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: Background — There is no r and omized , double-blind trial testing the prognostic effect of highly purified omega-3 fatty acids in addition to current guideline -adjusted treatment of acute myocardial infa rct ion . Methods and Results — OMEGA is a r and omized , placebo-controlled , double-blind , multicenter trial testing the effects of omega-3-acid ethyl esters-90 ( 1 g/d for 1 year ) on the rate of sudden cardiac death in survivors of acute myocardial infa rct ion , if given in addition to current guideline -adjusted treatment . Secondary end points were total mortality and nonfatal clinical events .  Patients ( n=3851 ; female , 25.6 % ; mean age , 64.0 years ) were r and omized in 104 German centers 3 to 14 days after acute myocardial infa rct ion from October 2003 until June 2007 .  Acute coronary angiography was performed in 93.8 % and acute percutaneous coronary intervention in 77.8 % of all patients . During a follow-up of 365 days , the event rates were ( omega and control groups ) as follows : sudden cardiac death , 1.5 % and 1.5 % ( P=0.84 ) ; total mortality , 4.6 % and 3.7 % ( P=0.18 ) ; major adverse cerebrovascular and cardiovascular events , 10.4 % and 8.8 % ( P=0.1 ) ; and revascularization in survivors , 27.6 % and 29.1 % ( P=0.34 ) . Conclusions — Guideline -adjusted treatment of acute myocardial infa rct ion results in a low rate of sudden cardiac death and other clinical events within 1 year of follow-up , which could not be shown to be further reduced by the application of omega-3 fatty acids . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00251134 BACKGROUND Epidemiological and clinical evidence suggests that an increased intake of long-chain n-3 fatty acids protects against mortality from coronary artery disease . We aim ed to test the hypothesis that long-term use of eicosapentaenoic acid ( EPA ) is effective for prevention of major coronary events in hypercholesterolaemic patients in Japan who consume a large amount of fish . METHODS 18 645 patients with a total cholesterol of 6.5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999 . Patients were r and omly assigned to receive either 1800 mg of EPA daily with statin ( EPA group ; n=9326 ) or statin only ( controls ; n=9319 ) with a 5-year follow-up . The primary endpoint was any major coronary event , including sudden cardiac death , fatal and non-fatal myocardial infa rct ion , and other non-fatal events including unstable angina pectoris , angioplasty , stenting , or coronary artery bypass grafting . Analysis was by intention-to-treat . The study was registered at Clinical Trials.gov , number NCT00231738 . FINDINGS At mean follow-up of 4.6 years , we detected the primary endpoint in 262 ( 2.8 % ) patients in the EPA group and 324 ( 3.5 % ) in controls-a 19 % relative reduction in major coronary events ( p=0.011 ) . Post-treatment LDL cholesterol concentrations decreased 25 % , from 4.7 mmol/L in both groups . Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events . Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group . Sudden cardiac death and coronary death did not differ between groups . In patients with a history of coronary artery disease who were given EPA treatment , major coronary events were reduced by 19 % ( secondary prevention subgroup : 158 [ 8.7 % ] in the EPA group vs 197 [ 10.7 % ] in the control group ; p=0.048 ) . In patients with no history of coronary artery disease , EPA treatment reduced major coronary events by 18 % , but this finding was not significant ( 104 [ 1.4 % ] in the EPA group vs 127 [ 1.7 % ] in the control group ; p=0.132 ) . INTERPRETATION EPA is a promising treatment for prevention of major coronary events , and especially non-fatal coronary events , in Japanese hypercholesterolaemic patients OBJECTIVES To investigate the impact of apolipoprotein E ( apoE ) genotype on the response of the plasma lipoprotein profile to eicosapentaenoic acid ( EPA ) versus docosahexaenoic acid ( DHA ) intervention in humans . METHODS AND RESULTS 38 healthy normolipidaemic males , prospect ively recruited on the basis of apoE genotype ( n=20 E3/E3 and n=18 E3/E4 ) , completed a double-blind placebo-controlled cross-over trial , consisting of 3 x 4 week intervention arms of either control oil , EPA-rich oil ( ERO , 3.3 g EPA/day ) or DHA-rich oil ( DRO , 3.7 g DHA/day ) in r and om order , separated by 10 week wash-out periods . A significant genotype-independent 28 % and 19 % reduction in plasma triglycerides in response to ERO and DRO was observed . For total cholesterol ( TC ) , no significant treatment effects were evident ; however a significant genotype by treatment interaction emerged ( P=0.045 ) , with a differential response to ERO and DRO in E4 carriers . Although the genotype x treatment interaction for LDL-cholesterol ( P=0.089 ) did not reach significance , within DRO treatment analysis indicated a 10 % increase in LDL ( P=0.029 ) in E4 carriers with a non-significant 4 % reduction in E3/E3 individuals . A genotype-independent increase in LDL mass was observed following DRO intervention ( P=0.018 ) . Competitive uptake studies in HepG2 cells using plasma very low density lipoproteins ( VLDL ) from the human trial , indicated that following DRO treatment , VLDL(2 ) fractions obtained from E3/E4 individuals result ed in a significant 32 % ( P=0.002 ) reduction in LDL uptake relative to the control . CONCLUSIONS High dose DHA supplementation is associated with increases in total cholesterol in E4 carriers , which appears to be due to an increase in LDL-C and may in part negate the cardioprotective action of DHA in this population subgroup Recent data suggest that treatment with n-3 fatty acids could enhance the susceptibility of plasma low-density-lipoprotein ( LDL ) to oxidation .  Twelve hypertriacylglycerolemic , hemodialyzed patients were treated with 2.5 g n-3 fatty acids/d for 2 mo . Treatment was then withdrawn for 2 mo ( washout phase ) . Plasma total cholesterol and LDL cholesterol increased significantly ( 9 % and 28 % ) and plasma triacylglycerols decreased significantly after the n-3 phase compared with baseline and washout values . LDL susceptibility to oxidation was tested by oxidation of LDL particles with 2,2'-azobis ( 2-amidinopropane ) dihydrochloride ( AAPH ) . No significant changes were observed for the lag phase and the peroxidation rate . The vitamin E content of LDL also did not change significantly . The results thus suggest that a daily dosage of 2.5 g n-3 fatty acids does not enhance LDL susceptibility to oxidation , while retaining its hypotriacylglycerolemic effect BACKGROUND Results of epidemiologic studies and clinical trials indicate that moderate doses of n-3 fatty acids reduce the risk of cardiovascular disease and may improve prognosis . OBJECTIVE The objective was to evaluate the effect of a high-dose ethylester concentrate of n-3 fatty acids administered early after an acute myocardial infa rct ion ( MI ) on subsequent cardiac events and serum lipids . DESIGN Three hundred patients with acute MI were r and omly assigned to a daily dose of either 4 g highly concentrated n-3 fatty acids or corn oil , administered in a double-blind manner over 12 - 24 mo . Median follow-up time was 1.5 y. Clinical follow-up , including the drawing of blood sample s , was performed after 6 wk of treatment and later at 0.5-year intervals . RESULTS Forty-two ( 28 % ) patients in the n-3 group and 36 ( 24 % ) in the corn oil group experienced at least one cardiac event ( cardiac death , resuscitation , recurrent MI , or unstable angina ) . No significant difference in prognosis was observed between groups for single or combined cardiac events . Total cholesterol concentrations decreased in both groups , with no significant intergroup differences . On average , the monthly increase in HDL cholesterol was 1.11 % in the n-3 group and 0.55 % in the corn oil group ( P = 0.0016 ) . Triacylglycerol concentrations decreased by 1.30%/mo in the n-3 group , whereas they increased by 0.35%/mo in the corn oil group ( P < 0.0001 ) . CONCLUSION No clinical benefit of a high-dose concentrate of n-3 fatty acids compared with corn oil was found despite a favorable effect on serum lipids We investigated the effect of incorporating n-3 polyunsaturated fatty acids ( PUFAs ) into the diet on the lipid-class composition of LDLs , their size , and their susceptibility to oxidation . Forty-seven healthy volunteers incorporated 30 g sunflower-oil ( SO ) margarine/d into their habitual diet during a 3-wk run-in period and then used either SO or a fish-oil-enriched sunflower oil ( FO ) margarine for the following 4 wk . Plasma concentrations of total cholesterol , triacylglycerols , HDL cholesterol , LDL cholesterol , and apolipoproteins A-I and B did not differ significantly between the groups during intervention . The FO margarine increased the concentration of n-3 very-long-chain PUFAs in the LDL particles , showing 93 % ( P < or = 0.0001 ) , 8 % ( P = 0.05 ) , and 35 % ( P = < 0.0001 ) increases in eicosapentaenoic acid , docosapentaenoic acid , and docosahexaenoic acid , respectively , in the FO group compared with 3 % , 7 % , and 7 % , respectively , in the SO group during the intervention . The cholesterol content of the LDL particles increased in the FO group [ total cholesterol : 6 % ( P = 0.008 ) ; cholesterol ester : 12 % ( P = 0.014 ) ] , although it was not significantly different from that in the control group , whereas the other lipid classes and the size of the LDL particles remained unchanged in both groups . A reduction in the alpha-tocopherol content in LDL ( 6 % , P = 0.005 ) was observed in the FO group . Ex vivo oxidation of LDL induced with Cu2 + showed a significantly reduced lag time ( from 91 to 86 min , P = 0.003 ) and lower maximum rate of oxidation ( from 10.5 to 10.2 nmol x mg(-1 ) x min(-1 ) , P = 0.003 ) after intake of the FO margarine . The results indicate that consumption of the FO compared with the SO margarine had no effect on LDL size and lipid composition and led to minor changes in LDL a-tocopherol content and oxidation resistance BACKGROUND The lipid-modulatory effects of high intakes of the fish-oil fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) are well established and likely to contribute to cardioprotective benefits . OBJECTIVES We aim ed to determine the effect of moderate EPA and DHA intakes ( < 2 g EPA+DHA/d ) on the plasma fatty acid profile , lipid and apolipoprotein concentrations , lipoprotein subclass distribution , and markers of oxidative status . We also aim ed to examine the effect of age , sex , and apolipoprotein E ( APOE ) genotype on the observed responses . DESIGN Three hundred twelve adults aged 20 - 70 y , who were prospect ively recruited according to age , sex , and APOE genotype , completed a double-blind placebo-controlled crossover study . Participants consumed control oil , 0.7 g EPA+DHA/d ( 0.7FO ) , and 1.8 g EPA+DHA/d ( 1.8FO ) capsules in r and om order , each for an 8-wk intervention period , separated by 12-wk washout periods . RESULTS In the group as a whole , 8 % and 11 % lower plasma triacylglycerol concentrations were evident after 0.7FO and 1.8FO , respectively ( P < 0.001 ) : significant sex x treatment ( P = 0.038 ) and sex x 
    Output:
    
agent
***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 — There is no r and omized , double-blind trial testing the prognostic effect of highly purified omega-3 fatty acids in addition to current guideline -adjusted treatment of acute myocardial infa rct ion . Methods and Results — OMEGA is a r and omized , placebo-controlled , double-blind , multicenter trial testing the effects of omega-3-acid ethyl esters-90 ( 1 g/d for 1 year ) on the rate of sudden cardiac death in survivors of acute myocardial infa rct ion , if given in addition to current guideline -adjusted treatment . Secondary end points were total mortality and nonfatal clinical events .  Patients ( n=3851 ; female , 25.6 % ; mean age , 64.0 years ) were r and omized in 104 German centers 3 to 14 days after acute myocardial infa rct ion from October 2003 until June 2007 .  Acute coronary angiography was performed in 93.8 % and acute percutaneous coronary intervention in 77.8 % of all patients . During a follow-up of 365 days , the event rates were ( omega and control groups ) as follows : sudden cardiac death , 1.5 % and 1.5 % ( P=0.84 ) ; total mortality , 4.6 % and 3.7 % ( P=0.18 ) ; major adverse cerebrovascular and cardiovascular events , 10.4 % and 8.8 % ( P=0.1 ) ; and revascularization in survivors , 27.6 % and 29.1 % ( P=0.34 ) . Conclusions — Guideline -adjusted treatment of acute myocardial infa rct ion results in a low rate of sudden cardiac death and other clinical events within 1 year of follow-up , which could not be shown to be further reduced by the application of omega-3 fatty acids . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00251134 BACKGROUND Epidemiological and clinical evidence suggests that an increased intake of long-chain n-3 fatty acids protects against mortality from coronary artery disease . We aim ed to test the hypothesis that long-term use of eicosapentaenoic acid ( EPA ) is effective for prevention of major coronary events in hypercholesterolaemic patients in Japan who consume a large amount of fish . METHODS 18 645 patients with a total cholesterol of 6.5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999 . Patients were r and omly assigned to receive either 1800 mg of EPA daily with statin ( EPA group ; n=9326 ) or statin only ( controls ; n=9319 ) with a 5-year follow-up . The primary endpoint was any major coronary event , including sudden cardiac death , fatal and non-fatal myocardial infa rct ion , and other non-fatal events including unstable angina pectoris , angioplasty , stenting , or coronary artery bypass grafting . Analysis was by intention-to-treat . The study was registered at Clinical Trials.gov , number NCT00231738 . FINDINGS At mean follow-up of 4.6 years , we detected the primary endpoint in 262 ( 2.8 % ) patients in the EPA group and 324 ( 3.5 % ) in controls-a 19 % relative reduction in major coronary events ( p=0.011 ) . Post-treatment LDL cholesterol concentrations decreased 25 % , from 4.7 mmol/L in both groups . Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events . Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group . Sudden cardiac death and coronary death did not differ between groups . In patients with a history of coronary artery disease who were given EPA treatment , major coronary events were reduced by 19 % ( secondary prevention subgroup : 158 [ 8.7 % ] in the EPA group vs 197 [ 10.7 % ] in the control group ; p=0.048 ) . In patients with no history of coronary artery disease , EPA treatment reduced major coronary events by 18 % , but this finding was not significant ( 104 [ 1.4 % ] in the EPA group vs 127 [ 1.7 % ] in the control group ; p=0.132 ) . INTERPRETATION EPA is a promising treatment for prevention of major coronary events , and especially non-fatal coronary events , in Japanese hypercholesterolaemic patients OBJECTIVES To investigate the impact of apolipoprotein E ( apoE ) genotype on the response of the plasma lipoprotein profile to eicosapentaenoic acid ( EPA ) versus docosahexaenoic acid ( DHA ) intervention in humans . METHODS AND RESULTS 38 healthy normolipidaemic males , prospect ively recruited on the basis of apoE genotype ( n=20 E3/E3 and n=18 E3/E4 ) , completed a double-blind placebo-controlled cross-over trial , consisting of 3 x 4 week intervention arms of either control oil , EPA-rich oil ( ERO , 3.3 g EPA/day ) or DHA-rich oil ( DRO , 3.7 g DHA/day ) in r and om order , separated by 10 week wash-out periods . A significant genotype-independent 28 % and 19 % reduction in plasma triglycerides in response to ERO and DRO was observed . For total cholesterol ( TC ) , no significant treatment effects were evident ; however a significant genotype by treatment interaction emerged ( P=0.045 ) , with a differential response to ERO and DRO in E4 carriers . Although the genotype x treatment interaction for LDL-cholesterol ( P=0.089 ) did not reach significance , within DRO treatment analysis indicated a 10 % increase in LDL ( P=0.029 ) in E4 carriers with a non-significant 4 % reduction in E3/E3 individuals . A genotype-independent increase in LDL mass was observed following DRO intervention ( P=0.018 ) . Competitive uptake studies in HepG2 cells using plasma very low density lipoproteins ( VLDL ) from the human trial , indicated that following DRO treatment , VLDL(2 ) fractions obtained from E3/E4 individuals result ed in a significant 32 % ( P=0.002 ) reduction in LDL uptake relative to the control . CONCLUSIONS High dose DHA supplementation is associated with increases in total cholesterol in E4 carriers , which appears to be due to an increase in LDL-C and may in part negate the cardioprotective action of DHA in this population subgroup Recent data suggest that treatment with n-3 fatty acids could enhance the susceptibility of plasma low-density-lipoprotein ( LDL ) to oxidation .  Twelve hypertriacylglycerolemic , hemodialyzed patients were treated with 2.5 g n-3 fatty acids/d for 2 mo . Treatment was then withdrawn for 2 mo ( washout phase ) . Plasma total cholesterol and LDL cholesterol increased significantly ( 9 % and 28 % ) and plasma triacylglycerols decreased significantly after the n-3 phase compared with baseline and washout values . LDL susceptibility to oxidation was tested by oxidation of LDL particles with 2,2'-azobis ( 2-amidinopropane ) dihydrochloride ( AAPH ) . No significant changes were observed for the lag phase and the peroxidation rate . The vitamin E content of LDL also did not change significantly . The results thus suggest that a daily dosage of 2.5 g n-3 fatty acids does not enhance LDL susceptibility to oxidation , while retaining its hypotriacylglycerolemic effect BACKGROUND Results of epidemiologic studies and clinical trials indicate that moderate doses of n-3 fatty acids reduce the risk of cardiovascular disease and may improve prognosis . OBJECTIVE The objective was to evaluate the effect of a high-dose ethylester concentrate of n-3 fatty acids administered early after an acute myocardial infa rct ion ( MI ) on subsequent cardiac events and serum lipids . DESIGN Three hundred patients with acute MI were r and omly assigned to a daily dose of either 4 g highly concentrated n-3 fatty acids or corn oil , administered in a double-blind manner over 12 - 24 mo . Median follow-up time was 1.5 y. Clinical follow-up , including the drawing of blood sample s , was performed after 6 wk of treatment and later at 0.5-year intervals . RESULTS Forty-two ( 28 % ) patients in the n-3 group and 36 ( 24 % ) in the corn oil group experienced at least one cardiac event ( cardiac death , resuscitation , recurrent MI , or unstable angina ) . No significant difference in prognosis was observed between groups for single or combined cardiac events . Total cholesterol concentrations decreased in both groups , with no significant intergroup differences . On average , the monthly increase in HDL cholesterol was 1.11 % in the n-3 group and 0.55 % in the corn oil group ( P = 0.0016 ) . Triacylglycerol concentrations decreased by 1.30%/mo in the n-3 group , whereas they increased by 0.35%/mo in the corn oil group ( P < 0.0001 ) . CONCLUSION No clinical benefit of a high-dose concentrate of n-3 fatty acids compared with corn oil was found despite a favorable effect on serum lipids We investigated the effect of incorporating n-3 polyunsaturated fatty acids ( PUFAs ) into the diet on the lipid-class composition of LDLs , their size , and their susceptibility to oxidation . Forty-seven healthy volunteers incorporated 30 g sunflower-oil ( SO ) margarine/d into their habitual diet during a 3-wk run-in period and then used either SO or a fish-oil-enriched sunflower oil ( FO ) margarine for the following 4 wk . Plasma concentrations of total cholesterol , triacylglycerols , HDL cholesterol , LDL cholesterol , and apolipoproteins A-I and B did not differ significantly between the groups during intervention . The FO margarine increased the concentration of n-3 very-long-chain PUFAs in the LDL particles , showing 93 % ( P < or = 0.0001 ) , 8 % ( P = 0.05 ) , and 35 % ( P = < 0.0001 ) increases in eicosapentaenoic acid , docosapentaenoic acid , and docosahexaenoic acid , respectively , in the FO group compared with 3 % , 7 % , and 7 % , respectively , in the SO group during the intervention . The cholesterol content of the LDL particles increased in the FO group [ total cholesterol : 6 % ( P = 0.008 ) ; cholesterol ester : 12 % ( P = 0.014 ) ] , although it was not significantly different from that in the control group , whereas the other lipid classes and the size of the LDL particles remained unchanged in both groups . A reduction in the alpha-tocopherol content in LDL ( 6 % , P = 0.005 ) was observed in the FO group . Ex vivo oxidation of LDL induced with Cu2 + showed a significantly reduced lag time ( from 91 to 86 min , P = 0.003 ) and lower maximum rate of oxidation ( from 10.5 to 10.2 nmol x mg(-1 ) x min(-1 ) , P = 0.003 ) after intake of the FO margarine . The results indicate that consumption of the FO compared with the SO margarine had no effect on LDL size and lipid composition and led to minor changes in LDL a-tocopherol content and oxidation resistance BACKGROUND The lipid-modulatory effects of high intakes of the fish-oil fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) are well established and likely to contribute to cardioprotective benefits . OBJECTIVES We aim ed to determine the effect of moderate EPA and DHA intakes ( < 2 g EPA+DHA/d ) on the plasma fatty acid profile , lipid and apolipoprotein concentrations , lipoprotein subclass distribution , and markers of oxidative status . We also aim ed to examine the effect of age , sex , and apolipoprotein E ( APOE ) genotype on the observed responses . DESIGN Three hundred twelve adults aged 20 - 70 y , who were prospect ively recruited according to age , sex , and APOE genotype , completed a double-blind placebo-controlled crossover study . Participants consumed control oil , 0.7 g EPA+DHA/d ( 0.7FO ) , and 1.8 g EPA+DHA/d ( 1.8FO ) capsules in r and om order , each for an 8-wk intervention period , separated by 12-wk washout periods . RESULTS In the group as a whole , 8 % and 11 % lower plasma triacylglycerol concentrations were evident after 0.7FO and 1.8FO , respectively ( P < 0.001 ) : significant sex x treatment ( P = 0.038 ) and sex x 
    Output:
    