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: This double-blind , r and omized crossover study investigated the effects of 6 weeks of treatment with prescription omega-3-acid ethyl esters ( POM3 , 4 g/day ) versus placebo ( soy oil ) on low-density lipoprotein cholesterol ( LDL-C ) and other aspects of the fasting lipid profile in 31 men and women with primary , isolated hypercholesterolemia ( LDL-C 130 - 220 mg/dL and triglycerides less than 150 mg/dL while free of lipid-altering therapies ) . Mean ± st and ard error of the mean baseline concentrations of total cholesterol , LDL-C , high-density lipoprotein cholesterol ( HDL-C ) , very-low-density lipoprotein cholesterol , and triglycerides were 229 ± 3 , 146 ± 3 , 60 ± 2 , 23 ± 2 , and 113 ± 8 mg/dL , respectively . POM3 produced a modest increase from baseline in LDL-C ( 3.4 % ) versus the placebo response ( -0.7 % , P = 0.010 ) . Significant changes ( P < 0.05 ) for POM3 ( placebo-corrected ) were observed for very-low-density lipoprotein cholesterol ( -18.8 % ) , triglycerides ( -18.7 % ) , and HDL-C ( 3.3 % ) . Nuclear magnetic resonance-determined very-low-density lipoprotein particle concentration and size and HDL particle concentration decreased significantly more with POM3 versus placebo , whereas LDL and HDL particle sizes increased significantly more with POM3 versus placebo . Total cholesterol , non-HDL-C , apolipoproteins A1 and B , and LDL particle concentration responses did not differ between treatments . These results did not confirm the hypothesis that POM3 treatment would lower LDL-C in primary , isolated hypercholesterolemia . Effects on other variables were consistent with prior results in mixed dyslipidemia Background — Nuclear magnetic resonance ( NMR ) spectroscopy measures the number and size of lipoprotein particles instead of their cholesterol or triglyceride content , but its clinical utility is uncertain . Methods and Results — Baseline lipoproteins were measured by NMR in 27 673 initially healthy women followed up for incident cardiovascular disease ( n=1015 ) over an 11-year period . After adjustment for nonlipid risk factors , hazard ratios and 95 % confidence intervals for the top versus the bottom quintile of NMR-measured lipoprotein particle concentration ( measured in particles per liter ) were 2.51 ( 1.91 to 3.30 ) for low-density lipoprotein ( LDLNMR ) , 0.91 ( 0.75 to 1.12 ) for high-density lipoprotein ( HDLNMR ) , 1.71 ( 1.38 to 2.12 ) for very low – density lipoprotein ( VLDLNMR ) , and 2.25 ( 1.80 to 2.81 ) for the LDLNMR/HDLNMR ratio . Similarly adjusted results for NMR-measured lipoprotein particle size ( measured in nanometers ) were 0.64 ( 0.52 to 0.79 ) for LDLNMR size , 0.65 ( 0.51 to 0.81 ) for HDLNMR size , and 1.37 ( 1.10 to 1.70 ) for VLDLNMR size . Hazard ratios for NMR measures were comparable but not superior to st and ard lipids ( total cholesterol 2.08 [ 1.63 to 2.67 ] , LDL cholesterol 1.74 [ 1.40 to 2.16 ] , HDL cholesterol 0.52 [ 0.42 to 0.64 ] , triglycerides 2.58 [ 1.95 to 3.41 ] , non-HDL cholesterol 2.52 [ 1.95 to 3.25 ] , total/HDL cholesterol ratio 2.82 [ 2.23 to 3.58 ] ) and apolipoproteins ( B100 2.57 [ 1.98 to 3.33 ] , A-1 0.63 [ 0.52 to 0.77 ] , and B100/A-1 ratio 2.79 [ 2.21 to 3.54 ] ) . Essentially no reclassification improvement was found with the addition of the LDLNMR particle concentration or apolipoprotein B100 to a model that already included the total/HDL cholesterol ratio and nonlipid risk factors ( net reclassification index 0 % and 1.9 % , respectively ) , nor did the addition of either variable result in a statistically significant improvement in the c-index . Conclusions — In this prospect i ve study of healthy women , cardiovascular disease risk prediction associated with lipoprotein profiles evaluated by NMR was comparable but not superior to that of st and ard lipids or apolipoproteins Background — Changes in conventional lipid risk factors with gemfibrozil treatment only partially explain the reductions in coronary heart disease ( CHD ) events experienced by men in the Veterans Affairs High-Density Lipoprotein Intervention Trial ( VA-HIT ) . We examined whether measurement of low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) particle subclasses provides additional information relative to CHD risk reduction . Methods and Results — This is a prospect i ve nested case-control study of 364 men with a new CHD event ( nonfatal myocardial infa rct ion or cardiac death ) during a 5.1-year ( median ) follow-up and 697 age-matched controls .  Nuclear magnetic resonance ( NMR ) spectroscopy was used to quantify levels of LDL and HDL particle subclasses and mean particle sizes in plasma obtained at baseline and after 7 months of treatment with gemfibrozil or placebo . Odds ratios for a 1-SD increment of each lipoprotein variable were calculated with adjusted logistic regression models . Gemfibrozil treatment increased LDL size and lowered numbers of LDL particles ( −5 % ) while raising numbers of HDL particles ( 10 % ) and small HDL subclass particles ( 21 % ) . Concentrations of these LDL and HDL particles achieved with gemfibrozil were significant , independent predictors of new CHD events . For total LDL and HDL particles , odds ratios predicting CHD benefit were 1.28 ( 95 % CI , 1.12 to 1.47 ) and 0.71 ( 95 % CI , 0.61 to 0.81 ) , respectively . Mean LDL and HDL particle sizes were not associated with CHD events . Conclusions — The effects of gemfibrozil on NMR-measured LDL and HDL particle subclasses , which are not reflected by conventional lipoprotein cholesterol measures , help to explain the demonstrated benefit of this therapy in patients with low HDL cholesterol BACKGROUND Icosapent ethyl ( IPE ; formerly AMR101 ) is a high-purity prescription form of eicosapentaenoic acid ethyl ester . In the MARINE study we evaluated the efficacy and safety of IPE in patients with very high triglycerides ( TG ; ≥500 mg/dL ) and previously demonstrated significant reductions in TG levels with no significant increases in low-density lipoprotein ( LDL ) cholesterol levels  . OBJECTIVES In this follow-up , exploratory analysis , we report the effects of IPE on lipoprotein particle concentration and size . METHODS MARINE was a phase 3 , multicenter , placebo-controlled , r and omized , double-blind , 12-week study . Hypertriglyceridemic patients ( N = 229 ) were r and omized to three treatment groups : IPE 4 g/day , IPE 2 g/day , or placebo . Lipoprotein particle concentrations and sizes were measured by nuclear magnetic resonance spectroscopy . RESULTS Compared with placebo , IPE 4 g/day significantly reduced median concentrations of large very-low-density lipoprotein ( VLDL ; -27.9 % ; P = .0211 ) , total LDL ( -16.3 % ; P = .0006 ) , small LDL ( -25.6 % ; P < .0001 ) , and total high-density lipoprotein ( HDL ; -7.4 % ; P = .0063 ) particles and reduced VLDL particle size ( -8.6 % ; P = .0017 ) . In this patient population with TG ≥500 mg/dL , IPE did not significantly change the overall sizes of LDL or HDL particles . CONCLUSION IPE 4 g/day significantly reduced large VLDL , total LDL , small LDL , and total HDL particle concentrations and VLDL particle size in patients with TG ≥500 mg/dL. Changes in VLDL particle concentration and size reflect the TG-lowering effects of eicosapentaenoic acid . The reduction in LDL particle concentration  with IPE is novel among ω-3 therapies and is consistent with the previously reported reduction in apolipoprotein B and lack of LDL-C increase with IPE in patients with very high TG levels . CLINICAL TRIAL REGISTRATION NUMBER NCT01047683 BACKGROUND To assess the lipid-lowering effects and safety of atorvastatin and niacin in patients with combined hyperlipidemia or isolated hypertriglyceridemia . METHODS We performed a r and omized , open-label , parallel- design , active-controlled , study in eight centers in the United States . We enrolled 108 patients with total cholesterol ( TC ) of > or = 200 mg/dL , serum triglycerides ( TG ) > or = 200 and < or = 800 mg/dL , and apolipoprotein B ( apo B ) > or = 110 mg/dL. Patients were r and omly assigned to receive atorvastatin 10 mg once daily ( n=55 ) or immediate-release niacin 1 g three times daily for 12 weeks ( n=53 ) . Patients were stratified based on low-density lipoprotein cholesterol ( LDL-C ) : Patients with LDL-C > or = 135 mg/dL were considered to have combined hyperlipidemia and patients with LDL-C < 135 mg/dL were considered to have isolated hypertriglyceridemia . The primary outcome measure was percent change from baseline in LDL-C. Other lipid levels were evaluated as secondary parameters . RESULTS Atorvastatin reduced LDL-C 30 % and TC 26 % from baseline , and increased high-density lipoprotein cholesterol ( HDL-C ) 4 % . Total TG were reduced 17 % . Niacin reduced LDL-C 2 % , TC 7 % , increased HDL-C 25 % , and reduced total TG 29 % from baseline . There was a significant difference in LDL-C reduction , the primary efficacy parameter , between the two treatment groups ( P < 0.05 , favoring atorvastatin ) , as well as a significant difference in the improvement in HDL-C ( P < 0.05 , favoring niacin ) . The effect of atorvastatin was relatively consistent between patients with combined hyperlipidemia and isolated hypertriglyceridemia , whereas there was more variability between these strata in the niacin treatment group . Atorvastatin was better tolerated than niacin . CONCLUSION Atorvastatin may allow patients with combined hyperlipidemia to be treated with monotherapy and offers an efficacious and well-tolerated alternative to niacin for the treatment of patients with isolated hypertriglyceridemia Aims A r and omized , double-blind , placebo-controlled study was conducted to investigate the safety and efficacy of mipomersen , an apolipoprotein B-100 ( apoB ) synthesis inhibitor , in patients who are statin intolerant and at high risk for cardiovascular disease ( CVD ) . Methods and results Thirty-three subjects , not receiving statin therapy because of statin intolerance , received a weekly subcutaneous dose of 200 mg mipomersen or placebo ( 2:1 r and omization ) for 26 weeks . The primary endpoint was per cent change in LDL cholesterol ( LDL-c ) from the baseline to Week 28 . The other efficacy endpoints were per cent change in apoB and lipoprotein a [ Lp(a ) ] . Safety was determined using the incidence of treatment-emergent adverse events ( AEs ) and clinical laboratory evaluations . After 26 weeks of mipomersen  administration , LDL-c was reduced by 47 ± 18 % ( P < 0.001 vs. placebo ) . apoB and Lp(a ) were also significantly reduced by 46 and 27 % , respectively ( P < 0.001 vs. placebo ) . Four mipomersen ( 19 % ) and two placebo subjects ( 17 % ) discontinued dosing prematurely due to AEs . Persistent liver transaminase increases ≥3 × the upper limit of normal were observed in seven ( 33 % ) subjects assigned to mipomersen . In selected subjects , liver fat content was assessed , during and after treatment , using magnetic resonance spectroscopy . Liver fat content in these patients ranged from 0.8 to 47. 
    Output:
    
agent
Conclusions Study -level data from this systemic review establish that different lipid lowering agents can lead to discordance between LDL-P and LDL-C , therefore , basing LDL-lowering therapy only on the achievement of cholesterol goals may result in a treatment gap .
Therefore , the use of LDL-P for monitoring lipid-lowering therapy , particularly for statins , can provide a more accurate assessment of residual cardiovascular risk
***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: This double-blind , r and omized crossover study investigated the effects of 6 weeks of treatment with prescription omega-3-acid ethyl esters ( POM3 , 4 g/day ) versus placebo ( soy oil ) on low-density lipoprotein cholesterol ( LDL-C ) and other aspects of the fasting lipid profile in 31 men and women with primary , isolated hypercholesterolemia ( LDL-C 130 - 220 mg/dL and triglycerides less than 150 mg/dL while free of lipid-altering therapies ) . Mean ± st and ard error of the mean baseline concentrations of total cholesterol , LDL-C , high-density lipoprotein cholesterol ( HDL-C ) , very-low-density lipoprotein cholesterol , and triglycerides were 229 ± 3 , 146 ± 3 , 60 ± 2 , 23 ± 2 , and 113 ± 8 mg/dL , respectively . POM3 produced a modest increase from baseline in LDL-C ( 3.4 % ) versus the placebo response ( -0.7 % , P = 0.010 ) . Significant changes ( P < 0.05 ) for POM3 ( placebo-corrected ) were observed for very-low-density lipoprotein cholesterol ( -18.8 % ) , triglycerides ( -18.7 % ) , and HDL-C ( 3.3 % ) . Nuclear magnetic resonance-determined very-low-density lipoprotein particle concentration and size and HDL particle concentration decreased significantly more with POM3 versus placebo , whereas LDL and HDL particle sizes increased significantly more with POM3 versus placebo . Total cholesterol , non-HDL-C , apolipoproteins A1 and B , and LDL particle concentration responses did not differ between treatments . These results did not confirm the hypothesis that POM3 treatment would lower LDL-C in primary , isolated hypercholesterolemia . Effects on other variables were consistent with prior results in mixed dyslipidemia Background — Nuclear magnetic resonance ( NMR ) spectroscopy measures the number and size of lipoprotein particles instead of their cholesterol or triglyceride content , but its clinical utility is uncertain . Methods and Results — Baseline lipoproteins were measured by NMR in 27 673 initially healthy women followed up for incident cardiovascular disease ( n=1015 ) over an 11-year period . After adjustment for nonlipid risk factors , hazard ratios and 95 % confidence intervals for the top versus the bottom quintile of NMR-measured lipoprotein particle concentration ( measured in particles per liter ) were 2.51 ( 1.91 to 3.30 ) for low-density lipoprotein ( LDLNMR ) , 0.91 ( 0.75 to 1.12 ) for high-density lipoprotein ( HDLNMR ) , 1.71 ( 1.38 to 2.12 ) for very low – density lipoprotein ( VLDLNMR ) , and 2.25 ( 1.80 to 2.81 ) for the LDLNMR/HDLNMR ratio . Similarly adjusted results for NMR-measured lipoprotein particle size ( measured in nanometers ) were 0.64 ( 0.52 to 0.79 ) for LDLNMR size , 0.65 ( 0.51 to 0.81 ) for HDLNMR size , and 1.37 ( 1.10 to 1.70 ) for VLDLNMR size . Hazard ratios for NMR measures were comparable but not superior to st and ard lipids ( total cholesterol 2.08 [ 1.63 to 2.67 ] , LDL cholesterol 1.74 [ 1.40 to 2.16 ] , HDL cholesterol 0.52 [ 0.42 to 0.64 ] , triglycerides 2.58 [ 1.95 to 3.41 ] , non-HDL cholesterol 2.52 [ 1.95 to 3.25 ] , total/HDL cholesterol ratio 2.82 [ 2.23 to 3.58 ] ) and apolipoproteins ( B100 2.57 [ 1.98 to 3.33 ] , A-1 0.63 [ 0.52 to 0.77 ] , and B100/A-1 ratio 2.79 [ 2.21 to 3.54 ] ) . Essentially no reclassification improvement was found with the addition of the LDLNMR particle concentration or apolipoprotein B100 to a model that already included the total/HDL cholesterol ratio and nonlipid risk factors ( net reclassification index 0 % and 1.9 % , respectively ) , nor did the addition of either variable result in a statistically significant improvement in the c-index . Conclusions — In this prospect i ve study of healthy women , cardiovascular disease risk prediction associated with lipoprotein profiles evaluated by NMR was comparable but not superior to that of st and ard lipids or apolipoproteins Background — Changes in conventional lipid risk factors with gemfibrozil treatment only partially explain the reductions in coronary heart disease ( CHD ) events experienced by men in the Veterans Affairs High-Density Lipoprotein Intervention Trial ( VA-HIT ) . We examined whether measurement of low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) particle subclasses provides additional information relative to CHD risk reduction . Methods and Results — This is a prospect i ve nested case-control study of 364 men with a new CHD event ( nonfatal myocardial infa rct ion or cardiac death ) during a 5.1-year ( median ) follow-up and 697 age-matched controls .  Nuclear magnetic resonance ( NMR ) spectroscopy was used to quantify levels of LDL and HDL particle subclasses and mean particle sizes in plasma obtained at baseline and after 7 months of treatment with gemfibrozil or placebo . Odds ratios for a 1-SD increment of each lipoprotein variable were calculated with adjusted logistic regression models . Gemfibrozil treatment increased LDL size and lowered numbers of LDL particles ( −5 % ) while raising numbers of HDL particles ( 10 % ) and small HDL subclass particles ( 21 % ) . Concentrations of these LDL and HDL particles achieved with gemfibrozil were significant , independent predictors of new CHD events . For total LDL and HDL particles , odds ratios predicting CHD benefit were 1.28 ( 95 % CI , 1.12 to 1.47 ) and 0.71 ( 95 % CI , 0.61 to 0.81 ) , respectively . Mean LDL and HDL particle sizes were not associated with CHD events . Conclusions — The effects of gemfibrozil on NMR-measured LDL and HDL particle subclasses , which are not reflected by conventional lipoprotein cholesterol measures , help to explain the demonstrated benefit of this therapy in patients with low HDL cholesterol BACKGROUND Icosapent ethyl ( IPE ; formerly AMR101 ) is a high-purity prescription form of eicosapentaenoic acid ethyl ester . In the MARINE study we evaluated the efficacy and safety of IPE in patients with very high triglycerides ( TG ; ≥500 mg/dL ) and previously demonstrated significant reductions in TG levels with no significant increases in low-density lipoprotein ( LDL ) cholesterol levels  . OBJECTIVES In this follow-up , exploratory analysis , we report the effects of IPE on lipoprotein particle concentration and size . METHODS MARINE was a phase 3 , multicenter , placebo-controlled , r and omized , double-blind , 12-week study . Hypertriglyceridemic patients ( N = 229 ) were r and omized to three treatment groups : IPE 4 g/day , IPE 2 g/day , or placebo . Lipoprotein particle concentrations and sizes were measured by nuclear magnetic resonance spectroscopy . RESULTS Compared with placebo , IPE 4 g/day significantly reduced median concentrations of large very-low-density lipoprotein ( VLDL ; -27.9 % ; P = .0211 ) , total LDL ( -16.3 % ; P = .0006 ) , small LDL ( -25.6 % ; P < .0001 ) , and total high-density lipoprotein ( HDL ; -7.4 % ; P = .0063 ) particles and reduced VLDL particle size ( -8.6 % ; P = .0017 ) . In this patient population with TG ≥500 mg/dL , IPE did not significantly change the overall sizes of LDL or HDL particles . CONCLUSION IPE 4 g/day significantly reduced large VLDL , total LDL , small LDL , and total HDL particle concentrations and VLDL particle size in patients with TG ≥500 mg/dL. Changes in VLDL particle concentration and size reflect the TG-lowering effects of eicosapentaenoic acid . The reduction in LDL particle concentration  with IPE is novel among ω-3 therapies and is consistent with the previously reported reduction in apolipoprotein B and lack of LDL-C increase with IPE in patients with very high TG levels . CLINICAL TRIAL REGISTRATION NUMBER NCT01047683 BACKGROUND To assess the lipid-lowering effects and safety of atorvastatin and niacin in patients with combined hyperlipidemia or isolated hypertriglyceridemia . METHODS We performed a r and omized , open-label , parallel- design , active-controlled , study in eight centers in the United States . We enrolled 108 patients with total cholesterol ( TC ) of > or = 200 mg/dL , serum triglycerides ( TG ) > or = 200 and < or = 800 mg/dL , and apolipoprotein B ( apo B ) > or = 110 mg/dL. Patients were r and omly assigned to receive atorvastatin 10 mg once daily ( n=55 ) or immediate-release niacin 1 g three times daily for 12 weeks ( n=53 ) . Patients were stratified based on low-density lipoprotein cholesterol ( LDL-C ) : Patients with LDL-C > or = 135 mg/dL were considered to have combined hyperlipidemia and patients with LDL-C < 135 mg/dL were considered to have isolated hypertriglyceridemia . The primary outcome measure was percent change from baseline in LDL-C. Other lipid levels were evaluated as secondary parameters . RESULTS Atorvastatin reduced LDL-C 30 % and TC 26 % from baseline , and increased high-density lipoprotein cholesterol ( HDL-C ) 4 % . Total TG were reduced 17 % . Niacin reduced LDL-C 2 % , TC 7 % , increased HDL-C 25 % , and reduced total TG 29 % from baseline . There was a significant difference in LDL-C reduction , the primary efficacy parameter , between the two treatment groups ( P < 0.05 , favoring atorvastatin ) , as well as a significant difference in the improvement in HDL-C ( P < 0.05 , favoring niacin ) . The effect of atorvastatin was relatively consistent between patients with combined hyperlipidemia and isolated hypertriglyceridemia , whereas there was more variability between these strata in the niacin treatment group . Atorvastatin was better tolerated than niacin . CONCLUSION Atorvastatin may allow patients with combined hyperlipidemia to be treated with monotherapy and offers an efficacious and well-tolerated alternative to niacin for the treatment of patients with isolated hypertriglyceridemia Aims A r and omized , double-blind , placebo-controlled study was conducted to investigate the safety and efficacy of mipomersen , an apolipoprotein B-100 ( apoB ) synthesis inhibitor , in patients who are statin intolerant and at high risk for cardiovascular disease ( CVD ) . Methods and results Thirty-three subjects , not receiving statin therapy because of statin intolerance , received a weekly subcutaneous dose of 200 mg mipomersen or placebo ( 2:1 r and omization ) for 26 weeks . The primary endpoint was per cent change in LDL cholesterol ( LDL-c ) from the baseline to Week 28 . The other efficacy endpoints were per cent change in apoB and lipoprotein a [ Lp(a ) ] . Safety was determined using the incidence of treatment-emergent adverse events ( AEs ) and clinical laboratory evaluations . After 26 weeks of mipomersen  administration , LDL-c was reduced by 47 ± 18 % ( P < 0.001 vs. placebo ) . apoB and Lp(a ) were also significantly reduced by 46 and 27 % , respectively ( P < 0.001 vs. placebo ) . Four mipomersen ( 19 % ) and two placebo subjects ( 17 % ) discontinued dosing prematurely due to AEs . Persistent liver transaminase increases ≥3 × the upper limit of normal were observed in seven ( 33 % ) subjects assigned to mipomersen . In selected subjects , liver fat content was assessed , during and after treatment , using magnetic resonance spectroscopy . Liver fat content in these patients ranged from 0.8 to 47. 
    Output:
    