TY - JOUR
T1 - Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease
T2 - a molecular and genetic association study
AU - GENIUS-CHD consortium
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 - Virani, Salim S.
N1 - Publisher Copyright:
© 2017 Elsevier Ltd
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.
UR - http://www.scopus.com/inward/record.url?scp=85019743146&partnerID=8YFLogxK
U2 - 10.1016/S2213-8587(17)30096-7
DO - 10.1016/S2213-8587(17)30096-7
M3 - Article
C2 - 28566218
AN - SCOPUS:85019743146
SN - 2213-8587
VL - 5
SP - 534
EP - 543
JO - The Lancet Diabetes and Endocrinology
JF - The Lancet Diabetes and Endocrinology
IS - 7
ER -