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 .
Clinical and Genetic Association of Serum Paraoxonase and Arylesterase Activities With Cardiovascular Risk
Objective —Diminished serum paraoxonase and arylesterase activities ( measures of paraoxonase-1 [ PON-1 ] function ) in humans have been linked to heightened systemic oxidative stress and atherosclerosis risk . The clinical prognostic use of measuring distinct PON-1 activities has not been established , and the genetic determinants of PON-1 activities are not known . Methods and Results —We established analytically robust high-throughput assays for serum paraoxonase and arylesterase activities and measured these in 3668 stable subjects undergoing elective coronary angiography without acute coronary syndrome and were prospect ively followed for major adverse cardiovascular events ( MACE= death , myocardial infa rct ion , stroke ) over 3 years . Low serum arylesterase and paraoxonase activities were both associated with increased risk for MACE , with arylesterase activity showing greatest prognostic value ( quartile 4 versus quartile 1 ; hazard ratio 2.63 ; 95 % CI , 1.97–3.50 ; P<0.01 ) . Arylesterase remained significant after adjusting for traditional risk factors , C-reactive protein , and creatinine clearance ( hazard ratio , 2.20 ; 95 % CI , 1.60–3.02 ; P<0.01 ) , predicted future development of MACE in both primary and secondary prevention population s , and reclassified risk categories incrementally to traditional clinical variables . A genome-wide association study identified distinct single nucleotide polymorphisms within the PON-1 gene that were highly significantly associated with serum paraoxonase ( 1.18 × 10 - 303 ) or arylesterase ( 4.99 × 10−116 ) activity but these variants were not associated with either 3-year MACE risk in an angiographic cohort ( n=2136 ) or history of either coronary artery disease or myocardial infa rct ion in the Coronary Artery Disease Genome-Wide Replication and Meta- Analysis consortium ( n≈80 000 subjects ) . Conclusion —Diminished serum arylesterase activity , but not the genetic determinants of PON-1 functional measures , provides incremental prognostic value and clinical reclassification of stable subjects at risk of developing MACE
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 .