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.

Authors:
Stephen Zewinger Marcus E Kleber Vinicius Tragante Raymond O McCubrey Amand F Schmidt Kenan Direk Ulrich Laufs Christian Werner Wolfgang Koenig Dietrich Rothenbacher Ute Mons Lutz P Breitling Herrmann Brenner Richard T Jennings Ioannis Petrakis Sarah Triem Mira Klug Alexandra Filips Stefan Blankenberg Christoph Waldeyer Christoph Sinning Renate B Schnabel Karl J Lackner Efthymia Vlachopoulou Ottar Nygård Gard Frodahl Tveitevåg Svingen Eva Ringdal Pedersen Grethe S Tell Juha Sinisalo Markku S Nieminen Reijo Laaksonen Stella Trompet Roelof A J Smit Naveed Sattar J Wouter Jukema Heinrich V Groesdonk Graciela Delgado Tatjana Stojakovic Anna P Pilbrow Vicky A Cameron A Mark Richards Robert N Doughty Yan Gong Rhonda Cooper-DeHoff Julie Johnson Markus Scholz Frank Beutner Joachim Thiery J Gustav Smith Ragnar O Vilmundarson Ruth McPherson Alexandre F R Stewart Sharon Cresci Petra A Lenzini John A Spertus Oliviero Olivieri Domenico Girelli Nicola I Martinelli Andreas Leiherer Christoph H Saely Heinz Drexel Axel Mündlein Peter S Braund Christopher P Nelson Nilesh J Samani Daniel Kofink Imo E Hoefer Gerard Pasterkamp Arshed A Quyyumi Yi-An Ko Jaana A Hartiala Hooman Allayee W H Wilson Tang Stanley L Hazen Niclas Eriksson Claes Held Emil Hagström Lars Wallentin Axel Åkerblom Agneta Siegbahn Igor Karp Christopher Labos Louise Pilote James C Engert James M Brophy George Thanassoulis Peter Bogaty Wojciech Szczeklik Marcin Kaczor Marek Sanak Salim S Virani Christie M Ballantyne Vei-Vei Lee Eric Boerwinkle Michael V Holmes Benjamin D Horne Aroon Hingorani Folkert W Asselbergs Riyaz S Patel Bernhard K Krämer Hubert Scharnagl Danilo Fliser Winfried März Thimoteus Speer

Lancet Diabetes Endocrinol 2017 07 26;5(7):534-543. Epub 2017 May 26.

Department of Internal Medicine IV, Saarland University Hospital, Homburg/Saar, Germany.

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.

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Source
http://dx.doi.org/10.1016/S2213-8587(17)30096-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651679PMC
July 2017
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