Atorvastatin reduces malondialdehyde concentrations in patients with polycystic ovary syndrome. Effects of pitavastatin and atorvastatin on lipoprotein oxidation biomarkers in patients with dyslipidemia. Effect of Sesamin Supplementation on Cardiovascular Risk Factors in Women with Rheumatoid Arthritis Rapid effect of pravastatin on endothelial function and lipid peroxidation in unstable angina. Malondialdehyde in plasma, a biomarker of global oxidative stress during mini-CABG compared to on- and off-pump CABG surgery: a pilot study. The differential effect of statins on oxidative stress and endothelial function: atorvastatin versus pravastatin. The effects of rosiglitazone and metformin on oxidative stress and homocysteine levels in lean patients with polycystic ovary syndrome. &ohgr;-3 fatty acid treatment in cardiac syndrome X: a double-blind, randomized, placebo-controlled clinical study Effect of (R)-α-Lipoic Acid Supplementation on Serum Lipids and Antioxidative Ability in Patients with Age-Related Macular Degeneration Relation of oxidative biomarkers, vascular dysfunction, and progression of coronary artery calcium. Vascular effects of diet and statin in hypercholesterolemic patients. The effect of calcitriol on lipid profile and oxidative stress in hyperlipidemic patients with type 2 diabetes mellitus Paraoxonase-1 activity, malondialdehyde and glutathione peroxidase in non-alcoholic fatty liver disease and the effect of atorvastatin. The influence of pravastatin and atorvastatin on markers of oxidative stress in hypercholesterolemic humans. Rapid, Direct Effects of Statin Treatment on Arterial Redox State and Nitric Oxide Bioavailability in Human Atherosclerosis via Tetrahydrobiopterin-Mediated Endothelial Nitric Oxide Synthase Coupling Pleiotropic effects of atorvastatin in heart failure: role in oxidative stress, inflammation, endothelial function, and exercise capacity. Xanthine-oxidase inhibitors and statins in chronic heart failure: effects on vascular and functional parameters.
BACKGROUND It has been shown that there is an increase in oxidative stress in polycystic ovary syndrome ( PCOS ) .  Statins are considered to have a pleiotropic effect other than their lipid-lowering effect . These effects may be mediated in part by reducing oxidative stress . METHODS This r and omized , double-blind , placebo-controlled study was conducted to assess the effect of atorvastatin on serum malondialdehyde ( MDA ) concentrations as a marker of oxidative stress in patients with PCOS . Forty medication-naïve patients with PCOS were r and omized to either atorvastatin 20 mg daily or placebo for 3 months . A 3-month extension study for both groups of patients was undertaken with metformin 1500 mg daily after completing initial 3 months of atorvastatin or placebo . RESULTS There was a significant decrease of MDA concentrations  with atorvastatin [ mean ( sem ) ] [ 0.29 ( 0.04 ) vs. 0.25 ( 0.02 ) μmol/liter ; P < 0.01 ] compared with placebo [ 0.28 ( 0.02 ) vs. 0.29 ( 0.12 ) μmol/liter ; P = 0.52 ] . Three months treatment with metformin result ed in further reduction of MDA levels  with atorvastatin compared with baseline [ 0.25 ( 0.02 ) baseline vs. 0.23 ( 0.03 ) μmol/liter for atorvastatin treated ; P = 0.02 ] . There was also a significant correlation between the reduction in MDA with a reduction in high-sensitivity C-reactive protein ( r = 0.71 , P < 0.01 ) , an increase in 25-hydroxyvitamin D ( 25OHD ; r = -0.68 , P = 0.02 ) , and a reduction in testosterone levels ( r = 0.63 , P = 0.01 ) . Multiple linear regression analysis revealed Δ25OHD , ΔC-reactive protein , and Δtestosterone were independent predictors of changes in MDA after atorvastatin treatment . No correlation was observed between the reductions in serum MDA concentrations with changes in the lipid parameters . CONCLUSIONS Twelve weeks of atorvastatin led to a significant reduction in oxidative stress as determined by MDA concentrations among patients with polycystic ovary syndrome that was independently predicted by changes in testosterone , 25OHD , and high-sensitivity C-reactive protein OBJECTIVE The effects of potent statins on oxidized lipoprotein biomarkers are not well defined . METHODS AND RESULTS The VISION ( Value of oxIdant lipid lowering effect by Statin InterventiON in hypercholesterolemia ) Trial r and omized patients with hypercholesterolemia to 12-week administration of  pitavastatin 2 mg/day ( n = 21 ) or atorvastatin 10 mg/day ( n = 21 ) and a variety of lipoprotein oxidative biomarkers were measured . Between-group analysis did not reveal any differences except in the ratio of malondialdehyde (MDA)-LDL over apolipoprotein B-100 ( MDA-LDL/apoB ) in pitavastatin vs. atorvastatin group ( -13 % vs. -0.7 % , p = 0.04 ) . Within-group changes from baseline to 12-week revealed significant increases in OxPL/apoB and reductions in small-dense LDL , MDA-LDL , and lipoprotein-associated phospholipase A(2 ) measured on circulating apoB particles ( Lp-PLA(2)/apoB ) in both groups and significant reductions in OxPL/apoAI in the atorvastatin group . CONCLUSIONS The VISION study describes the first comparison on lipoprotein oxidation biomarkers between pitavastatin and atorvastatin and suggests diverse effects on lipoprotein oxidation markers in patients with hypercholesterolemia Objective : Rheumatoid arthritis ( RA ) is an inflammatory disease with increased mortality from cardiovascular disease ( CVD ) . Oxidative stress has a critical role in the pathogenesis of RA and CVD . Sesamin , the main lignin constituent of sesame , has several antioxidant and anti-inflammatory effects . This study aim ed to investigate the effects of sesamin supplementation on anthropometric indices , lipid profile , blood pressure , and oxidative stress markers in women with RA . Methods : In this r and omized , double-blind , placebo-controlled clinical trial , 44 patients with RA were r and omly divided into 2 groups ( intervention and control ) . Patients consumed 200 mg/day sesamin supplement and placebo in the intervention and control groups , respectively , for 6 weeks ( spring 2014 ) . At baseline and at the end of the study , anthropometric indices and blood pressure were assessed . Serum concentrations of lipid profile , malondialdehyde ( MDA ) , and total antioxidant capacity ( TAC ) were also determined . Results : At the end of study , sesamin supplementation significantly decreased serum levels of MDA ( p = 0.018 ) and increased TAC and high-density lipoprotein cholesterol ( HDL-C ) levels in patients with RA ( p = 0.020 and p = 0.007 , respectively ) . In the sesamin group , the mean of weight , body mass index , waist-to-hip ratio , body fat , systolic blood pressure , and the concentration of other lipid profiles ( triglycerides , total cholesterol , and low-density lipoprotein cholesterol [ LDL-C ] ) were also significantly decreased at the end of study compared to baseline values ( p < 0.05 ) . However , the difference between the 2 groups was not statistically significant in this regard ( p > 0.05 ) . Conclusion : Sesamin exhibited a protective effect on cardiovascular risk factors in patients with RA . However , further investigation is suggested BACKGROUND Oxidative stress contributes to endothelial dysfunction , an important step to the pathogenesis of atherosclerosis and coronary events . Latest studies revealed the existence of pleiotropic and especially antioxidant properties of statins . We sought to examine the effects of pravastatin on lipid peroxidation and endothelial function , independently from lipid-lowering , in patients with unstable angina ( UA ) . METHODS Thirty-seven patients ( males ) , 64.46+/-9.09 years , suffering from UA enrolled in the study . Patients were not on statin medication before admission and they received after r and omization either 40 mg pravastatin daily ( group A , n = 20 ) , or placebo ( group B , n = 17 ) . Malondialdehyde ( MDA ) concentration , an index of lipid peroxidation and plaque instability , flow-mediated dilatation ( FMD ) of the brachial artery and blood lipids were measured on the second day of hospitalization and 10 days later . RESULTS MDA decreased significantly in both groups ( A , p = 0.008 ; B , p = 0.003 ) . FMD increased significantly in group A ( p = 0.007 ) , whereas in group B it did not change . Serum lipids remained unaltered in all three groups . CONCLUSIONS Pravastatin administration improved FMD within 10 days and this favorable effect occurred before any significant reduction in blood lipids , revealing its pleiotropic effects during the early phase of an acute coronary syndrome . Circulating lipid peroxidation products in patients with UA decreased significantly during the same period independently of endothelial function and pravastatin therapy In contrast to conventional on-pump coronary artery bypass grafting only mild increase of parameters of oxidative stress is reported during and after off-pump coronary artery bypass grafting . In an attempt to reduce the side effects of extra corporeal circulation the mini- extra corporeal circulation concept was introduced . In this study peroperative oxidative stress biomarkers were compared using three different techniques for CABG ( conventional , mini and off-pump ) . It concerns a prospect i ve r and omized pilot study of 60 aged patients ( 70 + years ) divided over 3 study groups . During the peroperative time points there was a significant increase in the mean concentration of uric acid for the CCABG group . On arrival at the intensive care unit the mean concentrations decreased significantly . During the per-operative period all groups showed significant increase in the concentration of malondialdehyde , however , this increase was the steepest for the CCABG group . On arrival at the intensive care unit the mean concentration decreased significantly for all groups . We found only mild organ ischemia/reperfusion injury and oxidative stress in the OPCAB group and the MCABG group with respect to the CCABG group BACKGROUND Atherogenic risk in subjects with metabolic syndrome is partly mediated by increased oxidative stress and subsequent endothelial dysfunction . Clinical trials have demonstrated differences in outcomes between subjects receiving lipophilic statins ( atorvastatin ) compared with hydrophilic statins ( pravastatin ) . However , whether these findings are attributable to differences in the doses administered or to nonlipid-lowering pleiotropic effects of statins on oxidative stress and vascular function remains unknown . We hypothesized that equipotent doses of these two statins will have divergent effects on markers of oxidative stress and endothelial function . METHODS Thirty-six subjects with hyperlipidemia and metabolic syndrome and /or diabetes were r and omized in a double-blind manner to either pravastatin 80 mg or atorvastatin 10 mg daily .  Oxidative stress ( dROMs assay that measures lipid hydroperoxides , plasma thiobarbituric acid reactive substances [ TBARS ] , and aminothiol levels ) and brachial artery flow-mediated dilation ( FMD ) were measured at baseline and after 12 weeks of statin therapy . RESULTS Statin therapy reduced serum low-density lipoprotein cholesterol levels equally in both groups . Atorvastatin therapy was associated with a significant reduction in TBARS ( P = .006 ) and dROMs levels ( P = .02 ) , which was not observed in subjects treated with pravastatin .  Endothelial function improved with statin therapy ( P = .02 ) , but there was no difference between the statin groups . CONCLUSION In hyperlipidemic subjects with metabolic syndrome , atorvastatin is associated with a greater reduction in lipid markers of oxidation compared with pravastatin . Whether these effects are responsible for the outcome differences in trials comparing these agents needs further investigation BACKGROUND Oxidative stress and hyperhomocysteinaemia are risk factors for cardiovascular diseases . The aim of this study was to assess the effects of rosiglitazone and metformin on cardiovascular disease risk factors such as insulin resistance , oxidative stress and homocysteine levels in lean patients with polycystic ovary syndrome ( PCOS ) . METHODS Fifty lean patients ( BMI < 25 kg/m2 ) with PCOS and 35 healthy subjects were included this study . Serum homocysteine , sex steroids , fasting insulin , fasting glucose and lipid levels were measured . Total antioxidant status ( TAS ; combines concentrations of individual antioxidants ) and malonyldialdehyde concentration ( MDA ) were determined . Insulin resistance was evaluated by using the homeostasis model insulin resistance index ( HOMA-IR ) , quantitative insulin sensitivity check index ( QUICKI ) , Area under the curve insulin ( AUCI ) and the insulin sensitivity index ( ISI ) . Patients were divided into two groups . One group was treated with metformin ( n = 25 ) and the other received rosiglitazone ( n = 25 ) for 12 weeks . All measurements were repeated at the end of 12 weeks . RESULTS Compared with healthy women , those with PCOS had significantly elevated serum MDA , homocysteine , HOMA-IR , AUCI and lipoprotein a levels , and significantly decreased serum TAS , QUICKI and ISI . Serum free testosterone levels showed a significant positive correlation with MDA , AUCI and HOMA-IR , and a negative correlation with TAS , ISI and QUICKI in PCOS patients . HOMA-IR and AUCI significantly decreased , while QUICKI and ISI significantly increased after treatment in both groups . Serum TAS level increased and serum MDA level decreased after the rosiglitazone treatment , but these parameters did not change after the metformin treatment . Serum homocysteine and lipid levels did not change in either group , while serum and rogen levels and LH/FSH ratio significantly decreased after the treatment period in only the rosiglitazone-treated group . CONCLUSION Elevated insulin resistance , oxidative stress and plasma homocysteine levels and changes in serum lipid profile ( risk factors for cardiovascular disease ) were observed in lean PCOS patients .  Rosiglitazone seemed to decrease elevated oxidative stress when compared with metformin treatment in lean PCOS patients Objective We conducted a clinical trial to examine the effect of & ohgr;-3 fatty acids in patients with cardiac syndrome X ( CSX ) . We aim ed to evaluate the potential impact of & ohgr;-3 fatty acids on endothelial function , oxidative stress , and symptom relief in the CSX . Methods and results Eighteen patients with CSX were enrolled according to a double-blind , r and omized , placebo-controlled design . Patients were r and omized to & ohgr;-3 fatty acids ( 1440 mg/day , n=8 ) or placebo ( n=10 ) for 4 months . We assessed plasma levels of malondialdehyde ( MDA ) , endothelium-dependent vasodilatation [ flow-mediated dilatation ( FMD ) ] , endothelium-independent vasodilatation [ nitroglycerin-mediated dilatation ( NMD ) ] , and status of symptom [ score with Seattle Angina Question naire ( SAQ ) ] before and after the treatment . After 4 months , patients who were treated with & ohgr;-3 fatty acids showed significant increases in the FMD ( from 47±48 to 104±23 % , P<0.05 ) and NMD ( from 51±53 to 93±35 % , P<0.05 ) values , and significant decreases in the plasma MDA levels ( 4.4±0.86 to 3.35±0.33 µmol/l , P=0.012 ) . SAQ scores were increased significantly in both groups ( from 60±14 to 73±15 % , P<0.05 placebo , from 67±10 to 81±9 % , P<0.05 treatment group ) . NMD was correlated negatively with the plasma MDA levels . Conclusion Four months of therapy with a moderate dose of & ohgr;-3 fatty acids improved the endothelial function and reduced oxidative stress in patients with CSX Background / Aims : Supplementation with antioxidants is of special interest in preventing or delaying the development and progression of age-related macular degeneration ( AMD ) . This investigation aim ed to assess the effect of α- lipoic acid ( LA ) on serum lipids , serum malondialdehyde ( MDA ) and superoxide dismutase ( SOD ) in patients with AMD . Methods : A total of 62 patients ( 50–75 years old ) with early and intermediate dry form of AMD were r and omly assigned to two groups , i.e. LA administration ( n = 32 ) and placebo ( n = 30 ) . The levels of serum lipids and MDA and SOD activity were measured before and after LA and placebo intervention . Results : Compared with the parameters at baseline , serum total cholesterol ( CHO ) , triglyceride and high- and low-density lipoprotein CHO ( HDL and LDL ) levels were not significantly different after LA and placebo intervention . There was a slight but statistically nonsignificant decrease in serum MDA levels and a statistically significant increase in serum SOD activity after LA intervention . There were no statistically significant differences in serum MDA levels or SOD activity after placebo intervention . Conclusion : The apparent increase in SOD activity caused by LA supplementation indicates that LA may have a possible preventive effect in the development of AMD through an antioxidant mechanism The relation between oxidative stress and coronary artery calcium ( CAC ) progression is currently not well described . The present study evaluated the relation among the biomarkers of oxidative stress , vascular dysfunction , and CAC .  Sixty asymptomatic subjects participated in a r and omized trial evaluating the effect of aged garlic extract plus supplement versus placebo and underwent measurement of CAC . The postcuff deflation temperature-rebound index of vascular function was assessed using a reactive hyperemia procedure . The content of oxidized phospholipids ( OxPL ) on apolipoprotein B-100 ( apoB ) particles detected by antibody E06 ( OxPL/apoB ) , lipoprotein(a ) , IgG and IgM autoantibodies to malondialdehyde-low-density lipoprotein and apoB-immune complexes were measured at baseline and after 12 months of treatment . CAC progression was defined as an annual increase in CAC > 15 % . Vascular dysfunction was defined according to the tertiles of temperature-rebound at 1 year of follow-up . From baseline to 12 months , a strong inverse correlation was noted between an increase in CAC scores and increases in temperature-rebound ( r(2 ) = -0.90 ) , OxPL/apoB ( r(2 ) = -0.85 ) , and lipoprotein(a ) ( r(2 ) = -0.81 ) levels ( p < 0.0001 for all ) . The improvement in temperature-rebound correlated positively with the increases in OxPL/apoB ( r(2 ) = 0.81 , p = 0.0008 ) and lipoprotein(a ) ( r(2 ) = 0.79 , p = 0.0001 ) but inversely with autoantibodies to malondialdehyde-low-density lipoprotein and apoB-immune complexes . The greatest CAC progression was noted with the lowest tertiles of increases in temperature-rebound , OxPL/apoB and lipoprotein(a ) and the highest tertiles of increases in IgG and IgM malondialdehyde-low-density lipoprotein . In conclusion , the present results have documented a strong relation among markers of oxidative stress , vascular dysfunction , and progression of coronary atherosclerosis . Increases in OxPL/apoB and lipoprotein(a ) correlated strongly with increases in vascular function and predicted a lack of progression of CAC OBJECTIVE We investigated whether statin improves nitric oxide ( NO ) bioactivity and reduces serological markers of oxidant stress and inflammation and whether statin-induced reduction in markers of oxidant stress and inflammation is mediated by improvement in NO bioactivity or lipoprotein changes , compared with American Heart Association Step I Diet ( Diet ) . METHODS We administered diet+placebo and diet+simvastatin 20 mg daily during 14 weeks with r and omized order to 31 and 32 patients with coronary artery disease , respectively , with a r and omized design . RESULTS Compared with diet alone , simvastatin significantly improved the percent flow-mediated dilator response to hyperemia and lowered plasma levels of tumor necrosis factor (TNF)-alpha , intercellular adhesion molecule type-1 ( ICAM-1 ) , serum levels of CRP , and fibrinogen ( P<0.001 , P<0.001 , P=0.035 , P<0.001 and P=0.014 , respectively ) . Compared with diet alone , simvastatin lowered but statistically insignificant plasma levels of nitrate and malondialdehyde ( MDA ) ( P=0.164 and P=0.150 , respectively ) . Further , we observed that patients with the highest pretreatment TNF-alpha , ICAM-1 , and CRP levels showed the greatest extent of reductions on simvastatin . There were significant inverse correlation between low-density lipoprotein ( LDL ) cholesterol or the ratio of LDL to HDL cholesterol levels and flow-mediated dilation percent ( r=-0.342 , P=0.009 and r=-0.356 , P=0.006 , respectively ) . Of interest , there were significant inverse correlations between flow-mediated dilation percent and TNF-alpha levels ( r=-0.329 , P=0.010 ) . However , no significant correlations between lipoprotein levels and levels of inflammation markers were determined . Despite the significant changes of lipoproteins , diet alone did not decrease the markers of inflammation . CONCLUSIONS Compared with diet alone , simvastatin significantly reduced markers of inflammation more . These effects were independent of lipoprotein changes BACKGROUND Cardiovascular mortality is high among diabetic patients due to abnormalities in the plasma lipid and lipoprotein metabolism , and increased oxidative stress . This study aim ed to investigate the effects of active vitamin D on serum lipids and oxidative stress markers in type 2 diabetic patients . METHODS A double-blind r and omized placebo-controlled trial was carried out in 70 participants with type 2 diabetes , aged 30 - 75 years of age . The participants were r and omly assigned to two groups . One group received two capsules of calcitriol ( 0.25 µg 1,25-dihydroxycholecalciferol per capsule ) per day . The second group received placebo tablets . All participants received their oral hypoglycemic drugs as prescribed by the endocrinologist . At the beginning , after 6 weeks , and at the end of the 12-week supplementation trial , serum total cholesterol , low-density lipoprotein ( LDL ) , high-density lipoprotein ( HDL ) , triglyceride ( TG ) , and serum malondialdehyde ( MDA ) levels were measured . RESULTS There was a significant reduction in total cholesterol , LDL-cholesterol , TG , and MDA levels in both treatment and placebo groups ( P < 0.05 ) . Serum HDL-cholesterol level decreased significantly in the placebo group ( P < 0.05 ) , while it remained unchanged in the treatment group . However , the P values related to the between group ’s comparisons were not significant for any variables . CONCLUSION Active vitamin D  reduced lipid profile and oxidative stress markers in diabetic patients compared to the control group , but these alterations were not statistically BACKGROUND AND STUDY AIMS The prevalence of non-alcoholic fatty liver disease ( NAFLD ) appears to be increasing . The aim of the present study was to investigate the relationship between hepatic antioxidant paraoxonase 1 ( PON1 ) activity , lipid peroxidation and antioxidant enzymes in patients with NAFLD and the effect of atorvastatin . PATIENTS AND METHODS This study was conducted on 50 patients with NAFLD and 20 normal subjects matched for age and sex . All of them were subjected to the following investigations : abdominal ultrasonography , serum PON1 activity level , liver function tests , serum lipid profile , fasting and postpr and ial blood glucose and serum levels of malondialdehyde ( MDA ) and glutathione peroxidase ( GP ) .  NAFLD patients were further r and omly classified into two groups ( 25 patients each ) , groups Ia and Ib . Only group Ia received atorvastatin 40 mg tablet for 8months . RESULTS Obesity , dyslipidaemia and impaired glucose tolerance were prevalent in group I. There was a significant decrease in serum PON1 activity with a significant increase in MDA and GP activity ( i.e. , there is a significant increase in lipid peroxidation rate ) in group I compared with group II . After atorvastatin therapy , there was a significant increase in serum PNO1 activity and significant decrease in serum MDA levels . CONCLUSION Patients with NAFLD show enhanced oxidative stress which may lead to non-alcoholic steatohepatitis ( NASH ) . Reduced PON1 activity and increased MDA could be considered a biochemical marker for lipid peroxidation , which require follow-up in patients with NAFLD . Atorvastatin may have a role in prevention of , or delay , the transformation of liver steatosis into NASH OBJECTIVES The aim of this study was to determine the effects of pravastatin and atorvastatin on markers of oxidative stress in plasma . BACKGROUND Hydroxymethylglutaryl coenzyme A reductase inhibitors reduce low-density lipoprotein cholesterol ( LDL-C ) and cardiovascular risk , but their effects on circulating biomarkers of oxidative stress are not well-defined . METHODS Hypercholesterolemic subjects ( n = 120 , ages 21 to 80 years with LDL-C 130 to 220 mg/dl ) were r and omized in a double-blind , parallel design to pravastatin 40 mg/day ( prava40 ) , atorvastatin 10 mg/day ( atorva10 ) , atorvastatin 80 mg/day ( atorva80 ) , or placebo . At baseline and 16 weeks , urinary isoprostanes ( 8 , 12-iso-iPF(2 alpha)-VI isoform ) , plasma lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) , Mercodia oxidized LDL ( OxLDL ) with antibody 4E6 , oxidized phospholipids/apolipoprotein B-100 particle ( OxPL/apoB ) with antibody E06 , immunoglobulin (Ig)G/IgM autoantibodies to malondialdehyde (MDA)-LDL , and apolipoprotein B (apoB)-immune complexes ( IC ) were measured . RESULTS After 16 weeks , there were no significant changes in urinary 8 , 12-iso-iPF(2 alpha)-VI . The Lp-PLA2 and OxLDL were reduced in statin-treated groups , but after adjusting for apoB , only prava40 led to a reduction in Lp-PLA2 ( -15 % , p = 0.008 ) and atorva10 to a decrease in OxLDL ( -12.9 % , p = 0.01 ) . The OxPL/apoB increased 25.8 % ( p < 0.01 ) with prava40 and 20.2 % ( p < 0.05 ) with atorva80 . There were no changes in MDA-LDL autoantibodies , but significant decreases in IC were noted . CONCLUSIONS This study suggests that statin therapy results in variable effects on oxidative stress markers in hypercholesterolemic subjects . Future outcome studies should collectively assess various oxidative markers to define clinical utility Background — Treatment with statins improves clinical outcome , but the exact mechanisms of pleiotropic statin effects on vascular function in human atherosclerosis remain unclear . We examined the direct effects of atorvastatin on tetrahydrobiopterin-mediated endothelial nitric oxide ( NO ) synthase coupling in patients with coronary artery disease . Methods and Results — We first examined the association of statin treatment with vascular NO bioavailability and arterial superoxide ( O2·− ) in 492 patients undergoing coronary artery bypass graft surgery . Then , 42 statin-naïve patients undergoing elective coronary artery bypass graft surgery were r and omized to atorvastatin 40 mg/d or placebo for 3 days before surgery to examine the impact of atorvastatin on endothelial function and O2·− generation in internal mammary arteries . Finally , segments of internal mammary arteries from 26 patients were used in ex vivo experiments to evaluate the statin-dependent mechanisms regulating the vascular redox state . Statin treatment was associated with improved vascular NO bioavailability and reduced O2·− generation in internal mammary arteries . Oral atorvastatin  increased vascular tetrahydrobiopterin bioavailability and reduced basal and N-nitro-L-arginine methyl ester – inhibitable O2·− in internal mammary arteries independently of low-density lipoprotein lowering . In ex vivo experiments , atorvastatin rapidly improved vascular tetrahydrobiopterin bioavailability by upregulating GTP-cyclohydrolase I gene expression and activity , result ing in improved endothelial NO synthase coupling and reduced vascular O2·−. These effects were reversed by mevalonate , indicating a direct effect of vascular hydroxymethylglutaryl-coenzyme A reductase inhibition . Conclusions — This study demonstrates for the first time in humans the direct effects of statin treatment on the vascular wall , supporting the notion that this effect is independent of low-density lipoprotein lowering . Atorvastatin directly improves vascular NO bioavailability and reduces vascular O2·− through tetrahydrobiopterin-mediated endothelial NO synthase coupling . These findings provide new insights into the mechanisms mediating the beneficial vascular effects of statins in humans . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01013103 BACKGROUND Increased oxidative stress , a common feature in chronic heart failure , has been associated with inflammation , endothelial dysfunction , and extracellular matrix degradation . Statins have known anti-inflammatory and anti-oxidant effects ; however , their role in chronic heart failure is still controversial . METHODS This was a prospect i ve study of 38 patients with stable systolic chronic heart failure . Patients received a 4-week placebo course , followed by atorvastatin 20 mg/day for 8 weeks .  Oxidative stress , inflammation and remodeling markers , brachial artery flow-mediated vasodilation , and 6-minute walk test were evaluated at baseline , 4 , and 8 weeks . RESULTS Mean age was 58 + /- 12 . Mean left ventricular ejection fraction was 27 % + /- 12 % . No significant differences were observed between measurements at baseline and after placebo . Atorvastatin induced a significant decrease of matrix metalloproteinase-9 activity , high-sensitivity C-reactive protein , tumor necrosis factor-alpha , interleukin-6 , and malondialdehyde , and a significant increase of endothelial superoxide dismutase activity when compared with placebo . No differences in tissue inhibitor of matrix metalloproteinase and matrix metalloproteinase-2 activities were observed . Atorvastatin use was associated with an improved flow-dependent brachial vasodilation and exercise capacity in the 6-minute walk test . CONCLUSIONS In chronic heart failure patients , atorvastatin therapy is associated with a decrease of inflammation and extracellular matrix remodeling , improving both endothelial function and exercise capacity BACKGROUND Increased oxidative stress in heart failure ( HF ) leads to inflammation and endothelial dysfunction ( ED ) . Both statins and allopurinol have known anti-oxidant properties , but their utility in HF has not been fully assessed . METHODS This investigation was a prospect i ve , double-blind , double-dummy study , performed between March 2007 and June 2009 . Seventy-four HF patients , with New York Heart Association ( NYHA ) Class II or III status and left ventricular ejection fraction ( LVEF ) < 40 % , were included . Patients received placebo during 4 weeks and were then r and omized to receive 4 weeks of either atorvastatin 20 mg/day plus placebo ( ATV+PLA group ) or atorvastatin 20 mg/day orally plus allopurinol 300 mg/day orally ( ATV+ALLO group )  . Malondialdehyde ( MDA ) , extracellular superoxide dismutase ( ecSOD ) activity and uric acid ( UA ) levels , among others , were determined at baseline and after 4 weeks of treatment . ED was assessed by flow-dependent endothelial-mediated vasodilation ( FDD ) , and functional capacity by 6-minute walk test ( 6MWT ) . RESULTS Thirty-two patients were r and omized to ATV+PLA and 38 to ATV+ALLO . Mean age was 59 ± 2 years , 82 % were male , and 22 % had an ischemic etiology . Hypertension was present in 60 % and diabetes in 15 % of those studied . No significant differences were observed between baseline measurements and after placebo . After 4 weeks of treatment , both groups showed a significant decrease on MDA ( 0.9 ± 0.1 to 0.8 ± 0.1 and 1.0 ± 0.5 to 0.9 ± 0.1 μmol/liter , p = 0.88 ) , UA ( 7.4 ± 0.4 to 6.8 ± 0.3 and 7.2 ± 0.4 to 5.0 ± 0.3 mg/dl , p < 0.01 ) and FDD ( 3.9 ± 0.2 % to 5.6 ± 0.4 % and 4.6 ± 0.3 % to 7.1 ± 0.5 % , p = 0.07 ) with increased ecSOD activity ( 109 ± 11 to 173 ± 13 and 98 ± 10 to 202 ± 16 , U/ml/min , p = 0.41 ) and improved 6MWT ( 447 ± 18 to 487 ± 19 and 438 ± 17 to 481 ± 21 m , p = 0.83 ) , with all values for ATV+PLA and ATV+ALLO , respectively ; p-values are for comparison between groups after treatment . CONCLUSION Short-term ATV treatment in heart failure ( HF ) patients  reduces oxidative stress and improves FDD and functional capacity . These beneficial effects are not strengthened by the addition of allopurinol
Conclusions : This systematic review and meta- analysis showed that statin treatment significantly reduces systemic MDA concentrations .
Background : The effect of statins on oxidative stress markers , such as malondialdehyde ( MDA ) , is still a matter of debate .
We sought to address this issue by conducting a systematic review and meta- analysis of published data on the effect of statin treatment on systemic MDA concentrations .