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
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
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
atherosclerosis, coronary disease, inflammation, lipoprotein, myocardial infarction
Cardiac and Cardiovascular Systems
IdentifiersURN: urn:nbn:se:uu:diva-308955DOI: 10.1161/JAHA.116.003407ISI: 000386712700045OAI: oai:DiVA.org:uu-308955DiVA: diva2:1052865