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Lipoprotein-Associa...
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Wallentin, LarsUppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)
(author)
Lipoprotein-Associated Phospholipase A(2) Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease
- Article/chapterEnglish2016
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LIBRIS-ID:oai:DiVA.org:uu-308955
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-308955URI
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https://doi.org/10.1161/JAHA.116.003407DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Background - We evaluated lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp-PLA(2) inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial.Methods and Results - Plasma Lp-PLA(2) activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100) at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp-PLA(2) activity levels and outcomes. At baseline, the median Lp-PLA(2) level was 172.4 mu mol/min per liter (interquartile range 143.1-204.2 mu mol/min per liter). Comparing the highest and lowest Lp-PLA(2) quartile groups, the hazard ratios were 1.50 (95% CI 1.23-1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29-2.93) for hospitalization for heart failure, 1.42 (1.07-1.89) for cardiovascular death, and 1.37 (1.03-1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a approximate to 65% persistent reduction in median Lp-PLA(2) activity. There were no associations between on-treatment Lp-PLA(2) activity or changes of Lp-PLA(2) activity and outcomes, and there were no significant interactions between baseline and on-treatment Lp-PLA(2) activity or changes in Lp-PLA(2) activity levels and the effects of darapladib on outcomes.Conclusions - Although high Lp-PLA(2) activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp-PLA(2) activity by approximate to 65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp-PLA(2) activity.
Subject headings and genre
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Held, ClaesUppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)(Swepub:uu)clahe947
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Armstrong, Paul W.Univ Alberta, Canadian VIGOUR Ctr, Edmonton, AB, Canada.
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Cannon, Christopher P.Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.;Harvard Clin Res Inst, Boston, MA USA.
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Davies, Richard Y.GlaxoSmithKline, Metab Pathways & Cardiovasc Therapeut Area, King Of Prussia, PA USA.
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Granger, Christopher B.Duke Univ, Med Ctr, Durham, NC USA.
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Hagström, EmilUppsala universitet,Kardiologi(Swepub:uu)emhag677
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Harrington, Robert A.Stanford Univ, Dept Med, Stanford, CA 94305 USA.
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Hochman, Judith S.NYU, Langone Med Ctr, Dept Med, New York, NY USA.
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Koenig, WolfgangUniv Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany.;Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany.
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Krug-Gourley, SueGlaxoSmithKline, Metab Pathways & Cardiovasc Therapeut Area, King Of Prussia, PA USA.
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Mohler, Emile R., IIIUniv Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
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Siegbahn, AgnetaUppsala universitet,Institutionen för medicinska vetenskaper,Uppsala kliniska forskningscentrum (UCR)(Swepub:uu)agsie424
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Tarka, ElizabethGlaxoSmithKline, Former Employee Metab Pathways & Cardiovasc Thera, King Of Prussia, PA USA.
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Steg, Philippe GabrielFACT, Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, DHU FIRE, Paris, France.;Hop Bichat Claude Bernard, INSERUM, U 1148, Paris, France.;Imperial Coll, Royal Brompton Hosp, ICMS, NHLI, London, England.
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Stewart, Ralph A. H.Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland 1, New Zealand.
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Weiss, RobertMaine Res Associates, Auburn, ME USA.
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östlund, OllieUppsala universitet,Uppsala kliniska forskningscentrum (UCR)(Swepub:uu)oos27600
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White, Harvey D.Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland 1, New Zealand.
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Uppsala universitetKardiologi
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In:Journal of the American Heart Association5:62047-9980
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