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Relationship of Lipoprotein-Associated Phospholipase A2 Mass and Activity With Incident Vascular Events Among Primary Prevention Patients Allocated to Placebo or to Statin Therapy: An Analysis From the JUPITER Trial
Study Questions:
Does measurement of lipoprotein-associated phospholipase A2 (Lp-PLA2) mass or activity continue to predict risk after low-density lipoprotein cholesterol (LDL-C) reduction by statin therapy?
Methods:
The authors measured Lp-PLA2 mass concentration and activity at baseline and after treatment in the JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial, which compared rosuvastatin 20 mg to placebo among 17,802 men and women without cardiovascular disease or diabetes at study entry. The relationships of Lp-PLA2 mass and activity with risk of future vascular events were evaluated in the placebo and rosuvastatin groups.
Results:
Before randomization, levels of Lp-PLA2 mass and activity correlated moderately with each other and with LDL-C. The magnitude of these correlations increased after statin therapy. Rosuvastatin reduced Lp-PLA2 mass by 33.8%, Lp-PLA2 activity by 33.2%, and LDL-C by 48.7% (all p < 0.0001). Among those allocated to placebo, increasing quartiles of Lp-PLA2 activity (Ptrend = 0.04), but not Lp-PLA2 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 Lp-PLA2 levels and subsequent vascular events. The ability of rosuvastatin to reduce vascular events was not significantly modified by baseline Lp-PLA2 level.
Conclusions:
The authors concluded that among JUPITER trial participants allocated to placebo, levels of Lp-PLA2 activity, but not mass, were associated with cardiovascular risk. However, Lp-PLA2 no longer predicted risk or modified clinical outcomes when participants were treated with rosuvastatin.
Perspective:
The assay for Lp-PLA2 has been problematic despite multiple studies suggesting its utility in many different settings. This analysis from the JUPITER trial and the accompanying editorial suggest that the middle ground is likely the proper place for this marker. It appears to have prognostic ability for predicting vascular events, although that effect is markedly attenuated by other underlying risk factors. It also appears that the activity assay, a more stable assay than the concentration assay, is the best way to measure Lp-PLA2.
Keywords: Fluorobenzenes, Cholesterol, Prognosis, Biomarkers, Cardiology, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiovascular Diseases, Lipoproteins, Pyrimidines, Risk Factors, Primary Prevention, Sulfonamides
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