Abstract 10560: Atorvastatin Enhances the Fractional Catabolism of C-Reactive Protein
Background: Atorvastatin is known to reduce plasma C-reactive protein (CRP) concentrations. Our goals were to define the mechanisms by which CRP was reduced by atorvastatin 80 mg/day, and to determine its relationships with lipoprotein metabolism.
Methods: Nine subjects with combined hyperlipidemia (5 men and 4 postmenopausal women) were enrolled in a randomized, placebo-controlled double-blind, cross over study. Subjects underwent a 15-hour primed-constant infusion with deuterated leucine after 8 weeks of placebo and atorvastatin treatment. CRP was purified from the plasma density fraction greater than 1.21 g/ml by affinity chromatography, and isotope enrichment was determined by gas chromatography/mass spectrometry. Kinetic parameters were determined using compartmental modeling. Paired t test and Wilcoxon signed ranks test were used to compare differences between placebo and atorvastatin.
Results: As compared to placebo, atorvastatin decreased CRP pool size (PS) by 26.04% (13.31±3.78 vs 10.26±3.93 mg; p=0.16). The CRP fractional catabolic rate (FCR) increased by 53.74% (0.34±0.06 vs 0.50±0.11 pools/day; p=0.09), while CRP production rate (PR) remained unchanged (0.050±0.01 vs 0.049±0.01 mg/kg/day; p=0.78). Changes in CRP PR were significantly correlated with changes in CRP PS (r=0.952, p<0.001) and changes in CRP FCR (r=0.762, p=0.028). There were significant inverse correlations between CRP FCR with triglyceride concentration (r= -0.881; p=0.004) and triglyceride rich lipoprotein apolipoproteinB48 pool size (r= -0.905; p=0.002).
Conclusion: Atorvastatin 80 mg/day reduced CRP pool size by 26.04%. The CRP reduction was resulted from a 53.74% increase in fractional catabolic rate.
- © 2011 by American Heart Association, Inc.