The effect of statin therapy on lipoprotein associated phospholipase A2 levels.
Lipoprotein associated phospholipase A2 (Lp-PLA2), a biomarker of oxidation and inflammation, has been associated with increased coronary heart disease (CHD) risk. To date, data examining the effect of HMG CoA reductase inhibitors on Lp-PLA2 are few. We evaluated the effect of pravastatin 40 mg daily versus placebo on Lp-PLA2 levels among 481 subjects free of cardiovascular disease (pravastatin N=246 and placebo N=235) who participated in the Pravastatin Inflammation/CRP Study (PRINCE). After 12 weeks, Lp-PLA2 levels decreased by 22.1% among pravastatin treated participants and by 7.8% among those randomized to placebo (p<0.001). These results were similar in all subgroups evaluated according to age, blood pressure, lipid parameters, diabetic status, smoking status, aspirin use, body mass index and gender. There were correlations between change in Lp-PLA2 levels and baseline Lp-PLA2 levels (r=-0.63, p<0.001), total cholesterol change (r=-0.26, p<0.001), LDL-C change (r=-0.32, p<0.001) and C-reactive protein (CRP) change (r=-0.13, p=0.05). Multivariate linear regression models that assessed the relationship between the log difference in Lp-PLA2 at 12 weeks and treatment revealed a beta-coefficient of 0.15 for the treatment variable (p<0.01). However, adjustment for change in LDL-C substantially attenuated the beta-coefficient associated with treatment to 0.07 (P<0.005) and after additional control for other potential confounders, the effect of treatment was no longer significant. Thus, Lp-PLA2 levels were significantly reduced at 12 weeks by pravastatin, an effect that was significantly related to LDL cholesterol reduction accounting for about 6% of the variability in this response. Moreover, pravastatin induced reduction in Lp-PLA2 was no longer significant after taking the latter into account.
Donald W. Reynolds Center for Cardiovascular Disease Research, Division of Cardiovascular Diseases and of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. maalbert@partners.org
Michelle A
MA
Albert
Robert J
RJ
Glynn
Robert L
RL
Wolfert
Paul M
PM
Ridker
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010741:Phospholipases A / Q000097:blood*; D054467:Phospholipases A2; D017035:Pravastatin / Q000008:administration & dosage*; D012044:Regression Analysis; D012307:Risk Factors
D000924:Anticholesteremic Agents; D015415:Biomarkers; D010741:Phospholipases A; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D017035:Pravastatin