Published Online
on March 14, 2006

A more recent version of this article appeared on April 11, 2006

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Submitted on January 25, 2006
Revised on March 2, 2006
Accepted on March 3, 2006

Lipoprotein-Associated Phospholipase A₂ 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

Michelle O’Donoghue MD, David A. Morrow MD, MPH^*, Marc S. Sabatine MD, MPH, Sabina A. Murphy MPH, Carolyn H. McCabe BS, Christopher P. Cannon MD, and Eugene Braunwald MD

From the Thrombolysis in Myocardial Infarction (TIMI) Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass.

^* To whom correspondence should be addressed. E-mail: dmorrow{at}partners.org.

Background--Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is associated with the risk of cardiovascular (CV) events in population-based studies. The prognostic value of Lp-PLA₂ in patients with acute coronary syndromes (ACS) has not been established.

Methods and Results--Plasma levels of Lp-PLA₂ 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-PLA₂ activity (P_trend=0.88). Overall, mean levels of Lp-PLA₂ 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-PLA₂ activity (P<0.001), whereas Lp-PLA₂ rose 3.6% with pravastatin 40 mg/d (P<0.001). Patients with 30-day Lp-PLA₂ 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-PLA₂ 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-PLA₂ is not useful for risk stratification when measured early after ACS. At 30 days, Lp-PLA₂ 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.

Key words: prognosis • inflammation • myocardial infarction • lipoproteins

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