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 .
Relationship of paraoxonase 1 (PON1) gene polymorphisms and functional activity with systemic oxidative stress and cardiovascular risk.
CONTEXT Paraoxonase 1 ( PON1 ) is reported to have antioxidant and cardioprotective properties . The relationship between PON1 genotypes and functional activity with systemic measures of oxidative stress and cardiovascular disease ( CVD ) risk in humans has not been systematic ally investigated . OBJECTIVE To investigate the relationship of genetic and biochemical determinants of PON1 activity with systemic measures of oxidative stress and CVD risk in humans . DESIGN , SETTING , AND PARTICIPANTS The association between systemic PON1 activity measures and a functional polymorphism ( Q192R ) result ing in high PON1 activity with prevalent CVD and future major adverse cardiac events ( myocardial infa rct ion , stroke , or death ) was evaluated in 1399 sequential consenting patients undergoing diagnostic coronary angiography between September 2002 and November 2003 at the Clevel and Clinic . Patients were followed up until December 2006 . Systemic levels of multiple structurally defined fatty acid oxidation products were also measured by mass spectrometry in 150 age- , sex- , and race-matched patients and compared with regard to PON1 genotype and activity . MAIN OUTCOME MEASURES Relationship between a functional PON1 polymorphism and PON1 activity with global indices of systemic oxidative stress and risk of CVD . RESULTS The PON1 genotype demonstrated significant dose-dependent associations ( QQ192 > QR192 > RR192 ) with decreased levels of serum PON1 activity and with increased levels of systemic indices of oxidative stress . Compared with participants with either the PON1 RR192 or QR192 genotype , participants with the QQ192 genotype demonstrated an increased risk of all-cause mortality ( 43/681 deaths [ 6.75 % ] in RR192 and QR192 and 62/584 deaths [ 11.1 % ] in QQ192 ; adjusted hazard ratio , 2.05 ; 95 % confidence interval [ CI ] , 1.32 - 3.18 ) and of major adverse cardiac events ( 88/681 events [ 13.6 % ] in RR192 and QR192 and 102/584 events [ 18.0 % ] in QQ192 ; adjusted hazard ratio , 1.48 ; 95 % CI , 1.09 - 2.03 ; P = .01 ) . The incidence of major adverse cardiac events was significantly lower in participants in the highest PON1 activity quartile ( 23/315 [ 7.3 % ] ) and 235/324 [ 7.7 % ] for paraoxonase and arylesterase , respectively ) compared with those in the lowest activity quartile ( 78/311 [ 25.1 % ] and 75/319 [ 23.5 % ] ; P < .001 for paraoxonase and arylesterase , respectively ) . The adjusted hazard ratios for major adverse cardiac events between the highest and lowest PON1 activity quartiles were , for paraoxonase , 3.4 ( 95 % CI , 2.1 - 5.5 ; P < .001 ) and for arylesterase , 2.9 ( 95 % CI , 1.8 - 4.7 ; P < .001 ) and remained independent in multivariate analysis . CONCLUSION This study provides direct evidence for a mechanistic link between genetic determinants and activity of PON1 with systemic oxidative stress and prospect i ve cardiovascular risk , indicating a potential mechanism for the atheroprotective function of PON1
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 .