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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
Saarland Univ Hosp, Dept Internal Med 4, Homburg, Germany..
Friedrich Schiller Univ, Inst Nutr, Jena, Germany..
Univ Utah Sch Med, Intermountain Heart Inst, Intermountain Med Ctr, Salt Lake City, UT USA..
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2017 (English)In: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 5, no 7, 534-543 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC , 2017. Vol. 5, no 7, 534-543 p.
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-329628DOI: 10.1016/S2213-8587(17)30096-7ISI: 000403672400019PubMedID: 28566218OAI: oai:DiVA.org:uu-329628DiVA: diva2:1144490
Available from: 2017-09-26 Created: 2017-09-26 Last updated: 2017-09-26Bibliographically approved

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Eriksson, NiclasHeld, ClaesHagström, EmilWallentin, LarsÅkerblom, AxelSiegbahn, A

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