Lipoprotein-Associated Phospholipase A 2 and Its Association With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes in the PROVE IT-TIMI 22 (PRavastatin Or atorVastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction) Trial

Abstract

Background— Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is associated with the risk of cardiovascular (CV) events in population-based studies. The prognostic value of Lp-PLA 2 in patients with acute coronary syndromes (ACS) has not been established. Methods and Results— Plasma levels of Lp-PLA 2 activity were measured at baseline (n=3648) and 30 days (n=3265) in patients randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d after ACS in the PROVE IT-TIMI 22 (PRavastatin Or atorVastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction) trial. The primary end point was death, myocardial infarction, unstable angina, revascularization, or stroke (mean follow-up 24 months). At baseline after ACS, the risk of recurrent CV events was similar across all quintiles of Lp-PLA 2 activity ( P trend =0.88). Overall, mean levels of Lp-PLA 2 were lower at 30 days of follow-up than at baseline (35.7 versus 40.9 nmol · min −1 · mL −1 , P <0.001). In particular, treatment with atorvastatin 80 mg/d was associated with a 20% reduction in Lp-PLA 2 activity ( P <0.001), whereas Lp-PLA 2 rose 3.6% with pravastatin 40 mg/d ( P <0.001). Patients with 30-day Lp-PLA 2 activity in the highest quintile were at significantly increased risk of recurrent CV events compared with those in the lowest quintile (26.4% versus 17.6%, P trend =0.002). After adjustment for cardiac risk factors, treatments, achieved low-density lipoprotein (LDL), and C-reactive protein, Lp-PLA 2 activity in the highest quintile remained independently associated with a higher risk of recurrent CV events (adjusted hazard ratio 1.33, 95% confidence interval [CI] 1.01 to 1.74). Conclusions— Lp-PLA 2 is not useful for risk stratification when measured early after ACS. At 30 days, Lp-PLA 2 activity is significantly lowered with high-dose statin therapy and is associated with an increased risk of CV events independent of C-reactive protein and LDL cholesterol levels.