Rationale and design of the Arterial Disease Multiple Intervention Trial (ADMIT) pilot study. Impact of combined lipid lowering with blood pressure control on coronary plaque regression: rationale and design of MILLION study Secondary prevention and lipid lowering: results and implications. Low-Density Lipoprotein Cholesterol Lowering With Evolocumab and Outcomes in Patients With Peripheral Artery Disease: Insights From the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) Examination of lower targets for low-density lipoprotein cholesterol and blood pressure in diabetes--the Stop Atherosclerosis in Native Diabetics Study (SANDS). Design and Rationale of the ARBITER 6 Trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol)-6-HDL and LDL Treatment Strategies in Atherosclerosis (HALTS) Longitudinal cohort study on the effectiveness of lipid apheresis treatment to reduce high lipoprotein(a) levels and prevent major adverse coronary events A controlled trial of plasma lipid reduction in peripheral atherosclerosis—an interim report Coronary Angiographic Changes with Lovastatin Therapy: The Monitored Atherosclerosis Regression Study (MARS) Effective and safe modification of multiple atherosclerotic risk factors in patients with peripheral arterial disease. A Program of 3 Physical Therapy Modalities Improves Peripheral Arterial Disease in Diabetes Type 2 Patients: A Randomized Controlled Trial Aggressive lipid lowering does not improve endothelial function in type 2 diabetes: the Diabetes Atorvastatin Lipid Intervention (DALI) Study: a randomized, double-blind, placebo-controlled trial. Computerized community cholesterol control (4C): meeting the challenge of secondary prevention. Rationale and design for the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT Research Group. Comprehensive cardiac rehabilitation improves the control of dyslipidemia in secondary prevention. Activating peripheral arterial disease patients to reduce cholesterol: a randomized trial. Effect of lipid-lowering therapy on early mortality after acute coronary syndromes: an observational study
The primary objectives of the pilot study were to : ( 1 ) evaluate the feasibility of recruiting patients with peripheral arterial disease ( PAD ) ; ( 2 ) measure the efficacy and safety of high-density lipoprotein (HDL)-raising treatment , low-density lipoprotein (LDL)-lowering therapy , antioxidant therapy , antithrombotic therapy , and their combinations ; and ( 3 ) assess adherence to a complex multiple drug regimen . Secondary objectives included measurement of the effect of the interventions on prespecified biochemical markers , maintenance of therapy masking ( in particular with niacin ) , and measurement of the intervention 's impact on functional status and on quality of life . To date , no secondary prevention trial has been conducted specifically among patients with PAD . Intermittent claudication affects about 0.5 % to 1.0 % of persons aged > 35 years . There is a striking increase in incidence of PAD with age , particularly among those aged > 50 years in both sexes , although men are twice as likely as women to develop PAD . The Arterial Disease Multiple Intervention Trial was a double-blind r and omized pilot trial of 468 participants with documented PAD . A 2 x 2 x 2 factorial design was used to evaluate the effect of 3 interventions . The pilot incorporated several major novel design features : first , the use of a simple noninvasive method ( measurement of ankle brachial index ) to identify a population with either symptomatic or asymptomatic PAD ; and second , a lipid modifying strategy to increase HDL with nicotinic acid in the intervention group while lowering LDL levels equally with an hydroxymethylglutaryl-coenzyme A reductase inhibitor as needed in the intervention and control group . Two other arms , the antioxidant arm ( consisting of beta-carotene and vitamins E and C ) and the antithrombotic arm ( using warfarin ) were also added . Adherence to therapy was measured by pill count , and success in treatment was measured by the proportion of values in target range for HDL , LDL , and the international normalized ratio A line of epidemiological studies suggests that the accumulation of coronary risk factors promotes the progression of coronary atherosclerosis . Recent clinical studies showed that aggressive low-density lipoprotein ( LDL ) cholesterol-lowering therapy using statins could regress coronary atheroma and reduce major cardiovascular events . Additionally , therapy that controlled amlodipine-based blood pressure reduced major cardiovascular events in patients with hypertension compared with an atenolol-based regimen . An open-label r and omized multicenter study is primarily planned to evaluate the changes in coronary atheroma volume using intravascular ultrasonography 18–24 months after intensive lowering of LDL-cholesterol and blood pressure compared with a st and ard therapy indicated by current guidelines in Japanese patients with coronary artery disease ( CAD ) . The secondary endpoints include changes in serum lipid levels , inflammatory markers , glucose markers and blood pressure .  In total , 100 subjects with CAD who are undergoing percutaneous coronary intervention will be tested . The MILLION study will provide new evidence and therapeutic st and ards for the prevention of CAD in Japanese patients by controlling both LDL-C levels and blood pressure In a secondary prevention trial conducted by the National Heart , Lung , and Blood Institute , the effect of lipid lowering by drug intervention on the progression of existing coronary artery disease ( CAD ) was evaluated in type II hyperlipidemic patients . This first r and omized , secondary prevention trial compared the effect of cholestyramine and diet with that of placebo and diet in 143 patients over a 5-year period . End points evaluated were progression or regression of CAD , as demonstrated by angiographic changes compared with baseline angiograms . The cholestyramine-treated group demonstrated a significant reduction in total cholesterol and in low-density lipoprotein cholesterol ( LDL ) levels as compared with placebo , and an 8 % increase in high-density lipoprotein cholesterol ( HDL ) . A statistically significant result supporting the use of cholestyramine treatment was found in one category of CAD progression Background : The PCSK9 ( proprotein convertase subtilisin/kexin type 9 ) inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER trial ( Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk ) . We investigated the efficacy and safety of evolocumab in patients with peripheral artery disease ( PAD ) as well as the effect on major adverse limb events . Methods : FOURIER was a r and omized trial of evolocumab versus placebo  in 27 564 patients with atherosclerotic disease on statin therapy followed for a median of 2.2 years . Patients were identified as having PAD at baseline if they had intermittent claudication and an ankle brachial index of < 0.85 , or if they had a prior peripheral vascular procedure . The primary end point was a composite of cardiovascular death , myocardial infa rct ion , stroke , hospital admission for unstable angina , or coronary revascularization . The key secondary end point was a composite of cardiovascular death , myocardial infa rct ion , or stroke . An additional outcome of interest was major adverse limb events defined as acute limb ischemia , major amputation , or urgent peripheral revascularization for ischemia . Results : Three thous and six hundred forty-two patients ( 13.2 % ) had PAD ( 1505 with no prior myocardial infa rct ion or stroke ) . Evolocumab significantly reduced the primary end point consistently in patients with PAD ( hazard ratio [ HR ] 0.79 ; 95 % confidence interval [ CI ] , 0.66–0.94 ; P=0.0098 ) and without PAD ( HR 0.86 ; 95 % CI , 0.80–0.93 ; P=0.0003 ; Pinteraction=0.40 ) . For the key secondary end point , the HRs were 0.73 ( 0.59–0.91 ; P=0.0040 ) for those with PAD and 0.81 ( 0.73–0.90 ; P<0.0001 ) for those without PAD ( Pinteraction=0.41 ) . Because of their higher risk , patients with PAD had larger absolute risk reductions for the primary end point ( 3.5 % with PAD , 1.6 % without PAD ) and the key secondary end point ( 3.5 % with PAD , 1.4 % without PAD ) . Evolocumab reduced the risk of major adverse limb events in all patients ( HR , 0.58 ; 95 % CI , 0.38–0.88 ; P=0.0093 ) with consistent effects in those with and without known PAD . There was a consistent relationship between lower achieved low-density lipoprotein cholesterol and lower risk of limb events ( P=0.026 for the beta coefficient ) that extended down to < 10 mg/dL. Conclusions : Patients with PAD are at high risk of cardiovascular events , and PCSK9 inhibition with evolocumab significantly reduced that risk with large absolute risk reductions . Moreover , lowering of low-density lipoprotein cholesterol with evolocumab reduced the risk of major adverse limb events . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifier : NCT01764633 Diabetes incidence is increasing rapidly in the United States . Diabetes increases the risk for cardiovascular disease , the major cause of death in diabetic individuals . The conventional cardiovascular risk factors of hyperlipidemia and hypertension worsen diabetic vascular disease . Treatment targets for low-density lipoprotein cholesterol ( LDL-C ) and blood pressure in diabetic individuals are being debated . The S AND S is a r and omized , open-label , 3-year trial to examine the effects of aggressive LDL-C ( goal < 70 mg/dL ) and blood pressure ( BP ) ( goal < 115/75 mm Hg ) reduction versus the st and ard goals of < 100 mg/dL for LDL-C and < 130/85 mm Hg for BP .  Five hundred forty-nine American-Indian men and women > 40 years old with type 2 diabetes were r and omized to 1 of 2 groups . Lipids and BP are managed using Food and Drug Administration-approved medications in an algorithmic approach . The presence and progression of atherosclerosis are evaluated by carotid ultrasonography ; echocardiography assesses cardiac function . The primary end point is the composite outcome of change in carotid artery intimal medial thickness and fatal/nonfatal cardiovascular events . These outcomes are combined by using a ranked analysis for carotid thickness and assigning a " worst rank " for a cardiovascular event . Secondary end points include carotid plaque score , left ventricular geometry and function , serum C-reactive protein , and safety measures . Unique aspects of the study design and analysis plan involve the use of a composite outcome and changes during the trial of LDL-C treatment goals for participants with baseline or incident cardiovascular disease in the conventional group because of changes in the st and ard of care . Study results will further underst and ing of the effects of aggressive risk factor reduction on atherosclerosis burden and cardiac function in diabetic individuals in US population s and will help determine optimal LDL-C and BP treatment goals for diabetic patients Background Recent evidence on the use of statin therapy indicates the potential for ultra-low levels of LDL-C to provide greater protection from recurrent coronary heart disease events . Guidelines for the treatment of lipid disorders were revised to indicate that an LDL-C treatment goal of 70 mg/dl was optional ( NCEP ATPIII ) . In these same guidelines , low levels of HDL-C are also suggested but not specifically proscribed as a target of therapy . Recently ARBITER 2 ( Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 2 ) has provided the first evidence of the potential of raising HDL-C with extended release niacin when added to statin monotherapy in secondary prevention . However , whether this approach would be superior to a strategy in which lower concentrations of LDL-C are targeted is unknown . Material s and methods ARBITER 6-HALTS ( HDL and LDL Treatment Strategies ) will be a r and omized , parallel group , open-label study comparing HDL-C and LDL-C focused strategies of lipid treatments for their effects on atherosclerosis . Up to 400 subjects will be assigned to either  intensified LDL-C lowering therapy with ezetimibe or HDL-C raising therapy with extended-release niacin . The primary endpoint is the mean change in the intima-media thickness of the common carotid artery after 14 months . Secondary endpoints include the change in lipid values and lipid subfractions , drug discontinuation due to adverse effects , change in quality of life , and a composite endpoint consisting of all major adverse cardiovascular events . Conclusion ARBITER 6-HALTS will guide clinicians on whether a lipid treatment strategy of raising HDL-C or further LDL-C reduction is superior in the secondary prevention of coronary heart disease Background We investigated in a longitudinal , multicenter , cohort study whether combined lipid apheresis and lipid-lowering medication can reduce extremely high levels of lipoprotein(a ) ( Lp[a ] ) and thus prevent major adverse coronary events ( MACE ) more efficaciously than lipid-lowering medication alone . Methods Eligible patients had coronary artery disease and Lp(a ) levels ≥2.14 µmol/l ( 95th percentile ) . All patients received lipid-lowering medications alone until maximally tolerated doses were no longer effective , followed by combined lipid apheresis and lipid-lowering medication . The rates of the primary outcome , MACE , were recorded for both periods . Results A total of 120 patients were included . The mean duration of lipid-lowering therapy alone was 5.6±5.8 years , and that of apheresis was 5.0±3.6 years . Median Lp(a ) concentration was reduced from 4.00 µmol/l to 1.07 µmol/l with apheresis treatment ( P<0.0001 ) ; the corresponding mean annual MACE rate per patient was 1.056 versus 0.144 ( P<0.0001 ) . Conclusions Lowering of Lp(a ) levels by apheresis was efficacious and safe , and we recommend this therapy for patients in whom maximally tolerated doses of medication alone have failed to control coronary artery disease-associated events The effects of plasma lipid reduction on the progression of femoral atherosclerosis have been studied in 24 hyperlipidaemic patients with stable intermittent claudication . The patients were r and omized into treatment or ‘ usual‐care ’ groups , the former receiving lipid‐lowering therapy by diet and drugs , and the latter no such treatment . Biplanar femoral arteriography was performed before and after a mean period of 19 months . In the treatment group plasma total cholesterol was decreased by a mean of 25 per cent and plasma triglyceride by more than 40 per cent . Plasma lipids were unchanged in the usual‐care group . Significantly fewer arterial segments showed detectable progression in the treatment group ( P < 0·01 ) . In addition , the mean increment in plaque area ( mm2 per segment per year ) in the treatment group was only 34 per cent of that in the usual‐care group ( P = 0.06 ) The role of lipid-lowering therapy in primary and secondary prevention of ischemic heart disease continues to be debated [ 1 ] . Concerns include whether lowering lipid levels consistently inhibits or reverses the development of coronary artery lesions , influences cardiac and all-cause morbidity and mortality , and offers a prudent use of medical re sources . Because ischemic heart disease remains the leading cause of death in developed countries , these are important questions . Early trials that assessed various lipid-lowering therapies reported little or no angiographic evidence of efficacy , in large part because of modest changes in serum lipids and lipoprotein levels , small sample sizes , and other method ologic problems [ 2 - 4 ] . However , beginning with the Cholesterol Lowering Atherosclerosis Study ( CLAS ) , seven lipid-lowering studies with interventions ranging from multifactorial lifestyle modification , to diet and exercise or diet and either monotherapy or combination drug therapy , to ileal bypass surgery , have shown clear reductions in the progression of atherosclerotic disease or actual lesion regression [ 5 - 12 ] , or both . In three trials , clinical coronary events were significantly reduced [ 7 , 8 , 10 ] . The Program on the Surgical Control of the Hyperlipidemias ( POSCH ) , which showed that cholesterol lowering ( through partial iliac bypass surgery ) had a beneficial effect on coronary artery lesions [ 8 ] , recently found that the 3-year global change score , an overall consensus judgment of angiographic changes in coronary lesions determined by blinded panels of experts , was predictive of subsequent coronary events ( P < 0.0001 ) , fatal coronary events ( P = 0.003 ) , and all-cause mortality ( P = 0.01 ) over 3 to 10 years [ 13 ] . Although not in the context of a lipid-lowering trial , Waters and colleagues [ 14 ] found that patients with angiographic progression of disease at 2 years ( by quantitative coronary angiography ) also had a significantly increased risk for clinical coronary events during a 44-month follow-up period . In CLAS , we showed that diet in conjunction with colestipol and niacin therapy had a beneficial effect on coronary artery lesions at 2 and 4 years based on the global change score [ 5 , 15 ] and at 2 years based on quantitative coronary angiography [ 16 ] ; CLAS was the only angiographic trial to have used both the findings of quantitative coronary angiography and the global change score as end points . We present the results of a second angiographic trial using these two end points . The Monitored Atherosclerosis Regression Study ( MARS ) was a double-blind , placebo-controlled , r and omized trial that tested the reduction of low-density lipoprotein ( LDL ) cholesterol levels using lovastatin , an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A ( HMG CoA ) reductase . We compare our results regarding the effect of reducing lipid levels on coronary artery status with those of the CLAS and POSCH trials . Methods Patients were enrolled in the study if they were younger than 70 years and had coronary artery disease in at least two segments , with at least one segment showing diameter stenosis of 50 % or more ( but not total occlusion ) and unaltered by percutaneous transluminal coronary angioplasty .  Total cholesterol levels ranged from 4.92 to 7.64 mmol/L ( 190 to 295 mg/dL ) . Major exclusion criteria included hypertension ( diastolic blood pressure > 115 mm Hg or , if the patient was receiving treatment , > 100 mm Hg ) , diabetes mellitus , and the use of lipid-lowering drugs within 2 months of r and omization . Women were excluded if they were premenopausal , unless they had undergone surgical sterilization . C and i date s for coronary artery bypass graft surgery were excluded , but c and i date s for percutaneous transluminal coronary angioplasty were not . Between 1985 and 1989 , 270 patients were r and omly assigned within one of eight blocks , defined by sex , smoking status ( current smoker or nonsmoker ) , and plasma total cholesterol ( 6.22 mmol/L [ 240 mg/dL ] or > 6.22 mmol/L ) to receive either lovastatin , 40 mg twice a day , or placebo . Treatment groups had identical targets for cholesterol and fat intake ( daily cholesterol intake 250 mg ; 27 % of calories as fat , with saturated fat constituting 7 % of total fat calories and monounsaturated and polyunsaturated fats each accounting for 10 % of fat calories ) . In 58 % of cases , patients were recruited through cardiac catheterization laboratories and had undergone baseline coronary arteriography for clinical indications . The percutaneous femoral technique was used , and sufficient right and left anterior oblique views were obtained to show all lesions clearly [ 11 ] . During the trial , back-titration of the lovastatin dosage , which was necessary if two consecutive total cholesterol levels were less than 3.11 mmol/L ( 120 mg/dL ) or if one total cholesterol level was less than 2.85 mmol/L ( 110 mg/dL ) , was done once for 15 patients and twice for 3 patients . To maintain the blind , the dosage for a matched placebo recipient was also back-titrated . Lipid , lipoprotein , and apolipoprotein levels were measured using st and ardized laboratory procedures [ 11 ] ; safety laboratory tests were done ; concomitant medications , drug and diet compliance [ 11 ] , lenticular opacification [ 17 ] , and symptoms and adverse events were assessed during the trial . A follow-up angiogram ( n = 247 ) , done 2 years after r and omization , duplicated the protocol followed for the baseline angiogram , including nitroglycerin use , except in the 25 patients ( 8 receiving lovastatin and 17 receiving placebo )  for whom nitroglycerin was required only at follow-up because of angina . Lesions in patients with a nitroglycerin mismatch were excluded from the quantitative coronary analyses . Baseline films and procedure reports , review ed before follow-up angiography was done , ensured matching of all variables including the sequence of arteriographic projections , roentgenographic field , and catheter size . An optional double-blind 2-year extension of the original r and omized therapy ( MARS-II ) was accepted by 70 % of the patients ( 98 receiving lovastatin and 75 receiving placebo ) . Results of MARS-II have not yet been reported . Evaluation of Coronary Angiograms All evaluable film pairs ( n = 246 ) showing identical coronary artery views , with treatment allocation and temporal order masked , were evaluated by an expert panel of two angiographers and a moderator [ 11 , 18 ] . ( One placebo recipient did not have an evaluable angiogram by panel procedures . ) Using the first film , the panel reached a consensus on lesion identification and percent diameter stenosis , and these data were recorded by the moderator . Using the second film , the panel reached a consensus on the degree of change in each lesion and obtained a global change score ( 0 [ no demonstrable change ] to 3 [ extreme change ] ) that integrated panel-based visual changes . A direction for change ( - for regression , + for progression ) was subsequently assigned by the study statistician when the temporal blind was broken . Quantitative coronary angiography analyses were done by a single technician blinded to treatment but not to temporal ordering [ 11 , 19 ] . Film pairs ( n = 220 ) were processed in t and em using dual projectors to match frames for orientation and degree of contrast filling , and arterial segments were defined from branch to branch . Three sequential frames exposed during end-diastole were digitized when possible ; if such a sequence was unavailable , three sequential frames from other phases of the cardiac cycle were digitized . The right anterior oblique view was preferred for the quantitative coronary angiography analysis , but other views were substituted if they were superior . Percent diameter stenosis and minimum lumen diameter were measured in each lesion identified by the panel and in lesions identified by the quantitative coronary angiography analyst but not by the panel ; these latter lesions tended to be in smaller segments and were less severe . Edge coordinates were corrected for pin-cushion distortion ( artifactual coronary artery edge distortion seen in angiographic films ) measured from the image of a 1-cm anteroposterior grid filmed at the beginning of each angiogram . Each end point was averaged over three sequential frames . The primary end point was the average ( per-patient ) change from baseline in percent diameter stenosis in all lesions that showed 20 % stenosis at baseline or at follow-up as evaluated by quantitative coronary angiography . Power calculations based on this end point ( and st and ard deviations estimated to be in the range of 6 % to 8 % ) indicated that an effective sample size of 250 patients had at least an 80 % power to detect a treatment difference of 2 % to 3 % in diameter stenosis at the 0.05 significance level ( two-sided ) [ 11 ] . Three equally weighted secondary end points were average ( per-patient ) change in minimum lumen diameter ( assessed by quantitative coronary angiography ) , the global change score ( assessed by the panel ) , and the proportion of patients with progression or regression of disease ( assessed by quantitative coronary angiography ) . A patient defined as having progression or regression had lesion change of one type only , either progressing or regressing , but not both types ; a patient with a mixed lesion response ( that is , with both progressing and regressing lesions ) was considered unchanged . A progressing or regressing lesion was defined by a change in percent diameter stenosis of 12 % or greater . This cutoff is equal to twice the st and ard deviation ( 5.7 % ) elicited by analysis of repeated angiograms ( at the beginning and end of the same angiographic session ) of the same lesion in 17 patients ( 55 lesions ) in the MARS study .  New lesions and new total occlusions were not counted as progressing lesions ; recanalizations were not counted as regressing lesions . Analyses of change in both percent diameter stenosis and minimum lumen diameter were specified a priori for large ( 50 % at baseline ) lesions [ 11 ] . BACKGROUND Patients with peripheral arterial disease ( PAD ) are at an increased risk of cardiovascular mortality and morbidity and thus are an excellent group in whom to evaluate the feasibility and the effect of an aggressive multifactorial intervention on atherosclerotic vascular disease risk factors . The Arterial Disease Multiple Intervention Trial ( ADMIT ) was design ed to determine the efficacy , safety , and compliance of an multifactorial therapy on selected atherosclerotic disease risk factors in patients with PAD . METHODS By a 2 x 2 x 2 factorial design , eligible participants ( N = 468 ) were r and omly assigned to low-dose warfarin , antioxidant vitamins , and niacin or its corresponding placebo , and followed up for 1 year . All participants were encouraged to use aspirin . Pravastatin was added to the drug regimen for those who needed to reduce LDL cholesterol to recommended levels . RESULTS Niacin increased HDL cholesterol levels by 30 % , with the majority of effect achieved at a dosage of 500 mg twice daily . Warfarin had an anticoagulant effect . The antioxidant vitamins result ed in a significant increase in vitamin E , C , and beta-carotene plasma levels . Overall , compliance was high and few adverse effects were reported . CONCLUSIONS ADMIT demonstrates that it is both feasible and safe to modify multiple atherosclerotic disease risk factors effectively with intensive combination therapy in patients with PAD Background and Objective : Type 2 diabetes is one of the main causes of peripheral vascular disease . The beneficial effects of exercise on glucose homeostasis include a marked stimulation of blood glucose utilization during and after its performance . The objective of this study was to determine the effects of a program of 3 physical therapy modalities on blood circulation in patients with type 2 diabetes with peripheral arterial disease . Subjects and Method : A r and omized controlled trial was undertaken . Sixty-eight patients with type 2 diabetes with Leriche-Fontaine stage I or IIa peripheral arterial disease were r and omly assigned to an exercise or placebo group . For 20 weeks , the exercise group underwent treatment comprising 3 exercises at proximal , medium , and distal segments of the lower limbs , and the placebo group received sham treatment with disconnected ultrasound equipment .  Peripheral arterial disease was determined by evaluating the ankle/brachial index ( ABI ) , Doppler flow velocity , blood parameters , cardiovascular risk score , and heart rate during exercise test . Results : After 20 weeks of treatment , significant differences between groups were found in the following : right ( P < .039 ) and left ( P < .023 ) ABI ; Doppler flow velocity ( cm/s ) in the right ( P < .010 ) and left ( P < .026 ) posterior tibial artery and in the right ( P < .012 ) and left ( P < .022 ) dorsalis pedis artery ; and fibrinogen ( P < .045 ) , hemoglobin ( P < .021 ) , cholesterol ( P < .012 ) , high-density lipoprotein cholesterol ( P < .031 ) , and HbA1c ( P < .034 ) values . There was no significant difference in low-density lipoprotein cholesterol values ( P < .110 ) between the groups . Conclusion : A program of these physical therapy modalities improves ABI , Doppler flow velocity , and blood parameters in patients with type 2 diabetes OBJECTIVE Endothelial dysfunction is considered an important early marker of atherosclerosis and cardiovascular risk and is currently used as a surrogate end point for cardiovascular risk in clinical trials . Type 2 diabetic patients show a characteristic dyslipidemia . Aggressive lipid lowering might be an effective method to improve endothelial function in these patients . RESEARCH DESIGN AND METHODS A r and omized , double-blind , placebo-controlled trial was completed to study the effect of 30 weeks ' administration of atorvastatin 10 mg and 80 mg on endothelial function , as assessed by B-mode ultrasound of the brachial artery , in 133 patients with type 2 diabetes without a history of cardiovascular disease . RESULTS Patients with diabetes and diabetic dyslipidemia had considerable endothelium-dependent and endothelium-independent dysfunction ; mean flow-mediated vasodilation ( SD ) was 3.16 % ( 3.56 ) , and mean response on sublingual nitroglycerin was 6.58 % ( 6.04 ) . Despite substantial lowering of all atherogenic lipid parameters , no improvement of endothelium-dependent vasodilatation was found ( P > 0.8 ) . CONCLUSIONS We observed considerable baseline endothelium-dependent and endothelium-independent dysfunction in patients with diabetes and diabetic dyslipidemia without a history of cardiovascular disease . Aggressive lipid lowering by administration of atorvastatin , result ing in substantial improvement of the lipid profile , did not reverse endothelial dysfunction BACKGROUND Dyslipidemia remains underdiagnosed and undertreated in patients with coronary artery disease . The Computer-based Clinical Decision Support System provides an opportunity t close these gaps . OBJECTIVES To study the impact of computerized intervention on secondary prevention of CAD . METHODS The CDSS was programmed to automatically detect patients with CAD and to evaluate the availability of an up date d  lipoprotein profile  and treatment with lipid-lowering drugs . The program produced automatic computer-generated monitoring and treatment recommendations . Adjusted primary clinics were r and omly assigned to intervention ( n=56 ) or st and ard care arms ( n=56 ) . Reminders were mailed to the primary medical teams in the intervention arm every 4 months updating them with current lipid levels and recommendations for further treatment . Compliance and lipid levels were monitored . The study group comprised all patients with CAD who were alive at least 3 months after hospitalization . RESULTS Follow-up was available for 7448 patients ( median 19.8 months , range 6 - 36 months ) . Overall , 51.7 % of patients were adequately screened , and 55.7 % of patients were compliant with treatment to lower lipid level . In patients with initial low density lipoprotein  > 120 mg/dl , a significant decrease in LDL levels was observed in both arms , but was more pronounced in the intervention arm : 121.9 + /- 34.2 vs. 124.3 + /- 34.6 mg/dl ( P < 0.02 ) . A significantly lower rate of cardiac rehospitalizations was documented in patients who were adequately treated with lipid-lowering drugs , 37 % vs. 40.9 % ( P < 0.001 ) . CONCLUSIONS This initial assessment of our data represent a real-world snapshot where physicians and CAD patients often do not adhere to clinical guidelines , presenting a major obstacle to implementing effective secondary prevention . Our automatic computerized reminders system substantially facilitates adherence to guidelines and supports wide-range implementation Are newer types of antihypertensive agents , which are currently more costly to purchase on average , as good or better than diuretics in reducing coronary heart disease incidence and progression ? Will lowering LDL cholesterol in moderately hypercholesterolemic older individuals reduce the incidence of cardiovascular disease and total mortality ? These important medical practice and public health questions are to be addressed by the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , a r and omized , double-blind trial in 40,000 high-risk hypertensive patients . ALLHAT is design ed to determine whether the combined incidence of fatal coronary heart disease ( CHD ) and nonfatal myocardial infa rct ion differs between persons r and omized to diuretic ( chlorthalidone ) treatment and each of three alternative treatments -- a calcium antagonist ( amlodipine ) , an angiotensin converting enzyme inhibitor ( lisinopril ) , and an alpha-adrenergic blocker ( doxazosin ) . ALLHAT also contains a r and omized , open-label , lipid-lowering trial design ed to determine whether lowering LDL cholesterol in 20,000 moderately hypercholesterolemic patients ( a subset of the 40,000 ) with a 3-hydroxymethylglutaryl coenzyme A ( HMG CoA ) reductase inhibitor , pravastatin  , will reduce all-cause mortality compared to a control group receiving  " usual care . "  ALLHAT 's main eligibility criteria are : 1 ) age 55 or older ; 2 ) systolic or diastolic hypertension ; and 3 ) one or more additional risk factors for heart attack ( eg , evidence of atherosclerotic disease or type II diabetes ) . For the lipid-lowering trial , participants must have an LDL cholesterol of 120 to 189 mg/dL ( 100 to 129 mg/dL for those with known CHD ) and a triglyceride level below 350 mg/dL. The mean duration of treatment and follow-up is planned to be 6 years . Further features of the rationale , design , objectives , treatment program , and study organization of ALLHAT are described in this article BACKGROUND Secondary prevention is an important goal of cardiac rehabilitation in patients with coronary heart disease ( CHD ) . Dyslipidemia is one of the major risk factors that is important to control to reduce the incidence of future ischemic coronary events . The aim of the present study was to assess whether control of dyslipidemia , in secondary prevention , could be improved by a comprehensive cardiac rehabilitation program . METHODS Fifty-two newly diagnosed hyperlipidemic men , who had experienced a recent CHD event , were separated in two equal groups of 26 patients : group CR+ , in which patients were included in a 2-month cardiac rehabilitation program including an extensive educational program on cardiovascular risk factors , lipids , and diet , and group CR-without any cardiac rehabilitation . Mean age , body mass index , initial levels of total cholesterol , triglycerides , high-density lipoprotein ( HDL ) cholesterol , low-density lipoprotein ( LDL ) cholesterol , and LDL/HDL ratio were not significantly different between the 2 groups . In both groups , each patient was referred to a dietitian and to the same lipidologist to start an appropriate hypolipidemic treatment . Treatment of coronary event , type of hyperlipidemia , and hypolipidemic treatment were not different between the two groups . RESULTS Lipid measurements , performed 3 months after the beginning of the hypolipidemic treatment , showed that patients from the CR+ group , compared with those from the CR-group , had a significantly greater reduction of total cholesterol ( 23 % versus 13 % ; P < 0.001 ) , of LDL cholesterol ( 28 % versus 12 % ; P < 0.001 ) , of LDL/HDL ratio ( 34 % versus 13 % ; P < 0.01 ) and of triglycerides ( 33 % versus 21 % ; P = 0.05 ) . CONCLUSIONS Patients with CHD included in a comprehensive cardiac rehabilitation program showed a significantly better response to the hypolipidemic treatment than patients without cardiac rehabilitation . These results could be attributable to the extensive educational program on secondary prevention performed during cardiac rehabilitation , leading to optimized knowledge on lipid-lowering diet and to improved diet and drug adherence . A secondary prevention educational program must be an important part of any comprehensive cardiac rehabilitation program in patients with CHD BACKGROUND Peripheral arterial disease patients are less likely than other high-risk patients to achieve ideal low-density lipoprotein ( LDL ) cholesterol levels . This r and omized controlled trial assessed whether a telephone counseling intervention , design ed to help peripheral arterial disease patients request more intensive cholesterol-lowering therapy from their physician , achieved lower LDL cholesterol levels than 2 control conditions . METHODS There were 355 peripheral arterial disease participants with baseline LDL cholesterol ≥70 mg/dL enrolled . The primary outcome was change in LDL cholesterol level at 12-month follow-up . There were 3 parallel arms : telephone counseling intervention , attention control condition , and usual care . The intervention consisted of patient-centered counseling , delivered every 6 weeks , encouraging participants to request increases in cholesterol-lowering therapy from their physician . The attention control condition consisted of telephone calls every 6 weeks providing information only . The usual care condition participated in baseline and follow-up testing . RESULTS At 12-month follow-up , participants in the intervention improved their LDL cholesterol level , compared with those in attention control ( -18.4 mg/dL vs -6.8 mg/dL , P=.010 ) but not compared with those in usual care ( -18.4 mg/dL vs -11.1 mg/dL , P=.208 ) . Intervention participants were more likely to start a cholesterol-lowering medication or increase their cholesterol-lowering medication dose than those in the attention control ( 54 % vs 18 % , P=.001 ) and usual care ( 54 % vs 31 % , P < .001 ) conditions . CONCLUSION Telephone counseling that helped peripheral arterial disease patients request more intensive cholesterol-lowering therapy from their physician achieved greater LDL cholesterol decreases than an attention control arm that provided health information alone BACKGROUND Lipid-lowering agents are known to reduce long-term mortality in patients with stable coronary disease or significant risk factors . However , the effect of lipid-lowering therapy on short-term mortality immediately after an acute coronary syndrome has not been determined . We did an observational study using data from two r and omised trials to investigate this issue . METHODS We used data from the GUSTO IIb and PURSUIT trials to compare all-cause mortality among patients with acute coronary syndromes who were discharged on lipid-lowering agents ( n=3653 ) with those who were not ( n=17,156 ) . A propensity analysis was done to adjust for presumed selection biases in the prescription of lipid-lowering agents . FINDINGS Lipid-lowering therapy was associated with a smaller proportion of deaths at 30 days ( 17 [ 0.5 % ] vs 179 [ 1.0 % ] , hazard ratio 0.44 [ 95 % CI 0.27 - 0.73 ] , p=0.001 ) and at 6 months ( 63 [ 1.7 % ] vs 605 [ 3.5 % ] , 0.48 [ 0.37 - 0.63 ] , p<0.0001 ) . After adjustment for the propensity to be prescribed lipid-lowering agents and other potential confounders , prescription of a lipid-lowering agent at discharge remained associated with a reduced risk of death at 6 months ( 0.67 [ 0.48 - 0.95 ] , p=0.023 ) . INTERPRETATION Prescription of a lipid-lowering drug at hospital discharge was independently associated with reduced short-term mortality among patients after an acute coronary syndrome
Lipid-lowering therapy is effective in reducing cardiovascular mortality and morbidity in people with PAD .
It may also improve local symptoms .
Until further evidence on the relative effectiveness of different lipid-lowering agents is available , use of a statin in people with PAD and a blood cholesterol level > /=3.5 mmol/litre is most indicated
BACKGROUND Lipid-lowering therapy is recommended for secondary prevention in people with coronary artery disease .
It may also reduce cardiovascular events and /or local disease progression in people with lower limb peripheral arterial disease ( PAD ) .
OBJECTIVES To assess the effects of lipid-lowering therapy on all-cause mortality , cardiovascular events and local disease progression in patients with PAD of the lower limb .