Lipoprotein-Associated Phospholipase A2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease

被引：65

作者：

Wallentin, Lars ^{[1
,2
]}

Held, Claes ^{[1
,2
]}

Armstrong, Paul W. ^{[4
]}

Cannon, Christopher P. ^{[5
,6
]}

Davies, Richard Y. ^{[7
]}

Granger, Christopher B. ^{[9
]}

Hagstrom, Emil ^{[1
,2
]}

Harrington, Robert A. ^{[10
]}

Hochman, Judith S. ^{[11
]}

Koenig, Wolfgang ^{[12
,13
,14
]}

Krug-Gourley, Sue ^{[7
]}

Mohler, Emile R., III ^{[15
]}

Siegbahn, Agneta ^{[2
,3
]}

Tarka, Elizabeth ^{[8
]}

Steg, Philippe Gabriel ^{[16
,17
,18
,19
]}

Stewart, Ralph A. H. ^{[20
,21
]}

Weiss, Robert ^{[22
]}

Ostlund, Ollie ^{[2
]}

White, Harvey D. ^{[20
,21
]}

机构：

[1] Uppsala Univ, Dept Med Sci, Cardiol, Uppsala, Sweden

[2] Uppsala Univ, Uppsala Clin Res Ctr UCR, Uppsala, Sweden

[3] Uppsala Univ, Dept Med Sci, Clin Chem, Uppsala, Sweden

[4] Univ Alberta, Canadian VIGOUR Ctr, Edmonton, AB, Canada

[5] Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA

[6] Harvard Clin Res Inst, Boston, MA USA

[7] GlaxoSmithKline, Metab Pathways & Cardiovasc Therapeut Area, King Of Prussia, PA USA

[8] GlaxoSmithKline, Former Employee Metab Pathways & Cardiovasc Thera, King Of Prussia, PA USA

[9] Duke Univ, Med Ctr, Durham, NC USA

[10] Stanford Univ, Dept Med, Stanford, CA 94305 USA

[11] NYU, Langone Med Ctr, Dept Med, New York, NY USA

[12] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany

[13] Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany

[14] DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany

[15] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[16] FACT, Paris, France

[17] Univ Paris Diderot, Sorbonne Paris Cite, DHU FIRE, Paris, France

[18] Hop Bichat Claude Bernard, INSERUM, U 1148, Paris, France

[19] Imperial Coll, Royal Brompton Hosp, ICMS, NHLI, London, England

[20] Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand

[21] Univ Auckland, Auckland 1, New Zealand

[22] Maine Res Associates, Auburn, ME USA

来源：

JOURNAL OF THE AMERICAN HEART ASSOCIATION | 2016年 / 5卷 / 06期

关键词：

atherosclerosis; coronary disease; inflammation; lipoprotein; myocardial infarction; ACTIVATING-FACTOR ACETYLHYDROLASE; C-REACTIVE PROTEIN; CARDIOVASCULAR OUTCOMES; ATHEROSCLEROTIC PLAQUE; LUDWIGSHAFEN RISK; ARTERY-DISEASE; EVENTS; DARAPLADIB; TRIAL; INFLAMMATION;

D O I：

10.1161/JAHA.116.003407

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页数：16

共 32 条

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