title: Rosuvastatin in the Prevention of Stroke Among Men and Women With Elevated Levels of C-Reactive Protein: Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) Testing cognitive function in elderly populations: the PROSPER study An Economic Evaluation of Atorvastatin for Primary Prevention of Cardiovascular Events in Type 2 Diabetes Stroke prediction and stroke prevention with atorvastatin in the Collaborative Atorvastatin Diabetes Study (CARDS) Pravastatin for Cardiovascular Event Primary Prevention in Patients With Mild-to-Moderate Hypertension in the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events? 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The West of Scotland coronary prevention study: economic benefit analysis of primary prevention with pravastatin Fluvastatin and lifestyle modification for reduction of carotid intima-media thickness and left ventricular mass progression in drug-treated hypertensives. Once‐daily pravastatin in patients with primary hypercholesterolemia: A dose‐response study [Statin therapy for hypertensive patients]. Effects of atorvastatin on dyslipidaemia in uraemic patients on peritoneal dialysis. Primary prevention of cardiovascular diseases among hypercholesterolemic Japanese with a low dose of pravastatin. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH) Standard-dose statin therapy provides incremental clinical benefits in normocholesterolemic diabetic patients. Comparative efficacy study of atorvastatin vs simvastatin, pravastatin, lovastatin and placebo in type 2 diabetic patients with hypercholesterolaemia. Simvastatin in the treatment of asthma: lack of steroid-sparing effect A randomized trial of rosuvastatin in the prevention of venous thromboembolism. Baseline risk factors and their association with outcome in the West of Scotland Coronary Prevention Study. The West of Scotland Coronary Prevention Study Group. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial Effects of lovastatin on the immune system. Influence of pravastatin and plasma lipids on clinical events in the West of Scotland Coronary Prevention Study (WOSCOPS). Statin Cost-Effectiveness in the United States for People at Different Vascular Risk Levels Effects of atorvastatin on kidney outcomes and cardiovascular disease in patients with diabetes: an analysis from the Collaborative Atorvastatin Diabetes Study (CARDS). Prognosis of hypercholesterolemic patients taking pravastatin for five years: the Chiba Lipid Intervention Program (CLIP) Study. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia. Fluvastatin Prevents Cardiac Death and Myocardial Infarction in Renal Transplant Recipients: Post‐Hoc Subgroup Analyses of the ALERT Study Treatment of early Parkinson's disease [Effect of atorvastatin on carotid intima-medial of thickness of primary hypertension patients of Han nationality in China]. Cerivastatin, a New Potent Synthetic HMG Co-A Reductase Inhibitor: Effect of 0.2 mg Daily in Subjects With Primary Hypercholesterolemia Long-term treatment with pitavastatin (NK-104), a new HMG-CoA reductase inhibitor, of patients with heterozygous familial hypercholesterolemia. Atorvastatin affects low density lipoprotein and non-high density lipoprotein cholesterol relations with apolipoprotein B in type 2 diabetes mellitus: modification by triglycerides and cholesteryl ester transfer protein C-reactive protein lowering with rosuvastatin in the METEOR study. Changes in sequential coronary arteriograms and subsequent coronary events. Surgical Control of the Hyperlipidemias (POSCH) Group. Lovastatin effects on bone mineral density in postmenopausal women with type 2 diabetes mellitus Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial Randomised placebo controlled trial of effect on mood of lowering cholesterol concentration Effects of statins vs. non-statin lipid-lowering therapy on bone formation and bone mineral density biomarkers in patients with hyperlipidemia. Pravastatin reduces carotid intima-media thickness progression in an asymptomatic hypercholesterolemic mediterranean population: the Carotid Atherosclerosis Italian Ultrasound Study. Tracking of high-sensitivity C-reactive protein after an initially elevated concentration: the JUPITER Study. Effect of pharmacologic lipid lowering on health-related quality of life in older persons: results from the Cholesterol Reduction in Seniors Program (CRISP) Pilot Study. Low-Dose Combined Therapy with Fluvastatin and Cholestyramine in Hyperlipidemic Patients Low-Dose Metoprolol CR/XL and Fluvastatin Slow Progression of Carotid Intima-Media Thickness: Main Results From the &bgr;-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS) Changes in cardiovascular risk factors by combined pharmacological and nonpharmacological strategies: the main results of the CELL Study. Design of the Collaborative AtoRvastatin Diabetes Study (CARDS) in patients with type 2 diabetes. The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study) Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial The CARDS trial: Diabetic patients dealt a winning hand Effects of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia. Fukuoka Atherosclerosis Trial (FAST). Compliance and adverse event withdrawal: their impact on the West of Scotland Coronary Prevention Study. Atorvastatin normalizes endothelial function in healthy smokers. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). Comparison of one-year efficacy and safety of atorvastatin versus lovastatin in primary hypercholesterolemia. Atorvastatin Study Group I. Effects of bezafibrate and of 2 HMG-CoA reductase inhibitors on lipoprotein (a) level in hypercholesterolemic patients. Long-term effects of pravastatin and fosinopril on peripheral endothelial function in albuminuric subjects. Different Effects of Antihypertensive Regimens Based on Fosinopril or Hydrochlorothiazide With or Without Lipid Lowering by Pravastatin on Progression of Asymptomatic Carotid Atherosclerosis: Principal Results of PHYLLIS—A Randomized Double-Blind Trial The risks of a new hypothesis: why did JUPITER patients have almost twice the predicted event rate of reduction? Expanded Clinical Evaluation of Lovastatin (EXCEL) study results: two-year efficacy and safety follow-up. Effect of Atorvastatin on Progression of Sensorineural Hearing Loss and Tinnitus in the Elderly: Results of a Prospective, Randomized, Double-Blind Clinical Trial Measuring the cost-effectiveness of lipid-lowering drugs in the elderly: the outcomes research and economic analysis components of the PROSPER trial. The JUPITER Trial: responding to the critics. Efficacy of rosuvastatin among men and women with moderate chronic kidney disease and elevated high-sensitivity C-reactive protein: a secondary analysis from the JUPITER (Justification for the Use of Statins in Prevention-an Intervention Trial Evaluating Rosuvastatin) trial. Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials. Rosuvastatin for Primary Prevention in Older Persons With Elevated C-Reactive Protein and Low to Average Low-Density Lipoprotein Cholesterol Levels: Exploratory Analysis of a Randomized Trial Statins for Asymptomatic Middle Cerebral Artery Stenosis: The Regression of Cerebral Artery Stenosis Study Effect of Lipid Lowering With Rosuvastatin on Progression of Aortic Stenosis: Results of the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) Trial
abstract: Background — Prior primary prevention trials of statin therapy that used cholesterol criteria for enrollment have not reported significant decreases in stroke risk . We evaluated whether statin therapy might reduce stroke rates among individuals with low levels of cholesterol but elevated levels of high-sensitivity C-reactive protein . Methods and Results — In Justification for the Use of statins in Prevention : an Intervention Trial Evaluating Rosuvastatin ( JUPITER ) , 17 802 apparently healthy men and women with low-density lipoprotein cholesterol levels < 130 mg/dL and high-sensitivity C-reactive protein levels ≥2.0 mg/L were r and omly allocated to rosuvastatin 20 mg daily or placebo and then followed up for the occurrence of a first stroke . After a median follow-up of 1.9 years ( maximum , 5.0 years ) , rosuvastatin result ed in a 48 % reduction in the hazard of fatal and nonfatal stroke as compared with placebo ( incidence rate , 0.18 and 0.34 per 100 person-years of observation , respectively ; hazard ratio 0.52 ; 95 % confidence interval , 0.34 to 0.79 ; P=0.002 ) , a finding that was consistent across all examined subgroups . This finding was due to a 51 % reduction in the rate of ischemic stroke ( hazard ratio , 0.49 ; 95 % confidence interval , 0.30 to 0.81 ; P=0.004 ) , with no difference in the rates of hemorrhagic stroke between the active and placebo arms ( hazard ratio , 0.67 ; 95 % confidence interval , 0.24 to 1.88 ; P=0.44 ) . Conclusion — Rosuvastatin reduces by more than half the incidence of ischemic stroke among men and women with low levels of low-density lipoprotein cholesterol levels who are at risk because of elevated levels of high-sensitivity C-reactive protein . Clinical Trial Registration — clinical trial.gov . Unique identifier : NCT00239681 Objectives : For large scale follow up studies with non-demented patients in which cognition is an endpoint , there is a need for short , inexpensive , sensitive , and reliable neuropsychological tests that are suitable for repeated measurements . The commonly used Mini-Mental-State-Examination fulfils only the first two requirements . Methods : In the PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) , 5804 elderly subjects aged 70 to 82 years were examined using a  learning test ( memory ) , a coding test ( general speed )  , and a short version of the Stroop test ( attention ) .  Data presented here were collected at dual baseline , before r and omisation for active treatment . Results : The tests proved to be reliable ( with test/retest reliabilities ranging from acceptable ( r=0.63 ) to high ( r=0.88 ) and sensitive to detect small differences in subjects from different age categories . All tests showed significant practice effects : performance increased from the first measurement to the first follow up after two weeks . Conclusion : Normative data are provided that can be used for one time neuropsychological testing as well as for assessing individual and group change . Methods for analysing cognitive change are proposed Objective The CARDS trial , a multicentre , r and omized , controlled trial , found that atorvastatin 10 mg/day for patients with type 2 diabetes mellitus and normal low-density lipoprotein (LDL)-cholesterol significantly reduced cardiovascular ( CV ) events , including stroke . We estimated the cost effectiveness of atorvastatin as primary prevention against CV disease from the short-term and lifetime US payer perspectives . Research design and methods We constructed a decision analytic ( Markov ) model to evaluate long-term costs and outcomes for atorvastatin 10 mg/day versus no HMG-CoA reductase inhibitor ( statin ) therapy for patients with type 2 diabetes and no history of a CV event .  CV event rates and survival were based on risk equations calibrated to CARDS and applied to a US type 2 diabetes population ; the atorvastatin effect on CV events was based on hazard ratios from CARDS ; direct medical care costs were based on US treatment patterns and published costs analyses of patients with diabetes . Costs were valued in $ US , year 2005 values ; costs and benefits were discounted at 3 % per annum . Results Within the time horizon of the trial ( 5 years ) , the cost effectiveness of atorvastatin was $ US137 276 per QALY . At 10 years , the incremental cost per QALY improved to $ US3640 per QALY . At 25 years , overall costs were lower and QALYs higher in the atorvastatin arm . Costs of managing CV events were lower after 5 years for patients treated with atorvastatin . Conclusions For patients with type 2 diabetes and one additional risk factor for CV disease , normal LDL-cholesterol and no history of a CV event , primary prevention with atorvastatin appears to be cost saving and improve outcomes over 25 years , although it is costly from a short-term US payer perspective . From both a medical and an economic viewpoint , primary prevention is desirable in this patient population Aims Patients with Type 2 diabetes have an elevated risk of stroke . The role of lipid levels and diabetes‐specific factors in risk prediction of stroke is unclear , and estimates of efficacy of lipid‐lowering therapy vary between trials . We examined predictors of stroke and the effect of atorvastatin on specific stroke subtypes in Type 2 diabetes in the Collaborative Atorvastatin Diabetes Study ( CARDS ) [ a trial of 2838 participants with mean low‐density lipoprotein cholesterol < 4.14 mmol/l , no history of macrovascular disease and r and omized to atorvastatin 10 mg daily or placebo ] Lipid-lowering therapy in individuals with high risk of cardiovascular disease reduces the incidence of coronary heart disease . However , few studies have assessed the benefits of cholesterol lowering for primary prevention of coronary heart disease in hypertensive patients with mild dyslipidemia or without conventional dyslipidemia . The large , r and omized Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese Study showed a 33 % reduction in coronary heart disease incidence with pravastatin as the primary prevention in Japanese patients . We conducted an exploratory analysis of the effect of diet plus pravastatin therapy on the primary prevention of cardiovascular events ( coronary heart disease , coronary heart disease plus cerebral infa rct ion , and cardiovascular disease ) in the 3277 patients with hypertension during the 5-year follow-up . There were no significant differences in mean baseline total cholesterol , blood pressure levels , or variation in blood pressure during the 5-year period between the diet ( n=1664 ) and diet plus pravastatin ( n=1613 ) groups . In the diet plus pravastatin group , the relative risk of coronary heart disease plus cerebral infa rct ion was reduced by 35 % ( hazard ratio : 0.65 ; CI : 0.46 to 0.93 ; P=0.02 ) , cerebral infa rct ion by 46 % ( hazard ratio : 0.54 ; CI : 0.29 to 0.98 ; P=0.04 ) , and cardiovascular disease by 33 % ( hazard ratio : 0.67 ; CI : 0.49 to 0.91 ; P=0.01 ) . In patients without a history of cardiovascular disease who have hypertension and mildly elevated cholesterol , pravastatin was effective in reducing the incidence of cardiovascular disease , particularly cerebral infa rct ion . Hence , in patients with hypertension with mildly elevated cholesterol levels , treatment with a statin is advisable to reduce the burden of cardiovascular disease CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P<.001 ; chi2 test ) . Logistic regression analyses indicated that funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data Background Simvastatin reduces cardiovascular mortality and morbidity but , as with other HMG-CoA reductase inhibitors , can cause significant muscle toxicity and has been associated with elevations of liver transaminases . Methods Muscle and liver adverse effects of simvastatin 40 mg daily were evaluated in a r and omized placebo-controlled trial involving 20,536 UK patients with vascular disease or diabetes ( in which a substantial reduction of cardiovascular mortality and morbidity has previously been demonstrated ) . Results The excess incidence of myopathy in the simvastatin group was < 0.1 % over the 5 years of the trial , and there were no significant differences between the treatment groups in the incidence of serious hepatobiliary disease . Conclusion Among the many different types of high-risk patient studied ( including women , older individuals and those with low cholesterol levels ) , there was a very low incidence ( < 0.1 % ) of myopathy during 5 years treatment with simvastatin 40 mg daily . The risk of hepatitis , if any , was undetectable even in this very large long-term trial . Routine monitoring of liver function tests during treatment with simvastatin 40 mg is not useful . Trial Registration IS RCT BACKGROUND Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events . Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol , we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment . METHODS We r and omly assigned 17,802 apparently healthy men and women with low-density lipoprotein ( LDL ) cholesterol levels of less than 130 mg per deciliter ( 3.4 mmol per liter ) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin , 20 mg daily , or placebo and followed them for the occurrence of the combined primary end point of myocardial infa rct ion , stroke , arterial revascularization , hospitalization for unstable angina , or death from cardiovascular causes . RESULTS The trial was stopped after a median follow-up of 1.9 years ( maximum , 5.0 ) . Rosuvastatin reduced LDL cholesterol levels by 50 % and high-sensitivity C-reactive protein levels by 37 % . The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups , respectively ( hazard ratio for rosuvastatin , 0.56 ; 95 % confidence interval [ CI ] , 0.46 to 0.69 ; P<0.00001 ) , with corresponding rates of 0.17 and 0.37 for myocardial infa rct ion ( hazard ratio , 0.46 ; 95 % CI , 0.30 to 0.70 ; P=0.0002 ) , 0.18 and 0.34 for stroke ( hazard ratio , 0.52 ; 95 % CI , 0.34 to 0.79 ; P=0.002 ) , 0.41 and 0.77 for revascularization or unstable angina ( hazard ratio , 0.53 ; 95 % CI , 0.40 to 0.70 ; P<0.00001 ) , 0.45 and 0.85 for the combined end point of myocardial infa rct ion , stroke , or death from cardiovascular causes ( hazard ratio , 0.53 ; 95 % CI , 0.40 to 0.69 ; P<0.00001 ) , and 1.00 and 1.25 for death from any cause ( hazard ratio , 0.80 ; 95 % CI , 0.67 to 0.97 ; P=0.02 ) . Consistent effects were observed in all subgroups evaluated . The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes . CONCLUSIONS In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels , rosuvastatin significantly reduced the incidence of major cardiovascular events . ( Clinical Trials.gov number , NCT00239681 . BACKGROUND Chronic kidney disease ( CKD ) is associated with an increased risk of incident cardiovascular disease ( CVD ) ; however , the role of statins for the primary prevention of acute cardiovascular events in patients with CKD and the effect of statins on kidney function loss in persons without prevalent CVD have not been studied . STUDY DESIGN Post hoc analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study . SETTING & PARTICIPANTS Multicenter , r and omized , double-blind , placebo-controlled trial of 5,608 men and 997 women without CVD r and omly assigned to treatment with lovastatin or placebo .  INTERVENTION Placebo or lovastatin , 20 mg/d . OUTCOMES & MEASUREMENTS First major acute cardiovascular event in participants with mild CKD and kidney function loss in persons with or without CKD .  Estimated glomerular filtration rate was calculated using the 4-variable Modification of Diet in Renal Disease Study equation . RESULTS At baseline ,  mean estimated glomerular filtration rate in participants with CKD ( n = 304 ) was 53.0 + /- 6.0 mL/min/1.73 m(2 ) . After an average follow-up of 5.3 + /- 0.8 years , the incidence of a fatal and nonfatal CVD event was lower in participants with CKD receiving lovastatin than in those receiving placebo ( adjusted relative risk [ RR ] , 0.31 ; 95 % CI , 0.13 - 0.72 ; P = 0.01 ) . Tests for interaction suggested that the benefit of lovastatin was independent of the presence of CKD . Lovastatin did not reduce the annualized mean decrease in estimated glomerular filtration rate ( -1.3 + /- 0.07 vs -1.4 + /- 0.07 mL/min/1.73 m(2)/y , respectively ; P = 0.1 ) or the frequency of a > or = 25 % decrease in kidney function ( adjusted RR , 1.10 ; 95 % CI , 0.96 - 1.28 ; P = 0.2 ) or incident CKD ( adjusted RR , 1.04 ; 95 % CI , 0.86 - 1.27 ; P = 0.6 ) . LIMITATIONS Unable to determine the cause and duration of kidney disease , and information regarding proteinuria was not available . CONCLUSIONS Lovastatin is effective for the primary prevention of CVD in patients with CKD , but is not effective in decreasing kidney function loss in persons with no CVD Conventional lipid-lowering agents displayed only limited efficacy in lowering total and LDL cholesterol and a high incidence of side effects .  Pravastatin is a new potent cholesterol-lowering agent , which selectively inhibits hepatic HMG-CoA-reductase . In a double-blind , placebo-controlled Swiss multicenter study with determination of lipids and lipoprotein in a central laboratory , the efficacy and safety of 6 months ' therapy with pravastatin was evaluated in 50 patients with mild hypercholesterolemia and additional coronary risk factors . Compared to baseline and after 26 weeks ' therapy , pravastatin significantly reduced total cholesterol  ( pravastatin vs placebo , -17 % vs + 7 % , p < 0.0001 ) and LDL cholesterol ( -26 vs + 2 % , p < 0.0001 ) . The total/HDL cholesterol ratio ( = " atherogenic index " ) was comparable in the two groups at baseline ( 5.9 + /- 1.1 vs 6.3 + /- 0.9 ) , and was distinctly lowered by pravastatin but not placebo ( -20 vs 0 % , p < 0.0001 ) . In 11 patients in whom the reduction of serum total cholesterol after 13 weeks ' treatment with 20 mg pravastatin was still below target ( on average -9.1 % ) , doubling of the dose produced a further decrease of 4.3 % . Serum HDL cholesterol and serum triglyceride levels did not change significantly during pravastatin treatment as compared to baseline and placebo . Pravastatin was well tolerated during the 26 weeks without relevant subjective side-effects . There were 5 dropouts during the study , 2 patients in the pravastatin group and 3 in the placebo group . These findings document that pravastatin , administered in a single daily dose of 20 to 40 mg , effectively lowers serum cholesterol and total-/HDL-cholesterol improving action and is well tolerated In the multicenter , double-blind EXCEL ( Exp and ed Clinical Evaluation of Lovastatin ) study the efficacy of lovastatin in modifying plasma lipids and lipoproteins in 8,245 participants with moderate primary hypercholesterolemia was evaluated . Patients were r and omly assigned to 48 weeks of treatment with diet and placebo or diet and lovastatin 20 or 40 mg once a day , or 20 or 40 mg twice a day . At all of these dosages , lovastatin produced substantial dose-dependent reductions in low-density-lipoprotein (LDL)-cholesterol levels , averaging 24 % ( 20 mg/day ) to 40 % ( 80 mg/day ) . The magnitude of the effect of this lipoprotein was further reflected by the percentage of patients who achieved National Cholesterol Education Program ( NCEP ) goals . In the absence of coronary artery disease ( CAD ) or two other CAD risk factors , the LDL-cholesterol goal of 4.14 mmol/L ( 160 mg/dL ) was attained by 22 % of patients in the placebo group and between 81 % ( 20 mg/day ) and 96 % ( 80 mg/day ) of those treated with lovastatin . For those with CAD or at least two other CAD risk factors , the LDL-cholesterol goal of 3.36 mmol/L ( 130 mg/dL ) was attained by 4 % of placebo patients and between 38 % ( 20 mg/day ) and 83 % ( 80 mg/day ) of those treated with lovastatin . Lovastatin also increased high-density-lipoprotein cholesterol ( 7 - 10 % ) and decreased triglycerides ( 10 - 19 % ) in a dose-dependent manner . Thus , when used as an adjunct to a prudent diet , lovastatin produces favorable changes in the entire lipoprotein profile and is a highly effective agent for managing patients with primary hypercholesterolemia OBJECTIVE Coronary artery disease is the most important cause of mortality in patients with type 2 diabetes . We aim ed to determine the prevalence of silent myocardial ischemia ( SMI ) and the effect of statin therapy on SMI in type 2 diabetic patients without manifest cardiovascular disease . RESEARCH DESIGN AND METHODS A r and omized , placebo-controlled , double-blind trial was performed in 250 patients with type 2 diabetes without manifest cardiovascular disease . Patients were given either 0.4 mg cerivastatin or placebo daily . In August 2001 , when cerivastatin was withdrawn from the market , cerivastatin 0.4 mg was replaced by 20 mg simvastatin without deblinding the study . The primary end point was the change in ischemic episodes , duration , and burden as measured by 48-h ambulatory electrocardiography ( AECG ) over 2 years . RESULTS At baseline , 47 of 233 ( 20 % ) evaluable ambulatory electrocardiograms showed evidence of ischemia . After 2 years , there was a trend toward more ischemia in both treatment groups , without significant differences between the changes in ischemic parameters ( episodes P = 0.498 ; duration P = 0.697 ; burden P = 0.798 ) in the two treatment groups . Cardiovascular events occurred in 12 patients in the placebo group and in two patients in the statin group ( P = 0.006 ) . There was no relationship between these cardiovascular events and the presence of SMI at baseline . CONCLUSIONS SMI occurred in 20 % of type 2 diabetes patients without manifest cardiovascular disease . There was no effect from 2 years of statin therapy on SMI . In contrast , we observed a significantly lower cardiovascular event rate on statin therapy . AECG may not be a proper tool for risk stratification in patients with type 2 diabetes CONTEXT Individuals with diabetes are at increased risk for cardiovascular disease ( CVD ) , but more aggressive targets for risk factor control have not been tested . OBJECTIVE To compare progression of sub clinical atherosclerosis in adults with type 2 diabetes treated to reach aggressive targets of low-density lipoprotein cholesterol ( LDL-C ) of 70 mg/dL or lower and systolic blood pressure ( SBP ) of 115 mm Hg or lower vs st and ard targets of LDL-C of 100 mg/dL or lower and SBP of 130 mm Hg or lower . DESIGN , SETTING , AND PARTICIPANTS A r and omized , open-label , blinded-to-end point , 3-year trial from April 2003-July 2007 at 4 clinical centers in Oklahoma , Arizona , and South Dakota . Participants were 499 American Indian men and women aged 40 years or older with type 2 diabetes and no prior CVD events . INTERVENTIONS Participants were r and omized to aggressive ( n=252 ) vs st and ard ( n=247 ) treatment groups with stepped treatment algorithms defined for both . MAIN OUTCOME MEASURES Primary end point was progression of atherosclerosis measured by common carotid artery intimal medial thickness ( IMT ) . Secondary end points were other carotid and cardiac ultrasonographic measures and clinical events . RESULTS Mean target LDL-C and SBP levels for both groups were reached and maintained . Mean ( 95 % confidence interval ) levels for LDL-C in the last 12 months were 72 ( 69 - 75 ) and 104 ( 101 - 106 ) mg/dL and SBP levels were 117 ( 115 - 118 ) and 129 ( 128 - 130 ) mm Hg in the aggressive vs st and ard groups , respectively . Compared with baseline , IMT regressed in the aggressive group and progressed in the st and ard group ( -0.012 mm vs 0.038 mm ; P < .001 ) ; carotid arterial cross-sectional area also regressed ( -0.02 mm(2 ) vs 1.05 mm(2 ) ; P < .001 ) ; and there was greater decrease in left ventricular mass index ( -2.4 g/m(2.7 ) vs -1.2 g/m(2.7 ) ; P = .03 ) in the aggressive group . Rates of adverse events ( 38.5 % and 26.7 % ; P = .005 ) and serious adverse events ( n = 4 vs 1 ; P = .18 ) related to blood pressure medications were higher in the aggressive group . Clinical CVD events ( 1.6/100 and 1.5/100 person-years ; P = .87 ) did not differ significantly between groups . CONCLUSIONS Reducing LDL-C and SBP to lower targets result ed in regression of carotid IMT and greater decrease in left ventricular mass in individuals with type 2 diabetes . Clinical events were lower than expected and did not differ significantly between groups . Further follow-up is needed to determine whether these improvements will result in lower long-term CVD event rates and costs and favorable risk-benefit outcomes . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00047424 A large well conducted r and omised controlled trial from Shanghai shows conclusively that teaching women how to examine their breasts  does not lead to a reduction in mortality due to breast cancer compared with no screening at all.1 The findings should bring to an end more than decade of controversy and confusion in the United Kingdom concerning the efficacy and effectiveness of  self examination of the breast  . In September 1991 , in his retirement speech , Chief Medical Officer Sir Donald Acheson announced that breast self examination was not effective and may give a false sense of security . His remarks outraged women 's health campaigners , fuelled by a media frenzy in favour of breast self examination that lasted several weeks . The introduction of a policy of breast awareness shortly afterwards only added to the confusion . Rather than ritually checking their breasts at a specific time each month according to a set technique , women were encouraged to take responsibility for their own health by taking convenient opportunities such as bathing or dressing to become familiar with their breasts at different times of the month and Background —We determined whether statin use ( versus nonuse ) is associated with superior lower-extremity functioning independently of cholesterol levels and other confounders in patients with and without peripheral arterial disease . Methods and Results — Participants included 392 men and women with an ankle brachial index ( ABI ) < 0.90 and 249 with ABI 0.90 to 1.50 . Functional outcomes included 6-minute walk distance and 4-meter walking velocity . A summary performance score combined performance in walking speed , st and ing balance , and time for 5 repeated chair rises into an ordinal score ranging from 0 to 12 ( 12=best ) . Adjusting for age , sex , ABI , comorbidities , education level , medical insurance status , cholesterol , and other confounders , participants taking statins  had better 6-minute walk performance ( 1276 versus 1218 feet , P = 0.045 ) , faster walking velocity ( 0.93 versus 0.89 m/s , P = 0.006 ) , and a higher summary performance score ( 10.2 versus 9.4 , P < 0.001 ) than participants not taking statins . Positive associations were attenuated slightly after additional adjustment for C-reactive protein level but remained statistically significant for walking velocity and the summary performance score . We did not find significant associations between lower-extremity functioning and  aspirin , ACE inhibitors , vasodilators , or & bgr;-blockers . Conclusions —Statin use is associated with superior leg functioning compared with no statin use , independent of cholesterol levels and other potential confounders . These data suggest that non – cholesterol-lowering properties of statins may favorably influence functioning in persons with and without peripheral arterial disease Atherosclerosis is a disease whose pathogenesis involves inflammatory and immunological mechanisms , including an autoimmune reaction against heat shock proteins ( Hsps ) . The purpose of this study was to analyze whether the antiatherogenic effect of statin therapy was not limited to its lipid lowering effect , but also included anti-inflammatory and immunomodulatory effects , paying special attention to the measurement of circulating concentrations of anti-Hsp70 and anti-Hsp60 antibodies previously related to vascular disease . Two-hundred and seventy-five subjects aged 40–60 years , r and omly selected in an epidemiological study on the incidence of vascular risk factors , were studied . Laboratory tests included a complete lipid profile after a 12-h fast and measurements of glucose , C-reactive-protein , anti-Hsp70 and anti-Hsp60 antibodies .  Subjects with hypercholesterolemia had significantly higher concentrations of anti-Hsp70 antibodies as compared to subjects with normal cholesterol concentrations . Statin therapy was associated with 11.63 and 15.3 % reductions in total and LDL-cholesterol ( P = 0.005 and 0.017 , respectively ) as compared to untreated subjects , and with lower concentrations of circulating anti-Hsp70 ( P = 0.016 ) antibodies . No differences were found in C-reactive-protein values . Since statin therapy not only reduces lipid profile , but also anti-Hsp70 and anti-Hsp60 antibody concentrations , without changing C-reactive-protein values , it is suggested that such an effect could not be accounted for by the anti-inflammatory properties of statins , but by their direct immunomodulatory properties through their effects on lymphocyte function BACKGROUND HDL-cholesterol concentrations are inversely associated with occurrence of  cardiovascular events . We addressed , using the JUPITER trial cohort , whether this association remains when LDL-cholesterol concentrations are reduced to the very low ranges with high-dose statin treatment . METHODS Participants in the r and omised placebo-controlled JUPITER trial were adults without diabetes or previous cardiovascular disease , and had baseline concentrations of LDL cholesterol of less than 3.37 mmol/L and high-sensitivity C-reactive protein of 2 mg/L or more . Participants were r and omly allocated by a computer-generated sequence  to receive rosuvastatin 20 mg per day or placebo , with participants and adjudicators masked to treatment assignment . In the present analysis , we divided the participants into quartiles of HDL-cholesterol or apolipoprotein A1 and sought evidence of association between these quartiles and the JUPITER primary endpoint of first non-fatal myocardial infa rct ion or stroke , hospitalisation for unstable angina , arterial revascularisation , or cardiovascular death . This trial is registered with Clinical Trials.gov , number NCT00239681 . FINDINGS For 17,802 patients in the JUPITER trial , rosuvastatin 20 mg per day reduced the incidence of the primary endpoint by 44 % ( p<0.0001 ) . In 8901 ( 50 % ) patients given placebo ( who had a median on-treatment LDL-cholesterol concentration of 2.80 mmol/L [ IQR 2.43 - 3.24 ] ) , HDL-cholesterol concentrations were inversely related to vascular risk both at baseline ( top quartile vs bottom quartile hazard ratio [ HR ] 0.54 , 95 % CI 0.35 - 0.83 , p=0.0039 ) and on-treatment ( 0.55 , 0.35 - 0.87 , p=0.0047 ) . By contrast , among the 8900 ( 50 % ) patients given rosuvastatin 20 mg ( who had a median on-treatment LDL-cholesterol concentration of 1.42 mmol/L [ IQR 1.14 - 1.86 ] ) , no significant relationships were noted between quartiles of HDL-cholesterol concentration and vascular risk either at baseline ( 1.12 , 0.62 - 2.03 , p=0.82 ) or on-treatment ( 1.03 , 0.57 - 1.87 , p=0.97 ) . Our analyses for apolipoprotein A1 showed an equivalent strong relation to frequency of primary outcomes in the placebo group but little association in the rosuvastatin group . INTERPRETATION Although measurement of HDL-cholesterol concentration is useful as part of initial cardiovascular risk assessment , HDL-cholesterol concentrations are not predictive of residual vascular risk among patients treated with potent statin therapy who attain very low concentrations of LDL cholesterol . FUNDING AstraZeneca BACKGROUND Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals , their efficacy and safety in elderly people is not fully established . Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with , or at high risk of developing , cardiovascular disease and stroke . METHODS We did a r and omised controlled trial in which we assigned 5804 men ( n=2804 ) and women ( n=3000 ) aged 70 - 82 years with a history of , or risk factors for , vascular disease to pravastatin ( 40 mg per day ; n=2891 ) or placebo ( n=2913 ) . Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death , non-fatal myocardial infa rct ion , and fatal or non-fatal stroke . Analysis was by intention-to-treat . FINDINGS Pravastatin lowered LDL cholesterol concentrations by 34 % and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo ( hazard ratio 0.85 , 95 % CI 0.74 - 0.97 , p=0.014 ) . Coronary heart disease death and non-fatal myocardial infa rct ion risk was also reduced ( 0.81 , 0.69 - 0.94 , p=0.006 ) . Stroke risk was unaffected ( 1.03 , 0.81 - 1.31 , p=0.8 ) , but the hazard ratio for transient ischaemic attack was 0.75 ( 0.55 - 1.00 , p=0.051 ) . New cancer diagnoses were more frequent on pravastatin than on placebo ( 1.25 , 1.04 - 1.51 , p=0.020 ) . However , incorporation of this finding in a meta- analysis of all pravastatin and all statin trials showed no overall increase in risk . Mortality from coronary disease fell by 24 % ( p=0.043 ) in the pravastatin group . Pravastatin had no significant effect on cognitive function or disability . INTERPRETATION Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals . PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people The PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) is a r and omized , double-blind , placebo-controlled trial design ed to test the hypothesis that treatment with pravastatin will diminish risk of subsequent major vascular events in a cohort of men and women ( 70 to 82 years old ) with preexisting vascular disease or significant risk of developing this condition . Five thous and eight hundred four men and women in addition to receiving advice on diet and smoking , have been r and omized equally to treatment with 40 mg pravastatin/day  or matching placebo in 3 centers ( Cork , Irel and , Glasgow , Scotl and , and Leiden , The Netherl and s ) . Following an average 3.5-year intervention period , a primary assessment will be made of the influence of this therapy on major vascular events ( a combination of coronary heart disease , death , nonfatal myocardial infa rct ion , and fatal and nonfatal stroke ) . A number of additional analyses will also be conducted on the individual components of the primary end point , on men , on women , and on subjects with and without previous evidence of vascular disease . Finally , an assessment will be made of the effects of treatment on cognitive function , disability , hospitalization or institutionalization , vascular mortality , and all-cause mortality Background —Microalbuminuria is associated with increased risk of cardiovascular events . We assessed whether therapeutic intervention aim ed at lowering urinary albumin excretion would reduce cardiovascular events in microalbuminuric subjects ( 15 to 300 mg/24 hours ) . Methods and Results —From the Prevention of Renal and Vascular Endstage Disease ( PREVEND ) cohort ( n=8592 ) , 1439 subjects fulfilled the inclusion criteria of the PREVEND Intervention Trial ( PREVEND IT ) . Of these subjects , 864 were r and omized to fosinopril 20 mg or matching placebo and to pravastatin 40 mg or matching placebo . The mean follow-up was 46 months , and the primary end point was cardiovascular mortality and hospitalization for cardiovascular morbidity . Mean age was 51±12 years ; 65 % of subjects were male , and 3.4 % had a previous cardiovascular event . Mean cholesterol level was 5.8±1.0 mmol/L , mean systolic/diastolic blood pressure was 130±18/76±10 mm Hg , and median urinary albumin excretion was 22.8 ( 15.8 to 41.3 ) mg/24 hours . The primary end point occurred in 45 subjects ( 5.2 % ) . Fosinopril  reduced urinary albumin excretion by 26 % ( P<0.001 ) . Subjects treated with fosinopril showed a 40 % lower incidence of the primary end point ( hazard ratio 0.60 [ 95 % CI 0.33 to 1.10 ] , P=0.098 , log-rank ) . Pravastatin did not reduce urinary albumin excretion , and subjects treated with pravastatin showed a 13 % lower incidence of the primary end point than subjects in the placebo group ( 0.87 [ 0.49 to 1.57 ] , P=0.649 , log-rank ) . Conclusions —In microalbuminuric subjects , treatment with fosinopril had a significant effect on urinary albumin excretion . In addition , fosinopril treatment was associated with a trend in reducing cardiovascular events  . Treatment with pravastatin did not result in a significant reduction in urinary albumin excretion or cardiovascular events OBJECTIVE —Rates of cardiovascular disease are highest in the elderly .  Lipid-lowering statin therapy reduces the proportional risk as effectively in older patients as in younger individuals ; however , limited data are available for elderly patients with type 2 diabetes . We conducted a post hoc analysis to compare the efficacy and safety of atorvastatin among 1,129 patients aged 65–75 years at r and omization with 1,709 younger patients in the Collaborative Atorvastatin Diabetes Study ( CARDS ) . RESEARCH DESIGN AND METHODS —CARDS was a r and omized  placebo-controlled trial of 10 mg/day atorvastatin for primary prevention of cardiovascular disease in patients aged 40–75 years with LDL cholesterol concentrations ≤4.14 mmol/l followed for a median of 3.9 years . The primary end point was time to first occurrence of acute coronary heart disease events , coronary revascularizations , or stroke . RESULTS —Atorvastatin treatment result ed in a 38 % reduction in relative risk ( [ 95 % CI −58 to −8 ] , P = 0.017 ) of first major cardiovascular events in older patients and a 37 % reduction ( [ −57 to −7 ] , P = 0.019 ) in younger patients . Corresponding absolute risk reductions were 3.9 and 2.7 % , respectively ( difference 1.2 % [ 95 % CI −2.8 to 5.3 ] , P = 0.546 ) ; numbers needed to treat for 4 years to avoid one event were 21 and 33 , respectively . All-cause mortality was reduced nonsignificantly by 22 % ( [ −49 to 18 ] , P = 0.245 ) and 37 % ( [ −64 to 9 ] , P = 0.98 ) , respectively . The overall safety profile of atorvastatin was similar between age-groups . CONCLUSIONS —Absolute and relative benefits of statin therapy in older patients with type 2 diabetes are substantial , and all patients warrant treatment unless specifically contraindicated The treatment of hypercholesterolemia may be associated with greater noncardiac mortality . This current pilot study sought to determine which behaviors , if any , are associated with decreases in cholesterol level .  Twelve subjects received one of two cholesterol-reducing drugs or placebo .  Cholesterol and behavioral ratings were measured at baseline , 4 , and 52 weeks with st and ardized scales . Cholesterol levels markedly declined with concomitant significant increases in impulsivity ratings at 4 weeks . At 52 weeks , the increase in impulsivity ratings was no longer apparent , but depression ratings showed a significant improvement . This pilot study , although limited in size , raises the possibility that cholesterol-lowering drugs are associated with mild , time-limited increases in impulsivity and with mild , time-delayed improvements in depression ratings Background — Recent clinical trials have suggested that intensive versus st and ard lipid-lowering therapy provides for additional benefit . Electron-beam computed tomography provides the opportunity to quantify the progression of coronary artery calcification ( CAC ) in serial measurements . Methods and Results — In a multicenter , r and omized , double-blind trial , 471 patients ( age 61±8 years ) who had no history of coronary artery disease and no evidence of high- grade coronary stenoses ( > 50 % diameter reduction ) were r and omized if they had ≥2 cardiovascular risk factors and moderate calcified coronary atherosclerosis as evidence d by a CAC score ≥30 . Patients were assigned to receive 80 mg or 10 mg of atorvastatin per day over 12 months . Progression of CAC volume scores could be analyzed in 366 patients . After pretreatment with 10 mg of atorvastatin for 4 weeks , 12 months of study medication reduced LDL cholesterol from 106±22 to 87±33 mg/dL in the group r and omized to receive 80 mg of atorvastatin ( P<0.001 ) , whereas levels remained stable in the group r and omized to receive 10 mg ( 108±23 at baseline , 109±28 mg/dL at the end of the study , P = NS ) . The mean progression of CAC volume scores , corrected for the baseline CAC volume score , was 27 % ( 95 % CI 20.8 % to 33.1 % ) in the 80-mg atorvastatin group and 25 % ( 95 % CI 19.1 % to 30.8 % ) in the 10-mg atorvastatin group ( P=0.65 ) . CAC progression showed no relationship with on-treatment LDL cholesterol levels . Conclusions — We did not observe a relationship between on-treatment LDL cholesterol levels and the progression of calcified coronary atherosclerosis . Over a period of 12 months , intensive atorvastatin therapy was unable to attenuate CAC progression  compared with st and ard atorvastatin therapy . The possibility remains that the time window was too short to demonstrate an effect 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 OBJECTIVE Cardiovascular disease ( CVD ) is the most important cause of mortality in patients with type 2 diabetes and is preceded by endothelial dysfunction . Flow-mediated dilation ( FMD ) is a noninvasive technique for measuring endothelial dysfunction . We aim ed to determine the effect of long-term statin therapy versus placebo on FMD in patients with type 2 diabetes without manifest CVD . RESEARCH DESIGN AND METHODS A r and omized , placebo-controlled , double-blind trial was performed with 250 type 2 diabetic patients . Patients were given 0.4 mg cerivastatin or placebo daily . In August 2001 , when cerivastatin was withdrawn from the market , the 0.4 mg cerivastatin was replaced by 20 mg simvastatin , without deblinding the study . The primary end point was the change in FMD , measured by B-mode ultrasound , after 2 years . RESULTS Determinants of baseline FMD were diabetes duration , common carotid intima-media thickness , and brachial artery diameter . FMD at baseline was 1.51 % in the placebo group and 1.66 % in the statin group and did not change significantly after 2 years . CONCLUSIONS The 2-year statin therapy had no effect on FMD in type 2 diabetes . Statin-induced improvement of cardiovascular risk in patients with type 2 diabetes may be mediated through mechanisms other than increased nitric oxide availability BACKGROUND A recent trial in Western countries has shown that rosuvastatin slows progression of carotid intima-media thickness ( IMT ) in patients with modest carotid IMT thickening and elevated levels of low-density lipoprotein cholesterol ( LDL-C ) . We conducted a prospect i ve , r and omized , open-label , blinded-endpoint trial to determine whether rosuvastatin is more effective than pravastatin in slowing progression of carotid  IMT in Japanese patients . METHODS AND RESULTS Adult patients with hypercholesterolemia who had a maximum IMT ≥1.1 mm were r and omly assigned to receive rosuvastatin or pravastatin . The primary endpoint was the percent change in the mean-IMT , which was measured by a single observer who was blinded to the treatment assignments . The trial was stopped on April 2011 according to the recommendation by the data and safety monitoring committee . A total of 348 patients ( 173 rosuvastatin ; 175 pravastatin ) were enrolled and 314 ( 159 rosuvastatin ; 155 pravastatin ) were included in the primary analysis . Mean ( SD ) percentage changes in the mean-IMT at 12 months were 1.91 % ( 10.9 ) in the rosuvastatin group and 5.8 % ( 12.0 ) in the pravastatin group , with a difference of 3.89 % ( 11.5 ) between the groups ( P=0.004 ) . At 12 months , 85 patients ( 59.4 % ) in the rosuvastatin group achieved a LDL-C/high-density lipoprotein cholesterol ratio ≤1.5 compared with 24 patients ( 16.4 % ) in the pravastatin group ( P<0.0001 ) . CONCLUSIONS Rosuvastatin significantly slowed progression of carotid IMT at 12 months compared with pravastatin In the Justification for Use of statins in Prevention : an Intervention Trial Evaluating Rosuvastatin ( JUPITER ) , r and om allocation of rosuvastatin compared to placebo among primary prevention patients with a low-density lipoprotein cholesterol level of < 130 mg/dl and a high-sensitivity C-reactive protein ( hs-CRP ) level of > or = 2 mg/L result ed in a highly significant 44 % reduction in major vascular events . However , the relation of baseline hs-CRP levels to risk within JUPITER has not previously been described and has been an area of controversy for study interpretation . As reported in the present study for the first time , despite enrolling patients with a constrained range of values , increasing baseline hs-CRP levels within JUPITER were nonetheless associated with increasing vascular risk in analyses treating hs-CRP as a continuous variable , as an ordinal variable , and as a threshold variable . As anticipated , the relative risk reduction associated with rosuvastatin was similar in magnitude across the tertile and threshold levels of entry hs-CRP . In conclusion , as the absolute risk increased with increasing hs-CRP , the absolute risk reduction associated with rosuvastatin within JUPITER was also greatest among those with the greatest entry hs-CRP levels Objective Older patients experience higher rates of cardiovascular disease than younger patients , but may be undertreated with statins due to doubts about efficacy and safety . The Lipid-Lowering Arm of the Anglo-Sc and inavian Cardiac Outcomes Trial allowed an evaluation of the efficacy and safety of atorvastatin among older ( ≥65 years ) and younger ( < 65 years ) patients with hypertension . Methods A total of 10 305 patients with hypertension , at least three other cardiovascular risk factors , total cholesterol concentrations of 251 mg/dl or less , and no known coronary heart disease ( CHD ) were r and omized to receive atorvastatin 10 mg or placebo . The primary endpoint was a composite of nonfatal myocardial infa rct ion and fatal CHD . Results There were 4445 patients in the older group ( mean 71 years ) and 5860 patients ( mean 57 years ) in the younger group . Among those taking placebo , the older group experienced a higher rate of primary endpoints than the younger group ( 11.7 vs. 7.6 events per 1000 patient years , respectively ) . After a median follow-up of 3.3 years , the primary endpoint was reduced by a similar proportion in both older and younger patients ( 37 vs. 33 % , respectively ) . Although older patients reported more serious adverse events than younger patients , there were no significant differences between atorvastatin and placebo within each age group . Conclusion Atorvastatin reduced the risk of major cardiovascular events to a similar relative extent in both older and younger patients with treated hypertension . However , given that event rates were higher in older patients , the absolute benefits of atorvastatin were greater for older than younger patients Background Traditional methods for analyzing clinical and epidemiological cohort study data have been focused on the first occurrence of a health outcome . However , in many situations , recurrent event data are frequently observed . It is inefficient to use methods for the analysis of first events to analyse recurrent event data . Methods We applied several semi-parametric proportional hazards models to analyze the risk of recurrent myocardial infa rct ion ( MI ) events based on data from a very large r and omized placebo-controlled trial of cholesterol-lowering drug .  The backward selection procedure was used to select the significant risk factors in a model . The best fitting model was selected using the log-likelihood ratio test , Akaike Information and Bayesian Information Criteria . Results A total of 8557 persons were included in the LIPID study . Risk factors such as age , smoking status , total cholesterol and high density lipoprotein cholesterol levels , qualifying event for the acute coronary syndrome , revascularization , history of stroke or diabetes , angina grade and treatment with pravastatin were significant for development of both first and subsequent MI events . No significant difference was found for the effects of these risk factors between the first and subsequent MI events . The significant risk factors selected in this study were the same as those selected by the parametric conditional frailty model . Estimates of the relative risks and 95 % confidence intervals were also similar between these two methods . Conclusions Our study shows the usefulness and convenience of the semi-parametric proportional hazards models for the analysis of recurrent event data , especially in estimation of regression coefficients and cumulative risks BACKGROUND The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome . No study , however , has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease ( CHD ) in hypertensive patients who are not conventionally deemed dyslipidaemic . METHODS Of 19342 hypertensive patients ( aged 40 - 79 years with at least three other cardiovascular risk factors ) r and omised to one of two antihypertensive regimens in the Anglo-Sc and inavian Cardiac Outcomes Trial , 10305 with non-fasting total cholesterol concentrations 6.5 mmol/L or less were r and omly assigned additional atorvastatin 10 mg or placebo .  These patients formed the lipid-lowering arm of the study . We planned follow-up for an average of 5 years , the primary endpoint being non-fatal myocardial infa rct ion and fatal CHD . Data were analysed by intention to treat . FINDINGS Treatment was stopped after a median follow-up of 3.3 years . By that time , 100 primary events had occurred in the atorvastatin group compared with 154 events in the placebo group ( hazard ratio 0.64 [ 95 % CI 0.50 - 0.83 ] , p=0.0005 ) . This benefit emerged in the first year of follow-up . There was no significant heterogeneity among prespecified subgroups . Fatal and non-fatal stroke ( 89 atorvastatin vs 121 placebo , 0.73 [ 0.56 - 0.96 ] , p=0.024 ) , total cardiovascular events ( 389 vs 486 , 0.79 [ 0.69 - 0.90 ] , p=0.0005 ) , and total coronary events ( 178 vs 247 , 0.71 [ 0.59 - 0.86 ] , p=0.0005 ) were also significantly lowered . There were 185 deaths in the atorvastatin group and 212 in the placebo group ( 0.87 [ 0.71 - 1.06 ] , p=0.16 ) . Atorvastatin lowered total serum cholesterol by about 1.3 mmol/L compared with placebo at 12 months , and by 1.1 mmol/L after 3 years of follow-up . INTERPRETATION The reductions in major cardiovascular events with atorvastatin are large , given the short follow-up time . These findings may have implication s for future lipid-lowering guidelines A double-blind , placebo-controlled , parallel-group study was performed to determine whether atorvastatin , a new HMG-CoA reductase inhibitor , could effectively and safely reduce plasma LDL-cholesterol concentrations in Japanese patients with type-2 diabetes without influencing glycemic control . The subjects were patients with hypercholesterolemia ( serum cholesterol concentration > or = 5.7 mmol/l ( 220 mg/dl ) ) and stable glycemic control . The fasting concentrations of hemoglobin A(1C ) ( HbA(1C ) ) , fructosamine , and 1,5-anhydroglucitol ( 1,5-AG ) were measured as indices of glycemic control . Plasma lipid concentrations and the safety of the drug were also examined . Forty eligible patients in two groups of 20 each were administered atorvastatin ( 10 mg/day ) or placebo . Neither atorvastatin nor placebo caused a significant change in HbA(1C ) , fructosamine , or 1,5-AG concentrations . Atorvastatin significantly reduced total cholesterol and LDL-cholesterol concentrations from baseline by 29.7 % ( p<0.0001 ) and 41.6 % ( p<0.0001 ) , respectively . The incidence of clinical adverse events and that of abnormal changes in laboratory test values did not differ between the two groups . In this trial , atorvastatin effectively and safely reduced LDL-cholesterol concentrations in diabetic patients with hypercholesterolemia without influencing glycemic control . These findings are clinical ly important because there are many diabetic patients with hypercholesterolemia and such patients have a high risk of developing arteriosclerotic disease CONTEXT Atherosclerosis is often advanced before symptoms appear and it is not clear whether treatment is beneficial in middle-aged individuals with a low Framingham risk score ( FRS ) and mild to moderate sub clinical atherosclerosis . OBJECTIVE To assess whether statin therapy could slow progression and /or cause regression of carotid intima-media thickness ( CIMT ) over 2 years . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled study ( Measuring Effects on Intima-Media Thickness : an Evaluation of Rosuvastatin [ METEOR ] ) of 984 individuals , with either age ( mean , 57 years ) as the only coronary heart disease risk factor or a 10-year FRS of less than 10 % , modest CIMT thickening ( 1.2-<3.5 mm ) , and elevated LDL cholesterol ( mean , 154 mg/dL ) ; conducted at 61 primary care centers in the United States and Europe between August 2002 and May 2006 . INTERVENTION Participants received either a 40-mg dose of rosuvastatin or placebo . MAIN OUTCOME MEASURES Rate of change in maximum CIMT ( assessed with B-mode ultrasound ) for 12 carotid sites ; changes in maximum CIMT of the common carotid artery , carotid bulb , and internal carotid artery sites and in mean CIMT of the common carotid artery sites . CIMT regression was assessed in the rosuvastatin group only . RESULTS Among participants in the rosuvastatin group , the mean ( SD ) baseline LDL cholesterol level of 155 ( 24.1 ) mg/dL declined to 78 ( 27.5 ) mg/dL , a mean reduction of 49 % ( P<.001 vs placebo group ) . The change in maximum CIMT for the 12 carotid sites was -0.0014 ( 95 % CI , -0.0041 to 0.0014 ) mm/y for the rosuvastatin group vs 0.0131 ( 95 % CI , 0.0087 - 0.0174 ) mm/y for the placebo group ( P<.001 ) . The change in maximum CIMT for the rosuvastatin group was -0.0038 ( 95 % CI , -0.0064 to -0.0013 ) mm/y for the common carotid artery sites ( P<.001 ) , -0.0040 ( 95 % CI , -0.0090 to 0.0010 ) mm/y for the carotid bulb sites ( P<.001 ) , and 0.0039 ( 95 % CI , -0.0009 to 0.0088 ) mm/y for the internal carotid artery sites ( P = .02 ) . The change in mean CIMT for the rosuvastatin group for the common carotid artery sites was 0.0004 ( 95 % CI , -0.0011 to 0.0019 ) mm/y ( P<.001 ) . All P values are vs placebo group . Overall , rosuvastatin was well tolerated with infrequent serious adverse cardiovascular events ( 6 participants [ 0.86 % ] had 8 events [ 1.1 % ] over 2 years ) . CONCLUSIONS In middle-aged adults with an FRS of less than 10 % and evidence of sub clinical atherosclerosis  , rosuvastatin result ed in statistically significant reductions in the rate of progression of maximum CIMT over 2 years vs placebo . Rosuvastatin did not induce disease regression . Larger , longer-term trials are needed to determine the clinical implication s of these findings . TRIAL REGISTRATION clinical trials.gov Identifier : Background —Cholesterol modification reduces cardiovascular events in patients with atherosclerosis , including those with peripheral arterial disease . The purpose of this study was to determine whether cholesterol lowering with atorvastatin improves walking performance in patients with intermittent claudication . Methods and Results —This r and omized , double-blind , parallel- design study included 354 persons with claudication attributable to peripheral arterial disease . Patients were treated with placebo , atorvastatin ( 10 mg per day ) , or atorvastatin ( 80 mg per day ) for 12 months . The outcome measures included change in treadmill exercise time and patient-reported measures of physical activity and quality of life based on question naires . Maximal walking time after 12 months of treatment with atorvastatin did not change significantly . However , there was improvement in pain-free walking time after 12 months of treatment for the 80-mg ( P = 0.025 ) group compared with placebo . A physical activity question naire demonstrated improvement in ambulatory ability for the 10- and 80-mg groups ( P = 0.011 ) , whereas 2 quality of life instruments , the Walking Impairment Question naire and Short Form 36 Question naire , did not show significant change . Conclusions —Atorvastatin improves pain-free walking distance and community-based physical activity in patients with intermittent claudication . When treated with atorvastatin , patients with peripheral arterial disease may experience improvement in symptoms to complement the anticipated reduction in cardiovascular events reported in other studies of statins Left ventricular ( LV ) mass is a powerful predictor for future cardiovascular events . Epidemiologic studies have shown that hyperlipidemia is associated with higher LV mass . The effects of statin therapy for hyperlipidemia on LV mass have not been studied . To determine the effects of statin therapy on LV mass , we prospect ively studied 3 groups of age and body surface area-matched patients : group 1 ( n = 20 ) , patients with systemic hypertension and hyperlipidemia treated with pravastatin plus anti-hypertensive drugs ; group 2 ( n = 20 ) , patients with hypertension and hyperlipidemia treated with hypertensive agents and diet control alone ; and group 3 ( n = 20 ) , hypertensive patients with normolipidemia treated with antihypertensive agents .  A group of controls without hypertension or hyperlipidemia  was used for comparison . Echocardiograms were recorded at baseline and after 6-month therapy . All hypertensive groups showed significant decreases in LV mass index after treatment . Group 1 had the greatest decrease in LV mass and it was significantly higher than in groups 2 and 3 . Multivariate analysis revealed that regression of LV mass was significantly correlated only with the use of statins and sex ( p = 0.005 and 0.01 , respectively , R(2 ) = 0.47 ) . Linear regression analysis in group 1 showed a significant correlation between changes in arterial compliance and LV mass regression ( r = 0.57 , p = 0.01 ) . Thus , the addition of a statin may have an additional effect on reducing LV mass , independent of lipid-lowering effects CONTEXT In pre clinical models , inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase have been shown to positively affect bone remodeling balance . Observational studies and secondary analyses from lipid-lowering trials have yielded inconsistent results regarding the effect of these agents on bone mineral density and fracture risk . OBJECTIVE Our objective was to determine whether clinical ly significant skeletal benefits result from hydroxymethylglutaryl-coenzyme A reductase inhibition in postmenopausal women . DESIGN AND SETTING We conducted a prospect i ve , r and omized , double-blind , placebo-controlled , dose-ranging comparative clinical trial at 62 sites in the United States . PARTICIPANTS Participants included 626 postmenopausal women with low-density lipoprotein cholesterol levels of at least 130 mg/dl ( 3.4 mmol/liter ) and less than 190 mg/dl ( 4.9 mmol/liter ) , and lumbar ( L1-L4 ) spine bone mineral density T-score between 0.0 and -2.5 . INTERVENTION Once-daily placebo or 10 , 20 , 40 , or 80 mg atorvastatin was administered . MAIN OUTCOME MEASURES We assessed percent change from baseline in lumbar ( L1-L4 ) spine bone mineral density with each dose of atorvastatin compared with placebo . RESULTS At 52 wk , there was no significant difference between each atorvastatin and placebo group or change from baseline at any tested dose of atorvastatin or placebo in lumbar ( L1-L4 ) spine bone mineral density . Nor did atorvastatin produce a significant change in bone mineral density at any other site . Changes in biochemical markers of bone turnover did not differ significantly between each atorvastatin and placebo group . All doses of atorvastatin were generally well tolerated , with similar incidences of adverse events across all dose groups and placebo . CONCLUSIONS Clinical ly relevant doses of atorvastatin that lower lipid levels had no effect on bone mineral density or biochemical indices of bone metabolism in this study , suggesting that such oral agents are not useful in the prevention or treatment of osteoporosis OBJECTIVE The aim of this study was to assess obese patients with hypercholesterolemia whom were prescribed a st and ardized diet , comparing the action of orlistat , fluvastatin , orlistat with fluvastatin , and placebo on anthropometric measurements , blood pressure ( BP ) , and lipid profile . METHODS This was a 1-year , r and omized , double-blind , placebo-controlled trial . The patients were prescribed a controlled-energy diet and were r and omly allocated to receive placebo , orlistat 120 mg TID ( O group ) , fluvastatin 80 mg/d ( F group ) , or olistat 120 mg TID with fluvastatin 80 mg/d ( OF group ) . Clinical measurements ( body weight , body mass index [ BMI ] , waist circumference , and BP ) and lipid profile assessment ( total cholesterol [ TC ] , low-density lipoprotein cholesterol [ LDL-C ] , high-density lipoprotein cholesterol [ HDL-C ] , and triglycerides [ TGs ] ) were performed at baseline and after 6 months and 1 year of treatment . RESULTS The study included 99 obese patients with hypercholesterolemia ( 48 men and 51 women ; mean [ SD ] age , 51 [ 9 ] years ) . There were no significant differences between groups in baseline demographic , BP , or plasma lipid values . Three patients dropped out ( 2 women in the O group and 1 man in the OF group ) due to adverse events related to orlistat treatment , including gastrointestinal events ( oily spotting and fecal urgency ) .  Ninety-six patients completed the study . There were significant differences from baseline ( mean [ SD ] ) in BMI , waist circumference reduction ( WCR ) , and body weight loss ( BWL ) at 6 months in the OF group ( 29.9 [ 1.1 ] kg/m(2 ) , 2.7 [ 0.8 ] cm , and 7.4 [ 0.9 ] kg , respectively ; all P < 0.05 ) , and BMI , WCR , and BWL at 1 year in the O group ( 29.0 [ 1.0 ] kg/m(2 ) , 3.0 [ 1.0 ] cm , and 8.6 [ 1.0 ] kg , respectively ; all P < 0.02 ) , the F group ( 29.3 [ 1.6 ] kg/m(2 ) , 2.4 [ 1.0 ] cm , and 8/0 [ 1.0 ] kg , respectively ; all P < 0.05 ) , and the OF group ( 28.4 [ 0.6 ] kg/m(2 ) , 4.0 [ 0.6 ] cm , and 11.4 [ 1.0 ] kg , respectively ; all P < 0.01 ) . Significant reductions from baseline in systolic and diastolic BP were observed at 1 year in the O and F groups ( all P < 0.05 ) and the OF group ( both P < 0.01 ) . At 6 months , there were significant reductions from baseline in TC and LDL-C in the F group ( both P < 0.05 ) and in TC , LDL-C , and TGs in the OF group ( P < 0.02 , P < 0.02 , and P < 0.05 , respectively ) , as well as a significant increase in HDL-C in the OF group ( P < 0.02 ) . At 1 year , there were significant reduction from baseline in TC in the O , F , and OF groups ( P < 0.05 and P < 0.01 , respectively ) , LDL-C ( P < 0.05 , P < 0.02 , and P < 0.01 , respectively ) , and TGs ( P < 0.02 , P < 0.05 , and P < 0.02 , respectively ) . Also at 1 year , HDL-C was significantly higher than baseline in the F and OF groups ( P < 0.02 and P < 0.01 , respectively ) . CONCLUSION Improvements in clinical and lipid-profile parameters were found at 1 year with all 3 treatments OBJECTIVE —Cardiovascular disease ( CVD ) risk is increased in type 2 diabetes . The purpose of this study was to assess the effect of 10 mg of atorvastatin versus placebo on CVD prevention in subjects with type 2 diabetes and LDL cholesterol levels below contemporary guideline targets . RESEARCH DESIGN AND METHODS —Subjects were r and omly assigned to receive 10 mg of atorvastatin or placebo in a 4-year , double-blind , parallel-group study . The composite primary end point comprised cardiovascular death , nonfatal myocardial infa rct ion , nonfatal stroke , recanalization , coronary artery bypass surgery , resuscitated cardiac arrest , and worsening or unstable angina requiring hospitalization . RESULTS —A total of 2,410 subjects with type 2 diabetes were r and omized .  Mean LDL cholesterol reduction in the atorvastatin group over 4 years was 29 % versus placebo ( P < 0.0001 ) . When we compared atorvastatin versus placebo , composite primary end point rates were 13.7 and 15.0 % , respectively ( hazard ratio 0.90 [ 95 % CI 0.73–1.12 ] ) . In the subset of 1,905 subjects without prior myocardial infa rct ion or interventional procedure , 10.4 % of atorvastatin- and 10.8 % of placebo-treated subjects experienced a primary end point ( 0.97 [ 0.74–1.28 ] ) . In the 505 subjects with prior myocardial infa rct ion or interventional procedure , 26.2 % of atorvastatin- and 30.8 % of placebo-treated subjects experienced a primary end point ( 0.82 [ 0.59–1.15 ] ) . Relative risk reductions in fatal and nonfatal myocardial infa rct ion were 27 % overall ( P = 0.10 ) and 19 % ( P = 0.41 ) and 36 % ( P = 0.11 ) for subjects without and with prior myocardial infa rct ion or interventional procedure , respectively . CONCLUSIONS —Composite end point reductions were not statistically significant . This result may relate to the overall study design , the types of subjects recruited , the nature of the primary end point , and the protocol changes required because of changing treatment guidelines . For these reasons , the results of the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus ( ASPEN ) did not confirm the benefit of therapy but do not detract from the imperative that the majority of diabetic patients are at risk of coronary heart disease and deserve LDL cholesterol lowering to the currently recommended targets BACKGROUND HMG CoA reductase inhibitors ( or statins ) , a new class of lipid-lowering compounds , have raised expectations for more widespread use than that of the older lipid-lowering drugs . Not only are they more effective in lowering LDL cholesterol , but they are better tolerated as well . No data exist concerning the effect of statins on early carotid atherosclerosis and clinical events in men and women who have moderately elevated LDL cholesterol levels but are free of symptomatic cardiovascular disease . METHODS AND RESULTS Lovastatin ( 20 to 40 mg/d ) or its placebo was evaluated in a double-blind , r and omized clinical trial with factorial design along with warfarin ( 1 mg/d ) or its placebo . This report is limited to the lovastatin component of the trial . Daily aspirin ( 81 mg/d ) was recommended for everyone . Enrollment included 919 asymptomatic men and women , 40 to 79 years old , with early carotid atherosclerosis as defined by B-mode ultrasonography and LDL cholesterol between the 60th and 90th percentiles . The 3-year change in mean maximum intimal-medial thickness ( IMT ) in 12 walls of the carotid arteries was the primary outcome ; change in single maximum IMT and incidence of major cardiovascular events were secondary outcomes . LDL cholesterol fell 28 % , from 156.6 mg/dL at baseline to 113.1 mg/dL at 6 months ( P < .0001 ) , in the lovastatin groups and was largely unchanged in the lovastatin-placebo groups . Among participants not on warfarin , regression of the mean maximum IMT was seen after 12 months in the lovastatin group compared with the placebo group ; the 3-year difference was statistically significant ( P = .001 ) . A larger favorable effect of lovastatin was observed for the change in single maximum IMT but was not statistically significant ( P = .12 ) . Five lovastatin-treated participants suffered major cardiovascular events -- coronary heart disease mortality , nonfatal myocardial infa rct ion , or stroke -- versus 14 in the lovastatin-placebo groups ( P = .04 ) . One lovastatin-treated participant died , compared with eight on lovastatin-placebo ( P = .02 ) . CONCLUSIONS In men and women with moderately elevated LDL cholesterol , lovastatin reverses progression of IMT in the carotid arteries and appears to reduce the risk of major cardiovascular events and mortality . Results from ongoing large-scale clinical trials may further establish the clinical benefit of statins OBJECTIVES The study sought to determine the effects of lipid-lowering with pravastatin on the systemic fibrinolytic profile and on thrombus formation under dynamic flow conditions . BACKGROUND Lowering cholesterol ( C ) decreases clinical events in coronary artery disease ( CAD ) patients , but an analysis of the effects of lipid-lowering on the entire hemostatic and thrombotic profile has not been conducted . METHODS We prospect ively studied 93 stable patients with untreated low-density lipoprotein cholesterol ( LDL-C ) > 145 mg/dl . The CAD patients received pravastatin , and non-CAD patients were r and omized to pravastatin versus placebo ( double-blind ) . Thrombus formation upon an injured vascular surface was assessed in a sub study of 40 patients with a previously vali date d ex vivo perfusion chamber system . Systemic hemostatic markers and thrombus formation were evaluated at baseline , three and six months . RESULTS Placebo produced no changes in either the lipid profile , any of the hemostatic markers , or the ex vivo thrombus formation . Both pravastatin groups ( CAD and non-CAD ) showed decreased LDL-C by 30 % within 6 weeks ( 188 to 126 mg/dl , p < 0.001 vs. baseline ) , and decreased plasminogen activator inhibitor-1 at 3- and 6-month follow-up compared to baseline ( 15 % to 18 % decrease at 3 months and 21 % to 23 % at 6 months ) . For the tissue plasminogen activator antigen , CAD and non-CAD groups showed significant decreases at 6 months compared to baseline ( 10 % and 13 % , respectively ) . No significant changes were observed with treatment in d-dimer , fibrinopeptide A , prothrombin fragment F1.2 , factor VIIa , von Willebr and factor , or C-reactive protein . Fibrinogen levels were significantly increased at 6 months compared to baseline , though still below the upper normal limit . In the perfusion chamber sub study , there was a decrease in thrombus area in non-CAD patients treated with pravastatin at both 3 and 6 months compared to baseline ( by 21 % and 34 % , respectively ) . The CAD patients showed decreases in thrombus formation by 13 % at 3 months , and by 16 % at 6 months . The change in LDL-C- correlated modestly with the change in thrombus formation ( r = 0.49 ; p < 0.01 ) . CONCLUSIONS Pravastatin therapy significantly decreased thrombus formation and improved the fibrinolytic profile in patients with and without CAD . These early effects may , in part , explain the benefit rendered in primary and secondary prevention of CAD OBJECTIVE --To examine the relation between serum cholesterol concentration and mortality ( from coronary heart disease and from other causes ) below the range of cholesterol values generally seen in Western population s. DESIGN -- Prospect i ve observational study based on 8 - 13 years of follow up of subjects in a population with low cholesterol concentrations . SETTING --Urban Shanghai , China . SUBJECTS--9021 Chinese men and women aged 35 - 64 at baseline . MAIN OUTCOME MEASURE -- Death from coronary heart disease and other causes . RESULTS --The average serum cholesterol concentration was 4.2 mmol/l at baseline examination , and only 43 ( 7 % ) of the deaths that occurred during 8 - 13 years of follow up were attributed to coronary heart disease . There was a strongly positive , and apparently independent , relation between serum cholesterol concentration and death from coronary heart disease ( z = 3.47 , p less than 0.001 ) , and within the range of usual serum cholesterol concentration studied ( 3.8 - 4.7 mmol/l ) there was no evidence of any threshold . After appropriate adjustment for the regression dilution bias , a 4 ( SD 1)% difference in usual cholesterol concentration was associated with a 21 ( SD 6)% ( 95 % confidence interval 9 % to 35 % ) difference in mortality from coronary heart disease . There was no significant relation between serum cholesterol concentration and death from stroke or all types of cancer . The 79 deaths due to liver cancer or other chronic liver disease were inversely related to cholesterol concentration at baseline . CONCLUSION --Blood cholesterol concentration was directly related to mortality from coronary heart disease even in those with what was , by Western st and ards , a " low " cholesterol concentration . There was no good evidence of an adverse effect of cholesterol on other causes of death The interlead variability of QT interval in the 12-lead electrocardiogram , QT dispersion ( QTd ) , has been shown to reflect dispersion of ventricular refractoriness and may provide a measure of arrhythmogenic potential in diabetic patients .  QTd and heart rate corrected QTd ( QTcd ) were also proposed to be accurate predictors of cardiac death in patients with diabetes . In recent years , experimental and clinical evidence demonstrates that statins exert antiarrhythmic properties . Therefore , in the present study , we have examined whether simvastatin treatment has any effect on the QTd and QTcd in patients with diabetes mellitus . Sixty type 2 diabetic patients without known coronary artery disease and low-density lipoprotein cholesterol > 100mg/dl and 30 age and sex-matched non-diabetic controls were included in a prospect i ve study . Out of 60 diabetic patients , 30 were treated with simvastatin 40 mg/day for 1 year and the remaining 30 subjects were served as diabetic controls . No lipid lowering therapy was administered to the diabetic and the non-diabetic controls . QTd and QTcd of treated diabetics and the non-diabetic controls were measured at baseline , 6 , 12 weeks and at 1 year . QTd and QTcd of the diabetic controls were obtained at baseline , 6 and 12 weeks . Both QTd and QTcd were significantly greater in patients with the diabetes than in the non-diabetic controls at baseline ( 52+/-13 ms vs. 41+/-12 ms , p<0.001 and 62+/-17 ms vs. 42+/-11 ms , p<0.001 , respectively ) . Simvastatin therapy significantly decreased both QTd and QTcd at the end of first year compared to baseline ( 51+/-15 ms vs. 33+/-11 ms , p<0.001 and 60+/-18 ms vs. 38+/-12 ms , p<0.001 , respectively ) . No significant change were found in QTd and QTcd in the non-diabetic ( p=0.29 and p=0.87 by ANOVA , respectively ) and in the diabetic controls ( p=0.72 and p=0.57 , by ANOVA , respectively ) . This study suggests for the first time that simvastatin treatment in diabetic patients with hyperlipidemia is associated with an improvement in the heterogeneity of cardiac repolarization . This may be one of the mechanisms for the reduction in clinical events reported in the survival studies with statins . Further prospect i ve r and omized studies are warranted to confirm our findings The r and omized , double-blind , placebo-controlled trial described in this report was undertaken to clarify the dose-response relation of lovastatin therapy to lipid-modifying efficacy ( lipid/lipoprotein modification ) and drug-related adverse events in a population with moderately elevated fasting plasma total cholesterol ( 240 to 300 mg/dl ) and low-density lipoprotein cholesterol ( greater than or equal to 160 mg/dl ) . Men or women ( postmenopausal or surgically sterile ) , aged 18 to 70 years , were entered into the trial with minimal exclusion criteria . After 4 to 6 weeks of an American Heart Association phase I diet or a more stringent diet , 8,245 patients from 362 sites were r and omized to 1 of 5 parallel diet and drug treatment groups : placebo ( n = 1,663 ) or lovastatin , 20 mg ( n = 1,642 ) and 40 mg ( n = 1,645 ) with the evening meal , and 20 mg ( n = 1,646 ) or 40 mg twice daily ( n = 1,649 ) . The regimen of diet and lovastatin ( or placebo ) was followed for 48 weeks . The 5 treatment groups were similar at baseline . The total cohort had the following characteristics : 59 % were men ( mean age 56 years ) ; 92 % were white ; 59 % had completed at least 1 year of education beyond high school ; 57 % had a history of cardiovascular and associated disease ; 40 % had a history of hypertension ; and 29 % had coronary artery disease .  Health habits were similar among groups , with 18 % of patients reporting cigarette smoking , 14 % reporting that they consume greater than 1 alcoholic beverage daily and 67 % reporting no strenous exercise . Mean lipid/lipoprotein levels were also similar among groups , with the following average levels : total cholesterol ( 258 mg/dl ) , low-density lipoprotein cholesterol ( 180 mg/dl ) , high-density lipoprotein cholesterol ( 45 mg/dl ) and triglycerides ( median = 155 mg/dl ) . The large size of this trial , its placebo-controlled , double-blind design and the similarity of treatment groups at baseline should allow clear documentation of the long-term effects of lovastatin treatment and generalization of the results to a substantial portion of patients who may be c and i date s for lipid-modifying therapy Statins are widely prescribed for the primary and secondary prevention of coronary artery disease . They act by inhibiting the enzyme HMG CoA reductase , which controls synthesis of cholesterol in the liver . Most manufacturers of statins recommend that they are taken at night , on the basis of physiological studies which show that most cholesterol is synthesis ed when dietary intake is at its lowest.1 One small clinical trial found that taking smaller doses of simvastatin than are used in treatment , in the morning , was less efficient.2 However , a trial using atorvastatin found no significant difference in cholesterol concentrations between patients taking the statin in the morning and those taking it in the evening.3 Doubt has been cast on whether statins need to be taken at night,4 particularly as many patients also receive treatment with other cardioprotective drugs and compliance may be compromised by multiple Background PROSPER was design ed to investigate the benefits of treatment with pravastatin in elderly patients for whom a typical doctor might consider the prescription of statin therapy to be a realistic option . Methods The PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) is a r and omised , double blind , placebo-controlled trial to test the hypothesis that treatment with pravastatin ( 40 mg/day ) will reduce the risk of coronary heart disease death , non-fatal myocardial infa rct ion , and fatal or non-fatal stroke in elderly men and women with pre-existing vascular disease or with significant risk of developing this condition . Results In Scotl and , Irel and , and the Netherl and s , 23,770 individuals were screened , and 5,804 subjects ( 2,804 men and 3,000 women ) , aged 70 to 82 years ( average 75 years ) and with baseline cholesterol 4.0–9.0 mmol/l , were r and omised . R and omised subjects had similar distributions with respect to age , blood pressure , and body mass index when compared to the entire group of screenees , but had a higher prevalence of smoking , diabetes , hypertension , and a history of vascular disease . The average total cholesterol level at baseline was 5.4 mmol/l ( men ) and 6.0 mmol/l ( women ) . Conclusions Compared with previous prevention trials of cholesterol-lowering drugs , the PROSPER cohort is significantly older and for the first time includes a majority of women . The study , having achieved its initial goal of recruiting more than 5,500 elderly high-risk men and women , aims to complete all final subject follow-up visits in the first half of 2002 with the main results being available in the fourth quarter of 2002 Abstract Objective To investigate risk factors , such as heavy alcohol consumption , that might explain any increased risk of  haemorrhagic stroke associated with low blood cholesterol . Design Prospect i ve cohort study . Setting Korea . Participants 787 442 civil servants ( 661 700 men , 125 742 women ) aged 30 - 64 . Main outcome measures Cardiovascular risk factors were assessed at biennial health check . Data on morbidity and mortality were ascertained from 1990 to 2001 using hospital admissions and mortality surveillance systems . Results 6328 cases of ischaemic stroke ( 6021 men , 307 women ) , 3947 cases of haemorrhagic stroke ( 3748 men , 199 women ) , 3170 cases of undefined stroke ( 2902 men , 268 women ) , and 4417 cases of myocardial infa rct ion ( 4305 men , 112 women ) occurred . Ischaemic stroke and myocardial infa rct ion were strongly and positively associated with blood cholesterol ( hazard ratio per 1 mmol/l cholesterol 1.20 ( 95 % confidence 1.16 to 1.24 ) and 1.48 ( 1.43 to 1.53 ) , respectively ) . Haemorrhagic stroke showed an inverse association in fully adjusted models ( 0.91 , 0.87 to 0.95 ) . This inverse association was confined to participants with hypertension . When stratified by concentration of γ glutamyl transferase ( GGT ) , an indicator of alcohol consumption , the association was not seen in participants with low concentrations of GGT , and it was independent of hypertension in those with high concentrations of GGT ( > 80 U/l ) . Conclusion High alcohol consumption may underlie the association between low blood cholesterol and increased risk of haemorrhagic stroke Simvastatin , a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor , has been administered to approximately 2,400 patients with primary hypercholesterolemia with a mean follow-up of 1 year in controlled clinical studies and their open extensions . Approximately 10 % of this population received simvastatin for a period of greater than or equal to 2 years . The population on whom this safety analysis is based had a mean age of 50 years ; 62 % were men and approximately 27 % had preexisting coronary artery disease .  Simvastatin was titrated to the maximal daily dose of 40 mg each evening in 56 % of the study population ( last recorded dose ) . The most frequently reported drug-related clinical adverse experiences were constipation ( 2.5 % ) , abdominal pain ( 2.2 % ) , flatulence ( 2.0 % ) and headaches ( 1 % ) . Persistent elevations of serum transaminase levels greater than 3 times the upper limit of normal were observed in only 1 % of this cohort with only 0.1 % of the total population requiring discontinuation of therapy . There were no clinical ly apparent episodes of hepatitis . Discontinuation of therapy due to myopathy was extremely rare ( 0.08 % ) . Only minimal increases in the frequency of lens opacities ( 1 % ) were observed from baseline to the last lens examination during follow-up , consistent with the expected increase in lens opacity development due to normal aging . Patients who were greater than or equal to 65 years old had a clinical and laboratory safety profile comparable to the nonelderly population . ( ABSTRACT TRUNCATED AT 250 WORDS PURPOSE Animal research and cross-sectional studies suggest that serum lipid concentrations may influence cognitive function , mood , and behavior , but few clinical trials have studied these effects . SUBJECTS AND METHODS In this double-blind investigation , 209 generally healthy adults with a serum low-density-lipoprotein ( LDL ) cholesterol level of 160 mg/dL or higher were r and omly assigned to 6-month treatment with lovastatin ( 20 mg ) or placebo . Assessment s of neuropsychological performance , depression , hostility , and quality of life were conducted at baseline and at the end of the treatment period . Summary effect sizes were estimated as z scores on a st and ard deviation ( SD ) scale . RESULTS Placebo-treated subjects improved between baseline and posttreatment periods on neuropsychological tests in all five performance domains , consistent with the effects of practice on test performance ( all P < 0.04 ) , whereas those treated with lovastatin improved only on tests of memory recall ( P = 0.03 ) . Comparisons of the changes in performance between placebo- and lovastatin-treated subjects revealed small , but statistically significant , differences for tests of attention ( z score = 0.18 ; 95 % confidence interval ( CI ) , 0.06 to 0.31 ; P = 0.005 ) and psychomotor speed ( z score = 0.17 ; 95 % CI , 0.05 to 0.28 ; P = 0 . 004 ) that were consistent with greater improvement in the placebo group . Psychological well-being , as measured several ways , was not affected by lovastatin . CONCLUSION Treatment of hypercholesterolemia with lovastatin did not cause psychological distress or substantially alter cognitive function . Treatment did result in small performance decrements on neuropsychological tests of attention and psychomotor speed , the clinical importance of which is uncertain BACKGROUND Evidence -based treatment for hypercholesterolaemia in Japan has been hindered by the lack of direct evidence in this population . Our aim was to assess whether evidence for treatment with statins derived from western population s can be extrapolated to the Japanese population . METHODS In this prospect i ve , r and omised , open-labelled , blinded study , patients with hypercholesterolaemia ( total cholesterol 5.69 - 6.98 mmol/L ) and no history of coronary heart disease or stroke were r and omly assigned diet or diet plus 10 - 20 mg pravastatin daily . The primary endpoint was the first occurrence of coronary heart disease . Statistical analyses were done by intention to treat . This trial is registered at Clinical Trials.gov , number NCT00211705 . FINDINGS 3966 patients were r and omly assigned to the diet group and 3866 to the diet plus pravastatin group . Mean follow-up was 5.3 years . At the end of study , 471 and 522 patients had withdrawn , died , or been lost to follow-up in the diet and diet plus pravastatin groups , respectively . Mean total cholesterol was reduced by 2.1 % ( from 6.27 mmol/L to 6.13 mmol/L ) and 11.5 % ( from 6.27 mmol/L to 5.55 mmol/L ) and mean LDL cholesterol by 3.2 % ( from 4.05 mmol/L to 3.90 mmol/L ) and 18.0 % ( from 4.05 mmol/L to 3.31 mmol/L ) in the diet and the diet plus pravastatin groups , respectively . Coronary heart disease was significantly lower in the diet plus pravastatin group than in the diet alone group ( 66 events vs 101 events ; HR 0.67 , 95 % CI 0.49 - 0.91 ; p=0.01 ) . There was no difference in the incidence of malignant neoplasms or other serious adverse events between the two groups . INTERPRETATION Treatment with a low dose of pravastatin reduces the risk of coronary heart disease in Japan by much the same amount as higher doses have shown in Europe and the USA BACKGROUND The West of Scotl and Coronary Prevention Study was a r and omized clinical trial comparing pravastatin with placebo in men with hypercholesterolemia who did not have a history of myocardial infa rct ion , with an average follow-up of approximately 5 years . The combined outcome of death from definite coronary heart disease or definite nonfatal myocardial infa rct ion was reduced from 7.9 to 5.5 % ( P<0.001 ) in the treatment group . Extended follow-up data were obtained for approximately 10 years after completion of the trial . METHODS For the survivors of the trial , all deaths , hospitalizations and deaths due to coronary events and stroke , and incident cancers and deaths from cancer were tracked with the use of a national computerized record-linkage system . The results were analyzed with time-to-event analyses and use of Cox proportional-hazards models . RESULTS Five years after the trial ended , 38.7 % of the original statin group and 35.2 % of the original placebo group were being treated with a statin . In the period approximately 10 years after completion of the trial , the risk of death from coronary heart disease or nonfatal myocardial infa rct ion was 10.3 % in the placebo group and 8.6 % in the pravastatin group ( P=0.02 ) ; over the entire follow-up period , the rate was 15.5 % in the placebo group and 11.8 % in the pravastatin group ( P<0.001 ) . Similar percentage reductions were seen in the combined rate of death from coronary heart disease and hospitalization for coronary events for both periods . The rate of death from cardiovascular causes was reduced ( P=0.01 ) , as was the rate of death from any cause ( P=0.03 ) , over the entire follow-up period . There were no excess deaths from noncardiovascular causes or excess fatal or incident cancers . CONCLUSIONS In this analysis , 5 years of treatment with pravastatin was associated with a significant reduction in coronary events for a subsequent 10 years in men with hypercholesterolemia who did not have a history of myocardial infa rct ion AIMS To assess the effect of statins on a range of health outcomes . METHODS We undertook a population -based cohort study to assess the effect of statins on a range of health outcomes using a propensity score-based method to control for differences between people prescribed and not prescribed statins .  We vali date d our design by comparing our results for vascular outcomes with the effects established in large r and omized trials . The study was based on the United Kingdom Health Improvement Network data base that includes the computerized medical records of over four and a half million patients . RESULTS People who initiated treatment with a statin ( n = 129,288 ) were compared with a matched sample of 600,241 people who did not initiate treatment , with a median follow-up period of 4.4 years . Statin use was not associated with an effect on a wide range of outcomes , including infections , fractures , venous thromboembolism , gastrointestinal haemorrhage , or on specific eye , neurological or autoimmune diseases . A protective effect against dementia was observed ( hazard ratio 0.80 , 99 % confidence interval 0.68 , 0.95 ) . There was no effect on the risk of cancer even after > or = 8 years of follow-up . The effect sizes for statins on vascular end-points and mortality were comparable to those observed in large r and omized trials , suggesting bias and confounding had been well controlled for . CONCLUSIONS We found little evidence to support wide-ranging effects of statins on health outcomes beyond their established beneficial effect on vascular disease Objective To quantify the unintended effects of statins according to type , dose , and duration of use . Design Prospect i ve open cohort study using routinely collected data . Setting 368 general practice s in Engl and and Wales supplying data to the Q Research data base . Participants 2 004 692 patients aged 30 - 84 years of whom 225 922 ( 10.7 % ) were new users of statins : 159 790 ( 70.7 % ) were prescribed simvastatin  , 50 328 ( 22.3 % ) atorvastatin , 8103 ( 3.6 % ) pravastatin , 4497 ( 1.9 % ) rosuvastatin , and 3204 ( 1.4 % ) fluvastatin . Methods Cox proportional hazards models were used to estimate effects of statin type , dose , and duration of use . The number needed to treat ( NNT ) or number needed to harm ( NNH ) was calculated and numbers of additional or fewer cases estimated for 10 000 treated patients . Main outcome measure First recorded occurrence of cardiovascular disease , moderate or serious myopathic events , moderate or serious liver dysfunction , acute renal failure , venous thromboembolism , Parkinson ’s disease , dementia , rheumatoid arthritis , cataract , osteoporotic fracture , gastric cancer , oesophageal cancer , colon cancer , lung cancer , melanoma , renal cancer , breast cancer , or prostate cancer . Results Individual statins were not significantly associated with risk of Parkinson ’s disease , rheumatoid arthritis , venous thromboembolism , dementia , osteoporotic fracture , gastric cancer , colon cancer , lung cancer , melanoma , renal cancer , breast cancer , or prostate cancer . Statin use was associated with decreased risks of oesophageal cancer but increased risks of moderate or serious liver dysfunction , acute renal failure , moderate or serious myopathy , and cataract . Adverse effects were similar across statin types for each outcome except liver dysfunction where risks were highest for fluvastatin . A dose-response effect was apparent for acute renal failure and liver dysfunction . All increased risks persisted during treatment and were highest in the first year . After stopping treatment the risk of cataract returned to normal within a year in men and women . Risk of oesophageal cancer returned to normal within a year in women and within 1 - 3 years in men . Risk of acute renal failure returned to normal within 1 - 3 years in men and women , and liver dysfunction within 1 - 3 years in women and from three years in men . Based on the 20 % threshold for cardiovascular risk , for women the NNT with any statin to prevent one case of cardiovascular disease over five years was 37 ( 95 % confidence interval 27 to 64 ) and for oesophageal cancer was 1266 ( 850 to 3460 ) and for men the respective values were 33 ( 24 to 57 ) and 1082 ( 711 to 2807 ) . In women the NNH for an additional case of acute renal failure over five years was 434 ( 284 to 783 ) , of moderate or severe myopathy was 259 ( 186 to 375 ) , of moderate or severe liver dysfunction was 136 ( 109 to 175 ) , and of cataract was 33 ( 28 to 38 ) . Overall , the NNHs and NNTs for men were similar to those for women , except for myopathy where the NNH was 91 ( 74 to 112 ) . Conclusions Cl aims of unintended benefits of statins , except for oesophageal cancer , remain unsubstantiated , although potential adverse effects at population level were confirmed and quantified . Further studies are needed to develop utilities to individualise the risks so that patients at highest risk of adverse events can be monitored closely OBJECTIVE Cardiovascular disease ( CVD ) is the most important cause of mortality in patients with type 2 diabetes . We aim ed to determine the effect of statin therapy versus placebo on the progression of carotid intima-media thickness ( IMT ) in type 2 diabetic patients without manifest CVD . RESEARCH DESIGN AND METHODS A r and omized , placebo-controlled , double-blind clinical trial was performed in 250 patients with type 2 diabetes . Patients were given either 0.4 mg cerivastatin or placebo daily . In August 2001 , when cerivastatin was withdrawn from the market , 0.4 mg cerivastatin was replaced by 20 mg simvastatin without deblinding the study . The primary end point was the change of mean common carotid IMT , as measured by B-mode ultrasound , over 2 years . RESULTS Common carotid IMT at baseline was 0.780 mm in the placebo group and 0.763 mm in the statin group and did not change significantly after 2 years . There was no significant difference in IMT change in any carotid segment between the groups . LDL cholesterol was reduced by 25 % in the statin group and increased by 8 % in the placebo group ( P < 0.001 ) . Cardiovascular events occurred in 12 patients in the placebo group and two patients in the statin group ( P=0.006 ) . CONCLUSIONS There was no effect of 2 years ' statin therapy on carotid IMT in type 2 diabetic subjects . The natural history of IMT in our patients was milder than anticipated . In contrast , we observed a significantly lower cardiovascular event rate on statin therapy . Prognostic tools other than IMT should be explored in this patient group BACKGROUND Statins improve lipid profiles and reduce cardiovascular morbidity and mortality but there are few data on their relative effects in different ethnic groups . METHODS We used data from the r and omised , placebo-controlled Anglo-Sc and inavian Cardiac Outcomes Trial-Lipid Lowering Arm ( ASCOT-LLA ) to conduct a prespecified comparison of the lipid-lowering efficacy of statin therapy among hypertensive participants from different ethnic groups in the UK and Irel and . The effects of atorvastatin ( 10 mg daily ) and placebo on fasting plasma lipid profiles were compared in matched groups of Whites and Blacks ( of African-Caribbean or African origin ) and Whites and South Asians ( from the Indian subcontinent ) , adjusting for placebo effect . RESULTS In the active treatment group , 156 Blacks and 72 South Asians were compared with 419 and 198 Whites , respectively . In multivariable analyses adjusted for baseline lipid levels and other potential confounders , atorvastatin reduced total cholesterol , low-density lipoprotein (LDL)-cholesterol and triglycerides from baseline in all ethnic groups . There were no clinical ly or statistically significant differences in the effect between Whites and Blacks or between Whites and South Asians after adjusting for placebo effect ; similar proportions in each group achieved lipid targets . There was no significant effect of atorvastatin on high-density lipoprotein (HDL)-cholesterol in any group . CONCLUSIONS A st and ard dose of atorvastatin improved lipid profiles to a similar extent in Whites , Blacks and South Asians . Given the proven benefits of statins , these results suggest that , when used in st and ard doses , they are likely to be similarly effective for cardiovascular disease prevention in all ethnic groups Objective To investigate the possibility that statins reduce blood pressure as well as cholesterol concentrations through clinic and 24 hour ambulatory blood pressure monitoring . Design R and omised placebo controlled double blind trial . Setting 13 hospitals in Italy Participants 508 patients with mild hypertension and hypercholesterolaemia , aged 45 to 70 years . Intervention Participants were r and omised to antihypertensive treatment ( hydrochlorothiazide 25 mg once daily or fosinopril 20 mg once daily ) with or without the addition of a statin ( pravastatin 40 mg once daily ) . Main outcome measures Clinic and ambulatory blood pressure measured every year throughout an average 2.6 year treatment period . Results Both the group receiving antihypertensive treatment without pravastatin ( n=254 ) ( with little change in total cholesterol ) and the group receiving antihypertensive treatment with pravastatin ( n=253 ) ( with marked and sustained reduction in total cholesterol and low density lipoprotein cholesterol ) had a clear cut sustained reduction in clinic measured systolic and diastolic blood pressure as well as in 24 hour , and day and night , systolic and diastolic blood pressure .  Pravastatin performed slightly worse than placebo , and between group differences did not exceed 1.9 ( 95 % confidence interval −0.6 to 4.3 , P=0.13 ) mm Hg throughout the treatment period . This was also the case when participants who remained on monotherapy with hydrochlorothiazide or fosinopril throughout the study were considered separately . Conclusions Administration of a statin in hypertensive patients in whom blood pressure is effectively reduced by concomitant antihypertensive treatment does not have an additional blood pressure lowering effect . Trial registration BRISQUI_*IV_2004_001 ( registered at Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali — National Monitoring Centre on Clinical Research with Medicines ) Aims On the basis of the JUPITER trial , European health authorities recently approved the use of rosuvastatin to reduce first major cardiovascular events among ‘ high ' global risk primary prevention patients defined either by Framingham risk score > 20 % or European systematic coronary risk evaluation ( SCORE ) ≥5 % . However , as these are post hoc analyses , data describing these subgroups have not previously been available to the clinical community . Methods and results We r and omized 17 802 apparently healthy men aged ≥50 and women ≥60 with low-density lipoprotein cholesterol ( LDL-C ) < 3.4 mmol/L , who were at an increased vascular risk due to elevated levels of C-reactive protein measured with a high-sensitivity ( hs ) assay to rosuvastatin 20 mg daily or placebo . Patients with high global cardiovascular risk at baseline were identified by 10-year Framingham risk score > 20 % or SCORE risk ≥5 % . During 1.8-year median follow-up ( maximum 5 years ) of patients with Framingham risk > 20 % , the rate of myocardial infa rct ion/stroke/cardiovascular death was 9.4 and 18.2 per 1000 person-years in rosuvastatin and placebo-allocated patients , respectively [ hazard ratio ( HR ) : 0.50 , 95 % confidence interval ( CI ) : 0.27–0.93 , P = 0.028 ] . Among patients with SCORE risk ≥5 % , the corresponding rates were 6.9 and 12.0 using a model extrapolating risk for age ≥65 years ( HR : 0.57 , 95 % CI : 0.43–0.78 , P = 0.0003 ) and rates were 5.9 and 12.7 when risk for age was capped at 65 years ( HR : 0.47 , 95 % CI : 0.32–0.68 , P < 0.0001 ) . Conclusion In primary prevention patients with elevated hs C-reactive protein who have high global cardiovascular risk ( 10-year Framingham risk score > 20 % or SCORE risk ≥5 % ) , but LDL-C levels not requiring pharmacologic treatment , rosuvastatin 20 mg significantly reduced major cardiovascular events . Clinical Trial.gov Identifier : Objectives . To investigate the independent and combined effects of lifestyle changes and statin treatment on soluble markers of atherosclerotic activity . Design . The study was a r and omised , 2 × 2 factorial 1 year intervention trial . Participants ( n=177 ) were sedentary , drug-treated , hypertensive men ( aged 40–74 years ) . They were r and omised to  placebo , lifestyle intervention ( diet and physical activity ) , fluvastatin 40 mg , or the combination of lifestyle and fluvastatin . Results . Lifestyle intervention significantly reduced intercellular adhesion molecule-1 ( sICAM-1 ) compared to usual care ( p=0.003 ) . Thrombomodulin level remained higher among individuals receiving lifestyle intervention ( p=0.025 ) . sICAM-1 was less reduced among fluvastatin treated participants compared to the placebo treated ( p=0.029 ) . Changes of blood pressure , weight or waist circumference were not significantly different between treatment groups . Individuals who achieved improvement of classical risk factors also had a significant reduction of endothelial markers ( E-selectin , von Willebr and s factor , tissue plasminogen activator antigen ) . Conclusions . One year of lifestyle intervention reduced the level of sICAM-1 in sedentary , drug-treated hypertensives , in spite of no impact on traditional risk factors . Low dose fluvastatin had no beneficial effect on the measured markers The Justification for the Use of Statins in Primary Prevention : An Intervention Trial Evaluating Rosuvastatin ( JUPITER ) study was the first large-scale , prospect i ve study to examine the benefits of statin therapy in subjects with elevated levels of high-sensitivity C-reactive protein but with low-to-normal LDL-cholesterol levels , who were not qualified for lipid-lowering treatment according to the current guidelines for primary prevention . The JUPITER study aim ed to determine whether rosuvastatin 20 mg daily would reduce the rate of first major cardiovascular events , including cardiovascular death , nonfatal stroke , nonfatal myocardial infa rct ion , hospitalization for unstable angina or arterial revascularization .  Rosuvastatin reduced LDL-cholesterol levels by 50 % and high-sensitivity C-reactive protein by 37 % . Compared with placebo , the combined primary end point was reduced in 44 % ( p < 0.00001 ) , and total mortality in 20 % ( p = 0.02 ) . The trial confirmed the relationship between the rates of major cardiovascular events with both high-sensitivity C-reactive protein and LDL-cholesterol levels achieved after statin treatment . Interestingly , this was the first large , prospect i ve statin trial to show benefit in the reduction of venous thromboembolism CONTEXT Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease ( CHD ) , it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol ( LDL-C ) in patients without CHD extends to individuals with average serum cholesterol levels , women , and older persons . OBJECTIVE To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinical ly evident atherosclerotic cardiovascular disease with average total cholesterol ( TC ) and LDL-C levels and below-average high-density lipoprotein cholesterol ( HDL-C ) levels . DESIGN A r and omized , double-blind , placebo-controlled trial . SETTING Outpatient clinics in Texas . PARTICIPANTS A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C ( as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [ NHANES ] III ) . Mean ( SD ) TC level was 5.71 ( 0.54 ) mmol/L ( 221 [ 21 ] mg/dL ) ( 51 st percentile ) , mean ( SD ) LDL-C level was 3.89 ( 0.43 ) mmol/L ( 150 [ 17 ] mg/dL ) ( 60th percentile ) , mean ( SD ) HDL-C level was 0.94 ( 0.14 ) mmol/L ( 36 [ 5 ] mg/dL ) for men and 1.03 ( 0.14 ) mmol/L ( 40 [ 5 ] mg/dL ) for women ( 25th and 16th percentiles , respectively ) , and median ( SD ) triglyceride levels were 1.78 ( 0.86 ) mmol/L ( 158 [ 76 ] mg/dL ) ( 63rd percentile ) . INTERVENTION Lovastatin ( 20 - 40 mg daily ) or placebo in addition to a low-saturated fat , low-cholesterol diet . MAIN OUTCOME MEASURES First acute major coronary event defined as fatal or nonfatal myocardial infa rct ion , unstable angina , or sudden cardiac death . RESULTS After an average follow-up of 5.2 years , lovastatin reduced the incidence of first acute major coronary events ( 1 83 vs 116 first events ; relative risk [ RR ] , 0.63 ; 95 % confidence interval [ CI ] , 0.50 - 0.79 ; P<.001 ) , myocardial infa rct ion ( 95 vs 57 myocardial infa rct ions ; RR , 0.60 ; 95 % CI , 0.43 - 0.83 ; P=.002 ) , unstable angina ( 87 vs 60 first unstable angina events ; RR , 0.68 ; 95 % CI , 0.49 - 0.95 ; P=.02 ) , coronary revascularization procedures ( 157 vs 106 procedures ; RR , 0.67 ; 95 % CI , 0.52 - 0.85 ; P=.001 ) , coronary events ( 215 vs 163 coronary events ; RR , 0.75 ; 95 % CI , 0.61 - 0.92 ; P = .006 ) , and cardiovascular events ( 255 vs 194 cardiovascular events ; RR , 0.75 ; 95 % CI , 0.62 - 0.91 ; P = .003 ) . Lovastatin ( 20 - 40 mg daily ) reduced LDL-C by 25 % to 2.96 mmol/L ( 115 mg/dL ) and increased HDL-C by 6 % to 1.02 mmol/L ( 39 mg/dL ) . There were no clinical ly relevant differences in safety parameters between treatment groups . CONCLUSIONS Lovastatin reduces the risk for the first acute major coronary event  in men and women with average TC and LDL-C levels and below-average HDL-C levels . These findings support the inclusion of HDL-C in risk-factor assessment , confirm the benefit of LDL-C reduction to a target goal , and suggest the need for re assessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention OBJECTIVES The aim of this study was to evaluate the effect of statin treatment in primary prevention of  cardiovascular events in different race/ethnic groups . BACKGROUND Clinical trial evidence about the efficacy of statins in the primary prevention of cardiovascular events among nonwhites is uncertain . METHODS JUPITER trial , a r and omized , double-blind , placebo-controlled evaluation of rosuvastatin 20 mg in the primary prevention of myocardial infa rct ion ( MI ) , stroke , arterial revascularization , hospitalization for unstable angina , and cardiovascular death included 12,683 whites and 5,117 nonwhites with low-density lipoprotein levels < 130 mg/dL and high-sensitivity C-reactive protein levels ≥2.0 mg/L. RESULTS R and om allocation to rosuvastatin result ed in a 45 % reduction in the primary end point among whites ( hazard ratio [ HR ] 0.55 , 95 % CI 0.43 - 0.69 ) and a 37 % reduction among nonwhites ( HR 0.63 , 95 % CI 0.41 - 0.99 ) . Blacks ( HR 0.65 , 95 % CI 0.35 - 1.22 ) and Hispanics ( HR 0.58 , 95 % CI 0.25 - 1.39 ) had similar risk reductions . Among nonwhites in the placebo group , the stroke rate exceeded the MI rate ( 0.44 vs 0.20 per 100 person-years ) ; an opposite pattern was observed among whites ( 0.31 vs 0.42 per 100 person-years ) . Nonwhites had higher death rates than whites ( 2.25 vs 0.93 per 100 person-years ) ; however , all-cause mortality was similar at 20 % with rosuvastatin treatment in both participant groups . CONCLUSIONS When used in primary prevention among individuals with low-density lipoprotein < 130 mg/dL and high-sensitivity C-reactive protein ≥2 mg/L , rosuvastatin significantly reduced first MI , stroke , arterial revascularization , hospitalization for unstable angina , and cardiovascular death among whites and nonwhites We undertook this prospect i ve double-blind , placebo-controlled study to evaluate the efficacy and safety of low-dose ( 15 mg ) pravastatin in elderly hypercholesterolemic hypertensive subjects with concurrent antihypertensive treatment and to determine whether fasting hyperinsulinemia could also be improved . At three hypertension and lipid clinics of two medical centers , 96 elderly ( 49 women , 47 men ) ambulatory subjects were r and omized to active treatment or placebo for 12 months after a 3-month single-blind lead-in period . Hypertensive subjects with plasma total cholesterol levels of at least 6.47 mmol/L ( 250 mg/dL ) and triglyceride levels less than 3.39 mmol/L ( 300 mg/dL ) were treated with 15 mg pravastatin for 12 months after receiving 3 months of the American Heart Association step I diet . Lipid , glucose , and fasting insulin levels were measured ; clinical laboratory tests included liver function and creatine kinase determinations . After 12 months of pravastatin therapy , plasma total cholesterol concentration decreased by 25.1 % ( from a mean of 7.29 to 5.47 mmol/L , P < .05 ) , low-density lipoprotein cholesterol decreased by 30.2 % ( from 5.27 to 3.68 mmol/L , P < .05 ) , and triglycerides decreased by 10.7 % ( from 1.68 to 1.50 mmol/L , P < .05 ) . High-density lipoprotein cholesterol increased by 9.2 % ( from 1.20 to 1.31 mmol/L , P < .05 ) . Fasting insulin levels decreased from 89.0 to 61.5 pmol/L ( P < .05 ) . All of these changes were greater ( P < .05 ) than any tendency toward change in the placebo group . Adverse events and clinical laboratory abnormalities were generally mild and transient in both placebo and pravastatin groups . Study drugs were withdrawn from one subject in each group with asymptomatic creatine kinase elevations . We conclude that low-dose pravastatin was effective and safe in the treatment of hypercholesterolemic hypertensive subjects on concurrent antihypertensive therapy . It also improved fasting hyperinsulinemia despite the use of beta-blockers and diuretics in these hypertensive subjects Objective : To assess the therapeutic value of treatment with an HMG-CoA reductase inhibitor in women with hypoestrogenic hyperlipidemia caused by menopause . Design : Fifty-six women with total cholesterol ( TC ) levels of 220 mg/dl or more who were within 7 years of menopause were r and omly assigned to receive an HMG-CoA reductase inhibitor ( pravastatin 10 mg/day ; treated group , 26 patients ) or no medical treatment ( nontreated group , 30 patients ) in this 6-month nonblinded prospect i ve trial . Results : In the treated group , the mean ( SD ) TC levels decreased significantly from 254.5 ± 22.3 mg/dl at baseline to 204.7 ± 22.2 mg/dl ( 19.6 % ) , and the mean low-density lipoprotein cholesterol ( LDL-C ) level decreased significantly from 146.7 ± 30.5 to 104.3 ± 22.5 mg/dl ( 28.9 % ) ; the mean arteriosclerotic index decreased significantly from 2.98 to 2.08 ( 30.2 % ) . There were no significant changes in either triglyceride levels or high-density lipoprotein cholesterol ( HDL-C ) levels . In the nontreated group , there were no significant changes in the TC , HDL-C , LDL-C , or triglyceride levels ; there was also no change in the arteriosclerotic index . After 6 months , the TC level , LDL-C level , and arteriosclerotic index were significantly lower in the treated group compared with the nontreated group ( p < 0.01 ) . Conclusions : The results indicate that the HMG-CoA reductase inhibitor lowered TC and LDL-C levels and was useful in the treatment of hypoestrogenic hyperlipidemia for periods of at least 6 months BACKGROUND Statins are commonly prescribed for management of dyslipidaemia and cardiovascular disease . Increased fitness is also associated with low mortality and is recommended as an essential part of promoting health . However , little information exists about the combined effects of fitness and statin treatment on all-cause mortality . We assessed the combined effects of statin treatment and fitness on all-cause mortality risk . METHODS In this prospect i ve cohort study , we included dyslipidaemic veterans from Veterans Affairs Medical Centers in Palo Alto , CA , and Washington DC , USA , who had had an exercise tolerance test between 1986 , and 2011 . We assigned participants to one of four fitness categories based on peak metabolic equivalents ( MET ) achieved during exercise test and eight categories based on fitness status and statin treatment . The primary endpoint was all-cause mortality adjusted for age , body-mass index , ethnic origin , sex , history of cardiovascular disease , cardiovascular drugs , and cardiovascular risk factors . We assessed mortality from Veteran 's Affairs ' records on Dec 31 , 2011 . We compared groups with Cox proportional hazard model . FINDINGS We assessed 10,043 participants ( mean age 58·8 years , SD 10·9 years ) . During a median follow-up of 10·0 years ( IQR 6·0 - 14·2 ) , 2318 patients died , with an average yearly mortality rate of 22 deaths per 1000 person-years . Mortality risk was 18·5 % ( 935/5046 ) in people taking statins versus 27·7 % ( 1386/4997 ) in those not taking statins ( p<0·0001 ) . In patients who took  statins , mortality risk decreased as fitness increased ; for highly fit individuals ( > 9 MET ; n=694 ) , the hazard ratio ( HR ) was 0·30 ( 95 % CI 0·21 - 0·41 ; p<0·0001 ) compared with least fit ( ≤5 METs ) patients ( HR 1 ; n=1060 ) . For those not treated with statins , the HR for least fit participants ( n=1024 ) was 1·35 ( 95 % CI 1·17 - 1·54 ; p<0·0001 ) and progressively decreased to 0·53 ( 95 % CI 0·44 - 0·65 ; p<0·0001 ) for those in the highest fitness category ( n=1498 ) . INTERPRETATION Statin treatment and increased fitness are independently associated with low mortality  among dyslipidaemic individuals . The combination of statin treatment and increased fitness result ed in substantially lower mortality risk than either alone , reinforcing the importance of physical activity for individuals with dyslipidaemia . FUNDING None Objectives : This study was conducted to evaluate the effect of simvastatin ( 40 mg/day ) as an adjuvant therapy to interferon beta ( IFNb 1a , 30 µg once weekly ) in relapsing — remitting multiple sclerosis patients , compared with placebo . Methods : We enrolled 85 patients with relapsing — remitting multiple sclerosis ( 71 % female ) who were already receiving IFNb 1a ( Avonex ) , with Exp and ed Disability Status Scale score of less than 5.0 . The patients were assigned ( in r and om and double-blinded fashion ) into the two groups of simvastatin and placebo . All patients continued to receive their current IFNb treatment . The outcome measures were total relapse rate , Exp and ed Disability Status Scale score , and the number of gadolinium-enhanced ( Gd+ ) and new T2 lesions in magnetic resonance imaging after a 1-year follow-up . We used Mann — Whitney and one-way multivariate analysis of variances to analyze the data . Results : Four patients in the placebo and two in the simvastatin group prematurely withdrew from the study due to experiencing two attacks . The total attack number in the simvastatin group was significantly lower than placebo group ( moderate effect size r = 0.29 ) ( p = 0.01 ) . The final Exp and ed Disability Status Scale scores were lower in the simvastatin group ( 1.01 ± 1.40 , mean ± SD ) than in the placebo group ( 1.73 ± 1.49 , mean ± SD ) , but this difference was not significant after controlling the baseline Exp and ed Disability Status Scale score ( p = 0.07 ) . In the simvastatin group , the mean ± SD of gadolinium-enhanced and new T2 lesions were 0.66 ± 1.18 and 3.39 ± 3.55 , respectively , ( compared with 0.74 ± 1.21 and 3.39 ± 3.55 in the placebo group ) . Although there was a decreasing trend in lesions on magnetic resonance imaging , this difference was not statistically significant ( p = 0.62 ) . The combination therapy was safe and well tolerated , and no serious adverse effect was noted . Conclusion : Our study supports the safety and efficacy of simvastatin as an add-on therapy to INFb 1a in patients with relapsing — remitting multiple sclerosis . TRIAL REGISTRATION : Clinical Trials.gov NCT00668343 . This interventional study provides Class I evidence stating that adding simvastatin 40 mg/day to IFNb 1a 30 µg a week in patients with relapsing — remitting multiple sclerosis may reduce the relapse rate ( moderate effect size r = 0.29 ) ( p = 0.01 ) compared with treatment with IFNb 1a alone OBJECTIVES Lipid-lowering drugs as 3-hydroxy-3-methyl glutaryl coenzyme A ( HMG-CoA ) reductase inhibitors and cholestyramine are effective in reducing cardiovascular morbidity both in primary and secondary prevention . Patient compliance is an important determinant of the outcome of therapy . This study was design ed to compare compliance with tolerance and lipid-lowering effectiveness of pravastatin and /or cholestyramine in primary care . DESIGN Nine hundred and eighty nine women and 1047 men were r and omized to treatment at 100 primary -care centres in Sweden . After dietary intervention , an eligible patient was r and omly assigned to one of four programs of daily treatment : group Q , 16 g cholestyramine , group QP , 8 g cholestyramine and 20 mg pravastatin , group P20 , 20 mg pravastatin or group P40 , 40 mg pravastatin . RESULTS In group Q , group QP , group P20 and group P40 the reductions in low density lipoprotein (LDL)-cholesterol were 26 % , 36 % , 27 % and 32 % . The dose actually taken was 91 - 95 % of the prescribed for the pravastatin treatment groups and 77 - 88 % for the cholestyramine groups . In the pravastatin and cholestyramine groups 76 - 78 % and 44 - 53 % , respectively , completed the trial . Only 8 - 27 % of the patients reached a serum cholesterol target level of 5.2 mmol L-1 . There was no difference in lipid-lowering effect between women and men . CONCLUSION Pravastatin alone is efficacious and compliance is high , independent of dose . Combined treatment with cholestyramine and pravastatin had a better cholesterol lowering effect ( although not statistically significant ) than 40 mg pravastatin . Despite this , only 8 - 27 % of the patients actually reached a serum cholesterol level of 5.2 mmol L-1 . No unexpected serious adverse events were detected in any of the treatment groups . As predicted , the gastrointestinal disturbances were more common on cholestyramine treatment . These two factors suggest that an increase in the dosage of the HMG-CoA reductase inhibitor may be appropriate . Results from other studies indicate that there also might be other positive effects of statin treatment beyond cholesterol lowering This study demonstrated that pravastatin 20 mg once daily significantly lowered total cholesterol ( by 19 % ) and LDL cholesterol by 25 % The Carotid Atherosclerosis Italian Ultrasound study ( CAIUS ) , a multicenter , double-blind clinical trial , performed in 305 asymptomatic , moderately hypercholesterolemic patients , clearly demonstrated beneficial effects of pravastatin on the carotid intima-media thickness ( IMT ) progression . The data base of the CAIUS study was examined in order to investigate the presence of a relationship , if any , between the activity of pravastatin on IMT progression rate and its hypocholesterolemic effect . Quantitative B-mode ultrasound imaging was used to quantify the individual mean maximum IMT progression rate in 3 years . In the overall group of patients ( placebo and pravastatin ) covariance analysis showed that while the variable ' treatment ' ( 0 = placebo , 1 = pravastatin ) was significantly related to the reduction of IMT progression ( F= 6.6 , P = 0.01 ) , the IMT progression did not correlate with the extent of LDL-C lowering ( F= 0.00 , P = 0.98 ) . To further investigate this issue . the pravastatin treated group was stratified into quartiles of LDL-C reduction . In contrast to what was observed in the placebo group , in which a positive mean IMT progression rate was observed , independent of the extent of LDL-C reduction , no IMT progressionwas observed in any subgroup treated with pravastatin . No significant difference was found among quartiles and no trend could be identified . In conclusion , the effect of pravastatin treatment on carotid IMT progression rate is beneficial ; however the CAIUS study demonstrated that lowering LDL-C by itself , does not explain the variability of beneficial changes in IMT The Justification for the Use of statins in Primary prevention : an Intervention Trial Evaluating Rosuvastatin ( JUPITER ) is a r and omized , double-blind , placebo-controlled primary prevention trial of statin therapy among persons with average to low levels of low-density lipoprotein ( LDL ) cholesterol who are at increased cardiovascular risk due to elevated plasma concentrations of the inflammatory biomarker high-sensitivity C-reactive protein ( hs-CRP ) . A total of 17,802 persons with LDL cholesterol<130 mg/dl ( 3.36 mmol/L ) and hs-CRP > or=2 mg/L were recruited from 26 countries and r and omly allocated to 20 mg/day rosuvastatin or placebo . In contrast to previous studies of statin therapy in primary prevention , JUPITER is evaluating a group with modest plasma concentrations of LDL cholesterol ( median 108 mg/dl , interquartile range 94 to 119 ) . Further , the trial includes 6,801 women ( 38.2 % ) and 5,577 participants with metabolic syndrome ( 32.1 % ) . Thus , in addition to broadening our underst and ing of statin therapy and inflammation , the JUPITER trial will provide important and clinical ly relevant information on primary prevention among patients who do not currently qualify for lipid-lowering therapy . In conclusion , as 20 mg of rosuvastatin can reduce LDL cholesterol by up to 50 % , JUPITER will also provide crucial safety data for several thous and patients who should achieve LDL cholesterol levels<50 mg/dl on a long-term basis Experimental evidence suggests that lipid lowering therapy could slow the progression of renal disease in humans . We have conducted a double-blind , placebo controlled trial of the HMG CoA reductase inhibitor simvastatin in patients with the nephrotic syndrome or significant proteinuria ( > 1 g/day ) and hypercholesterolemia ( > or = 6.5 mmol/liter ) . Patients were placed on a lipid lowering diet for at least 10 weeks before r and omization . After a four-week placebo run-in , 30 adults were r and omized to simvastatin or placebo therapy ( 10 mg/day , increasing to 20 to 40 mg/day as required ) for 24 weeks . There were seven dropouts , none of whom were " definitely " related to drug therapy . Total and LDL cholesterol levels fell by a mean of 33 and 31 % , respectively , in simvastatin treated patients , compared with only 5 and 1 % in patients on placebo ( P < 0.001 , P = 0.002 , respectively ) . Apolipoprotein B100 levels fell by a mean of 31 % in the simvastatin group but rose 0.3 % in the placebo group ( P = 0.014 ) . There were no significant changes in HDL levels . There were no significant differences between the groups in their urine protein levels , their rise in plasma creatinine , or decline in plasma inulin clearance .  Simvastatin is a safe , effective therapy for hypercholesterolemia in proteinuric states . A much larger trial is needed to show if potent lipid-lowering therapy slows progression of hypercholesterolemic proteinuric diseases BACKGROUND Total and lipoprotein cholesterol levels continue to be predictors of coronary heart disease risk in men and women over 65 years old . Cholesterol-lowering trials , however , while sometimes including such subjects , have not concentrated on this age group . The Cholesterol Reduction in Seniors Program was a five-center pilot study to assess feasibility of recruitment and efficacy of cholesterol lowering in this age group . METHODS The study was a r and omized , double-masked clinical trial with placebo , 20-mg lovastatin , and 40-mg lovastatin arms . Major efforts were made to recruit women and minorities . Participants were followed up for 1 year on a cholesterol-lowering diet plus placebo or study drug . End points were changes in blood lipid levels . Data on other blood chemistry values , as well as quality -of-life measures and coronary heart disease morbidity and mortality , were also collected . RESULTS Four hundred thirty-one subjects with low-density lipoprotein cholesterol levels greater than 4.1 and less than 5.7 mmol/L ( 159 and 221 mg/dL ) were r and omized , of whom 71 % were women and 21 % were African Americans ; the mean age was 71 years . In the 20- and 40-mg lovastatin groups , total cholesterol levels fell 17 % and 20 % ; low-density lipoprotein cholesterol levels fell 24 % and 28 % ; triglyceride levels fell 4.4 % and 9.9 % , respectively . High-density lipoprotein cholesterol levels rose 7.0 % and 9.0 % , respectively . No changes were observed in the placebo group . Gender , race , and age did not significantly affect responses . Coronary heart disease morbidity and mortality data were collected but not analyzed for this study . CONCLUSION Older subjects of both genders and a variety of racial and ethnic groups can be successfully recruited into a cholesterol-lowering trial . Lovastatin has effects similar to those reported in younger subjects in previous controlled trials . There is little advantage to the higher lovastatin daily dose . Side effects were remarkably low in all groups ABSTRACT Objective : Carotid intima-media thickness ( CIMT ) is an index for changes in atherosclerosis burden and changes in CIMT may relate to clinical events . We present baseline data from the METEOR study , a r and omized , placebo-controlled trial evaluating the efficacy of rosuvastatin 40 mg on changes in CIMT . We set out to compare differences in CIMT between several subgroups of individuals . Design and methods : A total of 984 individuals aged 45–70 years ( men ) or 55–70 ( women ) were r and omized . Participants were required to have : maximum CIMT ≥ 1.2– < 3.5 mm ; 2 + risk factors and 10-year coronary heart disease ( CHD ) risk < 10 % , or < 2 CHD risk factors . Demographic characteristics were compared in two groups : USA versus Europe , and individuals with maximum CIMT < 2 mm versus those with CIMT ≥ 2 mm . Baseline data : Overall , mean age was 57 years and mean low-density lipoprotein cholesterol was 152 mg/dL ( 3.9 mmol/L  ) . Body mass index ( BMI ) , triglyceride and high-sensitivity C-reactive protein levels were all higher in US individuals , whereas smoking , hypertension and high-density lipoprotein cholesterol levels were higher in Europeans . Mean CIMT levels were the same in both population s , and the percentage of individuals with ≥ 2 CHD risk factors was similar . Increased baseline CIMT ( > 2 mm ) was related to increasing age , male gender , smoking , hypertension and lipid levels . Conclusions : In this global trial , differences in baseline characteristics between participants from the USA and Europe are apparent . However , a strong association between CIMT and several cardiovascular risk factors was observed across the two continents . Trial registration : Clinical Trials.gov identifier : NCT00225589 BACKGROUND Percutaneous coronary revascularization is widely used in improving symptoms and exercise performance in patients with ischemic heart disease and stable angina pectoris . In this study , we compared percutaneous coronary revascularization with lipid-lowering treatment for reducing the incidence of ischemic events . METHODS We studied 341 patients with stable coronary artery disease , relatively normal left ventricular function , asymptomatic or mild-to-moderate angina , and a serum level of low-density lipoprotein ( LDL ) cholesterol of at least 115 mg per deciliter ( 3.0 mmol per liter ) who were referred for percutaneous revascularization .  We r and omly assigned the patients either to receive medical treatment with atorvastatin , at 80 mg per day ( 164 patients ) , or to undergo the recommended percutaneous revascularization procedure ( angioplasty ) followed by usual care , which could include lipid-lowering treatment ( 177 patients ) . The follow-up period was 18 months . RESULTS Twenty-two ( 13 percent ) of the patients who received aggressive lipid-lowering treatment with atorvastatin ( result ing in a 46 percent reduction in the mean serum LDL cholesterol level , to 77 mg per deciliter [ 2.0 mmol per liter ] ) had ischemic events , as compared with 37 ( 21 percent ) of the patients who underwent angioplasty ( who had an 18 percent reduction in the mean serum LDL cholesterol level , to 119 mg per deciliter [ 3.0 mmol per liter ] ) . The incidence of ischemic events was thus 36 percent lower in the atorvastatin group over an 18-month period ( P=0.048 , which was not statistically significant after adjustment for interim analyses ) . This reduction in events was due to a smaller number of angioplasty procedures , coronary-artery bypass operations , and hospitalizations for worsening angina . As compared with the patients who were treated with angioplasty and usual care , the patients who received atorvastatin had a significantly longer time to the first ischemic event ( P=0.03 ) . CONCLUSIONS In low-risk patients with stable coronary artery disease , aggressive lipid-lowering therapy is at least as effective as angioplasty and usual care in reducing the incidence of ischemic events BACKGROUND The atherosclerotic progression-reducing effect of LDL cholesterol ( LDL-C ) lowering has been established in subjects with severe atherosclerotic disease but not in persons with elevated LDL cholesterols without severe atherosclerosis . KAPS ( Kuopio Atherosclerosis Prevention Study ) is the first population -based trial in the primary prevention of carotid and femoral atherosclerosis . METHODS AND RESULTS The eligibility requirements were serum LDL-C > or = 4.0 mmol/L and total cholesterol < 7.5 mmol/L. Out of a geographically defined population , 447 men aged 44 to 65 years ( mean , 57 ) were r and omized to pravastatin ( 40 mg/d  ) or placebo for 3 years . Less than 10 % of the subjects had prior myocardial infa rct ion . Thirty-nine men discontinued study medication ; however , efficacy data were available for 424 men . The primary outcome was the rate of carotid atherosclerotic progression , measured as the linear slope over annual ultrasound examinations in the average of the maximum carotid intima-media thickness ( IMT ) of the far wall of up to four arterial segments ( the right and left distal common carotid artery and the right and left carotid bulb ) . For the carotid arteries , at the overall mean baseline IMT of 1.66 mm , the rate of progression of carotid atherosclerosis was 45 % ( 95 % CI , 16 to 69 % ) less in the pravastatin ( 0.017 mm/y ) than the placebo ( 0.031 mm/y ) group ( P = .005 ) . In the common carotid artery there was a treatment effect of 66 % ( 95 % CI , 30 to 95 % ; pravastatin 0.010 mm/y ; placebo 0.029 mm/y ; P < .002 ) at the overall mean baseline IMT of 1.35 mm . A treatment effect of 30 % ( 95 % CI , -1 % to 54 % ) was found for the carotid bulb ( pravastatin , 0.028 ; placebo , 0.040 ; P = .056 ) at the overall mean baseline IMT of 2.0 mm . The treatment effect was larger in subjects with higher baseline IMT values , in smokers and in those with low plasma vitamin E levels . There was no significant treatment effect on atherosclerotic progression in the femoral arteries . CONCLUSIONS These data establish the antiatherogenic effect of LDL-C lowering by pravastatin in hypercholesterolemic men in a primary prevention setting and suggest a greater effect in smokers than in nonsmokers Among hypertensive patients , cardiovascular disease morbidity is common , even in those who are adequately treated . New pharmacological strategies to mitigate the burden of arterial hypertension are needed . This 12-month , r and omized , double-blind placebo-controlled study investigated the effect of statin ( fluvastatin ) treatment on ambulatory blood pressure ( ABP ) , exercise blood pressure ( EBP ) , myocardial structure , endothelial function and insulin resistance in 50 hypertensive patients . At baseline , the groups were comparable in terms of demographic characteristics , ABP , EBP , endothelial function and homeostasis model assessment of insulin resistance ( HOMA-IR ) . At the end of the study , there was no difference between groups in terms of resting systolic blood pressure . However , maximum systolic EBP was lower in the treatment group than in the placebo group ( 175±18 vs 192±23 mm Hg , P<0.05 ) , as was left ventricular mass index ( LVMI ; 82±15 vs 100±23 , P<0.05 ) , and HOMA-IR index was lower after fluvastatin treatment ( 2.77±1.46 vs 3.33±1.73 , P<0.05 ) . Changes in lipid profile were not correlated with blood pressure , endothelial function , LVMI or HOMA-IR data . In hypertensive patients , fluvastatin can improve maximum systolic EBP , myocardial remodelling and insulin resistance , independently of lipid profile variations and endothelial function BACKGROUND In several statin trials , vascular event rates for treatment groups begin to separate 1 year after commencement of treatment . For atherosclerosis progression , the temporal sequence of the effect has not been defined . We used data from the Measuring Effects on intima media Thickness : an Evaluation Of Rosuvastatin ( METEOR ) trial to determine the earliest time point at which significant differences in atherosclerosis progression rates could be detected after initiation of statin therapy . METHODS The METEOR trial was a double-blind , r and omized placebo-controlled trial that studied the effect of LDL-C lowering with 40 mg rosuvastatin on the rate of change of carotid intima media thickness ( CIMT ) measured by B-mode ultrasound amongst 984 low risk subjects . Ultrasound assessment s were made at baseline and every 6 months up to 2 years . RESULTS Rosuvastatin treatment was associated with a 49 % reduction in LDL-C-C , a 34 % reduction in total cholesterol , an 8.0 % increase in HDL-C and a 16 % reduction in triglycerides ( all P < 0.0001 compared with placebo ) . The difference in rate of mean maximum CIMT progression between the rosuvastatin and placebo groups ( based on near and far wall measurements from both left and right common carotid and internal carotid segments and carotid bifurcation ) was not statistically significant after 6 months ( 0.0023 mm year(-1 ) and 0.0106 mm year(-1 ) , respectively P = 0.34 ) . After 12 months , CIMT progression rates were significantly different between the groups : 0.0032 mm year(-1 ) and 0.0133 mm year(-1 ) in the rosuvastatin-treated and placebo-treated groups , respectively ( P = 0.049 ) . This divergence grew with further follow-up : -0.0009 mm year(-1 ) and 0.0131 mm year(-1 ) after 18 months ( P < 0.001 ) and -0.0014 mm year(-1 ) and 0.0131 mm year(-1 ) after 24 months of treatment ( P < 0.001 ) . Results were stronger for the mean common CIMT progression ( based on near and far wall measurements from both left and right common carotid segments ) . CONCLUSION Aggressive LDL-C lowering seems to exert its beneficial effect on atherosclerosis progression during the first 12 months of treatment . This parallels the timing of event reduction seen in clinical trials and suggests that the efficacy of lipid lowering treatment on CIMT progression can be evaluated in trials with a duration of 1 year , given sufficient sample size , high precision of measurements and a treatment effect comparable to that seen in METEOR OBJECTIVE To evaluate the effect of diet and drug intervention separately and combined in the treatment of primary hypercholesterolemia . DESIGN The study was conducted as a r and omized , placebo-controlled factorial trial , double-blinded for drug intervention . SETTING Subjects were recruited from a population -based cholesterol screening programme . SUBJECTS 215 middle-aged men with primary hypercholesterolemia , free from cardiovascular disease . INTERVENTIONS Subjects were r and omized to one of four intervention groups : ( 1 ) placebo and US National Cholesterol Education Program step 1 diet ; ( 2 ) placebo and step 2 diet ; ( 3 ) pravastatin 20 mg day-1 and step 1 diet ; or ( 4 ) pravastatin 20 mg day-1 and step 2 diet . The intervention period was 6 months . MAIN OUTCOME MEASUREMENTS Efficacy measurements included : serum total cholesterol , HDL cholesterol , triglycerides , apolipoproteins A1 and B. LDL cholesterol was calculated . For safety , values of ALAT , ASAT and CK were measured . RESULTS In the group receiving the step 1 diet only , lipid values were stable during the study period . In the placebo group on the step 2 diet , total cholesterol decreased by 6.3 % ( 0.47 mmol L-1 ( 95 % CI : 0.28 , 0.67 ) ) during 6 months . In the group receiving both pravastatin and the step 1 diet , there was a mean reduction in serum total cholesterol of 19.4 % ( 1.46 mmol L-1 ( 95 % CI : 1.20 , 1.72 ) ) . In the group treated with pravastatin and the step 2 diet , the 6 months of data show a reduction of 20.7 % ( 1.55 mmol L-1 ( 95 % CI : 1.30 , 1.80 ) ) . CONCLUSIONS If drug therapy with a HMG-CoA reductase inhibitor is considered necessary , a step 2 diet has no additional lipid-lowering effect compared with a step 1 diet in men with primary hypercholesterolaemia . However , favourable ' side-effects ' of a lipid-lowering diet , such as weight loss and lowering of blood pressure , may still warrant a low-fat diet in these cases OBJECTIVES We sought to analyze the disease-free intervals and calculate the freedom from atherosclerosis events in the Program on the Surgical Control of the Hyperlipidemias ( POSCH ) . BACKGROUND The POSCH study was a r and omized , secondary lipid/atherosclerosis intervention trial that provided strong evidence for reduction in atherosclerosis progression as demonstrated by clinical and arteriographic end points . The 417 control group patients received American Heart Association phase II diet instruction , and the 421 intervention group patients received identical dietary instruction and underwent a partial ileal bypass operation . METHODS Four outcome measures were determined : 1 ) overall mortality , 2 ) coronary heart disease mortality , 3 ) coronary heart disease mortality and confirmed nonfatal myocardial infa rct ion , and 4 ) coronary/cardiac interventions . RESULTS An overall mortality rate of 10 % occurred at 6.7 years in the control group and 9.4 years in the intervention group , for a gain in disease-free interval of 2.7 years in the intervention group ( p = 0.032 ) . A coronary heart disease mortality rate of 8 % occurred at 7.2 years in the control group and 11 years in the intervention group , for a gain of 3.8 years ( p = 0.046 ) . Twenty percent of patients demonstrated the combined end point of coronary heart disease mortality and confirmed nonfatal myocardial infa rct ion at 5.9 years in the control group and 11.4 years in the intervention group , for a gain of 5.5 years ( p < 0.001 ) . Twenty-five percent of patients underwent either coronary artery bypass graft surgery , percutaneous transluminal coronary angioplasty or heart transplantation at 5.4 years in the control group and 12.4 years in the intervention group , for a gain of 7 years ( p < 0.001 ) . CONCLUSIONS The marked lipid modification achieved by partial ileal bypass in the POSCH trial led to demonstrable increases in the disease-free intervals for overall mortality , coronary heart disease mortality , coronary heart disease mortality and confirmed nonfatal myocardial infa rct ion , and coronary intervention procedures . For the clinician and the patient , estimation of disease-free intervals may be more relevant than assessment of differences in incidence rates and risk ratios Statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals but their efficacy and safety in elderly people has not been confirmed . Several clinical trials including the Cholesterol and Recurrent Events ( CARE ) and Long-term Intervention with Pravastatin in Ischemic Disease ( LIPID ) , have sub-analysed their results for the ' elderly ' cohort , but the Prospect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) trial is the first trial to specifically evaluate the benefits of statin therapy on vascular risk in elderly men and women . The results have shown that pravastatin , given for 3 years , reduced the risk of coronary heart disease in elderly individuals . Within this same time frame , there was no significant benefit on the risk reduction of stroke but there was a trend to reduce the risk of transient ischemic attacks . It was discovered that those patients with the lowest baseline high-density lipoprotein cholesterol gained the most benefit from the intervention . Drug interactions between pravastatin and the concomitant medications seen in this elderly cohort , was not a significant clinical issue . Therefore , PROSPER extends to elderly individuals the treatment strategy currently used in middle-aged people The Program on the Surgical Control of the Hyperlipidemias ( POSCH ) provided the clearest and the most convincing evidence supporting the beneficial effects of cholesterol lowering in hypercholesterolemic survivors of a myocardial infa rct ion . In POSCH , 78 of the 838 patients ( 9.3 % ) were women , with 32 r and omized to the diet-control group and 46 to the diet plus partial ileal bypass surgery-intervention group .  At 5 years , the mean per cent change from baseline was -23.9 % for total plasma cholesterol ( p < 0.0001 ) , -36.1 % for low-density lipoprotein cholesterol ( p < 0.0001 ) , and + 8.5 % for high-density lipoprotein cholesterol ( p = not significant ) . Because of the small number of women , no statistically significant changes in clinical event rates were observed between the control and the surgery groups . A comparison of 162 coronary arteriography film pairs in the POSCH women , between baseline and 3 , 5 , 7 , and 10 years , consistently showed less disease progression in the surgery group ( p = 0.013 for combined assessment s of the baseline to the longest follow-up film ) . Because the lipid and coronary arteriography findings in the POSCH women paralleled these findings in the total POSCH population and in the POSCH men , and because the arteriography changes in POSCH have previously been demonstrated to be statistically significant surrogate end points for certain clinical events and predictors of overall and atherosclerotic coronary heart disease mortality rates , we conclude that the lipid modification achieved in the POSCH women by partial ileal bypass reduced their atherosclerosis progression . The POSCH findings in women support the aggressive treatment of hyperlipidemia in the general management of atherosclerosis in women Abstract Objective : To estimate the economic efficiency of using pravastatin to prevent the transition from health to cardiovascular disease in men with hypercholesterolaemia . Design : Economic benefit analysis based on data from the West of Scotl and coronary prevention study . Treatment specific hazards of developing cardiovascular disease according to various definitions were estimated . Scottish record linkage data provided disease specific survival . Cost estimates were based on extracontractual tariffs and event specific average lengths of stay calculated from the West of Scotl and coronary prevention study . Subjects : Men with hypercholesterolaemia similar to the subjects in the West of Scotl and coronary prevention study . Main outcome : Cost consequences , the number of transitions from health to cardiovascular disease prevented , the number needed to start treatment , and cost per life year gained . Results : If 10 000 of these men started taking pravastatin  , 318 of them would not make the transition from health to cardiovascular disease ( number needed to treat , 31.4 ) , at a net discounted cost of £ 20 m over 5 years . These benefits imply an undiscounted gain of 2460 years of life , and thus £ 8121 per life year gained , or £ 20 375 per life year gained if benefits are discounted . Restriction to the 40 % of men at highest risk reduces the number needed to treat to 22.5 ( £ 5601 per life year gained ( undiscounted ) and £ 13 995 per life year gained ( discounted ) ) . Conclusions : In subjects without evidence of prior myocardial infa rct ion but who have hypercholesterolaemia , the use of pravastatin yields substantial health benefits at a cost that is not prohibitive overall and can be quite efficient in selected high risk subgroups . Key messages The West of Scotl and coronary prevention study showed that pravastatin can prevent cardiovascular disease in men with hypercholesterolaemia So far , reports have deemed this prevention unjustified due to adverse economic implication s This analysis , based on data from the West of Scotl and coronary prevention study and extensive data from the Scottish record linkage system , shows that using pravastatin in this way is worth considering because of its substantial clinical benefit at a reasonable cost Practitioners must now consider using pravastatin to prevent cardiovascular disease in men with hypercholesterolaemia Increased economic efficiency may be obtained by restricting prevention to patients with additional risk OBJECTIVES The Hypertension High Risk Management trial ( HYRIM ) investigated the effect of fluvastatin treatment and lifestyle intervention on development of carotid intima-media thickness ( IMT ) in drug-treated hypertensive patients . METHODS AND RESULTS HYRIM was a placebo-controlled , 2 x 2 factorial trial in which 568 drug-treated hypertensive men aged 40 - 74 years with total cholesterol 4.5 - 8.0 mmol/L , triglycerides < 4.5 mmol/L , body mass index 25 - 35 kg/m2 , and a sedentary lifestyle were r and omized to receive either fluvastatin , 40 mg daily , or placebo , and either intensive lifestyle intervention ( physical activity and diet ) or usual care ( treatment of hypertension and other disorders by own private physician ) . Carotid IMT was assessed by B-mode ultrasound vasculography and left ventricular ( LV ) mass was calculated from ultrasound recordings of the heart . Fluvastatin alone reduced the primary study endpoint of 4-year development of IMT in the common carotid artery ( CCA ) compared with placebo ( p=0.0297 ) . Carotid bulb IMT progression over 4 years was also significantly ( p=0.0214 ) reduced by fluvastatin compared with placebo . Fluvastatin significantly lowered LDL-C levels ( mean net difference through 4 years , 0.6 mmol/L ; p<0.0001 ) , and reduced the 2-year development of LV mass ( p=0.0144 ) compared with placebo . Lifestyle intervention had no significant effect on LDL-C , carotid IMT or LV mass , and did not increase the effects of fluvastatin . CONCLUSIONS In drug-treated hypertensive patients in a usual care setting , fluvastatin treatment reduces progression of carotid IMT and LV mass This multicenter , double‐blind , placebo‐controlled study was conducted to evaluate dose‐response effects and safety of once‐daily administration of pravastatin , a new inhibitor of 3‐hydroxy‐3‐methylglutaryl coenzyme A ( HMG‐CoA ) reductase . Pravastatin 5 , 10 , 20 , 40 mg or placebo was administered at bedtime to 150 patients with primary hypercholesterolemia inadequately controlled on a low‐fat , low‐cholesterol ( AHA Phase I ) diet . After 8 weeks of treatment , pravastatin produced dose‐dependent reductions in low‐density lipoprotein ( LDL ) cholesterol of 19.2 to 34.1 % ( p⩽.001 vs. baseline and placebo ) and reductions in total cholesterol of 14.3 to 25.1 % ( p⩽.01 to p⩽.001 vs. placebo and p⩽.001 vs. baseline ) . The relationship between the loge dose of pravastatin and decrease in LDL cholesterol was linear ( p<0.002 ) . High‐density‐lipoprotein cholesterol increased up to 11.7 % and triglycerides decreased by as much as 23.9 % . Pravastatin was well tolerated ; no patient withdrew from the study as a consequence of treatment‐related adverse events . Despite its relatively short serum half‐life of approximately 2 h , once‐daily administration of pravastatin provides a safe and effective means of reducing elevated LDL and total cholesterol BACKGROUND The majority of cardiovascular events and deaths attributable to both raised blood pressure and dyslipidaemia occur in subjects with relatively " normal " blood pressure and lipid levels respectively . The study was design ed to evaluate the potential benefits of cholesterol lowering in the primary prevention of coronary heart disease in hypertensive subjects with average and below average levels of serum cholesterol . MATERIAL AND METHODS Out of 19 342 hypertensive subjects ( aged 40 - 79 ) who were initially r and omized to one of two antihypertensive treatment strategies in the Anglo-Sc and inavian Cardiac Outcomes Trial ( ASCOT ) , 10 305 subjects with total cholesterol levels < or = 6.5 mmol/L were additionally r and omized to either 10 mg atorvastatin or placebo . The primary endpoint was non-fatal myocardial infa rct ion or fatal coronary heart disease . RESULTS The lipid arm of the study was prematurely stopped after a median follow-up period of 3.3 years . One hundred events occurred in those r and omized to atorvastatin compared to 154 events in those receiving placebo , a 36 % relative risk reduction ( p = 0.0005 ) in the primary endpoint . Among secondary and tertiary endpoints , stroke was reduced with 27 % ( p = 0.02 ) . There was a non-significant 13 % reduction in total mortality . Non-cardiovascular mortality was similar in the two treatment limbs of the trial . After three years of follow-up , atorvastatin lowered total serum cholesterol by 1.1 mmol/L compared with placebo . INTERPRETATION Treatment with 10 mg atorvastatin o.d . in hypertensive patients at moderate risk gives a significant risk reduction of coronary heart disease , independent of baseline level of total cholesterol BACKGROUND Our purpose was to evaluate the efficacy and safety of atorvastatin , a potent cholesterol- and triglyceride-lowering agent , in peritoneal dialysis patients with dyslipidaemia . METHODS Peritoneal dialysis patients with hypercholesterolaemia were treated for 4 months with atorvastatin at a starting dose of 10 mg . The dose could be increased to 20 or 40 mg in order to achieve the following targets : plasma LDL-cholesterol of 130 mg/dl for primary prevention of coronary heart disease , plasma LDL cholesterol of 100 mg/dl for secondary prevention , and plasma triglycerides of 200 mg/dl . Plasma lipid profile and liver and muscle enzyme levels were assessed at baseline and then monthly during treatment . RESULTS Thirty-one patients with hypercholesterolaemia were included ( 16 males and 15 females ; mean age 57+/-16 years ; mean duration of peritoneal dialysis 27+/-17 months ) . Nineteen of the patients also had hypertriglyceridaemia and seven had diabetes . Twenty patients had no coronary history ( primary prevention ) , whereas nine had experienced a coronary event ( secondary prevention ) . In the primary and the secondary prevention patients , mean LDL-cholesterol levels ( mg/dl ) decreased significantly by 42 and 46 % from 204+/-23 to 119+/-27 ( P<0 . 001 ) and 198+/-37 to 104+/-21 ( P<0.001 ) , and mean triglyceride levels ( mg/dl ) decreased by 37 and 26 % from 289+/-132 to 186+/-92 ( P<0.001 ) and 201+/-62 to 150+/-54 ( P<0.001 respectively ) . Nineteen primary prevention and seven secondary prevention patients achieved the LDL-cholesterol target . The triglyceride target was achieved by 15 of the 19 hypertriglyceridaemic patients . Two patients stopped treatment ( one because of gastrointestinal disturbances , the other because of an allergic skin reaction ) . After 4 months , there were no changes in enzyme levels . CONCLUSION Atorvastatin is an effective and safe lipid-lowering agent for peritoneal dialysis patients with mixed dyslipidaemia The MEGA Study was Japan 's first primary prevention trial of cardiovascular disease ( CVD ) by cholesterol lowering with low-dose pravastatin .  Included were postmenopausal women aged < or = 70 years and men aged 40 - 70 years with mildly elevated total cholesterol ( TC ) level 220 - 270 mg/dL. In all , 8214 out patients were r and omly assigned to receive diet alone or diet plus pravastatin 10 - 20mg/day for an average follow-up of 5.3 years . The primary endpoint was a composite of fatal and nonfatal MI , angina , cardiac and sudden death , and coronary revascularization . TC was reduced by 11.5 % in the diet plus pravastatin group versus 2.1 % in the diet alone group . LDL-C was reduced by 18 % and 3.2 % in the two groups , respectively . TC was reduced to < 220 mg/dL and LDL-C to < 130 mg/dL in patients in the diet plus pravastatin group . There was a significant 33 % reduction of the primary endpoint in the diet plus pravastatin group compared with the diet alone group . Notable findings of the MEGA Study included the observation that despite pravastatin 's modest LDL-C reductions in this low-risk population , a 33 % reduction of CHD events was achieved . Even though 68 % of patients were women , who have been traditionally considered at less risk than men , significant CHD risk reduction was observed across all groups BACKGROUND AND METHODS The Program on the Surgical Control of the Hyperlipidemias ( POSCH ) , a r and omized clinical trial , was design ed to test whether cholesterol lowering induced by the partial ileal bypass operation would favorably affect overall mortality or mortality due to coronary heart disease . The study population consisted of 838 patients ( 417 in the control group and 421 in the surgery group ) , both men ( 90.7 percent ) and women , with an average age of 51 years , who had survived a first myocardial infa rct ion . The mean follow-up period was 9.7 years . RESULTS When compared with the control group at five years , the surgery group had a total plasma cholesterol level 23.3 percent lower ( 4.71 + /- 0.91 vs. 6.14 + /- 0.89 mmol per liter [ mean + /- SD ] ; P less than 0.0001 ) , a low-density lipoprotein cholesterol level 37.7 percent lower ( 2.68 + /- 0.78 vs. 4.30 + /- 0.89 mmol per liter ; P less than 0.0001 ) , and a high-density lipoprotein cholesterol level 4.3 percent higher ( 1.08 + /- 0.26 vs. 1.04 + /- 0.25 mmol per liter ; P = 0.02 ) . Overall mortality and mortality due to coronary heart disease were reduced , but not significantly so ( deaths overall [ control vs. surgery ] , 62 vs. 49 , P = 0.164 ; deaths due to coronary disease , 44 vs. 32 , P = 0.113 ) . The overall mortality in the surgery subgroup with an ejection fraction greater than or equal to 50 percent was 36 percent lower ( control vs. surgery , 39 vs. 24 ; P = 0.021 ) . The value for two end points combined -- death due to coronary heart disease and confirmed nonfatal myocardial infa rct ion -- was 35 percent lower in the surgery group ( 125 vs. 82 events ; P less than 0.001 ) . During follow-up , 137 control-group and 52 surgery-group patients underwent coronary-artery bypass grafting ( P less than 0.0001 ) . A comparison of base-line coronary arteriograms with those obtained at 3 , 5 , 7 , and 10 years consistently showed less disease progression in the surgery group ( P less than 0.001 ) . The most common side effect of partial ileal bypass was diarrhea ; others included occasional kidney stones , gallstones , and intestinal obstruction . CONCLUSIONS Partial ileal bypass produces sustained improvement in the blood lipid patterns of patients who have had a myocardial infa rct ion and reduces their subsequent morbidity due to coronary heart disease . The role of this procedure in the management of hypercholesterolemia remains to be determined . These results provide strong evidence supporting the beneficial effects of lipid modification in the reduction of atherosclerosis progression BACKGROUND R and omized trials have established statins as an agent for prevention of coronary heart disease ( CHD ) . The purpose of this study was to assess the hypothesis that st and ard-dose statin therapy has a beneficial effect in normocholesterolemic diabetic patients with CHD . METHODS AND RESULTS A prospect i ve , r and omized , open , blinded-endpoint trial was conducted from 2002 to 2004 at 55 hospitals in Japan to evaluate the effect of statins on subsequent cardiovascular events . A total number of 1,016 CHD patients ( 301 patients with type 2 diabetes mellitus [ DM ] and 715 non-DM patients ) with serum total cholesterol levels of 180 - 240 mg/dl were r and omly divided into non-statin and statin treatments . Clinical parameters were comparable between DM and non-DM groups . Serum low-density lipoprotein (LDL)-cholesterol levels were equally decreased after statin treatment in the 2 groups . Statin treatment improved prognosis in both the DM and non-DM groups ; however , the number needed to treat ( NNT ) and relative risk reduction ( RRR ) were remarkable especially in the DM group ( NNT=8 , RRR=67 % ) compared with the non-DM group ( NNT=30 , RRR=24 % ) . CONCLUSIONS St and ard-dose statin therapy provides incremental clinical benefits in DM patients with normal cholesterol levels compared with non-DM patients . The data suggest that DM patients may enjoy the pleiotropic effects of statins , independent of the LDL-cholesterol lowering effects of these agents Although there is little information from primary or secondary prevention trials on cholesterol-lowering medication in diabetic patients , the reduction of elevated cholesterol is widely recommended for this group . The American Diabetes Association ( ADA ) recommends drug therapy in diabetic patients if low density lipoprotein (LDL)-cholesterol remains at > 130 mg/dl , or > 100 mg/dl in patients with macroangiopathy , after dietary intervention . When cholesterollowering medication is indicated , the choice of the drug must take into account the other lipid abnormalities that are often present and the need to maintain optimal glycaemic control . In the present study we compared the efficacy and safety of the novel HMG-CoA reductase inhibitor atorvastatin at the dose of 10 mg/day with simvastatin , lovastatin and pravastatin at doses of 10 , 20 and 20 mg/day , respectively , and placebo , in type 2 diabetic patients with moderate elevation of LDL-cholesterol with or without elevation of triglycerides .  All the quoted agents are enzyme inhibitors effective in lowering LDL-cholesterol in humans . The efficacy endpoints were the mean per cent changes in plasma LDL-cholesterol ( primary ) , total cholesterol , triglycerides , and high-density lipoprotein (HDL)-cholesterol concentrations from baseline to the end of treatment ( 24 weeks ) . Atorvastatin at a dose of 10 mg/day produced : ( 1 ) a significant reduction in LDL-cholesterol ( -37 % ) in comparison with equivalent doses of simvastatin ( -26 % ) , pravastatin ( -23 % ) , lovastatin ( -21 % ) , and placebo ( -1 % ) ; ( 2 ) HDL-cholesterol increases ( 7.4 % ) comparable to or greater than those obtained with simvastatin ( 7.1 % ) , pravastatin ( 3.2 % ) , lovastatin ( 7.21 % ) , and placebo ( -0.5 % ) ; ( 3 ) a significantly greater reduction in total cholesterol ( - 29 % ) than that obtained with simvastatin ( -21 % ) , pravastain ( -16 % ) , lovastatin ( -18 % ) , and placebo ( 1 % ) ; and ( 4 ) a significantly greater reduction in triglycerides than that obtained with all the other drugs and placebo . In all treatment groups no significant variation in fibrinogen concentration was observed . All reductase inhibitors studied had similar levels of tolerance . There were no incidents of persistent elevations of serum aminotransferases or myositis Background Statins have anti-inflammatory actions which in theory are potentially beneficial in asthma . Small trials have failed to show a significant benefit , but a systematic study to evaluate the steroid-sparing effect of statin treatment has not been carried out . Methods A r and omised , placebo-controlled , crossover trial was conducted of simvastatin 40 mg at night with simultaneous stepwise reduction of fluticasone propionate dose until loss of control occurred , followed by an increase until regain of control ( ‘ minimum ’ dose required ) in 51 patients with asthma and sputum eosinophils ( steroid-free ) ≥2 % . Results 43 patients completed the study . There was no significant difference in ‘ minimum ’ inhaled corticosteroid ( ICS ) dose requirement  between simvastatin and placebo : ( median ( IQR ) 50 μg daily ( 0–250 ) vs 100 μg daily ( 0–250 ) , p=0.931 ) . ‘ Minimum ’ dose distribution was similar ( p=0.269 ) . The fluticasone dose at which loss of control occurred did not differ significantly between simvastatin and placebo ( p=0.404 ) . In patients with loss of control in both treatment arms , fluticasone dose at loss of control was similar with simvastatin and placebo ( median ( IQR ) 50 μg daily ( 0–100 ) for both , p=0.620 ) . In those patients who reached 0 μg/day ( n=18 ) , Astma Control Question naire ( ACQ ) was lower ( p=0.037 ) , forced expiratory volume in 1 s ( FEV1 ) higher ( p<0.01 ) and sputum eosinophils lower with simvastatin compared with placebo ( 9.5 % compared with 25.4 % , p=0.033 ) . Conclusions Simvastatin does not have clinical ly important steroid-sparing effects in patients with eosinophilic asthma . In the absence of steroid , simvastatin is associated with minor improvements in symptoms and lung function , and a reduction in sputum eosinophils . Clinical trial number ACTRN12606000531516 BACKGROUND Controversy persists regarding the extent of shared pathways between arterial and venous thrombosis and whether treatments of known efficacy for one disease process have consistent benefits for the other . Observational studies have yielded variable estimates of the effect of statin therapy on the risk of venous thromboembolism , and evidence from r and omized trials is lacking . METHODS We r and omly assigned 17,802 apparently healthy men and women with both low-density lipoprotein ( LDL ) cholesterol levels of less than 130 mg per deciliter ( 3.4 mmol per liter ) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to receive  rosuvastatin , 20 mg per day , or placebo . We followed participants for the first occurrence of pulmonary embolism or deep-vein thrombosis and performed analyses of the data on an intention-to-treat basis . RESULTS During a median follow-up period of 1.9 years ( maximum , 5.0 ) , symptomatic venous thromboembolism occurred in 94 participants : 34 in the rosuvastatin group and 60 in the  placebo group . The rates of venous thromboembolism were 0.18 and 0.32 event per 100 person-years of follow-up in the rosuvastatin and placebo groups , respectively ( hazard ratio with rosuvastatin , 0.57 ; 95 % confidence interval [ CI ] , 0.37 to 0.86 ; P=0.007 ) ; the corresponding rates for unprovoked venous thromboembolism ( i.e. , occurring in the absence of a known malignant condition , trauma , hospitalization , or surgery ) were 0.10 and 0.17 ( hazard ratio , 0.61 ; 95 % CI , 0.35 to 1.09 ; P=0.09 ) and for provoked venous thromboembolism ( i.e. , occurring in patients with cancer or during or shortly after trauma , hospitalization , or surgery ) , 0.08 and 0.16 ( hazard ratio , 0.52 ; 95 % CI , 0.28 to 0.96 ; P=0.03 ) . The rates of pulmonary embolism were 0.09 in the rosuvastatin group and 0.12 in the placebo group ( hazard ratio , 0.77 ; 95 % CI , 0.41 to 1.45 ; P=0.42 ) , whereas the rates of deep-vein thrombosis only were 0.09 and 0.20 , respectively ( hazard ratio , 0.45 ; 95 % CI , 0.25 to 0.79 ; P=0.004 ) . Consistent effects were observed in all the subgroups examined . No significant differences were seen between treatment groups in the rates of bleeding episodes . CONCLUSIONS In this trial of apparently healthy persons , rosuvastatin significantly reduced the occurrence of symptomatic venous thromboembolism . ( Clinical Trials.gov number , NCT00239681 . The West of Scotl and Coronary Prevention Study recently demonstrated the benefits of pravastatin therapy in the prevention of coronary heart disease events in middle-aged hypercholesterolemic men without prior myocardial infa rct ion . We present an analysis of the influence of baseline risk factors on coronary events and total mortality in the trial , and their interaction with therapy , using the Cox proportional hazards model . The multivariate predictors of fatal or nonfatal coronary events were treatment allocation ( pravastatin or placebo ) , current smoking , diabetes mellitus , nitrate consumption , minor electrocardiographic abnormalities , angina pectoris , family history of premature coronary death , widowhood , blood pressure , and total cholesterol/high density lipoprotein cholesterol ratio . Independent of other risk factors , pravastatin reduced the risk of definite coronary heart disease death or nonfatal myocardial infa rct ion by 32 % ( 95 % confidence interval 17 to 44 , p = 0.0001 ) , definite or suspected coronary heart disease death by 35 % ( 3 to 56 , p = 0.035 ) , cardiovascular death by 33 % ( 4 to 53 , p = 0.027 ) , coronary revascularization procedures by 38 % ( 11 to 56 , p = 0.009 ) , and all-cause mortality by 24 % ( 2 to 41 , p = 0.037 ) . The 5-year risk of fatal or nonfatal myocardial infa rct ion , calculated using the predictors identified in the Cox analysis , ranged from < 4.4 % in the lowest quartile of risk to > 9.6 % in the highest quartile . The proportional benefit achieved by pravastatin was independent of other risk factors ; hence , the absolute benefit of therapy was greatest in subjects with the highest baseline risk . Such subjects can be identified easily in the population and deserve high priority for treatment BACKGROUND Type 2 diabetes is associated with a substantially increased risk of cardiovascular disease , but the role of lipid-lowering therapy with statins for the primary prevention of cardiovascular disease in diabetes is inadequately defined . We aim ed to assess the effectiveness of atorvastatin 10 mg daily for primary prevention of major cardiovascular events in patients with type 2 diabetes without high concentrations of LDL-cholesterol . METHODS 2838 patients aged 40 - 75 years in 132 centres in the UK and Irel and were r and omised to placebo  ( n=1410 ) or atorvastatin 10 mg daily ( n=1428 ) . Study entrants had no documented previous history of cardiovascular disease , an LDL-cholesterol concentration of 4.14 mmol/L or lower , a fasting triglyceride amount of 6.78 mmol/L or less , and at least one of the following : retinopathy , albuminuria , current smoking , or hypertension . The primary endpoint was time to first occurrence of the following : acute coronary heart disease events , coronary revascularisation , or stroke . Analysis was by intention to treat . FINDINGS The trial was terminated 2 years earlier than expected because the prespecified early stopping rule for efficacy had been met . Median duration of follow-up was 3.9 years ( IQR 3.0 - 4.7 ) . 127 patients allocated placebo ( 2.46 per 100 person-years at risk ) and 83 allocated atorvastatin ( 1.54 per 100 person-years at risk ) had at least one major cardiovascular event ( rate reduction 37 % [ 95 % CI -52 to -17 ] , p=0.001 ) . Treatment would be expected to prevent at least 37 major vascular events per 1000 such people treated for 4 years . Assessed separately , acute coronary heart disease events were reduced by 36 % ( -55 to -9 ) , coronary revascularisations by 31 % ( -59 to 16 ) , and rate of stroke by 48 % ( -69 to -11 ) . Atorvastatin reduced the death rate by 27 % ( -48 to 1 , p=0.059 ) . No excess of adverse events was noted in the atorvastatin group . INTERPRETATION Atorvastatin 10 mg daily is safe and efficacious in reducing the risk of first cardiovascular disease events , including stroke , in patients with type 2 diabetes without high LDL-cholesterol . No justification is available for having a particular threshold level of LDL-cholesterol as the sole arbiter of which patients with type 2 diabetes should receive statins . The debate about whether all people with this disorder warrant statin treatment should now focus on whether any patients are at sufficiently low risk for this treatment to be withheld Laboratory investigations have demonstrated that blockade of HMG-CoA reductase in vitro reduces lymphocyte proliferation in response to mitogens as well as other facets of the immune system , such as natural killer cell cytotoxicity . However , in this r and omized and double-blind clinical investigation , treatment with 20-mg lovastatin for 6 months did not significantly alter several enumerative and functional characteristics of circulating immune cells BACKGROUND The West of Scotl and Coronary Prevention Study was a primary prevention trial that demonstrated the effectiveness of pravastatin ( 40 mg/d ) in reducing morbidity and mortality from coronary heart disease ( CHD ) in moderately hypercholesterolemic men . The present analysis examines the extent to which differences in LDL and other plasma lipids both at baseline and on treatment influenced CHD risk reduction . METHODS AND RESULTS Relationships between baseline lipid concentrations and incidence of all cardiovascular events and between on-treatment lipid concentrations and risk reduction in patients taking pravastatin  were examined by use of Cox regression models and by division of the cohort into quintiles . Variation in plasma lipids at baseline did not influence the relative risk reduction generated by pravastatin therapy . Fall in LDL level in the pravastatin-treated group did not correlate with CHD risk reduction in multivariate regression . Furthermore , maximum benefit of an approximately 45 % risk reduction was observed in the middle quintile of LDL reduction ( mean 24 % fall ) ; further mean decrements in LDL ( up to 39 % ) were not associated with a greater decrease in CHD risk . Comparison of event rates between placebo- and pravastatin-treated subjects with the same LDL cholesterol level provided evidence for an apparent treatment effect that was independent of LDL . CONCLUSIONS We conclude that the treatment effect of 40 mg/d of pravastatin is proportionally the same regardless of baseline lipid phenotype . There is no CHD risk reduction unless LDL levels are reduced , but a fall in the range of 24 % is sufficient to produce the full benefit in patients taking this dose of pravastatin .  LDL reduction alone does not appear to account entirely for the benefits of pravastatin therapy Background —Statins reduce the rates of heart attacks , strokes , and revascularization procedures ( ie , major vascular events ) in a wide range of circumstances . R and omized controlled trial data from 20 536 adults have been used to estimate the cost-effectiveness of prescribing statin therapy in the United States for people at different levels of vascular disease risk and to explore whether wider use of generic statins beyond the population s currently recommended for treatment in clinical guidelines is indicated . Methods and Results —R and omized controlled trial data , an internally vali date d vascular disease model , and US costs of statin therapy and other medical care were used to project lifetime risks of vascular events and evaluate the cost-effectiveness of 40 mg simvastatin daily . For an average of 5 years , allocation to simvastatin reduced the estimated US costs of hospitalizations for vascular events by ≈20 % ( 95 % CI , 15 to 24 ) in the different subcategories of participants studied . At a daily cost of $ 1 for 40 mg generic simvastatin , the estimated costs of preventing a vascular death within the 5-year study period ranged from a net saving of $ 1300 ( 95 % CI , $ 15 600 saving to $ 13 200 cost ) among participants with a 42 % 5-year major vascular event risk to a net cost of $ 216 500 ( $ 123 700 to $ 460 000 cost ) among those with a 12 % 5-year risk . The costs per life year gained with lifetime simvastatin treatment ranged from $ 2500 ( −$40 to $ 3820 ) in people aged 40 to 49 years with a 42 % 5-year major vascular event risk to $ 10 990 ( $ 9430 to $ 14 700 ) in people aged 70 years and older with a 12 % 5-year risk . Conclusions —Treatment with generic simvastatin appears to be cost-effective for a much wider population in the United States than that recommended by current guidelines BACKGROUND We examined whether atorvastatin affects diabetic kidney disease and whether the effect of atorvastatin on cardiovascular disease ( CVD ) varies by kidney status in patients with diabetes . STUDY DESIGN The Collaborative Atorvastatin Diabetes Study ( CARDS ) r and omized placebo-controlled trial . SETTING & PARTICIPANTS Patients with type 2 diabetes and no prior CVD ( n = 2,838 ) . INTERVENTION R and om allocation to atorvastatin , 10 mg/d , or placebo , with a median follow-up of 3.9 years . OUTCOMES Estimated glomerular filtration rate ( eGFR ) , albuminuria , CVD . MEASUREMENTS Baseline and follow-up GFRs were estimated by using the Modification of Diet in Renal Disease Study equation . Urinary albumin-creatinine ratio was measured on spot urine sample s. RESULTS At baseline , 34 % of patients had an eGFR of 30 to 60 mL/min/1.73 m(2 ) . Atorvastatin treatment was associated with a modest improvement in annual change in eGFR ( net , 0.18 mL/min/1.73 m(2)/y ; 95 % confidence interval [ CI ] , 0.04 to 0.32 ; P = 0.01 ) that was most apparent in those with albuminuria ( net improvement , 0.38 mL/min/1.73 m(2)/y ; P = 0.03 ) . At baseline , 21.5 % of patients had albuminuria and an additional 6.8 % developed albuminuria during follow-up . Atorvastatin did not influence the incidence of albuminuria ( hazard ratio , 1.49 ; 95 % CI , 0.73 to 3.04 ; P = 0.3 ) or regression to normoalbuminuria ( hazard ratio , 1.19 ; 95 % CI , 0.57 to 2.49 ; P = 0.6 ) . In 970 patients with a moderately decreased eGFR of 30 to 60 mL/min/1.73 m(2 ) , there was a 42 % reduction in major CVD events with treatment , including a 61 % reduction in stroke . This treatment effect was similar to the 37 % ( 95 % CI , 17 to 52 ; P < 0.001 ) reduction in CVD observed in the study overall ( P = 0.4 for the eGFR-treatment interaction ) . LIMITATIONS Low incidence rates of albuminuria and transition to more severe kidney status limit power to detect treatment effects . CONCLUSIONS A modest beneficial effect of atorvastatin on eGFR , particularly in those with albuminuria , was observed . Atorvastatin did not influence albuminuria incidence .  Atorvastatin was effective at decreasing CVD in those with and without a moderately decreased eGFR and achieved a high absolute benefit The Chiba Lipid Intervention Program ( CLIP ) Study was design ed to clarify the prognosis of Japanese hypercholesterolemic patients taking pravastatin for 5 years . Hypercholesterolemic patients ( n = 2,529 ) with a total cholesterol level > or = 220 mg/dl and without histories of ischemic coronary heart disease and /or cerebral infa rct ion were administered pravastatin ( 10 - 20 mg/day ) . Among them , 2,131 took pravastatin fully ( Pravastatin-continued  group ) , and 398 discontinued the treatment ( Discontinued group ) . The baseline total cholesterol level was 264.3 + /- 34.7 mg/dl ( mean + /- st and ard deviation ) . The mean reduction rates of total cholesterol and low-density lipoprotein ( LDL ) cholesterol were 18.0 % and 27.2 % , respectively . Mild and moderate adverse events occurred in 86 cases ( 3.6 % ) . Serious adverse events were not observed . Death rates of the pravastatin-continued group and of the discontinued group were 2.6 and 16.0/1,000 persons/year , respectively . Cardiac events ( fatal and nonfatal myocardial infa rct ion , cardiac death , angina pectoris ) in all , occurred in 35 patients ( incidence rate = 2.77/1,000 persons/year ) . In the pravastatin continued group , 9 causes of fatal and nonfatal myocardial infa rct ion occurred ( 0.84/1,000 persons/year ) , whereas in the discontinued group , 4 cases occurred ( 2.06/1,000 persons/ year ) . The risk ratio for cardiac events was correlated with the number of risks . In the low-risk group ( < or = 1 risk ) , decreased rates of LDL-cholesterol were less in the cardiac event group than the non-cardiac event group ( LDL-cholesterol ; 16 % vs 25 % , p = 0.04 ) . These results suggested the following ; 1 ) Pravastatin maintained a cholesterol lowering effect long-term without serious complications . 2 ) Pravastatin administration might reduce the mortality rate and myocardial infa rct ion . 3 ) The combination of multiple risks is a strong factor for a cardiac event in addition to hypercholesterolemia In the Exp and ed Clinical Evaluation of Lovastatin ( EXCEL ) Study , a multicenter , double-blind , diet- and placebo-controlled trial , we evaluated the efficacy and safety of lovastatin in 8245 patients with moderate hypercholesterolemia . Patients were r and omly assigned to receive placebo or lovastatin at a dosage of 20 mg once daily , 40 mg once daily , 20 mg twice daily , or 40 mg twice daily for 48 weeks . Lovastatin produced sustained , dose-related ( P less than .001 ) changes as follows ( for dosages of 20 to 80 mg/d ) : decreased low-density lipoprotein-cholesterol level ( 24 % to 40 % ) , increased high-density lipoprotein-cholesterol level ( 6.6 % to 9.5 % ) , decreased total cholesterol level ( 17 % to 29 % ) , and decreased triglyceride level ( 10 % to 19 % ) . The National Cholesterol Education Program 's low-density lipoprotein-cholesterol level goal of less than 4.14 mmol/L ( 160 mg/dL ) was achieved by 80 % to 96 % of patients , while the less than 3.36 mmol/L ( 130 mg/dL ) goal was achieved by 38 % to 83 % of patients . The difference between lovastatin and placebo in the incidence of clinical adverse experiences requiring discontinuation was small , ranging from 1.2 % at 20 mg twice daily to 1.9 % at 80 mg/d . Successive transaminase level elevations greater than three times the upper limit of normal were observed in 0.1 % of patients receiving placebo and 20 mg/d of lovastatin , increasing to 0.9 % in those receiving 40 mg/d and 1.5 % in those receiving 80 mg/d of lovastatin ( P less than .001 for trend ) . Myopathy , defined as muscle symptoms with a creatine kinase elevation greater than 10 times the upper limit of normal , was found in only one patient ( 0.1 % ) receiving 40 mg once daily and four patients ( 0.2 % ) receiving 80 mg/d of lovastatin . Thus , lovastatin , when added after an adequate trial of a prudent diet , is a highly effective and generally well-tolerated treatment for patients with moderate hypercholesterolemia Renal transplant recipients have a greatly increased risk of  premature cardiovascular disease . The ALERT study was a multicenter , r and omized , double‐blind , placebo‐controlled trial of fluvastatin ( 40–80 mg/day ) in 2102 renal transplant recipients followed for 5–6 years . The main study used a composite cardiac end‐point including myocardial infa rct ion , cardiac death and cardiac interventions . Although reduced by fluvastatin , this primary end‐point failed to achieve statistical significance thus precluding analysis of predefined subgroups . Therefore , in the present survival analysis , we used an alternative primary end‐point of cardiac death or definite nonfatal myocardial infa rct ion ( as used in other cardiac outcome trials ) which was significantly reduced by Fluvastatin therapy and permits subgroup analysis . Fluvastatin  reduced LDL‐cholesterol by 1 mmol/L compared with placebo , and the incidence of cardiac death or definite myocardial infa rct ion was reduced from 104 to 70 events ( RR 0.65 ; 95 % CI 0.48 , 0.88 ; p = 0.005 ) . Fluvastatin use was associated with reduction in cardiac death or nonfatal myocardial infa rct ion , which achieved statistical significance in many subgroups . The subgroups included patients at lower cardiovascular risk , who were younger , nondiabetic , nonsmokers and without pre‐existing CVD . These data support the early introduction of statins following renal transplantation Parkinson 's disease , a progressive neurodegenerative disorder , affects about 1 % of the population over the age of 50 . While it has no cure , it is the only neurodegenerative disorder with a range of medical and neurosurgical treatments that substantially reduce clinical symptoms.1 However , medical management of early Parkinson 's disease is controversial because of the potential risks and benefits to patients . Some clinicians prefer to use levodopa , a dopamine precursor , since it promptly relieves symptoms . Others prescribe dopamine agonists and withhold levodopa because of its long term complications , namely abnormal involuntary movements and potential neurotoxicity . Inevitably , managing the side effects of antiparkinsonian drugs becomes a therapeutic focus along with treating the primary motor abnormalities.1 Extended controlled clinical trials are the only means of obtaining evidence based guidance on the use of dopamine agonists or levodopa for the management of early Parkinson 's disease . The results of a recent multisite , five year , r and omised , double blind study comparing the incidence of dyskinesia with levodopa or ropinirole , a dopamine D2 receptor agonist,2 should sway practitioners towards initial treatment with agonists for early Parkinson 's disease . In contrast to the hypokinesis that characterises Parkinson 's disease , dyskinesias related to antiparkinsonian drugs involve hyperkinetic choreoathetoid , lurching , and jerky movements . These movements are thought OBJECTIVES To investigate the efficacy of 10 mg or 20 mg atorvastatin + long acting antihypertensive in carotid intima-medial thickness ( IMT ) . METHODS 151 patients of Han nationality in South China with mild hypertensive were r and omly divided into 3 groups : atorvastatin 10 mg group ( n = 50 ) receive 10 mg atorvastatin and amlodipine + benazepril ; atorvastatin 20 mg group ( n = 61 ) receive 20 mg atorvastatin and amlodipine + benazepril ; the control group ( n = 40 ) receive amlodipine + benazepril . The patients were detected IMT , vascular function , lipids and inflammatory factor in pretherapy and every 3 months . RESULTS atorvastatin 10 mg or 20 mg groups have significantly change contrast to control group : ( 1 ) IMT was decreased ( P < 0.01 ) . ( 2 ) Deltadia-P% and Deltadia-N% were increased ( P < 0.01 ) . ( 3 ) LDL-C level was decreased by 30 % in a atorvastatin 10 mg group and 40.48 % in 20 mg group respectively ( P < 0.01 ) . CONCLUSION Atorvastatin delays the development of atherosclerosis in hypertensive patients , improves endothelial function , and strengthens the effect of lipid-lowering Background : Reduction of serum cholesterol , most notably low-density lipoprotein choles terol is associated with reductions in cardiovascular morbidity and mortality . Statins have been shown to effectively reduce low-density lipoprotein cholesterol via inhibition of the hydroxymethyl-coenzyme A ( HMG-CoA ) reductase . Cerivastatin is the most potent HMG- CoA reductase inhibitor currently under study in the United States . Methods and Results : A parallel group , r and omized , placebo-controlled , double-blind , mul ticenter study was conducted to compare the efficacy and safety of three different dosing reg imens of 0.2 mg/day of cerivastatin , a new HMG-CoA reductase inhibitor , in patients with hypercholesterolemia . After a 10-week diet-placebo lead-in period , 319 patients with low- density lipoprotein cholesterol > 160 mg/dL were r and omized to 4 weeks of treatment with one of the following regimens : cerivastatin 0.1 mg twice daily , cerivastatin 0.2 mg once daily with the evening meal , cerivastatin 0.2 mg once daily at bedtime or placebo . All three active treatment groups produced statistically significant ( P < .05 ) changes compared to baseline and placebo in total cholesterol ( 0.1 mg twice daily -18.9 % ; 0.2 mg once daily with the evening meal : -21.9 % ; 0.2 mg once daily at bedtime : -22.1 % ; placebo : 0.0 % ) , low-density lipoprotein cholesterol ( 0.1 mg twice daily : -25.7 % ; 0.2 mg once daily with the evening meal : -29.4 % ; 0.2 mg once daily at bedtime : -30.4 % ; placebo : 1.4 % ) and high-density lipoprotein cholesterol ( 0.1 mg twice daily : 5.3 % ; 0.2 mg once daily with the evening meal : 2.3 % ; 0.2 mg once daily at bedtime : 3.2 % ; placebo : -1.2 % ) . Triglycerides , compared to baseline and placebo , were also reduced by all active treatments ( 0.1 mg twice daily : -11.6 % [ P = .05 ] ; 0.2 mg once daily with the evening meal : -11.6 % [ P = .05 ] ; and 0.2 mg at bed time : -10.9 % [ P = .07 ] ) . The percentage change in total cholesterol and low-density lipopro tein cholesterol after 4 weeks of therapy for the once-daily cerivastatin groups was statisti cally significantly greater ( P < .05 ) than the cerivastatin twice daily regimen . A treatment response was seen by 1 week of therapy and was maximal by 3 weeks . The drug was well tolerated in all three dosing regimens and result ed in no significant increase in biochemical or clinical side effects compared to placebo . Conclusion : Cerivastatin is a novel , highly potent , well-tolerated HMG-CoA reductase inhibitor that produces low-density lipoprotein cholesterol reductions of approximately 30 % when administered at 0.2 mg once a day in the evenings The clinical efficacy and safety of pitavastatin ( NK-104 ) , a novel HMG-CoA reductase inhibitor , during long-term treatment , were examined in 25 patients ( male/female=11/14 , mean age=53+/-13 ( mean+/-SD ) years ) with heterozygous familial hypercholesterolemia ( FH ) . After a period on placebo of > 4 weeks , 2 mg/day of pitavastatin was administered for 8 weeks , and the dose was increased to 4 mg/day for up to 104 weeks . Total cholesterol ( TC ) decreased by 31 % from the initial value of 340+/-57 to 237+/-40 mg/dl ( P<0.0001 ) at week 8 . During treatment with the higher dose , TC decreased even further to 212+/-35 mg/dl at week 12 ; it decreased by 37 % from the initial value ( P<0.0001 ) . Similarly , the baseline low-density lipoprotein (LDL)-cholesterol ( LDL-C ) decreased by 41 % at week 8 , and by 49 % at week 12 , from 267+/-61 mg/dl at baseline . These findings indicate a dose-dependent effect of the drug on TC and LDL-C concentrations . To examine whether the levels of circulating matrix metalloproteinases ( MMPs ) and their endogenous inhibitors ( tissue inhibitors of metalloproteinases : TIMPs ) are altered during lipid-lowering therapy , we also measured their plasma levels . The mean levels of MMP-2 and -3 were significantly increased . No significant alteration was found in MMP-9 , TIMP-1 and -2 levels . As for the safety of pitavastatin , adverse reactions were observed in one case ( 4 % ) of subjective and objective symptoms . The effects of pitavastatin on TC and LDL-C were stable during long treatment of patients with heterozygous FH Objectives : Non-HDL-cholesterol ( non-HDL-C ) and apolipoprotein ( apo ) B are proposed as treatment targets . The extent to which statin therapy affects relationships of LDL-C and non-HDL-C with apoB was examined in type 2 diabetes . Methods : Analyses were performed in 217 hypertriglyceridaemic type 2 diabetic patients ( Diabetes Atorvastatin Lipid Intervention ( DALI ) cohort ) . 61 patients r and omized to placebo , 70 to 10 mg atorvastatin daily and 65 – 80 mg atorvastin daily completed follow-up . Results : Baseline fasting LDL-C of 2.42 mmol/l and non-HDL-C of 3.69 mmol/l corresponded to the apoB guideline target of 0.90 g/l . During atorvastatin ( 10 and 80 mg daily ) , the LDL-C target was achieved most frequently , and lower LDL-C ( 2.38 and 2.29 mmol/l ) and non-HDL-C ( 3.24 and 3.19 mmol/l ) concentrations corresponded to this apoB goal . Decreases in LDL-C during  atorvastatin  treatment were negatively related ( p < 0.001 ) , but decreases in non-HDL-C were positively related to changes in triglycerides ( p < 0.001 ) , independently from decreases in apoB ( p < 0.001 for all ) . Decreases in LDL-C and non-HDL-C were positively associated with decreases in cholesteryl ester transfer protein mass ( p < 0.001 ) . Conclusions : During atorvastatin  lower LDL-C and non-HDL-C levels correspond to the apoB guideline target , which would favour its use as treatment target OBJECTIVES In addition to its LDL-C-lowering effects , statin treatment reduces the level of C-reactive protein ( CRP ) . Long-term data on this effect in low-risk population s are limited . Furthermore , whether the CRP reduction is a consequence of LDL-C lowering or occurs independently remains unclear . We studied these aspects in the Measuring Effects on intima media Thickness : an Evaluation Of Rosuvastatin ( METEOR ) study , a r and omized placebo-controlled trial amongst 984 low-risk subjects . METHODS METEOR is a r and omized placebo-controlled trial that evaluated the effect of 40 mg of rosuvastatin on 2-year change in carotid intima media thickness ( CIMT ) amongst 984 low-risk patients ( 10-year Framingham risk < 10 % ) with modest CIMT ( CIMT > or = 1.2 and < 3.5 mm ) and elevated LDL-C.  CRP levels were measured at baseline and after 2 years of treatment . RESULTS Median baseline CRP was 1.4 mg L(-1 ) . Rosuvastatin lowered CRP significantly compared with placebo : -36 % in the rosuvastatin group versus no change in the placebo group . There was no relation between change in CRP and change in LDL-C ( Spearman correlation : 0.08 ; SE : 0.04 ) . Stratified analyses showed that the CRP-lowering effect was present amongst all strata of baseline characteristics , including baseline lipids and CRP levels . However , the magnitude of CRP reduction was larger amongst women and participants older than 60 years . CONCLUSIONS Rosuvastatin ( 40 mg ) lowers CRP independently from its effects on LDL-C in low-risk subjects with normal baseline CRP levels and modest CIMT OBJECTIVE Assessment of the relationship between changes in sequential coronary arteriograms and subsequent clinical coronary events . DESIGN The Program on the Surgical Control of the Hyperlipidemias , a r and omized secondary atherosclerosis intervention trial , obtained coronary arteriograms at baseline , 3 , 5 , and 7 or 10 years of follow-up . Assessment s of changes between pairs of coronary arteriograms were made by two-member panels blinded to the patients ' assigned treatment and to the temporal sequence of the films . The relationship of changes between the baseline and the 3-year follow-up arteriograms and subsequent clinical coronary events was examined . SETTING Three university hospitals and one private primary care facility . PATIENTS A total of 838 patients , with 417 patients r and omized to the control group and 421 to the intervention group . Of all patients , 695 had baseline and 3-year arteriograms . INTERVENTION The control group received American Heart Association Phase II diet instruction and the intervention group received identical dietary instruction plus a partial ileal bypass operation . MAIN OUTCOME MEASURE The use of arteriographic changes as a predictor of subsequent clinical coronary events . RESULTS Changes between the baseline and the 3-year coronary arteriographic overall disease assessment were significantly associated with subsequent overall and atherosclerotic coronary heart disease mortality ( P less than .01 ) . For the combined end point of atherosclerotic coronary heart disease mortality or confirmed nonfatal myocardial infa rct ion , a significant relationship between the overall disease assessment and subsequent clinical events was found in the control group ( P less than .0001 ) and in the surgery group ( P = .04 ) . For this combined end point , however , the control and the surgery groups were different with respect to clinical coronary events after 3 years , stratified by the baseline to 3-year overall disease assessment ( P less than .001 , unadjusted ; P = .06 , adjusted for 3-year clinical covariates ) . CONCLUSIONS Coronary arteriographic changes can be used in atherosclerosis intervention trials as a limited surrogate end point for certain clinical coronary events . This relationship is statistically compelling for overall mortality and atherosclerotic coronary heart disease mortality . For an individual patient , changes in the severity of coronary atherosclerosis seen on sequential coronary arteriograms can serve as prognostic indicators for subsequent overall or atherosclerotic coronary heart disease mortality The objective of this study was to examine the effects of lovastatin on bone mineral density ( BMD ) of postmenopausal women with type 2 diabetes mellitus ( DM ) . The study was an open-label clinical trial conducted from March 2002 to November 2003 . Fifty-five postmenopausal women age 54–67 years with type 2 DM were allocated to lovastatin-treated and control ( without lovastatin ) groups based on low-density lipoprotein cholesterol ( LDL-C ) > 130 or ≤130 mg/dl . The first group received lovastatin ( 20 mg daily titrated every 3 months to keep LDL-C less than 130 mg/dl ) for a total of 18 months . The second group received their own diabetic regimen without statin . The BMD of the lumbar spine ( L1-L4 ) , femoral neck , Wards triangle , trochanter and total hip was measured by dual-energy X-ray absorptiometry at baseline and after 18 months . In the 28 women treated with lovastatin  , the BMD increased in lumbar spine ( from 0.946 ( 0.122 ) to 0.978 ( 0.135 ) g/cm2 , p<0.01 ) and Ward ’s triangle ( from 0.685 ( 0.123 ) to 0.780 ( 0.186 ) g/cm2 , p<0.01 ) . In the 27 women not treated with statin , the changes in BMD at all bone sites were not statistically significant . BMD was higher in femoral neck ( 1.2 % vs. −2.7 % , p<0.05 ) , Ward ’s triangle ( 13.9 % vs. 3.3 % , p<0.05 ) , trochanter ( −0.1 % vs. −2.9 % , p<0.05 ) , total hip ( 1.2 % vs. −1.4 % , p<0.05 ) and lumbar spine ( 3.4 % vs. 1.2 % , p>0.05 ) at the end of the study . Treatment with lovastatin may prevent bone loss in postmenopausal women with type 2 DM Objective To test the primary hypothesis that a newer antihypertensive treatment regimen ( calcium channel blocker ± an angiotensin converting enzyme inhibitor ) is more effective than an older regimen ( β-blocker ± a diuretic ) in the primary prevention of coronary heart disease ( CHD ) . To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol ⩽ 6.5 mmol/l . Design Prospect i ve , r and omized , open , blinded endpoint trial with a double-blinded 2 × 2 factorial component . Setting Patients were recruited mainly from general practice s. Patients Men and women aged 40–79 were eligible if their blood pressure was ⩾160 mmHg systolic or ⩾ 100 mmHg diastolic ( untreated ) or ⩾140 mmHg systolic or ⩾ 90 mmHg diastolic ( treated ) at r and omization . Interventions Patients received either amlodipine ( 5/10 mg ) ± perindopril ( 4/8 mg ) or atenolol ( 50/100 mg ) ± bendroflumethiazide ( 1.25/2.5 mg ) + K+ with further therapy as required to reach a blood pressure of ⩽140 mmHg systolic and 90 mmHg diastolic . Patients with a total cholesterol of ⩽ 6.5 mmol/l were further r and omized to receive either atorvastatin 10 mg or placebo daily . Main outcome measure Non-fatal myocardial infa rct ion ( MI ) and fatal coronary heart disease ( CHD ) . Results 19 342 men and women were initially r and omized , of these 10 297 were also r and omized into the lipid-lowering limb . All patients had three or more additional cardiovascular risk factors . Conclusions The study has 80 % power ( at the 5 % level ) to detect a relative difference of 20 % in CHD endpoints between the calcium channel blocker-based regimen and the β-blocker-based regimen . The lipid-lowering limb of the study has 90 % power at the 1 % level to detect a relative difference of 30 % in CHD endpoints between groups Abstract Objective : To evaluate the effects on mood of a substantial and prolonged reduction in total cholesterol concentration . Design : R and omised placebo controlled comparison of patients who had been allocated to receive simvastatin 20 mg or 40 mg daily versus those allocated matching placebo  in a ratio of 2:1 . Follow up at an average of 152 weeks after r and omisation . Subjects : Men and women aged between 40 and 75 years at entry with blood total cholesterol of 3.5 mmol/l or greater , who were considered to be at higher than average risk of coronary heart disease based on medical history . Main outcome measures : The shortened profile of mood states question naire , reported use of psychotropic medication , and symptoms possibly related to mood . Results : Simvastatin reduced total cholesterol by 1.9 mmol/l ( 26.7 % ) at the time of follow up . Among all 621 patients r and omised to simvastatin ( 414 patients ) or placebo ( 207 patients ) there were no significant differences in the use of psychotropic medication or in reports of symptoms possibly related to mood . Of these patients , 491 ( 334 simvastatin , 157 placebo ) completed the mood question naire , and there were no significant differences between the treatment groups in total or subscale scores , even when patients with low baseline cholesterol concentrations or elderly subjects were considered separately . Conclusion : These results do not support the hypothesis that treatment to lower cholesterol concentration causes mood disturbance . Key messages A r and omised placebo controlled trial of simvas- tatin ( a drug that lowers cholesterol concentration substantially ) showed no associated mood distur- bance over a period of nearly three years in subjects with cardiovascular disease and no pre-existing psychiatric conditions No effects on mood were seen in individuals with low baseline cholesterol concentrations or in older individuals , and there were no differences in use of psychotropic drugs between the treatment groups These results give little support to the idea that reducing cholesterol concentration has adverse effects on INTRODUCTION The 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitors , named statins , are well-established cholesterol-lowering drugs able to reduce cardiovascular risk in hypercholesterolemic patients . The possible effect of statin on bone tissue , so-called pleiotropic effects has received particular attention . Studies reported a positive effect of statin on bone tissue in both of animal and human study by enhancing the expression of the bone morphogenetic proteins ( BMPs ) , in particular of BMP2 , which in turn leads to osteoblast differentiation and bone formation including interfering with osteoclastic activity . In a systematic review , the lipophilic statin as simvastatin had positive effect to bone mineral density ( BMD ) better than the more hydrophilic statin such as atorvastatin and fluvastatin . This study was aim ed to compare efficacy of medical therapy between HMG-CoA reductase inhibitor and non-HMG-CoA reductase inhibitor group to changing of bone mineral density and bone markers in the patients with hyperlipidemia . MATERIAL S AND METHODS A prospect i ve r and omized control trial study enrolled the 212 hyperlipidemia with osteopenia patients to study in year 2006 - 2008 . All subjects were r and omized to 2 groups between  statin and non-statin group ; the patients were screened by inclusion criteria and measured in bone mineral density ( BMD ) , bone marker and blood chemistry . All data were analyzed by difference of changing in bone marker and BMD between statin and non-statin groups using paired t test . RESULTS The present study showed 212 hyperlipidemia with osteopenia patients of which 106 patients in statin group had mean age ( 63.17+/-9.51 years ) and the same number of patients in non-statin group had mean age ( 60.96+/-8.9 years ) . All subjects were 63 patients in male and 149 patients in female . Difference of bone formation marker and BMD between after and before was significantly higher than in statin group and the difference of bone resorption marker was also significantly lower than in statin group . CONCLUSION The lipophilic statin as moderate to high dose of simvastatin had beneficial positive effect to increasing BMD and could be additive use for prevention of bone loss in hyperlipidemia patients PURPOSE The Carotid Atherosclerosis Italian Ultrasound Study ( CAIUS ) was performed to test the effects of lipid lowering on the progression of carotid intima-media thickness ( IMT ) in 305 asymptomatic patients from a Mediterranean country . PATIENTS AND METHODS Eligibility included hypercholesterolemia ( baseline means : low-density lipoprotein [ LDL ] = 4.68 mmol/L , high-density lipoprotein [ HDL ] = 1.37 mmol/L ) , and at least one 1.3 < IMT < 3.5 mm in the carotid arteries . Patients ( mean age 55 years , 53 % male ) were assigned to pravastatin ( 40 mg/day , n = 151 ) or placebo ( n not equal to 154 ) . Ultrasound imaging was used to quantify IMT at baseline , and semiannually thereafter for up to 3 years . The mean of the 12 maximum IMTs ( MMaxIMT ) , was calculated for each patient visit , and used to determine each patient 's longitudinal progression slope . The intention-to-treat group difference in the MMaxIMT progression was chosen a priori as the primary end point . RESULTS Five serious cardiovascular events ( 1 fatal myocardial infa rct ion ) , and 7 drop-outs for cancer were registered . In the pravastatin group , LDL decreased -0.22 after 3 months versus -0.01 in the placebo group , and remained substantially unchanged afterward ( -0.23 versus + 0.01 at 36 months , respectively ) . Progression of the MMaxIMT was 0.009 + /- 0.0027 versus -0.0043 + /- 0.0028 mm/year ( mean + /- SE , P < 0.0007 ) in the placebo and pravastatin groups , respectively . IMT progression slopes diverged after 6 months of treatment . CONCLUSIONS Pravastatin stops the progression of carotid IMT in asymptomatic , moderately hypercholesterolemic men and women . This finding extends the beneficial effects of cholesterol lowering to the primary prevention of atherosclerosis in a population with relatively low cardiovascular event rates , and suggests that this benefit is mediated by specific morphological effects on early stages of plaque development BACKGROUND The JUPITER ( Justification for the Use of Statins in Prevention : An Intervention Trial Evaluating Rosuvastatin ) trial suggests that increased high-sensitivity C-reactive protein ( hsCRP ) concentrations may be useful in decisions about the initiation of statin therapy for primary prevention of vascular disease . Although studies of specific population s have suggested that hsCRP is a reliable longitudinal marker , it is unclear how strongly hsCRP tracks in individuals after a single increased concentration . METHODS We evaluated tracking of hsCRP in 8901 individuals r and omized to placebo in the JUPITER trial . These individuals had screening LDL cholesterol concentrations < 130 mg/dL ( < 3.37 mmol/L ) and hsCRP concentrations > or = 2 mg/L , with subsequent hsCRP measurements made before r and omization ; at 13 weeks ; 1 , 2 , 3 , and 4 years later ; and at trial termination . Longitudinal trends and associations were evaluated nonparametrically with box plots and Spearman correlations . After data transformation to achieve normality , repeated- measures regression models estimated the intraclass correlation of hsCRP , with and without controlling for known demographic , lifestyle , and medical determinants of hsCRP concentration . For comparison , we evaluated tracking of systolic and diastolic blood pressure ; total , LDL , and HDL cholesterol ; and fasting triglycerides . RESULTS The median hsCRP concentration in these untreated individuals showed modest regression to the mean over time , declining from 3.8 mg/L at r and omization to 3.4 mg/L at 4 years . Tracking correlations for hsCRP over time were comparable to those for blood pressure and LDL cholesterol , but lower than those for HDL , fasting triglycerides , and total cholesterol . The intraclass correlation for repeated hsCRP measurements was 0.54 ( 95 % CI , 0.53 - 0.55 ) without covariate adjustment and 0.50 ( 95 % CI , 0.49 - 0.51 ) after adjustment for demographic , lifestyle , and comorbidity determinants . CONCLUSIONS Concentrations of hsCRP show strong tracking , even after selection of individuals with initially high values . Without statin therapy , increased concentrations of hsCRP generally remain high over time OBJECTIVE To determine the effect of lovastatin therapy on health-related quality of life in older persons . DESIGN A prospect i ve , r and omized , double blind clinical trial . SETTING Four university medical center research clinics . PARTICIPANTS There were 431 men and women , primarily 65 years of age or older , with low density lipoprotein levels greater than 159 mg/dL and less than 221 mg/dL. Exclusion criteria included a Mini-Mental state score less than 24 or presence of recent cardiovascular events or other serious chronic disease likely to shorten survival . INTERVENTION All participants were administered the National Cholesterol Education Program step one diet and were then r and omized to placebo , 20 mg lovastatin , or 40 mg lovastatin . MEASUREMENTS Areas of health-related quality of life assessed in the Cholesterol Reduction in Seniors Program ( CRISP ) included : ( 1 ) physical functioning , ( 2 ) sleep behavior , ( 3 ) social support , ( 4 ) depression , ( 5 ) cognitive function , and ( 6 ) health perception . Three global change questions asked the patients to judge change in general health since starting the study diet or the study medication and change in ability to function or care for self . Although some patients were followed for a total of 12 months , all participants were followed for 6 months , and 6-month data have been used for the primary analysis in this paper . RESULTS Patients treated with 20 mg of lovastatin had a 17 % and 24 % reduction in total cholesterol and LDL-cholesterol , respectively . Patients treated with the 40-mg lovastatin dose achieved reductions of 20 % for total cholesterol and 28 % for LDL-cholesterol . Complaints of possible adverse events were remarkably similar in the two active treatment groups and the placebo group . At 6 months of follow-up there were no statistically significant differences found in mean change scores from baseline between treatment groups on the health-related quality of life measures ( physical functioning , sleep , social support , depression , cognitive function scales , health perception ) or global questions . CONCLUSIONS This study demonstrates that lovastatin was extremely well tolerated in an older cohort , both with regard to symptoms and to health-related quality of life Table . SI Units and Drugs Many reports have shown the efficacy of the combination of bile-absorbing resin and 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitor ( statin class ) therapies [ 1 - 4 ] . Primarily , this resin-statin treatment regimen has been targeted to patients with low-density lipoprotein ( LDL ) cholesterol levels greater than 6.47 mmol/L ( > 250 mg/dL ) , a population presumably enriched with familial hypercholesterolemic patients . Consequently , dosages have been large , with both the statin and resin agents administered at the upper ends of their respective dosing ranges . However , this group of markedly hypercholesterolemic patients does not represent the typical person identified through the adult National Cholesterol Education Program guidelines . For the considerably larger pool of persons with LDL cholesterol between 4.14 mmol/L and 6.21 mmol/L ( 160 mg/dL and 240 mg/dL ) , a safe , convenient , well-tolerated , and effective dosing method is essential . Low-dose combination therapy is thought to be beneficial because long-term compliance is enhanced and safety maximized while efficacy is preserved . It has been suggested that side effects with statin agents are dose-dependent , thereby implying a benefit with routine use of lower dosing . In contrast , side effects attributed to resin are equivalent at varying doses within the usual dosing range [ 5 , 6 ] . Thus , the benefit of lower resin dose would be confined to enhanced palatability and tolerability . The overall cholesterol lowering with such a low-dose combination , however , still remains unknown . Fluvastatin sodium ( Lescol , S and oz ; East Hanover , New Jersey ) , a new water-soluble cholesterol-lowering agent that acts through the inhibition of HMG-CoA reductase , is the first entirely synthetic HMG-CoA reductase inhibitor and differs structurally from the fungal derivatives of compactin [ 7 ] . Fluvastatin has a distinctive biopharmaceutical profile ; it has a high rate of absorption that is not influenced by food intake , possesses no circulating active metabolites , is 98 % protein-bound , does not cross the blood-brain barrier , has a systemic half-life of 30 minutes , and is 95 % excreted by the liver [ 8 ] . We evaluated the LDL cholesterol-lowering efficacy of various combinations of low-dose resin and statin treatments , using cholestyramine ( Questran Light ; Bristol ) and fluvastatin . The study population included mostly patients with hypercholesterolemia who would , according to the new National Cholesterol Education Program guidelines for adults ( LDL cholesterol > 4.91 mmol/L [ > 190 mg/dL ] or LDL cholesterol > 4.14 mmol/L [ > 160 mg/dL ] with two risk factors ) , be advised to receive medication . Methods The study protocol was design ed by mutual consent of the investigators and S and oz Research Institute , with all data collected by the investigators subject to review and analysis by S and oz Research Institute . The interpretation of the data in this article is based on the mutual consent of all su bmi tting authors . All patients were consecutively r and omized based on a diagnosis of hypercholesterolemia confirmed during drug washout with an LDL cholesterol level of at least 4.14 mmol/L ( 160 mg/dL ) , despite dietary intervention , and a plasma triglyceride level of no more than 3.39 mmol/L ( 300 mg/dL ) . Persons were excluded if they had a history of homozygous familial hypercholesterolemia , secondary hyperlipidemia , liver disease , renal disease , diabetes , myocardial infa rct ion or angioplasty within 6 months of study entry , or uncontrolled hypertension . The patients ' mean age was 54.1 years ; 54 % were male ; 95 % were white and 3 % were black . The treatment groups did not differ in baseline demographic characteristics . The study was approved by the institutional review boards for human research of all participating institutions . Informed consent was obtained from all patients . Treatment Plan This study consisted of a 6-week , single-blind , placebo washout period followed by a 24-week , double-blind treatment period divided into three phases ( Figure 1 ) . Patients were withdrawn from hypolipidemic therapy for at least 4 weeks ( 1 year for probucol ) before entry into the washout period . In addition , patients were instructed by a registered dietitian to follow a cholesterol-lowering diet ( American Heart Association or National Cholesterol Education Program step 1 ) for at least 8 weeks before entry into the washout period and throughout the study , and a Food Record Rating score of 15 or less was required for study entry [ 9 ] . Patients with  aspartate aminotransferase or alanine aminotransferase values greater than 1.5 times the upper limit of laboratory normal during the washout period were excluded from the study . Figure 1 . Study design and numbers of patients initially assigned to each treatment group . At the end of the placebo washout period , patients who satisfied all entry criteria entered the 24-week , double-blind treatment period , which consisted of three 8-week phases . For the first 8 weeks ( phase 1 ) , patients were assigned r and omly into six groups receiving blinded study medication : two groups receiving placebo ; two receiving 10 mg of fluvastatin ; and two receiving 20 mg of fluvastatin . In phases 2 and 3 of the study , one placebo group , one 10-mg fluvastatin group , and one 20-mg fluvastatin group received open-label cholestyramine in addition to the blinded study drug , whereas the other three groups remained on fluvastatin or placebo monotherapy for the rest of the trial . In phase 2 , the dose of cholestyramine added to the regimen of patients in the three combination groups was 4 g twice daily . In phase 3 , the dose of cholestyramine was increased to 8 g twice a day for these patients . Blinded medication was taken once daily at bedtime , approximately 4 hours after the evening meal . Patients receiving open-label cholestyramine took their medication just before breakfast and dinner . Compliance with all treatment regimens was assessed by pill or packet count . Study Evaluations Patients were assessed every 2 weeks during the placebo washout period and every 4 weeks during the 24-week treatment period . Dietary compliance was determined by Food Record Rating scores derived from dietary records collected throughout the study [ 9 ] . Twelve-hour fasting blood sample s were obtained at each visit for lipid determinations , which were done by a central laboratory ( Medical Research Laboratories ; Cincinnati , Ohio ) . Low-density lipoprotein cholesterol was calculated according to the Friedewald formula [ 10 ] . Total cholesterol , high-density lipoprotein cholesterol , and plasma triglycerides were measured on a 737 Hitachi analyzer ( Boehringer Mannheim Diagnostics ; Indianapolis , Indiana ) with microenzymatic procedures [ 11 ] fully st and ardized , and part 3 was monitored through the National Heart , Lung , and Blood Institute and Centers for Disease Control and Prevention Lipid St and ardization Program [ 12 , 13 ] . Safety was evaluated at baseline and at intervals throughout the study . These evaluations included measurements of blood pressure and pulse ; physical , ophthalmologic , and electrocardiographic examinations ; and routine laboratory tests . Investigators were asked to assess , in a blinded fashion , each adverse event and laboratory abnormality for a potential relation to blinded study drug administration , based on their clinical experience and judgment . Statistical Analysis All statistical comparisons were made using two-tailed tests at the P < 0.05 level . Data were pooled across all clinical centers for analysis . The Statistical Analysis System ( SAS Institute , Inc. ; Cary , North Carolina ) software was used for all analyses . All confidence intervals are 95 % and represent the difference in mean percent change from baseline between two treatment groups of interest . For each patient , the baseline lipid value was defined as the average of the week 2 and week 0 lipid measurements during the washout phase . In evaluating efficacy by treatment phase , lipid results were calculated as the averages of the values for weeks 4 and 8 , weeks 12 and 16 , and weeks 20 and 24 . For end-point analyses , the end point was defined as the last active treatment phase visit for which lipid data were available . One-way analysis of variance models were used to compare the mean percentage change in total cholesterol , LDL cholesterol , high-density lipoprotein cholesterol , and triglycerides between the treatment groups . In each model , we did tests of significance of the percentage change from baseline within each group and of differences in mean percentage change between treatment groups . In determining safety , a newly occurring abnormality was defined as an abnormality reported during the active treatment period but not reported during the placebo washout period , and a worsening abnormality was an abnormality that worsened from the placebo washout period to the active treatment period . The number of patients with newly occurring or worsening abnormalities in each treatment group was determined , and the proportions were compared using the Fisher exact test . Results Of 460 patients from nine study centers screened , 224 met study criteria and were r and omized into the double-blind treatment period of this study ; 203 completed all phases of treatment . Fifteen ( 10 % ) of 150 fluvastatin-treated patients and 6 ( 8 % ) of 74 placebo- or cholestyramine-treated or both ( that is , non-fluvastatin-treated ) patients were dropped during the double-blind treatment period . Five fluvastatin-treated patients ( 1 receiving concomitant cholestyramine ) and 1 placebo-treated patient ( receiving concomitant cholestyramine ) dropped out because of adverse events . These events , each of which occurred in one patient , were angina , myalgia , stomatitis and glossitis , heartburn and indigestion , elevated transaminase levels , and alopecia . Of these , only the instance of stomatitis and glossitis was judged by the investigator to be definitely related to the drug . One patient Background Statins reduce cardiovascular events and progression of carotid intima-media thickness ( IMT ) . & bgr;-Blockers are also known to reduce cardiovascular events , but less is known about their effects on carotid IMT . Methods and Results We conducted a r and omized , double-blind , placebo-controlled , single-center trial to compare the effects of low-dose metoprolol CR/XL ( 25 mg once daily ) and fluvastatin ( 40 mg once daily ) on the progression of carotid IMT during 36 months of treatment in 793 subjects who had carotid plaque but no symptoms of carotid artery disease . Changes in mean IMT in the common carotid artery and maximal IMT in the bulb were the main outcome variables . Death and cardiovascular events were monitored . Progression of IMTmax in the carotid bulb at both 18 and 36 months was reduced by metoprolol CR/XL ( −0.058 mm/y ; 95 % CI , −0.094 to −0.023;P = 0.004 ; and −0.023 mm/y ; 95 % CI , −0.044 to −0.003;P = 0.014 , respectively ) . Incidence of cardiovascular events tended to be lower in metoprolol CR/XL – treated patients ( 5 versus 13 patients , P = 0.055 ) . Rate of IMTmean progression in the common carotid at 36 months was reduced by fluvastatin ( −0.009 mm/y ; 95 % CI , −0.015 to −0.003;P = 0.002 ) . Women in the fluvastatin group had increased frequency of transiently high liver enzymes . Conclusions This is the first r and omized trial to show that a & bgr;-blocker can reduce the rate of progression of carotid IMT in clinical ly healthy , symptom-free subjects with carotid plaque . This suggests that & bgr;-blockers may have a favorable effect on atherosclerosis development OBJECTIVE The objectives of the Cost Effectiveness of Lipid Lowering ( CELL ) study were twofold : ( i ) to evaluate the effect on overall cardiovascular risk of two types of health care advice ( " usual ' and " intensive ' ) given in primary care , with or without pharmacological medication , with the target being to attain a moderate decrease in cholesterol ; ( ii ) to evaluate the ritual of daily medication on compliance with the health care advice . DESIGN A prospect i ve , double-blind , r and omized , controlled trial of 18 months ' duration . SETTING The study was carried out in 32 health centres ( out of a total of approximately 850 ) in Sweden . SUBJECTS In all , 681 subjects , aged 30 - 59 years , were r and omized . They had at least two cardiovascular risk factors in addition to moderate primary hyperlipidaemia ( total cholesterol of at least 6.50 mmol L-1 on three occasions measured by Reflotron triglycerides less than 4.0 mmol L-1 and an LDL : HDL cholesterol ratio of more than 4.0 ) . Most ( 87 % ) of the subjects were males ; 626 subjects ( 92 % ) completed the 18-month follow-up . INTERVENTION Half the subjects were r and omized to ' intensive advice ' given in group sessions led by doctors and nurses in primary care . The other half received ' usual advice ' . In each of the two advice groups , one-third received an active lipid-lowering drug ( pravastatin ) , one-third placebo , and one-third no drug at all . The tablets were titrated to achieve a 15 % reduction in cholesterol . MAIN OUTCOME MEASURES Changes in the overall Framingham risk score , and the development of adverse events in each group . RESULTS The change in Framingham risk score was significantly reduced only in subjects taking lipid-lowering medication ( together with intensive advice -0.13 ; 95 % CI-0.20 , -0.06 , and together with usual advice -0.16 ; 95 % CI -0.23 , -0.09 ) . The other subjects receiving intensive advice tended to fare better than those on usual advice . Lifestyle was not influenced significantly over the study period . The ritual of daily medication did not affect the outcome . CONCLUSION As expected , lipid-lowering medication reduced serum cholesterol as well as overall cardiovascular risk in subjects with several risk factors for cardiovascular disease . There was no additive effect of intensive advice to these subjects . However , there was a meagre but significant effect of intensive advice in subjects not receiving active lipid-lowering drugs . One explanation for this difference may be that those on active lipid-lowering medication who had substantial drops in cholesterol might have felt less inclined to change their lifestyle compared with those on other treatment regimens who had less successful drops in cholesterol . There was no benefit from the ritual of taking daily medication BACKGROUND There are few data on the role of lipid lowering in the primary prevention of  coronary heart disease ( CHD ) in diabetic patients . This paper describes the design of a collaborative clinical trial between Diabetes UK , the NHS Research and Development Directorate and Pfizer UK , that addresses this question . METHODS The Collaborative AtoRvastatin Diabetes Study ( CARDS ) is a multicentre , r and omized , placebo-controlled , double-blind clinical trial of primary prevention of cardiovascular disease in patients with Type 2 diabetes . The primary objective is to investigate whether treatment with the hydroxymethylglutaryl coenzyme A reductase inhibitor , atorvastatin , reduces the incidence of major cardiovascular events . At entry patients have at least one other risk factor for CHD in addition to diabetes , namely current smoking , hypertension , retinopathy , or micro- or macroalbuminuria . At r and omization patients have been selected for a serum low-density lipoprotein ( LDL ) cholesterol concentration < or = 4.14 mmol/l ( 160 mg/dl ) and triglycerides < or = 6.78 mmol/l ( 600 mg/dl ) . R and omization was completed in June 2001 . Patients will be followed until 304 primary endpoints have accrued ( expected date early 2005 ) . The trial includes 2838 men and women aged 40 - 75 years . This report describes the design and administration of the study and review s the evidence to date of the effectiveness of  lipid-lowering therapy in Type 2 diabetes . CONCLUSIONS The case for lipid-lowering therapy for the primary prevention of CHD in diabetes has not been demonstrated . CARDS will provide essential information on the extent of any benefits and adverse effects of lipid-lowering therapy in diabetic patients without prior CHD BACKGROUND Patients with coronary artery disease and abnormalities of serum lipids often have endothelial vasodilator dysfunction , which may contribute to ischemic cardiac events . Whether cholesterol-lowering or antioxidant therapy can restore endothelium-dependent coronary vasodilation is unknown . METHODS We r and omly assigned 49 patients ( mean serum cholesterol level , 209 + /- 33 mg per deciliter [ 5.40 + /- 0.85 mmol per liter ] ) to receive one of three treatments : an American Heart Association Step 1 diet ( the diet group , 11 patients ) ; lovastatin and cholestyramine ( the low-density lipoprotein [LDL]-lowering group , 21 patients ) ; or lovastatin and probucol ( the LDL-lowering-antioxidant group , 17 patients ) . Endothelium-dependent coronary-artery vasomotion in response to an intracoronary infusion of acetylcholine ( 10(-8 ) to 10(-6 ) M ) was assessed at base line and after one year of therapy . Vasoconstrictor responses to these doses of acetylcholine are considered to be abnormal . RESULTS Treatment result ed in significant reductions in LDL cholesterol levels of 41 + /- 22 percent in the LDL-lowering-antioxidant group and 38 + /- 20 percent in the LDL-lowering group ( P < 0.001 vs. the diet group ) . The maximal changes in coronary-artery diameter with acetylcholine at base line and at follow-up were -19 and -2 percent , respectively , in the LDL-lowering-antioxidant group , -15 and -6 percent in the LDL-lowering group , and -14 and -19 percent in the diet group ( P < 0.01 for the LDL-lowering-antioxidant group vs. the diet group ; P = 0.08 for the LDL-lowering group vs. the diet group ) . ( The negative numbers indicate vasoconstriction ) . Thus , the greatest improvement in the vasoconstrictor response was seen in the LDL-lowering-antioxidant group . CONCLUSIONS The improvement in endothelium-dependent vasomotion with cholesterol-lowering and antioxidant therapy may have important implication s for the activity of myocardial ischemia and may explain in part the reduced incidence of adverse coronary events that is known to result from cholesterol-lowering therapy The objective of this multicenter , r and omized , open-label , parallel-group , 8-week study was to evaluate the comparative dose efficacy of the 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitor atorvastatin 10 , 20 , 40 , and 80 mg compared with simvastatin 10 , 20 , and 40 mg , pravastatin 10 , 20 , and 40 mg , lovastatin 20 , 40 , and 80 mg , and fluvastatin 20 and 40 mg . Investigators enrolled 534 hypercholesterolemic patients ( low-density lipoprotein [ LDL ] cholesterol > or = 160 mg/dl [ 4.2 mmol/L ] and triglycerides < or = 400 mg/dl [ 4.5 mmol/L ] ) . The efficacy end points were mean percent change in plasma LDL cholesterol ( primary ) , total cholesterol , triglycerides , and high-density lipoprotein cholesterol concentrations from baseline to the end of treatment ( week 8) . Atorvastatin 10 , 20 , and 40 mg produced greater ( p < or = 0.01 ) reductions in LDL cholesterol , -38 % , -46 % , and -51 % , respectively , than the milligram equivalent doses of simvastatin , pravastatin , lovastatin , and fluvastatin . Atorvastatin 10 mg produced LDL cholesterol reductions comparable to or greater than ( p < or = 0.02 ) simvastatin 10 , 20 , and 40 mg , pravastatin 10 , 20 , and 40 mg , lovastatin 20 and 40 mg , and fluvastatin 20 and 40 mg . Atorvastatin 10 , 20 , and 40 mg produced greater ( p < or = 0.01 ) reductions in total cholesterol than the milligram equivalent doses of simvastatin , pravastatin , lovastatin , and fluvastatin . All reductase inhibitors studied had similar tolerability . There were no incidences of persistent elevations in serum transaminases or myositis BACKGROUND Statins lower high-sensitivity C-reactive protein ( hsCRP ) and cholesterol concentrations , and hypothesis generating analyses suggest that clinical outcomes improve in patients given statins who achieve hsCRP concentrations less than 2 mg/L in addition to LDL cholesterol less than 1.8 mmol/L ( < 70 mg/dL ) . However , the benefit of lowering both LDL cholesterol and hsCRP after the start of statin therapy is controversial . We prospect ively tested this hypothesis . METHODS In an analysis of 15 548 initially healthy men and women participating in the JUPITER trial ( 87 % of full cohort ) , we prospect ively assessed the effects of rosuvastatin 20 mg versus placebo on rates of non-fatal myocardial infa rct ion , non-fatal stroke , admission for unstable angina , arterial revascularisation , or cardiovascular death ( prespecified endpoints ) during a maximum follow-up of 5 years ( median 1.9 years ) , according to on-treatment concentrations of LDL cholesterol ( > /=1.8 mmol/L or < 1.8 mmol/L ) and hsCRP ( > /=2 mg/L or < 2 mg/L ) . We included all events occurring after r and omisation . This trial is registered with Clinical Trials.gov , number NCT00239681 . FINDINGS Compared with placebo , participants allocated to rosuvastatin who achieved LDL cholesterol less than 1.8 mmol/L had a 55 % reduction in vascular events ( event rate 1.11 vs 0.51 per 100 person-years ; hazard ratio [ HR ] 0.45 , 95 % CI 0.34 - 0.60 , p<0.0001 ) , and those achieving hsCRP less than 2 mg/L a 62 % reduction ( event rate 0.42 per 100 person-years ; HR 0.38 , 95 % CI 0.26 - 0.56 , p<0.0001 ) . Although LDL cholesterol and hsCRP reductions were only weakly correlated in individual patients ( r values < 0.15 ) , we recorded a 65 % reduction in vascular events in participants allocated to rosuvastatin who achieved both LDL cholesterol less than 1.8 mmol/L and hsCRP less than 2 mg/L ( event rate 0.38 per 100 person-years ; adjusted HR 0.35 , 95 % CI 0.23 - 0.54 ) , versus a 33 % reduction in those who achieved one or neither target ( event rate 0.74 per 100 person-years ; HR 0.67 , 95 % CI 0.52 - 0.87 ) ( p across treatment groups < 0.0001 ) . In participants who achieved LDL cholesterol less than 1.8 mmol/L and hsCRP less than 1 mg/L , we noted a 79 % reduction ( event rate 0.24 per 100 person-years ; HR 0.21 , 95 % CI 0.09 - 0.52 ) . Achieved hsCRP concentrations were predictive of event rates irrespective of the lipid endpoint used , including the apolipoprotein B to apolipoprotein AI ratio . INTERPRETATION For people choosing to start pharmacological prophylaxis , reduction in both LDL cholesterol and hsCRP are indicators of successful treatment with rosuvastatin Until recently , the role of statin therapy in diabetic patients without clinical signs or symptoms of coronary heart disease had been inadequately defined . The Collaborative Atorvastatin Diabetes Study ( CARDS ) is a prospect i ve , r and omized , placebo-controlled trial design ed to compare the effects of atorvastatin with placebo in preventing primary coronary events in diabetic patients . After a median of only 3.9 years ( the study was terminated approximately 2 years early due to the magnitude of benefit attributable to atorvastatin therapy ) , risk for major cardiovascular events was decreased by 37 % , acute coronary heart disease-related events were also reduced by 36 % , coronary revascularizations by 31 % , and stroke by 48 % . Benefit emerged within 1 year of initiating therapy OBJECTIVES This study investigated the effect of reducing serum lipids on carotid artery intima-media thickness ( IMT ) in asymptomatic patients with hypercholesterolemia from Fukuoka , Japan . BACKGROUND Carotid atherosclerosis is a strong , independent predictor of morbidity and mortality in patients with coronary heart disease ( CHD ) . METHODS A total of 246 asymptomatic hypercholesterolemic patients ( mean age 66 years ) were r and omized to receive either probucol ( 500 mg/day , n = 82 ) or pravastatin ( 10 mg/day , n = 83 ) or to enter a control group ( diet alone , n = 81 ) ; they were followed for two years . The change in IMT in the common carotid artery was the primary end point measure , and the incidence of major cardiovascular events was the secondary measure . RESULTS Over the two-year period , serum low-density lipoprotein ( LDL ) cholesterol was significantly reduced in the pravastatin group ( 36 % ) , the probucol group ( 29 % ) and the control group ( 12 % ) ( p < 0.0001 , p < 0.0001 and p < 0.05 , respectively ) . After two years , the probucol and pravastatin groups showed a significant reduction in IMT ( -13.9 % and -13.9 % and p < 0.01 and p < 0.01 , respectively ) , but there was significant IMT thickening ( 23.2 % ; p < 0.05 ) in the control group . Probucol reduced the rate of IMT increase , independently of its reduction of LDL or high-density lipoprotein cholesterol . Moreover , there was a significantly lower incidence of cardiac events in the probucol group ( 2.4 % ) than in the control group ( 13.6 % ) ( p = 0.0136 ) . CONCLUSIONS Probucol reduced cholesterol levels and stabilized plaque , leading to a lower incidence of cardiac events in these hypercholesterolemic patients AIMS To assess the additional benefit gained from high  compliance in the West of Scotl and Coronary Prevention Study and to examine cases where withdrawal from trial medication was due to an adverse event . METHODS The incidence of definite coronary heart disease or non-fatal myocardial infa rct ion , cardiovascular mortality , definite or suspect coronary heart disease death or non-fatal myocardial infa rct ion , the need for coronary revascularization procedures , all-cause mortality and incident cancers were measured in the entire cohort and compared with the high compliance group . The adverse events associated with withdrawal were coded by body system . RESULTS In subjects with compliance > or = 75 % , treatment with pravastatin result ed in a 38 % risk reduction for definite coronary heart disease death or non-fatal myocardial infa rct ion and for cardiovascular mortality , a 46 % reduction in risk or coronary revascularization and a 32 % risk reduction ( P = 0.015 ) for all-cause mortality . CONCLUSIONS The analysis of the effect of pravastatin in the subgroup of high compliers to r and omized medication demonstrated a substantial increase in the estimated risk reductions in comparison with that achieved in the intention-to-treat analysis . This result has significant implication s for the motivation of high compliance among patients and for the assessment of the cost-effectiveness of treatment Endothelial function is known to predict cardiovascular disease . The aim of the present study was to examine whether endothelial function in smokers with normal cholesterol levels could be normalized by treatment with 80 mg of atorvastatin in comparison with a control group . Healthy smokers ( n=20 ) and non-smokers ( n=20 ) were r and omized to receive 80 mg of atorvastatin or placebo in an open r and omized cross-over study , followed by measurement of endothelial functional [ FMD ( flow-mediated dilation ) ] . At baseline , smokers had a lower FMD compared with the non-smoking group ( 2.2+/-0.5 and 4.5+/-0.8 % respectively ; P<0.05 ) . In the smoking group , FMD increased significantly ( P<0.05 ) to 4.0+/-0.8 % during treatment with atorvastatin and returned to basal levels during placebo ( 2.3+/-0.6 % ) . In the non-smoking group , FMD was unaffected by both atorvastatin and placebo . The net change of total cholesterol or LDL ( low-density lipoprotein)-cholesterol was not associated with the net change in FMD when the study group was considered as a whole or the smoking group was considered separately . In conclusion , improved endothelial function was observed in a group of smokers when they were received 80 mg of atorvastatin , whereas atorvastatin had no effect on endothelial function in the non-smoking group . The improved FMD among smokers was independent of the decrease in LDL-cholesterol during atorvastatin treatment . The results show that poor endothelial function in smokers with normal lipid levels can be improved by a statin treatment CONTEXT Studies have demonstrated that statins administered to individuals with risk factors for coronary heart disease ( CHD ) reduce CHD events . However , many of these studies were too small to assess all-cause mortality or outcomes in important subgroups . OBJECTIVE To determine whether pravastatin compared with usual care reduces all-cause mortality in older , moderately hypercholesterolemic , hypertensive participants with at least 1 additional CHD risk factor . DESIGN AND SETTING Multicenter ( 513 primarily community-based North American clinical centers ) , r and omized , nonblinded trial conducted from 1994 through March 2002 in a subset of participants from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) . PARTICIPANTS Ambulatory persons ( n = 10 355 ) , aged 55 years or older , with low-density lipoprotein cholesterol ( LDL-C ) of 120 to 189 mg/dL ( 100 to 129 mg/dL if known CHD ) and triglycerides lower than 350 mg/dL , were r and omized to  pravastatin  ( n = 5170 ) or to  usual care  ( n = 5185 ) . Baseline mean total cholesterol was 224 mg/dL ; LDL-C , 146 mg/dL ; high-density lipoprotein cholesterol , 48 mg/dL ; and triglycerides , 152 mg/dL. Mean age was 66 years , 49 % were women , 38 % black and 23 % Hispanic , 14 % had a history of CHD , and 35 % had type 2 diabetes . INTERVENTION Pravastatin , 40 mg/d , vs usual care . MAIN OUTCOME MEASURES The primary outcome was all-cause mortality , with follow-up for up to 8 years . Secondary outcomes included nonfatal myocardial infa rct ion or fatal CHD ( CHD events ) combined , cause-specific mortality , and cancer . RESULTS Mean follow-up was 4.8 years . During the trial , 32 % of usual care participants with and 29 % without CHD started taking lipid-lowering drugs . At year 4 , total cholesterol levels were reduced by 17 % with pravastatin vs 8 % with usual care ; among the r and om sample who had LDL-C levels assessed , levels were reduced by 28 % with pravastatin vs 11 % with usual care .  All-cause mortality was similar for the 2 groups ( relative risk [ RR ] , 0.99 ; 95 % confidence interval [ CI ] , 0.89 - 1.11 ; P = .88 ) , with 6-year mortality rates of 14.9 % for pravastatin vs 15.3 % with usual care .  CHD event rates were not significantly different between the groups ( RR , 0.91 ; 95 % CI , 0.79 - 1.04 ; P = .16 ) , with 6-year CHD event rates of 9.3 % for pravastatin and 10.4 % for usual care . CONCLUSIONS Pravastatin did not reduce either all-cause mortality or CHD significantly when compared with usual care in older participants with well-controlled hypertension and moderately elevated LDL-C. The results may be due to the modest differential in total cholesterol ( 9.6 % ) and LDL-C ( 16.7 % ) between pravastatin and usual care compared with prior statin trials supporting cardiovascular disease prevention This double-blind study to evaluate long-term efficacy and safety of atorvastatin was performed in 31 community- and university-based research centers in the USA to directly compare a new 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor ( reductase inhibitor ) to an accepted drug of this class in patients with moderate hypercholesterolemia . Participants remained on a cholesterol-lowering diet throughout the study . One thous and forty-nine patients were r and omized to receive atorvastatin 10 mg , lovastatin 20 mg , or placebo . At 16 weeks the placebo group was r and omized to either atorvastatin or lovastatin treatment . At 22 weeks , patients who had not met low-density lipoprotein ( LDL ) cholesterol target levels doubled the dose of reductase inhibitor . Efficacy evaluation was mean percent change from baseline in LDL cholesterol , triglycerides , total cholesterol , high-density-lipoprotein cholesterol , and apolipoprotein B ( apoB ) . Safety profiles as determined by change from baseline in laboratory evaluations , ophthalmologic parameters , and reporting of adverse events were similar for the 2 reductase inhibitors . After 52 weeks , the atorvastatin group maintained a significantly greater reduction in LDL cholesterol ( -37 % vs -29 % ) , triglyceride ( -16 % vs -8 % ) , total cholesterol ( -27 % vs -21 % ) , and apoB ( -30 % vs -22 % ) ( p < 0.05 ) . More patients receiving atorvastatin achieved LDL cholesterol target levels than did lovastatin patients ( 78 % vs 63 % , respectively ) , particularly those with coronary heart disease ( 37 % vs 11 % , respectively ) . Atorvastatin is highly effective and well tolerated in patients with primary hypercholesterolemia with no increased risk of adverse events Lp(a ) level is relatively stable in each individual and is mainly under genetic control . Attempts made to lower Lp(a ) with pharmacological means gave conflicting results . In order to further evaluate the effect of hypocholesterolemic drugs on Lp(a ) level , 66 patients with primary hypercholesterolemia were selected . The vast majority of the patients had Lp(a ) concentration at the low end of the range of distribution , 7 had undetectable Lp(a ) levels and only 2 had Lp(a ) higher than 30 mg/dl . No relationship was found between Lp(a ) level and serum and lipoprotein lipids . In 12 patients serum cholesterol was well controlled by diet alone and the patients continued the diet for up to 8 months . The other patients were r and omly subdivided into 3 groups of therapy . The first group received slow release bezafibrate 400 mg once a day , the second one pravastatin 20 mg once a day and the third one simvastatin 10 - 40 mg once a day . Drug therapy lasted for 8 months . At the end of the period , 22 of 29 patients treated with the 2 HMG-CoA reductase inhibitors had Lp(a ) higher than baseline . The difference was statistically significant in both groups of patients . No significant change in Lp(a ) was observed in diet and in bezafibrate group . Serum and LDL cholesterol significantly decreased in all the 3 drug groups . The increase in Lp(a ) after the 2 HMG-CoA reductase was small enough to have negligible effects on cardiovascular risk , but raises the problem of the role of LDL receptor in the catabolism of Lp(a ) The purpose of this double-blind , r and omized , placebo-controlled trial was to determine the long-term effects of pravastatin and fosinopril treatment on peripheral endothelial function in subjects with albuminuria . Subjects ( mean age 51 years , 63 % male ) were r and omized to pravastatin 40 mg or matching placebo and  to  fosinopril 20 mg or matching placebo . Using high resolution ultrasound , flow-mediated dilation ( FMD ) and nitroglycerin-induced dilation ( NID ) was assessed at baseline and after 4 years of treatment in a total of 276 subjects . At baseline , mean+/-st and ard error FMD was 4.73+/-0.49 % and NID was 10.86+/-0.67 % . Pravastatin significantly reduced total cholesterol and LDL cholesterol ( p<0.01 ) and r and omization to pravastatin was associated with a non-significant improvement of 18.9 % in FMD ( + 0.80+/-0.95 , p=0.09 ) , without a significant change in NID . Interestingly , pravastatin significantly increased FMD by 34.9 % in men ( + 1.23 , p=0.04 ) , but only 1.1 % in women ( + 0.06 , p=0.95 ) . Fosinopril was not associated with a change in FMD or NID despite significantly decreasing urinary albumin excretion , systolic and diastolic blood pressure ( all p<0.01 ) . In conclusion , after 4 years of follow-up , pravastatin treatment tended to increase FMD and this effect was predominantly present in men . Fosinopril treatment did not modify FMD during long-term follow-up Background and Purpose — The Plaque Hypertension Lipid-Lowering Italian Study ( PHYLLIS ) tested whether ( 1 ) the angiotensin-converting enzyme ( ACE ) inhibitor fosinopril ( 20 mg per day ) was more effective on carotid atherosclerosis progression than the diuretic hydrochlorothiazide ( 25 mg per day ) , ( 2 ) pravastatin ( 40 mg per day ) was more effective than placebo when added to either hydrochlorothiazide or fosinopril , and ( 3 ) there were additive effects of ACE inhibitor and lipid-lowering therapies . Methods — A total of 508 hypertensive , hypercholesterolemic patients with asymptomatic carotid atherosclerosis were r and omized to : ( A ) hydrochlorothiazide ; ( B ) fosinopril ; ( C ) hydrochlorothiazide plus pravastatin ; and ( D ) fosinopril plus pravastatin , and followed up blindly for 2.6 years . B-Mode carotid scans were performed yearly by certified sonographers in 13 hospitals and read central ly . Corrections for drift were calculated from readings repeated at study end . Primary outcome was change in mean maximum intima-media thickness of far and near walls of common carotids and bifurcations bilaterally ( CBMmax ) . Results — CBMmax significantly progressed ( 0.010±0.004 mm per year ; P=0.01 ) in group A ( hydrochlorothiazide alone ) but not in groups B , C , and D. CBMmax changes in groups B , C , and D were significantly different from changes in group A. Changes in group A were concentrated at the bifurcations . “ Clinic ” and “ ambulatory ” blood pressure reductions were not significantly different between groups , but total and low-density lipoprotein cholesterol decreased by ≈1 mmol/L in groups C and D. Conclusions — Progression of carotid atherosclerosis occurred with hydrochlorothiazide but not with fosinopril . Progression could also be avoided by associating pravastatin with hydrochlorothiazide High serum cholesterol levels are associated with death from coronary heart disease and statin therapy has been demonstrated to effectively lower low-density lipoprotein ( LDL ) cholesterol and reduce coronary events in broad sections of the population . Recently , the Justification for the Use of Statins in Primary Prevention : an Intervention Trial Evaluating Rosuvastatin  ( JUPITER ) r and omized 17 802 apparently healthy individuals , with levels of LDL cholesterol below current treatment thresholds but with elevated levels of high-sensitivity C-reactive protein , to rosuvastatin 20 mg daily , or placebo . At a median follow-up of almost 2 years , compared to placebo , rosuvastatin treatment was associated with a significant reduction in the incidence of major cardiovascular or cerebrovascular events , that is , almost twice the magnitude found in previous statin trials . Such a noteworthy finding is discussed herein The Exp and ed Clinical Evaluation of Lovastatin study , a r and omized , double-blind , placebo- and diet-controlled multicenter trial , evaluated the efficacy and tolerability of lovastatin over 48 weeks in 8,245 patients with moderately severe hypercholesterolemia . During year 1 of follow-up of the full cohort , lovastatin at 20 or 40 mg/day , or 20 or 40 mg twice daily , produced dose-dependent decreases in low-density lipoprotein ( LDL ) cholesterol ( 24 % to 40 % ) and triglyceride levels ( 10 % to 19 % ) , and increases in high-density lipoprotein ( HDL ) cholesterol ( 6.6 % to 9.5 % ) . In all , 977 patients continued their original blinded treatment for an additional year . In year 2 , the LDL cholesterol response to lovastatin was maintained , the triglyceride reductions were somewhat less , and the increases in HDL cholesterol were moderately greater than in year 1 . Successive transaminase elevations > 3 times the upper limit of normal were observed in only 1 patient in year 2 , yielding a cumulative 2-year incidence of from 0.1 % ( placebo or lovastatin 20 mg/day ) to 1.9 % ( lovastatin 80 mg/day ) . Myopathy occurred in only 1 patient during year 2 , and over the 2-year study was observed rarely and only at lovastatin dosages of 40 and 80 mg/day . This study indicates that lovastatin maintains its efficacy over long-term follow-up , particularly in effectively lowering LDL cholesterol , is generally well tolerated , and has a favorable safety profile Objective : To test whether the 3-hydroxy-3-methylglutaryl- coenzyme A reductase inhibitor atorvastatin can slow down the progression of presbycusis . Patients : Fifty patients 60- to 75-years-old with presbycusis and moderately elevated serum cholesterol . Intervention(s ) : In a double-blind design , patients were r and omly assigned to treatment with either atorvastatin ( 40 mg/d orally ) or placebo . Main Outcome Measure(s ) : Pure-tone audiometry and tinnitus evaluation at enrolment and after 7 and 13 months . Results : Development of hearing thresholds after 7 and 13 months showed no significant differences between the groups . Tinnitus score continuously improved in the atorvastatin group ( 34.8 at 7 and 27.6 at 13 mo ) , whereas it slightly deteriorated in the placebo group ( 24.8 at 7 and 26.8 at 13 mo ) . The effect on tinnitus was a tendency without statistic significance ( p = 0.0833 ) . Conclusion : Atorvastatin had no effect on the development of hearing thresholds , but result ed in a trend toward a relief of tinnitus Little information exists to quantify the functional status and economic consequences of lipid-lowering therapy in elderly patients . We describe the design of the cost-effectiveness component of the first large , r and omized , placebo-controlled trial of lipid-lowering therapy in subjects aged 70 years or older . The PROspect i ve Study of Pravastatin in the Elderly at Risk has r and omized 5804 men and women 70 - 82 years old , with existing vascular disease or related risk factors , to receive 40 mg/d of pravastatin or placebo . The cost-effectiveness study will be based on within-trial observations of differences between the two study arms in rates of myocardial infa rct ion , stroke and related vascular disease outcomes ( including vascular dementia ) . In addition to comparing within-trial clinical outcomes , we will model the projected changes in life expectancy and cardiovascular outcome rates that would be seen with lifelong use of the drug , based on the risk reduction rates seen in the trial as well as baseline observational data from the three countries where the trial is being conducted ( Scotl and , Irel and and the Netherl and s ) . A state transition ( Markov ) model will be constructed to estimate the likely states of health , functional status and health care re source utilization ( including lipid-lowering drug costs ) in a cohort of elderly patients with versus without pravastatin therapy over a series of 1-year cycles until death . In addition , a st and ard measure of utility ( the Health Utilities Index ) will be administered to all study subjects to permit calculation of quality -adjusted life-years gained with this regimen . This approach will make it possible to go beyond the calculation of a single endpoint for each subject , and to translate the trial findings into definitions of effectiveness and outcomes that will be relevant to the ongoing debate concerning how best to relate the benefits of such medications to their costs p w A s l fi r t t u w h In January 2003 , the Justification for the Use of statins in revention : an Intervention Trial Evaluating Rosuvastatin JUPITER ) investigators began to enroll 17,802 men and omen with no evidence of cardiovascular disease and ormal to low levels of low-density lipoprotein ( LDL ) choesterol into a controversial trial testing whether subjects ith enhanced inflammatory responses might benefit from ggressive statin therapy . At study entry , the mean LDL holesterol level for enrolled participants was just above 00 mg/dl , nearly half had Framingham scores of 10 % , nd none were considered c and i date s for statin therapy under ny current set of prevention guidelines . However , all trial articipants had levels of the inflammatory biomarker highensitivity C-reactive protein ( hsCRP ) 2 mg/L , putting them t substantial risk for future cardiovascular disease . As the JUPITER investigators have since reported in a eries of rigorously peer- review ed reports published in the ew Engl and Journal of Medicine , The Lancet , the nnals of Internal Medicine , Circulation , the Journal of he American College of Cardiology , and The American ournal of Cardiology , r and om allocation to rosuvastatin 0 mg compared to placebo within the trial population esulted in a 54 % reduction in myocardial infa rct ion ( p .0002 ) , a 51 % reduction in ischemic stroke ( p 0.004 ) , a 6 % reduction in need for bypass surgery or angioplasty p 0.0001 ) , a 43 % reduction in venous thromboembolism p 0.002 ) , and a 20 % reduction in all-cause mortality p 0.02 ) . For the JUPITER primary end point of OBJECTIVES We evaluated the efficacy of statin therapy in primary prevention among individuals with moderate chronic kidney disease ( CKD ) . BACKGROUND Whether patents with moderate CKD ( estimated glomerular filtration rate [ eGFR ] < 60 ml/min/1.73 m(2 ) ) benefit from statin therapy is uncertain , particularly among those without hyperlipidemia or known cardiovascular disease . METHODS Within the JUPITER ( Justification for the Use of statins in Prevention-an Intervention Trial Evaluating Rosuvastatin ) primary prevention trial of rosuvastatin 20 mg compared with placebo among men and women free of cardiovascular disease who had low-density lipoprotein cholesterol ( LDL-C ) < 130 mg/dl and high-sensitivity C-reactive protein ( hsCRP ) > or=2 mg/l , we performed a secondary analysis comparing cardiovascular and mortality outcomes among those with moderate CKD at study entry ( n = 3,267 ) with those with baseline eGFR > or=60 ml/min/1.73 m(2 ) ( n = 14,528 ) . Median follow-up was 1.9 years ( maximum 5 years ) . RESULTS Compared with those with eGFR > or=60 ml/min/1.73 m(2 ) , JUPITER participants with moderate CKD had higher vascular event rates ( hazard ratio [ HR ] : 1.54 , 95 % confidence interval [ CI ] : 1.23 to 1.92 , p = 0.0002 ) . Among those with moderate CKD , rosuvastatin was associated with a 45 % reduction in risk of myocardial infa rct ion , stroke , hospital stay for unstable angina , arterial revascularization , or confirmed cardiovascular death ( HR : 0.55 , 95 % CI : 0.38 to 0.82 , p = 0.002 ) and a 44 % reduction in all-cause mortality ( HR : 0.56 , 95 % CI : 0.37 to 0.85 , p = 0.005 ) . Median LDL-C and hsCRP reductions as well as side effect profiles associated with rosuvastatin were similar among those with and without CKD . Median eGFR at 12 months was marginally improved among those allocated to rosuvastatin as compared with placebo . CONCLUSIONS Rosuvastatin reduces first cardiovascular events and all-cause mortality among men and women with LDL-C < 130 mg/dl , elevated hsCRP , and concomitant evidence of moderate CKD . ( JUPITER-Crestor 20 mg Versus Placebo in Prevention of Cardiovascular [ CV ] Events ; NCT00239681 ) OBJECTIVES We sought to examine the incidence and clinical predictors of  new-onset type 2 diabetes mellitus ( T2DM )  within 3 large r and omized trials with atorvastatin . BACKGROUND Statin therapy might modestly increase the risk of new-onset T2DM . METHODS We used a st and ard definition of diabetes and excluded patients with prevalent diabetes at baseline . We identified baseline predictors of new-onset T2DM and compared the event rates in patients with and without new-onset T2DM . RESULTS In the TNT ( Treating to New Targets ) trial , 351 of 3,798 patients r and omized to 80 mg of atorvastatin  and 308 of 3,797 r and omized to 10 mg developed new-onset T2DM ( 9.24 % vs. 8.11 % , adjusted hazard ratio [ HR ] : 1.10 , 95 % confidence interval [ CI ] : 0.94 to 1.29 , p = 0.226 ) . In the IDEAL ( Incremental Decrease in End Points Through Aggressive Lipid Lowering ) trial , 239 of 3,737 patients r and omized to atorvastatin 80 mg/day and 208 of 3,724 patients r and omized to simvastatin 20 mg/day developed new-onset T2DM ( 6.40 % vs. 5.59 % , adjusted HR : 1.19 , 95 % CI : 0.98 to 1.43 , p = 0.072 ) . In the SPARCL ( Stroke Prevention by Aggressive Reduction in Cholesterol Levels ) trial , new-onset T2DM developed in 166 of 1,905 patients r and omized to atorvastatin 80 mg/day and in 115 of 1,898 patients in the placebo group ( 8.71 % vs. 6.06 % , adjusted HR : 1.37 , 95 % CI : 1.08 to 1.75 , p = 0.011 ) . In each of the 3 trials , baseline fasting blood glucose , body mass index , hypertension , and fasting triglycerides were independent predictors of new-onset T2DM . Across the 3 trials , major cardiovascular events occurred in 11.3 % of patients with and 10.8 % of patients without new-onset T2DM ( adjusted HR : 1.02 , 95 % CI : 0.77 to 1.35 , p = 0.69 ) . CONCLUSIONS High-dose atorvastatin treatment compared with placebo in the SPARCL trial is associated with a slightly increased risk of new-onset T2DM . Baseline fasting glucose level and features of the metabolic syndrome are predictive of new-onset T2DM across the 3 trials BACKGROUND R and omized data on statins for primary prevention in older persons are limited , and the relative hazard of cardiovascular disease associated with an elevated cholesterol level weakens with advancing age . OBJECTIVE To assess the efficacy and safety of rosuvastatin in persons 70 years or older . DESIGN Secondary analysis of JUPITER ( Justification for the Use of statins in Prevention : an Intervention Trial Evaluating Rosuvastatin ) , a r and omized , double-blind , placebo-controlled trial . SETTING 1315 sites in 26 countries r and omly assigned participants in JUPITER . PARTICIPANTS Among the 17 802 participants r and omly assigned with low-density lipoprotein ( LDL ) cholesterol levels less than 3.37 mmol/L ( < 130 mg/dL ) and high-sensitivity C-reactive protein levels of 2.0 mg/L or more without cardiovascular disease , 5695 were 70 years or older . INTERVENTION Participants were r and omly assigned in a 1:1 ratio to receive 20 mg of rosuvastatin daily or placebo . MEASUREMENTS The primary end point was the occurrence of a first cardiovascular event ( myocardial infa rct ion , stroke , arterial revascularization , hospitalization for unstable angina , or death from cardiovascular causes ) . RESULTS The 32 % of trial participants 70 years or older accrued 49 % ( n = 194 ) of the 393 confirmed primary end points . The rates of the primary end point in this age group were 1.22 and 1.99 per 100 person-years of follow-up in the rosuvastatin and placebo groups , respectively ( hazard ratio , 0.61 [ 95 % CI , 0.46 to 0.82 ] ; P < 0.001 ) . Corresponding rates of all-cause mortality in this age group were 1.63 and 2.04 ( hazard ratio , 0.80 [ CI , 0.62 to 1.04 ] ; P = 0.090 ) . Although no significant heterogeneity was found in treatment effects by age , absolute reductions in event rates associated with rosuvastatin were greater in older persons . The relative rate of any serious adverse event among older persons in the rosuvastatin versus placebo group was 1.05 ( CI , 0.93 to 1.17 ) . LIMITATION Effect estimates from this exploratory analysis with age cut-point chosen after trial completion should be viewed in the context of the overall trial results . CONCLUSION In apparently healthy older persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels , rosuvastatin reduces the incidence of major cardiovascular events . PRIMARY FUNDING SOURCE AstraZeneca Background : The progression of cerebral atherosclerosis increases the risk of stroke and vascular events . Given the known benefits of statins in retarding coronary and carotid atherosclerosis progression , we studied the effects of statins on asymptomatic middle cerebral artery ( MCA ) stenosis progression . Methods : We conducted a r and omized , double-blind , placebo-controlled study to evaluate the effects of simvastatin on the progression of MCA stenosis among stroke-free individuals who had mild to moderately elevated LDL cholesterol ( 3.0–5.0 mmol/l ) . Two hundred and twenty-seven subjects were r and omized to either placebo ( n = 114 ) or simvastatin 20 mg daily ( n = 113 ) . The severity of MCA stenosis at baseline and at the end of the study was grade d by MRA into normal , minimal ( < 10 % ) , mild ( 10–49 % ) , moderate ( 50–90 % ) and severe ( > 90 % ) . The primary outcome was the change in grading of MCA stenosis over 2 years . Results : At the end of the study , the LDL cholesterol level decreased by 1.43 and 0.12 mmol/l for the active and placebo groups , respectively ( p < 0.001 ) . There was no significant difference in the proportion of patients having stable , progressive and regressive MCA stenosis between the placebo ( 72 , 22 and 6 % ) and active groups ( 78.6 , 15.5 and 5.8 % ) . The all-cause mortality was significantly lower in the active group ( n = 0 ) relative to the placebo group ( n = 7 , p = 0.014 ) . Any clinical events were also lower in the active group ( n = 5 ) than in the placebo group ( n = 13 , p = 0.052 ) . Conclusions : Simvastatin 20 mg daily had no apparent effect upon the evolution of asymptomatic MCA stenosis over 2 years Background — Aortic stenosis ( AS ) is an active process with similarities to atherosclerosis . The objective of this study was to assess the effect of cholesterol lowering with rosuvastatin on the progression of AS . Methods and Results — This was a r and omized , double-blind , placebo-controlled trial in asymptomatic patients with mild to moderate AS and no clinical indications for cholesterol lowering . The patients were r and omized to receive either placebo or rosuvastatin 40 mg daily . A total of 269 patients were r and omized : 134 patients to rosuvastatin 40 mg daily and 135 patients to placebo . Annual echocardiograms were performed to assess AS progression , which was the primary outcome ; the median follow-up was 3.5 years . The peak AS gradient increased in patients receiving rosuvastatin from a baseline of 40.8±11.1 to 57.8±22.7 mm Hg at the end of follow-up and in patients with placebo from 41.6±10.9 mm Hg at baseline to 54.8±19.8 mm Hg at the end of follow-up . The annualized increase in the peak AS gradient was 6.3±6.9 mm Hg in the rosuvastatin group and 6.1±8.2 mm Hg in the placebo group ( P=0.83 ) . Treatment with rosuvastatin was not associated with a reduction in AS progression in any of the predefined subgroups . Conclusion — Cholesterol lowering with rosuvastatin 40 mg did not reduce the progression of AS in patients with mild to moderate AS ; thus , statins should not be used for the sole purpose of reducing the progression of AS . Clinical Trial Registration Information— URL : http://www.controlled-trials.com/. Clinical trial registration number : IS RCT N 32424163
target: Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects .
  There was no evidence of any serious harm caused by statin prescription .
  Evidence available to date showed that primary prevention with statins is likely to be cost-effective and may improve patient quality of life .
  Recent findings from the Cholesterol Treatment Trialists study using individual patient data meta- analysis indicate that these benefits are similar in people at lower ( < 1 % per year ) risk of a major cardiovascular event .
  AUTHORS ' CONCLUSIONS Reductions in all-cause mortality , major vascular events and revascularisations were found with no excess of adverse events among people without evidence of CVD treated with statins
background: BACKGROUND Reducing high blood cholesterol , a risk factor for cardiovascular disease ( CVD ) events in people with and without a past history of CVD is an important goal of pharmacotherapy .
  Statins are the first-choice agents .
  Previous review s of the effects of statins have highlighted their benefits in people with CVD .
  The case for primary prevention was uncertain when the last version of this review was published ( 2011 ) and in light of new data an up date of this review is required .
  OBJECTIVES To assess the effects , both harms and benefits , of statins in people with no history of CVD .