Relationship of lipoprotein-Associated phospholipase A 2 mass and activity with incident vascular events among primary prevention patients allocated to placebo or to statin therapy: An analysis from the JUPITER trial

摘要

BACKGROUND: Although lipoprotein-Associated phospholipase A 2 (L p-PLA2) levels are associated with cardiovascular events, L p-PLA 2 is physically linked to LDL cholesterol (LDL-C). Whether measures of L p-PLA2 mass or activity continue to predict risk after LDL-C reduction by statin therapy is uncertain. METHODS: L p-PLA 2 mass concentration and activity were evaluated at baseline and after treatment in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial comparing rosuvastatin 20 mg to placebo among 17 802 men and women without cardiovascular disease or diabetes at study entry. The relationships of L p-PLA 2 mass and activity with risk of future vascular events were evaluated in the placebo and rosuvastatin groups. RESULTS: Before randomization, levels of L p-PLA2 mass and activity correlated moderately with each other and with LDL-C. The magnitude of these correlations increased after statin therapy. Rosuvastatin reduced L p-PLA 2 mass by 33.8%, L p-PLA 2 activity by 33.2%, and LDL-C by 48.7% (all P 0.0001). Among those study participants allocated to placebo, increasing quartiles of L p-PLA 2 activity (Ptrend0.04) but not L p-PLA 2 mass (Ptrend 0.92) were associated with incident cardiovascular events after adjustment for LDL-C and conventional risk factors. Comparable analyses conducted among those allocated to rosuvastatin revealed no significant relationship between L p-PLA 2 levels and subsequent vascular events. The ability of rosuvastatin to reduce vascular events was not significantly modified by baseline L p-PLA 2 level. CONCLUSIONS: Among JUPITER trial participants allocated to placebo, levels of L p-PLA 2 activity, but not mass, were associated with cardiovascular risk. However, L p-PLA 2 no longer predicted risk or modified clinical outcomes when participants were treated with rosuvastatin.