title: Effects of atorvastatin on serum lipids, serum inflammation and plaque morphology in patients with stable atherosclerotic plaques Effect of rosuvastatin on C-reactive protein and renal function in patients with chronic kidney disease. Very low-dose fluvastatin-valsartan combination decreases parameters of inflammation and oxidative stress in patients with type 1 diabetes mellitus. A multicenter, randomized, double-blind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia. Effects of atorvastatin on biomarkers of inflammation in chronic kidney disease. Effects of atorvastatin on reactive hyperemia and inflammatory process in patients with congestive heart failure. High-Dose Atorvastatin Enhances the Decline in Inflammatory Markers in Patients With Acute Coronary Syndromes in the MIRACL Study Hypotensive effect of atorvastatin is not related to changes in inflammation and oxidative stress. Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients. The effect of early treatment by cerivastatin on the serum level of C-reactive protein, interleukin-6, and interleukin-8 in patients with unstable angina and non-Q-wave myocadial infarction Effects of tirofiban and statins on high-sensitivity C-reactive protein, interleukin-6, and soluble CD40 ligand following percutaneous coronary interventions in patients with stable coronary artery disease. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. The Effect of HMG-CoA Reductase Inhibitor on Insulin Resistance in Patients Undergoing Peritoneal Dialysis Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke Effect of rosuvastatin on plasma levels of asymmetric dimethylarginine in patients with hypercholesterolemia. Effects of rosuvastatin on myeloperoxidase levels in patients with chronic heart failure: a randomized placebo-controlled study. Atorvastatin increases 25-hydroxy vitamin D concentrations in patients with polycystic ovary syndrome. Statin therapy worsens insulin sensitivity in women with polycystic ovary syndrome (PCOS): a prospective, randomized, double-blind, placebo-controlled study. Atorvastatin Therapy Modulates Telomerase Activity in Patients Free of Atherosclerotic Cardiovascular Diseases Long-term statin therapy in patients with systolic heart failure and normal cholesterol: effects on elevated serum markers of collagen turnover, inflammation, and B-type natriuretic peptide. The influence of low dose atorvastatin on inflammatory marker levels in patients with acute coronary syndrome and its potential clinical value. The impact of early administration of low-dose atorvastatin treatment on inflammatory process, in patients with unstable angina and low cholesterol level. Effects of lipid-lowering therapy with rosuvastatin on kidney function and oxidative stress in patients with diabetic nephropathy. Synergistic effect of amlodipine and atorvastatin on blood pressure, left ventricular remodeling, and C-reactive protein in hypertensive patients with primary hypercholesterolemia Identical LDL-cholesterol lowering but non-identical effects on NF-κB activity: High dose simvastatin vs combination therapy with ezetimibe. The beneficial effect of high loading dose of rosuvastatin before percutaneous coronary intervention in patients with acute coronary syndrome. Effect of atorvastatin and fish oil on plasma high-sensitivity C-reactive protein concentrations in individuals with visceral obesity. Improved Preservation of Residual Beta Cell Function by Atorvastatin in Patients with Recent Onset Type 1 Diabetes and High CRP Levels (DIATOR Trial) Concomitant reduction of low-density lipoprotein-cholesterol and biomarkers of inflammation with low-dose simvastatin therapy in patients with type 1 diabetes. Fluvastatin prevents development of arterial stiffness in haemodialysis patients with type 2 diabetes mellitus. Rapid immunomodulation by rosuvastatin in patients with acute coronary syndrome. Effects of combined administration of low dose atorvastatin and vitamin E on inflammatory markers and endothelial function in patients with heart failure. Anti-inflammatory effect of atorvastatin (80 mg) in unstable angina pectoris and non-Q-wave acute myocardial infarction. Atorvastatin affects C-reactive protein levels in patients with coronary artery disease Vascular effects of diet and statin in hypercholesterolemic patients. Strong decrease of high sensitivity C-reactive protein with high-dose atorvastatin in patients with type 2 diabetes mellitus. Effects of Atorvastatin on Lp(a) and Lipoprotein Profiles in Hemodialysis Patients Reduction in serum levels of adhesion molecules, interleukin-6 and C-reactive protein following short-term low-dose atorvastatin treatment in patients with non-familial hypercholesterolemia. Effects of simvastatin on C-reactive protein in mixed hyperlipidemic and hypertriglyceridemic patients. Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial. Effect of NCB-02, Atorvastatin and Placebo on Endothelial Function, Oxidative Stress and Inflammatory Markers in Patients with Type 2 Diabetes Mellitus Effects of atorvastatin on vascular function, inflammation, and androgens in women with polycystic ovary syndrome: a double-blind, randomized, placebo-controlled trial. Atorvastatin lowers C-reactive protein and improves endothelium-dependent vasodilation in type 2 diabetes mellitus. The effect of different doses of fluvastatin on inflammatory markers in the early phase of acute coronary syndrome. Efficacy and safety of the coadministration of ezetimibe/simvastatin with fenofibrate in patients with mixed hyperlipidemia. Changes in serum interleukin-6 and high-sensitivity C-reactive protein levels in patients with acute coronary syndrome and their responses to simvastatin Does atorvastatin influence serum C-reactive protein levels in patients on long-term hemodialysis? Effects of atorvastatin on low-density lipoprotein cholesterol phenotype and C-reactive protein levels in patients undergoing long-term dialysis. Anti-inflammatory interventions in end-stage kidney disease: a randomized, double-blinded, controlled and crossover clinical trial on the use of pravastatin in continuous ambulatory peritoneal dialysis. Statin therapy increases carotid plaque echogenicity in hypercholesterolemic patients. Ezetimibe and simvastatin combination inhibits and reverses the pro-inflammatory and pro-atherogenic effects of cream in obese patients. Effect of a Single High Loading Dose of Rosuvastatin on Percutaneous Coronary Intervention for Acute Coronary Syndromes Simvastatin treatment reduces heat shock protein 60, 65, and 70 antibody titers in dyslipidemic patients: A randomized, double-blind, placebo-controlled, cross-over trial. Efficacy and safety of ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia: a randomized, double-blind, placebo-controlled trial. Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure. Effect of statin and fibrate treatment on inflammation in type 2 diabetes. A randomized, cross-over study. Effects of simvastatin on circulating autoantibodies to oxidized LDL antigens: relation with immune stimulation markers Short-term effect of simvastatin treatment on inflammatory parameters in peritoneal dialysis patients The effects of atorvastatin on endothelial function in diabetic patients and subjects at risk for type 2 diabetes. Effects of simvastatin on high-sensitivity C-reactive protein and serum albumin in hemodialysis patients. Lipid-lowering treatment and inflammatory mediators in diabetes and chronic kidney disease. Prevention of radiocontrast medium-induced nephropathy using short-term high-dose simvastatin in patients with renal insufficiency undergoing coronary angiography (PROMISS) trial--a randomized controlled study. Efficacy and Safety of Loading-Dose Rosuvastatin Therapy in Elderly Patients with Acute Coronary Syndromes Undergoing Elective Percutaneous Coronary Intervention Effects of atorvastatin on inflammatory and fibrinolytic parameters in patients with chronic kidney disease. Effects of 4 weeks of atorvastatin administration on the antiinflammatory cytokine interleukin-10 in patients with unstable angina. Rosuvastatin in hemodialysis: short-term effects on lipids and C-reactive protein. Microvascular endothelial function in subjects with Type 2 diabetes and the effect of lipid-lowering therapy. Rosuvastatin may reduce the incidence of cardiovascular events in patients with acute coronary syndromes receiving percutaneous coronary intervention by suppressing miR-155/SHIP-1 signaling pathway. Statin therapy improves brachial artery vasodilator function in patients with Type 1 diabetes and microalbuminuria Atorvastatin has an important acute anti-inflammatory effect in patients with acute coronary syndrome: results of a randomized, double-blind, placebo-controlled study. Effects of lipid-lowering therapy with rosuvastatin on atherosclerotic burden in patients with chronic kidney disease. Effects of statin therapy on the production of monocyte pro-inflammatory cytokines, cardiac function, and long-term prognosis in chronic heart failure patients with dyslipidemia. How does short-term low-dose simvastatin influence serum prohepcidin levels in patients with end-stage renal disease? A pilot study. Can a High Reloading Dose of Atorvastatin Prior to Percutaneous Coronary Intervention Reduce Periprocedural Myocardial Infarction?
abstract: Statin treatment in patients with coronary heart disease is associated with a reduced incidence of short-term adverse events and endpoint cardiac events . However , the effects of statin treatment on atherosclerotic plaques , particularly stable plaques , remain poorly defined . In total , 228 consecutive patients with stable atherosclerotic plaques who had undergone coronary arteriography ( CAG ) and intravascular ultrasound ( IVUS ) were r and omly assigned to receive placebo ( placebo group , n=54 ) or atorvastatin ( ATOR ) at a single daily dose of 10 mg ( ATOR 10 mg group , n=47 ) , 20 mg ( ATOR 20 mg group , n=45 ) , 40 mg ( ATOR 40 mg group , n=43 ) or 80 mg ( ATOR 80 mg group , n=39 ) . Endpoints , including serum lipids , serum inflammation , plaque volume and percentage of plaque necrosis were assessed after 3–6 months . At baseline , mean low-density lipoprotein ( LDL ) , high-density lipoprotein ( HDL ) and high-sensitivity C-reactive protein ( hs-CRP ) levels , as well as plaque volumes and percentages of plaque necrosis , were similar between all groups . At 6 months of follow-up , the LDL levels in the ATOR groups were below those at their respective baselines ( P<0.01 ) . HDL levels in the ATOR 80 mg group following treatment were significantly higher compared with baseline ( P=0.001 ) . Additionally , they were significantly higher compared with those in the placebo , ATOR 10 , 20 and 40 mg groups ( P<0.01 , P=0.001 , P=0.048 , P=0.047 , respectively ) . Hs-CRP levels in the placebo group following treatment were higher compared with baseline levels ( 6.87±2.62 vs. 5.07±1.80 , P<0.01 ) , but hs-CRP levels in the ATOR 80 mg group following treatment were lower compared with baseline ( 3.59±1.07 vs. 6.10±2.12 , P<0.01 ) . According to the virtual histology ( VH ) of IVUS , the percentages of plaque necrosis following treatment in the placebo and ATOR 10 mg groups rose above baseline levels ( 15.51±12.56 vs. 7.69±1.31 % , 13.54±11.76 vs. 7.83±1.43 % , P<0.01 ) and conformed to the diagnostic criteria for unstable plaques ( 15.51±12.56 , 13.54±11.76 % ) . By contrast , in the ATOR 20 , 40 and 80 mg groups , percentages of plaque necrosis remained stable following treatment compared with baseline ( P=0.069 , 0.846 and 0.643 , respectively ) . Plaque volumes following treatment in the placebo , ATOR 10 and 20 mg groups were similar to baseline levels . However , in the ATOR 40 and 80 mg groups , plaque volumes decreased following treatment compared with baseline plaque volumes ( 30.69±8.12 vs. 37.09±12.01 mm3 , 24.99±1.01 vs. 36.47±14.68 mm3 , P=0.019 , P<0.01 , respectively ) . ATOR ( 20 mg/day ) is able to lower LDL to st and ard levels while ATOR 40 mg/day was superior to 20 mg/day and had similar effects to 80 mg/day . Only ATOR 80 mg/day was able to increase HDL levels . Hs-CRP in patients without ATOR was higher and ATOR 80 mg/day decreased levels . ATOR ≥20 mg/day is able to stabilize plaques and ATOR 80 mg/day was superior to 20 and 40 mg/day . Thus , ATOR 40–80 mg/day reduces the volume of plaques The purpose of this 20-week , open-label , r and omized clinical trial was to evaluate the effect of rosuvastatin on fasting serum lipids and lipoproteins , high-sensitivity C-reactive protein ( hs-CRP ) , and the glomerular filtration rate ( GFR ) in 91 patients with chronic kidney disease . Patients were r and omized to rosuvastatin 10 mg/day ( n = 48 ) or to  no lipid-lowering treatment ( n = 43 ) for 20 weeks . In contrast to patients not receiving rosuvastatin , patients receiving rosuvastatin tended to derive more favorable improvements from baseline values in low-density lipoprotein cholesterol ( -43 % , p < 0.001 , vs 7 % , p = NS ; p < 0.001 for change with rosuvastatin treatment vs change with no antilipemic treatment ) , hs-CRP ( -47 % , p < 0.001 , vs 7 % , p = NS ; p < 0.001 for change with rosuvastatin treatment vs change with no antilipemic treatment ) , and GFR ( 11 % , p < 0.05 , vs 4 % , p = NS ; p = NS for change with rosuvastatin treatment vs change with no antilipemic treatment ) AIMS Previously we revealed the effectiveness of a new therapeutic approach with a short-term , very-low dose fluvastatin-valsartan combination on the improvement of arterial function in type 1 diabetes mellitus patients ( T1DM ) . In this study we explored whether this approach influences inflammation and oxidative stress and explored any association of these effects with arterial function improvement . METHODS This was a supplementary analysis of the two previous double blind r and omized studies ( included 44 T1DM patients ) . Treatment group received very-low dose fluvastatin-valsartan , the control group received placebo . Blood sample s were collected and inflammation parameters : high-sensitivity CRP ( hsCRP ) , interleukin 6 ( IL-6 ) , vascular cell adhesion molecule-1 ( VCAM-1 ) and oxidative stress parameter total antioxidant status ( TAS ) were measured . RESULTS Treatment decreased hsCRP values ( by 56.5 % , P<0.05 ) and IL-6 values ( by 33.6 % , P<0.05 ) and increased TAS values ( by 21.1 % ; P<0.05 ) after 30days of treatment . High sensitivity CRP and TAS remained decreased 3months after treatment discontinuation . Importantly , the anti-inflammatory and anti-oxidative action significantly correlated with arterial function improvement . CONCLUSIONS The approach consisting of short-term ( 30days ) treatment with a very low-dose fluvastatin-valsartan combination acts anti-inflammatory and anti-oxidative in T1DM patients . These observations along with the improvement of arterial function support the assumption that this approach could have an important clinical benefit in T1DM patients OBJECTIVE The purpose of this study was to evaluate the efficacy and safety profile of ezetimibe/simvastatin(EZE/SIMVA ) combination tablet , relative to ezetimibe ( EZE ) and simvastatin ( SIMVA ) monotherapy , in patients with primary hypercholesterolemia . METHODS This was a r and omized , multicenter , double-blind , placebo-controlled , factorial design study After a 6- to 8-week washout period and 4-week , single-blind , placebo run in , hypercholesterolemic patients ( low-density lipoprotein cholesterol [ LDL-C ] , 145 - 250 mg/dL ; triglycerides [ TG ] , < or = 350 mg/dL ) were r and omized equally to 1 of 10 daily treatments for 12 weeks : EZE/SIMVA 10/10 , 10/20 , 10/40 , or 10/80 mg ; SIMVA 10 , 20 , 40 , or 80 mg ; EZE 10 mg ; or placebo . The primary efficacy analysis was mean percent change from baseline in LDL-C to study end point Secondary end points included percent changes in other lipid variables and C-reactive protein [ CRP ] . RESULTS There were 1528 patients r and omized to treatment ( 792 women , 736 men ) ; mean ( SD ) age ranged from 54.9 ( 112 ) years to 56.4 ( 10.6 ) years across pooled treatment groups . The treatment groups were well balanced for baseline demographics . Pooled EZE/SIMVA was associated with greater reductions in LDL-C than pooled SIMVA or EZE alone ( P < 0.001 ) . Depending on dose , EZE/SIMVA was associated with reductions in LDL-C of -44.8 % to -602 % , non-high-density lipoprotein cholesterol of -40.5 % to -55.7 % , and TG of -22.5 % to -30.7 % ; high-density lipoprotein cholesterol increased by 5.5 % to 9.8 % . EZE/SIMVA was associated with greater reductions in CRP and remnant-like particle-cholesterol than SIMVA alone ( P < 0.001 ) . More patients receiving EZE/SIMVA versus SIMVA achieved LDL-C concentrations < 100 mg/dL ( 78.6 % vs 45.9 % ; P < 0.001 ) . EZE/SIMVA was generally well tolerated , with a safety profile similar to SIMVA monotherapy There were no significant differences between EZE/SIMVA and SIMVA in the incidence of consecutive liver transaminase levels > or =3 times the upper limit of normal ( ULN ) ( 1 .5 % for EZE/SIMVA and 1.1 % for SIMVA ; P = NS ) or creature kinase levels > or = 10 times ULN ( 0.0 % for EZE/SIMVA and 02 % for SIMVA ; P = NS ) . CONCLUSION The EZE/SIMVA tablet was a highly effective and well-tolerated LDL-C-lowering therapy in this study of patients with primary hypercholesterolemia BACKGROUND Chronic kidney disease ( CKD ) is associated with inflammation . The effects of atorvastatin on biomarkers of inflammation were assessed in CKD patients in the LORD trial . METHODS 117 patients with serum creatinine > 120 μmol/L were r and omized to receive atorvastatin 10 mg/day ( 56 ) or placebo ( 61 ) and followed for a mean of 2.5 years . 33 individuals with normal kidney function were controls . Outcomes included comparison of changes in pentraxin-3 ( PTX3 ) , TNF-α , CRP , IL-6 , IL-8 , and IL-10 between atorvastatin and placebo-treated patients . RESULTS At baseline , compared with controls , CKD patients had increased PTX3 ( mean , 1.08 vs. 0.58 ng/mL ; p < 0.001 ) , CRP ( 4.9 vs. 1.5 mg/L ; p < 0.001 ) , IL-8 ( 6.00 vs. 4.58 pg/mL ; p = 0.001 ) , IL-10 ( 59.0 vs. 17.6 pg/mL ; p = 0.007 ) , and TNF-α ( 18.0 vs. 5.6 ng/mL ; p < 0.001 ) . In patients with raised baseline plasma IL-6/8/10 and /or PTX3 the eGFR decline during the trial was significantly less in those treated with atorvastatin compared to placebo ( mean change , -3.36 ; vs. + 1.25 mL/min/1.73 m2/year ; difference , 4.61 95 % CI 0.98 - 8.25 ; p = 0.002 ) , whilst those without raised inflammatory biomarkers showed no difference . Placebo treated patients with raised TNF-α levels had no eGFR decline ( p > 0.90 ) , whereas in atorvastatin-treated patients eGFR declined ( p = 0.05 ) . CONCLUSIONS CKD patients with inflammation treated with atorvastatin had significantly less eGFR decline . Larger studies using statin therapy , specifically enrolling CKD patients with inflammation , may be worthwhile exploring Purpose of the study was to investigate whether short-term atorvastatin treatment improves endothelial function and affects inflammatory process in patients with heart failure ( HF ) and normal cholesterol levels . HF is characterized by endothelial dysfunction and increased inflammatory process , while statins restore endothelial function having also anti-inflammatory effects in hypercholesterolemic patients . We investigated the effect of 4-week atorvastatin treatment ( 10 mg/day ) on endothelial function and inflammatory markers in patients with HF and cholesterol levels < 220 mg/dl . Patients were r and omly allocated into groups and received atorvastatin  ( n=19 ) or no statin ( n=19 ) . Forearm blood flow was measured using gauge-strain plethysmography .  Serum levels of tumor necrosis factor alpha ( TNF-alpha ) , interleukin 6 ( IL-6 ) , and soluble vascular cell adhesion molecule ( sVCAM-1 ) were determined with ELISA . Data are expressed as median [ 25th-75th percentile ] . Forearm vasodilatory response to reactive hyperemia was significantly improved in atorvastatin-treated patients ( from 38.1 % [ 32.0 - 59.1 ] to 70.0 % [ 61.1 - 106.3 ] , P<0.01 ) , while it remained unaffected in the control group . Levels of IL-6 , TNF-alpha and sVCAM-1 were decreased in atorvastatin-treated group ( from 7.8 pg/ml [ 4.8 - 9.5 ] , 3.2 pg/ml [ 2.7 - 4.8 ] and 595 ng/ml [ 440 - 810 ] to 5.6 pg/ml [ 2.5 - 9.0 ] , 2.8 pg/ml [ 2.0 - 3.6 ] and 289 ng/ml [ 169 - 368 ] , respectively , P<0.05 for all ) but not in the control group . These findings indicate that atorvastatin may improve forearm vasodilatory response to reactive hyperemia and depress inflammatory process in patients with heart failure and normal baseline cholesterol levels Background —Inflammation promotes acute coronary syndromes and ensuing clinical complications . Although statins reduce inflammatory markers in asymptomatic adults or in patients with stable angina , the effect of statins on the markedly heightened inflammation in patients with acute coronary syndromes is unknown . Methods and Results —We measured C-reactive protein ( CRP ) , serum amyloid A ( SAA ) , and interleukin 6 ( IL-6 ) in 2402 subjects enrolled the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering ( MIRACL ) study . Subjects with unstable angina or non – Q-wave myocardial infa rct ion were r and omized to atorvastatin 80 mg/d or placebo within 24 to 96 hours of hospital admission and treated for 16 weeks . The effect of treatment on inflammatory markers was assessed by ANCOVA after adjustment for presenting syndrome , country , and initial level of marker . All 3 markers were markedly elevated at r and omization and declined over the 16 weeks in both treatment groups . Compared with placebo , atorvastatin significantly reduced CRP , −83 % ( 95 % CI , −84 % , −81 % ) versus −74 % ( 95 % CI , −75 % , −71 % ) ( P < 0.0001 ) and SAA , −80 % ( 95 % CI , −82 % , −78 % ) versus −77 % ( −79 % , −75 % ) ( P = 0.0006 ) but not IL-6 , −55 % ( 95 % CI , −57 % , −53 % ) versus −53 % ( 95 % CI , −55 % , −51 % ) ( P = 0.3 ) . Reductions in CRP and SAA were observed in patients with unstable angina and non – Q-wave myocardial infa rct ion , with initial LDL cholesterol < 3.2 or ≥3.2 mmol/L ( 125 mg/dL ) , age ≥65 or < 65 years , and in men and women . By 16 weeks , CRP was 34 % lower with atorvastatin than with placebo . Conclusions —High-dose atorvastatin potentiated the decline in inflammation in patients with acute coronary syndromes . This supports the value of early statin therapy in these patients We sought to determine if atorvastatin lowers blood pressure in patients with previously diagnosed and well-controlled essential arterial hypertension and if this effect could be related to anti-inflammatory and anti-oxidative effects . Among 92 patients with essential arterial hypertension , we studied 56 non-smoking and normolipemic : 39 were r and omized to receive 80 mg atorvastatin daily for 3 months ( statin-treated patients , ST ) , and the rest continued a previous hypotensive therapy ( statin-free patients , SF ) . Blood pressure was measured using a 24-h ambulatory blood pressure measurement device . Serum levels of high-sensitivity C-reactive protein ( hs-CRP ) , total antioxidant status ( TAS ) and plasma peroxides ( assessed by Oxystat ) were measured in both groups . The mean change in systolic BP ( SBP ) for atorvastatin was -5.7 mmHg ( 95 % confidence interval CI , -4.1 to -7.2 mmHg ) , and the mean change in diastolic BP ( DBP ) was -3.9 mmHg ( 95 % CI , -2.7 to -5.0 mmHg ) . No change in BP in SF patients was observed . In the ST group , hs-CRP and peroxides did not significantly decrease . In the SF group , concentrations of hs-CRP proceeded to decrease while peroxides increased . In the ST group , changes in hs-CRP correlated with changes in total cholesterol and low-density lipoprotein cholesterol ( r = 0.41 , p = 0.013 and r = 0.35 , p = 0.04 , respectively ) but did not correlate with changes in BP . The hypotensive statin effect was independent of the hypolipemic effect . During three months of observation , TAS concentrations in both groups remained stable . In this r and omized study , additionally administered atorvastatin to non-smoking and normolipemic patients with well-controlled essential arterial hypertension result ed in reduction of BP . This effect was not followed by significant changes in hs-CRP , TAS or Oxystat concentrations . The hypotensive effect of atorvastatin did not depend on anti-inflammatory , anti-oxidative or hypolipemic actions OBJECTIVES We investigated whether atorvastatin might decrease insulin sensitivity and increase ambient glycemia in hypercholesterolemic patients . BACKGROUND Clinical trials suggest that some statin treatments might increase the incidence of diabetes despite reductions in low-density lipoprotein ( LDL ) cholesterol and improvement in endothelial dysfunction . METHODS A r and omized , single-blind , placebo-controlled parallel study was conducted in 44 patients taking placebo and in 42 , 44 , 43 , and 40 patients given daily atorvastatin 10 , 20 , 40 , and 80 mg , respectively , during a 2-month treatment period . RESULTS Atorvastatin 10 , 20 , 40 , and 80 mg significantly reduced LDL cholesterol ( 39 % , 47 % , 52 % , and 56 % , respectively ) and apolipoprotein B levels ( 33 % , 37 % , 42 % , and 46 % , respectively ) after 2 months of therapy when compared with either baseline ( all p < 0.001 by paired t test ) or placebo ( p < 0.001 by analysis of variance [ ANOVA ] ) . Atorvastatin 10 , 20 , 40 , and 80 mg significantly increased fasting plasma insulin ( mean changes : 25 % , 42 % , 31 % , and 45 % , respectively ) and glycated hemoglobin levels ( 2 % , 5 % , 5 % , and 5 % , respectively ) when compared with either baseline ( all p < 0.05 by paired t test ) or placebo ( p = 0.009 for insulin and p = 0.008 for glycated hemoglobin by ANOVA ) . Atorvastatin 10 , 20 , 40 , and 80 mg decreased insulin sensitivity ( 1 % , 3 % , 3 % , and 4 % , respectively ) when compared with either baseline ( p = 0.312 , p = 0.008 , p < 0.001 , and p = 0.008 , respectively , by paired t test ) or placebo ( p = 0.033 by ANOVA ) . CONCLUSIONS Despite beneficial reductions in LDL cholesterol and apolipoprotein B , atorvastatin treatment result ed in significant increases in fasting insulin and glycated hemoglobin levels consistent with insulin resistance and increased ambient glycemia in hypercholesterolemic patients . ( Effects of Atorvastatin on Adiponectin Levels and Insulin Sensitivity In Hypercholesterolemic Patients ; NCT00745836 ) The aim of our study was to evaluate whether a single dose of cerivastatin at the time of admission of patients with unstable angina pectoris ( UAP ) or non-Q-wave myocardial infa rct ion ( NQMI ) can influence the serum level of C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) and interleukin-8 ( IL-8 ) 24 h later . Forty-four patients with rest chest pain and subendocardial ischemia on ECG were r and omized to receive cerivastatin 0.3 mg at the time of admission ( group C+ ) to st and ard therapy or to remain just on st and ard therapy ( group C− ) . Blood sample s for determination of troponin I ( TI ) , CRP , IL-6 and IL-8 were collected at admission ( entry level ) and 24 h later ( final level ) . Patients with non-physiological baseline levels of TI  , as well as patients with progression to Q wave MI were excluded . All baseline , clinical and demographic data and final values of TI were comparable in the two groups . In patients treated with cerivastatin ( group C+ , n = 13 ) we observed decrease in the CRP level ( −6.73 ± 3.93 mg/L ) ; on the other h and , in group C− ( n = 17 ) the CRP level increased ( + 7.92 ± 2.77 mg/L , p = 0.004 ) . Similar differences were observed also in IL-6 : in group C+ the level was significantly reduced as compared with the increase in group C− ( −0.76 ± 0.52 vs. 4.58 ± 1.49 ng/L , p = 0.005 ) . The level of IL-8 was not affected . Our results suggest that early treatment with cerivastatin can decrease the serum level of CRP and IL-6 in patients with UAP/NQMI ; this might positively influence their prognosis . Nevertheless , further studies are needed to support this hypothesis This study assessed the effects of tirofiban and statins on high-sensitivity C-reactive protein , interleukin-6 , and soluble CD40 lig and after percutaneous coronary intervention in patients who had stable coronary artery disease .  Tirofiban insignificantly limited the increase of soluble CD40 lig and after revascularization , especially in patients who had high levels of this marker at baseline ( p = 0.06 ) , whereas statins significantly inhibited increases in interleukin-6 and , to a lesser extent , high-sensitivity C-reactive protein without affecting the soluble CD40 lig and BACKGROUND Elevated levels of C-reactive protein , even in the absence of hyperlipidemia , are associated with an increased risk of coronary events . Statin therapy reduces the level of C-reactive protein independently of its effect on lipid levels . We hypothesized that statins might prevent coronary events in persons with elevated C-reactive protein levels who did not have overt hyperlipidemia . METHODS The level of C-reactive protein was measured at base line and after one year in 5742 participants in a five-year r and omized trial of lovastatin for the primary prevention of acute coronary events . RESULTS The rates of coronary events increased significantly with increases in the base-line levels of C-reactive protein . Lovastatin therapy reduced the C-reactive protein level by 14.8 percent ( P<0.001 ) , an effect not explained by lovastatin-induced changes in the lipid profile . As expected , lovastatin was effective in preventing coronary events in participants whose base-line ratio of total cholesterol to high-density lipoprotein ( HDL ) cholesterol was higher than the median ratio , regardless of the level of C-reactive protein ( number needed to treat for five years to prevent 1 event , 47 ; P=0.005 ) . However , lovastatin was also effective among those with a ratio of total to HDL cholesterol that was lower than the median and a C-reactive protein level higher than the median ( number needed to treat , 43 ; P=0.02 ) . In contrast , lovastatin was ineffective among participants with a ratio of total to HDL cholesterol and a C-reactive protein level that were both lower than the median ( number needed to treat , 983 ; P=0.80 ) . CONCLUSIONS Statin therapy may be effective in the primary prevention of coronary events among subjects with relatively low lipid levels but with elevated levels of C-reactive protein Background Insulin resistance is associated with the progression of atherosclerosis and is reported to predict cardiovascular mortality in patients with end-stage renal disease ( ESRD ) . Although statins exert pleiotropic effects , it is uncertain whether statin therapy improves insulin resistance in these patients . In this prospect i ve r and omized controlled trial , we aim ed to evaluate the effects of statin on insulin resistance among 70 patients undergoing peritoneal dialysis ( PD ) . Methods Patients were r and omized into a statin group ( n = 35 ) or a control group ( n = 35 ) . The statin group received 10 mg per day of rosuvastatin for 6 months . We determined insulin resistance by homeostatic model assessment of insulin resistance ( HOMA-IR ) index . Serum concentrations of adipokines such as adiponectin , leptin , and resistin were measured using enzyme-linked immunosorbent ( ELISA ) assay . As inflammatory markers , high sensitive C-reactive protein ( hsCRP ) and interleukin-6 were also measured . Results There were no significant differences in baseline characteristics between the two groups . Compared to baseline value , statin treatment significantly decreased HOMA-IR index from 2.37 ± 1.08 to 2.05 ± 0.82 ( P = 0.014 ) . There was a concordant decrease in hsCRP levels in the statin group ( 2.05 ± 1.57 to 1.21 ± 0.84 mg/L , P < 0.001 ) , but such improvements were not observed in the control group . When between-group differences in these parameters were compared , hsCRP levels were more decreased in the statin group than in the control group ( P = 0.021 for between-group difference ) , whereas HOMA-IR index was not ( P = 0.189 for between-group difference ) . During this period , statin treatment did not result in the improved adipokine profiles . Conclusion This study showed that statin therapy failed to improve insulin resistance in PD patients despite a significant decline in hsCRP levels after statin treatment . Our finding suggests that reducing inflammation by statin is of limited help to fully attenuate insulin resistance in these patients Abstract Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion . The primary hypothesis of this r and omized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators . We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke ( LAAS ) r and omly assigned in a r and omized parallel trial to the following groups : Group A , 22 patients treated with atorvastatin 80 mg ( once-daily ) from admission day until discharge ; Group B , 20 patients not treated with atorvastatin 80 mg until discharge , and after discharge , treatment with atorvastatin has been started . At 72 hours and at 7 days after acute ischemic stroke , subjects of group A showed significantly lower plasma levels of tumor necrosis factor-&agr ; , interleukin (IL)-6 , vascular cell adhesion molecule-1 , whereas no significant difference with regard to plasma levels of IL-10 , E-Selectin , and P-Selectin was observed between the 2 groups . At 72 hours and 7 days after admission , stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores . Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile Elevated plasma levels of asymmetric dimethylarginine ( ADMA ) have been associated with attenuated endothelium-dependent vasodilation in hypercholesterolemic patients . However , whether lowering of plasma cholesterol concentration by hydroxymethylglutaryl coenzyme A reductase inhibitors ( statins ) can reduce plasma ADMA levels is still not clear . This study was a multicenter , r and omized , double-blind , placebo-controlled design including 46 patients with elevated low-density lipoprotein cholesterol levels . Patients were r and omized into 2 groups : rosuvastatin 10 mg/day and placebo for 6 weeks . Plasma levels of ADMA , 8-isoprostane ( as a marker of oxidative stress ) , homocysteine , and high-sensitivity C-reactive protein were measured at baseline and 6 weeks later . Endothelial function assessed by flow-mediated vasodilation of the brachial artery was performed in 11 patients in the rosuvastatin group and in 12 in the placebo group . Baseline characteristics of both groups were similar , and the plasma ADMA levels were significantly correlated with 8-isoprostane ( r = 0.388 , p = 0.008 ) . After 6 weeks of treatment , plasma ADMA levels were significantly reduced in the rosuvastatin group ( from 0.60 + /- 0.19 to 0.49 + /- 0.10 micromol/L , p < 0.001 ) . Increases in flow-mediated vasodilation were positively correlated with reductions in plasma levels of ADMA ( p = 0.017 ) and low-density lipoprotein cholesterol ( p < 0.001 ) . Thus , our findings suggest that treatment with rosuvastatin in patients with hypercholesterolemia may lead to a significant reduction in plasma ADMA levels , which appear to be related to the improvement in endothelial function by rosuvastatin BACKGROUND Studies indicate that myeloperoxidase ( MPO ) is associated with disease progression and severity in heart failure ( HF ) , while it may provide a mechanistic link between inflammation and adverse cardiac remodeling . The mechanisms that regulate MPO are unclear , while it is unknown whether specific treatments such as HMG-CoA reductase inhibitors and xanthine oxidase inhibitors may modify MPO . Therefore in the present study we examined the effects of rosuvastatin and allopurinol on MPO levels in patients HF . METHODS Sixty clinical ly stable patients with systolic HF were r and omized to receive rosuvastatin 10mg/day , allopurinol 300mg/day or placebo and followed up for 1 month . Plasma levels of MPO and serum levels of soluble CD40 lig and , interleukin-6 , and oxidized LDL were determined using ELISA . All measurements were made before and after 1-month treatment . RESULTS Rosuvastatin significantly reduced plasma levels of MPO ( p=0.003 ) , which remained unchanged in the other groups . Furthermore , the change of MPO levels in the rosuvastatin-treated group was significantly different compared with the other groups ( p<0.05 ) . Rosuvastatin administration also led to a significant decrease in oxidized LDL ( p=0.009 ) , while the other inflammatory markers remained unchanged in all groups . In the total population , a significant correlation was observed between the baseline levels of MPO and hsCRP ( r=0.275 , p=0.027 ) , fibrinogen ( r=0.278 , p=0.025 ) , and sCD40L ( r=0.288 , p=0.021 ) . CONCLUSIONS Short-term treatment with rosuvastatin regulates inflammatory process in patients with heart failure by significantly reducing plasma levels of MPO . This finding reveals a novel pleiotropic effect of statins in patients with heart failure , and provides further insights into the pathophysiological mechanisms of MPO in heart failure BACKGROUND It has been shown that many women with polycystic ovary syndrome ( PCOS ) are 25-hydroxyvitamin D ( 25OHD ) insufficient . Both statin treatment and vitamin D supplementation have been shown to improve biochemical hyper and rogenemia , insulin resistance , and markers of inflammation in patients with PCOS , raising the possibility that some of the statin effects are mediated through vitamin D. METHODS We conducted this r and omized , double-blind placebo controlled study to assess the effect of atorvastatin on serum 25OHD concentrations in patients with PCOS . Forty medication-naive patients with PCOS were r and omized to either atorvastatin 20 mg daily or placebo for 3 months . After completing the initial 3 months of atorvastatin or placebo , both groups of patients participated in a 3-month extension study with metformin 1500 mg daily . We measured changes in 25OHD concentrations by use of t and em mass spectrometry . RESULTS Mean ( SD ) baseline 25OHD concentrations were comparable between the 2 groups [ 45.9 ( 2.4 ) vs 44.8 ( 1.8 ) nmol/L ; P = 0.7 ] . There was a significant increase in 25OHD concentrations with atorvastatin [ 45.9 ( 2.4 ) vs 60.8 ( 3.5 ) nmol/L ] compared with placebo [ 44.8 ( 1.8 ) vs 41.8 ( 3.2 ) nmol/L ; P = 0.02 ] . Three-month treatment with metformin maintained the improvement of 25OHD  with atorvastatin compared to baseline [ 45.9 ( 2.4 ) vs 61.8 ( 3.5 ) , P ≤ 0.01 ) . There were no significant changes in 25OHD concentrations in the placebo group after 12 weeks of metformin . CONCLUSIONS Among patients with polycystic ovary syndrome , 12 weeks of atorvastatin led to a clinical ly significant rise in 25OHD concentrations . This may represent a beneficial pleiotropic effect of statins on 25OHD concentrations CONTEXT Statins have been shown to improve hyper and rogenism in women with polycystic ovary syndrome ( PCOS ) . However , their use has also been associated with impairment of glucose metabolism and an increased risk of type 2 diabetes mellitus . Because women with PCOS are prone to disturbances in glucose metabolism , statin therapy could also have negative effects . OBJECTIVE Our objective was to explore the effects of atorvastatin therapy on hormonal and metabolic parameters in women with PCOS . DESIGN AND SETTING We conducted a r and omized , double-blind , placebo-controlled 6-month follow-up study conducted at Oulu University Hospital , Finl and . PATIENTS Women with PCOS ( Rotterdam criteria ) were treated with atorvastatin ( 20 mg/d , n = 15 ) or placebo  ( n = 13 ) for 6 months . INTERVENTIONS Fasting serum sample s were collected at baseline and at 3 and 6 months . Oral and iv glucose tolerance tests were performed at 0 and 6 months . MAIN OUTCOME MEASURES And rogen secretion and glucose metabolism were measured . RESULTS Fasting levels and area under the curve of insulin increased significantly and insulin sensitivity ( insulinogenic and Matsuda indexes ) decreased during 6 months of atorvastatin therapy . Serum levels of dehydroepi and rosterone sulfate decreased in the atorvastatin group , whereas no change was observed in serum testosterone levels . Levels of C-reactive protein , total and low-density lipoprotein-cholesterol , and triglycerides decreased significantly during statin therapy . CONCLUSIONS Atorvastatin therapy improves chronic inflammation and lipid profile , but it impairs insulin sensitivity in women with PCOS . Because women with PCOS have an increased risk of developing type 2 diabetes mellitus , the results suggest that statin therapy should be initiated on the basis of generally accepted criteria and individual risk assessment of cardiovascular disease , and not only because of PCOS Background : Telomerase activity ( TA ) is considered as the biomarker for cardiovascular aging and cardiovascular diseases ( CVDs ) . Recent studies suggest a link between statins and telomere biology that may be explained by anti-inflammatory actions of statins and their positive effect on TA . Until now , this effect has not been investigated in prospect i ve r and omized studies . We hypothesized that 12 months of atorvastatin therapy increased TA in peripheral blood mononuclear cells . Methods : In a r and omized , placebo-controlled study 100 hypercholesterolemic patients , aged 35–75 years , free of known CVDs and diabetes mellitus type 2 received 20 mg of atorvastatin daily or placebo for 12 months .  TA was measured by quantitative polymerase chain reaction . Results : At study end , 82 patients had sufficient peripheral blood mononuclear cells needed for longitudinal analysis . TA expressed as natural logarithms changed from 0.46 ± 0.05 to 0.68 ± 0.06 ( p = 0.004 ) in the atorvastatin group and from 0.67 ± 0.06 to 0.60 ± 0.07 ( p = 0.477 ) in the control group . In multiple regression analysis , atorvastatin therapy was the only independent predictor ( p = 0.05 ) of the changes in TA independently of markers of chronic inflammation and oxidative stress . Atorvastatin therapy was associated with increases in interleukin-6 within the normal range and a tendency toward reduction in blood urea . Conclusion : These initial observations suggest atorvastatin can act as telomerase activator and potentially as effective geroprotector . Trial registration : The trial was registered in IS RCT N registry IS RCT N55050065 BACKGROUND The role of statin therapy in heart failure ( HF ) is unclear . The amino-terminal propeptide of procollagen type III ( PIIINP ) predicts outcome in HF , and yet there are conflicting reports of statin therapy effects on PIIINP . OBJECTIVES This study determined whether there was an increase in serum markers of inflammation , fibrosis ( including PIIINP ) , and B-type natriuretic peptide ( BNP ) in patients with systolic HF and normal total cholesterol and determined the effects of long-term treatment with atorvastatin on these markers . METHODS Fifty-six white patients with systolic HF and normal cholesterol levels ( age 72 [ 13 ] years ; 68 % male ; body mass index 27.0 [ 7.3 ] kg/m(2 ) ; ejection fraction 35 [13]% ; 46 % with history of smoking ) were r and omly allocated to atorvastatin treatment for 6 months , titrated to 40 mg/d ( A group ) or not ( C group ) . Age- and /or sex-matched subjects without HF ( N group ) were also recruited . Biomarkers were measured at baseline ( all groups ) and 6 months ( A and C groups ) . RESULTS Serum markers of collagen turnover , inflammation , and BNP were significantly elevated in HF patients compared with normal participants ( all P < 0.05 ) . There were correlations between these markers in HF patients but not in normal subjects . Atorvastatin treatment for 6 months caused a significant reduction in the following biomarkers compared with baseline : BNP , from median ( interquartile range ) 268 ( 190 - 441 ) pg/mL to 185 ( 144 - 344 ) pg/mL ; high-sensitivity C-reactive protein ( hs-CRP ) , from 5.26 ( 1.95 -9.29 ) mg/L to 3.70 ( 2.34 - 6.81 ) mg/L ; and PIIINP , from 4.65 ( 1.86 ) to 4.09 ( 1.25 ) pg/mL ( all P < 0.05 baseline vs 6 months ) . Between-group differences were significant for PIIINP only ( P = 0.027 ) . There was a positive interaction between atorvastatin effects and baseline hs-CRP and PIIINP ( P < 0.01 ) . CONCLUSIONS Long-term statin therapy reduced PIIINP in this small , selected HF population with elevated baseline levels . Further evaluation of statin therapy in the management of HF patients with elevated PIIINP is warranted BACKGROUND High-dose statins are used in acute coronary syndromes ( ACS ) to reduce inflammation . The aim of the study was the evaluation of the influence of low-dose atorvastatin ( 20 mg ) on selected inflammatory parameters and clinical outcomes after ACS . METHODS Seventy eight patients ( pts ) with ACS were r and omly divided into group A ( 39 pts ) taking atorvastatin , and group NA ( 39 pts ) not taking any statin for the following six weeks . C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , monocyte chemoattractant protein-1 ( MCP-1 ) and tumour necrosis factor alpha ( TNFa ) levels were measured on the first and the fifth days and six weeks after ACS . RESULTS There was no significant CRP and IL-6 level decrease in group A ( CRP--62 % ; IL-6 - 73 % ) or group NA ( CRP-44 % ; IL-6 - 62 % ) . There was also no significant change in TNFa levels . The MCP-1 level finally reached the level of significant difference ( p < 0.04 ) . Cardiovascular events ( MACE ) and the restenosis rates did not differ between the groups . CONCLUSIONS Low-dose atorvastatin does not have a significant influence on cooling down inflammation in ACS , and MCP-1 can be used as an early indicator of statin anti-inflammatory activity . Furthermore , it does not reduce MACE or restenosis rates despite its influence on MCP-1 levels BACKGROUND Lipid-lowering agents are known to reduce long-term mortality in patients with stable angina or multiple risk factors . However , the effects of lipid-lowering treatment on inflammatory process during and immediately after the acute phase of unstable angina remain unclear . In this study we assessed the effects of low-dose atorvastatin treatment , on inflammatory process in patients admitted for unstable angina with low cholesterol level . METHODS Forty-seven normocholesterolemic patients with unstable angina were r and omized into two groups , and received atorvastatin 10 mg/day ( n = 24 ) or no statin ( n = 23 ) for 6 weeks . Circulating levels of inteleukin 6 ( IL-6 ) , monocyte chemoattractant protein-1 ( MCP-1 ) , tumor necrosis factor alpha ( TNF-alpha ) and soluble vascular cell adhesion molecule ( sVCAM-1 ) were measured by their admission , and at the 1st and 6th week of the study . RESULTS Serum levels of MCP-1 and sVCAM-1 were significantly increased in the control group ( p < 0.05 ) while remained unaffected in the atorvastatin-treated group six weeks after admission . However , IL-6 and TNF-alpha levels were similarly decreased in both atorvastatin-treated and control groups . CONCLUSION Low-dose atorvastatin treatment modifies inflammatory process in patients with unstable angina and low cholesterol level , an effect seen at 6 weeks but not 1 week after admission AIM We aim ed to assess the effects of rosuvastatin treatment on lipid levels , a biomarker of oxidative stress , albuminuria , and kidney function in patients with diabetic nephropathy . METHODS We conducted a prospect i ve , open-label , parallel group , controlled study of 104 patients with diabetic nephropathy , low-density lipoprotein cholesterol ( LDL-C ) levels of > 120 mg/dL , and well-controlled blood pressure who were undergoing treatment with renin angiotensin system inhibitors .  Patients were r and omly assigned to two groups : the rosuvastatin group ( n = 52 ; 2.5 mg/day rosuvastatin , increased to 10 mg/day ) and the control group ( n = 52 ; no rosuvastatin administered ) . We determined the efficacy of rosuvastatin by monitoring serum lipid profiles , high sensitivity C-reactive protein ( hs-CRP ) , malondialdehyde-modified LDL ( MDA-LDL ) , and cystatin C levels . In addition , urinary albumin , 8-hydroxydeoxyguanosine ( 8-OHdG ) and liver-type fatty acid-binding protein ( L-FABP ) levels were measured before and 6 months after rosuvastatin was added to the treatment . RESULTS Rosuvastatin effectively reduced total cholesterol , LDL-C , triglycerides , non-high-density lipoprotein cholesterol ( non-HDL-C ) levels , and the LDL-C/ HDL-C ratio in the rosuvastatin group . These parameters remained unchanged in patients who were not treated with rosuvastatin . Although there was no significant change in the estimated glomerular filtration rate level , serum cystatin C levels and urinary albumin excretion rates were significantly decreased in the rosuvastatin group . In addition , rosuvastatin significantly reduced hs-CRP and MDA-LDL levels . Moreover , urinary 8-OHdG and L-FABP levels at baseline ( 13.5±5.1 and 41.7±26.1 ng/mgCr , respectively ) decreased significantly at 6 months ( 11.5±4.0 and 26.9±13.4 ng/mgCr , respectively ) , and there was a significant correlation ( r = 0.48 , p < 0.01 ) . Multivariate analysis revealed that albuminuria was significantly correlated with only rosuvastatin use ( p = 0.0006 , R(2)= 0.53 ) . CONCLUSION Rosuvastatin administration reduced albuminuria , oxidative stress , and serum cystatin C levels , independent of blood pressure and lipid levels Our aim in this study was to investigate the changes of serum high-sensitive C-reactive protein ( hs-CRP ) and uric acid ( UA ) , and evaluate the synergistic effect of amlodipine and atorvastatin on blood pressure and left ventricular remodeling in hypertensive patients with primary hypercholesterolemia . One hundred and twenty-six hypertensive patients with hypercholesterolemia were r and omized into amlodipine group ( 10 mg/day , group A , n = 65 ) and amlodipine ( 10 mg/day ) plus atorvastatin group ( 20 mg/day , group B , n = 61 ) , treated for 4 months continuously . Serum concentrations of total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , triglycerides , hs-CRP , and UA were determined , and blood pressure of both groups was examined before and after treatment . Left ventricular posterior wall thickness and interventricular spectum thickness were measured by echocardiography , and left ventricular mass index ( LVMI ) was calculated . After 4-months of treatment with atorvastatin , serum concentrations of total cholesterol , low-density lipoprotein cholesterol , triglycerides , hs-CRP , and UA were significantly decreased in group B ( P < 0.05 , P < 0.01 ) , while serum concentrations of high-density lipoprotein cholesterol was elevated ( P < 0.05 ) . Meanwhile , systolic blood pressure and diastolic blood pressure were reduced in both groups ( P < 0.05 ) , and blood pressure in group B was markedly lower than that in group A after treatment ( P < 0.05 ) . Compared with that before treatment , LVMI in both groups decreased ( P < 0.05 ) , to a significantly lower degree in group B than in group A ( P < 0.05 ) . Atorvastatin can decrease serum concentrations of hs-CRP and UA . The amlodipine-atorvastatin combination markedly reduces blood pressure and reverses left ventricular hypertrophy more than amlodipine monotherapy . The positive effect suggests that in hypertensive and hypercholesterolemic patients , the combination of amlodipine and atorvastatin could be the treatment of choice OBJECTIVE Lowering LDL-cholesterol by statins has been proven to be associated with reduction of proinflammatory regulators e.g. activation of the transcription factor NF-κB. To our knowledge , anti-inflammatory potential of newer cholesterol lowering agents such as ezetimibe is less intensively studied . Therefore we analyzed the effects of equipotent LDL-lowering therapy with simvastatin alone compared to a combination with ezetimibe on NF-κB activation in peripheral blood mononuclear cells ( P BMC s ) of patients with type 2 diabetes . METHODS Thirty-one patients with type 2 diabetes were included in a double-blind , r and omized trial receiving either 80 mg simvastatin ( sim80 ; n = 10 ) or a combination of 10 mg simvastatin and 10 mg ezetimibe ( sim10eze10 ; n = 11 ) or placebo ( n = 9 ) for eight weeks . NF-κB binding activity and inflammatory markers ( IL-6 , hsCRP ) were analyzed at baseline and after eight weeks of treatment . NF-κB binding activity was analyzed by electrophoretic mobility shift assay . IL-6 and hsCRP were measured by ELISA . RESULTS After eight weeks of treatment LDL-cholesterol was lowered to the same extent in both treatment groups ( p = 0.40 ) but not in placebo . However , patients  taking sim80  showed a significant reduction of mononuclear NF-κB binding activity compared to baseline ( p = 0.009 ) while no effect was observed in the sim10eze10 group ( p = 0.79 ) . Similar differences in anti-inflammatory effects were also observed when analyzing hsCRP ( sim80 : p = 0.03 ; sim10eze10 : p = 0.40 ) and IL-6 levels  ( sim80 : p = 0.15 ; sim10eze10 : p = 0.95 ) . CONCLUSION High dose simvastatin therapy reduces proinflammatory transcription factor NF-κB binding activity and hsCRP levels , while combination of low dose simvastatin with ezetimibe result ing in a similar LDL-reduction does not affect these inflammatory markers BACKGROUND Statin therapy prior to percutaneous coronary intervention ( PCI ) is associated with reduced mortality and periprocedural myocardial injury after PCI . We studied whether single high dose statin loading is beneficial on the outcome of patients with acute coronary syndrome ( ACS ) underwent PCI . METHODS Consecutive 445 patients with ACS who underwent PCI were r and omly assigned to either the group of no statin treatment before PCI ( Control group : n=220 , 63+/-11 years , male 62 % ) or the group of 40 mg rosuvastatin loading before PCI ( Rosuvastatin group : n=225 , 64+/-10 years , male 60 % ) . Incidence of periprocedural myocardial injury was assessed by analysis of creatinine kinase-MB ( CK-MB ) and cardiac troponin T before PCI , at 6 h and the next morning after PCI . RESULT There were no significant differences in clinical characteristics between the two groups . After PCI , incidence of periprocedural myocardial injury was higher in control than in rosuvastatin group ( 11.4 % versus 5.8 % , p=0.035 ) . Mean preprocedural CK-MB and high sensitivity C-reactive protein were similar between the two groups , whereas after PCI , peak values of both markers were elevated significantly higher in control than in rosuvastatin group . Multivariate analysis revealed that no prior use of statin ( OR=2.2 ; 95 % CI=1.1 - 4.6 ; p=0.029 ) , procedural complication ( OR=3.1 ; 95 % CI=1.4 - 6.9 ; p=0.007 ) and multi-vessel disease ( OR=2.6 ; 95 % CI=1.0 - 6.6 ; p=0.039 ) were the independent predictors for periprocedural myocardial infa rct ion . CONCLUSION Single high dose of rosuvastatin prior to PCI reduces periprocedural myocardial injury in patients with ACS BACKGROUND Chronic low- grade inflammation may contribute to the increased risk of atherosclerosis in visceral obesity .  Statin and fish oil have been reported to have antiinflammatory effects . We studied whether dyslipidemic , obese individuals have increased plasma high-sensitivity C-reactive protein ( hs-CRP ) concentrations and whether treatment with atorvastatin and fish oil lowered plasma hs-CRP concentrations . METHODS We compared plasma hs-CRP , interleukin-6 ( IL-6 ) , and tumor necrosis factor-alpha ( TNF-alpha ) concentrations in 48 obese individuals with the concentrations in 10 lean normolipidemic men . The obese individuals were then r and omized to treatment with atorvastatin ( 40 mg/day ) , fish oil ( 4 g/day ) , atorvastatin plus fish oil , or matching placebo for 6 weeks . RESULTS Compared with controls , obese individuals had increased hs-CRP [ geometric mean , 2.19 mg/L ( 95 % confidence interval , 2.15 - 3.15 mg/L ) vs 0.49 mg/L ( 0.30- 0.93 mg/L ) ; P < 0.001 ] and IL-6 [ 351 pg/L ( 318 - 449 pg/L ) vs 251 pg/L ( 211 - 305 pg/L ) ; P < 0.01 ] . Atorvastatin treatment had a significant main effect of decreasing plasma hs-CRP ( -0.87 mg/L ; 95 % confidence interval , -0.10 to -1.60 mg/L ; P < 0.01 ) and IL-6 ( -70 pg/L ; 10 to -140 pg/L ; P < 0.01 ) , but this was not seen with fish oil . The reductions in hs-CRP with atorvastatin were not significantly correlated to changes in plasma lipids , IL-6 , insulin resistance , or cholesterogenesis . Plasma TNF-alpha concentrations in obese individuals , however , were neither statistically different from concentrations in the lean controls nor altered with atorvastatin or fish oil treatment . CONCLUSIONS This study shows that visceral obesity is associated with increased plasma hs-CRP and IL-6 and , hence , a low- grade chronic inflammatory state and that treatment with atorvastatin or atorvastatin with fish oil , but not fish oil alone , reverses this abnormality Background A recent r and omized placebo-controlled trial of the effect of atorvastatin treatment on the progression of newly diagnosed type 1 diabetes suggested a slower decline of residual beta cell function with statin treatment . Aim of this secondary analysis was to identify patient subgroups which differ in the decline of beta cell function during treatment with atorvastatin . Methodology /Principal Findings The r and omized placebo-controlled Diabetes and Atorvastatin ( DIATOR ) Trial included 89 patients with newly diagnosed type 1 diabetes and detectable islet autoantibodies ( mean age 30 years , 40 % females ) , in 12 centers in Germany . Patients received placebo or 80 mg/d atorvastatin for 18 months . As primary outcome stimulated serum C-peptide levels were determined 90 min after a st and ardized liquid mixed meal . For this secondary analysis patients were stratified by single baseline characteristics which were considered to possibly be modified by atorvastatin treatment . Subgroups defined by age , sex or by baseline metabolic parameters like body mass index ( BMI ) , total serum cholesterol or fasting C-peptide did not differ in C-peptide outcome after atorvastatin treatment . However , the subgroup defined by high ( above median ) baseline C-reactive protein ( CRP ) concentrations exhibited higher stimulated C-peptide secretion after statin treatment ( p = 0.044 ) . Individual baseline CRP levels correlated with C-peptide outcome in the statin group ( r2 = 0.3079 , p<0.004 ) . The subgroup with baseline CRP concentrations above median differed from the corresponding subgroup with lower CRP levels by higher median values of BMI , IL-6 , IL-1RA , sICAM-1 and E-selectin . Conclusions / Significance Atorvastatin treatment may be effective in slowing the decline of beta cell function in a patient subgroup defined by above median levels of CRP and other inflammation associated immune mediators . Trial Registration Clinical Trials.gov CONTEXT Cardiovascular disease is a major cause of mortality in type 1 diabetes ( TIDM ) . TIDM is a proinflammatory state . Whereas there is consensus on lipid management in type 2 diabetes , there is a lack of data in type 1 diabetes . In addition to benefits on the lipid profile , statin therapy is antiinflammatory . OBJECTIVE There are scant data on statin therapy in T1DM . Thus , we tested the effect of simvastatin , compared with placebo , on biomarkers of inflammation and monocyte function in TIDM patients . DESIGN This was a double-blind , r and omized , placebo-controlled study of T1DM patients , r and omized to placebo or simvastatin , 20 mg/d for 3 months . SETTING The study was conducted at the University of California , Davis , Medical Center . PARTICIPANTS Participants included patients with T1DM . METHODS AND RESULTS Analytes measured at baseline and 3 months included liver function tests , creatinine , hemoglobin AIC , high-sensitivity C-reactive protein , soluble CD40 lig and , monocyte O(2)(- ) , cytokines , nuclear factor-kappaB.  Simvastatin therapy result ed in significant reduction in low-density lipoprotein and non-high-density lipoprotein cholesterol , high-sensitivity C-reactive protein ( 18 % reduction , P < 0.001 ) and soluble CD40 lig and ( 22 % reduction , P < 0.05 ) , compared with placebo . Simvastatin therapy significantly inhibited lipopolysaccharide-activated monocyte release of O(2)(- ) ( P < 0.0005 ) , IL-8 ( P < 0.03 ) , and TNF ( P < 0.02 ) . Simvastatin therapy significantly inhibited monocyte IL-6 release , compared with baseline ( P = 0.02 ) . Simvastatin therapy also significantly reduced monocytic nuclear factor-kappaB p65 activity , compared with placebo ( P < 0.01 ) . CONCLUSIONS This study demonstrates that simvastatin ( 20 mg/d ) is safe in T1DM patients and has concomitant benefits on the lipid profile and biomarkers of inflammation . These novel findings could have implication s for developing policy guidelines for statin therapy in forestalling vascular complications in young T1DM BACKGROUND Arterial stiffness assessed by pulse wave velocity ( PWV ) predicts all-cause and cardiovascular mortality in diabetic patients with end-stage renal disease . We studied the preventive effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor , fluvastatin , on arterial PWV values in this population . METHODS Twenty-two patients with normal serum lipid levels received fluvastatin ( 20 mg/day p.o . ) or a placebo for 6 months . Their serum lipid levels , serum levels of C-reactive protein ( CRP ) , arterial PWV , and ankle brachial indexes ( ABI ) were determined before , and 3 and 6 months after taking the medication to evaluate arterial stiffness . RESULTS At the beginning of the follow-up , there were no differences in age , blood pressure , body mass index , serum haemoglobin A1c level , serum CRP level , serum lipid levels , PWV or ABI between the placebo- ( n=10 ) and the fluvastatin-treated patients ( n=12 ) . After 6 months , the PWV and the serum oxidized low-density lipoprotein cholesterol ( LDL-C ) level increased significantly ( from 1969+/-140 to 2326+/-190 cm/s and 70.4+/-13.8 to 91.8+/-15.5 U/l , respectively ) in the placebo-treated patients . However , the fluvastatin group had a significantly reduced PWV ( from 1991+/-162 to 1709+/-134 cm/s ) , oxidized LDL-C serum levels ( from 89.0+/-9.6 to 73.0+/-5.8 U/l ) and CRP serum levels ( from 0.97+/-0.32 to 0.26+/-0.16 mg/dl ) compared with those in the placebo group . CONCLUSIONS Long-term administration of fluvastatin prevents further worsening of arterial biomechanics in haemodialysis patients with type 2 diabetes mellitus , even in the presence of serum lipid levels in the normal range AIMS HMG-CoA reductase inhibitors ( statins ) reduce cardiovascular mortality and morbidity in patients with stable coronary artery disease as well as acute coronary syndrome ( ACS ) . It is unclear how rapidly the beneficial effects of statins occur in patients with ACS and whether these drug properties are related to lipid lowering . METHODS AND RESULTS Patients with troponin-positive ACS ( n=35 ) were r and omized to 20 mg/day rosuvastatin therapy or to placebo treatment . Anti-inflammatory effects of rosuvastatin measured by lymphocyte intracellular cytokine production were taken before initiation of treatment and on days 1 , 3 , and 42 . Compared with placebo , rosuvastatin treatment significantly reduced plasma concentrations of pro-inflammatory cytokines TNF-alpha and IFN-gamma at 72 h. Rosuvastatin also induced a rapid and significant reduction of TNF-alpha and IFN-gamma production in stimulated T-lymphocytes at 72 h. When compared with placebo , rosuvastatin inhibited the Th-1-immune response measured at 72 h. CONCLUSION Rosuvastatin exerts rapid immunomodulatory effects on the level of T-cell activation in patients with ACS BACKGROUND Heart failure has been associated with impaired endothelial function , increased inflammatory process and elevated oxidative stress status . Both statins and vitamin E separately improve endothelial function in patients with hypercholesterolemia and /or advanced atherosclerosis . AIM To evaluate the effect of atorvastatin alone or in combination with vitamin E on endothelial function and serum levels of interleukin-6 ( IL-6 ) , tumor necrosis factor alpha ( TNF-alpha ) and vascular cells adhesion molecule ( sVCAM-1 ) in patients with ischemic heart failure . METHODS Thirty-eight male patients with ischemic cardiomyopathy were r and omly divided into three groups and received either atorvastatin 10 mg/day ( n = 14 ) , a combination of atorvastatin 10 mg/day plus vitamin E 400 IU/day ( n = 12 ) , or no statin or antioxidant treatment ( n=12 , controls ) for 4 weeks . Forearm blood flow ( FBF ) was measured using venous occlusion strain-gauge plethysmography . Forearm vasodilatory response to reactive hyperemia ( RH% ) or to nitrate ( NTG% ) was defined as the percent change of FBF from rest to the maximum flow during reactive hyperemia or after nitrate administration , respectively . RESULTS RH% was significantly improved in both the atorvastatin-treated ( p < 0.01 ) and atorvastatin plus vitamin E groups ( p < 0.05 ) , but the increase was significantly higher in the atorvastatin-treated group ( p < 0.05 ) . Serum levels of IL-6 , TNF-alpha and sVCAM-1 were decreased in the atorvastatin-treated group ( p < 0.05 for all ) , but remained unaffected in the other two groups ( p = NS for all ) . CONCLUSIONS Low dose atorvastatin treatment improves endothelial function and reduces the expression of proinflammatory cytokines and adhesion molecules in patients with ischemic heart failure , an effect partly depressed by vitamin In this r and omized trial , C-reactive protein increased during the first 5 days of an acute coronary syndrome in patients treated with placebo , but this phenomenon was not observed in those r and omized to atorvastatin 80 mg/day . This suggests that short-term statin therapy inhibits inflammation in patients with non-ST-elevation acute coronary syndromes SUMMARY Background : Elevated levels of C-reactive protein ( CRP ) are considered to be one of the indicators of poor prognosis in coronary artery disease ( CAD ) . The aim of this study was to evaluate anti-inflammatory effects of atorvastatin in patients with CAD by measuring serum CRP levels . Methods : After measuring the baseline levels of CRP and lipid fractions , the patients were divided into two groups . In Group A ( n = 46 ) , atorvastatin ( 20 mg/day ) was administered in addition to classic antianginal treatment ( beta-blocker , nitrate and aspirin ) . In Group B ( n = 32 ) , the usual antianginal treatment was continued . Following 4 weeks of treatment the same measurements were repeated . Results : In Group A , CRP decreased from 20.3 mg/dl ( 95 % CI , 9 - 31.8 ) to 10.8 mg/dl ( 95 % CI , 2.7 - 18.9 ) ( p < 0.001 ) . In Group B , CRP decreased from 17 mg/dl ( 95 % CI , 13.1 - 21 ) to 12.8 mg/dl ( 95 % CI , 9.7 - 15.9 ) ( p < 0.01 ) . The decrease in group A was more than in group B ( p = 0.003 ) . Conclusions : In patients with CAD , atorvastatin exerted an anti-inflammatory effect represented by decreasing CRP levels . This effect was independent of the change in low density lipoprotein cholesterol ( LDL-C ) or high density lipoprotein cholesterol ( HDL-C ) levels 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 OBJECTIVE Statins are known to reduce CRP concentrations , but whether high doses are more effective is not known . METHODS In a prospect i ve double-blind multicenter study in 186 DM2 patients without manifest coronary artery disease and with dyslipidemia , the effect of a 30-week treatment with 10 and 80 mg atorvastatin or placebo on the reduction of hs-CRP levels was measured . RESULTS Median CRP levels increased with 6.6 % in the placebo group and were reduced by 15 and 47 % , respectively , with atorvastatin 10 and 80 mg ( P<0.001 ; significantly different from 10 mg atorvastatin and from placebo ( P<0.001 ) . Variation in IL-6 and plasma lipids associated for 21 and 8 % , respectively , with variation in CRP levels ( P<0.001 and P=0.01 ) . Of patients with a baseline CRP level above an arbitrary threshold of 3.0 mg/l , 56 % in the 80 mg atorvastatin group reached a level of less than 3.0 mg/l , versus 23 % r and omized to 10 mg atorvastatin ( P<0.01 ) and 17 % in the placebo group ( P<0.005 ) . CONCLUSIONS In DM2 patients high dose atorvastatin induced a strong reduction in CRP levels . The decrease in CRP was mainly independent of effects on lipid lowering and changes in IL-6 levels . The pleiotropic effect of high-dose atorvastatin on inflammation could add to its cardioprotective effect in high-risk patients Background : Dialysis patients have many underlying traditional and nontraditional risk factors that may predispose them to a high prevalence of cardiovascular disease . The effects of statins ( eg , atorvastatin ) on altering nontraditional lipoprotein measures in dialysis patients have not been extensively investigated . Objective : To evaluate the efficacy of atorvastatin compared with a control group in inducing changes in lipoprotein(a ) [ Lp(a ) ] , apolipoprotein ( Apo ) A-1 , Apo-B , and fibrinogen levels , as well as the conventional lipoprotein profile , in hemodialysis patients over 36 weeks ; secondary objectives were to assess changes in C-reactive protein , albumin , and safety measures . Methods : Forty-five hemodialysis patients with low-density lipoprotein cholesterol ( LDL-C ) levels greater than 100 mg/dL were r and omized to parallel groups : atorvastatin ( n = 19 ) or no treatment ( n = 26 ) . The atorvastatin dose was titrated from 10 mg to achieve an LDL-C goal of 100 mg/dL or less and therapy was continued for 36 weeks . Biochemical and lipoprotein laboratory tests for efficacy outcomes were obtained at baseline , 12 weeks , and 36 weeks . Results : The atorvastatin group exhibited clinical ly significant reductions ( mean ± SD ) compared with controls in total cholesterol ( –21.7 ± 41.7 vs –3.2 ± 40.0 mg/dL , respectively ; p = 0.017 ) and LDL-C ( –13.1 ± 32.0 vs –1.1 ± 38.4 mg/dL. respectively ; p = 0.056 ) levels , as well as Lp(a ) ( –10.6 ± 27 vs 3.5 ± 17.8 mg/dL , respectively ; p = 0.046 ) . Statistical analyses included analysis of variance on ranked measures for multivariable modeling and paired t-test to determine changes in efficacy measures between baseline and 36 weeks within groups . Conclusions : Atorvastatin was safe and effective in reducing Lp(a ) , total cholesterol , and LDL-C levels . Given the prevalence of atherosclerosis in hemodialysis patients , therapy aim ed at reducing traditional and nontraditional risk factors may be beneficial Hypercholesterolemia causes endothelial dysfunction , an early feature of atherosclerosis , leading to increased production of adhesion molecules and cytokines . The aim of this study was to investigate the effects of three months of treatment with low dose atorvastatin on serum levels of adhesion molecules , interleukin-6 ( IL-6 ) and highly sensitive C-reactive protein ( hs-CRP ) in patients with non-familial hypercholesterolemia . Fifty-five patients with non-familial hypercholesterolemia were r and omized to treatment with atorvastatin 10 mg/day or placebo for 3 months . Soluble intercellular adhesion molecules-1 ( ICAM-1 ) , vascular cell adhesion molecule-1 ( VCAM-1 ) , E-selectin , IL-6 and hs-CRP levels were measured to assess the inflammatory activity of the endothelium . There was a significant reduction in ICAM-1 at 2 weeks ( p<0.0001 ) with further reduction at 3 months ( p<0.0001 ) . At 3 months , there were significant reductions in VCAM-1 ( p<0.02 ) , IL-6 ( p<0.0001 ) and hs-CRP ( p<0.01 ) , but an increase in E-selectin levels ( p<0.002 ) . Treatment with statin was an independent determinant of change in ICAM-1 ( p<0.05 ) and IL-6 levels ( p<0.05 ) after correcting for anthropometric indices , blood pressure and lipid profile . Low-dose atorvastatin treatment leads to reduction in proinflammatory markers of endothelial function , suggesting an attenuation of endothelial activation and improvement in endothelial function , independent of lipid lowering . This may lead to a reduction in the progression of atherosclerosis This study examined the effects of simvastatin on C-reactive protein ( CRP ) and other inflammatory markers in study subjects with significant elevations in triglyceride ( TG ) blood levels .  CRP , vascular cellular adhesion molecule ( VCAM ) , serum amyloid A ( SAA ) , and interleukin 6 ( IL-6 ) were measured in archived plasma sample s from 2 multicenter , r and omized , double-blind , placebo-controlled studies design ed to examine the lipid-altering efficacy of simvastatin in study subjects with elevated TGs . In the first study , 130 study subjects with mixed hyperlipidemia ( low-density lipoprotein [ LDL ] cholesterol > or = 130 mg/dl ; TGs 300 to 700 mg/dl ) received placebo or simvastatin 40 or 80 mg once daily for three 6-week periods in a complete-block crossover design . In the second study , 195 study subjects with hypertriglyceridemia ( TGs 300 to 900 mg/dl ) received daily doses of placebo or simvastatin 20 , 40 , or 80 mg for 6 weeks . Significant but weak correlations were observed between baseline CRP values and baseline levels of LDL cholesterol and high-density lipoprotein ( HDL ) cholesterol , but not with TGs . CRP was also correlated with body mass index and fasting levels of glucose and insulin . Treatment with simvastatin 20 , 40 , and 80 mg led to significant reductions in CRP plasma levels versus placebo ( p < 0.05 ) . Although CRP change was weakly correlated with changes in LDL cholesterol , TGs , and HDL cholesterol , results of regression analyses showed that only baseline CRP and treatment allocation were significant predictors of CRP response after 6 weeks of study drug administration . Simvastatin had no effect on VCAM , SAA , or IL-6 . In summary , simvastatin significantly reduced CRP in patients with mixed hyperlipidemia and hypertriglyceridemia OBJECTIVES This study sought to investigate potential protective effects of atorvastatin in patients with acute coronary syndromes ( ACS ) undergoing percutaneous coronary intervention ( PCI ) . BACKGROUND R and omized studies have shown that pretreatment with atorvastatin may reduce periprocedural myocardial infa rct ion in patients with stable angina during elective PCI ; however , this therapy has not been tested in patients with ACS . METHODS A total of 171 patients with non-ST-segment elevation ACS were r and omized to pretreatment with atorvastatin  ( 80 mg 12 h before PCI , with a further 40-mg preprocedure dose [ n = 86 ] ) or placebo ( n = 85 ) . All patients were given a clopidogrel 600-mg loading dose . All patients received long-term atorvastatin treatment thereafter ( 40 mg/day ) . The main end point of the trial was a 30-day incidence of major adverse cardiac events ( death , myocardial infa rct ion , or unplanned revascularization ) . RESULTS The primary end point occurred in 5 % of patients in the atorvastatin arm and in 17 % of those in the placebo arm ( p = 0.01 ) ; this difference was mostly driven by reduction of myocardial infa rct ion incidence ( 5 % vs. 15 % ; p = 0.04 ) . Postprocedural elevation of creatine kinase-MB and troponin-I was also significantly lower in the atorvastatin group ( 7 % vs. 27 % , p = 0.001 and 41 % vs. 58 % , p = 0.039 , respectively ) . At multivariable analysis , pretreatment with atorvastatin conferred an 88 % risk reduction of 30-day major adverse cardiac events ( odds ratio 0.12 , 95 % confidence interval 0.05 to 0.50 ; p = 0.004 ) . CONCLUSIONS The ARMYDA-ACS trial indicates that even short-term pretreatment with atorvastatin may improve outcomes in patients with ACS undergoing early invasive strategy . These findings may support routine use of high-dose statins before intervention in patients with ACS 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 To determine the effects of statins on vascular function , inflammation , and and rogen levels in women with polycystic ovary syndrome ( PCOS ) , we r and omized 20 women with PCOS who had low-density lipoprotein cholesterol levels > 100 mg/dL to  atorvastatin ( 40 mg/day ) or  placebo  for 6 weeks and found that atorvastatin reduced and rogen levels , biomarkers of inflammation , and blood pressure ; increased insulin levels and brachial artery conductance during reactive hyperemia ; and failed to improve brachial artery flow-mediated dilation . We conclude that until additional studies demonstrate a clear risk-to-benefit ratio favoring statin therapy in PCOS , statins should only be used in women with PCOS who meet current indications for statin treatment Endothelial dysfunction is frequently found in diabetic subjects . This study was performed to investigate whether atorvastatin therapy was able to reverse endothelial dysfunction in type 2 diabetes and , if so , whether the effect was due to its antiinflammatory action . Eighty patients ( baseline low density lipoprotein , 4.37 + /- 0.71 mmol/liter ) were r and omized to atorvastatin ( 10 mg daily for 3 months , followed by 20 mg daily for 3 months ) or placebo in a double blind study . Endothelial function was assessed by high resolution vascular ultrasound , and high sensitivity C-reactive protein ( CRP ) was assessed by immunoturbidimetric assay . Diabetic patients had higher CRP ( P < 0.01 ) than matched nondiabetic controls , and both endothelium-dependent and independent vasodilation were impaired ( P < 0.01 ) . Atorvastatin ( 10 and 20 mg ) lowered plasma cholesterol by 32.9 % and 38.0 % , triglyceride by 15.4 % and 23.1 % , and low density lipoprotein by 43.4 % and 50.1 % , respectively . At 6 months , plasma CRP decreased in the atorvastatin group compared with baseline ( P < 0.05 ) . Endothelium-dependent vasodilation improved in the atorvastatin group compared with the placebo group ( P < 0.05 ) . The percent change in endothelium-dependent vasodilation at 6 months correlated with the percent change in CRP ( r = -0.44 ; P < 0.05 ) , but not with changes in plasma lipids . In conclusion , treatment with atorvastatin in type 2 diabetes led to a significant improvement in endothelium-dependent vasodilation , which might be partly related to its anti-inflammatory effect BACKGROUND Inflammation promotes acute coronary syndromes ( ACS ) and ensuing clinical complications . It is well known that statins decrease the risk of coronary events and may benefit the stabilization of atherosclerotic plaque with their anti-inflammatory effects . We investigated the effects of different doses of fluvastatin on serum concentrations of high-sensitive C-reaction protein ( hs-CRP ) and tumor necrosis factor-alpha ( TNF-alpha ) in the early phase of ACS . METHODS We prospect ively r and omized 60 patients with ACS to 3 groups : ( 1 ) group A ( n=20 ) : were given routine therapy ; ( 2 ) group B ( n=20 ) : were administrated routine therapy with 40 mg/d oral fluvastatin ;  ( 3 ) group C ( n=20 ) : received routine therapy with 80 mg/d oral fluvastatin .  Twenty patients with stable coronary heart disease served as controls . The following-up period was 7 days . By immunoturbidimetric assay and ELISA methods the serum concentrations of hs-CRP and TNF-alpha were measured before and after therapy . RESULTS ( 1 ) The serum concentrations of hs-CRP and TNF-alpha in patients with ACS was significantly higher than those in the control group ( P<0.05 ) . ( 2 ) After 1 week of therapy , the serum concentrations of hs-CRP and TNF-alpha were significantly lower in group B and group C ( all P<0.01 ) , especially in group C. ( 3 ) The serum concentrations of hs-CRP and TNF-alpha did not correlate to the concentrations of TC , TG , LDL-C , or HDL-C. CONCLUSION Early fluvastatin intervention decreases dose-dependently the serum concentrations of hs-CRP and TNF-alpha of patients with ACS . The high-dose fluvastatin invention may play a stronger anti-inflammatory effect in ACS patients . The anti-inflammatory effect of fluvastatin may be beyond the lipid lowering BACKGROUND Mixed hyperlipidemia is characterized by elevated low-density lipoprotein cholesterol ( LDL-C ) , triglyceride ( TG ) , and TG-rich lipoprotein levels . METHODS In a multicenter , r and omized , double-blind , placebo-controlled , parallel arm trial , eligible patients were 18 to 79 years of age , with mixed hyperlipidemia ( LDL-C 130 - 220 mg/dL , TG 150 - 500 mg/dL ) . Patients with type 2 diabetes were limited to those with LDL-C of 100 to 180 mg/dL. Patients ( N = 611 ) were r and omized in a 3:3:3:1 ratio to one of 4 treatment arms for 12 weeks : ezetimibe/simvastatin 10/20 mg ( EZE/SIMVA ) + fenofibrate 160 mg ( FENO ) , EZE/SIMVA 10/20 mg , FENO 160 mg , or placebo . The primary objective was to evaluate the LDL-C-lowering efficacy of EZE/SIMVA + FENO versus FENO monotherapy . RESULTS Low-density lipoprotein cholesterol level was significantly ( P < .05 ) reduced with EZE/SIMVA + FENO ( -45.8 % ) compared with FENO ( -15.7 % ) or placebo ( -3.5 % ) , but not when compared with EZE/SIMVA ( -47.1 % ) . High-density lipoprotein cholesterol and apolipoprotein A-I levels were significantly increased with EZE/SIMVA + FENO ( 18.7 % and 11.1 % , respectively ) treatment compared with EZE/SIMVA ( 9.3 % and 6.6 % ) or placebo ( 1.1 % and 1.6 % ) , but not when compared with FENO ( 18.2 % and 10.8 % ) . Triglyceride , non-high-density lipoprotein cholesterol , and apolipoprotein B levels were significantly reduced with EZE/SIMVA + FENO ( -50.0 % , -50.5 % , and -44.7 % , respectively ) versus all other treatments . Treatment with EZE/SIMVA + FENO was generally well tolerated with a safety profile similar to the EZE/SIMVA and FENO therapies . CONCLUSIONS Coadministration of EZE/SIMVA + FENO effectively improved the overall atherogenic lipid profile of patients with mixed hyperlipidemia . Clinical trial registry number : NCT 00093899 ( http://www . Clinical Trials.gov ) The role of inflammation in acute coronary syndrome ( ACS ) and the mechanism by which statin treats ACS is explored . Serum high-sensitivity C-reactive protein ( hs-CRP ) and interleukin-6 ( IL-6 ) levels were measured in 50 patients with ACS [ including 30 cases with unstable angina ( UA ) and 20 patients with acute myocardial infa rct ion ( AMI ) ] , 34 patients with stable angina ( SA ) , and 30 controls . Patients in the ACS group were r and omly assigned to a simvastatin group ( including a simvastatin AMI subgroup , n = 11 and a simvastatin UA subgroup , n = 14 ) and a routine group ( including a routine AMI subgroup , n = 9 and a routine UA subgroup , n = 16 ) . The simvastatin group was given simvastatin 20 mg/day and the routine group a placebo . After a 3-week follow-up , serum hs-CRP , IL-6 levels , and serum lipid concentrations were measured again . Both serum IL-6 and hs-CRP levels were significantly higher in the ACS group ( including the UA and AMI subgroups ) than in the SA and control groups ( P < 0.001 ) . After 3 weeks of treatment with simvastatin , the serum IL-6 , hs-CRP , total cholesterol , and low-density lipoprotein cholesterol levels were decreased significantly in the simvastatin group ( P < 0.001 ) , but no significant changes were observed in the routine group . No relationship was observed between the rate of decrease of serum IL-6 or hs-CRP and serum lipids levels . The hs-CRP level showed a significant correlation with IL-6 by Spearman ’s rank correlation analysis ( P < 0.01 ) . Inflammation plays an important role in the initiation of ACS . Simvastatin possesses an anti-inflammatory effect , independent of its lipid-lowering action , which may play an important role in the early treatment of ACS BACKGROUND The increase in serum C-reactive protein ( CRP ) levels is an independent determinant of cardiovascular events in long-term hemodialysis ( HD ) patients . Recently , statins have shown anti-inflammatory properties in addition to their lipid-lowering effect . METHODS We design ed a 6-month , prospect i ve , r and omized , controlled study to assess the safety and efficacy of atorvastatin in reducing serum CRP levels in long-term HD patients . Patients on HD therapy for at least 6 months , with autologous vascular access , were included . Patients presenting with illnesses and /or use of drugs that may affect CRP levels were excluded . After r and omization , group A included 16 patients treated with atorvastatin ( 10 mg/d orally ) , and group B included 17 patients treated with placebo .  Body mass index , Kt/V , normalized protein catabolic rate , mean blood pressure , and levels of hemoglobin , serum CRP , albumin , creatinine , lipids , and enzymes were recorded at baseline and after 6 months . RESULTS Qualitative/quantitative parameters were homogeneous between the groups at baseline . In group A , median serum CRP levels decreased from 9 mg/L ( range , 5 to 22 mg/L ) at baseline to 5 mg/L ( range , 3 to 16 mg/L ) after 6 months ( P = 0.004 ) . In group B , values were 8 mg/L ( range , 4 to 14 mg/L ) at baseline and 7 mg/L ( range , 3 to 17 mg/L ) after 6 months ( P = 0.98 ) . Serum CRP levels were lower in group A than group B at month-4 ( 5 mg/L ; range , 3 to 11 mg/L versus 7 mg/L ; range , 3 to 10 mg/L , respectively ; P = 0.054 ) and month-6 evaluations ( 5 mg/L ; range , 3 to 16 mg/L versus 7 mg/L ; range , 3 to 17 mg/L , respectively ; P = 0.060 ) . After 6 months , only in group A was there a significant decrease in serum cholesterol levels ( P = 0.041 ) and a significant increase in serum albumin levels ( P = 0.004 ) . Enzyme levels were stable during the study in both groups . CONCLUSION Administration of atorvastatin is safe in patients on long-term HD therapy and , in addition to its beneficial effects on lipid levels , induces a significant decrease in serum CRP levels , with a consequential increase in serum albumin  levels STUDY OBJECTIVES To determine the effects of atorvastatin on low-density lipoprotein cholesterol ( LDL ) particle size and C-reactive protein ( CRP ) concentrations in patients undergoing long-term hemodialysis . Another objective was to compare the effects of atorvastatin on lipoprotein profiles as determined by direct versus indirect assessment of lipoprotein composition . DESIGN R and omized , parallel-group sub study . SETTING Two university-affiliated outpatient hemodialysis centers . PATIENTS Nineteen patients with LDL levels above 100 mg/dl and with at least two cardiovascular risk factors . INTERVENTION Patients were r and omized in a 1:1 ratio to atorvastatin 10 mg/day or no treatment ( control ) for 20 weeks . MEASUREMENTS AND MAIN RESULTS We compared the differences between LDL particle size and CRP levels at baseline and 20 weeks in the atorvastatin versus control groups . Baseline demographic characteristics were similar between the two groups . Atorvastatin therapy was associated with no change in mean LDL particle size ( p=0.23 ) and with a 90 % decrease in mean CRP level ( p=0.52 ) . When evaluated by st and ard chemical analysis , atorvastatin therapy reduced total cholesterol levels by 29 % ( p=0.025 ) and result ed in nonsignificant reductions in LDL , high-density lipoprotein cholesterol , and triglyceride levels . Treatment with atorvastatin was not associated with significant changes in lipoprotein profile as determined by nuclear magnetic resonance ( NMR ) spectroscopy . CONCLUSION Treatment with atorvastatin did not affect LDL particle size but was associated with a sizable , yet nonsignificant , reduction in CRP concentrations . The drug had variable effects on lipoprotein concentrations as determined by chemical and NMR analytical methods . A larger study is necessary to provide definitive information on the effects of atorvastatin on LDL phenotype and CRP in patients with kidney disease BACKGROUND AND AIMS Inflammation is highly prevalent in patients on dialysis .  Statins have anti-inflammatory actions but their use has been scarcely studied in continuous ambulatory peritoneal dialysis ( CAPD ) . We undertook this study to compare the effect of pravastatin vs. placebo on the serum concentrations of C-reactive protein ( CRP ) in patients on CAPD . METHODS In a double-blind , controlled and crossover clinical trial , 76 CAPD patients were r and omized to either pravastatin or placebo for 2 months . After this first period of treatment , patients had a 1-month wash-out period and , finally , they were crossed-over to receive the other drug ( or placebo ) for 2 more months . Measurement of clinical and biochemical variables and CRP was performed at the beginning and at the end of each treatment period . RESULTS Median CRP was only significantly decreased in the pravastatin group in both periods of treatment : first period ( baseline vs. final , mg/L ) : pravastatin 7.4 ( 2 - 21 ) vs. 2.6 ( 1 - 6 ) , p < 0.05 ; placebo 3.9 ( 2 - 10 ) vs. 6.8 ( 3 - 12 ) , pNS ; second period : pravastatin 4.3 ( 2 - 15 ) vs. 1.9 ( 1 - 7 ) , p < 0.05 ; placebo 4.9 ( 2 - 17 ) vs. 6.8 ( 2 - 19 ) , p < 0.05 . Results were significantly different ( p < 0.05 ) between groups only at the end of each treatment period . Additionally , total and LDL-cholesterol significantly decreased in the pravastatin group . CONCLUSIONS Pravastatin significantly reduced serum levels of CRP and total and LDL-cholesterol compared to placebo . This treatment may be of great help to decrease the inflammatory status and probably the cardiovascular disease of CAPD patients Stabilization of carotid artery plaques by pharmacologic intervention is a promising strategy for the prevention of ischemic stroke . In this study , we examined the effect of 12 months of statin therapy on carotid plaque echogenicity . This study included 81 hypercholesterolemic patients with carotid atherosclerotic plaques . Echogenicity of the largest plaque in each patient was evaluated by ultrasound with integrated backscatter analysis . All patients underwent dietary modification . Forty patients were treated with simvastatin ( 10 mg/day , n = 24 ) or atorvastatin ( 5 mg/day , n = 16 ) according to the choice by each attending physician . Carotid plaques were monitored by measuring plaque thickness and echogenicity during a 12-month follow-up period . Levels of serum high-sensitivity CRP ( hs-CRP ) , interleukin (IL)-6 and IL-18 were determined in all patients . Total cholesterol , triglyceride , hs-CRP and IL-18 were significantly decreased after 12 months of statin therapy . The change in IL-6 level was not significant . Significant increases in echogenicity of carotid plaques and decreases in plaque thickness were noted after statin therapy . In the 41 patients without statin therapy  , carotid plaque echogenicity , plaque thickness and serum levels of inflammatory markers were not significantly altered . Our results suggest that statin therapy in hypercholesterolemic patients for 12 months increases carotid plaque echogenicity and decreases plaque thickness , in addition to lowering serum levels of lipids and inflammatory markers BACKGROUND AND AIMS Inflammation and postpr and ial lipemia are associated with increased cardiovascular disease . We investigated whether ezetimibe and simvastatin combination , a lipid lowering combination of simvastatin and ezetimibe , exerts an anti-inflammatory effect in the fasting state and after dairy cream intake . METHODS Twenty obese patients were r and omized to either ezetimibe and simvastatin combination or placebo treatment for 6 weeks . All patients were asked to ingest 33 ml of dairy cream ( 300 Calories ) at the beginning and at the end of intervention . Fasting and post-cream blood sample s were obtained . RESULTS At 0 week , ingestion of cream induced significant increases in MNC expression of IL-1β ( 105 ± 18 % ) , TNFα ( 97 ± 12 % ) , CD68 ( 48 ± 8 % ) , CD16 ( 141 ± 39 % ) , MMP-9 ( 122 ± 31 % ) , PECAM ( 66 ± 10 % ) , TLR-4 ( 84 ± 11 % ) and TLR-2 ( 67 ± 9 % ) and in endotoxin ( LPS ) concentrations ( 49 ± 7 % ) ( p < 0.05 ) . Ezetimibe and simvastatin combination treatment lowered fasting total cholesterol , LDLc and Lp(a ) concentrations and Apo B/A1 ratio and suppressed the MNC expression of IL-1β and CD68 ( by 21 ± 7 and 24 ± 10 , p < 0.05 ) and the concentrations of LPS , CRP , FFA and IL-18 by 24 ± 7 % , 32 ± 11 % , 19 ± 8 % 15 ± 4 % , respectively , ( p < 0.05 ) . Cream-induced increases in the expression of IL-1β , CD68 , CD16 , MMP-9 , TNFα and PECAM were reduced in the ezetimibe and simvastatin combination group by 74 ± 15 % , 68 ± 13 % , 57 ± 13 % , 64 ± 16 % , 67 ± 14 % and 45 ± 9 % , respectively , while those of LPS and MMP-9 concentrations were reduced by 53 ± 9 % and 38 ± 8 % , respectively , compared to the increases at week 0 ( p < 0.05 ) . There was a suppression of TLR-2 and TLR-4 expression by 21 ± 8 % and 18 ± 7 % , respectively , compared to 0-h baseline , after cream intake following ezetimibe and simvastatin combination treatment . CONCLUSIONS Ezetimibe and simvastatin combination exerts a profound anti-inflammatory effect both in the fasting state and acutely after the ingestion of saturated fat Objectives : A high loading dose of atorvastatin has been confirmed to reduce postprocedural events in patients undergoing percutaneous coronary intervention ( PCI ) . In this study , we sought to investigate the protective effects of rosuvastatin in patients with acute coronary syndromes ( ACS ) undergoing PCI and to determine the effect of rosuvastatin pretreatment on the postprocedural levels of high-sensitivity C-reactive protein ( hs-CRP ) , interleukin 6 ( IL-6 ) , and monocyte chemotactic protein 1 ( MCP-1 ) . Methods : A total of 125 patients with non-ST-segment elevation ACS were r and omized to pretreatment with rosuvastatin ( 20 mg 2 - 4 hours before PCI [ n = 62 ] ) or placebo ( n = 63 ) . All the patients received subsequent long-term rosuvastatin treatment ( 10 mg/d ) . The main end point of the trial was the 30-day incidence of major adverse cardiac events ( death , myocardial infa rct ion , or unplanned revascularization ) . Plasma levels of hs-CRP , IL-6 , and MCP-1 were detected before PCI and 6 hours , 24 hours , and 3 days after PCI . Results : The primary end point occurred in 8.1 % of the patients in the rosuvastatin arm and 22.2 % in the placebo arm ( P < .01 ) ; this difference was entirely attributed to a reduced incidence of myocardial infa rct ion ( 8.1 % vs 22.2 % ; P < .01 ) . The postprocedural elevation in creatine kinase-MB and troponin I was also significantly lower in the rosuvastatin group at 6 hours , 24 hours , and 3 days . Plasma levels of hs-CRP , IL-6 , and MCP-1 increased significantly after PCI in both the rosuvastatin and control groups ; however , the postprocedural elevations in hs-CRP and IL-6 levels were significantly lower in the rosuvastatin group than the control group . Conclusions : A single , high dose ( 20 mg ) of rosuvastatin prior to PCI reduces postprocedural myocardial injury in patients with ACS , with a concomitant attenuation of the postprocedural increase in hs-CRP and IL-6 levels OBJECTIVE This study aim ed to evaluate the effects of statin therapy on serum levels of antibodies to several specific heat shock proteins ( HSPs ) in dyslipidemic patients . DESIGN AND METHODS Participants ( n=102 ) were treated with simvastatin ( 40mg/day ) , or placebo in a r and omized , double-blind , placebo-controlled , cross-over trial . Anti-HSP60 , 65 , 70 , and hs-CRP levels were measured before and after each treatment period . Seventy-seven subjects completed the study . RESULTS Treatment with simvastatin was associated with significant reductions in serum anti-HSP60 , 65 , and 70 titers in the dyslipidemic patients ( 10 % , 14 % , and 15 % decrease , respectively ) ( p<0.001 ) . There have been previous reports of reductions in serum CRP with statin treatment , and although median CRP levels were 9 % lower on simvastatin treatment , this did not achieve statistical significance . CONCLUSION While it is unclear whether HSP antibodies are directly involved in atherogenesis , our findings suggest that simvastatin inhibits autoimmune responses that may contribute to the development of cardiovascular disease OBJECTIVE To compare the efficacy and safety of 10 mg of ezetimibe coadministered with simvastatin with the safety and efficacy of simvastatin monotherapy for patients with hypercholesterolemia . PATIENTS AND METHODS This multicenter double-blind , placebo-controlled , factorial study enrolled 887 patients with hypercholesterolemia ( low-density lipoprotein cholesterol [ LDL-C ] , 145 - 250 mg/dL ; triglycerides , < or = 350 mg/dL ) . Patients were r and omized to 1 of 10 treatments -- placebo , ezetimibe at 10 mg/d , simvastatin at 10 , 20 , 40 , or 80 mg/d , or simvastatin at 10 , 20 , 40 , or 80 mg/d plus ezetimibe at 10 mg/d for 12 weeks . The study began March 13 , 2001 , and ended January 8 , 2002 . The primary efficacy end point was the mean percent change in LDL-C levels from baseline to study end point ( last available postbaseline LDL-C measurement ) for the pooled ezetimibe/simvastatin group vs the pooled simvastatin monotherapy group . RESULTS Coadministration of ezetimibe/simvastatin was significantly ( P<.001 ) more effective than simvastatin alone in reducing LDL-C levels for the pooled ezetimibe/simvastatin vs pooled simvastatin analysis and at each specific dose comparison . The decrease in LDL-C levels with coadministration of ezetimibe and the lowest dose of simvastatin , 10 mg , was similar to the decrease with the maximum dose of simvastatin , 80 mg . A significantly ( P<.001 ) greater proportion of patients in the ezetimibe/simvastatin group achieved target LDL-C levels compared with those in the monotherapy group . Treatment with ezetimibe/simvastatin also led to greater reductions in total cholesterol , triglyceride , non-high-density lipoprotein cholesterol , and apolipoprotein B levels compared with simvastatin alone ; both treatments increased high-density lipoprotein cholesterol levels similarly . The safety and tolerability profiles for the ezetimibe/simvastatin and monotherapy groups were similar . CONCLUSION Through dual inhibition of cholesterol absorption and synthesis , coadministration of ezetimibe/simvastatin offers a highly efficacious and well-tolerated lipid-lowering strategy for treating patients with primary hypercholesterolemia OBJECTIVES This study examined the effect of statin therapy on vascular markers of inflammation and echocardiographic findings in patients with nonischemic forms of cardiomyopathy . BACKGROUND Despite advances in therapy , morbidity and mortality from heart failure ( HF ) remain high . We wished to determine whether treatment with atorvastatin affects left ventricular ( LV ) systolic function and markers of inflammation in patients with nonischemic HF . METHODS A total of 108 patients with nonischemic HF and a left ventricular ejection fraction ( LVEF ) < or = 35 % were r and omized to either atorvastatin 20 mg/day or placebo in a double-blinded fashion for a 12-month period . The LVEF and LV end-diastolic diameter ( LVEDD ) and left ventricular end-systolic diameter ( LVESD ) were determined by echocardiography . Serum markers of inflammation and oxidation were also measured . RESULTS The LVEF increased from 0.33 + /- 0.05 to 0.37 + /- 0.04 ( p = 0.01 ) in the atorvastatin group over the 12-month follow-up period , whereas those patients in the placebo group experienced a decline in ejection fraction during the same time period . In addition , LVEDD was reduced from 57.1 + /- 5.9 mm to 53.4 + /- 5.1 mm ( p = 0.007 ) and LVESD was reduced from 42.4 + /- 3.8 mm to 39.1 + /- 3.8 mm ( p = 0.02 ) in the cohort of patients treated with atorvastatin ; these dimensions increased in the placebo group . There was an increase in erythrocyte superoxide dismutase ( E-SOD ) activity , and there were significant reductions in serum levels of high sensitivity C-reactive protein , interleukin-6 ( IL-6 ) , and tumor necrosis factor-alpha receptor II ( TNF-alpha RII ) in the atorvastatin group . CONCLUSIONS The use of atorvastatin in patients with nonischemic HF improves LVEF and attenuates adverse LV remodeling . The effects on soluble levels of several inflammatory markers with atorvastatin suggest , in part , mechanisms by which statins might exert their beneficial effects in nonischemic HF A r and omized , crossover study compared the effects of atorvastatin , gemfibrozil and their combination on inflammatory markers in type 2 diabetes .  C-reactive protein ( CRP ) , lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) , secretory phospholipase A2 ( sPLA2 ) , interleukin 8 ( IL8 ) , monocyte chemotactic protein 1 ( MCP1 ) and tumor necrosis factor α ( TNFα ) were measured . Both lipid-lowering drugs had positive , complementary and additive effects on inflammatory markers , which were closely related to baseline inflammatory status Statins exert a number of anti-inflammatory and immunomodulatory effects in vitro . However , the immunomodulatory effects in vivo are less clarified . In the present study , we investigated whether simvastatin treatment changed the levels of autoantibodies against specific oxidized LDL ( oxLDL ) antigens as well as their association with leukocyte activation markers . Eighty volunteers with mild-to-moderate hypercholesterolemia were r and omized to either simvastatin 40 mg or placebo for 6 weeks . Autoantibodies against apo B peptide antigens , C-reactive protein ( CRP ) and interleukin (IL)-6 in plasma were determined by ELISA . Subsets of circulating B and T cells were studied by flow cytometry . Simvastatin significantly reduced CRP by 26 % , whereas IL-6 remained unchanged . Levels of IgG against the apo B peptide P-240 ( amino acids 3586–3605 ) increased by 16 % ( p = 0.03 ) in the simvastatin group whereas autoantibody levels to other apo B peptides did not change . At baseline and after 6 weeks , the P-240 IgG levels were significantly correlated with the number of CD57+CD28 − CD8+T cells but not to other lymphocyte subsets or inflammatory markers . The P-240 IgG levels after 6 weeks simvastatin therapy was strongly correlated to the relative increase in CD57+CD28 − CD8+T cells ( p = 0.003 ) . Simvastatin treatment induced an increase in autoantibodies against an oxLDL antigen . The effect was related to an expansion of a CD8+T cell subset and may involve an immunostimulation by simvastatin Objective . Increased serum pro-inflammatory cytokine levels are associated with an increased mortality rate in end-stage renal disease ( ESRD ) patients .  Statins decrease cardiovascular mortality and serum C-reactive protein ( CRP ) levels in hemodialysis patients . As the anti-inflammatory effect of statins has not previously been studied in peritoneal dialysis ( PD ) patients with a non-inflammatory status , we wanted to investigate the anti-inflammatory effect of simvastatin in these patients . Material and methods . Forty-eight PD patients were r and omly allocated to either simvastatin treatment ( n=25 ) or placebo ( n=23 ) . Patients in the active-treatment group received simvastatin 20mg/day for 1 month . At baseline and after 1 month of treatment , blood sample s were drawn and high-sensitivity CRP , interleukin-6 , tumor necrosis factor (TNF)-α and plasma lipid profiles were determined . These parameters were compared between the groups at baseline and at the end of the study period . Results . Twenty-five subjects in the treatment group and 20 in the placebo group completed the study . Three patients in the placebo group were excluded from the study due to the occurrence of bacterial peritonitis during the study period . Clinical characteristics and baseline parameters were similar in both groups . Serum total and low-density lipoprotein cholesterol levels , and triglyceride and serum TNF-α levels decreased significantly compared to baseline in the treatment group ; there were no corresponding differences in the placebo group . Conclusions . Simvastatin decreased the serum TNF-α level in PD patients with a non-inflammatory status . A decrease in the TNF-α level could be one of the possible mechanisms of the anti-atherogeneic effect of simvastatin . We suggest that different treatment strategies aim ed at decreasing serum cytokine levels could be evaluated to decrease cardiovascular morbidity and mortality in the dialysis population We have investigated the effect of atorvastatin on the endothelial function of patients with diabetes and subjects at risk for type 2 diabetes in a 12-wk , prospect i ve , r and omized , placebo-controlled , double-blind clinical trial . The flow- mediated dilation ( FMD ; endothelium dependent ) and nitroglycerin-induced dilation ( endothelium independent ) in the brachial artery and the vascular reactivity at the forearm skin were measured . FMD improved in the atorvastatin-treated , at-risk subjects [ median ( 25 - 75 percentile ) , 7.2 % ( 2.9 - 9.6 % ) at exit visit vs. 6.6 % ( 2.9 - 9.5 % ) at baseline ; P < 0.05 ] . A similar improvement of FMD was found in atorvastatin-treated  diabetic patients [ median ( 25 - 75 percentile ) , 5.6 ( 3.9 - 7.9 ) at exit visit vs. 4.2 ( 3.2 - 7.2 ) at baseline ; P = 0.07 ] . No changes were observed in nitroglycerin-induced dilation and the microcirculation reactivity measurements in either group . In the at-risk group , there was a decrease in the C-reactive protein [ median ( 25 - 75 percentile ) , 0.12 mg/dl ( 0.07 - 0.27 mg/dl ) at exit visit vs. 0.24 mg/dl ( 0.07 - 0.35 mg/dl ) at baseline ; P < 0.05 ] and TNF alpha [ median ( 25 - 75 percentile ) , 2.6 pg/ml ( 1.8 - 4.1 pg/ml ) at exit visit vs. 4.4 pg/ml ( 3.6 - 6.0 pg/ml ) at baseline ; P < 0.05 ] in the atorvastatin-treated patients , whereas in the diabetes group , a decrease in endothelin-1 ( mean + /- SD , 0.97 + /- 0.29 pg/ml at exit visit vs. 1.19 + /- 0.42 pg/ml at baseline ; P < 0.05 ) and plasminogen activator inhibitor-1 [ median ( 25 - 75 percentile ) , 18 ng/ml ( 9 - 24 ng/ml ) at exit visit vs. 27 ng/ml ( 7 - 41 ng/ml ) at baseline ; P < 0.05 ] were observed . We conclude that atorvastatin improves endothelial function and decreases levels of markers of endothelial activation and inflammation 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 BACKGROUND Inflammation may contribute to the high cardiovascular risk in diabetes mellitus ( DM ) and chronic kidney disease ( CKD ) . Monocyte chemoattractant protein-1 ( MCP-1 ) facilitates the recruitment of monocytes into atherosclerotic lesions and is involved in diabetic nephropathy . Interferon gamma ( IFNγ ) is important in atherosclerosis and increases the synthesis of chemokines including MCP-1 . Lipid-lowering treatment ( LLT ) with statins may have anti-inflammatory effects , and ezetimibe cotreatment provides additional cholesterol lowering . METHODS After a placebo run-in period , the effects of simvastatin alone ( S ) or simvastatin + ezetimibe ( S+E ) were compared in a r and omized , double-blind , cross-over study on inflammatory parameters . Eighteen DM patients with estimated glomerular filtration rate ( eGFR ) 15 - 59 mL/min × 1·73 m(2 ) ( CKD stages 3 - 4 ) ( DM-CKD ) and 21 DM patients with eGFR > 75 mL/min ( DM only ) were included . RESULTS At baseline , monocyte chemoattractant protein 1 ( MCP-1 ) ( P = 0·03 ) , IFNγ ( P = 0·02 ) , tumour necrosis factor-α ( TNFα ) ( P < 0·01 ) and soluble vascular adhesion molecule ( sVCAM ) ( P = 0·001 ) levels were elevated in DM-CKD compared with DM-only patients . LLT with S and S+E reduced MCP-1 levels ( P < 0·01 by anova ) and IFNγ levels ( P < 0·01 ) in DM-CKD patients but not in DM-only patients . Reductions were most pronounced with the combination treatment . CONCLUSIONS DM patients with CKD stages 3 - 4 had increased inflammatory activity compared with DM patients with normal GFR . Lipid-lowering treatment decreased the levels of MCP-1 and IFNγ in DM patients with concomitant CKD , which may be beneficial with regard to the progression of both atherosclerosis and diabetic nephropathy BACKGROUND Contrast media cause oxidative stress , which has been suggested as one possible mechanism responsible for contrast-induced nephropathy . Statins appear to have pleiotropic effects , including antioxidant properties . We investigated to determine whether simvastatin pretreatment reduces the risk of contrast-induced nephropathy in a high-risk population of patients with renal insufficiency undergoing coronary angiography . METHODS We conducted a prospect i ve , r and omized , double-blind , placebo-controlled , 2-center trial , involving 247 consecutive patients with chronic renal insufficiency ( calculated creatinine clearance < or = 60 mL/min and /or serum creatinine > or = 1.1 mg/dL ) undergoing coronary angiography .  Patients were r and omized to  simvastatin  ( n = 124 ; 160 mg total , 40 mg orally every 12 hours starting the evening before and ending the morning after the procedure ) or placebo ( n = 123 ) . All patients received pre - and postprocedure hydration . The iso-osmolar contrast agent iodixanol was used for coronary angiography in all patients . RESULTS There was no difference between simvastatin and placebo in mean peak increase in serum creatinine measured within 48 hours after coronary angiography , the primary study end point ( 0.002 + /- 0.164 vs 0.017 + /- 0.230 mg/mL respectively , P = .559 ) . The incidence of contrast-induced nephropathy , a secondary end point defined as increase of either > or = 25 % or > or = 0.5 mg/dL in serum creatinine , was 2.5 % in simvastatin-treated patients ( 3/118 ) and 3.4 % in placebo-treated patients ( 4/118 ) , a nonsignificant difference ( P = 1.00 ) . There were also no differences between the 2 groups in length of hospital stay or 1- and 6-month clinical outcomes . CONCLUSIONS Simvastatin pretreatment for short-term at high dose do not prevent renal function deterioration after administration of contrast medium in patients with baseline renal insufficiency undergoing coronary angiography Objectives The aim of this work was to investigate the efficacy and safety of loading-dose rosuvastatin therapy in elderly patients with non-ST-segment elevation acute coronary syndromes ( NSTEACS ) undergoing elective percutaneous coronary intervention ( PCI ) . Methods A total of 126 patients ( ≥70 years old ) with NSTEACS were r and omly divided into two groups : ( 1 ) loading-dose rosuvastatin-treated group , treated with rosuvastatin 20 mg 12 h prior to PCI , with a second dose administered just before PCI ( n = 62 ) , and ( 2 ) control-treated group , treated with the st and ard method according to ACC/AHA guidelines in UAP/NSTEMI 2007 ( n = 64 ) . All patients were required to take rosuvastatin 10 mg once a day starting 24 h after the surgery irrespective of the initial r and omization assignment . The serum soluble lectin-like oxidized low-density lipoprotein receptor-1 ( sLox-1 ) , high-sensitivity C-reactive protein ( hs-CRP ) , creatinine kinase (CK)-MB , cardiac troponin I ( cTnI ) , and brain natriuretic peptide ( BNP ) levels were measured prior to PCI and at 24 h and 30 days after PCI in both groups . The left ventricular ejection fraction ( LVEF ) levels were recorded prior to PCI and 30 days after PCI in both groups . Results Compared to pre-PCI , the serum sLox-1 , hs-CRP , CK-MB , and cTnI levels were increased at 24 h after PCI ( all p < 0.05 ) in both groups . However , the increased sLox-1 , hs-CRP , CK-MB , and cTnI values were significantly lower in the loading-dose rosuvastatin-treated group than in the control-treated group ( p < 0.05 ) . In addition the serum sLox-1 and hs-CRP levels were lower in the loading-dose rosuvastatin-treated group than in the control-treated group at 30 days after PCI . However , the decreased values of sLox-1 and hs-CRP from 24 h after PCI to 30 days after PCI did not show any significant difference between the two groups . No significant difference was found in the serum ALT and Scr levels between the two groups before and after PCI . Compared to the control-treated group , the serum BNP level decreased ( p < 0.05 ) and LVEF ( p < 0.05 ) increased in the loading-dose rosuvastatin-treated group at 30 days after PCI . Conclusion The loading-dose rosuvastatin therapy in elderly patients with non-ST-segment elevation acute coronary syndromes undergoing elective PCI can attenuate the increase in serum hs-CRP , sLox-1 , CK-MB , and cTnI levels , reduce myocardial injury and inflammatory reaction caused by PCI , and improve the LVEF level at 30 days after PCI , ensuring an effective and safe therapy Although substantial evidence suggests that treatment of dyslipidemia with statins reduces mortality and morbidity that are associated with cardiovascular disease , only a few studies have examined the efficacy of statins on inflammatory and fibrinolytic status in patients with chronic kidney disease ( CKD ) . A 6-mo , prospect i ve , r and omized study was design ed to assess the efficacy of atorvastatin in reducing circulating inflammatory and fibrinolytic parameters in patients with CKD . Sixty-six patients with CKD ( stages 2 , 3 , and 4 ) and LDL cholesterol levels > or = 100 mg/dl were r and omly assigned ( 2:1 ) to receive 20 mg/d atorvastatin ( n = 44 ) or nonatorvastatin therapy ( n = 22 ) . Lipid profile , renal function , fibrinolytic balance ( tissue plasminogen activator [ t-PA ] and plasminogen activator inhibitor-1 ) , and inflammatory markers ( C-reactive protein [ CRP ] , IL-1 beta , IL-6 , and TNF-alpha ) were measured before and 6 mo after atorvastatin was added to the treatment . Twenty-five age-matched individuals with normal renal function ( estimated GFR > 90 ml/min ) were used as healthy control subjects . Patients with CKD had higher CRP , IL-1 beta , TNF-alpha , and IL-6 levels than age-matched population with normal renal function . t-PA concentration was higher in patients with CKD ( P = 0.000 ) . Plasminogen activator inhibitor-1 values were comparable in all patients . Total cholesterol and LDL cholesterol were significantly reduced only in patients who received atorvastatin . In addition to the hypolipidemic effect , atorvastatin treatment significantly reduced inflammatory parameters : CRP ( median 4.1 to 2.9 ; P = 0.015 ) , TNF-alpha ( 6.0 + /- 2.7 to 4.7 + /- 2.4 ; P = 0.046 ) , and IL-1 beta levels ( 1.9 + /- 0.7 to 1.2 + /- 0.7 ; P = 0.001 ) . These parameters remained unchanged in patients who were not treated with atorvastatin . Fibrinolytic parameters were not modified by atorvastatin treatment . Patients with CKD showed higher levels of inflammatory parameters and t-PA levels than age-matched healthy control subjects . Atorvastatin treatment , in addition to its beneficial effect on cholesterol levels , improved the inflammatory state of these patients without modifying fibrinolytic balance Atherosclerosis is currently considered a chronic inflammatory disease of the vessel wall . Systemic markers of inflammation have been shown to be of significant prognostic relevance for assessing the risk of atherosclerotic disease progression (1)(2)(3)(4 ) . Previous data showed that proinflammatory markers , such as C-reactive protein ( CRP ) , play an important role in acute coronary events (5)(6)(7 ) and that decreased plasma concentrations of antiinflammatory cytokines , for example , interleukin-10 ( IL-10 ) were also associated with acute coronary syndrome ( ACS ) (8)(9)(10 ) . Statins , 3-hydroxy-3-methyglutaryl-coenzyme A reductase inhibitors , represent a well-established class of drugs that effectively lower serum cholesterol concentrations and are widely used for the treatment of cardiovascular disease (11)(12)(13 ) . In addition to their cholesterol-lowering activity , statins have been demonstrated to possess pleiotropic effects , including antiinflammatory effects (14)(15)(16)(17 ) . Results obtained in numerous investigations have suggested that administration of statins could modify concentrations of CRP and other proinflammatory cytokines with a concurrent decrease in cardiovascular events . However , the potential influence of statins on the antiinflammatory cytokine IL-10 in patients with ACS has not been investigated . In the present study , 42 patients with unstable angina ( UA ) were r and omly assigned immediately after admission to st and ard therapy  plus either 20 mg/day atorvastatin or placebo . The st and ard therapy included aspirin , beta-blockers , heparin/low – molecular-weight heparin , angiotensin-converting enzyme inhibitors , and oral nitrates . The protocol s of the study were approved by the Ethics Review Board of the Hospital , and all patients gave written , informed consent . The patients with UA presented with  ischemic chest pain  at rest in the absence of extracardiac cause with ST-segment depression ≥0.1 mV in 2 or more contiguous leads on 12-lead electrocardiograms at administration . Echocardiography was performed in all patients to exclude patients with an impaired left BACKGROUND Patients on regular hemodialysis present high cardiovascular mortality . Uremic dyslipidemia and inflammation take part in the etiology of atherosclerosis . Rosuvastatin calcium has not been studied in patients on dialysis to date . We sought to evaluate the results of rosuvastatin therapy regarding lipids , lipoproteins and a marker of inflammation in hemodialysis patients . METHODS In a double-blind r and omized placebo-controlled trial , 59 patients on hemodialysis ( 31 in the placebo group , and 28 taking rosuvastatin 10 mg/day ) were followed for 3 months . Lipids , lipoproteins and high-sensitivity C-reactive protein ( hs-CRP ) were measured at baseline , 30 days and 3 months . RESULTS In the rosuvastatin group , there was a significant decrease from baseline to the study end in total cholesterol ( 163+/-53 mg/dL to 142+/-43 mg/dL ; p<0.05 ) , in LDL cholesterol ( 90+/-39 mg/dL to 69+/-32 mg/dL ; p<0.05 ) and in non-HDL cholesterol ( 121+/-46 mg/dL to 99+/-39 mg/dL ; p<0.05 ) . In the placebo group , no significant decrease was observed . High-sensitivity CRP was lower in the rosuvastatin than in the placebo group at 3 months ( p<0.01 ) . CONCLUSIONS Rosuvastatin calcium at 10 mg/day was effective in lowering total cholesterol , LDL cholesterol , non-HDL cholesterol and hs-CRP in hemodialysis patients AIMS Abnormalities of microvascular and endothelial function are present in subjects with Type 2 diabetes . Although statin therapy improves cardiovascular risk in diabetes , dyslipidaemia in diabetes may be more responsive to combined statin and fibrate therapy . We examined the effect of cerivastatin and fenofibrate on microvascular function in subjects with Type 2 diabetes with no clinical evidence of cardiovascular disease and near normal lipid levels . METHODS Age- , sex- , lipid- and blood pressure-matched subjects with Type 2 diabetes were r and omized in double-blind fashion to one of four treatment groups : group 1 placebo/placebo ( n=12 ) , group 2 fenofibrate/placebo ( n=10 ) , group 3 cerivastatin/placebo ( n=20 ) and group 4 cerivastatin/fenofibrate ( n=11 ) . The subjects were recruited from the Lipid in Diabetes Study .  Microvascular function was assessed by skin blood flow response to iontophoresis of acetylcholine and sodium nitroprusside and by skin maximum hyperaemia to local heating . Measurements were carried out at baseline and 3 months later . RESULTS Although all lipid parameters improved in groups 2 - 4 after 3 months ' therapy , no difference was detected in skin blood flow to iontophoresis or maximum hyperaemia in any of the groups . Highly sensitive c-reactive protein ( Hs-CRP ) did not change with therapy . CONCLUSIONS In conclusion , we were unable to demonstrate any improvement in microvascular endothelial function in non-hyperlipidaemic Type 2 diabetic subjects treated with single or combination lipid-lowering therapy PURPOSE The beneficial effect of rosuvastatin against percutaneous coronary intervention ( PCI ) related procedural myocardial injury has been determined mostly in patients with acute coronary syndromes ( ACS ) . However , the detailed therapeutic mechanism has not been well studied . METHODS Patients with ACS receiving PCI ( n = 159 ) were r and omized to control group ( placebo treatment ) or to rosuvastatin group ( 20 mg 12 h before PCI , and a further 20 mg 2 h preprocedure dose ) . Levels of INF-γ , TNF-α , IL-6 , miR-155/SHIP-1 , and CD4(+)FoxP3(+)Treg in peripheral blood were detected before PCI and 24 h after PCI . Clinical data of these patients were also collected in this prospect i ve study . RESULTS Compared with placebo , rosuvastatin treatment significantly reduced the incidence of periprocedural myocardial infa rct ion ( PMI ) and levels of cardiac troponin I ( cTnI ) associated with decreased relative expression of serum miR-155 , levels of inflammatory cytokines ( INF-γ , TNF-α , and IL-6 ) , increased SHIP-1 expression and CD4(+)FoxP3(+)Treg percentage values ( P < 0.05 ) . In addition , patients with rosuvastatin pretreatment also reduced incidence of 30 days major adverse cardiac events ( MACE ) compared to the patients with placebo treatment ( 16 patients vs. 28 patients , P = 0.038 ) . CONCLUSIONS Our study suggests that high loading dose rosuvastatin pretreatment may reduce the incidence of cardiovascular events and levels of inflammatory markers in patients with ACS receiving PCI , which may be explained at least in part , by mechanism involving suppression of miR-155/SHIP-1 signaling pathway Aims Type 1 diabetes mellitus patients with microalbuminuria have endothelial dysfunction associated with the degree of albuminuria but not with LDL‐cholesterol levels . Lipid‐lowering agents such as statins may still be of benefit as they can correct endothelial dysfunction by both lipid and non‐lipid mechanisms . We therefore examined the effects of atorvastatin on brachial artery endothelial dysfunction in these patients BACKGROUND C-reactive protein ( CRP ) levels are associated with cardiovascular risk . We assessed the hypothesis that atorvastatin might have anti-inflammatory effects in acute coronary syndromes ( ACS ) as shown by CRP reduction . METHODS This study was a prospect i ve , r and omized , double-blind , placebo-controlled study of 90 consecutive patients admitted within 48 hours of onset of ACS with CRP levels > or = 1.4 mg/dL. Patients were assigned to atorvastatin 40 mg daily or placebo over 30 days . C-reactive protein levels , lipid profiles , serum fibrinogen , white cell count , and erythrocyte sedimentation rate were measured at entry , hospital discharge , and 1 month later . RESULTS Baseline clinical characteristics did not differ between  atorvastatin and placebo groups ( mean age 59.3 + /- 13.4 vs 61.1 + /- 11.5 , P = ns ) ; myocardial infa rct ion 52.3 % versus 67.4 % ( P = ns ) . In both groups , median baseline CRP levels were comparable ( 5.97 + /- 6.2 vs 4.64 + /- 4.2 mg/dL , P = ns ) . C-reactive protein levels were lower in the atorvastatin group versus control group at discharge ( 1.68 + /- 1.65 vs 4.12 + /- 4.18 mg/dL ) and at 30 days ( 0.50 + /- 0.71 vs 2.91 + /- 2.68 mg/dL , both P < .0001 ) . C-reactive protein levels significantly decreased from baseline to discharge and 1 month later in placebo and atorvastatin groups ( both P < .0001 ) ; however , the reduction was greater in the atorvastatin group ( 62 % vs 11 % at discharge [ P < .0001 ] ; 84 % vs 30 % at 1 month [ P < .0001 ] ) . In addition , atorvastatin was associated with a reduction in total and low-density lipoprotein cholesterol and erythrocyte sedimentation rate at discharge and at 30 days ( P < .0001 for all comparisons ) . No correlation was found between changes in CRP and cholesterol levels . CONCLUSIONS C-reactive protein levels in ACS were rapidly reduced with atorvastatin . These data provide evidence that statins have fast and early anti-inflammatory effects in addition to lipid-lowering effects in ACS OBJECTIVE Although previous studies suggest that treatment of dyslipidemia with statins reduces mortality and morbidity that are associated with cardiovascular disease , only a few studies have examined the efficacy of statins on atherosclerotic status in patients with chronic kidney disease ( CKD ) . MATERIAL S AND METHODS A 12-month , prospect i ve , r and omized study was design ed to assess the efficacy of rosuvastatin in reducing circulating atherosclerotic parameters and renal function in patients with CKD . Thirty-eight patients with CKD and LDL cholesterol levels > or = 100 mg/dL were r and omly assigned to receive 2.5 mg/dL rosuvastatin ( group A , n=22 ) or nonrosuavastatin therapy ( group B , n=16 ) . Lipid profile , estimated glomerular filtration rate ( eGFR ) , high sensitivity C-reactive protein ( hs-CRP ) , and intima-media thickness ( IMT ) were measured before and 12 months after rosuvastatin was added to the treatment . RESULTS Total cholesterol , low-density lipoprotein cholesterol , remnant-like particle-cholesterol and triglycerides were significantly reduced only in patients who received rosuvastatin . These parameters remained unchanged in patients who were not treated with rosuvastatin .  eGFR was significantly increased from 50.7+/-18.7 mL/min/1.73 m(2 ) to 53.3+/-20.1 mL/min/1.73 m(2 ) and a significant reduction of U-P was detected in group A patients ( 0.17+/-0.29 vs. 0.13+/-0.3 g/day ; p<0.01 ) . In addition to the hypolipidemic effect , rosuvastatin treatment significantly reduced hs-CRP ( p=0.0054 ) . Moreover , maximal IMT at the baseline ( 1.89+/-0.98 mm ) decreased significantly to 1.75+/-0.87 mm at 12 months ( p=0.0231 ) . CONCLUSION Rosuvastatin treatment , in addition to its beneficial effect on cholesterol levels , reduced maximal IMT and modified the inflammatory state of these patients BACKGROUND The effects of statin therapy on the production of monocyte pro-inflammatory cytokines , cardiac function and the long-term prognosis in chronic heart failure ( CHF ) patients with dyslipidemia remain unclear . METHODS AND RESULTS A total of 146 CHF patients with a mean left ventricular ejection fraction ( LVEF ) of 26.9 ± 6.6 % were divided into 2 groups based on whether or not statins were included in their treatment : a statin group ( n=63 ) and a no statin group ( n=83 ) . Only patients with dyslipidemia were treated with statins . Peripheral blood mononuclear cells ( P BMC s ) were isolated , and the production of monocyte tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured at baseline and after 6 months of treatment , and the data expressed as mean ± SD ( pg·ml(-1)·10(-6 ) P BMC s ) . The LVEF in the statin group improved , and the monocyte TNF-α and IL-6 production decreased ( respectively , P<0.001 ) , but the LVEF and cytokine production remained unchanged in the no statin group . Multivariate Cox hazard analysis showed that statin therapy ( hazard ratio , 0.14 ; 95 % confidence interval : 0.02 - 0.97 , P=0.046 ) was an independent predictor of cardiac events . CONCLUSIONS Statin therapy attenuates the production of monocyte pro-inflammatory cytokines , and ameliorates the cardiac function and may improve long-term prognosis in CHF patients with dyslipidemia Anemia is a common clinical problem in end-stage renal disease ( ESRD ) . Despite adequate erythropoiesis-stimulating agent ( ESA ) supplementation , some ESRD patients still have suboptimal hemoglobin levels , and iron deficiency and inflammation are recognized as the two most common causes . Hepcidin , a newly discovered key regulator of iron homeostasis , is found to be accumulated in ESRD . As it controls iron uptake and release , better reflecting real-time iron dem and and availability , hepcidin might become a target in the management of iron deficiency and ESA resistance in dialysis patients . For their pleiotropic functions apart from lipid-modulation , statins are also used as anti-inflammatory or immune-modulating agents . In this study , we applied simvastatin for the purpose of influencing serum prohepcidin level in a group of maintenance hemodialysis patients . Thirty-three ESRD patients undergoing hemodialysis were enrolled and assigned to experimental and hemodialysis control groups according to their lipid profile . Nineteen healthy adults were chosen as a normal control group . The subjects in the experimental group took 20 mg simvastatin orally per night for eight weeks , and those in the hemodialysis control group took no statins or any other lipid-modulating drugs . Before and after the experiment , the serum prohepcidin concentrations , plasma IL-6 , and serum C-reactive protein ( CRP ) , ferritin , hemoglobin , albumin , total cholesterol , glycerinate , and LDL and HDL cholesterol levels were determined . Of the 33 hemodialysis patients , the serum prohepcidin concentration was ( 175.8 + /- 52.9 ) ng/mL , significantly higher than that in the normal control group ( 149.5 + /- 24.2 ) ng/mL ( P = 0.048 ) . In the experimental group , the serum prohepcidin level was ( 156.7 + /- 51.9 ) ng/mL before treatment , and ( 190.6 + /- 49.6 ) ng/mL after eight weeks ( P = 0.127 ) . In the hemodialysis control group , the serum prohepcidin level was ( 190.6 + /- 49.6 ) ng/mL at the beginning , and ( 193.5 + /- 36.0 ) ng/mL after eight weeks ( P = 0.728 ) . In the experimental group , after taking simvastatin for eight weeks the serum total cholesterol and triglyceride levels had lowered by 18.6 % ( P = 0.004 ) and 55.1 % ( P = 0.007 ) , respectively . The plasma IL-6 , serum CRP , ferritin , hemoglobin , albumin , and LDL and HDL cholesterol levels in both the hemodialysis group remained unchanged . According to our preliminary study , eight weeks of 20 mg simvastatin did not significantly change the serum prohepcidin , high-sensitive CRP , or IL-6 concentrations in the group of maintenance hemodialysis patients Abstract Background : Periprocedural myocardial infa rct ion ( MI ) is a common complication following percutaneous coronary intervention ( PCI ) and statins have been shown to reduce MI in statin-naïve patients . We aim ed to identify whether a high reloading dose of atorvastatin can prevent MI following PCI in patients who were already being treated with statins . Material and methods : In this triple-blind controlled r and omized clinical trial , 190 c and i date s for elective PCI , who were already using statins and /or other lipid lowering agents such as fibrates  , were r and omly assigned to two equal groups to receive either atorvastatin ( 80 mg ) or placebo within 24 hours before the procedure . Serum levels of creatinine kinase myocardial isoenzyme ( CK-MB ) , cardiac troponin I ( cTNI ) and high-sensitive C-reactive protein ( hs-CRP ) were measured at baseline and then 6 and 12 hours following PCI . Post-procedural MI was defined as troponin elevation > 5-fold in patients with normal baseline or > 20 % in those with elevated baseline measurements with or without chest pain or ST segment or T wave abnormalities . Results : Frequency of MI in the atorvastatin group was 3 ( 3.1 % ) vs. 10 ( 10.5 % ) in the placebo group ( p = 0.04 ) . The CK-MB rise within 6 hours following PCI was 0.6 ± 0.3 mg/dl in the intervention group versus 3.0 ± 1.6 mg/dl in the placebo group . Also , the levels of cTNI within 6 and 12 hours in the intervention group was significantly lower than the placebo group ( p = 0.01 and 0.008 , respectively ) . hs-CRP was significantly lower in the intervention group after 12 hours ( p = 0.004 ) . Conclusion : Administration of a high reloading dose of atorvastatin within 24 hours before PCI could significantly reduce the frequency of periprocedural MI . Clinical trial registration code : I RCT 201205209768N1
target: Our meta‐ analysis showed beneficial effects  of statin use  on reducing inflammatory markers in patients with MetS and related disorders
background: & NA ; Current evidence suggests that statin use decreases the incidence of cardiovascular diseases ( CVD ) through reducing LDL cholesterol and decreasing inflammation .
  Metabolic syndrome ( MetS ) is usually associated with increased inflammatory markers and increased risk of CVD .