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: OBJECTIVE This study evaluated the effect of a atorvastatin-fenofibrate combination on lipid profile , in comparison to each drug alone , in patients with type 2 diabetes and combined hyperlipidemia ( CHL ) . RESEARCH DESIGN AND METHODS A total of 120 consecutive patients , who were free of coronary artery disease ( CAD ) at entry , were studied for a period of 24 weeks . These patients were r and omly assigned to atorvastatin ( 20 mg/day , n = 40 ) , micronized fenofibrate ( 200 mg/day , n = 40 ) , or a combination of both ( atorvastatin 20 mg/day plus fenofibrate 200 mg/day , n = 40 ) . The effect of treatment on LDL cholesterol , triglycerides ( TGs ) , HDL cholesterol , apolipoprotein A-I and B , lipoprotein(a ) , and plasma fibrinogen ( PF ) was recorded . Moreover , the percentage of patients that reached the American Diabetes Association treatment goals and the estimated CAD risk status were calculated . RESULTS No patient was withdrawn from the study because of side effects . The atorvastatin-fenofibrate combination reduced total cholesterol by 37 % , LDL cholesterol by 46 % , TGs by 50 % , and PF by 20 % , whereas it increased HDL cholesterol by 22 % ( P < 0.0001 for all ) . These changes were significantly better than those of both monotherapies . Of the patients on drug combination , 97.5 % reached the LDL cholesterol treatment goal of < 100 mg/dl , 100 % reached the desirable TG levels of < 200 mg/dl , and 60 % reached the optimal HDL cholesterol levels of > 45 mg/dl . These rates were significantly higher than those of both monotherapies . Combined treatment reduced the 10-year probability for myocardial infa rct ion from 21.6 to 4.2 % . CONCLUSIONS The atorvastatin-fenofibrate combination has a highly beneficial effect on all lipid parameters and PF in patients with type 2 diabetes and CHL . It improved patients ' CAD risk status significantly more than each drug alone Abstract —Interindividual variability in low density lipoprotein ( LDL ) cholesterol ( LDL-C ) response during treatment with statins is well documented but poorly understood . To investigate potential metabolic and genetic determinants of statin responsiveness , 19 patients with refractory heterozygous familial hypercholesterolemia were sequentially treated with placebo , atorvastatin ( 10 mg/d ) , bile acid sequestrant , and the 2 combined , each for 4 weeks . Levels of LDL-C , mevalonic acid ( MVA ) , 7-&agr;-OH-4-cholesten-3-one , and leukocyte LDL receptor and hydroxymethylglutaryl coenzyme A reductase mRNA were determined after each treatment period . Atorvastatin ( 10 mg/d ) reduced LDL-C by an overall mean of 32.5 % . Above-average responders ( & Dgr;LDL-C −39.5 % ) had higher basal MVA levels ( 34.4±6.1 & mgr;mol/L ) than did below-average responders ( & Dgr;LDL-C −23.6 % , P < 0.02 ; basal MVA 26.3±6.1 & mgr;mol/L , P < 0.01 ) . Fewer good responders compared with the poor responders had an apolipoprotein E4 allele ( 3 of 11 versus 6 of 8 , respectively;P < 0.05 ) . There were no baseline differences between them in 7-&agr;-OH-4-cholesten-3-one , hydroxymethylglutaryl coenzyme A reductase mRNA , or LDL receptor mRNA , but the latter increased in the good responders on combination therapy ( P < 0.05 ) . Severe mutations were not more common in poor than in good responders . We conclude that poor responders to statins have a low basal rate of cholesterol synthesis that may be secondary to a genetically determined increase in cholesterol absorption , possibly mediated by apolipoprotein E4 . If so , statin responsiveness could be enhanced by reducing dietary cholesterol intake or inhibiting absorption OBJECTIVE It has been repeatedly proven that statins improve endothelial function in isolated hypercholesterolaemia but there is far less evidence in the case of combined hyperlipidaemia . Studies assessing the effects of fibrates on endothelium have been neglected . Therefore , we conducted a trial in which the effects of fenofibrate and atorvastatin monotherapy on both endothelium-dependent vascular reactivity and biochemical parameters were compared in patients with combined hyperlipidaemia . METHODS 29 otherwise healthy males ( aged 47.4+/-7.8 years ) with combined hyperlipidaemia ( total cholesterol 7.55+/-1.20 mmol/l , triglycerides 5.41+/-4.54 mmol/l ) were included into the r and omised , single-blind , cross-over study to receive either 200 mg of micronised fenofibrate or 10 mg of atorvastatin daily -- each of the drugs for a period of 10 weeks . Analysed biochemical parameters were as follows : serum total- , LDL- and HDL-cholesterol , apolipoproteins A-I and B , triglycerides , fibrinogen , uric acid , C-reactive protein ( CRP ) , insulin , and homocysteine . Endothelial function was investigated by duplex Doppler ultrasonography at the brachial artery . Two indices of endothelial-dependent postischaemic changes were used - the recently introduced index of peak blood flow ( PBF ) representing the level of reactive hyperaemia and traditional flow-mediated dilatation ( FMD ) . RESULTS We observed a small improvement in FMD after both fenofibrate and atorvastatin ( from 2.26 % to 2.98 % and 2.87 % , respectively ; NS ) . PBF increased from 448 ml/min to 536 ml/min after fenofibrate ( P=0.04 ) and to 570 ml/min after atorvastatin ( P=0.03 ) . The effects of both fenofibrate and atorvastatin on endothelial function did not differ significantly ( P-values of 0.82 and 0.47 for FMD and PBF , respectively ) . Significant correlations ( P<0.01 ) between the changes of vascular reactivity and biochemical indices were found between FMD and CRP ( r=-0.60 ) and between both FMD and PBF , and insulinaemia ( r=-0.48 and -0.56 , respectively ) only during treatment with fenofibrate . CONCLUSIONS Both fenofibrate and atorvastatin significantly improved endothelium-dependent vascular reactivity without mutual difference . The PBF was superior to FMD for the detection of this improvement . The beneficial effect of both drugs did not correlate with the change of lipid profile during therapy . The improvement of vascular reactivity during treatment with fenofibrate ( opposed to atorvastatin ) was related to the reduction of indirect marker of chronic vessel wall inflammation and of insulin resistance . The PBF was more reproducible than FMD because of considerably lower intra-subject variability Abstract . Objectives : In patients with mixed lipid disorders , monotherapy may not effectively control all lipid abnormalities . We undertook this study to assess the efficacy of fenofibrate in combination with atorvastatin in patients with severe mixed dyslipidemia . Methods : This was an 18-week , open-label study conducted in our lipid clinic . After a 6-week dietary baseline phase , patients received 200 mg/day micronised fenofibrate for 6 weeks . At the end of this period the subjects discontinued this treatment and received 40 mg/day atorvastatin for 6 weeks . Finally 200 mg/day of micronised fenofibrate was added to the statin therapy . Results : Administration of micronised fenofibrate reduced serum triglycerides ( P<0.01 ) and total cholesterol and low-density lipoprotein ( LDL ) cholesterol ( P<0.05 for both parameters ) , while it evoked a significant increase in serum high-density lipoprotein ( HDL ) cholesterol levels ( P<0.05 ) . Atorvastatin monotherapy induced a more pronounced decrease of total and LDL cholesterol . However , plasma triglycerides , although significantly lower than baseline values ( P<0.05 ) , were higher than the values observed during treatment with fenofibrate . Moreover , serum HDL cholesterol concentrations were higher during fibrate therapy than during the statin one . During the combination therapy , the decrease in triglycerides was greater than that observed with fenofibrate alone , while the decrease in LDL cholesterol was more pronounced than that observed with atorvastatin alone . Conclusion : The combination of atorvastatin with micronised fenofibrate in patients with severe mixed dyslipidemia may have a favourable effect on some major coronary artery disease risk factors An elevated plasma fibrinogen level is increasingly accepted as an independent risk indicator of cardiovascular disease . This has enhanced the interest in identifying agents that can normalize elevated plasma fibrinogen levels . One group of agents with this capacity are the fibric acid derivatives , e.g. ciprofibrate and gemfibrozil . We studied fibrinogen levels after 12 weeks of treatment with ciprofibrate  ( n = 48 ) and gemfibrozil  ( n = 51 ) in hypercholesterolenic patients . The correlation of the decrease in fibrinogen with lipid lowering and the contribution of the acute phase and genetic polymorphisms to this decrease were also evaluated . After 12 weeks of treatment , the fibrinogen levels were significantly decreased ( p < 0.0005 ) with both drugs , although the decrease in the ciprofibrate group ( mean 3.4 g/l pre-treatment to 2.4 g/l after 12 weeks ) was larger than in the gemfibrozil group ( mean 3.4 g/l to 3.0 g/l ) . The lipid lowering effect was comparable for the two drugs but there was no correlation for either ciprofibrate or gemfibrozil between the lipid lowering and the magnitude or the velocity of the fibrinogen lowering effect . An attenuation of the major regulatory mechanism of plasma fibrinogen levels , the acute phase reaction , was invoked as the underlying mechanism . However , pre-treatment C-reactive protein levels were not increased and did not change after treatment . Moreover , no effects of the polymorphisms of the fibrinogen beta-gene on the decrease of the plasma fibrinogen levels were observed . This suggests that a new , as yet unknown , mechanism is involved in fibrinogen lowering by fibrates OBJECTIVE To determine the efficacy and safety of a statin-fibrate combination in diabetes patients . DESIGN . : An open 21-month trial in which each patient first received the single drug for 6 months and then a combination of the two for 1 year . SETTING Three lipid clinics in university-based tertiary care hospitals . PATIENTS One hundred and forty-eight patients with type 2 ( non-insulin-dependent , NIDDM ) diabetes mellitus under stable control for 3 months by means of diet and oral hypoglycaemic medication . INTERVENTION Patients from one clinic ( n = 48 ) received bezafibrate slow release ( 400 mg day-1 ) , and patients from the other two clinics ( n = 100 ) received simvastatin 20 mg day-1 . Six months later , all patients were switched to a daily combination of 400 mg bezafibrate slow release and 20 mg simvastatin for 1 year . RESULTS The combination of statin and fibrate led to a 23 % reduction in total cholesterol , 42 % reduction in triglycerides , 29 % reduction in LDL-c , 25 % increase in HDL-c , 10 % decrease in fibrinogen and 19 % reduction of Lp(a ) levels , and a decrease in the cholesterol/HDL-c ratio ( from 8.9 to 5.4 ) in all 148 patients . Cardiovascular ( CV ) event rate was significantly reduced from 9.5 % during the first 6 months of the study to less than 2 % during the last year of the study ( whilst on combination Rx ) . Side-effects with all treatments included only two patients who developed myopathy when on the combined regimen and one on the single statin regimen . However , plasma creatinine phosphokinase ( CPK ) levels doubled ( but remained within the normal range ) in most of the patients on combination therapy , compared with only a mild increase in patients receiving a single medication . CONCLUSIONS The statin and fibrate combination was found to be more efficacious than a single medication for treatment of diabetic dyslipidaemia , as evidence d by improvement in the lipoprotein profile , reductions in Lp(a ) , fibrinogen and CV event rate , and almost no clinical ly significant side-effects OBJECTIVES We compared vascular and metabolic responses ( and adverse responses ) to statin and fibrate therapies alone or in combination in patients with combined hyperlipidemia . BACKGROUND The mechanisms of action for statins and fibrates are distinct . M 
    Output:
    
agent
Monotherapy with either fibrates or statins suggested a significantly greater effect of fibrates in lowering plasma Fib concentrations .
According to these findings , mechanisms associated with fibrinogen metabolism might be responsible for the distinct effects of statins and fibrates in reducing cardiovascular endpoints
***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: OBJECTIVE This study evaluated the effect of a atorvastatin-fenofibrate combination on lipid profile , in comparison to each drug alone , in patients with type 2 diabetes and combined hyperlipidemia ( CHL ) . RESEARCH DESIGN AND METHODS A total of 120 consecutive patients , who were free of coronary artery disease ( CAD ) at entry , were studied for a period of 24 weeks . These patients were r and omly assigned to atorvastatin ( 20 mg/day , n = 40 ) , micronized fenofibrate ( 200 mg/day , n = 40 ) , or a combination of both ( atorvastatin 20 mg/day plus fenofibrate 200 mg/day , n = 40 ) . The effect of treatment on LDL cholesterol , triglycerides ( TGs ) , HDL cholesterol , apolipoprotein A-I and B , lipoprotein(a ) , and plasma fibrinogen ( PF ) was recorded . Moreover , the percentage of patients that reached the American Diabetes Association treatment goals and the estimated CAD risk status were calculated . RESULTS No patient was withdrawn from the study because of side effects . The atorvastatin-fenofibrate combination reduced total cholesterol by 37 % , LDL cholesterol by 46 % , TGs by 50 % , and PF by 20 % , whereas it increased HDL cholesterol by 22 % ( P < 0.0001 for all ) . These changes were significantly better than those of both monotherapies . Of the patients on drug combination , 97.5 % reached the LDL cholesterol treatment goal of < 100 mg/dl , 100 % reached the desirable TG levels of < 200 mg/dl , and 60 % reached the optimal HDL cholesterol levels of > 45 mg/dl . These rates were significantly higher than those of both monotherapies . Combined treatment reduced the 10-year probability for myocardial infa rct ion from 21.6 to 4.2 % . CONCLUSIONS The atorvastatin-fenofibrate combination has a highly beneficial effect on all lipid parameters and PF in patients with type 2 diabetes and CHL . It improved patients ' CAD risk status significantly more than each drug alone Abstract —Interindividual variability in low density lipoprotein ( LDL ) cholesterol ( LDL-C ) response during treatment with statins is well documented but poorly understood . To investigate potential metabolic and genetic determinants of statin responsiveness , 19 patients with refractory heterozygous familial hypercholesterolemia were sequentially treated with placebo , atorvastatin ( 10 mg/d ) , bile acid sequestrant , and the 2 combined , each for 4 weeks . Levels of LDL-C , mevalonic acid ( MVA ) , 7-&agr;-OH-4-cholesten-3-one , and leukocyte LDL receptor and hydroxymethylglutaryl coenzyme A reductase mRNA were determined after each treatment period . Atorvastatin ( 10 mg/d ) reduced LDL-C by an overall mean of 32.5 % . Above-average responders ( & Dgr;LDL-C −39.5 % ) had higher basal MVA levels ( 34.4±6.1 & mgr;mol/L ) than did below-average responders ( & Dgr;LDL-C −23.6 % , P < 0.02 ; basal MVA 26.3±6.1 & mgr;mol/L , P < 0.01 ) . Fewer good responders compared with the poor responders had an apolipoprotein E4 allele ( 3 of 11 versus 6 of 8 , respectively;P < 0.05 ) . There were no baseline differences between them in 7-&agr;-OH-4-cholesten-3-one , hydroxymethylglutaryl coenzyme A reductase mRNA , or LDL receptor mRNA , but the latter increased in the good responders on combination therapy ( P < 0.05 ) . Severe mutations were not more common in poor than in good responders . We conclude that poor responders to statins have a low basal rate of cholesterol synthesis that may be secondary to a genetically determined increase in cholesterol absorption , possibly mediated by apolipoprotein E4 . If so , statin responsiveness could be enhanced by reducing dietary cholesterol intake or inhibiting absorption OBJECTIVE It has been repeatedly proven that statins improve endothelial function in isolated hypercholesterolaemia but there is far less evidence in the case of combined hyperlipidaemia . Studies assessing the effects of fibrates on endothelium have been neglected . Therefore , we conducted a trial in which the effects of fenofibrate and atorvastatin monotherapy on both endothelium-dependent vascular reactivity and biochemical parameters were compared in patients with combined hyperlipidaemia . METHODS 29 otherwise healthy males ( aged 47.4+/-7.8 years ) with combined hyperlipidaemia ( total cholesterol 7.55+/-1.20 mmol/l , triglycerides 5.41+/-4.54 mmol/l ) were included into the r and omised , single-blind , cross-over study to receive either 200 mg of micronised fenofibrate or 10 mg of atorvastatin daily -- each of the drugs for a period of 10 weeks . Analysed biochemical parameters were as follows : serum total- , LDL- and HDL-cholesterol , apolipoproteins A-I and B , triglycerides , fibrinogen , uric acid , C-reactive protein ( CRP ) , insulin , and homocysteine . Endothelial function was investigated by duplex Doppler ultrasonography at the brachial artery . Two indices of endothelial-dependent postischaemic changes were used - the recently introduced index of peak blood flow ( PBF ) representing the level of reactive hyperaemia and traditional flow-mediated dilatation ( FMD ) . RESULTS We observed a small improvement in FMD after both fenofibrate and atorvastatin ( from 2.26 % to 2.98 % and 2.87 % , respectively ; NS ) . PBF increased from 448 ml/min to 536 ml/min after fenofibrate ( P=0.04 ) and to 570 ml/min after atorvastatin ( P=0.03 ) . The effects of both fenofibrate and atorvastatin on endothelial function did not differ significantly ( P-values of 0.82 and 0.47 for FMD and PBF , respectively ) . Significant correlations ( P<0.01 ) between the changes of vascular reactivity and biochemical indices were found between FMD and CRP ( r=-0.60 ) and between both FMD and PBF , and insulinaemia ( r=-0.48 and -0.56 , respectively ) only during treatment with fenofibrate . CONCLUSIONS Both fenofibrate and atorvastatin significantly improved endothelium-dependent vascular reactivity without mutual difference . The PBF was superior to FMD for the detection of this improvement . The beneficial effect of both drugs did not correlate with the change of lipid profile during therapy . The improvement of vascular reactivity during treatment with fenofibrate ( opposed to atorvastatin ) was related to the reduction of indirect marker of chronic vessel wall inflammation and of insulin resistance . The PBF was more reproducible than FMD because of considerably lower intra-subject variability Abstract . Objectives : In patients with mixed lipid disorders , monotherapy may not effectively control all lipid abnormalities . We undertook this study to assess the efficacy of fenofibrate in combination with atorvastatin in patients with severe mixed dyslipidemia . Methods : This was an 18-week , open-label study conducted in our lipid clinic . After a 6-week dietary baseline phase , patients received 200 mg/day micronised fenofibrate for 6 weeks . At the end of this period the subjects discontinued this treatment and received 40 mg/day atorvastatin for 6 weeks . Finally 200 mg/day of micronised fenofibrate was added to the statin therapy . Results : Administration of micronised fenofibrate reduced serum triglycerides ( P<0.01 ) and total cholesterol and low-density lipoprotein ( LDL ) cholesterol ( P<0.05 for both parameters ) , while it evoked a significant increase in serum high-density lipoprotein ( HDL ) cholesterol levels ( P<0.05 ) . Atorvastatin monotherapy induced a more pronounced decrease of total and LDL cholesterol . However , plasma triglycerides , although significantly lower than baseline values ( P<0.05 ) , were higher than the values observed during treatment with fenofibrate . Moreover , serum HDL cholesterol concentrations were higher during fibrate therapy than during the statin one . During the combination therapy , the decrease in triglycerides was greater than that observed with fenofibrate alone , while the decrease in LDL cholesterol was more pronounced than that observed with atorvastatin alone . Conclusion : The combination of atorvastatin with micronised fenofibrate in patients with severe mixed dyslipidemia may have a favourable effect on some major coronary artery disease risk factors An elevated plasma fibrinogen level is increasingly accepted as an independent risk indicator of cardiovascular disease . This has enhanced the interest in identifying agents that can normalize elevated plasma fibrinogen levels . One group of agents with this capacity are the fibric acid derivatives , e.g. ciprofibrate and gemfibrozil . We studied fibrinogen levels after 12 weeks of treatment with ciprofibrate  ( n = 48 ) and gemfibrozil  ( n = 51 ) in hypercholesterolenic patients . The correlation of the decrease in fibrinogen with lipid lowering and the contribution of the acute phase and genetic polymorphisms to this decrease were also evaluated . After 12 weeks of treatment , the fibrinogen levels were significantly decreased ( p < 0.0005 ) with both drugs , although the decrease in the ciprofibrate group ( mean 3.4 g/l pre-treatment to 2.4 g/l after 12 weeks ) was larger than in the gemfibrozil group ( mean 3.4 g/l to 3.0 g/l ) . The lipid lowering effect was comparable for the two drugs but there was no correlation for either ciprofibrate or gemfibrozil between the lipid lowering and the magnitude or the velocity of the fibrinogen lowering effect . An attenuation of the major regulatory mechanism of plasma fibrinogen levels , the acute phase reaction , was invoked as the underlying mechanism . However , pre-treatment C-reactive protein levels were not increased and did not change after treatment . Moreover , no effects of the polymorphisms of the fibrinogen beta-gene on the decrease of the plasma fibrinogen levels were observed . This suggests that a new , as yet unknown , mechanism is involved in fibrinogen lowering by fibrates OBJECTIVE To determine the efficacy and safety of a statin-fibrate combination in diabetes patients . DESIGN . : An open 21-month trial in which each patient first received the single drug for 6 months and then a combination of the two for 1 year . SETTING Three lipid clinics in university-based tertiary care hospitals . PATIENTS One hundred and forty-eight patients with type 2 ( non-insulin-dependent , NIDDM ) diabetes mellitus under stable control for 3 months by means of diet and oral hypoglycaemic medication . INTERVENTION Patients from one clinic ( n = 48 ) received bezafibrate slow release ( 400 mg day-1 ) , and patients from the other two clinics ( n = 100 ) received simvastatin 20 mg day-1 . Six months later , all patients were switched to a daily combination of 400 mg bezafibrate slow release and 20 mg simvastatin for 1 year . RESULTS The combination of statin and fibrate led to a 23 % reduction in total cholesterol , 42 % reduction in triglycerides , 29 % reduction in LDL-c , 25 % increase in HDL-c , 10 % decrease in fibrinogen and 19 % reduction of Lp(a ) levels , and a decrease in the cholesterol/HDL-c ratio ( from 8.9 to 5.4 ) in all 148 patients . Cardiovascular ( CV ) event rate was significantly reduced from 9.5 % during the first 6 months of the study to less than 2 % during the last year of the study ( whilst on combination Rx ) . Side-effects with all treatments included only two patients who developed myopathy when on the combined regimen and one on the single statin regimen . However , plasma creatinine phosphokinase ( CPK ) levels doubled ( but remained within the normal range ) in most of the patients on combination therapy , compared with only a mild increase in patients receiving a single medication . CONCLUSIONS The statin and fibrate combination was found to be more efficacious than a single medication for treatment of diabetic dyslipidaemia , as evidence d by improvement in the lipoprotein profile , reductions in Lp(a ) , fibrinogen and CV event rate , and almost no clinical ly significant side-effects OBJECTIVES We compared vascular and metabolic responses ( and adverse responses ) to statin and fibrate therapies alone or in combination in patients with combined hyperlipidemia . BACKGROUND The mechanisms of action for statins and fibrates are distinct . M 
    Output:
    