TY - JOUR
T1 - Changes in lipoprotein-associated phospholipase A2 activity predict coronary events and partly account for the treatment effect of pravastatin
T2 - results from the long-term intervention with pravastatin in ischemic disease study
AU - White, Harvey D.
AU - Simes, John
AU - Stewart, Ralph A H
AU - Blankenberg, Stefan
AU - Barnes, Elizabeth H.
AU - Marschner, Ian C.
AU - Thompson, Peter
AU - West, Malcolm
AU - Zeller, Tanja
AU - Colquhoun, David M.
AU - Nestel, Paul
AU - Keech, Anthony C.
AU - Sullivan, David R.
AU - Hunt, David
AU - Tonkin, Andrew
AU - The LIPID Study Investigators
PY - 2013/10/23
Y1 - 2013/10/23
N2 - Background--Lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are associated with coronary heart disease (CHD) in healthy individuals and in patients who have had ischemic events. Methods and Results--The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study randomized 9014 patients with cholesterol levels of 4.0 to 7.0 mmol/L to placebo or pravastatin 3 to 36 months after myocardial infarction or unstable angina and showed a reduction in CHD and total mortality. We assessed the value of baseline and change in Lp-PLA2 activity to predict outcomes over a 6-year follow-up, the effect of pravastatin on Lp-PLA2 levels, and whether pravastatin treatment effect was related to Lp-PLA2 activity change. Lp-PLA2 was measured at randomization and 1 year, and levels were grouped as quartiles. The prespecified end point was CHD death or nonfatal myocardial infarction. Baseline Lp-PLA2 activity was positively associated with CHD events (P<0.001) but not after adjustment for 23 baseline factors (P=0.66). In 6518 patients who were event free at 1 year, change in Lp-PLA2 was a significant independent predictor of subsequent CHD events after adjustment for these risk factors, including LDL cholesterol and LDL cholesterol changes (P<0.001). Pravastatin reduced Lp-PLA2 by 16% compared with placebo (P<0.001). After adjustment for Lp-PLA2 change, the pravastatin treatment effect was reduced from 23% to 10% (P=0.26), with 59% of the treatment effect accounted for by changes in Lp-PLA2. Similar reductions in treatment effect were seen after adjustment for LDL cholesterol change. Conclusion--Reduction in Lp-PLA2 activity during the first year was a highly significant predictor of CHD events, independent of change in LDL cholesterol, and may account for over half of the benefits of pravastatin in the LIPID study.
AB - Background--Lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are associated with coronary heart disease (CHD) in healthy individuals and in patients who have had ischemic events. Methods and Results--The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study randomized 9014 patients with cholesterol levels of 4.0 to 7.0 mmol/L to placebo or pravastatin 3 to 36 months after myocardial infarction or unstable angina and showed a reduction in CHD and total mortality. We assessed the value of baseline and change in Lp-PLA2 activity to predict outcomes over a 6-year follow-up, the effect of pravastatin on Lp-PLA2 levels, and whether pravastatin treatment effect was related to Lp-PLA2 activity change. Lp-PLA2 was measured at randomization and 1 year, and levels were grouped as quartiles. The prespecified end point was CHD death or nonfatal myocardial infarction. Baseline Lp-PLA2 activity was positively associated with CHD events (P<0.001) but not after adjustment for 23 baseline factors (P=0.66). In 6518 patients who were event free at 1 year, change in Lp-PLA2 was a significant independent predictor of subsequent CHD events after adjustment for these risk factors, including LDL cholesterol and LDL cholesterol changes (P<0.001). Pravastatin reduced Lp-PLA2 by 16% compared with placebo (P<0.001). After adjustment for Lp-PLA2 change, the pravastatin treatment effect was reduced from 23% to 10% (P=0.26), with 59% of the treatment effect accounted for by changes in Lp-PLA2. Similar reductions in treatment effect were seen after adjustment for LDL cholesterol change. Conclusion--Reduction in Lp-PLA2 activity during the first year was a highly significant predictor of CHD events, independent of change in LDL cholesterol, and may account for over half of the benefits of pravastatin in the LIPID study.
UR - http://www.scopus.com/inward/record.url?scp=84980053737&partnerID=8YFLogxK
U2 - 10.1161/JAHA.113.000360
DO - 10.1161/JAHA.113.000360
M3 - Article
C2 - 24152981
AN - SCOPUS:84891705653
VL - 2
SP - 1
EP - 12
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
SN - 2047-9980
IS - 5
M1 - e000360
ER -