Coronary Angiographic Changes with Lovastatin Therapy: The Monitored Atherosclerosis Regression Study (MARS) Comprehensive cardiac rehabilitation improves the control of dyslipidemia in secondary prevention. Lipid-lowering medication for secondary prevention of coronary heart disease in a German outpatient population: the gap between treatment guidelines and real life treatment patterns. Effectiveness of a planned strategy using cardiac rehabilitation nurses for the management of dyslipidemia in patients with coronary artery disease. Influence of cholesterol on survival after stroke: retrospective study Effect of long-term beta-carotene and vitamin A on serum cholesterol and triglyceride levels among participants in the Carotene and Retinol Efficacy Trial (CARET) Multifactorial intervention to prevent recurrent cardiovascular events in patients 75 years or older: the Drugs and Evidence-Based Medicine in the Elderly (DEBATE) study: a randomized, controlled trial. PREVENTION OF ATHEROSCLEROSIS WITH LDL-C LOWERING - LIPOPROTEIN CHANGES AND INTERACTIONS: THE SANDS STUDY. The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. Rationale and design of a secondary prevention trial of increasing serum high-density lipoprotein cholesterol and reducing triglycerides in patients with clinically manifest atherosclerotic heart disease (the Bezafibrate Infarction Prevention Trial). Secondary Prevention of New Vascular Events with Lifestyle Intervention in Patients with Noncardioembolic Mild Ischemic Stroke: A Single-Center Randomized Controlled Trial Impact of combined lipid lowering with blood pressure control on coronary plaque regression: rationale and design of MILLION study The Lipoprotein and Coronary Atherosclerosis Study (LCAS): design, methods, and baseline data of a trial of fluvastatin in patients without severe hypercholesterolemia. Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. Nurse case management of hypercholesterolemia in patients with coronary heart disease: results of a randomized clinical trial. Should both HDL-C and LDL-C be targets for lipid therapy? A review of current evidence.
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 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 Few published data in particular from the United States indicate that the implementation of guidelines for prevention of coronary heart disease ( CHD ) is far from optimal . The objective of our study was to identify the type and prevalence of lipid-lowering medications in a German outpatient CHD population and to examine the impact of applied treatment regimens on serum lipid levels . METHODS Retrospective analysis of the washout phase of 2,856 CHD patients requiring lipid-lowering medication .  Data are derived from a multicenter , r and omized , open-label , parallel group clinical trial comparing the safety and efficacy of atorvastatin versus simvastatin in 591 centers in Germany . Medical history , physical examination , and serum lipid levels were obtained at the beginning of the washout phase ( Week -6 ) and at the end of the washout phase ( Week -1 , i.e. , 5 weeks after the discontinuation of all prior lipid-lowering medications ) . The data at Week -6 represented the lipid levels under real life conditions . The difference from the data at Week -1 reflected the therapeutic effects achieved by the previous lipid-lowering treatment . RESULTS The mean low-density lipoprotein cholesterol ( LDL-C ) level at Week -6 was 173.4 + /- 42.5 mg/dl . Only 176 ( 6.2 % ) of 2,856 CHD patients were found to meet the target LDL-C level of < 115 mg/dl at Week -6 , only 76 ( 2.7 % ) patients had LDL-C levels < 100 mg/dl , and 363 ( 12.7 % ) patients had LDL-C levels < 130 mg/dl . After discontinuation of all prior lipid-lowering medications , mean LDL-C increased to 187.2 + /- 44.0 mg . This means that only a marginal 7.4 % reduction in LDL-C level was achieved under real life treatment conditions . This limited LDL-C reduction was due mainly to the low prevalence of lipid-lowering treatment ( 65.5 % of patients did not receive any medication at all ) and inadequate dosing . With respect to the effect on LDL-C and total cholesterol , statins alone were superior to fibrates . CONCLUSION The study shows that there is a wide gap between treatment guidelines and real life treatment patterns in Germany . Awareness of the risks of high cholesterol levels has to be increased among both patients and physicians . Available treatment guidelines should be better implemented BACKGROUND Firm evidence exists for reduction in mortality and morbidity by lipid-lowering therapy in patients with coronary artery disease ( CAD ) , yet a significant proportion remain untreated . This prospect i ve study determined the effectiveness of a planned strategy of management using a cardiac rehabilitation nurse in achieving ( 1 ) lower 6-month low-density lipoprotein ( LDL ) levels and ( 2 ) a higher proportion of patients on pharmacologic therapy .  METHODS A cardiac rehabilitation nurse arranged for the lipid profiles and initiated pharmacologic therapy as soon as possible after the diagnosis of CAD . In phase 1 , this  planned- strategy intervention group ( n = 80 ) was compared with the usual-care control group ( n = 189 ) , where the management was left at the discretion of the attending cardiologist with the assignment to the 2 groups based on the weekly on-call rotations of the attending cardiologists in a nonr and omized manner . In phase 2 of the study all patients ( n = 366 ) were enrolled in the planned strategy of management . RESULTS There were no significant differences in the baseline lipid values between the control and intervention groups . The 6-month cholesterol and LDL values and the percentage of patients on lipid-lowering medications were significantly better in the intervention group ( P = .01 ) . In phase 2 the results obtained in the intervention group were duplicated in a much larger group of consecutive patients . The 6-month ( millimoles per liter ) results in the control , intervention , and phase 2 groups ( respectively ) were cholesterol 4.92 + /- 0.06 , 4.60 + /- 0.07 , 4.30 + /- 0.05 ; low-density lipoprotein 2.91 + /- 0.06 , 2.68 + /- 0.07 , 2.4 + /- 0.06 ; high-density lipoprotein 1.18 + /- 0.07 , 1.12 + /- 0.09 , 1.10 + /- 0.01 ; triglycerides 1.89 + /- 0.12 , 1.78 + /- 0.09 , 1.70 + /- 0.05 ; and on medications 49 % , 83 % , and 84 % . CONCLUSION A planned strategy of management with use of early pharmacologic therapy with a cardiac rehabilitation nurse assigned to obtain and follow lipid profiles and initiate therapy is more effective in controlling dyslipidemia than leaving the management to the cardiologist Abstract Objective : To investigate the association between serum cholesterol concentration and cerebrovascular disease . Design : Retrospective study . Setting : Acute stroke unit of inner city general hospital . Subjects : 977 patients with acute stroke . Main outcome measures : Serum total cholesterol concentration , type of stroke investigated by computed tomography or magnetic resonance imaging  , three month outcome ( good ( alive at home ) or bad ( dead or in care ) ) , long term mortality . Results : After adjustment for known prognostic factors , higher serum cholesterol concentrations were associated with reduced long term mortality after stroke ( relative hazard 0.91 ( 95 % confidence interval 0.84 to 0.98 ) per mmol/l increase in cholesterol ) independently of stroke type , vascular territory and extent , age , and hyperglycaemia . Three month outcome was also influenced independently by serum cholesterol ( P=0.024 ) . Conclusions : Our data suggest an association between poor stroke outcome and lower serum cholesterol concentration . Until a prospect i ve controlled study has confirmed the benefits of lowering cholesterol concentration in elderly subjects , the application of cholesterol lowering guidelines can not be justified as secondary prevention of acute stroke . Key messages Although the link between cholesterol and stroke is controversial , the balance of evidence suggests higher cholesterol is associated with an increased risk of atherothrombotic stroke but a reduced risk of intracerebral haemorrhage Trials of lipid lowering drugs have concentrated on middle aged patients with a relatively low incidence of stroke events We investigated the association between serum cholesterol and cerebrovascular disease in 977 patients hospitalised with acute stroke and found that higher serum total cholesterol concentrations were associated with a reduction in long term mortality after stroke This relation was independent of the type or extent of the stroke , vascular territory , age , and hyperglycaemia – all factors known to influence survival independently after stroke Until conclusive benefit is shown in elderly patients with cerebrovascular disease , the routine application of lipid lowering treatment after stroke can not be OBJECTIVE The Carotene and Retinol Efficacy Lung Cancer Chemoprevention Trial ( CARET ) ended prematurely due to the unexpected findings that the active treatment group on the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate had a 46 % increased lung cancer mortality and a 26 % increased cardiovascular mortality compared with placebo . This study was design ed when the CARET intervention was halted to evaluate the effects of long-term supplementation with beta-carotene and retinol on serum triglyceride and cholesterol levels , in an attempt to explore possible explanations for the CARET result . METHODS Serum triglyceride levels , and total , high-density lipoprotein ( HDL ) , and low-density lipoprotein ( LDL ) cholesterol levels were determined in a subgroup of 52 CARET participants . Baseline and mid-trial levels were available on 23 participants on placebo and 29 on active treatment  who were then serially followed for 10 months after trial termination . RESULTS Triglyceride , and total , HDL and LDL cholesterol levels were similar in the two groups at baseline . After a mean of 5 years on the intervention there was a small nonsignificant increase in serum triglyceride levels in the active group , but no difference in total , HDL , or LDL cholesterol levels . After stopping the intervention there was a decrease in triglyceride levels in the active intervention group , and no change in the other parameters . CONCLUSION Based on a small convenience sample , CARET participants in the active treatment arm had a small nonsignificant increase in serum triglyceride levels while on the intervention , and a decrease in serum triglyceride levels after the intervention was discontinued . No significant changes in total or HDL cholesterol were noted . These results argue against a major contribution of treatment-induced changes in serum lipid and lipoprotein levels to the increased cardiovascular mortality in the active treatment group OBJECTIVE We aim ed to examine whether better use of preventive methods and treatments of cardiovascular disease would reduce recurrent events in home-dwelling patients 75 years or older . METHODS This was a r and omized , controlled trial ( a practical clinical trial , the DEBATE ) , conducted in 2000 to 2003 in Helsinki , Finl and . We recruited 400 vascular patients with mean age of 80 years from the community , and they were r and omly assigned to the intervention group ( n = 199 ) where both nonpharmacological and pharmacological cardiovascular treatments were optimized by a geriatrician according to current guidelines . The control group ( n = 201 ) received the usual care . Main outcome measures were major cardiovascular disease events and total mortality and changes in risk factors and medications . RESULTS The groups were balanced at baseline . Mean duration of follow-up was 3.4 years . At 3 years , drug treatments had become more evidence -based in the intervention group . Consequently , total and low-density lipoprotein cholesterol levels ( P < .0001 ) and systolic ( P = .005 ) and diastolic ( P = .009 ) blood pressure were significantly improved in the intervention group . However , neither primary end points ( 52 and 53 events in the intervention and control groups , respectively ) nor total mortality ( 36 and 35 deaths ) were significantly different between the two groups . No special adverse effects were encountered . CONCLUSION It was possible and safe to institute evidence -based cardiovascular treatments and improve risk factors in patients 75 years or older in a pragmatic setting . During 3.4 years , however , this was not converted to clinical benefits BACKGROUND : Lowering low-density lipoprotein cholesterol ( LDL-C ) with statins reduces atherosclerosis . LDL and high-density lipoprotein ( HDL ) are commonly measured by their cholesterol content , but non-HDL cholesterol , LDL particle number ( LDL-P ) , or total apolipoprotein B ( apoB ) may better predict cardiovascular risk . Few studies have examined relations among lipoprotein levels and composition before and after interventions to lower LDL-C and non-HDL-C. OBJECTIVE : To measure changes in carotid artery intimal media thickness ( CIMT ) and lipid concentration and composition during 36 months of statin therapy . METHODS : Analyses were conducted on 418 diabetic individuals , with complete data and no prior cardiovascular events , who were r and omized to aggressive ( AG ) versus st and ard ( STD ) treatment for LDL-C , non-HDL-C , and systolic blood pressure ( SBP ) as part of the Stop Atherosclerosis in Native Diabetics Study ( S AND S ) . RESULTS : The AG group achieved average LDL-C and non-HDL-C of 71mg/dL and 100mg/dL and a decrease in CIMT . No significant interactions were observed between treatment effect and initial levels of LDL-C , non-HDL-C , HDL-C , triglycerides , apoB , or LDL-P. Decreases in LDL-C ( p<.005 ) and non-HDL-C ( p<.001 ) were independently correlated with CIMT regression in the AG group . Changes in apoB and LDL-P showed borderline correlations with CIMT regression ( p=.07 and p=.09 ) . CONCLUSIONS : In diabetic adults with no prior cardiovascular events , treatment to current targets for lipids and SBP reduces atherosclerosis progression and when more aggressive targets are met , atherosclerosis regresses . The aggressive targets for LDL-C and non-HDL-C appeared to be the main determinants of CIMT regression and were more predictive of this outcome than changes in LDL-P or In the Lipid Research Clinics Coronary Primary Prevention Trial ( LRC-CPPT ) , a 19 % lower incidence of coronary heart disease ( CHD ) in  cholestyramine-treated men was accompanied by mean falls of 8 % and 12 % in plasma total ( TOTAL-C ) and low-density lipoprotein ( LDL-C ) cholesterol levels relative to levels in  placebo-treated men . When the cholestyramine treatment group was analyzed separately , a 19 % reduction in CHD risk was also associated with each decrement of 8 % in TOTAL-C or 11 % in LDL-C levels ( P less than .001 ) . Moreover , CHD incidence in men sustaining a fall of 25 % in TOTAL-C or 35 % in LDL-C levels , typical responses to the prescribed dosage ( 24 g/day ) of cholestyramine resin , was half that of men who remained at pretreatment levels . Adherence to medication was associated with reduced incidence of CHD only when accompanied by falls in TOTAL-C and LDL-C levels . Small increases in high-density lipoprotein cholesterol levels , which accompanied cholestyramine treatment , independently accounted for a 2 % reduction in CHD risk . Thus , the reduction of CHD incidence in the cholestyramine  group seems to have been mediated chiefly by reduction of TOTAL-C and LDL-C levels BACKGROUND AND METHODS The effect of intensive lipid-lowering therapy on coronary atherosclerosis among men at high risk for cardiovascular events was assessed by quantitative arteriography . Of 146 men no more than 62 years of age who had apolipoprotein B levels greater than or equal to 125 mg per deciliter , documented coronary artery disease , and a family history of vascular disease , 120 completed the 2 1/2-year double-blind study , which included arteriography at base line and after treatment . Patients were given dietary counseling and were r and omly assigned to one of three treatments : lovastatin ( 20 mg twice a day ) and colestipol ( 10 g three times a day ) ; niacin ( 1 g four times a day ) and colestipol ( 10 g three times a day ) ; or conventional therapy with placebo ( or colestipol if the low-density lipoprotein [ LDL ] cholesterol level was elevated ) . RESULTS The levels of LDL and high-density lipoprotein ( HDL ) cholesterol changed only slightly in the conventional-therapy group ( mean changes , -7 and + 5 percent , respectively ) , but more substantially among patients treated with lovastatin and colestipol ( -46 and + 15 percent ) or niacin and colestipol ( -32 and + 43 percent ) . In the conventional-therapy group , 46 percent of the patients had definite lesion progression ( and no regression ) in at least one of nine proximal coronary segments ; regression was the only change in 11 percent . By comparison , progression ( as the only change ) was less frequent among patients who received lovastatin and colestipol ( 21 percent ) and those who received niacin and colestipol ( 25 percent ) , and regression was more frequent ( lovastatin and colestipol , 32 percent ; niacin and colestipol , 39 percent ; P less than 0.005 ) . Multivariate analysis indicated that a reduction in the level of apolipoprotein B ( or LDL cholesterol ) and in systolic blood pressure , and an increase in HDL cholesterol correlated independently with regression of coronary lesions . Clinical events ( death , myocardial infa rct ion , or revascularization for worsening symptoms ) occurred in 10 of 52 patients assigned to conventional therapy , as compared with 3 of 46 assigned to receive lovastatin and colestipol and 2 of 48 assigned to receive niacin and colestipol ( relative risk of an event during intensive treatment , 0.27 ; 95 percent confidence interval , 0.10 to 0.77 ) . CONCLUSIONS In men with coronary artery disease who were at high risk for cardiovascular events , intensive lipid-lowering therapy reduced the frequency of progression of coronary lesions , increased the frequency of regression , and reduced the incidence of cardiovascular events Controlled clinical trials have demonstrated the efficacy of reducing the blood levels of low-density lipoprotein cholesterol in reducing the incidence of coronary artery disease in hypercholesterolemic middle-aged men . However , a similar reversibility of the risk of coronary artery disease has not been demonstrated for high-density lipoprotein cholesterol elevation and triglyceride reduction . Therefore , the effect of administering 400 mg of bezafibrate retard daily versus placebo ( double blind ) to patients with myocardial infa rct ion preceding r and omization by 6 months to 5 years , or a clinical ly manifest anginal syndrome documented by objective evidence of dynamic myocardial ischemia , or both , is being investigated . Three thous and subjects ( aged 45 to 74 years ) are being enrolled from 19 cardiac departments in Israel , with total serum cholesterol between 180 and 250 mg/dl , high-density lipoprotein cholesterol < or = 45 mg/dl and triglycerides < or = 300 mg/dl . In addition , low-density lipoprotein cholesterol concentrations are required to be < or = 180 mg/dl ( < or = 160 mg/dl for patients aged < 50 years ) . Patients needing lipid-modifying therapy , exhibiting > or = 1 prespecified exclusion criterion or not giving informed consent , or a combination , are not r and omized . The primary end points for evaluating efficacy are the incidence of fatal and nonfatal myocardial infa rct ion , and sudden death . The hypothesized effect of bezafibrate administration under the aforementioned protocol is to reduce an estimated cumulative end point event incidence of > or = 15 % by 20 to 25 % over an average follow-up period of 6.25 years , through early 1998 , when the last patient recruited will have completed 5 years . ( ABSTRACT TRUNCATED AT 250 WORDS Background : Lifestyle modification is associated with a substantially decreased risk of cardiovascular events . However , the role of lifestyle intervention for secondary prevention in patients with noncardioembolic ischemic stroke is inadequately defined . We assessed the hypothesis that lifestyle intervention can reduce the onset of new vascular events in patients with noncardioembolic mild ischemic stroke . Methods : We conducted an observer-blind r and omized controlled trial that enrolled 70 patients ( 48 men , mean age 63.5 years ) with acute noncardioembolic mild ischemic stroke . The patients were allocated in equal numbers to a lifestyle intervention group or a control group . We performed lifestyle interventions , which comprised exercise training , salt restriction and nutrition advice for 24 weeks . Then all patients were prospect ively followed up for occurrence of the primary endpoints , including hospitalization due to stroke recurrence and the onset of other vascular events . We also evaluated systolic blood pressure ( SBP ) at the clinic and at home , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , hemoglobin A1c ( HbA1c ) and high-sensitivity C-reactive protein ( hs-CRP ) to compare the efficacy of the lifestyle interventions . Results : This trial was terminated earlier than expected because of the prespecified early stopping rule for efficacy . After the 24-week intervention period , the intervention group showed a significant increase in daily physical activity and a significant decrease in salt intake ( physical activity , p = 0.012 ; salt intake , p < 0.001 ) , with a significant difference between the r and omized groups ( physical activity , p < 0.001 ; salt intake , p = 0.018 ) . Similarly , blood pressure was decreased and the HDL-C levels were increased in the intervention group ( SBP , p < 0.001 ; HDL-C , p = 0.018 ) , with significant differences between the r and omized groups ( SBP , p < 0.001 ; HDL-C , p = 0.022 ) . In contrast , LDL-C , HbA1c and hs-CRP tended to decrease in the intervention group , but this decrease did not achieve significance . After a median follow-up period of 2.9 years , 12 patients allocated to the control group and 1 patient in the lifestyle intervention group experienced at least 1 vascular event . A sequential plans analysis indicated the superiority of the lifestyle intervention in interim analysis . Kaplan-Meier survival curves after the log-rank test showed a significant prognostic difference between the r and omized groups ( p = 0.005 ) . Conclusions : Lifestyle intervention with appropriate medication is beneficial for reducing the incidence of new vascular events and improving vascular risk factors in patients with noncardioembolic mild ischemic stroke 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 Few direct clinical data are available regarding whether cholesterol-lowering therapy should be extended to patients with coronary heart disease ( CHD ) and normal or only slightly elevated plasma cholesterol concentrations . The one published angiographic trial design ed to examine this question found no benefit . Additional prospect i ve data will be provided by the Lipoprotein and Coronary Atherosclerosis Study ( LCAS ) , a r and omized , double-blind , placebo-controlled trial of fluvastatin therapy ( 20 mg twice daily ) monitored by both quantitative coronary angiography ( QCA ) and , in a subset of patients , positron-emission tomography ( PET ) .  Eligible subjects in LCAS were men and women 35 - 75 years of age with low-density lipoprotein ( LDL ) cholesterol of 115 - 190 mg/dL on stable dietary therapy and with angiographic evidence by caliper measurement of at least one coronary atherosclerotic lesion causing 30 - 75 % diameter stenosis . Among the 429 patients r and omized ( mean age 58.8 , 81 % male ) , mean baseline LDL cholesterol was only 145.6 mg/dL. Any patient with mean prer and omization  LDL cholesterol  of 160 mg/dL or higher also received open-label adjunctive cholestyramine . The primary endpoint is within-patient per-lesion change in minimum lumen diameter ( MLD ) as measured by QCA at baseline and 2.5-year follow-up . All evaluable lesions had MLD at least 0.8 mm less than the reference lumen diameter at either baseline or follow-up and MLD at least 25 % of the reference lumen diameter at baseline . Data obtained on myocardial perfusion changes ( 99 patients underwent initial PET ) , special lipid particles , and coagulation factors may help define which patients with CHD and relatively low LDL cholesterol will benefit from lipid-lowering treatment CONTEXT Multiple epidemiologic studies and some trials have linked diet with cardiovascular disease ( CVD ) prevention , but long-term intervention data are needed . OBJECTIVE To test the hypothesis that a dietary intervention , intended to be low in fat and high in vegetables , fruits , and grains to reduce cancer , would reduce CVD risk . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial of 48,835 postmenopausal women aged 50 to 79 years , of diverse background s and ethnicities , who participated in the Women 's Health Initiative Dietary Modification Trial . Women were r and omly assigned to an intervention ( 19,541 [ 40 % ] ) or comparison group ( 29,294 [ 60 % ] ) in a free-living setting . Study enrollment occurred between 1993 and 1998 in 40 US clinical centers ; mean follow-up in this analysis was 8.1 years . INTERVENTION Intensive behavior modification in group and individual sessions design ed to reduce total fat intake to 20 % of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d . The comparison group received diet-related education material s. MAIN OUTCOME MEASURES Fatal and nonfatal coronary heart disease ( CHD ) , fatal and nonfatal stroke , and CVD ( composite of CHD and stroke ) . RESULTS By year 6 , mean fat intake decreased by 8.2 % of energy intake in the intervention vs the comparison group , with small decreases in saturated ( 2.9 % ) , monounsaturated ( 3.3 % ) , and polyunsaturated ( 1.5 % ) fat ; increases occurred in intakes of vegetables/fruits ( 1.1 servings/d ) and grains ( 0.5 serving/d ) . Low-density lipoprotein cholesterol levels , diastolic blood pressure , and factor VIIc levels were significantly reduced by 3.55 mg/dL , 0.31 mm Hg , and 4.29 % , respectively ; levels of high-density lipoprotein cholesterol , triglycerides , glucose , and insulin did not significantly differ in the intervention vs comparison groups . The numbers who developed CHD , stroke , and CVD ( annualized incidence rates ) were 1000 ( 0.63 % ) , 434 ( 0.28 % ) , and 1357 ( 0.86 % ) in the intervention and 1549 ( 0.65 % ) , 642 ( 0.27 % ) , and 2088 ( 0.88 % ) in the comparison group . The diet had no significant effects on incidence of CHD ( hazard ratio [ HR ] , 0.97 ; 95 % confidence interval [ CI ] , 0.90 - 1.06 ) , stroke ( HR , 1.02 ; 95 % CI , 0.90 - 1.15 ) , or CVD ( HR , 0.98 ; 95 % CI , 0.92 - 1.05 ) . Excluding participants with baseline CVD ( 3.4 % ) , the HRs ( 95 % CIs ) for CHD and stroke were 0.94 ( 0.86 - 1.02 ) and 1.02 ( 0.90 - 1.17 ) , respectively . Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits . CONCLUSIONS Over a mean of 8.1 years , a dietary intervention that reduced total fat intake and increased intakes of vegetables , fruits , and grains did not significantly reduce the risk of CHD , stroke , or CVD  in postmenopausal women and achieved only modest effects on CVD risk factors , suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk . CLINICAL TRIALS REGISTRATION Clinical Trials.gov Identifier : NCT00000611 BACKGROUND Despite the large body of evidence confirming the effectiveness of lipid lowering for the secondary prevention of coronary heart disease ( CHD ) events , undertreatment of hyperlipidemia is common . This study tested the effectiveness of a nurse case management program to lower blood lipids in patients with CHD . METHODS A total of 228 consecutive , eligible adults with hypercholesterolemia and CHD were recruited during hospitalization after coronary revascularization . Patients were r and omized to receive lipid management , including individualized lifestyle modification and pharmacologic intervention , from a nurse practitioner for 1 year after discharge in addition to their usual care ( NURS ) , or to usual care enhanced with feedback on lipids to their primary provider and /or cardiologist ( EUC ) . RESULTS Significantly more patients in the NURS group than in the EUC group achieved low-density lipoprotein cholesterol ( LDL-C ) levels < 2.59 mmol/dL ( 100 mg/dL , 65 % vs 35 % , P = .0001 ) . Favorable changes in lipids and lipoproteins were accompanied by significant improvements in dietary and exercise patterns in the NURS group . In a multivariate analysis adjusting for other covariates , being assigned to the NURS group ( P = .0001 ) and being on a lipid-lowering medication ( P = .001 ) were significant independent predictors of LDL-C level . CONCLUSIONS Control of hypercholesterolemia in patients who have undergone coronary revascularization can be improved by a nurse case-management program . Because the National Cholesterol Education Program Adult Treatment Panel III guidelines have broadened the definition of high-risk population s that warrant aggressive treatment , nurse case-management programs may offer key opportunities to enhance appropriate application of new treatment paradigms The current guidelines for treatment of high-risk of lipid disorders do not specify a therapeutic target level of high-density lipoprotein cholesterol ( HDL-C ) for prevention of vascular disease in high-risk population s. However , there is a substantial body of evidence from basic science and epidemiologic studies and from clinical trials , providing the strong , consistent message that raising HDL-C by therapeutic means will effectively and independently reduce cardiovascular risk . This review summarizes epidemiologic evidence and the results of a meta- analysis of 23 published , prospect i ve , r and omized , placebo-controlled clinical trials . It focuses on the effects of lipid therapies on coronary stenosis progression , as measured by quantitative arteriography and /or , on clinical cardiovascular endpoints . Among the seven drug/treatment classes into which individual study results were categorized and averaged , reduction in stenosis progression and reduction in clinical events are both very highly correlated with the composite lipid variable ( % ΔHDL-C - % Δ low-density lipoprotein cholesterol [ LDL-C ] ; where % Δ is percent change relative to the placebo group response ) . This holds true for all lipid drug classes or combinations of lipid drug therapy , with the exception of the unexpectedly anomalous effects of the torcetrapib-atorvastatin combination . There is a strong and consistent body of evidence that therapeutic HDL-C-raising is at least as effective as comparable percentages of LDL-C-lowering for reduction of atherosclerosis progression or clinical cardiovascular events over a broad range of risk levels . Adoption of this strategy into guidelines probably awaits results of at least one large controlled HDL-C-raising clinical trial , of which two are ongoing and one other is planned
There is evidence that statin therapy in patients with a history of ischaemic stroke or TIA significantly reduces subsequent major coronary events but only marginally reduces the risk of stroke recurrence .
There is no clear evidence of beneficial effect from statins in those with previous haemorrhagic stroke and it is unclear whether statins should be started immediately post stroke or later .
BACKGROUND Studies have shown that interventions which reduce total and low-density lipoprotein cholesterol levels also reduce coronary heart disease ( CHD ) and stroke events in those with a history of CHD .
However , it is uncertain whether treatment to alter cholesterol levels can prevent recurrence of either stroke or subsequent cardiovascular events and whether differences in outcomes exist between classes of lipid-lowering therapy .
This is an up date of a Cochrane review first published in 2002 .
OBJECTIVES To investigate the effect of altering serum lipids pharmacologically for preventing subsequent cardiovascular disease and stroke recurrence in patients with a history of stroke .