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Genotype-Dependent ...
Genotype-Dependent Effects of Dalcetrapib on Cholesterol Efflux and Inflammation Concordance With Clinical Outcomes
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Tardif, Jean-Claude (author)
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Rhainds, David (author)
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Brodeur, Mathieu (author)
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Feroz Zada, Yassamin (author)
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Fouodjio, Rene (author)
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Provost, Sylvie (author)
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Boule, Marie (author)
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Alem, Sonia (author)
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Gregoire, Jean C. (author)
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LAllier, Philippe L. (author)
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Ibrahim, Reda (author)
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Guertin, Marie-Claude (author)
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Mongrain, Ian (author)
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Olsson, Anders (author)
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Schwartz, Gregory G. (author)
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Rheaume, Eric (author)
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Dube, Marie-Pierre (author)
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- LIPPINCOTT WILLIAMS & WILKINS 2016
- 2016
- English.
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In: Circulation. - 1942-325X. ; 9:4, 340-348
Abstract
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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
- Medical and Health Sciences (hsv)
- Clinical Medicine (hsv)
- Cardiac and Cardiovascular Systems (hsv)
- Medicin och hälsovetenskap (hsv)
- Klinisk medicin (hsv)
- Kardiologi (hsv)
Keyword
- reactive protein; cholesterol efflux; dalcetrapib; HDL; pharmacogenetics
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- By the author/editor
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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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show more...
-
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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show less...
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