***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 
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    ***EXAMPLES*** 
    Input: BACKGROUND AND AIMS Increased arterial stiffness is closely linked with raised blood pressure that contributes substantially to enhanced risk of coronary heart disease in high risk individuals with familial hypercholesterolaemia ( FH ) .  Omega-3 fatty acid ( ω3-FA ) supplementation has been demonstrated to lower blood pressure in subjects with a high cardiovascular disease risk . Whether ω3-FA supplementation improves arterial stiffness in FH subjects , on background statin therapy , has yet to be investigated . METHOD AND RESULTS We carried out an 8-week r and omized , crossover intervention trial to test the effect of 4 g/d ω3-FA supplementation ( 46 % eicosapentaenoic acid and 38 % docosahexaenoic acid ) on arterial elasticity in 20 adults with FH on optimal cholesterol-lowering therapy .  Large and small artery elasticity were measured by pulse contour analysis of the radial artery . ω3-FA supplementation significantly ( P < 0.05 in all ) increased large artery elasticity ( + 9 % ) and reduced systolic blood pressure ( -6 % ) and diastolic blood pressure ( -6 % ) , plasma triglycerides ( -20 % ) , apoB concentration ( -8 % ) . In contrast , ω3-FAs had no significant effect on small artery elasticity . The change in large artery elasticity was not significantly associated with changes in systolic blood pressure or plasma triglyceride concentration . CONCLUSIONS ω3-FA supplementation  improves large arterial elasticity and arterial blood pressure independent of statin therapy in adults with FH . CLINICAL TRIAL REGISTRATION https://www . clinical trials.com/NCT01577056 BACKGROUND The efficacy and safety of atorvastatin in children/adolescents aged 10 - 17 years with heterozygous familial hypercholesterolemia ( HeFH ) have been demonstrated in trials of up to 1 year in duration . However , the efficacy/safety of > 1 year use of atorvastatin in children/adolescents with HeFH , including children from 6 years of age , has not been assessed . OBJECTIVE To characterize the efficacy and safety of atorvastatin over 3 years and to assess the impact on growth and development in children aged 6 - 15 years with HeFH . METHODS A total of 272 subjects aged 6 - 15 years with HeFH and low-density lipoprotein cholesterol ( LDL-C ) ≥4.0 mmol/L ( 154 mg/dL ) were enrolled in a 3-year study ( NCT00827606 ) . Subjects were initiated on atorvastatin ( 5 mg or 10 mg ) with doses increased to up to 80 mg based on LDL-C levels . RESULTS Mean percentage reductions from baseline in LDL-C at 36 months/early termination were 43.8 % for subjects at Tanner stage ( TS ) 1 and 39.9 % for TS ≥2 . There was no evidence of variations in the lipid-lowering efficacy  of atorvastatin between the TS groups analyzed ( 1 vs ≥2 ) or in subjects aged < 10 vs ≥10 years , and the treatment had no adverse effect on growth or maturation  . Atorvastatin had a favorable safety and tolerability profile , and only 6 ( 2.2 % ) subjects discontinued because of adverse events . CONCLUSIONS Atorvastatin over 3 years was efficacious , had no impact on growth/maturation , and was well tolerated in children and adolescents with HeFH aged 6 - 15 years OBJECTIVES This study was undertaken to evaluate the efficacy and safety of rosuvastatin therapy for children with familial hypercholesterolemia . BACKGROUND Familial hypercholesterolemia is a common inherited disorder causing markedly elevated low-density lipoprotein cholesterol ( LDL-C ) levels from birth and result ing in premature atherosclerosis . In children , statins have been shown to be effective in reducing LDL-C , restoring flow-mediated dilation , and slowing carotid intima-media thickening . However , few children in these trials achieved current LDL-C goals . METHODS This study comprised a 12-week double-blind , r and omized , placebo-controlled trial , followed by a 40-week open-label , titration-to- goal extension phase in 177 pubertal children , ages 10 to 17 years , with familial hypercholesterolemia . Participants were r and omly assigned to placebo or rosuvastatin 5 , 10 , or 20 mg once daily . RESULTS Compared with placebo , rosuvastatin 5 , 10 , and 20 mg reduced LDL-C by 38 % , 45 % , and 50 % , respectively ( p < 0.001 for each group vs. placebo ) . With a maximum allowed dose of 20 mg , 40 % achieved the treatment goal of < 110 mg/dl during the open-label , titration-to- goal phase . Rosuvastatin was well tolerated , with no apparent adverse impact on growth or development . CONCLUSIONS In children with familial hypercholesterolemia , rosuvastatin 20 mg daily reduced LDL-C by 50 % . Nonetheless , only 40 % attained the consensus LDL-C target of < 110 mg/dl , reflecting these patients ' high baseline LDL-C levels ( mean , 232 mg/dl ) . ( Pediatric Lipid-Reduction Trial of Rosuvastatin [ PLUTO ] ; NCT00355615 ) As part of a r and omised trial [ Genetic Risk Assessment for Familial Hypercholesterolaemia ( FH ) Trial ] of the psychological consequences of DNA-based and non-DNA-based diagnosis of FH , 338 prob and s with a clinical diagnosis of FH ( 46 % with tendon xanthomas ) were recruited . In the DNA-based testing arm ( 245 prob and s ) , using single-str and conformation polymorphism of all exons of the low-density lipoprotein receptor ( LDLR ) gene , 48 different pathogenic mutations were found in 62 prob and s ( 25 % ) , while 7 ( 2.9 % ) of the patients had the R3500Q mutation in the apolipoprotein B ( APOB ) gene . Compared to those with no detected mutation , mean untreated cholesterol levels in those with the APOB mutation were similar , while in those with an LDLR mutation levels were significantly higher ( None=9.15±1.62 vs LDLR=9.13±1.16 vs APOB=10.26±2.07 mmol/l p<0.001 , respectively ) . Thirty seven percent of the detected mutations were in exon 3/4 of LDLR , and this group had significantly higher untreated cholesterol than those with other LDLR mutations ( 11.71±2.39 mmol/l vs 9.88±2.44 mmol/l , p=0.03 ) , and more evidence of coronary disease compared to those with other LDLR or APOB mutations ( 36 vs 13 % p=0.04 ) . Of the prob and s with a detected mutation , 54 first-degree relatives were identified , of whom 27 ( 50 % ) had a mutation . Of these , 18 had untreated cholesterol above the 95th percentile for their age and gender , but there was overlap with levels in the non-carrier relatives such that 12 % of subjects would have been incorrectly diagnosed on lipid levels alone . In the non-DNA-based testing arm ( 82 prob and s ) only 19 of the 74 relatives identified had untreated cholesterol above the 95th percentile for their age and gender , which was significantly lower ( p<0.0005 ) than the 50 % expected for monogenic inheritance . These data confirm the genetic heterogeneity of LDLR mutations in the UK and the deleterious effect of mutations in exon 3 or 4 of LDLR on receptor function , lipids and severity of coronary heart disease . In patients with a clinical diagnosis of FH but no detectable mutation , there is weaker evidence for a monogenic cause compared with relatives of prob and s with LDLR mutations . This supports the usefulness of DNA testing to confirm diagnosis of FH for the treatment of hyperlipidaemia and for further cascade screening The relationship between molecular defect and clinical phenotype has been examined in 42 patients with heterozygous familial hypercholesterolaemia ( FH ) and premature coronary heart disease . The defined defects included mutations in the low density lipoprotein (LDL)-receptor gene ( 23/42 ) or the apolipoprotein B Arg3500Gln mutation ( 5/42 ) . Mean LDL-cholesterol was higher , both before and during treatment with simvastatin and bile acid sequestrants , in patients predicted as having a ' severe ' mutation than in those with a ' mild ' mutation ( 8.72 + /- 2.02 mmol/l vs 6.63 + /- 1.8 , P = 0.05 before and 4.51 + /- 0.90 mmol/l vs 3.19 + /- 0.58 , P = 0.05 during treatment ) . Maximum inducible LDL-receptor activity in cultured lymphoblasts was inversely correlated with LDL-cholesterol before ( r2 = 0.499 , P = 0.002 ) and during ( r2 = 0.478 , P = 0.004 ) treatment in patients with a defined mutation in the LDL-receptor gene , but not in the 14 patients with no detectable molecular defect . LDL-cholesterol concentrations before and during treatment were significantly correlated in patients with a defined LDL-receptor gene mutation ( r2 = 0.548 , P = 0.0001 ) , but not in those with no detectable genetic defect . All these correlations were weak , however and there were no differences in the response to treatment in terms of either relative reduction or absolute decrease in LDL-cholesterol concentration between patients with different LDL-receptor defects . We conclude that only part of the variable phenotype of heterozygous FH patients is explained by different LDL-receptor defects and that other factors determine the severity of their hypercholesterolaemia and the onset of coronary disease Objective . The present study was design ed to evaluate the lipid-altering efficacy , safety , and tolerability of lovastatin treatment in adolescent girls with heterozygous familial hypercholesterolemia . Methods . A total of 54 postmenarchal girls , aged 10 to 17 years , were enrolled in a 24-week , double-blind , r and omized , placebo-controlled study . After a 4-week diet/placebo run-in period , patients were r and omized to 1 of 2 groups : ( 1 ) treatment with diet plus lovastatin 20 mg/day for 4 weeks , followed by diet plus lovastatin 40 mg/day for 20 weeks , or ( 2 ) diet plus placebo for 24 weeks . Results . Baseline values of lipids , lipoproteins , and apolipoproteins ( apo ) were comparable between treatment groups . Lovastatin treatment was efficacious at reducing low-density lipoprotein cholesterol by 23 % to 27 % , total cholesterol by 17 % to 22 % , and apo B by 20 % to 23 % at weeks 4 and 24 , respectively . Between-treatment group differences were not statistically significant for triglycerides , very-low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , or apo A-I.  Lovastatin was generally safe and well tolerated . There were no clinical ly significant alterations in vital signs ( blood pressure and pulse rate ) , anthropomorphic measurements ( height , weight , and BMI ) , hormone levels ( luteinizing hormone , follicle-stimulating hormone , dehydroepi and rosterone sulfate , estradiol , and cortisol ) , menstrual cycle length , or tests of liver and muscle function . Conclusions . Lovastatin offers an efficacious and well-tolerated treatment option for improving lipid profiles in adolescent girls with familial hypercholesterolemia Background —A multicenter , r and omized , double-blind , placebo-controlled study was conducted to evaluate LDL cholesterol – lowering efficacy , overall safety , and tolerability and the influence on growth and pubertal development of simvastatin in a large cohort of boys and girls with heterozygous familial hypercholesterolemia ( heFH ) . Methods and Results —A total of 173 heFH children ( 98 boys and 75 girls ) were included in this study . After a 4-week diet/placebo run-in period , children with heFH were r and omized to either simvastatin or placebo in a ratio of 3:2 . Simvastatin was started at 10 mg/d and titrated at 8-week intervals to 20 and then 40 mg/d . During a 24-week extension period , the patients continued to receive simvastatin ( 40 mg ) or placebo according to their assignment . After 48 weeks of simvastatin therapy , there were 
    Output:
    
Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low-density lipoprotein cholesterol levels .
Serum aspartate and alanine aminotransferase , as well as creatinine kinase concentrations , did not differ between treated and placebo groups at any time point ( low quality evidence ) .
Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia .
No significant safety issues were identified .
Statin treatment seems to be safe in the short term , but long-term safety remains unknown .