***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 Background —Oxidized phospholipids ( OxPL ) circulate on apolipoprotein B-100 particles ( OxPL/apoB ) , and primarily on Lp(a ) lipoprotein ( a ) [ Lp(a ) ] . The relationship of OxPL/apoB levels to future cardiovascular events is not known . Methods and Results —The Bruneck study is a prospect i ve population -based survey of 40- to 79-year-old men and women recruited in 1990 .  Plasma levels of OxPL/apoB and lipoprotein ( a ) [ Lp(a ) ]  were measured in 765 subjects in 1995 and incident cardiovascular disease ( CVD ) , defined as cardiovascular death , myocardial infa rct ion , stroke , and transient ischemic attack , was assessed from 1995 to 2005 . During the follow-up period , 82 subjects developed CVD . In multivariable analysis , which included traditional risk factors , high sensitivity C-reactive protein ( hsCRP ) , and lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) activity , subjects in the highest tertile of OxPL/apoB had a significantly higher risk of cardiovascular events than those in the lowest tertile ( hazard ratio[95 % CI ] 2.4[1.3 to 4.3 ] , P=0.004 ) . The strength of the association between OxPL/apoB and CVD risk was amplified with increasing Lp-PLA2 activity ( P=0.018 for interaction ) . Moreover , OxPL/apoB levels predicted future cardiovascular events beyond the information provided by the Framingham Risk Score ( FRS ) . The effects of OxPL/apoB and Lp(a ) were not independent of each other but they were independent of all other measured risk factors . Conclusions —This study demonstrates that OxPL/apoB levels predict 10-year CVD event rates independently of traditional risk factors , hsCRP , and FRS . Increasing Lp-PLA2 activity further amplifies the risk of CVD mediated by BACKGROUND Oxidized phospholipids on apolipoprotein B-100 ( OxPL-apoB ) is a biomarker of increased risk for major adverse cardiovascular events ( MACE ) in community cohorts , but its role in patients with stable coronary heart disease ( CHD ) is unknown . OBJECTIVES This study sought to examine the relationship between these oxidative biomarkers and cardiovascular outcomes in patients with established CHD . METHODS In a r and om sample from the TNT ( Treating to New Targets ) trial , OxPL-apoB levels were measured in 1,503 patients at r and omization ( after an 8-week run-in period taking atorvastatin 10 mg ) and 1 year after being r and omized to atorvastatin 10 or 80 mg . We examined the association between baseline levels of OxPL-apoB and MACE , defined as death from CHD , nonfatal myocardial infa rct ion , resuscitation after cardiac arrest , and fatal/nonfatal stroke , as well as the effect of statin therapy on OxPL-apoB levels and MACE . RESULTS Patients with events ( n = 156 ) had higher r and omization levels of OxPL-apoB than those without events ( p = 0.025 ) . For the overall cohort , r and omization levels of OxPL-apoB predicted subsequent MACE ( hazard ratio [ HR ] : 1.21 ; 95 % confidence interval : 1.04 to 1.41 ; p = 0.018 ) per doubling and tertile 3 versus tertile 1 ( hazard ratio : 1.69 ; 95 % confidence interval [ CI ] : 1.14 to 2.49 ; p = 0.01 ) after multivariate adjustment for age , sex , body mass index , among others , and treatment assignment . In the atorvastatin 10-mg group , tertile 3 was associated with a higher risk of MACE compared to the first tertile ( HR : 2.08 ; 95 % CI : 1.20 to 3.61 ; p = 0.01 ) but this was not significant in the atorvastatin 80-mg group ( HR : 1.40 ; 95 % CI : 0.80 to 2.46 ; p = 0.24 ) . CONCLUSIONS Elevated OxPL-apoB levels predict secondary MACE in patients with stable CHD , a risk that is mitigated by atorvastatin 80 mg . ( A Study to Determine the Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target Levels [ TNT ] ; NCT00327691 ) OBJECTIVES The aim of this study was to determine the effects of pravastatin and atorvastatin on markers of oxidative stress in plasma . BACKGROUND Hydroxymethylglutaryl coenzyme A reductase inhibitors reduce low-density lipoprotein cholesterol ( LDL-C ) and cardiovascular risk , but their effects on circulating biomarkers of oxidative stress are not well-defined . METHODS Hypercholesterolemic subjects ( n = 120 , ages 21 to 80 years with LDL-C 130 to 220 mg/dl ) were r and omized in a double-blind , parallel design to pravastatin 40 mg/day ( prava40 ) , atorvastatin 10 mg/day ( atorva10 ) , atorvastatin 80 mg/day ( atorva80 ) , or placebo . At baseline and 16 weeks , urinary isoprostanes ( 8 , 12-iso-iPF(2 alpha)-VI isoform ) , plasma lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) , Mercodia oxidized LDL ( OxLDL ) with antibody 4E6 , oxidized phospholipids/apolipoprotein B-100 particle ( OxPL/apoB ) with antibody E06 , immunoglobulin (Ig)G/IgM autoantibodies to malondialdehyde (MDA)-LDL , and apolipoprotein B (apoB)-immune complexes ( IC ) were measured . RESULTS After 16 weeks , there were no significant changes in urinary 8 , 12-iso-iPF(2 alpha)-VI . The Lp-PLA2 and OxLDL were reduced in statin-treated groups , but after adjusting for apoB , only prava40 led to a reduction in Lp-PLA2 ( -15 % , p = 0.008 ) and atorva10 to a decrease in OxLDL ( -12.9 % , p = 0.01 ) . The OxPL/apoB increased 25.8 % ( p < 0.01 ) with prava40 and 20.2 % ( p < 0.05 ) with atorva80 . There were no changes in MDA-LDL autoantibodies , but significant decreases in IC were noted . CONCLUSIONS This study suggests that statin therapy results in variable effects on oxidative stress markers in hypercholesterolemic subjects . Future outcome studies should collectively assess various oxidative markers to define clinical utility BACKGROUND Lipoprotein(a ) ( Lp[a ] ) is a risk factor for cardiovascular disease and calcific aortic valve stenosis . No effective therapies to lower plasma Lp(a ) concentrations exist . We have assessed the safety , pharmacokinetics , and pharmacodynamics of ISIS-APO(a)Rx , a second-generation antisense drug design ed to reduce the synthesis of apolipoprotein(a ) ( apo[a ] ) in the liver . METHODS In this r and omised , double-blind , placebo-controlled , phase 1 study at the PAREXEL Clinical Pharmacology Research Unit ( Harrow , Middlesex , UK ) , we screened for healthy adults aged 18 - 65 years , with a body-mass index less than 32·0 kg/m(2 ) , and Lp(a ) concentration of 25 nmol/L ( 100 mg/L ) or more . Via a r and omisation technique , we r and omly assigned participants to receive a single subcutaneous injection of ISIS-APO(a)Rx ( 50 mg , 100 mg , 200 mg , or 400 mg ) 
    Output:
    
This study demonstrates differential changes in OxPL-apoB and Lp(a ) with various lipid-lowering approaches .
These changes in OxPL-apoB and Lp(a ) may provide insights into the results and interpretation of recent cardiovascular disease outcomes trials