Abstract 14857: Changes in Lp-PLA2 Activity in Secondary Prevention Predict Coronary Events and Treatment Effect by Pravastatin in the Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) Trial
Background Elevated levels of the pro-inflammatory enzyme, lipoprotein-associated phospholipase 2 (Lp-PLA2) are associated with increased cardiovascular risk in healthy individuals, but have not been assessed in CHD patients. Effects of statins on CHD are largely explained by LDL-C lowering, but some of the treatment effect may also be explained by an effect on Lp-PLA2 levels.
Objectives To assess the value of Lp-PLA2 to predict coronary events (CHD death or nonfatal MI), the effect of pravastatin on Lp-PLA2 levels, and the extent of the pravastatin treatment effect explained by effects on Lp-PLA2.
Methods The LIPID trial randomized 9014 patients with cholesterol levels 4.0-7.0 mmol/L to 6 years of placebo or pravastatin after an MI or unstable angina. Lp-PLA2 activity (DiaDexus assay) was measured at randomization and 1 year. Baseline Lp-PLA2 activity (<229, 229-261, 261-293, >293 nmol min-1 ml-1) and changes to 1 year (<-46.6, -46.6 to -19.8, -19.8 to 2.9, >2.9) were grouped as quartiles.
Results Pravastatin reduced Lp-PLA2 activity over 1 year by 15.7% more than placebo (P<0.001). Baseline Lp-PLA2 activity was positively associated with CHD event rate (P<0.001), but not after adjustment for other baseline factors (P=0.91). In 6518 patients event-free at 1 year, change in Lp-PLA2 from baseline remained a significant independent predictor of subsequent CHD events after adjustment for 23 traditional risk factors, including LDL-C (P<0.001), or changes in LDL-C alone (P<0.001), but baseline Lp-PLA2 did not (P=0.66). The reduction in CHD events by pravastatin was no longer significant, hence partly accounted for, by adjustment for change in Lp-PLA2, but not accounted for by adjustment for changes in other biomarkers including CRP, BNP, and TnI.
Conclusion Reduction in Lp-PLA2 activity during the first year was a highly significant predictor of CHD events, independent of treatment or change in LDL-C, and may partly account for the benefits of pravastatin treatment.
- © 2011 by American Heart Association, Inc.