***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: 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 OBJECTIVES This study was design ed to determine whether simvastatin improves endothelial function in children with familial hypercholesterolemia ( FH ) . BACKGROUND Endothelial function measured by flow-mediated dilation of the brachial artery ( FMD ) is used as a surrogate marker of cardiovascular disease ( CVD ) . Adult studies have shown that statins reverse endothelial dysfunction and therefore reduce the risk for future CVD . METHODS The study included 50 children with FH ( 9 to 18 years ) and 19 healthy , non-FH controls . Children with FH were r and omized to receive simvastatin or placebo for 28 weeks . The FMD was performed at baseline and at 28 weeks of treatment . RESULTS At baseline , FMD was impaired in children with FH versus non-FH controls ( p < 0.024 ) . In the simvastatin FH group , FMD improved significantly , whereas the FMD remained unaltered in the placebo FH group throughout the study period ( absolute increase 3.9 % + /- 4.3 % vs. 1.2 % + /- 3.9 % , p < 0.05 ) . In the simvastatin FH group , FMD increased to a level similar to the non-FH controls ( 15.6 % + /- 6.8 % vs. 15.5 % + /- 5.4 % , p = 0.958 ) . Upon treatment , the simvastatin FH group showed significant absolute reductions of total cholesterol ( TC ) ( -2.16 + /- 1.04 mmol/l , 30.1 % ) and low-density lipoprotein cholesterol ( LDL-C ) ( -2.13 + /- 0.99 mmol/l , 39.8 % ) . The absolute change of FMD after 28 weeks of therapy was inversely correlated to changes of TC ( r = -0.31 , p < 0.05 ) and LDL-C ( r = -0.31 , p < 0.05 ) . CONCLUSIONS Our data show significant improvement of endothelial dysfunction towards normal levels after short-term simvastatin therapy in children with FH . These results emphasize the relevance of statin therapy in patients with FH at an early stage , when the atherosclerotic process is still reversible The relation of peripheral flow-mediated vasodilation and coronary arterial calcium was studied in young patients with heterozygous familial hypercholesterolemia ( FH ) using high-resolution ultrasound and multi-detector computed tomography ( MDCT ) . We found that peripheral flow mediated vasodilation , a precursor of atherosclerosis , is altered in young heterozygous patients with FH . This alteration occurs before coronary arterial or aortic root calcium can be detected by MDCT and is independently related to hypercholesterolemia Objective To quantify the unintended effects of statins according to type , dose , and duration of use . Design Prospect i ve open cohort study using routinely collected data . Setting 368 general practice s in Engl and and Wales supplying data to the Q Research data base . Participants 2 004 692 patients aged 30 - 84 years of whom 225 922 ( 10.7 % ) were new users of statins : 159 790 ( 70.7 % ) were prescribed simvastatin  , 50 328 ( 22.3 % ) atorvastatin , 8103 ( 3.6 % ) pravastatin , 4497 ( 1.9 % ) rosuvastatin , and 3204 ( 1.4 % ) fluvastatin . Methods Cox proportional hazards models were used to estimate effects of statin type , dose , and duration of use . The number needed to treat ( NNT ) or number needed to harm ( NNH ) was calculated and numbers of additional or fewer cases estimated for 10 000 treated patients . Main outcome measure First recorded occurrence of cardiovascular disease , moderate or serious myopathic events , moderate or serious liver dysfunction , acute renal failure , venous thromboembolism , Parkinson ’s disease , dementia , rheumatoid arthritis , cataract , osteoporotic fracture , gastric cancer , oesophageal cancer , colon cancer , lung cancer , melanoma , renal cancer , breast cancer , or prostate cancer . Results Individual statins were not significantly associated with risk of Parkinson ’s disease , rheumatoid arthritis , venous thromboembolism , dementia , osteoporotic fracture , gastric cancer , colon cancer , lung cancer , melanoma , renal cancer , breast cancer , or prostate cancer . Statin use was associated with decreased risks of oesophageal cancer but increased risks of moderate or serious liver dysfunction , acute renal failure , moderate or serious myopathy , and cataract . Adverse effects were similar across statin types for each outcome except liver dysfunction where risks were highest for fluvastatin . A dose-response effect was apparent for acute renal failure and liver dysfunction . All increased risks persisted during treatment and were highest in the first year . After stopping treatment the risk of cataract returned to normal within a year in men and women . Risk of oesophageal cancer returned to normal within a year in women and within 1 - 3 years in men . Risk of acute renal failure returned to normal within 1 - 3 years in men and women , and liver dysfunction within 1 - 3 years in women and from three years in men . Based on the 20 % threshold for cardiovascular risk , for women the NNT with any statin to prevent one case of cardiovascular disease over five years was 37 ( 95 % confidence interval 27 to 64 ) and for oesophageal cancer was 1266 ( 850 to 3460 ) and for men the respective values were 33 ( 24 to 57 ) and 1082 ( 711 to 2807 ) . In women the NNH for an additional case of acute renal failure over five years was 434 ( 284 to 783 ) , of moderate or severe myopathy was 259 ( 186 to 375 ) , of moderate or severe liver dysfunction was 136 ( 109 to 175 ) , and of cataract was 33 ( 28 to 38 ) . Overall , the NNHs and NNTs for men were similar to those for women , except for myopathy where the NNH was 91 ( 74 to 112 ) . Conclusions Cl aims of unintended benefits of statins , except for oesophageal cancer , remain unsubstantiated , although potential adverse effects at population level were confirmed and quantified . Further studies are needed to develop utilities to individualise the risks so that patients at highest risk of adverse events can be monitored closely Background — The lipid-lowering effects of statin therapy show considerable interindividual variation in patients with familial hypercholesterolemia ( FH ) . Whether the type of LDL receptor mutation predicts the response to statin treatment is not yet established . We analyzed the relationship between LDL receptor genotype and response to pravastatin treatment in children with FH using carotid intima-media thickness ( IMT ) to measure efficacy . Methods and Results — In a r and omized , placebo-controlled , double-blind , 2-year trial with pravastatin , 193 children had genetically confirmed FH and were included in the present sub study . At baseline , children with null alleles had higher LDL cholesterol levels ( difference , 0.94±0.19 mmol/L [ SEM ] ; P<0.001 ) and a greater carotid IMT ( difference , 0.019±0.01 mm ; P=0.02 ) compared with children with receptor-defective mutations . The decrease in carotid IMT during the trial was not significantly different in children with null alleles and receptor-defective mutations ( 0.018±0.012 and 0.012±0.010 mm ; 2-way ANCOVA , P=0.7 ) . After 2 years of treatment , the children with null alleles continued to have greater carotid IMT than children with receptor-defective mutations ( difference , 0.016±0.01 mm ; P=0.02 ) . LDL cholesterol lowering tended to be less in carriers of null alleles compared with carriers of receptor-defective mutations ( 1.30±0.25 and 1.85±0.20 mmol/L ; 2-way ANCOVA , P=0.08 ) . Conclusions — In FH children , we found that the null allele genotype was associated with a greater carotid 
    Output:
    
Statins reduced the mean LDL cholesterol concentration at all time points .
The risks of myopathy and clinical adverse events were very low and also similar in both groups .
AUTHORS ' CONCLUSIONS Statin treatment is an efficient 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 is unknown .