini, Petra A; Spertus, John A; Olivieri, Oliviero; Girelli, Domenico; Martinelli, Nicola I; Leiherer, Andreas; Saely, Christoph H; Drexel, Heinz; Mündlein, Axel; Braund, Peter S; Nelson, Christopher P; Samani, Nilesh J; Kofink, Daniel; Hoefer, Imo E; Pasterkamp, Gerard; Quyyumi, Arshed A; Ko, Yi-An; Hartiala, Jaana A; Allayee, Hooman; Tang, W H Wilson; Hazen, Stanley L; Eriksson, Niclas; Held, Claes; Hagström, Emil; Wallentin, Lars; Åkerblom, Axel; Siegbahn, Agneta; Karp, Igor; Labos, Christopher; Pilote, Louise; Engert, James C; Brophy, James M; Thanassoulis, George; Bogaty, Peter; Szczeklik, Wojciech; Kaczor, Marcin; Sanak, Marek; Virani, Salim S; Ballantyne, Christie M; Lee, Vei-Vei; Boerwinkle, Eric; Holmes, Michael V; Horne, Benjamin D; Hingorani, Aroon; Asselbergs, Folkert W; Patel, Riyaz S; Krämer, Bernhard K; Scharnagl, Hubert; Fliser, Danilo; März, Winfried; Speer, Thimoteus; GENIUS-CHD consortium.
in: LANCET DIABETES ENDO, Jahrgang 5, Nr. 7, 07.2017, S. 534-543.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - 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
AU - Zewinger, Stephen
AU - Kleber, Marcus E
AU - Tragante, Vinicius
AU - McCubrey, Raymond O
AU - Schmidt, Amand F
AU - Direk, Kenan
AU - Laufs, Ulrich
AU - Werner, Christian
AU - Koenig, Wolfgang
AU - Rothenbacher, Dietrich
AU - Mons, Ute
AU - Breitling, Lutz P
AU - Brenner, Herrmann
AU - Jennings, Richard T
AU - Petrakis, Ioannis
AU - Triem, Sarah
AU - Klug, Mira
AU - Filips, Alexandra
AU - Blankenberg, Stefan
AU - Waldeyer, Christoph
AU - Sinning, Christoph
AU - Schnabel, Renate B
AU - Lackner, Karl J
AU - Vlachopoulou, Efthymia
AU - Nygård, Ottar
AU - Svingen, Gard Frodahl Tveitevåg
AU - Pedersen, Eva Ringdal
AU - Tell, Grethe S
AU - Sinisalo, Juha
AU - Nieminen, Markku S
AU - Laaksonen, Reijo
AU - Trompet, Stella
AU - Smit, Roelof A J
AU - Sattar, Naveed
AU - Jukema, J Wouter
AU - Groesdonk, Heinrich V
AU - Delgado, Graciela
AU - Stojakovic, Tatjana
AU - Pilbrow, Anna P
AU - Cameron, Vicky A
AU - Richards, A Mark
AU - Doughty, Robert N
AU - Gong, Yan
AU - Cooper-DeHoff, Rhonda
AU - Johnson, Julie
AU - Scholz, Markus
AU - Beutner, Frank
AU - Thiery, Joachim
AU - Smith, J Gustav
AU - Vilmundarson, Ragnar O
AU - McPherson, Ruth
AU - Stewart, Alexandre F R
AU - Cresci, Sharon
AU - Lenzini, Petra A
AU - Spertus, John A
AU - Olivieri, Oliviero
AU - Girelli, Domenico
AU - Martinelli, Nicola I
AU - Leiherer, Andreas
AU - Saely, Christoph H
AU - Drexel, Heinz
AU - Mündlein, Axel
AU - Braund, Peter S
AU - Nelson, Christopher P
AU - Samani, Nilesh J
AU - Kofink, Daniel
AU - Hoefer, Imo E
AU - Pasterkamp, Gerard
AU - Quyyumi, Arshed A
AU - Ko, Yi-An
AU - Hartiala, Jaana A
AU - Allayee, Hooman
AU - Tang, W H Wilson
AU - Hazen, Stanley L
AU - Eriksson, Niclas
AU - Held, Claes
AU - Hagström, Emil
AU - Wallentin, Lars
AU - Åkerblom, Axel
AU - Siegbahn, Agneta
AU - Karp, Igor
AU - Labos, Christopher
AU - Pilote, Louise
AU - Engert, James C
AU - Brophy, James M
AU - Thanassoulis, George
AU - Bogaty, Peter
AU - Szczeklik, Wojciech
AU - Kaczor, Marcin
AU - Sanak, Marek
AU - Virani, Salim S
AU - Ballantyne, Christie M
AU - Lee, Vei-Vei
AU - Boerwinkle, Eric
AU - Holmes, Michael V
AU - Horne, Benjamin D
AU - Hingorani, Aroon
AU - Asselbergs, Folkert W
AU - Patel, Riyaz S
AU - Krämer, Bernhard K
AU - Scharnagl, Hubert
AU - Fliser, Danilo
AU - März, Winfried
AU - Speer, Thimoteus
AU - GENIUS-CHD consortium
N1 - Copyright © 2017 Elsevier Ltd. All rights reserved.
PY - 2017/7
Y1 - 2017/7
N2 - BACKGROUND: 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.METHODS: 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.FINDINGS: 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.INTERPRETATION: 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.FUNDING: 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.
AB - BACKGROUND: 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.METHODS: 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.FINDINGS: 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.INTERPRETATION: 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.FUNDING: 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.
KW - Biomarkers/blood
KW - Cohort Studies
KW - Coronary Disease/blood
KW - Europe/epidemiology
KW - Female
KW - Genetic Association Studies
KW - Humans
KW - Lipoprotein(a)/blood
KW - Male
KW - Middle Aged
KW - Polymorphism, Single Nucleotide
KW - Prognosis
KW - Risk Factors
KW - Survival Rate
U2 - 10.1016/S2213-8587(17)30096-7
DO - 10.1016/S2213-8587(17)30096-7
M3 - SCORING: Journal article
C2 - 28566218
VL - 5
SP - 534
EP - 543
JO - LANCET DIABETES ENDO
JF - LANCET DIABETES ENDO
SN - 2213-8587
IS - 7
ER -