title: Effects of Ezetimibe/Simvastatin and Rosuvastatin on Oxidative Stress in Diabetic Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial Simvastatin and oxidative stress in humans: A randomized, double-blinded, placebo-controlled clinical trial Oxidative stress improvement is associated with increased levels of taurine in CKD patients undergoing lipid-lowering therapy Paraoxonase-1 activity, malondialdehyde and glutathione peroxidase in non-alcoholic fatty liver disease and the effect of atorvastatin. Simvastatin Preserves Coronary Endothelial Function in Hypercholesterolemia in the Absence of Lipid Lowering Modulating effect of atorvastatin on paraoxonase 1 activity in type 2 diabetic Egyptian patients with or without nephropathy. Combined therapy with ramipril and simvastatin has beneficial additive effects on tissue factor activity and prothrombin fragment 1+2 in patients with type 2 diabetes. Lipid-independent effects of statins on endothelial function and bioavailability of nitric oxide in hypercholesterolemic patients. No effect of atorvastatin and simvastatin on oxidative stress in patients at high risk for cardiovascular disease. Atorvastatin effect on high-density lipoprotein-associated paraoxonase activity and oxidative DNA damage Additive beneficial effects of atorvastatin combined with amlodipine in patients with mild-to-moderate hypertension. Atorvastatin treatment increases plasma bilirubin but not HMOX1 expression in stable angina patients Effect of NCB-02, Atorvastatin and Placebo on Endothelial Function, Oxidative Stress and Inflammatory Markers in Patients with Type 2 Diabetes Mellitus Rapid effect of pravastatin on endothelial function and lipid peroxidation in unstable angina. Impact of Vitamin E supplementation on lipoprotein peroxidation and composition in Type 1 diabetic patients treated with Atorvastatin. Effects of pravastatin on lipid levels, in vitro oxidizability of non-HDL lipoproteins and microalbuminuria in IDDM patients. Statins as immunomodulators in systemic sclerosis. Effect of Atorvastatin on Inflammation and Modification of Vascular Risk Factors in Rheumatoid Arthritis The differential effect of statins on oxidative stress and endothelial function: atorvastatin versus pravastatin. Effect of simvastatin on the lipid profile of hemodialysis patients. Effects of simvastatin on high-sensitivity C-reactive protein and serum albumin in hemodialysis patients. Simvastatin Combined With Ramipril Treatment in Hypercholesterolemic Patients Effect of simvastatin and fenofibrate on endothelium in Type 2 diabetes. Comparison of the effect of simvastatin versus simvastatin/ezetimibe versus rosuvastatin on markers of inflammation and oxidative stress in subjects with hypercholesterolemia. The effects of lipid-lowering therapy on paraoxonase activities and their relationships with the oxidant–antioxidant system in patients with dyslipidemia Effect of Atorvastatin on Type 2 Diabetic Dyslipidemia Atorvastatin reduces malondialdehyde concentrations in patients with polycystic ovary syndrome. Pleiotropic effects of atorvastatin in heart failure: role in oxidative stress, inflammation, endothelial function, and exercise capacity. Vascular effects of simvastatin combined with ramipril in hypercholesterolemic patients with coronary artery disease, compared with simvastatin alone: a randomized, double-blind, placebo-controlled, crossover study.
abstract: Objective . To evaluate the effects of ezetimibe/simvastatin ( EZE/SIMV ) and rosuvastatin ( ROSUV ) on oxidative stress ( OS ) markers in patients with diabetic polyneuropathy ( DPN ) . Methods . We performed a r and omized , double-blind , placebo-controlled phase III clinical trial in adult patients with Type 2 Diabetes Mellitus ( T2DM ) and DPN , as evaluated by composite scores and nerve conduction studies ( NCS ) . Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to placebo , EZE/SIMV 10/20 mg , or ROSUV 20 mg for 16 weeks . All patients were assessed before and after treatment : primary outcomes were lipid peroxidation ( LPO ) , and nitric oxide ( NO ) surrogate levels in plasma ; secondary outcomes included NCS , neuropathic symptom scores , and metabolic parameters . Data were expressed as mean ± SD or SEM , frequencies , and percentages ; we used nonparametric analysis . Results . LPO levels were reduced in both statin arms after 16 weeks of treatment ( p < 0.05 versus baseline ) , without changes in the placebo group . NO levels were not significantly affected by statin treatment , although a trend towards significance concerning increased NO levels was noted in both statin arms . No significant changes were observed for the NCS or composite scores . Discussion . EZE/SIMV and ROSUV are superior to placebo in reducing LPO in subjects with T2DM suffering from polyneuropathy . This trial is registered with NCT02129231 Simvastatin reduces the blood concentration of cholesterol by inhibiting hydroxymethylglutaryl-coenzyme A reductase , the rate-limiting enzyme in cholesterol synthesis , and thereby reduces the risk of cardiovascular disease . In addition , simvastatin treatment leads to a reduction in fluxes in mitochondrial respiratory complexes I and II and might thereby reduce the formation of reactive oxygen species , which have been implicated in the pathogenesis of arteriosclerosis . Therefore , we hypothesized that simvastatin may reduce oxidative stress in humans in vivo . We conducted a r and omized , double-blinded , placebo-controlled study in which subjects were treated with either 40 mg of simvastatin or placebo for 14 days . The endpoints were six biomarkers for oxidative stress , which represent intracellular oxidative stress to nucleic acids , lipid peroxidation and plasma antioxidants , that were measured in urine and plasma sample s. A total of 40 participants were included , of which 39 completed the trial . The observed differences between simvastatin and placebo groups in the primary outcomes , DNA and RNA oxidation , were small and nonsignificant ( p=0.68 ) , specifically , 3 % in the simvastatin group compared to 7.1 % in the placebo group for DNA oxidation and 7.3 % in the simvastatin group compared to 3.4 % in the placebo group . The differences in biomarkers related to plasma were not statistically significant between the treatments groups , with the exception of total vitamin E levels , which , as expected , were reduced in parallel with the reduction in plasma cholesterol . In healthy young male volunteers , short-term simvastatin treatment , which considerably reduces cholesterol , does not lead to a clinical ly relevant reduction in a panel of measures of oxidative stress . Whether simvastatin has effects on oxidative stress in diseased population s , such as diabetes or hemochromatosis , where oxidative stress is prominent , is unknown but seems unlikely Lipid-lowering therapy has been reported to reduce several oxidative stress ( OS ) markers in hypercholesterolemia . Since OS is frequently associated with renal dysfunction , we aim ed to investigate the effect of hypolipidemic drugs on oxidative stress and plasma taurine ( Tau ) , a sulfur amino acid with a marked antioxidant effect , in chronic kidney disease ( CKD ) . We enrolled 30 CKD r and omized to receive three different hypolipidemic regimens for 12 months : simvastatin alone ( 40 mg/day ) or ezetimibe/simvastatin combined therapy ( 10/20 or 10/40 mg/day ) .  Low molecular weight ( LMW ) thiols including homocysteine , cysteine , cysteinylglycine , glutathione , and glutamylcysteine in their reduced and total form and oxidative stress indices as malondialdehyde ( MDA ) and allantoin/uric acid ( All/UA ) ratio were also evaluated . Tau concentration significantly increased throughout the therapy . The rise of taurine was more striking for the group with the concomitant administration of ezetimibe/simvastatin 10/40 mg/day ( + 31.6 % after 1 year of therapy ) . A significant decrease of both MDA and All/UA ratio was observed during therapy for all patients ( −19 % for both MDA and All/UA ratio ) with a more pronounced effect in patients treated with ezetimibe/simvastatin 10/40 mg/day ( −26 % for MDA and −28 % for All/UA ratio ) . Besides , an increase of thiols reduced forms was found ( + 20.7 % of LMW thiols redox status ) with a greater effect in subjects treated with ezetimibe/simvastatin 10/40 mg/day ( + 24.7 % ) . Moreover , we demonstrated that oxidative stress improvement during therapy was correlated with increased taurine levels . We hypothesize that taurine may be responsible for the oxidative stress improvement observed during lipid-lowering treatment through the reduction of superoxide anion production at the respiratory chain activity level 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 Abstract —Recent evidence suggests that some benefit from the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may occur independent of lipid lowering . We aim ed to determine the effect of simvastatin on coronary endothelial function , endothelial NO synthase ( eNOS ) expression , and oxidative stress in experimental hypercholesterolemia ( HC ) in the absence of cholesterol lowering . Pigs were r and omized to 3 experimental groups : normal diet ( N group ) , high cholesterol diet ( HC group ) , and HC diet with simvastatin ( HC+S group ) for 12 weeks . Low density lipoprotein cholesterol was similarly increased in the HC and HC+S groups compared with the N group . In vitro analysis of coronary large- and small-vessel endothelium-dependent vasorelaxation was performed . The mean vasorelaxation of epicardial vessels to bradykinin was significantly attenuated in the HC group compared with the N group ( 32.3±1.2 % versus 42.9±1.6 % , respectively;P < 0.0001 ) . This attenuation was significantly reversed in the HC+S group ( 38.7±1.5 % , P < 0.005 versus HC group ) . The maximal vasorelaxation to substance P was significantly attenuated in the HC group compared with the N group ( 50.5±11.9 % versus 79.3±5.3 % , respectively;P < 0.05 ) . This attenuated response was normalized in the HC+S group ( 74.9±4.1 % , P < 0.05 versus HC group ) . The maximal arteriolar vasorelaxation to bradykinin was also significantly attenuated in the HC group compared with the N group ( 71.9±4.9 % versus 96.8±1.34 % , respectively;P < 0.005 ) . This was reversed in the HC+S group ( 98.4±0.6 % , P < 0.0001 versus HC group ) . Western blotting of coronary tissue homogenates for eNOS demonstrated a decrease in protein levels in the HC group compared with the N group , with normalization in the HC+S group . Elevation of plasma F2-isoprostanes and thiobarbituric acid – reactive substances , markers of oxidative stress , occurred in the HC compared with the N group . These changes were reversed in the HC+S group . In summary , simvastatin preserves endothelial function in coronary epicardial vessels and arterioles in experimental HC ( in the absence of cholesterol lowering ) in association with an increase in coronary eNOS levels and a decrease in oxidative stress . These alterations may play a role in the reduction in cardiac events after treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors The aim of this study was to investigate the modulating effect of atorvastatin on serum paraoxonase 1 enzyme ( PON1 ) activity in type 2 diabetic Egyptian patients with or without nephropathy . The present study was carried out on the following groups : control group , which consisted of 30 healthy persons ; Group I , which consisted of 20 type 2 diabetic patients without nephropathy ; and Group II , which consisted of 20 type 2 diabetic patients with nephropathy . All the patients selected were under an antidiabetic regimen of insulin  , and patients receiving antihypertensive agents were excluded from the follow-up study to avoid drug interaction fallacies . Twenty-two patients ( 15 without nephropathy and seven with nephropathy ) received atorvastatin in individually adjusted oral dosage ( range 10 - 20 mg ) once per day for 12 weeks . All cases were subjected to thorough clinical examination and history taking and measurement of serum levels of PON1 activity , malondialdehyde ( MDA ) , glutathione reductase activity , fasting glucose , total cholesterol , triglycerides , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) , urea , and creatinine . Urine sample s were collected for determination of proteinuria . The obtained results showed that PON1 activity and HDL significantly decreased and fasting glucose significantly increased in Group I and Group II when compared to the control group , with significant difference in their levels between Group II and Group I. MDA , total cholesterol , and LDL levels significantly increased and glutathione reductase activity significantly decreased in Group I and Group II when compared to the control group . Urea , creatinine , and proteinuria levels showed significant increase in Group II when compared to the control group and Group I , with nonsignificant difference between control group and Group I. Atorvastatin therapy caused a significant increase in PON1 activity , and serum levels of MDA and glutathione reductase activity were significantly decreased and increased , respectively . Also , total cholesterol , triglyceride and LDL-cholesterol levels were significantly reduced with a significant increase in HDL-cholesterol levels . There was a significant modest reduction in serum urea and creatinine levels as well as in proteinuria level . Fasting glucose level was significantly reduced under the antidiabetic regimen of insulin through the follow-up period . PON1 activity showed a significant negative correlation with glucose and LDL , and a significant positive correlation with HDL in all the studied groups . It could be concluded that atorvastatin with its pleiotropic effects could provide optimal therapeutic intervention to control not only dyslipidemia , but also oxidative stress status with consequent improvement in the course of type 2 diabetes and diabetic nephropathy . More specifically , restoration of PON1 activity by atorvastatin opens a window to investigate other drugs that could provide a new adjuvant therapeutic line for better control of diabetes and diabetic nephropathy . Further research is also recommended to study the distribution of PON1 genetic polymorphism among the Egyptian population to explain the variability in its activity and its relationship with other factors that associate diabetes and its complications Tissue factor ( TF ) plays a pivotal role in thrombus formation . Statins and angiotensin converting enzyme inhibitors attenuate expression of TF by distinct mechanism . Therefore , we hypothesized that combined therapy with simvastatin and ramipril may have additive beneficial anti-atherogenic effects to lower TF activity when compared with either drug alone . This was a r and omized , double-blind , placebo-controlled cross-over trial with three treatment arms ( each 2 months ) and two washout periods ( each 2 months ) . Fifty patients with type 2 diabetes were given simvastatin 20 mg and placebo , simvastatin 20 mg and ramipril 10 mg , or ramipril 10 mg and placebo daily during each treatment period . Simvastatin and ramipril monotherapy tended to reduce TF activity ( 0.53 to 0.46 nM , P=0.056 ; 0.54 to 0.50 nM , P=0.167 , respectively ) while combined therapy had a significant effect ( 0.64 to 0.43 nM , P<0.001 ) . All three therapies significantly reduced prothrombin fragment 1 + 2 ( F1 + 2 ) levels from their respective baselines ( P=0.037 , P<0.001 , and P=0.057 , respectively ) . Combined therapy significantly reduced TF activity and F1 + 2 levels to a greater extent than either simvastatin or ramipril alone ( P=0.029 and P=0.040 by ANOVA , respectively ) . Percent changes in TF activity and percent changes in F1 + 2 levels were significantly correlated . All three therapies reduced CD40 lig and levels from their respective baselines ( P=0.098 , P<0.001 , and P=0.002 , respectively ) with no significant differences among these three therapies ( P=0.204 by ANOVA ) . Ramipril combined with simvastatin significantly reduces plasma TF activity and F1 + 2 levels to a greater extent than monotherapy with either drug in patients with type 2 diabetes BACKGROUND Experimental evidence suggests a lipid-independent effect of statins on endothelial function and nitric oxide ( NO ) availability in humans . We investigated whether improvement in NO availability in hypercholesterolemia can be achieved rapidly with statins before lipid-lowering therapy is complete . METHODS We studied 41 patients ( 52 + /- 11 years ) with low-density lipoprotein ( LDL ) cholesterol > or = 130 mg/dL ( 179 + /- 45 mg/dL ) r and omly assigned to treatment either with atorvastatin ( 20 mg/day ) or cerivastatin ( 0.4 mg/day ) .  Endothelium-dependent vasodilation of the forearm vasculature was measured by plethysmography and intra-arterial infusion of acetylcholine ( ACh ) after 3 days ( n = 18 ) and 14 days ( n = 39 ) of treatment . NO availability and oxidative stress were assessed by coinfusion of l-NMMA and vitamin C. RESULTS After 3 days of treatment , LDL-cholesterol decreased by 11.9 % with a further decrease to 29.6 % after 14 days ( P < .001 ) . Endothelium-dependent vasodilation improved by + 46.7 % after 3 days of statin therapy compared with before therapy ( ACh 48 microg/min : + 15.7 + /- 10.6 vs + 10.7 + /- 10.8 mL/min per 100 mL , P < .05 ) . No further improvement in endothelium-dependent vasodilation ( + 42.7 % compared with before therapy ) could be demonstrated after 14 days of treatment ( ACh 48 microg/min : + 17.7 + /- 10.3 vs + 12.4 + /- 9.3 mL/min per 100 mL before therapy , P < .001 ) . Coinfusion of ACh plus vitamin C was able to improve endothelium-dependent vasodilation before but not after 3 or 14 days of statin therapy either . The improvement in endothelium-dependent vasodilation after therapy was no longer observed when the NO-synthase inhibitor l-NMMA was coinfused together with ACh . CONCLUSIONS Short-term lipid-lowering therapy with statins is able to improve endothelial function and NO availability almost completely after 3 days in hypercholesterolemic patients probably by decreasing oxidative stress . This improvement seems to be more rapid than the accompanying decline in LDL-cholesterol and not related to these lipid changes . This finding can support the concept of lipid-independent effects of statins in humans BACKGROUND Statins are thought to have anti-atherogenic effects beyond cholesterol lowering . One such mechanism may involve reduction of oxidative stress . The aim of our study was to investigate and to compare the oxidative stress lowering capacity of atorvastatin with that of simvastatin in patients at high risk for cardiovascular disease using conventional markers and sensitive markers measured by highly specific techniques such as liquid chromatography t and em mass spectrometry . METHODS We included 30 statin-naive patients with diabetes mellitus , and /or obesity , and /or hypertension ( 12 male , 18 female , mean age 44.8±11.1 years ) , and r and omised them to receive either atorvastatin 10 mg or simvastatin 40 mg daily to obtain an equimolar cholesterol reduction . Blood and urine sample s were obtained at baseline and at 1 , 6 and 12 weeks . RESULTS Low-density lipoprotein ( LDL ) cholesterol and coenzyme Q10 decreased significantly in both groups . Simvastatin caused a faster initial LDL cholesterol lowering  than atorvastatin ( p=0.01 ) , but the overall effect after 12 weeks of atorvastatin and simvastatin was similar . Plasma myeloperoxidase and malondialdehyde did not change during the study period in the two groups . Urinary F2-isoprostanes decreased gradually and significantly in the atorvastatin group but not in the simvastatin group , but the between-group difference was not significant . Urinary 8-hydroxy-2-deoxyguanosine did not change in the two groups Objective High-density lipoprotein (HDL)-associated antioxidant paraoxonase ( PON ) may reduce low-density lipoprotein ( LDL ) oxidation and prevent atherosclerosis . The aim of this present study was to investigate the effect of the 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitor atorvastatin on hydrogen-peroxide-induced DNA damage by comet assay and the correlation between oxidative DNA damage and antioxidant PON activity . Methods Thirteen type-II/a hyperlipidemic patients were enrolled in the study . We examined the effect of 10 mg/day atorvastatin treatment on lipid levels and the degree of DNA damage in lymphocytes separated from hyperlipidemic patients , nitric oxide ( NO ) , thiobarbituric acid-reactive substances ( TBARS ) , PON levels and activity . Results After 6 months , atorvastatin treatment significantly decreased serum cholesterol and LDL-cholesterol levels . The triglyceride level did not change , and there was no significant change in the HDL cholesterol level . The visual score characteristic to the degree of DNA damage in comet assay was significantly decreased , as well as the TBARS level , while the level of NO was non-significantly increased . PON activity and the PON/HDL ratio were significantly increased after atorvastatin treatment . There was a negative correlation between DNA damage and PON activity , as well as between DNA damage and the PON/HDL ratio before and after atorvastatin treatment . Conclusion These findings show that atorvastatin treatment favorably affected the lipid profile , increasing the activity of HDL-associated PON and decreasing the cytotoxic effect of oxidative stress BACKGROUND We hypothesized that atorvastatin combined with amlodipine has additive beneficial vascular and metabolic effects that are superior to monotherapy in patients with hypertension . METHODS Forty-two patients were given atorvastatin 20mg/day and placebo , atorvastatin 20mg/day and amlodipine 10mg/day , or amlodipine 10mg/day and placebo during each 2-month treatment period of a r and omized , single-blind , placebo-controlled cross-over trial with two 2-month washout periods . RESULTS Atorvastatin combined with amlodipine or amlodipine alone significantly reduced blood pressure to a greater extent than atorvastatin alone ( all P < 0.001 by ANOVA ) . Atorvastatin combined with amlodipine significantly reduced plasma malondialdehyde and improved flow-mediated dilation to a greater extent than atorvastatin or amlodipine alone ( all P < 0.001 by ANOVA ) . Atorvastatin therapy significantly increased insulin levels ( P = 0.004 ) and decreased plasma adiponectin levels ( P = 0.016 ) and insulin sensitivity ( determined by QUICKI ; P = 0.026 ) relative to baseline measurements . Amlodipine therapy significantly decreased insulin levels ( P = 0.001 ) and increased adiponectin levels ( P < 0.001 ) and insulin sensitivity ( P = 0.003 ) relative to baseline measurements . Atorvastatin combined with amlodipine therapy significantly increased adiponectin levels ( P < 0.001 ) and insulin sensitivity ( P = 0.034 ) relative to baseline measurements . Effects of all three therapeutic arms on adiponectin levels and insulin sensitivity were statistically significant ( P < 0.001 by ANOVA ) . CONCLUSIONS Atorvastatin combined with amlodipine therapy improves endothelial function and increases adiponectin levels and insulin sensitivity to a greater extent than monotherapy with either drug in hypertensive patients Abstract Background . In vitro and animal studies indicate that statins increase heme oxygenase-1 gene ( HMOX1 ) expression , which then , presumably , increases plasma bilirubin concentration . However , clinical confirmation that statins concomitantly increase HMOX1 expression and plasma bilirubin concentration is lacking . We hypothesized that in patients with stable angina  atorvastatin therapy ( 20 mg/day for 10 weeks ) concomitantly increases total bilirubin concentration and HMOX1 expression , as assessed non-invasively by plasma analysis . Methods . In 44 patients with stable angina plasma concentrations of total bilirubin , HMOX1 mRNA and HMOX1 protein were measured before and after the statin treatment , as well as plasma concentrations of oxidized low-density lipoprotein ( OxLDL ) , malondialdehyde ( MDA ) , monocyte chemoattractant protein ( MCP-1 ) and C-reactive protein ( CRP ) . Results . Atorvastatin treatment increased total bilirubin concentration ( median 6.95 μmol/L vs. 8.55 , + 23.02 % ; p < 0.001 ) , but did not change plasma HMOX1 mRNA and HMOX1 protein concentrations . Plasma concentrations of OxLDL ( − 31.85 % , p < 0.001 ) , MCP-1 ( − 16.20 % , p = 0.020 ) and CRP ( − 7.32 % , p = 0.010 ) were decreased but MDA was not decreased ( 15.32 % , p = 0.107 ) . Within subjects , increment of plasma bilirubin concentration did not correlate with the changes in HMOX1 mRNA and protein concentrations , but correlated with low-density lipoprotein cholesterol decrement ( r = − 0.374 , p = 0.012 ) . Bilirubin increment did not correlate with the changes in oxidative and inflammatory markers . Conclusion . Our prospect i ve observational trial finally confirms that atorvastatin ( 20 mg/day for 10 weeks ) increases plasma total bilirubin concentration . However , it seems that this effect is HMOX1-independent Abstract Background and objective : Hyperglycaemia leads to increased oxidative stress result ing in endothelial dysfunction . ACE inhibitors , antioxidants and HMG-CoA reductase inhibitors ( statins ) have been shown to improve endothelial function . The aim of this study was to compare the effects of NCB-02 ( a st and ardized preparation of curcuminoids ) , atorvastatin and placebo on endothelial function and its biomarkers in patients with type 2 diabetes mellitus . Methods : A total of 72 patients with type 2 diabetes were r and omized to receive NCB-02 ( two capsules containing curcumin 150 mg twice daily ) , atorvastatin 10 mg once daily or placebo for 8 weeks . Endothelial function assessment was performed at baseline and post-treatment using digital volume plethysmography ( salbutamol [ albuterol ] challenge test ) to measure change in reflective index , an indicator of arterial vascular tone . Blood sample s were similarly collected at baseline and post-treatment for estimations of malondialdehyde , endothelin-1 ( ET-1 ) , interleukin-6 ( IL-6 ) and tumour necrosis factor-α ( TNFα ) . Pre- and posttreatment safety assessment s were also conducted . ANOVA and paired t-test evaluations were used for comparison . Results : A total of 67 patients completed the study . At baseline , there was no significant difference in the various parameters tested . In all three groups , the change in reflective index at baseline was < 6 % as assessed by the salbutamol challenge test , indicating the presence of endothelial dysfunction . Compared with baseline , there was a significant improvement in endothelial function after treatment with atorvastatin ( mean ± SD : −3.63 ± 3.17 % vs −8.95 ± 6.80 % , respectively ) and NCB-02 ( −2.69 ± 3.02 % vs −8.19 ± 5.73 % , respectively ) . Similarly , patients receiving atorvastatin or NCB-02 showed significant reductions in the levels of malondialdehyde , ET-1 , IL-6 and TNFα . No significant improvements were obtained in patients administered placebo . Conclusion : NCB-02 had a favourable effect , comparable to that of atorvastatin , on endothelial dysfunction in association with reductions in inflammatory cytokines and markers of oxidative stress . Further studies are needed to evaluate the potential long-term effects of NCB-02 and its combination with other herbal antioxidants 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 OBJECTIVE To investigate the impact of Vitamin E on lipids and peroxidation during statin treatment . RESEARCH DESIGN AND METHODS T1DM patients with high cholesterol received  Atorvastatin 20 mg with either placebo ( group AP , n = 11 ) or d-alpha-tocopherol 750 IU ( group AE , n = 11 ) daily . They were monitored for blood biochemistry , low-density lipoprotein ( LDL ) subfractions and lipid peroxidation at inclusion and after 3 and 6 months . RESULTS Serum cholesterol and triglycerides decreased to the same extent ( 29 and 21 % respectively ) in both groups . Serum tocopherol decreased by 18 % in AP and increased by 50 % in AE ( P < 0.0001 , between-group comparison by repeated measures ANOVA ) but relative to lipids it increased by 15 % in AP and by 100 % in AE . Copper-induced production of thiobarbituric reactive substances in the LDL + VLDL fraction increased by 18 % in AP and did not change in AE ( P = 0.02 ) . The lagtime for the production of fluorescent products was prolonged by 13 min only in group AE ( P = 0.028 ) . Plasma malondialdehyde decreased by 35 % in both groups ( P = 0.002 ) but not when adjusted for lipids . CONCLUSIONS In T1DM Vitamin E supplements do not affect the lowering of lipids and plasma malondialdehyde achieved by Atorvastatin . They reverse the increase of in vitro peroxidation caused by Atorvastatin but do not achieve the decreases observed in patients not receiving lipid-lowering drugs . These results indicate that the antioxidant effect of Vitamin E is attenuated when given in conjunction with this statin The effects of pravastatin on plasma lipid levels , in vitro oxidizability of the non-HDL fraction , metabolic control , urinary albumin excretion , and four serum enzymes ( SGPT , SGOT , GT and CPK ) were studied in 20 insulin-dependent diabetic patients ( IDDM ) with incipient nephropathy . The patients were divided into two groups and the study was carried out by a crossover design . After 12 weeks pravastatin treatment ( 20 mg daily ) , plasma cholesterol , LDL-cholesterol and apolipoprotein B ( Apo B ) decreased by 22 , 19 and 15 % , respectively . The thiobarbituric acid reactive substances ( TBARS ) formation and the oxidation lagtime of the non-HDL fraction during the in vitro incubation with copper were not changed before and after treatment . The HbA1c and blood glucose levels , urinary albumin excretion , SGOT , SGPT and GT were not influenced by pravastatin treatment . CPK activity was elevated after 12 weeks of pravastatin treatment , and this elevation persisted even after the 12 weeks placebo period . So , pravastatin could be used as an effective drug for IDDM patients with incipient nephropathy , but close monitoring of the CPK activity is recommended Systemic sclerosis ( SSc ) has the highest case-specific mortality among the rheumatic diseases . Vascular dysfunction and structural wall abnormalities are among the earliest and fundamental alterations in SSc . Statins have a number of immunomodulating effects on vascular wall cells , which may modify the progression of vascular injury . The aim of this study was to evaluate the potential efficacy of statin therapy in ameliorating endothelial dysfunction ( ED ) in SSc by investigating the effect of statins on some markers that reflect endothelial activation in SSc . Forty patients with SSc were r and omized into two groups to receive 6 months ' treatment with atorvastatin ( n = 20 ; dose , 40 mg/day ) or placebo ( n = 20 ) as an adjuvant to existing therapy . Markers of ED including ET-1 , plasma nitrate levels , and thrombomodulin ( TM ) were evaluated by the enzyme-linked immunosorbent assay ( ELISA ) technique . Fibrinogen , high-sensitivity C-reactive protein ( hsCRP ) , ESR , lipid peroxide ( LP ) , and malonylaldehyde ( MDA ) levels were also assessed . Brachial flow-mediated vasodilatation was assessed by ultrasonography . Patients were studied at base line and after 6 months of statin therapy . After 6 months of therapy , ET-1 , ICAM-1 , sE-selectin , vWF , fibrinogen , ESR , hsCRP as well as LP and MDA levels declined and NO increased significantly in the statin-treated SSc group when compared to the placebo-treated group . Endothelium-dependent vasodilatation ( EDV ) improved significantly in the atorvastatin-treated group . The findings of this study demonstrated statin-mediated improvements in the endothelial function of SSc patients as well as immunomodulating effects . Statins may thus prove to be an invaluable addition to the therapy of the vasculopathy of SSc Objective . To investigate the effect of atorvastatin therapy on inflammation , disease activity , endothelial dysfunction , and arterial stiffness in patients with rheumatoid arthritis ( RA ) . Methods . This study included 30 patients with early RA , r and omly divided into 2 groups . Group 1 ( n = 15 ) received methotrexate ( MTX ; 0.2 mg/kg/week ; mean ( 15.5 ± SD 1.3 ) plus prednisone ( 10 mg/day ) . Group 2 ( n = 15 ) received MTX and prednisone with the same previous doses plus atorvastatin therapy ( 40 mg/day ) . Ten healthy individuals of similar age and sex served as controls  . Disease activity , lipid profile , serum malondialdehyde ( MDA ) , tumor necrosis factor-α ( TNF-α ) , resistin , adiponectin , and brachial artery flow-mediated dilation ( FMD ) were measured before and after 6 months of treatment . Results . Atorvastatin combined with MTX therapy significantly reduced serum total cholesterol , low-density lipoprotein cholesterol , and triglycerides , and increased high-density lipoprotein cholesterol ( p < 0.001 ) . Disease activity variables , serum MDA , TNF-α , resistin , adiponectin , and FMD were significantly improved by the drug combinations ( p < 0.001 ) . Conclusion . Atorvastatin therapy in patients with RA  reduced disease activity and conventional and novel vascular risk factors that promote the atheromatous lesion . Therapy was also associated with concomitant improvement in endothelial function 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 Simvastatin , a 3-hydroxy 3-methylglutaryl co-enzyme A ( HMG-CoA ) reductase inhibitor , is used widely for treatment of hypercholesterolemia .  Simvastatin may be a suitable treatment for dyslipidemia in hemodialysis ( HD ) patients . However , investigation of the side-effects and safety of long-term administration of simvastatin to HD patients has been limited . In this study , we investigated the effects and safety of simvastatin and its effects on lipoprotein metabolism in hypercholesterolemic patients on HD . METHODS Simvastatin was administered at a dosage of 5 mg/day for 24 weeks to 38 HD patients with high serum total cholesterol ( TC ) levels ( 200 mg/dl ) or low high-density lipoprotein cholesterol ( HDL-C ) levels ( 35 mg/dl ) . Every four weeks , serum lipids , apolipoprotein , lipoprotein ( a ) [ Lp(a ) ] and malondialdehyde ( MDA ) levels were measured . In addition , lipid levels were determined in each lipoprotein fraction separated by ultracentrifugation . RESULTS After 24 weeks of simvastatin administration , TC significantly decreased by 25.7 % , and low-density lipoprotein cholesterol ( LDL-C ) was significantly decreased by 33.6 % . Triglyceride ( TG ) and HDL-C showed no significant changes . Apolipoprotein ( apo ) B significantly decreased by 24.5 % and apo E by 30.0 % . No significant changes were observed in the other apolipoproteins . MDA was also significantly decreased , whereas Lp(a ) was not significantly altered . In the lipoprotein fractions , very LDL cholesterol ( VLDL-C ) , intermediate-density lipoprotein cholesterol ( IDL-C ) , LDL1 cholesterol ( LDL1-C ) , and LDL2 cholesterol ( LDL2-C ) showed significant decreases . No particular side-effects were observed during the 12 months of simvastatin administration . CONCLUSIONS These results suggest that simvastatin appears to be safe and effective in HD patients with hypercholesterolemia A 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor is recommended in hemodialysis ( HD ) patients with hypercholesterolemia to improve their lipid profiles . We evaluated effects of simvastatin on markers for inflammation , oxidative stress , and coagulation in HD patients . Sixty-two maintenance HD patients with serum cholesterol levels of 200 mg/dL or greater were r and omly assigned to the treatment group ( n = 31 ; 8 men , 23 women ; age , 63 + /- 11 years ) and administered simvastatin , 20 mg/d , for 8 weeks or to the  control group ( n = 31 ; 10 men , 21 women ; age , 60 + /- 12 years ) . We measured cholesterol , albumin , high-sensitivity C-reactive protein ( hs-CRP ) , malondialdehyde ( MDA ; an index of lipid peroxidation ) , and D-dimer ( a marker of intravascular coagulation ) in blood at baseline and again at 8 weeks . Fifty-eight of 62 patients completed the study . In the control group , total cholesterol , serum albumin , hs-CRP , MDA , and D-dimer levels did not change . In the treatment group , simvastatin administration for 8 weeks significantly reduced total cholesterol levels from 232 + /- 25 to 165 + /- 39 mg/dL ( P < 0.001 ) and hs-CRP levels from a median of 0.23 mg/dL ( range , 0.05 to 1.63 mg/dL ) to 0.12 mg/dL ( range , < 0.006 to 1.45 mg/dL ; P < 0.01 ) , whereas it increased serum albumin levels from 3.4 + /- 0.3 to 3.6 + /- 0.4 g/dL ( P < 0.001 ) . Administration of simvastatin did not affect MDA and D-dimer levels . These results suggest that in addition to the lipid-lowering effect , simvastatin had an antiinflammatory effect in HD patients . Considering that atherosclerosis is inflammation of the vascular wall , simvastatin may have a beneficial effect on cardiovascular disease , in part because it alleviates inflammation Mechanisms underlying biological effects of statin and angiotensin-converting enzyme inhibitor therapies differ . Thus , we studied vascular responses to combination therapy in hypercholesterolemic patients . A r and omized , double-blind , placebo-controlled , crossover trial was conducted with 50 hypercholesterolemic patients with simvastatin and either placebo or ramipril ( study I ) and in 45 hypercholesterolemic diabetic patients with simvastatin or ramipril with placebo or simvastatin combined with ramipril ( study II ) for 2 months with 2 months washout . In study I simvastatin combined with ramipril significantly reduced blood pressure after 2 months . Simvastatin alone or combined with ramipril significantly changed lipoproteins , improved percent flow-mediated dilator response to hyperemia by 30±5 % and 53±6 % , respectively ( P < 0.001 ) , and reduced plasma levels of malondialdehyde by 4±7 % ( P = 0.026 ) and 25±4 % ( P < 0.001 ) , respectively . Monocyte chemoattractant protein-1 levels decreased by 3±3 % and 12±2 % , respectively ( P = 0.049 and P < 0.001 , respectively ) , C-reactive protein levels changed by 0 % and 18 % , respectively ( P = 0.036 and P < 0.001 , respectively ) , and plasminogen activator inhibitor-1 antigen levels changed by −7±7 % and 17±5 % , respectively ( P = 0.828 and P < 0.001 , respectively ) . In study II ramipril alone did not significantly change lipoproteins and C-reactive protein levels , however , simvastatin combined with ramipril significantly changed lipoproteins and C-reactive protein levels more than ramipril alone ( P < 0.001 and P = 0.048 by ANOVA , respectively ) . Ramipril alone or simvastatin combined with ramipril significantly improved the percent flow-mediated dilator response to hyperemia ( both P < 0.001 ) , however , simvastatin combined with ramipril showed significantly more improvement than ramipril alone ( P < 0.001 by ANOVA ) . Simvastatin combined with ramipril  significantly improved endothelium-dependent vasodilation and fibrinolysis potential and reduced plasma levels of oxidant stress and inflammation markers in hypercholesterolemic patients Statins and fibrates influence endothelial activity and consequently atherogenesis but the mechanisms are not well understood . Twenty Type 2 diabetic patients with dyslipidemia were treated 3 months with simvastatin ( 20 mg daily ) and then 3 months with fenofibrate ( 200 mg daily ) with 2 months of wash-out between the two treatments . Laboratory parameters of oxidative stress , fibrinolysis and endothelial function were evaluated before and at the end of each treatment period . The significant decrease in serum total and LDL-cholesterol concentrations ( P<0.0001 ) caused by simvastatin was associated with an increase in serum N-acetyl-beta-glucosaminidase activity ( P<0.001 ) , ascorbic acid ( P<0.001 ) , plasminogen activator inhibitor ( PAI-1 ) ( P<0.01 ) , vonWillebr and factor ( P<0.05 ) , E-selectin ( P<0.01 ) and vascular endothelial growth factor ( P<0.05 ) concentrations and with a decrease in plasma glutathione ( P<0.01 ) levels . Fenofibrate caused a significant decrease in serum triglyceride concentration ( P<0.0001 ) associated with a decrease in plasma malondialdehyde ( P<0.001 ) and an increase in plasma PAI-1 ( P<0.05 ) and P-selectin ( P<0.05 ) concentrations . We conclude that simvastatin and fenofibrate interact , by different mechanisms , with oxidative stress , a key factor in the modification of fibrinolysis and endothelial function in Type 2 diabetes OBJECTIVES Statins may exhibit anti-inflammatory and antioxidant effects . Whether different statins at equivalent doses or the combination of low-dose statin with ezetimibe have comparable anti-inflammatory and antioxidant effects is unknown . The aim of this study was to compare the effects of simvastatin , simvastatin/ezetimibe or rosuvastatin at equivalent low-density lipoprotein cholesterol lowering doses on inflammation and oxidative stress indices in subjects with hypercholesterolemia . METHODS This was a pre-specified analysis of a prospect i ve , r and omized , open-label , blinded endpoint ( PROBE ) study . We enrolled one hundred and fifty three ( n = 153 ) hypercholesterolemic subjects who were r and omized to receive simvastatin 40 mg or simvastatin/ezetimibe 10/10 mg or rosuvastatin 10 mg daily .  Plasma 8-Epi prostagl and in F2 alpha ( 8-epiPGF2a ) , oxidized LDL ( oxLDL ) and lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) activity and mass were measured at baseline and following 12 weeks of treatment . RESULTS A significant reduction in plasma 8-isoprostane and oxLDL levels was observed in all treatment groups [ by 10 % , 8 % and 6 % ( p < 0.05 compared with baseline ) and 41 % , 40 % and 39 % ( p < 0.001 compared with baseline ) in simvastatin , simvastatin/ezetimibe and rosuvastatin groups , respectively ] . In all treatment groups a significant reduction in total plasma Lp-PLA2 activity and mass was observed ( by 36 % , 31 % and 38 % and 36 % , 32 % and 32 % for simvastatin , simvastatin/ezetimibe and rosuvastatin , respectively , p < 0.001 compared with baseline ) . No intergroup differences were observed . CONCLUSIONS Simvastatin 40 mg , simvastatin/ezetimibe 10/10 mg and rosuvastatin 10 mg significantly reduced 8-epiPGF2a , oxLDL and Lp-PLA2 activity and mass to a similar extent Background Atorvastatin , an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase , which is used for lipid-lowering therapy , is an effective statin modulating process involved in atherosclerosis . Paraoxonase ( PON ) associated with high-density lipoprotein ( HDL ) has been postulated to have a role in protecting low-density lipoprotein ( LDL ) against oxidative modification . Oxidation of serum LDL is an important early step in the development of atherosclerosis and auto-antibodies against oxidized LDL ( AuAb-oxLDL ) reflect in-vivo LDL oxidation . Design and methods To examine the effect of atorvastatin ( 10 mg/day ) therapy on PON activity in serum and HDL , the study group included 40 patients with dyslipidemia ( 19 women and 21 men ) , 25 of whom had hypercholesterolemia and of 15 of whom had mixed-type hyperlipidemia . By taking blood sample s from the patients , levels of serum lipids , lipid peroxidation product as malondialdehyde ( MDA ) , total antioxidant status ( TAS ) and AuAb-oxLDL and the activities of PON in serum and isolated HDL were determined . Results The mean levels of total cholesterol , triglyceride , LDL-cholesterol , MDA and AuAb-oxLDL were decreased while HDL-cholesterol and TAS were increased significantly after lipid-lowering therapy in patients with dyslipidemia . On the other h and , PON activities in serum and HDL were increased significantly . The percentage increase in serum PON activity was associated significantly with the percentage decrease in serum AuAb-oxLDL ( r=−0.32 , P=0.047 ) and that of HDL PON activity was associated with the percentage increase in HDL-cholesterol level after atorvastatin therapy ( r=0.52 , P=0.001 ) . The therapy was more effective in increasing PON activity in patients with HDL levels above 35 mg/dl . Conclusion It was concluded that atorvastatin therapy in dyslipidemic patients decreases the level of oxidative stress and increases PON activity , especially in patients with HDL levels above 35 mg/dl Hyperlipidemia is commonly observed in patients with type 2 diabetes and is an independent risk factor for cardiovascular disease . The authors tested the effect of atorvastatin ( 10 mg/d ) on 110 hyperlipidemic type 2 diabetes patients with low-density lipoprotein cholesterol ( LDL-C ) levels exceeding 130 mg/d . The primary efficacy end point was the percentage change in LDL-C and high-density lipoprotein cholesterol ( HDL-C ) , and secondary efficacy included the percentage change in apolipoproteins at weeks 6 , 12 , and 24 . The tertiary goal was percentage change in free radical scavenger enzymes and oxidative stress . LDL-C was reduced by 25 % , 39.3 % , and 49.2 % . A similar trend was observed in total cholesterol , triglyceride , non-HDL-C , and apolipoprotein ( apo ) B-100 . HDL-C was raised by 3.2 % , 6 % , and 8.2 % . A similar trend was seen in apo A-1 . Copper zinc-superoxide dismutase and glutathione were raised significantly ( P < .001 ) ; however , changes in glutathione-S-transferase and glutathione peroxidase activities were nonsignificant . Malondialdehyde was decreased significantly ( P < .001 ) . Atorvastatin improves the lipoprotein profile and oxidative status in patients with type 2 diabetes 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 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 Because the mechanisms of the biological effects of statin and angiotensin converting enzyme inhibitor therapies differ , we studied the vascular responses to these therapies in hypercholesterolemic patients with coronary artery disease . We administered simvastatin 20 mg and placebo or ramipril 10 mg daily during 2 months with washout 2 months to 32 hypercholesterolemic patients with coronary artery disease . This study was r and omized , double-blind , placebo-controlled , crossover in design . Simvastatin alone or combined with ramipril significantly changed lipoproteins , and improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements by 33 + /- 6 % and by 50 + /- 14 % , respectively ( both P < 0.001 ) and reduced plasma levels of nitrate relative to baseline measurements ( P=0.413 and 0.037 , respectively ) , the plasma MDA levels relative to baseline measurements by 8 + /- 8 % and by 18 + /- 9 % ( P=0.039 and P < 0.001 , respectively ) and MCP-1 relative to baseline measurements by 7 + /- 4 % and by 13 + /- 3 % , respectively ( P=0.019 and P < 0.001 , respectively ) , and CRP from 0.22 to 0.14 mg/dl and from 0.22 to 0.15 mg/dl , respectively ( P=0.124 and 0.002 , respectively ) , and PAI-1 antigen relative to baseline measurements ( P=0.690 and 0.018 , respectively ) . However , simvastatin combined with ramipril changed to greater but statistically insignificant extent the percent flow-mediated dilator response to hyperemia and plasma levels of nitrate , MDA , MCP-1 , and PAI-1 antigen than simvastatin alone . Simvastatin alone or combined with ramipril showed significant beneficial effects on endothelial function in hypercholesterolemic patients with coronary artery disease . However , simvastatin combined with ramipril did not significantly change , compared with simvastatin alone
target: Conclusions : This systematic review and meta- analysis showed that statin treatment significantly reduces systemic MDA concentrations .
background: 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 .