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.
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.


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 (Ptrend=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%, Ptrend=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.
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Michelle
M
O'Donoghue
David A
DA
Morrow
Marc S
MS
Sabatine
Sabina A
SA
Murphy
Carolyn H
CH
McCabe
Christopher P
CP
Cannon
Eugene
E
Braunwald
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000208:Acute Disease; D000069059:Atorvastatin; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004798:Enzymes / Q000097:blood; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D010741:Phospholipases A / Q000097:blood*; D054467:Phospholipases A2; D017035:Pravastatin / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D016019:Survival Analysis; D013577:Syndrome; D015912:Thrombolytic Therapy; D016896:Treatment Outcome
D004798:Enzymes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D010741:Phospholipases A; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D017035:Pravastatin