***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: The British Regional Heart Study ( BRHS ) reported in 1986 that much of the inverse relation of high-density lipoprotein cholesterol ( HDLC ) and incidence of coronary heart disease was eliminated by covariance adjustment . Using the proportional hazards model and adjusting for age , blood pressure , smoking , body mass index , and low-density lipoprotein cholesterol , we analyzed this relation separately in the Framingham Heart Study ( FHS ) , Lipid Research Clinics Prevalence Mortality Follow-up Study ( LRCF ) and Coronary Primary Prevention Trial ( CPPT ) , and Multiple Risk Factor Intervention Trial ( MRFIT ) . In CPPT and MRFIT ( both r and omized trials in middle-age high-risk men ) , only the control groups were analyzed . A 1-mg/dl ( 0.026 mM ) increment in HDLC was associated with a significant coronary heart disease risk decrement of 2 % in men ( FHS , CPPT , and MRFIT ) and 3 % in women ( FHS ) . In LRCF , where only fatal outcomes were documented , a 1-mg/dl increment in HDLC was associated with significant 3.7 % ( men ) and 4.7 % ( women ) decrements in cardiovascular disease mortality rates . The 95 % confidence intervals for these decrements in coronary heart and cardiovascular disease risk in the four studies overlapped considerably , and all contained the range 1.9 - 2.9 % . HDLC levels were essentially unrelated to non-cardiovascular disease mortality . When differences in analytic methodology were eliminated , a consistent inverse relation of HDLC levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies BACKGROUND Since inflammation is believed to have a role in the pathogenesis of cardiovascular events , measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation . The markers included high-sensitivity C-reactive protein ( hs-CRP ) , serum amyloid A , interleukin-6 , and soluble intercellular adhesion molecule type 1 ( sICAM-1 ) . We also studied homocysteine and a variety of lipid and lipoprotein measurements .  Cardiovascular events were defined as death from coronary heart disease , nonfatal myocardial infa rct ion or stroke , or the need for coronary-revascularization procedures . RESULTS Of the 12 markers measured , hs-CRP was the strongest univariate predictor of the risk of cardiovascular events ; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 ( 95 percent confidence interval , 2.2 to 8.9 ) . Other markers significantly associated with the risk of cardiovascular events were serum amyloid A ( relative risk for the highest as compared with the lowest quartile , 3.0 ) , sICAM-1 ( 2.6 ) , interleukin-6 ( 2.2 ) , homocysteine ( 2.0 ) , total cholesterol ( 2.4 ) , LDL cholesterol ( 2.4 ) , apolipoprotein B-100 ( 3.4 ) , HDL cholesterol ( 0.3 ) , and the ratio of total cholesterol to HDL cholesterol ( 3.4 ) . Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone ( P<0.001 ) . The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter ( 3.4 mmol per liter ) , the target for primary prevention established by the National Cholesterol Education Program . In multivariate analyses , the only plasma markers that independently predicted risk were hs-CRP ( relative risk for the highest as compared with the lowest quartile , 1.5 ; 95 percent confidence interval , 1.1 to 2.1 ) and the ratio of total cholesterol to HDL cholesterol ( relative risk , 1.4 ; 95 percent confidence interval , 1.1 to 1.9 ) . CONCLUSIONS The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events 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 OBJECTIVE To test the safety , tolerance , and efficacy of extended-release niacin monotherapy on dyslipidemia in persons with chronic tetraplegia . DESIGN Placebo-controlled , blinded , multicenter , r and omized controlled trial . SETTING Three spinal cord injury research /rehabilitation centers . PARTICIPANTS Persons with chronic tetraplegia ( N=54 ) and low plasma high-density lipoprotein cholesterol ( HDL-C ) levels . INTERVENTION Extended-release niacin monotherapy ( 48 weeks ; n=31 ) on a dose-titration schedule versus matched placebo ( n=23 ) . MAIN OUTCOME MEASURES Safety was assessed by using percentages of treatment-emergent adverse events and increased levels of hepatic transaminases , uric acid , glycosylated hemoglobin , and fasting glucose . Tolerance was assessed by using participant reports for frequency and intensity of adverse effects of extended-release niacin . Primary effectiveness outcomes were fasting HDL-C level and plasma total cholesterol (TC)/HDL-C ratio . Secondary outcomes included plasma low-density lipoprotein cholesterol ( LDL-C ) and TC levels and LDL-C/HDL-C ratio . RESULTS Significant increases in fasting HDL-C levels ( 24.5 % ) were accompanied by decreases in TC/HDL-C and LDL-C/HDL-C ratios , LDL-C levels , and TC levels ( all P<.05 ) . No evidence of sustained hepatotoxicity or hyperglycemia was observed . Treatment-emergent withdrawals ( 12.9 % ) accompanied flushing ( n=1 ) , hypotension/presyncope ( n=1 ) , and diarrhea ( n=2 ) . One subject experienced transient hyperuricemia . Other drug-reported symptoms did not differ from those for placebo . CONCLUSIONS Extended-release niacin monotherapy is safe , tolerated , and effective for most persons with chronic tetraplegia . Special pre caution s for changes in bowel habits and postadministration hypotension should be observed BACKGROUND In patients with established cardiovascular disease , residual cardiovascular risk persists despite the achievement of target low-density lipoprotein ( LDL ) cholesterol levels with statin therapy . It is unclear whether extended-release niacin added to simvastatin to raise low levels of high-density lipoprotein ( HDL ) cholesterol is superior to simvastatin alone in reducing such residual risk . METHODS We r and omly assigned eligible patients to receive extended-release niacin , 1500 to 2000 mg per day , or matching placebo . All patients received simvastatin , 40 to 80 mg per day , plus ezetimibe , 10 mg per day , if needed , to maintain an LDL cholesterol level of 40 to 80 mg per deciliter ( 1.03 to 2.07 mmol per liter ) . The primary end point was the first event of the composite of death from coronary heart disease , nonfatal myocardial infa rct ion , ischemic stroke , hospitalization for an acute coronary syndrome , or symptom-driven coronary or cerebral revascularization . RESULTS A total of 3414 patients were r and omly assigned to receive niacin ( 1718 ) or placebo ( 1696 ) . The trial was stopped after a mean follow-up period of 3 years owing to a lack of efficacy . At 2 years , niacin therapy had significantly increased the median HDL cholesterol level from 35 mg per deciliter ( 0.91 mmol per liter ) to 42 mg per deciliter ( 1.08 mmol per liter ) , lowered the triglyceride level from 164 mg per deciliter ( 1.85 mmol per liter ) to 122 mg per deciliter ( 1.38 mmol per liter ) , and lowered the LDL cholesterol level from 74 mg per deciliter ( 1.91 mmol per liter ) to 62 mg per deciliter ( 1.60 mmol per liter ) . The primary end point occurred in 282 patients in the niacin group ( 16.4 % ) and in 274 patients in the placebo group ( 16.2 % ) ( hazard ratio , 1.02 ; 95 % confidence interval , 0.87 to 1.21 ; P=0.79 by the log-rank test ) . CONCLUSIONS Among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less than 70 mg per deciliter ( 1.81 mmol per liter ) , there was no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up period , despite significant improvements in HDL cholesterol and triglyceride levels . ( Funded by the National Heart , Lung , and Blood Institute and Abbott Laboratories ; AIM -HIGH Clinical Trials.gov number , NCT00120289 . ) The Coronary Drug Project was conducted between 1966 and 1975 to assess the long-term efficacy and safety of five lipid-influencing drugs in 8,341 men aged 30 to 64 years with electrocardiogram-documented previous myocardial infa rct ion . The two estrogen regimens and dextrothyroxine were discontinued early because of adverse effects . No evidence of efficacy was found for the clofibrate treatment . Niacin treatment showed modest benefit in decreasing definite nonfatal recurrent myocardial infa rct ion but did not decrease total mortality . With a mean follow-up of 15 years , nearly 9 years after termination of the trial , mortality from all causes in each of the drug groups , except for niacin , was similar to that in the placebo group . Mortality in the niacin group was 11 % lower than in the placebo group ( 52.0 versus 58.2 % ; p = 0.0004 ) . This late benefit of niacin , occurring after discontinuation of the drug , may be a result of a translation into a mortality benefit over subsequent years of the early favorable effect of niacin in decreasing nonfatal reinfa rct ion or a result of the cholesterol-lowering effect of niacin , or both CONTEXT Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease ( CHD ) , it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol ( LDL-C ) in patients without CHD extends to individuals with average serum cholesterol levels , women , and older persons . OBJECTIVE To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinical ly evident atherosclerotic cardiovascular disease with average total cholesterol ( TC ) and LDL-C levels and below-average high-density lipoprotein cholesterol ( HDL-C ) levels . DESIGN A r and omized , double-blind , placebo-controlled trial . SETTING Outpatient clinics in Texas . PARTICIPANTS 
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RESULTS Compared with controls , individuals with SCI had significantly lower total cholesterol ( TC ) ( 183.4 mg/dL versus 194.9 mg/dL , p = 0.019 ) and high-density lipoprotein cholesterol ( HDL-C ) ( 41.0 mg/dL versus 49.6 mg/dL , p < 0.001 ) and higher TC/HDL-C ratios ( 4.5 versus 4.0 , p = 0.002 ) , though no significant differences were found for triglyceride ( TG ) and non-HDL-C values .
CONCLUSIONS SCI represents an increasingly common chronic condition , now secondarily characterized by heightened CVD risk potentially in part due to unique lipid profiles characterized primarily by low HDL-C and an increased TC/HDL-C ratio .