human
***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: AIMS Patients with peripheral arterial obstructive disease require treatment to prevent major cardiovascular events and to relieve intermittent claudication . The walking performance of peripheral arterial obstructive disease patients was used to evaluate the usefulness of sulodexide , a glycosaminoglycan containing fast moving heparin and dermatan sulphate . METHODS AND RESULTS A r and omized , multicentre , double-blind , placebo-controlled study was performed in 286 patients with Leriche-Fontaine stage II peripheral arterial obstructive disease . Patients received placebo ( n=143 ) or sulodexide ( n=143 ) for 27 weeks . The primary end-point was the doubling of the pain-free walking distance at the end of treatment , and this was achieved by 23.8 % of patients treated with sulodexide and 9.1 % of those on placebo ( P=0.001 ) . The pain-free walking distance increased on average ( + /-SE ) by 83.2+/-8.6 m ( + 64.7 % from baseline ) with sulodexide and 36.7+/-6.2 m ( + 29.9 % from baseline ) with placebo ( P=0.001 ) . The maximum walking distance increased by 142.3+/-15.8 m ( + 76.0 % from baseline ) and 54.5+/-8.4 m ( + 27.9 % from baseline ) ( P<0.001 ) , respectively . Results for patients with type II diabetes were similar to those for non-diabetic patients .  Plasma fibrinogen decreased with sulodexide , but increased with placebo . CONCLUSION Sulodexide improved the walking ability of peripheral arterial obstructive disease patients to a significantly greater extent than placebo , with a concurrent significant decrease in fibrinogen . The treatment was well tolerated The present study describes a clinical trial in which Spanish patients suffering from peripheral vascular disease ( Fontaine stage II ) were given specific lipid supplements . Design ed as a longitudinal intervention study , patients were provided with olive oil for 3 months , followed by a 3 month wash-out period , then supplemented with a combination of fish oil and olive oil for the final 3 months . Changes in plasma and lipoprotein fatty acid composition and susceptibility of LDL to in vitro oxidation were examined . Furthermore , lipid-supplement-induced changes in LDL properties were measured as relative electrophoretic mobility and macrophage uptake . In addition , thirteen patients not provided with olive oil and fish oil were included as a control group and twenty healthy age-matched individuals were used as a reference group . A complete clinical study and a nutritional survey concerning food habits and lifestyle were performed every 3 months . Yao indices and claudicometry did not change significantly with dietary intervention although changes in plasma lipid composition suggested an improvement in the condition of the patients . The intake of the fish-oil supplement result ed in significantly increased plasma levels of eicosapentaenoic acid ( 20:5n-3 ) and docosahexaenoic acid ( 22:6n-3 ) in comparison with baseline concentrations , olive-oil and control groups . Fish-oil consumption significantly decreased plasma triacylglycerol levels compared with the olive-oil period , control and reference groups . The susceptibility of LDL to Cu-mediated oxidation was lower in the patients consuming olive oil and the fish-oil supplement than in the control group , and the uptake of LDL by macrophages was significantly lower in the group supplemented with fish oil . In conclusion , consumption of olive oil together with a dietary supplement of fish oil may be useful in the nutritional management of patients suffering from peripheral vascular disease in terms of increasing plasma n-3 long-chain polyunsaturated fatty acids and decreasing susceptibility of LDL to oxidation The ability of glycosaminoglycans to bind to a wide number of biologically active macromolecules has already been investigated . Recent clinical trials on the possible therapeutic benefits of glycosaminoglycans must be placed in perspective , even if they appear to be particularly encouraging , especially as regards the glycosaminoglycan effects on certain coagulation factors . A multicenter , medium-term , double-blind , crossover trial was performed by several Italian Lipid Clinics to determine whether administration of a medium molecular weight glycosaminoglycan ( Sulodexide ) has a significant clinical effect . Patients affected by peripheral vascular disease and /or hyperlipidemia ( type IIa , IIb and IV ) were su bmi tted to a 4-week wash-out period , followed by parenteral Sulodexide ( S ) or placebo ( P ) administration for 2 weeks , another 2 week wash-out period , parenteral crossover drug or P administration for 2 weeks and , finally , oral S administration for 6 months . Sulodexide lowered plasma viscosity and plasma fibrinogen in all patients . There was also a drop in triglycerides together with a rise in apo A-I and HDL-C in type IV hyperlipoproteinemics , whereas there was no significant effect on total or LDL-plasma cholesterol in type IIa and IIb patients . Moreover , there was a percent increase in peak flow and rest flow in the lower limbs of peripheral vascular disease patients . No side effects or intolerance phenomena were detected . The results indicate that Sulodexide administration may be useful in long-term treatment of patients with peripheral vascular disease and a concomitant increase in plasma triglycerides and /or fibrinogen and /or viscosity The aim of this study was to analyse the in vivo effect of a diet rich in extra-virgin olive oil and a fish-oil supplement on plasma and lipoprotein fatty-acid composition and on LDL susceptibility to oxidative modification in free-living Spanish male patients with peripheral vascular disease . A total of 12 patients were included in the experimental group which received extra virgin olive oil and a fish oil supplement ( group OF ) . On the other h and , 13 patients which had refined olive oil as the main visible fat were considered as Control group . Plasma triglycerides decreased significantly after three months of dietary intervention . The LDL and plasma fatty-acid pattern in the group OF was characterized by a significant increase in n-3 polyunsaturated fatty acids , mainly 20:5 n-3 and 22:6 n-3 . The slopes of LDL oxidative susceptibility were similar between baseline and endpoint values in both groups . However , the uptake of oxidized LDL by macrophages was significantly reduced in OF patients in comparison with the Control group . In conclusion , the daily intake of about 40 g/d of extra-virgin olive oil in combination with a daily supplement of 16 g of fish oil for 3 months in patients with peripheral vascular disease leads to a plasma-lipid profile less atherogenic than in patients having refined olive oil as the main visible food fat . The simultaneous consumption of alpha-tocopherol and natural antioxidants provided by extra-virgin olive oil seems to have a protective effect on the LDL susceptibility to oxidative modifications in spite of a higher proportion of n-3 polyunsaturated fatty acids The aim of the Probucol  Quantitative Regression Swedish Trial ( PQRST ) ( n = 303 ) was to investigate whether probucol ( 0.5 g BID ) added to diet and cholestyramine ( 8 g BID ) could retard progression or induce regression of femoral atherosclerosis in hypercholesterolemic ( > 6.86 mmol/L ) subjects .  Probucol did not induce regression over the 3-year trial period as estimated by change in lumen volume on quantitative arteriography of a 20-cm segment of the femoral artery . In this report we studied in a representative subgroup ( n = 72 ) whether the reduction in HDL concentrations induced by probucol could explain the failure of the drug to be effective . We analyzed the effects of treatment on HDL particle size subclasses . Probucol lowered the relative level of HDL2b , comprising the largest HDL particles , by 53 % and the protein concentration of HDL2b by 67 % . The protein reduction in HDL was mainly confined to the apolipoprotein A-I moiety . The change in lumen volume correlated significantly with change in HDL , ie , HDL cholesterol ( r = .34 , P < .01 ) , HDL2 cholesterol ( r = .37 , P < .01 ) , HDL2b protein ( r = .44 , P < .001 ) , and the relative HDL2b value ( r = .51 , P < .001 ) . The corresponding values for relative HDL2b , distribution calculated on the active ( n = 35 ) and placebo ( n = 37 ) groups separately were also significant ( r = .39 and .32 , respectively ; both P < .05 ) . The correlation between drug-induced change in the relative HDL2b concentration and change in atherosclerosis was independent of the alteration in triglyceride concentration and could not be explained by treatment interaction . ( ABSTRACT TRUNCATED AT 250 WORDS The Cholesterol Lowering Atherosclerosis Study ( CLAS ) is a prospect i ve , placebo-controlled , angiographic trial design ed to test the hypothesis that aggressive lowering of LDL cholesterol with concomitant increase in HDL cholesterol will reverse or retard the atherosclerotic process . Specifically , CLAS was design ed to determine whether combined therapy with colestipol plus niacin will produce clinical ly significant change in coronary , carotid , and femoral artery atherosclerosis and coronary bypass graft lesions . To this purpose , 188 subjects were r and omized to diet plus drug or diet plus placebo .  We report on method ological aspects of planning and evaluating this study , including the choice of the study population , procedures for recruitment , the experimental design including sample size considerations , methods for evaluating outcome , and methods for evaluating compliance to treatment . Comparison of baseline data indicated no significant differences between groups at the time of r and omization . Subjects were predominantly male , Caucasian , 54 years of age , 20 % above ideal weight , with normal blood pressure . The average age at bypass was 50 years . The average lipids were cholesterol ( 243 mg/dL ) , HDL ( 45 mg/dL ) , and LDL ( 168 mg/dL ) . Finally , the distribution of baseline coronary stenosis was equivalent between the two groups ( average number of lesions per subject = 10.6 ) BACKGROUND AND AIMS epidemiological studies suggest polyunsaturated fatty acids protect against the development of atherosclerosis . The aim of this study was to perform a r and omized controlled trial of gamma-linolenic and eicosapentaenoic acids in patients with lower limb atherosclerosis . Main outcome measures were : cholesterol and lipoprotein concentrations ; haemostatic and rheological variables ; the ankle brachial pressure index ; walking distance ; and cardiovascular events and death . METHODS 120 men and women with stable intermittent claudication were r and omized to 2 years treatment with either a combination of gamma-linolenic and eicosapentaenoic acids , or placebo . RESULTS 39 ( 65.0 cent ) of those taking fatty acids and 36 ( 60.0 cent ) of those taking placebo completed the trial . Lipid concentrations did not differ significantly during the trial . In those taking fatty acids , haematocrit was significantly higher than in the placebo group after 6 months ( 46.1 cent compared with 44.6 cent , P < /= 0.01 ) , and systolic blood pressure was significantly lower after 2 years ( 150|mmHg compared with 161.8|mmHg , < /= 0.05 ) . There was no difference in walking distance , but there was a small reduction in non-fatal coronary events in the fatty acid group ( 10 cent compared with 15 cent , P > 0.05 ) . CONCLUSIONS a combination of polyunsaturated fatty acids produced a statistically significant reduction in systolic blood pressure , but no other significant benefits on risk factors . The trend towards fewer coronary events in those taking fatty acids warrants further investigation The effects of 3-glucosaminoglycan sulfate on lipids and the hemorheologic parameters were observed in a preliminary double-blind crossover study in 30 hyperlipidemic peripheral vascular disease ( PVD ) patients . Parenteral adminis tration of the test drug was associated with a reduction in serum lipids , espe cially in triglyceride levels , and a lowering of fibrinogen , plasma viscosity , and whole blood viscosity levels . These effects justify the drug 's use in the treatment of PVD , especially when associated with hypertriglyceridemia and hemorheo logic disturbances The 2-year therapy effect on femoral atherosclerosis was evaluated in the Cholesterol Lowering Atherosclerosis Study ( CLAS ) , a r and omized , placebo-plus-diet-controlled angiographic trial of colestipol-niacin therapy plus diet in men with previous coronary bypass surgery . Different diet compositions were prescribed to enhance the differential in blood cholesterol responses between the two groups . The annual rate of change in computer-estimated atherosclerosis ( CEA ) , a measure of lumen abnormality , was evaluated between treatment groups . A significant per-segment therapy effect was found in segments with moderately severe atherosclerosis ( p less than 0.04 ) and in proximal segments ( p less than 0.02 ) . When segmental CEA measures were combined into a per-patient score using an adaptation of the National Heart 
    Output:
    
agent
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
***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: AIMS Patients with peripheral arterial obstructive disease require treatment to prevent major cardiovascular events and to relieve intermittent claudication . The walking performance of peripheral arterial obstructive disease patients was used to evaluate the usefulness of sulodexide , a glycosaminoglycan containing fast moving heparin and dermatan sulphate . METHODS AND RESULTS A r and omized , multicentre , double-blind , placebo-controlled study was performed in 286 patients with Leriche-Fontaine stage II peripheral arterial obstructive disease . Patients received placebo ( n=143 ) or sulodexide ( n=143 ) for 27 weeks . The primary end-point was the doubling of the pain-free walking distance at the end of treatment , and this was achieved by 23.8 % of patients treated with sulodexide and 9.1 % of those on placebo ( P=0.001 ) . The pain-free walking distance increased on average ( + /-SE ) by 83.2+/-8.6 m ( + 64.7 % from baseline ) with sulodexide and 36.7+/-6.2 m ( + 29.9 % from baseline ) with placebo ( P=0.001 ) . The maximum walking distance increased by 142.3+/-15.8 m ( + 76.0 % from baseline ) and 54.5+/-8.4 m ( + 27.9 % from baseline ) ( P<0.001 ) , respectively . Results for patients with type II diabetes were similar to those for non-diabetic patients .  Plasma fibrinogen decreased with sulodexide , but increased with placebo . CONCLUSION Sulodexide improved the walking ability of peripheral arterial obstructive disease patients to a significantly greater extent than placebo , with a concurrent significant decrease in fibrinogen . The treatment was well tolerated The present study describes a clinical trial in which Spanish patients suffering from peripheral vascular disease ( Fontaine stage II ) were given specific lipid supplements . Design ed as a longitudinal intervention study , patients were provided with olive oil for 3 months , followed by a 3 month wash-out period , then supplemented with a combination of fish oil and olive oil for the final 3 months . Changes in plasma and lipoprotein fatty acid composition and susceptibility of LDL to in vitro oxidation were examined . Furthermore , lipid-supplement-induced changes in LDL properties were measured as relative electrophoretic mobility and macrophage uptake . In addition , thirteen patients not provided with olive oil and fish oil were included as a control group and twenty healthy age-matched individuals were used as a reference group . A complete clinical study and a nutritional survey concerning food habits and lifestyle were performed every 3 months . Yao indices and claudicometry did not change significantly with dietary intervention although changes in plasma lipid composition suggested an improvement in the condition of the patients . The intake of the fish-oil supplement result ed in significantly increased plasma levels of eicosapentaenoic acid ( 20:5n-3 ) and docosahexaenoic acid ( 22:6n-3 ) in comparison with baseline concentrations , olive-oil and control groups . Fish-oil consumption significantly decreased plasma triacylglycerol levels compared with the olive-oil period , control and reference groups . The susceptibility of LDL to Cu-mediated oxidation was lower in the patients consuming olive oil and the fish-oil supplement than in the control group , and the uptake of LDL by macrophages was significantly lower in the group supplemented with fish oil . In conclusion , consumption of olive oil together with a dietary supplement of fish oil may be useful in the nutritional management of patients suffering from peripheral vascular disease in terms of increasing plasma n-3 long-chain polyunsaturated fatty acids and decreasing susceptibility of LDL to oxidation The ability of glycosaminoglycans to bind to a wide number of biologically active macromolecules has already been investigated . Recent clinical trials on the possible therapeutic benefits of glycosaminoglycans must be placed in perspective , even if they appear to be particularly encouraging , especially as regards the glycosaminoglycan effects on certain coagulation factors . A multicenter , medium-term , double-blind , crossover trial was performed by several Italian Lipid Clinics to determine whether administration of a medium molecular weight glycosaminoglycan ( Sulodexide ) has a significant clinical effect . Patients affected by peripheral vascular disease and /or hyperlipidemia ( type IIa , IIb and IV ) were su bmi tted to a 4-week wash-out period , followed by parenteral Sulodexide ( S ) or placebo ( P ) administration for 2 weeks , another 2 week wash-out period , parenteral crossover drug or P administration for 2 weeks and , finally , oral S administration for 6 months . Sulodexide lowered plasma viscosity and plasma fibrinogen in all patients . There was also a drop in triglycerides together with a rise in apo A-I and HDL-C in type IV hyperlipoproteinemics , whereas there was no significant effect on total or LDL-plasma cholesterol in type IIa and IIb patients . Moreover , there was a percent increase in peak flow and rest flow in the lower limbs of peripheral vascular disease patients . No side effects or intolerance phenomena were detected . The results indicate that Sulodexide administration may be useful in long-term treatment of patients with peripheral vascular disease and a concomitant increase in plasma triglycerides and /or fibrinogen and /or viscosity The aim of this study was to analyse the in vivo effect of a diet rich in extra-virgin olive oil and a fish-oil supplement on plasma and lipoprotein fatty-acid composition and on LDL susceptibility to oxidative modification in free-living Spanish male patients with peripheral vascular disease . A total of 12 patients were included in the experimental group which received extra virgin olive oil and a fish oil supplement ( group OF ) . On the other h and , 13 patients which had refined olive oil as the main visible fat were considered as Control group . Plasma triglycerides decreased significantly after three months of dietary intervention . The LDL and plasma fatty-acid pattern in the group OF was characterized by a significant increase in n-3 polyunsaturated fatty acids , mainly 20:5 n-3 and 22:6 n-3 . The slopes of LDL oxidative susceptibility were similar between baseline and endpoint values in both groups . However , the uptake of oxidized LDL by macrophages was significantly reduced in OF patients in comparison with the Control group . In conclusion , the daily intake of about 40 g/d of extra-virgin olive oil in combination with a daily supplement of 16 g of fish oil for 3 months in patients with peripheral vascular disease leads to a plasma-lipid profile less atherogenic than in patients having refined olive oil as the main visible food fat . The simultaneous consumption of alpha-tocopherol and natural antioxidants provided by extra-virgin olive oil seems to have a protective effect on the LDL susceptibility to oxidative modifications in spite of a higher proportion of n-3 polyunsaturated fatty acids The aim of the Probucol  Quantitative Regression Swedish Trial ( PQRST ) ( n = 303 ) was to investigate whether probucol ( 0.5 g BID ) added to diet and cholestyramine ( 8 g BID ) could retard progression or induce regression of femoral atherosclerosis in hypercholesterolemic ( > 6.86 mmol/L ) subjects .  Probucol did not induce regression over the 3-year trial period as estimated by change in lumen volume on quantitative arteriography of a 20-cm segment of the femoral artery . In this report we studied in a representative subgroup ( n = 72 ) whether the reduction in HDL concentrations induced by probucol could explain the failure of the drug to be effective . We analyzed the effects of treatment on HDL particle size subclasses . Probucol lowered the relative level of HDL2b , comprising the largest HDL particles , by 53 % and the protein concentration of HDL2b by 67 % . The protein reduction in HDL was mainly confined to the apolipoprotein A-I moiety . The change in lumen volume correlated significantly with change in HDL , ie , HDL cholesterol ( r = .34 , P < .01 ) , HDL2 cholesterol ( r = .37 , P < .01 ) , HDL2b protein ( r = .44 , P < .001 ) , and the relative HDL2b value ( r = .51 , P < .001 ) . The corresponding values for relative HDL2b , distribution calculated on the active ( n = 35 ) and placebo ( n = 37 ) groups separately were also significant ( r = .39 and .32 , respectively ; both P < .05 ) . The correlation between drug-induced change in the relative HDL2b concentration and change in atherosclerosis was independent of the alteration in triglyceride concentration and could not be explained by treatment interaction . ( ABSTRACT TRUNCATED AT 250 WORDS The Cholesterol Lowering Atherosclerosis Study ( CLAS ) is a prospect i ve , placebo-controlled , angiographic trial design ed to test the hypothesis that aggressive lowering of LDL cholesterol with concomitant increase in HDL cholesterol will reverse or retard the atherosclerotic process . Specifically , CLAS was design ed to determine whether combined therapy with colestipol plus niacin will produce clinical ly significant change in coronary , carotid , and femoral artery atherosclerosis and coronary bypass graft lesions . To this purpose , 188 subjects were r and omized to diet plus drug or diet plus placebo .  We report on method ological aspects of planning and evaluating this study , including the choice of the study population , procedures for recruitment , the experimental design including sample size considerations , methods for evaluating outcome , and methods for evaluating compliance to treatment . Comparison of baseline data indicated no significant differences between groups at the time of r and omization . Subjects were predominantly male , Caucasian , 54 years of age , 20 % above ideal weight , with normal blood pressure . The average age at bypass was 50 years . The average lipids were cholesterol ( 243 mg/dL ) , HDL ( 45 mg/dL ) , and LDL ( 168 mg/dL ) . Finally , the distribution of baseline coronary stenosis was equivalent between the two groups ( average number of lesions per subject = 10.6 ) BACKGROUND AND AIMS epidemiological studies suggest polyunsaturated fatty acids protect against the development of atherosclerosis . The aim of this study was to perform a r and omized controlled trial of gamma-linolenic and eicosapentaenoic acids in patients with lower limb atherosclerosis . Main outcome measures were : cholesterol and lipoprotein concentrations ; haemostatic and rheological variables ; the ankle brachial pressure index ; walking distance ; and cardiovascular events and death . METHODS 120 men and women with stable intermittent claudication were r and omized to 2 years treatment with either a combination of gamma-linolenic and eicosapentaenoic acids , or placebo . RESULTS 39 ( 65.0 cent ) of those taking fatty acids and 36 ( 60.0 cent ) of those taking placebo completed the trial . Lipid concentrations did not differ significantly during the trial . In those taking fatty acids , haematocrit was significantly higher than in the placebo group after 6 months ( 46.1 cent compared with 44.6 cent , P < /= 0.01 ) , and systolic blood pressure was significantly lower after 2 years ( 150|mmHg compared with 161.8|mmHg , < /= 0.05 ) . There was no difference in walking distance , but there was a small reduction in non-fatal coronary events in the fatty acid group ( 10 cent compared with 15 cent , P > 0.05 ) . CONCLUSIONS a combination of polyunsaturated fatty acids produced a statistically significant reduction in systolic blood pressure , but no other significant benefits on risk factors . The trend towards fewer coronary events in those taking fatty acids warrants further investigation The effects of 3-glucosaminoglycan sulfate on lipids and the hemorheologic parameters were observed in a preliminary double-blind crossover study in 30 hyperlipidemic peripheral vascular disease ( PVD ) patients . Parenteral adminis tration of the test drug was associated with a reduction in serum lipids , espe cially in triglyceride levels , and a lowering of fibrinogen , plasma viscosity , and whole blood viscosity levels . These effects justify the drug 's use in the treatment of PVD , especially when associated with hypertriglyceridemia and hemorheo logic disturbances The 2-year therapy effect on femoral atherosclerosis was evaluated in the Cholesterol Lowering Atherosclerosis Study ( CLAS ) , a r and omized , placebo-plus-diet-controlled angiographic trial of colestipol-niacin therapy plus diet in men with previous coronary bypass surgery . Different diet compositions were prescribed to enhance the differential in blood cholesterol responses between the two groups . The annual rate of change in computer-estimated atherosclerosis ( CEA ) , a measure of lumen abnormality , was evaluated between treatment groups . A significant per-segment therapy effect was found in segments with moderately severe atherosclerosis ( p less than 0.04 ) and in proximal segments ( p less than 0.02 ) . When segmental CEA measures were combined into a per-patient score using an adaptation of the National Heart 
    Output:
    