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: CONTEXT High levels of lipoprotein(a ) are associated with increased risk of myocardial infa rct ion ( MI ) . OBJECTIVE To assess whether genetic data are consistent with this association being causal . DESIGN , SETTING , AND PARTICIPANTS Three studies of white individuals from Copenhagen , Denmark , were used : the Copenhagen City Heart Study ( CCHS ) , a prospect i ve general population study with 16 years of follow-up ( 1991 - 2007 , n = 8637 , 599 MI events ) ; the Copenhagen General Population Study ( CGPS ) , a cross-sectional general population study ( 2003 - 2006 , n = 29 388 , 994 MI events ) ; and the Copenhagen Ischemic Heart Disease Study ( CIHDS ) , a case-control study ( 1991 - 2004 , n = 2461 , 1231 MI events ) . MAIN OUTCOME MEASURES Plasma lipoprotein(a ) levels , lipoprotein(a ) kringle IV type 2 ( KIV-2 ) size polymorphism genotype , and MIs recorded from 1976 through July 2007 for all participants . RESULTS In the CCHS , multivariable-adjusted hazard ratios ( HRs ) for MI for elevated lipoprotein(a ) levels were 1.2 ( 95 % confidence interval [ CI ] , 0.9 - 1.6 ; events/10,000 person-years , 59 ) for levels between the 22nd and 66th percentile , 1.6 ( 95 % CI , 1.1 - 2.2 ; events/10,000 person-years , 75 ) for the 67th to 89th percentile , 1.9 ( 95 % CI , 1.2 - 3.0 ; events/10,000 person-years , 84 ) for the 90th to 95th percentile , and 2.6 ( 95 % CI , 1.6 - 4.1 ; events/10,000 person-years , 108 ) for levels greater than the 95th percentile , respectively , vs levels less than the 22nd percentile ( events/10,000 person-years , 55 ) ( trend P < .001 ) . Numbers of KIV-2 repeats ( sum of repeats on both alleles ) ranged from 6 to 99 and on analysis of variance explained 21 % and 27 % of all variation in plasma lipoprotein(a ) levels in the CCHS and CGPS , respectively . Mean lipoprotein(a ) levels were 56 , 31 , 20 , and 15 mg/dL for the first , second , third , and fourth quartiles of KIV-2 repeats in the CCHS , respectively ( trend P < .001 ) ; corresponding values in the CGPS were 60 , 34 , 22 , and 19 mg/dL ( trend P < .001 ) . In the CCHS , multivariable-adjusted HRs for MI were 1.5 ( 95 % CI , 1.2 - 1.9 ; events/10,000 person-years , 75 ) , 1.3 ( 95 % CI , 1.0 - 1.6 ; events/10,000 person-years , 66 ) , and 1.1 ( 95 % CI , 0.9 - 1.4 ; events/10,000 person-years , 57 ) for individuals in the first , second , and third quartiles , respectively , as compared with individuals in the fourth quartile of KIV-2 repeats ( events/10,000 person-years , 51 ) ( trend P < .001 ) . Corresponding odds ratios were 1.3 ( 95 % CI , 1.1 - 1.5 ) , 1.1 ( 95 % CI , 0.9 - 1.3 ) , and 0.9 ( 95 % CI , 0.8 - 1.1 ) in the CGPS ( trend P = .005 ) , and 1.4 ( 95 % CI , 1.1 - 1.7 ) , 1.2 ( 95 % CI , 1.0 - 1.6 ) , and 1.3 ( 95 % CI , 1.0 - 1.6 ) in the CIHDS ( trend P = .01 ) . Genetically elevated lipoprotein(a ) was associated with an HR of 1.22 ( 95 % CI , 1.09 - 1.37 ) per doubling of lipoprotein(a ) level on instrumental variable analysis , while the corresponding value for plasma lipoprotein(a ) levels on Cox regression was 1.08 ( 95 % CI , 1.03 - 1.12 ) . CONCLUSION These data are consistent with a causal association between elevated lipoprotein(a ) levels and increased risk of MI Objective — Lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) is a predictor for incident atherosclerotic disease . We investigated the effect of 3 hypolipidemic drugs that exert their action through different mechanisms on plasma and lipoprotein-associated Lp-PLA2 activity and mass . Methods and Results — In 50 patients with Type IIA dyslipidemia were administered rosuvastatin ( 10 mg daily ) , whereas in 50 Type IIA dyslipidemic patients exhibiting intolerance to previous statin therapy were administered ezetimibe as monotherapy ( 10 mg daily ) . Fifty patients with Type IV dyslipidemia were given micronised fenofibrate ( 200 mg daily ) . Low- and high-density lipoprotein ( LDL and HDL , respectively ) subclass analysis was performed electrophoretically , whereas lipoprotein subfractions were isolated by ultracentrifugation . Ezetimibe reduced plasma Lp-PLA2 activity and mass attributable to the reduction in plasma levels of all LDL subfractions . Rosuvastatin reduced enzyme activity and mass because of the decrease in plasma levels of all LDL subfractions and especially the Lp-PLA2 on dense LDL subfraction ( LDL-5 ) . Fenofibrate preferentially reduced the Lp-PLA2 activity and mass associated with the VLDL+IDL and LDL-5 subfractions . Among studied drugs only fenofibrate increased HDL-associated Lp-PLA2 ( HDL-Lp-PLA2 ) activity and mass attributable to a preferential increase in Lp-PLA2 associated with the HDL-3c subfraction . Conclusion — Ezetimibe , rosuvastatin , and fenofibrate reduce Lp-PLA2 activity and mass associated with the atherogenic apoB-lipoproteins . Furthermore , fenofibrate improves the enzyme specific activity on apoB-lipoproteins and induces the HDL-Lp-PLA2 . The clinical implication s of these effects remain to be established Lipoprotein ( a ) [ Lp(a ) ] is an independent risk factor for cardiovascular disease . There are currently limited therapeutic options to lower Lp(a ) levels . l-Carnitine has been reported to reduce Lp(a ) levels . The aim of this study was to compare the effect of l-carnitine/simvastatin co-administration with that of simvastatin monotherapy on Lp(a ) levels in subjects with mixed hyperlipidemia and elevated Lp(a ) concentration . Subjects with levels of low-density lipoprotein cholesterol ( LDL-C ) > 160 mg/dL , triacylglycerol ( TAG ) > 150 mg/dL and Lp(a ) > 20 mg/dL were included in this study . Subjects were r and omly allocated to receive l-carnitine 2 g/day plus simvastatin 20 mg/day ( N = 29 ) or placebo plus simvastatin 20 mg/day ( N = 29 ) for a total of 12 weeks . Lp(a ) was significantly reduced in the l-carnitine/simvastatin group [ −19.4 % , from 52 ( 20–171 ) to 42 ( 15–102 ) mg/dL ; p = 0.01 ] , but not in the placebo/simvastatin group [ −6.7 % , from 56 ( 26–108 ) to 52 ( 27–93 ) mg/dL , p = NS versus baseline and p = 0.016 for the comparison between groups ] . Similar significant reductions in total cholesterol , LDL-C , apolipoprotein ( apo ) B and TAG were observed in both groups . Co-administration of l-carnitine with simvastatin was associated with a significant , albeit modest , reduction in Lp(a )  compared with simvastatin monotherapy in subjects with mixed hyperlipidemia and elevated baseline Lp(a ) levels Background : Raised plasma lipoprotein(a ) ( Lp(a ) ) is associated with increased risk of cardiovascular disease . It is unknown whether increased Lp(a ) is an additional risk factor for coronary artery disease in familial hypercholesterolaemia ( FH ) or whether statin treatment can reduce Lp(a ) concentrations in the long term . Objective : To investigate Lp(a ) concentrations in relation to statin treatment and the progression of atherosclerosis in a large cohort of FH patients . Design : A two year , r and omised , double blind trial ( the ASAP trial ) . Patients : 325 heterozygous FH patients . Intervention : Treatment with 80 mg atorvastatin or 40 mg simvastatin . Main outcome measure : Change in Lp(a ) concentrations and intima – media thickness of carotid artery segments at one year and two years . Results : At baseline , median Lp(a ) concentrations were 327 mg/l and 531 mg/l in the atorvastatin and simvastatin arms , respectively ( p = 0.03 ) . In the atorvastatin arm , Lp(a ) concentrations decreased to 243 mg/l after one year ( p < 0.001 ) and to 263 mg/l after two years ( p < 0.001 ) . In the simvastatin arm , Lp(a ) concentrations decreased to 437 mg/l after one year ( p < 0.001 ) and to 417 mg/l after two years ( p < 0.001 ) . The difference in Lp(a ) reduction between the two treatment arms was significant after one year ( p = 0.004 ) , but not after two years ( p = 0.086 ) . Lp(a ) concentrations at baseline were not related to cardiovascular events at baseline . There was no correlation between baseline Lp(a ) concentrations and low density lipoprotein cholesterol concentrations or intima – media thickness at baseline . Change in Lp(a ) concentrations was not correlated with change in intima – media thickness after one or two years . Conclusions : Long term statin treatment significantly lowers Lp(a ) in FH patients . However , this reduction was unrelated to changes in intima – media thickness and casts doubt on the importance of Lp(a ) in the progression of atherosclerotic disease in these patients 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 P 
    Output:
    
agent
Conclusions Fibrates have a significantly greater effect in reducing plasma Lp(a ) concentrations than statins .
Addition of fibrates to statins can enhance the Lp(a)-lowering effect of statins
***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: CONTEXT High levels of lipoprotein(a ) are associated with increased risk of myocardial infa rct ion ( MI ) . OBJECTIVE To assess whether genetic data are consistent with this association being causal . DESIGN , SETTING , AND PARTICIPANTS Three studies of white individuals from Copenhagen , Denmark , were used : the Copenhagen City Heart Study ( CCHS ) , a prospect i ve general population study with 16 years of follow-up ( 1991 - 2007 , n = 8637 , 599 MI events ) ; the Copenhagen General Population Study ( CGPS ) , a cross-sectional general population study ( 2003 - 2006 , n = 29 388 , 994 MI events ) ; and the Copenhagen Ischemic Heart Disease Study ( CIHDS ) , a case-control study ( 1991 - 2004 , n = 2461 , 1231 MI events ) . MAIN OUTCOME MEASURES Plasma lipoprotein(a ) levels , lipoprotein(a ) kringle IV type 2 ( KIV-2 ) size polymorphism genotype , and MIs recorded from 1976 through July 2007 for all participants . RESULTS In the CCHS , multivariable-adjusted hazard ratios ( HRs ) for MI for elevated lipoprotein(a ) levels were 1.2 ( 95 % confidence interval [ CI ] , 0.9 - 1.6 ; events/10,000 person-years , 59 ) for levels between the 22nd and 66th percentile , 1.6 ( 95 % CI , 1.1 - 2.2 ; events/10,000 person-years , 75 ) for the 67th to 89th percentile , 1.9 ( 95 % CI , 1.2 - 3.0 ; events/10,000 person-years , 84 ) for the 90th to 95th percentile , and 2.6 ( 95 % CI , 1.6 - 4.1 ; events/10,000 person-years , 108 ) for levels greater than the 95th percentile , respectively , vs levels less than the 22nd percentile ( events/10,000 person-years , 55 ) ( trend P < .001 ) . Numbers of KIV-2 repeats ( sum of repeats on both alleles ) ranged from 6 to 99 and on analysis of variance explained 21 % and 27 % of all variation in plasma lipoprotein(a ) levels in the CCHS and CGPS , respectively . Mean lipoprotein(a ) levels were 56 , 31 , 20 , and 15 mg/dL for the first , second , third , and fourth quartiles of KIV-2 repeats in the CCHS , respectively ( trend P < .001 ) ; corresponding values in the CGPS were 60 , 34 , 22 , and 19 mg/dL ( trend P < .001 ) . In the CCHS , multivariable-adjusted HRs for MI were 1.5 ( 95 % CI , 1.2 - 1.9 ; events/10,000 person-years , 75 ) , 1.3 ( 95 % CI , 1.0 - 1.6 ; events/10,000 person-years , 66 ) , and 1.1 ( 95 % CI , 0.9 - 1.4 ; events/10,000 person-years , 57 ) for individuals in the first , second , and third quartiles , respectively , as compared with individuals in the fourth quartile of KIV-2 repeats ( events/10,000 person-years , 51 ) ( trend P < .001 ) . Corresponding odds ratios were 1.3 ( 95 % CI , 1.1 - 1.5 ) , 1.1 ( 95 % CI , 0.9 - 1.3 ) , and 0.9 ( 95 % CI , 0.8 - 1.1 ) in the CGPS ( trend P = .005 ) , and 1.4 ( 95 % CI , 1.1 - 1.7 ) , 1.2 ( 95 % CI , 1.0 - 1.6 ) , and 1.3 ( 95 % CI , 1.0 - 1.6 ) in the CIHDS ( trend P = .01 ) . Genetically elevated lipoprotein(a ) was associated with an HR of 1.22 ( 95 % CI , 1.09 - 1.37 ) per doubling of lipoprotein(a ) level on instrumental variable analysis , while the corresponding value for plasma lipoprotein(a ) levels on Cox regression was 1.08 ( 95 % CI , 1.03 - 1.12 ) . CONCLUSION These data are consistent with a causal association between elevated lipoprotein(a ) levels and increased risk of MI Objective — Lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) is a predictor for incident atherosclerotic disease . We investigated the effect of 3 hypolipidemic drugs that exert their action through different mechanisms on plasma and lipoprotein-associated Lp-PLA2 activity and mass . Methods and Results — In 50 patients with Type IIA dyslipidemia were administered rosuvastatin ( 10 mg daily ) , whereas in 50 Type IIA dyslipidemic patients exhibiting intolerance to previous statin therapy were administered ezetimibe as monotherapy ( 10 mg daily ) . Fifty patients with Type IV dyslipidemia were given micronised fenofibrate ( 200 mg daily ) . Low- and high-density lipoprotein ( LDL and HDL , respectively ) subclass analysis was performed electrophoretically , whereas lipoprotein subfractions were isolated by ultracentrifugation . Ezetimibe reduced plasma Lp-PLA2 activity and mass attributable to the reduction in plasma levels of all LDL subfractions . Rosuvastatin reduced enzyme activity and mass because of the decrease in plasma levels of all LDL subfractions and especially the Lp-PLA2 on dense LDL subfraction ( LDL-5 ) . Fenofibrate preferentially reduced the Lp-PLA2 activity and mass associated with the VLDL+IDL and LDL-5 subfractions . Among studied drugs only fenofibrate increased HDL-associated Lp-PLA2 ( HDL-Lp-PLA2 ) activity and mass attributable to a preferential increase in Lp-PLA2 associated with the HDL-3c subfraction . Conclusion — Ezetimibe , rosuvastatin , and fenofibrate reduce Lp-PLA2 activity and mass associated with the atherogenic apoB-lipoproteins . Furthermore , fenofibrate improves the enzyme specific activity on apoB-lipoproteins and induces the HDL-Lp-PLA2 . The clinical implication s of these effects remain to be established Lipoprotein ( a ) [ Lp(a ) ] is an independent risk factor for cardiovascular disease . There are currently limited therapeutic options to lower Lp(a ) levels . l-Carnitine has been reported to reduce Lp(a ) levels . The aim of this study was to compare the effect of l-carnitine/simvastatin co-administration with that of simvastatin monotherapy on Lp(a ) levels in subjects with mixed hyperlipidemia and elevated Lp(a ) concentration . Subjects with levels of low-density lipoprotein cholesterol ( LDL-C ) > 160 mg/dL , triacylglycerol ( TAG ) > 150 mg/dL and Lp(a ) > 20 mg/dL were included in this study . Subjects were r and omly allocated to receive l-carnitine 2 g/day plus simvastatin 20 mg/day ( N = 29 ) or placebo plus simvastatin 20 mg/day ( N = 29 ) for a total of 12 weeks . Lp(a ) was significantly reduced in the l-carnitine/simvastatin group [ −19.4 % , from 52 ( 20–171 ) to 42 ( 15–102 ) mg/dL ; p = 0.01 ] , but not in the placebo/simvastatin group [ −6.7 % , from 56 ( 26–108 ) to 52 ( 27–93 ) mg/dL , p = NS versus baseline and p = 0.016 for the comparison between groups ] . Similar significant reductions in total cholesterol , LDL-C , apolipoprotein ( apo ) B and TAG were observed in both groups . Co-administration of l-carnitine with simvastatin was associated with a significant , albeit modest , reduction in Lp(a )  compared with simvastatin monotherapy in subjects with mixed hyperlipidemia and elevated baseline Lp(a ) levels Background : Raised plasma lipoprotein(a ) ( Lp(a ) ) is associated with increased risk of cardiovascular disease . It is unknown whether increased Lp(a ) is an additional risk factor for coronary artery disease in familial hypercholesterolaemia ( FH ) or whether statin treatment can reduce Lp(a ) concentrations in the long term . Objective : To investigate Lp(a ) concentrations in relation to statin treatment and the progression of atherosclerosis in a large cohort of FH patients . Design : A two year , r and omised , double blind trial ( the ASAP trial ) . Patients : 325 heterozygous FH patients . Intervention : Treatment with 80 mg atorvastatin or 40 mg simvastatin . Main outcome measure : Change in Lp(a ) concentrations and intima – media thickness of carotid artery segments at one year and two years . Results : At baseline , median Lp(a ) concentrations were 327 mg/l and 531 mg/l in the atorvastatin and simvastatin arms , respectively ( p = 0.03 ) . In the atorvastatin arm , Lp(a ) concentrations decreased to 243 mg/l after one year ( p < 0.001 ) and to 263 mg/l after two years ( p < 0.001 ) . In the simvastatin arm , Lp(a ) concentrations decreased to 437 mg/l after one year ( p < 0.001 ) and to 417 mg/l after two years ( p < 0.001 ) . The difference in Lp(a ) reduction between the two treatment arms was significant after one year ( p = 0.004 ) , but not after two years ( p = 0.086 ) . Lp(a ) concentrations at baseline were not related to cardiovascular events at baseline . There was no correlation between baseline Lp(a ) concentrations and low density lipoprotein cholesterol concentrations or intima – media thickness at baseline . Change in Lp(a ) concentrations was not correlated with change in intima – media thickness after one or two years . Conclusions : Long term statin treatment significantly lowers Lp(a ) in FH patients . However , this reduction was unrelated to changes in intima – media thickness and casts doubt on the importance of Lp(a ) in the progression of atherosclerotic disease in these patients 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 P 
    Output:
    