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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
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
Univ Alberta, Canadian VIGOUR Ctr, Edmonton, AB, Canada..
Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.;Harvard Clin Res Inst, Boston, MA USA..
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2016 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 5, no 6, e003407Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 5, no 6, e003407
Keyword [en]
atherosclerosis, coronary disease, inflammation, lipoprotein, myocardial infarction
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-308955DOI: 10.1161/JAHA.116.003407ISI: 000386712700045OAI: oai:DiVA.org:uu-308955DiVA: diva2:1052865
Funder
GlaxoSmithKline (GSK)
Available from: 2016-12-07 Created: 2016-12-01 Last updated: 2016-12-07Bibliographically approved

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Wallentin, LarsHeld, ClaesHagström, EmilSiegbahn, Agneta
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CardiologyUCR-Uppsala Clinical Research CenterDepartment of Medical Sciences
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