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
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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. / White, Harvey D; Simes, John; Stewart, Ralph A H; Blankenberg, Stefan; Barnes, Elizabeth H; Marschner, Ian C; Thompson, Peter; West, Malcolm; Zeller, Tanja; Colquhoun, David M; Nestel, Paul; Keech, Anthony C; Sullivan, David R; Hunt, David; Tonkin, Andrew; LIPID Study Investigators.
In: J AM HEART ASSOC, Vol. 2, No. 5, 23.10.2013, p. e000360.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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, 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 - 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.
KW - 1-Alkyl-2-acetylglycerophosphocholine Esterase/blood
KW - Adult
KW - Aged
KW - Anticholesteremic Agents/pharmacology
KW - Coronary Disease/blood
KW - Double-Blind Method
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Myocardial Infarction/blood
KW - Myocardial Ischemia/blood
KW - Pravastatin/pharmacology
KW - Predictive Value of Tests
KW - Time Factors
U2 - 10.1161/JAHA.113.000360
DO - 10.1161/JAHA.113.000360
M3 - SCORING: Journal article
C2 - 24152981
VL - 2
SP - e000360
JO - J AM HEART ASSOC
JF - J AM HEART ASSOC
SN - 2047-9980
IS - 5
ER -
