***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Studies have shown that treatment of hyperlipidemia , especially lowering of plasma LDL levels , retards the progression of coronary atherosclerosis and prevents clinical cardiovascular events . No such studies have focused on subjects with low levels of HDL cholesterol . METHODS AND RESULTS We r and omly assigned 395 post-coronary bypass men , who had an HDL cholesterol concentration < or = 1.1 mmol/L and LDL cholesterol < or = 4.5 mmol/L , to receive gemfibrozil 1200 mg/d or placebo . Coronary angiography was performed at baseline and after , on average , 32 months of therapy . Changes in coronary dimensions were assessed by computer-assisted analysis . Average on-trial serum triglyceride concentrations were 1.69+/-0.68 and 1.02+/-0.37 , total cholesterol 5.48+/-0.68 and 4.83+/-0.63 , LDL cholesterol 3.84+/-0.59 and 3.39+/-0.56 , and HDL cholesterol 0.88+/-0.15 and 0.98+/-0.17 mmol/L in the placebo and gemfibrozil groups , respectively ( mean+/-SD , each P<.001 ) . The change in per-patient means of average diameters of native coronary segments was -0.04+/-0.11 mm in the placebo group and -0.01+/-0.10 mm in the gemfibrozil group ( P=.009 ) . The equivalent changes in minimum luminal diameters of stenoses were -0.09+/-0.18 and -0.04+/-0.15 mm , respectively ( P=.002 ) . A similar , albeit nonsignificant , trend toward treatment benefit was found in the predefined primary study end point , segments unaffected by grafts and those distal to graft insertions . In aortocoronary bypass grafts , 23 subjects ( 14 % ) assigned to placebo had new lesions in the follow-up angiogram , compared with 4 subjects ( 2 % ) assigned to gemfibrozil ( P<.001 ) . CONCLUSIONS Gemfibrozil therapy retarded the progression of coronary atherosclerosis and the formation of bypass-graft lesions after coronary bypass surgery in men with low HDL cholesterol as their main lipid abnormality In a double-blind clinical trial of clofibrate versus identical quantity of corn oil 497 patients with ischaemic heart disease were observed over a period of five years . The death rate and the rate of non-fatal infa rcts were significantly less among the clofibrate group , and the difference was greatest in respect of sudden deaths and among patients who had previously suffered from angina rather than infa rct ion . The cholesterol- and triglyceride-reducing properties of clofibrate were maintained throughout the period of the trial and side effects were very few . But the protective action of the drug against new infa rcts and death bore no apparent relation to these properties Objective : To assess the effect of bezafibrate on the risk of coronary heart disease and stroke in men with lower extremity arterial disease . Design : Double blind placebo controlled r and omised trial . Setting : 85 general practice s and nine hospital vascular clinics . Participants : 1568 men , mean age 68.2 years ( range 35 to 92 ) at recruitment . Interventions : Bezafibrate 400 mg daily ( 783 men ) or placebo ( 785 men ) . Main outcome measures : Combination of coronary heart disease and of stroke . All coronary events , fatal and non-fatal coronary events separately , and strokes alone ( secondary end points ) . Results : Bezafibrate did not reduce the incidence of coronary heart disease and stroke . There were 150 and 160 events in the active and placebo groups respectively ( relative risk 0.96 , 95 % confidence interval 0.76 to 1.21 ) . There were 90 and 111 major coronary events in the active and placebo groups respectively ( 0.81 , 0.60 to 1.08 ) , of which 64 and 65 were fatal ( 0.95 , 0.66 to 1.37 ) and 26 and 46 non-fatal ( 0.60 , 0.36 to 0.99 ) . Beneficial effects on non-fatal events were greatest in men aged < 65 years at entry , in whom benefit was also seen for all coronary events ( 0.38 , 0.20 to 0.72 ) . There were no significant effects in older men . There were 60 strokes in those on active treatment and 49 in those on placebo ( 1.34 , 0.80 to 2.01 ) . There were 204 and 195 deaths from all causes in the two groups respectively ( 1.03 , 0.83 to 1.26 ) . Bezafibrate reduced the severity of intermittent claudication for up to three years . Conclusions : Bezafibrate has no effect on the incidence of coronary heart disease and of stroke combined but may reduce the incidence of non-fatal coronary events , particularly in those aged < 65 years at entry , in whom all coronary events may also be reduced Background We studied the joint effect of baseline triglyceride and lipoprotein cholesterol levels on the incidence of cardiac end points in the trial group ( n = 4,081 ) of the Helsinki Heart Study , a 5-year r and omized coronary primary prevention trial among dyslipidemic middle-aged men . The relative risks ( RR ) were calculated using Cox proportional hazards models with a dummy variable technique that allows simultaneous study of subgroup combinations from the placebo and treatment groups . Methods and Results In the  placebo group ( n = 2,045 ) , the low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol ( HDL-C ) ratio was the best single predictor of cardiac events . This ratio in combination with the serum triglyceride level revealed a high-risk subgroup : subjects with LDL-C/HDL-C ratio > 5 and triglycerides > 2.3 mmol/1 had a RR of 3.8 ( 95 % CI , 2.2 - 6.6 ) compared with those with LDL-C/HI)L-C ratio ≤5 and triglyceride concentration ≤2.3 mmol/1 . In subjects with triglyceride concentration > 2.3 mmol/l and LDL-C/H1)L-C ratio ≤5 , RR was close to unity ( 1.1 ) , whereas in those with triglyceride level ≤2.3 mmoVIl and LDL-C/HDL-C ratio > 5 , RR was 1.2 . The high-risk group with LDL-C/HDL-C ratio > 5 and triglyceride level > 2.3 mmol/1 profited most from treatment with gemfibrozil , with a 71 % lower incidence of coronary heart disease events than the corresponding placebo subgroup . In all other subgroups , the reduction in CHD incidence was substantially smaller Conclusions Serum triglyceride concentration has prognostic value , both for assessing coronary heart disease risk and in predicting the effect of gemfibrozil treatment , especially when used in combination with HDL-C and OBJECTIVE To determine whether serum lipid intervention , in addition to conventional diabetes treatment , could alter cardiovascular outcomes in type 2 diabetes . RESEARCH DESIGN AND METHODS There were 164 type 2 diabetic subjects ( 117 men , 47 women ) without a history of clinical cardiovascular disease r and omized to receive either bezafibrate or placebo daily on a double-blind basis in addition to routine diabetes treatment and followed prospect ively for a minimum of 3 years . Serial biochemical and noninvasive vascular assessment s , carotid and femoral artery B-mode ultrasound measurements , and those pertaining to coronary heart disease (CHD)— clinical history , the World Health Organization ( WHO ) cardiovascular question naire , and resting and exercise electrocardiogram (ECG)—were recorded . RESULTS Bezafibrate treatment was associated with significantly greater reductions over 3 years in median serum triglyceride ( −32 vs. 4 % , P = 0.001 ) , total cholesterol ( −7 vs. −0.3 % , P = 0.004 ) , and total−to-HDL cholesterol ratio ( −12 vs. −0.0 % , P = 0.001 ) , and an increase in HDL cholesterol ( 6 vs. −2 % , P = 0.02 ) as compared with placebo . There was a trend toward a greater reduction of fibrinogen ( −18 vs. −6 % , P = 0.08 ) at 3 years . No significant differences between the two groups were found in the progress of ultrasonically measured arterial disease . In those treated with bezafibrate , there was a significant reduction ( P = 0.01 , log-rank test ) in the combined incidence of Minnesota-coded probable ischemic change on the resting ECG and of documented myocardial infa rct ion . CONCLUSIONS Improving dyslipidemia in type 2 diabetic subjects had no effect on the progress of ultrasonically measured arterial disease , although the lower rate of “ definite CHD events ” in the treated group suggests that this might result in a reduction in the incidence of coronary heart disease BACKGROUND We investigated whether combination therapy with a statin plus a fibrate , as compared with statin monotherapy , would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease . METHODS We r and omly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo .  The primary outcome was the first occurrence of nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes . The mean follow-up was 4.7 years . RESULTS The annual rate of the primary outcome was 2.2 % in the fenofibrate group and 2.4 % in the placebo group ( hazard ratio in the fenofibrate group , 0.92 ; 95 % confidence interval [ CI ] , 0.79 to 1.08 ; P=0.32 ) . There were also no significant differences between the two study groups with respect to any secondary outcome . Annual rates of death were 1.5 % in the fenofibrate group and 1.6 % in the placebo group ( hazard ratio , 0.91 ; 95 % CI , 0.75 to 1.10 ; P=0.33 ) . Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex , with a benefit for men and possible harm for women ( P=0.01 for interaction ) , and a possible interaction according to lipid subgroup , with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol ( P=0.057 for interaction ) . CONCLUSIONS The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events , nonfatal myocardial infa rct ion , or nonfatal stroke , as compared with simvastatin alone . These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes . ( Clinical Trials.gov number , NCT00000620 . Objective In a r and omized 5-yr multi-intervention trial , we tested the efficacy of intensified health education ( IHE ) in improving metabolic control and reducing the level of coronary risk factors and incidence of ischemic heart disease ( IHD ) . Research Design and Methods Within the intervention group , the benefit of clofibric acid was evaluated in a double-blind study . One thous and one hundred thirty-nine newly diagnosed middle-aged ( 30- to 55-yr-old ) patients with non-insulindependent diabetes mellitus ( NIDDM ) entered the study . They were classified as diet controlled after a 6- wk screening phase with conventional dietary treatment . During the follow-up , the control group ( n = 378 ) was cared for at different diabetes outpatient clinics with a st and ardized surveillance . The intervention group ( n = 761 ) had a structured IHE that included dietary advice , antismoking and antialcohol education , and ways to enhance physical activity . Results R and omly , 379 of the IHE patients received 1.6 g clofibric acid/day , and the others received placebo . IHE result ed in improved glucose control ( adjusted fasting blood glucose ) levels after 5 yr ( control subjects 9.27 mM , IHE group 8.71 mM , and IHE plus clofibric acid group 8.60 mM , P < 0.01 ) . The better glycemic control was achieved with fewer antidiabetic drugs . After 5 yr , antidiabetic drugs were prescribed to 47 % of the control subjects , 28 % of the IHE group , and 34 % of the IHE plus clofibric acid group ( cutoff limit for drug application was postpr and ial blood glucose of ≥13.87 mM ) . The ratio of polyunsaturated to saturated fatty acids ( 0.26 vs. 0.40 , P 
    Output:
    
INTERPRETATION Fibrates can reduce the risk of major cardiovascular events predominantly by prevention of coronary events , and might have a role in individuals at high risk of cardiovascular events and in those with combined dyslipidaemia .