***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: BACKGROUND There is conflicting evidence on the benefits of foods rich in vitamin E ( alpha-tocopherol ) , n-3 polyunsaturated fatty acids ( PUFA ) , and their pharmacological substitutes . We investigated the effects of these substances as supplements in patients who had myocardial infa rct ion . METHODS From October , 1993 , to September , 1995 , 11,324 patients surviving recent ( < or = 3 months ) myocardial infa rct ion were r and omly assigned supplements of n-3 PUFA ( 1 g daily , n=2836 ) , vitamin E ( 300 mg daily , n=2830 ) , both ( n=2830 ) , or none ( control , n=2828 ) for 3.5 years . The primary combined efficacy endpoint was death , non-fatal myocardial infa rct ion , and stroke . Intention-to-treat analyses were done according to a factorial design ( two-way ) and by treatment group ( four-way ) . FINDINGS Treatment with n-3 PUFA , but not vitamin E , significantly lowered the risk of the primary endpoint ( relative-risk decrease 10 % [ 95 % CI 1 - 18 ] by two-way analysis , 15 % [ 2 - 26 ] by four-way analysis ) . Benefit was attributable to a decrease in the risk of death ( 14 % [ 3 - 24 ] two-way , 20 % [ 6 - 33 ] four-way ) and cardiovascular death ( 17 % [ 3 - 29 ] two-way , 30 % [ 13 - 44 ] four-way ) . The effect of the combined treatment was similar to that for n-3 PUFA for the primary endpoint ( 14 % [ 1 - 26 ] ) and for fatal events ( 20 % [ 5 - 33 ] ) . INTERPRETATION Dietary supplementation with n-3 PUFA led to a clinical ly important and statistically significant benefit . Vitamin E had no benefit . Its effects on fatal cardiovascular events require further exploration BACKGROUND The objective of this study was to examine the association of Joint National Committee ( JNC-V ) blood pressure and National Cholesterol Education Program ( NCEP ) cholesterol categories with coronary heart disease ( CHD ) risk , to incorporate them into coronary prediction algorithms , and to compare the discrimination properties of this approach with other noncategorical prediction functions . METHODS AND RESULTS This work was design ed as a prospect i ve , single-center study in the setting of a community-based cohort . The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up . During the 12 years of follow-up , a total of 383 men and 227 women developed  CHD , which was significantly associated with categories of blood pressure , total cholesterol , LDL cholesterol , and HDL cholesterol ( all P<.001 ) . Sex-specific prediction equations were formulated to predict CHD risk according to age , diabetes , smoking , JNC-V blood pressure categories , and NCEP total cholesterol and LDL cholesterol categories . The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used . After adjustment for other factors , approximately 28 % of CHD events in men and 29 % in women were attributable to blood pressure levels that exceeded high normal ( > or = 130/85 ) . The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ( > or = 200 mg/dL ) was 27 % in men and 34 % in women . CONCLUSIONS Recommended guidelines of blood pressure , total cholesterol , and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample . A simple coronary disease prediction algorithm was developed using categorical variables , which allows physicians to predict multivariate CHD risk in patients without overt CHD Drug therapy for hypercholesterolaemia has remained controversial mainly because of insufficient clinical trial evidence for improved survival . The present trial was design ed to evaluate the effect of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease ( CHD ) . 4444 patients with angina pectoris or previous myocardial infa rct ion and serum cholesterol 5.5 - 8.0 mmol/L on a lipid-lowering diet were r and omised to double-blind treatment with simvastatin or placebo . Over the 5.4 years median follow-up period , simvastatin produced mean changes in total cholesterol , low-density-lipoprotein cholesterol , and high-density-lipoprotein cholesterol of -25 % , -35 % , and + 8 % , respectively , with few adverse effects . 256 patients ( 12 % ) in the placebo group died , compared with 182 ( 8 % ) in the simvastatin group . The relative risk of death in the simvastatin group was 0.70 ( 95 % CI 0.58 - 0.85 , p = 0.0003 ) . The 6-year probabilities of survival in the placebo and simvastatin groups were 87.6 % and 91.3 % , respectively . There were 189 coronary deaths in the placebo group and 111 in the simvastatin group ( relative risk 0.58 , 95 % CI 0.46 - 0.73 ) , while noncardiovascular causes accounted for 49 and 46 deaths , respectively . 622 patients ( 28 % ) in the placebo group and 431 ( 19 % ) in the simvastatin group had one or more major coronary events . The relative risk was 0.66 ( 95 % CI 0.59 - 0.75 , p < 0.00001 ) , and the respective probabilities of escaping such events were 70.5 % and 79.6 % . This risk was also significantly reduced in subgroups consisting of women and patients of both sexes aged 60 or more . Other benefits of treatment included a 37 % reduction ( p < 0.00001 ) in the risk of undergoing myocardial revascularisation procedures . This study shows that long-term treatment with simvastatin is safe and improves survival in CHD patients A double-blind , placebo-controlled study was conducted to compare the efficacy and safety of low-dose ( 10 mg ) prevastatin and squalene ( 860 mg ) , either alone or in combination therapy , with placebo in the treatment of elderly patients with hypercholesterolemia . Ambulatory elderly patients ( N = 102 ) were assigned in r and omized fashion to receive active treatment or placebo for 20 weeks after a single-blind placebo lead-in period of 8 weeks . Total cholesterol and triglyceride levels in plasma were at least 250 mg/dL and less than 300 mg/dL , respectively . Concentrations of lipids and lipoproteins were measured , and clinical laboratory tests included liver function and creatine kinase determinations . Pravastatin 10 mg daily was more effective than squalene in reducing total cholesterol , low-density lipoprotein ( LDL ) cholesterol , and triglycerides and in increasing levels of high-density lipoprotein ( HDL ) cholesterol . Combination therapy significantly reduced total cholesterol and LDL cholesterol and increased HDL cholesterol to a greater extent than either drug alone . Adverse events and clinical laboratory abnormalities were generally mild and transient in all groups , and all but two patients finished the study . The incidence of side effects was low ; myopathy did not occur . Coadministration of pravastatin and squalene combined the specific effects of the two drugs on lipoprotein concentrations . This combination may be useful and more cost-effective in elderly patients with hypercholesterolemia , who might have a higher incidence of side effects when using larger doses of pravastatin alone Studies considering long-term squalene consumption have revealed no consistent effects on serum cholesterol levels but the immediate effect of dietary squalene on cholesterol synthesis has not been studied . Thus , the effect of a single dose of dietary squalene on postpr and ial lipid metabolism was studied in 16 male volunteeers aged 22 - 79 years .  Two oral fat meals a week apart were administered to every subject , one without ( control ) and the other with 500 mg of squalene . Lipids , retinyl palmitate , squalene and non-cholesterol sterols  were measured at baseline and after 3 , 4 , 6 , 9 , 12 and 24 h postpr and ially in plasma , chylomicron , VLDL and VLDL bottom and , in six r and omly chosen subjects , also in IDL , LDL and HDL . In the fasting sample s , squalene was mainly transported in LDL and HDL , whereas in squalene-supplemented postpr and ium most of squalene was carried in the triglyceride-rich lipoproteins . Postpr and ial squalene and retinyl palmitate curves closely resembled each other . After the squalene-enriched dietary fat load , squalene was significantly increased compared to control fat loads in plasma , chylomicrons , VLDL and IDL . Squalene addition increased significantly lathosterol/campesterol ratio in chylomicrons and VLDL at 12 h and in VLDL bottom at 9 - 12 h , and increased significantly VLDL lanosterol/campesterol ratio at 12 h , indicating enhanced cholesterol synthesis caused by squalene . Plasma plant sterol levels remained unchanged . In conclusion , a single oral dose of squalene representing a potential daily dietary amount increases cholesterol synthesis within 9 - 12 h detected in chylomicrons , VLDL and VLDL bottom Background Several case reports and a single epidemiologic study indicate that use of statins occasionally may have a deleterious effect on the peripheral nervous system . The authors therefore performed a population -based study to estimate the relative risk of idiopathic polyneuropathy in users of statins . Method The authors used a population -based patient registry to identify first-time-ever cases of idiopathic polyneuropathy registered in the 5-year period 1994 to 1998 . For each case , vali date d according to predefined criteria , 25 control subjects were r and omly selected among subjects from the background population matched for age , sex , and calendar time . The authors used a prescription register to assess exposure to drugs and estimated the odds ratio of use of statins  ( ever and current use ) in cases of idiopathic polyneuropathy compared with control subjects . Results The authors verified a diagnosis of idiopathic polyneuropathy in 166 cases . The cases were classified as definite ( 35 ) , probable ( 54 ) , or possible ( 77 ) . The odds ratio linking idiopathic polyneuropathy with statin use was 3.7 ( 95 % CI 1.8 to 7.6 ) for all cases and 14.2 ( 5.3 to 38.0 ) for definite cases . The corresponding odds ratios in current users were 4.6 ( 2.1 to 10.0 ) for all cases and 16.1 ( 5.7 to 45.4 ) for definite cases . For patients treated with statins for 2 or more years the odds ratio of definite idiopathic polyneuropathy was 26.4 ( 7.8 to 45.4 ) . Conclusions Long-term exposure to statins may substantially increase the risk of polyneuropathy BACKGROUND In patients with high cholesterol levels , lowering the cholesterol level reduces the risk of coronary events , but the effect of lowering cholesterol levels in the majority of patients with coronary disease , who have average levels , is less clear . METHODS In a double-blind trial lasting five years we administered either 40 mg of pravastatin per day or placebo to 4159 patients ( 3583 men and 576 women ) with myocardial infa rct ion who had plasma total cholesterol levels below 240 mg per deciliter ( mean , 209 ) and low-density lipoprotein ( LDL ) cholesterol levels of 115 to 174 mg per deciliter ( mean , 139 ) . The primary end point was a fatal coronary event or a nonfatal myocardial infa rct ion . RESULTS The frequency of the primary end point was 10.2 percent in the pravastatin group and 13.2 percent in the placebo group , an absolute difference of 3 percentage points and a 24 percent reduction in risk ( 95 percent confidence interval , 9 to 36 percent ; P = 0.003 ) . Coronary bypass surgery was needed in 7.5 percent of the patients in the pravastatin group and 10 percent of those in the placebo group , a 26 percent reduction ( P=0.005 ) , and coronary angioplasty was needed in 8.3 percent of the pravastatin group and 10.5 percent of the placebo group , a 23 percent reduction ( P=0.01 ) . The frequency of stroke was reduced by 31 percent ( P=0.03 ) . There were no significant differences in overall mortality or mortality from noncardiovascular causes . Pravastatin lowered the rate of coronary events more among women than among men . The reduction in coronary events was also greater in patients with higher pretreatment levels of LDL cholesterol . CONCLUSIONS These results demonstrate that the benefit of ch 
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CONCLUSIONS This evidence -based review emphasizes the potential of SQ being used for cardiovascular-related diseases .