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Genotype-Dependent ...
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Tardif, Jean-ClaudeMontreal Heart Institute, Canada; University of Montreal, Canada
(author)
Genotype-Dependent Effects of Dalcetrapib on Cholesterol Efflux and Inflammation Concordance With Clinical Outcomes
- Article/chapterEnglish2016
Publisher, publication year, extent ...
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LIPPINCOTT WILLIAMS & WILKINS,2016
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:liu-131911
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-131911URI
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https://doi.org/10.1161/CIRCGENETICS.116.001405DOI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Funding Agencies|F. Hoffmann-La Roche
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Background-Dalcetrapib effects on cardiovascular outcomes are determined by adenylate cyclase 9 gene polymorphisms. Our aim was to determine whether these clinical end point results are also associated with changes in reverse cholesterol transport and inflammation. Methods and Results-Participants of the dal-OUTCOMES and dal-PLAQUE-2 trials were randomly assigned to receive dalcetrapib or placebo in addition to standard care. High-sensitivity C-reactive protein was measured at baseline and at end of study in 5243 patients from dal-OUTCOMES also genotyped for the rs1967309 polymorphism in adenylate cyclase 9. Cholesterol efflux capacity of high-density lipoproteins from J774 macrophages after cAMP stimulation was determined at baseline and 12 months in 171 genotyped patients from dal-PLAQUE-2. Treatment with dalcetrapib resulted in placebo-adjusted geometric mean percent increases in high-sensitivity C-reactive protein from baseline to end of trial of 18.1% (P=0.0009) and 18.7% (P=0.00001) in participants with the GG and AG genotypes, respectively, but the change was -1.0% (P=0.89) in those with the protective AA genotype. There was an interaction between the treatment arm and the genotype groups (P=0.02). Although the mean change in cholesterol efflux was similar among study arms in patients with GG genotype (mean: 7.8% and 7.4%), increases were 22.3% and 3.5% with dalcetrapib and placebo for those with AA genotype (P=0.005). There was a significant genetic effect for change in efflux for dalcetrapib (P=0.02), but not with placebo. Conclusions-Genotype-dependent effects on C-reactive protein and cholesterol efflux are supportive of dalcetrapib benefits on atherosclerotic cardiovascular outcomes in patients with the AA genotype at polymorphism rs1967309.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Rhainds, DavidMontreal Heart Institute, Canada
(author)
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Brodeur, MathieuMontreal Heart Institute, Canada
(author)
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Feroz Zada, YassaminUniversity of Montreal, Canada
(author)
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Fouodjio, ReneUniversity of Montreal, Canada
(author)
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Provost, SylvieUniversity of Montreal, Canada
(author)
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Boule, MarieMontreal Heart Institute, Canada
(author)
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Alem, SoniaMontreal Heart Institute, Canada
(author)
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Gregoire, Jean C.Montreal Heart Institute, Canada; University of Montreal, Canada
(author)
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LAllier, Philippe L.Montreal Heart Institute, Canada; University of Montreal, Canada
(author)
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Ibrahim, RedaMontreal Heart Institute, Canada; University of Montreal, Canada
(author)
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Guertin, Marie-ClaudeMontreal Health Innovat Coordinating Centre, Canada
(author)
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Mongrain, IanUniversity of Montreal, Canada
(author)
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Olsson, AndersLinköpings universitet,Medicinska fakulteten,Avdelningen för kardiovaskulär medicin,Region Östergötland, Endokrinmedicinska kliniken(Swepub:liu)andol21
(author)
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Schwartz, Gregory G.Vet Affairs Medical Centre, CO USA; University of Colorado, CO USA
(author)
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Rheaume, EricMontreal Heart Institute, Canada; University of Montreal, Canada
(author)
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Dube, Marie-PierreMontreal Heart Institute, Canada; University of Montreal, Canada; University of Montreal, Canada
(author)
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Montreal Heart Institute, Canada; University of Montreal, CanadaMontreal Heart Institute, Canada
(creator_code:org_t)
Related titles
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In:Circulation: LIPPINCOTT WILLIAMS & WILKINS9:4, s. 340-3481942-325X1942-3268
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Tardif, Jean-Cla ...
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Rhainds, David
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Brodeur, Mathieu
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Feroz Zada, Yass ...
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Fouodjio, Rene
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Provost, Sylvie
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Boule, Marie
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Alem, Sonia
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Gregoire, Jean C ...
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LAllier, Philipp ...
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Ibrahim, Reda
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Guertin, Marie-C ...
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Mongrain, Ian
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Olsson, Anders
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Schwartz, Gregor ...
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Rheaume, Eric
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Dube, Marie-Pier ...
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- MEDICAL AND HEALTH SCIENCES
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Circulation
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Linköping University