TY - JOUR
T1 - Changes in lipoprotein-Associated phospholipase A2 activity predict coronary events and partly account for the treatment effect of pravastatin: results from the Long-Term Intervention with Pravastatin in Ischemic Disease study.
AU - White, H.D.
AU - Simes, J.
AU - Stewart, R.A.
AU - Blankenberg, S.
AU - Barnes, E.H.
AU - Marschner, I.C.
AU - Thompson, Peter
AU - West, M.
AU - Zeller, T.
AU - Colquhoun, D.M.
AU - Nestel, P.
AU - Keech, A.C.
AU - Sullivan, D.R.
AU - Hunt, D.
AU - Tonkin, A.
AU - Study Investigators, L
AU - 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. ( J Am Heart Assoc.
2013;2:e000360 doi: 10.1161/JAHA.113.000360)
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. ( J Am Heart Assoc.
2013;2:e000360 doi: 10.1161/JAHA.113.000360)
U2 - 10.1161/JAHA.113.000360
DO - 10.1161/JAHA.113.000360
M3 - Article
C2 - 24152981
SN - 2047-9980
VL - 2
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 5
ER -