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: We compared the effect of simvastatin versus simvastatin combined with ezetimibe on hemostasis and inflammation after acute coronary events [ acute coronary syndromes ( ACS ) ] . In an investigator-initiated , double-blind , placebo-controlled , r and omized study , patients with ACS were assigned to 40 mg/d of simvastatin + 10 mg/d of ezetimibe ( n = 26 ) or 40 mg/d of simvastatin + placebo ( n = 28 ) administered for 2 months . Markers of coagulation ( prothrombin fragments 1.2 , thrombin-antithrombin complexes , free tissue factor pathway inhibitor ) , fibrinolysis [ plasminogen activator inhibitor-1 , clot lysis time ( CLT ) ] , platelet activation ( soluble CD40 lig and , β-thromboglobulin , thromboxane B2 ) , oxidative stress [ 8-iso-prostagl and in F2α ( 8-iso-PGF2α ) ] , and inflammation ( interleukin-6 , interleukin-18 , and interleukin-1β ) were measured within the first 12 hours of ACS and at 1 and 2 months of therapy . A final analysis comprised 20 patients in the simvastatin + ezetimibe group and 26 patients in the simvastatin + placebo group . Both groups were similar with regard to demographics , risk factors , medications , and routine laboratory results . Inflammatory , coagulation , and platelet markers did not differ between both treatment groups at all time points . Reductions in low-density lipoprotein cholesterol , CLT , plasminogen activator inhibitor-1 , and 8-iso-PGF2α were significantly greater ( by 10 % , 8.7 % , 17.5 % , and 22.4 % ) in the simvastatin + ezetimibe group after 1 month , with further decreases in CLT and 8-iso-PGF2α at 2 months ( all P < 0.05 ) . These changes were not associated with lipid and inflammatory parameters . In conclusion , compared with simvastatin alone , simvastatin + ezetimibe results in a greater suppression of oxidative stress and enhanced fibrinolysis in patients with ACS , indicating that ezetimibe might exert cholesterol-independent actions in humans ( NCT00725829 ) The aim of this study was to assess the strength of hemostatic effects of ezetimibe , administered alone or in combination with simvastatin , in patients with isolated hypercholesterolemia . One hundred and four patients with isolated primary hypercholesterolemia were r and omized to one of four treatment groups , simultaneously treated for 90 days with ezetimibe ( 10 mg daily ) , simvastatin ( 40 mg daily ) , ezetimibe ( 10 mg daily ) plus simvastatin ( 40 mg daily ) , or placebo .  Plasma lipids/lipoproteins and hemostatic cardiovascular risk factors were assessed on the day of r and omization and after 30 and 90 days of therapy . Despite improving lipid/lipoprotein profile by both simvastatin and ezetimibe , only simvastatin reduced plasma levels/activity of fibrinogen , factor VII , factor X , von Willebr and factor , and plasminogen activator inhibitor-1 . The strongest effects on plasma lipids/lipoproteins and the assessed hemostatic variables were observed when patients were treated with both simvastatin and ezetimibe . With the exception of oxidized low-density lipoproteins , the hemostatic effects of simvastatin or simvastatin plus ezetimibe did not correlate with the changes in plasma lipids/lipoproteins . Our study shows that simvastatin is a more effective agent than ezetimibe in affecting coagulation and fibrinolysis in individuals with isolated hypercholesterolemia . It also suggests that the combined administration of simvastatin and ezetimibe may bring more benefits to patients than monotherapy with only one of these agents Adiponectin can suppress atherogenesis by inhibiting the adherence of monocytes , reducing their phagocytic activity , and suppressing the accumulation of modified lipoproteins in the vascular wall . Contradictory data have been reported about the effect of statins on adiponectin plasma levels . In this work , adiponectin plasma levels were measured in 102 statin-free subjects from the Spanish population of the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration ( ACTFAST ) study , a 12-week , prospect i ve , multi-centre , open-label trial which enrolled subjects with coronary heart disease , coronary heart disease-equivalent or a 10-year coronary heart disease risk > 20 % . Subjects were assigned to atorvastatin ( 10 - 80 mg/day ) based on low-density lipoprotein (LDL)-cholesterol concentration at screening . For comparison , age and gender-matched blood donors ( N=40 ) were used as controls . Control subjects did not present hypertension , hypercholesterolemia , diabetes , metabolic syndrome and history of cardiovascular diseases . Adiponectin levels were diminished in patients at high cardiovascular risk compared with control subjects [ 4166 ( 3661 - 4740 ) vs 5806 ( 4764 - 7075 ) ng/ml respectively ; geometric mean ( 95 % CI ) ; P<0.0001 ] . In the whole population , atorvastatin treatment increased adiponectin levels [ 9.7 (3.2 - 16.7);% Change ( 95 % CI ) ; P=0.003 ] . This increment was in a dose-dependent manner ; maximal effect observed with atorvastatin 80 mg/d [ 24.7 ( 5.7 - 47.1 ) ; P=0.01 ] . Adiponectin concentrations were positively correlated with high-density lipoprotein-cholesterol both before and after atorvastatin treatment . No association was observed between adiponectin and LDL-cholesterol before and after atorvastatin treatment . In conclusion , atorvastatin increased adiponectin plasma levels in subjects at high cardiovascular risk , revealing a novel anti-inflammatory effect of this drug AIM Ezetimibe selectively blocks intestinal cholesterol absorption by inhibiting Niemann-Pick C1-like 1 ( NPC1L1 ) and reducing LDL cholesterol ( LDL-C ) . In animals , ezetimibe reversed diet-induced obesity , liver steatosis , and insulin resistance . In humans , its potential effects on liver steatosis and insulin resistance have been suggested . We investigated the effects of ezetimibe on postpr and ial hyperlipidaemia and hyperglycaemia in obese subjects with dyslipidaemia in a double-blind r and omized crossover trial . METHODS Twenty obese men with hypertriglyceridaemia were assigned r and omly to an ezetimibe- or a placebo-precedence-treated group . Subjects in the ezetimibe group were treated with ezetimibe ( 10 mg/day ) for the first 4 weeks , followed by a 4-week interval and then treated with placebo for another 4 weeks . The placebo group received these treatments in reverse order . Subjects were requested to fast for at least 12 hours and then received a st and ard meal . Blood sample s were collected at 0 , 30 , 60 , 120 , 240 , 360 and 480 minutes after the meal on Days 0 , 28 , 56 and 84 and were used to measure the lipid and glucose metabolism markers . RESULTS Ezetimibe significantly decreased the postpr and ial serum triglyceride excursion ( p=0.01 ) and fasting serum LDL-C , remnant-like particles(RLP ) and ApoB48 levels ( p<0.05 ) . Postpr and ial glucose excursion , serum insulin levels , serum glucose-dependent insulinotropic polypeptide ( GIP ) and active glucagon-like peptide-1 ( GLP-1 ) were not significantly affected by ezetimibe treatment . CONCLUSION Ezetimibe restored the postpr and ial dysregulation of lipid but did not affect glucose metabolism in a double-blind r and omized crossover trial Background — Statins lower low-density lipoprotein cholesterol ( LDL-C ) and high-sensitivity C-reactive protein ( hs-CRP ) ; addition of ezetimibe to statins further reduces LDL-C and hs-CRP . An analysis of the relationship between achieved LDL-C and hs-CRP targets and outcomes for simvastatin and ezetimibe/simvastatin was prespecified in Improved Reduction of Outcomes : Vytorin Efficacy International Trial ( IMPROVE-IT ) . Methods and Results — The IMPROVE-IT trial r and omly assigned 18 144 patients stabilized after acute coronary syndrome to simvastatin or ezetimibe/simvastatin .  LDL-C and hs-CRP were measured at baseline and 1 month after r and omization . Outcomes were assessed in those achieving one or both of the prespecified targets of LDL-C<70 mg/dL and hs-CRP<2 mg/L versus achieving neither target , adjusting for differences in baseline characteristics . An exploratory analysis examined targets of LDL-C<50 mg/dL and hs-CRP<1 mg/L. Patients meeting both targets at baseline , with no 1-month values , or with end points before 1 month were excluded . Of 15 179 patients , 39 % achieved the dual LDL-C ( < 70 mg/dL ) and hs-CRP ( < 2 mg/L ) targets at 1 month , 14 % met neither target , 14 % met only the hs-CRP target , and 33 % met only the LDL-C target . Those achieving dual targets had lower primary end point rates than those meeting neither target ( cardiovascular death , major coronary event , or stroke ; 38.9 % versus 28.0 % ; adjusted hazard ratio , 0.73 ; 0.66–0.81 ; P<0.001 ) . More patients treated with ezetimibe/simvastatin  met dual targets than those treated with simvastatin alone ( 50 % versus 29 % , P<0.001 ) . The association of dual-target attainment with improved outcomes was similar irrespective of treatment assignment ( P-interaction=0.65 ) . Similar findings were observed using the exploratory targets . Conclusions — Significantly more patients treated with ezetimibe/simvastatin  met prespecified and exploratory dual LDL-C and hs-CRP targets than patients treated with simvastatin alone . Reaching both LDL-C and hs-CRP targets was associated with improved outcomes after multivariable adjustment . Clinical Trial Registration — URL : http://www . clinical trials.gov ; Unique identifier : NCT00202878 Lipid-lowering therapy is associated with  reduced cardiovascular risk .  The aim of the present study was to investigate whether lipid-lowering therapy might be associated with changes in the concentrations of metabolically important hormone concentrations . We performed a r and omised cross-over open-label trial with atorvastatin ( 10 mg/day ) and fenofibrate ( 200 mg/day ) , each for 6 weeks separated by a 6-week washout period in 13 patients ( 5 men , 8 women , age 60.0±6.8 years , body mass index 30.0±3.0 kg/m2 ) with type 2 diabetes mellitus and mixed hyperlipoproteinaemia .  Plasma ghrelin ( RIA , Phoenix Pharmaceuticals , Mountain View , CA , USA ) , adiponectin ( ELISA , Biovendor , Heidelberg , Germany ) as well as resistin ( ELISA , Linco Research , St. Charles , MO , USA ) concentrations were measured before and after atorvastatin as well as before and after fenofibrate . Ghrelin ( 462±84 pg/ml before vs. 464±102 pg/ml after atorvastatin , n.s . ; 454±85 pg/ml before vs. 529±266 pg/ml after fenofibrate , n.s . ) , resistin ( 24.4±7.4 pg/ml before vs. 23.7±9.1 pg/ml after atorvastatin , n.s . ; 23.4±8.2 pg/ml before vs. 19.9±5.5 pg/ml after fenofibrate , n.s . ) , adiponectin ( 10.89±5.33 pg/ml before vs. 12.41±5.75 pg/ml after atorvastatin , n.s . ; 12.58±9.87 pg/ml before vs. 10.27±5.23 pg/ml after fenofibrate , n.s . ) and insulin levels did not change significantly during lipid-lowering therapy . In patients with type 2 diabetes and mixed hyperlipoproteinaemia , short-term atorvastatin as well as fenofibrate therapy had no significant effects on adiponectin , ghrelin or resistin levels Weight loss and hypolipidemic drugs can improve lipid and adip 
    Output:
    
agent
CONCLUSIONS The results suggested that ezetimibe add-on to statin therapy is associated with an enhanced TNF-α-lowering effect  compared with statin monotherapy .
***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: We compared the effect of simvastatin versus simvastatin combined with ezetimibe on hemostasis and inflammation after acute coronary events [ acute coronary syndromes ( ACS ) ] . In an investigator-initiated , double-blind , placebo-controlled , r and omized study , patients with ACS were assigned to 40 mg/d of simvastatin + 10 mg/d of ezetimibe ( n = 26 ) or 40 mg/d of simvastatin + placebo ( n = 28 ) administered for 2 months . Markers of coagulation ( prothrombin fragments 1.2 , thrombin-antithrombin complexes , free tissue factor pathway inhibitor ) , fibrinolysis [ plasminogen activator inhibitor-1 , clot lysis time ( CLT ) ] , platelet activation ( soluble CD40 lig and , β-thromboglobulin , thromboxane B2 ) , oxidative stress [ 8-iso-prostagl and in F2α ( 8-iso-PGF2α ) ] , and inflammation ( interleukin-6 , interleukin-18 , and interleukin-1β ) were measured within the first 12 hours of ACS and at 1 and 2 months of therapy . A final analysis comprised 20 patients in the simvastatin + ezetimibe group and 26 patients in the simvastatin + placebo group . Both groups were similar with regard to demographics , risk factors , medications , and routine laboratory results . Inflammatory , coagulation , and platelet markers did not differ between both treatment groups at all time points . Reductions in low-density lipoprotein cholesterol , CLT , plasminogen activator inhibitor-1 , and 8-iso-PGF2α were significantly greater ( by 10 % , 8.7 % , 17.5 % , and 22.4 % ) in the simvastatin + ezetimibe group after 1 month , with further decreases in CLT and 8-iso-PGF2α at 2 months ( all P < 0.05 ) . These changes were not associated with lipid and inflammatory parameters . In conclusion , compared with simvastatin alone , simvastatin + ezetimibe results in a greater suppression of oxidative stress and enhanced fibrinolysis in patients with ACS , indicating that ezetimibe might exert cholesterol-independent actions in humans ( NCT00725829 ) The aim of this study was to assess the strength of hemostatic effects of ezetimibe , administered alone or in combination with simvastatin , in patients with isolated hypercholesterolemia . One hundred and four patients with isolated primary hypercholesterolemia were r and omized to one of four treatment groups , simultaneously treated for 90 days with ezetimibe ( 10 mg daily ) , simvastatin ( 40 mg daily ) , ezetimibe ( 10 mg daily ) plus simvastatin ( 40 mg daily ) , or placebo .  Plasma lipids/lipoproteins and hemostatic cardiovascular risk factors were assessed on the day of r and omization and after 30 and 90 days of therapy . Despite improving lipid/lipoprotein profile by both simvastatin and ezetimibe , only simvastatin reduced plasma levels/activity of fibrinogen , factor VII , factor X , von Willebr and factor , and plasminogen activator inhibitor-1 . The strongest effects on plasma lipids/lipoproteins and the assessed hemostatic variables were observed when patients were treated with both simvastatin and ezetimibe . With the exception of oxidized low-density lipoproteins , the hemostatic effects of simvastatin or simvastatin plus ezetimibe did not correlate with the changes in plasma lipids/lipoproteins . Our study shows that simvastatin is a more effective agent than ezetimibe in affecting coagulation and fibrinolysis in individuals with isolated hypercholesterolemia . It also suggests that the combined administration of simvastatin and ezetimibe may bring more benefits to patients than monotherapy with only one of these agents Adiponectin can suppress atherogenesis by inhibiting the adherence of monocytes , reducing their phagocytic activity , and suppressing the accumulation of modified lipoproteins in the vascular wall . Contradictory data have been reported about the effect of statins on adiponectin plasma levels . In this work , adiponectin plasma levels were measured in 102 statin-free subjects from the Spanish population of the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration ( ACTFAST ) study , a 12-week , prospect i ve , multi-centre , open-label trial which enrolled subjects with coronary heart disease , coronary heart disease-equivalent or a 10-year coronary heart disease risk > 20 % . Subjects were assigned to atorvastatin ( 10 - 80 mg/day ) based on low-density lipoprotein (LDL)-cholesterol concentration at screening . For comparison , age and gender-matched blood donors ( N=40 ) were used as controls . Control subjects did not present hypertension , hypercholesterolemia , diabetes , metabolic syndrome and history of cardiovascular diseases . Adiponectin levels were diminished in patients at high cardiovascular risk compared with control subjects [ 4166 ( 3661 - 4740 ) vs 5806 ( 4764 - 7075 ) ng/ml respectively ; geometric mean ( 95 % CI ) ; P<0.0001 ] . In the whole population , atorvastatin treatment increased adiponectin levels [ 9.7 (3.2 - 16.7);% Change ( 95 % CI ) ; P=0.003 ] . This increment was in a dose-dependent manner ; maximal effect observed with atorvastatin 80 mg/d [ 24.7 ( 5.7 - 47.1 ) ; P=0.01 ] . Adiponectin concentrations were positively correlated with high-density lipoprotein-cholesterol both before and after atorvastatin treatment . No association was observed between adiponectin and LDL-cholesterol before and after atorvastatin treatment . In conclusion , atorvastatin increased adiponectin plasma levels in subjects at high cardiovascular risk , revealing a novel anti-inflammatory effect of this drug AIM Ezetimibe selectively blocks intestinal cholesterol absorption by inhibiting Niemann-Pick C1-like 1 ( NPC1L1 ) and reducing LDL cholesterol ( LDL-C ) . In animals , ezetimibe reversed diet-induced obesity , liver steatosis , and insulin resistance . In humans , its potential effects on liver steatosis and insulin resistance have been suggested . We investigated the effects of ezetimibe on postpr and ial hyperlipidaemia and hyperglycaemia in obese subjects with dyslipidaemia in a double-blind r and omized crossover trial . METHODS Twenty obese men with hypertriglyceridaemia were assigned r and omly to an ezetimibe- or a placebo-precedence-treated group . Subjects in the ezetimibe group were treated with ezetimibe ( 10 mg/day ) for the first 4 weeks , followed by a 4-week interval and then treated with placebo for another 4 weeks . The placebo group received these treatments in reverse order . Subjects were requested to fast for at least 12 hours and then received a st and ard meal . Blood sample s were collected at 0 , 30 , 60 , 120 , 240 , 360 and 480 minutes after the meal on Days 0 , 28 , 56 and 84 and were used to measure the lipid and glucose metabolism markers . RESULTS Ezetimibe significantly decreased the postpr and ial serum triglyceride excursion ( p=0.01 ) and fasting serum LDL-C , remnant-like particles(RLP ) and ApoB48 levels ( p<0.05 ) . Postpr and ial glucose excursion , serum insulin levels , serum glucose-dependent insulinotropic polypeptide ( GIP ) and active glucagon-like peptide-1 ( GLP-1 ) were not significantly affected by ezetimibe treatment . CONCLUSION Ezetimibe restored the postpr and ial dysregulation of lipid but did not affect glucose metabolism in a double-blind r and omized crossover trial Background — Statins lower low-density lipoprotein cholesterol ( LDL-C ) and high-sensitivity C-reactive protein ( hs-CRP ) ; addition of ezetimibe to statins further reduces LDL-C and hs-CRP . An analysis of the relationship between achieved LDL-C and hs-CRP targets and outcomes for simvastatin and ezetimibe/simvastatin was prespecified in Improved Reduction of Outcomes : Vytorin Efficacy International Trial ( IMPROVE-IT ) . Methods and Results — The IMPROVE-IT trial r and omly assigned 18 144 patients stabilized after acute coronary syndrome to simvastatin or ezetimibe/simvastatin .  LDL-C and hs-CRP were measured at baseline and 1 month after r and omization . Outcomes were assessed in those achieving one or both of the prespecified targets of LDL-C<70 mg/dL and hs-CRP<2 mg/L versus achieving neither target , adjusting for differences in baseline characteristics . An exploratory analysis examined targets of LDL-C<50 mg/dL and hs-CRP<1 mg/L. Patients meeting both targets at baseline , with no 1-month values , or with end points before 1 month were excluded . Of 15 179 patients , 39 % achieved the dual LDL-C ( < 70 mg/dL ) and hs-CRP ( < 2 mg/L ) targets at 1 month , 14 % met neither target , 14 % met only the hs-CRP target , and 33 % met only the LDL-C target . Those achieving dual targets had lower primary end point rates than those meeting neither target ( cardiovascular death , major coronary event , or stroke ; 38.9 % versus 28.0 % ; adjusted hazard ratio , 0.73 ; 0.66–0.81 ; P<0.001 ) . More patients treated with ezetimibe/simvastatin  met dual targets than those treated with simvastatin alone ( 50 % versus 29 % , P<0.001 ) . The association of dual-target attainment with improved outcomes was similar irrespective of treatment assignment ( P-interaction=0.65 ) . Similar findings were observed using the exploratory targets . Conclusions — Significantly more patients treated with ezetimibe/simvastatin  met prespecified and exploratory dual LDL-C and hs-CRP targets than patients treated with simvastatin alone . Reaching both LDL-C and hs-CRP targets was associated with improved outcomes after multivariable adjustment . Clinical Trial Registration — URL : http://www . clinical trials.gov ; Unique identifier : NCT00202878 Lipid-lowering therapy is associated with  reduced cardiovascular risk .  The aim of the present study was to investigate whether lipid-lowering therapy might be associated with changes in the concentrations of metabolically important hormone concentrations . We performed a r and omised cross-over open-label trial with atorvastatin ( 10 mg/day ) and fenofibrate ( 200 mg/day ) , each for 6 weeks separated by a 6-week washout period in 13 patients ( 5 men , 8 women , age 60.0±6.8 years , body mass index 30.0±3.0 kg/m2 ) with type 2 diabetes mellitus and mixed hyperlipoproteinaemia .  Plasma ghrelin ( RIA , Phoenix Pharmaceuticals , Mountain View , CA , USA ) , adiponectin ( ELISA , Biovendor , Heidelberg , Germany ) as well as resistin ( ELISA , Linco Research , St. Charles , MO , USA ) concentrations were measured before and after atorvastatin as well as before and after fenofibrate . Ghrelin ( 462±84 pg/ml before vs. 464±102 pg/ml after atorvastatin , n.s . ; 454±85 pg/ml before vs. 529±266 pg/ml after fenofibrate , n.s . ) , resistin ( 24.4±7.4 pg/ml before vs. 23.7±9.1 pg/ml after atorvastatin , n.s . ; 23.4±8.2 pg/ml before vs. 19.9±5.5 pg/ml after fenofibrate , n.s . ) , adiponectin ( 10.89±5.33 pg/ml before vs. 12.41±5.75 pg/ml after atorvastatin , n.s . ; 12.58±9.87 pg/ml before vs. 10.27±5.23 pg/ml after fenofibrate , n.s . ) and insulin levels did not change significantly during lipid-lowering therapy . In patients with type 2 diabetes and mixed hyperlipoproteinaemia , short-term atorvastatin as well as fenofibrate therapy had no significant effects on adiponectin , ghrelin or resistin levels Weight loss and hypolipidemic drugs can improve lipid and adip 
    Output:
    