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 .
A prospective study of paraoxonase gene Q/R192 polymorphism and severity, progression and regression of coronary atherosclerosis, plasma lipid levels, clinical events and response to fluvastatin.
Human serum paraoxonase ( PON1 ) is a high-density lipoprotein (HDL)-associated enzyme that is responsible for the protective effect of HDL against oxidation of low-density lipoprotein ( LDL ) . PON1 has a Glu to Arg polymorphism at codon 192 ( CGA-->CAA ) which is design ated R/Q192 . The R/Q192 polymorphism has been associated with coronary artery disease ( CAD ) in several , but not all , case-control studies . We prospect ively studied the association of the Q/R192 genotypes with the severity , progression and regression of CAD , plasma lipid levels , clinical events and response to treatment with fluvastatin in a well-characterized cohort . Genotypes were determined by polymerase chain reaction ( PCR ) and restriction mapping with AlwI enzyme in 356 subjects in the Lipoprotein and Coronary Atherosclerosis Study ( LCAS ) .  Fasting plasma lipids were measured and quantitative coronary angiograms were obtained at baseline and 2.5 years following r and omization to fluvastatin or placebo . A total of 177 ( 50 % ) , 142 ( 40 % ) and 37 ( 10 % ) subjects had Q/Q , Q/R and R/R genotypes , respectively . Baseline and final plasma levels of HDL , LDL , triglyceride and other lipoproteins , lesion-specific minimum lumen diameters ( MLD ) , mean MLD , number of coronary lesions and total occlusions at baseline and follow-up and clinical event rates were not significantly different among the genotypes . There was no genotype-treatment interaction with respect to plasma lipid levels and angiographic indices of CAD . The Q/R192 variants of PON1 are not associated with severity , progression or regression of coronary atherosclerosis , plasma lipid levels , clinical events , or response to treatment with fluvastatin .  Thus , the Q/R192 polymorphism is not a major risk factor in susceptibility to CAD in the LCAS population
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 .