RESULTS Meta- analysis suggested that statin therapy is associated with a significant elevation of PON1 paraoxonase and arylesterase activities , but not PON1 protein concentration .
The PON1-enhancing effects of statins were robust in the sensitivity analyses and were independent of statin dose , treatment duration and changes in plasma low-density lipoprotein cholesterol concentration .
CONCLUSION The increase of paraoxonase and arylesterase activities with statins is a pleiotropic lipid-independent clinical benefit that may partly explain the putative effects of statins in preventing cardiovascular outcomes
BACKGROUND Decreased activity of the enzyme paraoxonase-1 ( PON1 ) has been demonstrated in cardiovascular diseases .
Statins , the forefront of pharmacotherapy for dyslipidemia , have been shown to enhance PON1 activity but clinical findings have not been conclusive .
OBJECTIVE To systematic ally review the clinical findings on the impact of statin therapy on PON1 status ( protein concentrations and activities of paraoxonase and arylesterase ) and calculate an effect size for the mentioned effects through meta- analysis of available data .
Effect of Simvastatin Therapy on Paraoxonase Activity and Related Lipoproteins in Familial Hypercholesterolemic Patients
Human paraoxonase ( PON1 ) is a calcium-dependent esterase closely associated with high density lipoprotein (HDL)-containing apolipoprotein AI ( apoAI ) , which has been shown to confer antioxidant properties to HDL . PON1 has been recently implicated in the pathogenesis of atherosclerosis . Low PON1 activities have been found in familial hypercholesterolemia ( FH ) and diabetes mellitus . We have undertaken a study of the effect of the lipid-lowering drug simvastatin on serum PON1 activity ( in relation to paraoxon and arylesterase activity ) , on apoAI-containing and apolipoprotein B (apoB)-containing lipoproteins , and on lipid peroxide concentrations in 64 ( 39 women and 25 men ) unrelated FH patients . We have also analyzed the influence of the PON1 - 192 and PON1 - 55 genetic polymorphisms on the response of PON1 activity to simvastatin therapy . A venous blood sample for a baseline analysis and another after 4 months of simvastatin therapy at a dosage of 20 mg per day were taken . The major effect of simvastatin on lipid traits was to decrease serum cholesterol , low density lipoprotein ( LDL ) cholesterol , and lipid peroxide concentrations by 19.9 % , 26.3 % , and 37.3 % , respectively . There was also a significant decrease in serum apoB , LDL apoB , and triglyceride concentrations ( 20.5 % , 21.1 % , and 15.6 % , respectively ) . Conversely , simvastatin had no significant influence on very low density lipoprotein – lipid content , HDL cholesterol , apoAI concentrations , and lipoprotein AI and AI : AII particles . Remarkably , serum PON1 activity toward paraoxon significantly increased during treatment with simvastatin ( 168.7±100.3 U/L before therapy versus 189.5±116.5 U/L after therapy , P = 0.005 ) . Arylesterase activity displayed only a nonsignificant trend to increase after therapy . Whereas PON1 activity levels were significantly lower in FH patients  before simvastatin therapy compared with those of 124 normolipidemic subjects ( 168.7±100.3 versus 207.6±125.2 U/L , respectively;P < 0.05 ) , this difference disappeared after simvastatin therapy . After simvastatin therapy , a significantly negative correlation between PON1 activity and lipid peroxide concentration was observed ( r = −0.35 , P = 0.028 ) . The latter also strongly correlated with LDL cholesterol concentration ( r = 0.64 , P < 0.001 ) . Serum PON1 activity levels were significantly lower in the low-activity PON1 - 192 QQ and PON1 - 55 M carriers than in R carriers and in LL carriers , respectively . No significant differences were found in the therapeutic response of PON1 activity between genotype groups ( 8.5 % and 11.1 % increase for QQ homozygous and R-carrier FH patients , respectively , and 12.7 % and 9.5 % increase for LL homozygotes and M carriers , respectively ) . We conclude that simvastatin may have important antioxidant properties through increasing serum PON1 activity , perhaps as a consequence of reducing oxidative stress , by a mechanism independent of apoAI-containing lipoprotein concentration and without the influence of PON1 - 192 and PON1 - 55 genetic polymorphisms . Further studies are clearly warranted to clarify the precise mechanism by which simvastatin therapy is associated with increased PON1 activity
RESULTS Meta- analysis suggested that statin therapy is associated with a significant elevation of PON1 paraoxonase and arylesterase activities , but not PON1 protein concentration .
The PON1-enhancing effects of statins were robust in the sensitivity analyses and were independent of statin dose , treatment duration and changes in plasma low-density lipoprotein cholesterol concentration .
CONCLUSION The increase of paraoxonase and arylesterase activities with statins is a pleiotropic lipid-independent clinical benefit that may partly explain the putative effects of statins in preventing cardiovascular outcomes
BACKGROUND Decreased activity of the enzyme paraoxonase-1 ( PON1 ) has been demonstrated in cardiovascular diseases .
Statins , the forefront of pharmacotherapy for dyslipidemia , have been shown to enhance PON1 activity but clinical findings have not been conclusive .
OBJECTIVE To systematic ally review the clinical findings on the impact of statin therapy on PON1 status ( protein concentrations and activities of paraoxonase and arylesterase ) and calculate an effect size for the mentioned effects through meta- analysis of available data .