***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 — High-density lipoprotein (HDL)–raising therapies are currently under intense evaluation , but the effects of HDL may be highly heterogeneous . We therefore compared the endothelial effects of HDL from healthy subjects and from patients with type 2 diabetes mellitus and low HDL ( meeting the criteria for metabolic syndrome ) , who are frequently considered for HDL-raising therapies . Moreover , in diabetic patients , we examined the impact of extended-release ( ER ) niacin therapy on the endothelial effects of HDL . Methods and Results — HDL was isolated from healthy subjects ( n=10 ) and patients with type 2 diabetes ( n=33 ) by sequential ultracentrifugation . Effects of HDL on endothelial nitric oxide and superoxide production were characterized by electron spin resonance spectroscopy analysis . Effects of HDL on endothelium-dependent vasodilation and early endothelial progenitor cell – mediated endothelial repair were examined . Patients with diabetes were r and omized to a 3-month therapy with ER niacin ( 1500 mg/d ) or placebo , and endothelial effects of HDL were characterized . HDL from healthy subjects stimulated endothelial nitric oxide production , reduced endothelial oxidant stress , and improved endothelium-dependent vasodilation and early endothelial progenitor cell – mediated endothelial repair . In contrast , these beneficial endothelial effects of HDL were not observed in HDL from diabetic patients , which suggests markedly impaired endothelial-protective properties of HDL . ER niacin therapy improved the capacity of HDL to stimulate endothelial nitric oxide , to reduce superoxide production , and to promote endothelial progenitor cell – mediated endothelial repair . Further measurements suggested increased lipid oxidation of HDL in diabetic patients , and a reduction after ER niacin therapy . Conclusions — HDL from patients with type 2 diabetes mellitus and metabolic syndrome has substantially impaired endothelial-protective effects compared with HDL from healthy subjects . ER niacin therapy not only increases HDL plasma levels but markedly improves endothelial-protective functions of HDL in these patients , which is potentially more important . Clinical Trial Registration — clinical trials.gov . Identifier : NCT00346970 Fasting hypertriglyceridemia relates with high-density lipoprotein ( HDL ) cholesterol , but it is not known whether low HDL cholesterol is associated with disturbances of chylomicron metabolism . To clarify this issue this metabolism was studied in subjects with low HDL cholesterol together with vascular reactivity and evaluation of no-flush niacin treatment . Thirty men with HDL < 1.04 mmol/L and no other risk factors for coronary artery disease ( CAD ) and 11 normal controls with HDL > 1.04 mmol/L were studied . The plasma kinetics of a chylomicron-like emulsion labeled with 14C-cholesterol oleate ( CO ) and 3H-triolein ( TG ) was determined and the fractional clearance rate ( FCR , min(-1 ) ) was calculated . Vascular reactivity was evaluated using high-resolution ultrasonography . CO FCR was markedly reduced in the low HDL group compared to controls ( 3.6 x 10(-3 ) + /- 5.1 x 10(-3 ) min(-1 ) versus 12.2 x 10(-3 ) + /- 8.4 x 10(-3 ) min(-1 ) , p < 0.001 ) but TG FCR was similar . Flow-mediated dilation ( FMD ) was diminished in low HDL ( 7.4 + /- 4.1 versus 12.8 + /- 4.6 % , p < 0.001 ) , whereas nitrate-mediated dilation was similar . Twenty-two low HDL subjects with reduced FMD were r and omized into two groups , one given 1.5 g/day niacin and a placebo group . After 3-month treatment , plasma lipids and chylomicron kinetics were not changed by niacin treatment but FMD improved to normal values ( 5.44 + /- 1.89 to 11.13 + /- 3.4 % , p < 0.01 ) . In conclusion , isolated low HDL cholesterol subjects may also bear chylomicron remnant accumulation and endothelial dysfunction , which highlight the importance of their preventive treatment Objective : To assess the short-term effects of extended-release niacin ( ERN ) on endothelial function in HIV-infected patients with low high-density lipoprotein-cholesterol ( HDL-c ) levels . Methods : R and omized controlled study to determine the short-term effects of ERN on endothelial function , measured by flow-mediated vasodilation ( FMD ) of the brachial artery , in HIV-infected adults with low HDL-c . Participants on stable HAART with fasting HDL-c less than 40 mg/dl and low-density lipoprotein-cholesterol less than 130 mg/dl were r and omized to ERN or control arms . ERN treatment started at 500 mg/night and titrated to 1500 mg/night for 12 weeks . Controls received the same follow-up but were not given ERN ( no placebo ) .  Participants were excluded if they had a history of cardiac disease , uncontrolled hypertension , diabetes mellitus , or were on lipid-lowering medications such as statins and fibrates .  Change in FMD was compared between arms with respect to baseline HDL-c . Results : Nineteen participants were enrolled : 89 % men , median age 50 years , 53 % white/non-Hispanic , median CD4 cell count 493 cells/μl , and 95 % of them had HIV RNA below 50 copies/ml . Participants receiving ERN had a median HDL-c ( interquartile range ) increase of 3.0 mg/dl ( 0.75 to 5.0 ) compared with −1.0 mg/dl in controls ( −6.0 to 2.5 ) , a P value is equal to 0.04 . The median change in FMD was 0.91 % ( −2.95 to 2.21 ) for ERN and −0.48 % ( −2.65 to 0.98 ) for controls ( P = 0.67 ) . However , end of study FMD for ERN was significantly different from controls after adjusting for baseline differences in FMD and HDL-c , 6.36 % ( 95 % confidence interval 4.85–7.87 ) and 2.73 % ( 95 % confidence interval 0.95–4.51 ) respectively , a P value is equal to 0.048 . Conclusion : This pilot study demonstrated that short-term niacin therapy could improve endothelial function in HIV-infected patients with low HDL-c CONTEXT The Heart and Estrogen/progestin Replacement Study ( HERS ) found no overall reduction in risk of coronary heart disease ( CHD ) events among postmenopausal women with CHD . However , in the hormone group , findings did suggest a higher risk of CHD events during the first year , and a decreased risk during years 3 to 5 . OBJECTIVE To determine if the risk reduction observed in the later years of HERS persisted and result ed in an overall reduced risk of CHD events with additional years of follow-up . DESIGN AND SETTING R and omized , blinded , placebo-controlled trial of 4.1 years ' duration ( HERS ) and subsequent unblinded follow-up for 2.7 years ( HERS II ) conducted at outpatient and community setting s at 20 US clinical centers . PARTICIPANTS A total of 2763 postmenopausal women with CHD and average age of 67 years at enrollment in HERS ; 2321 women ( 93 % of those surviving ) consented to follow-up in HERS II . INTERVENTION Participants were r and omly assigned to receive 0.625 mg/d of conjugated estrogens and 2.5 mg of medroxyprogesterone acetate ( n = 1380 ) , or placebo ( n = 1383 ) during HERS ; open-label hormone therapy was prescribed at personal physicians ' discretion during HERS II . The proportions with at least 80 % adherence to hormones declined from 81 % ( year 1 ) to 45 % ( year 6 ) in the hormone group , and increased from 0 % ( year 1 ) to 8 % ( year 6 ) in the placebo group . MAIN OUTCOME MEASURES The primary outcome was nonfatal myocardial infa rct ion and CHD death . Secondary cardiovascular events were coronary revascularization , hospitalization for unstable angina or congestive heart failure , nonfatal ventricular arrhythmia , sudden death , stroke or transient ischemic attack , and peripheral arterial disease . RESULTS There were no significant decreases in rates of primary CHD events or secondary cardiovascular events among women assigned to the hormone group compared with the placebo group in HERS , HERS II , or overall . The unadjusted relative hazard ( RH ) for CHD events in HERS was 0.99 ( 95 % confidence interval [ CI ] , 0.81 - 1.22 ) ; HERS II , 1.00 ( 95 % CI , 0.77 - 1.29 ) ; and overall , 0.99 ( 0.84 - 1.17 ) . The overall RHs were similar after adjustment for potential confounders and differential use of statins between treatment groups ( RH , 0.97 ; 95 % CI , 0.82 - 1.14 ) , and in analyses restricted to women who were adherent to r and omized treatment assignment ( RH , 0.96 ; 95 % CI , 0.77 - 1.19 ) . CONCLUSIONS Lower rates of CHD events among women in the hormone group in the final years of HERS did not persist during additional years of follow-up . After 6.8 years , hormone therapy did not reduce risk of cardiovascular events in women with CHD . Postmenopausal hormone therapy should not be used to reduce risk for CHD events in women with CHD Background —Hyperlipidemia is associated with endothelial dysfunction , an early event in atherosclerosis and predictor of risk for future coronary artery disease . Epidemiological studies suggest that increased dietary intake of antioxidants reduces the risk of coronary artery disease . The purpose of this study was to determine whether antioxidant vitamin therapy improves endothelial function and affects surrogate biomarkers for oxidative stress and inflammation in hyperlipidemic children . Methods and Results —In a r and omized , double-blind , placebo-controlled trial , the effects of antioxidant vitamins C ( 500 mg/d ) and E ( 400 IU/d ) for 6 weeks and the National Cholesterol Education Program Step II ( NCEP-II ) diet for 6 months on endothelium-dependent flow-mediated dilation ( FMD ) of the brachial artery were examined in 15 children with familial hypercholesterolemia ( FH ) or the phenotype of familial combined hyperlipidemia ( FCH ) .  Antioxidant vitamin therapy  improved FMD of the brachial artery compared with baseline ( P < 0.001 ) without an effect on biomarkers for oxidative stress ( autoantibodies to epitopes of oxidized LDL , F2-isoprostanes , 8-hydroxy-2′-deoxyguanosine ) , inflammation ( C-reactive protein ) , or levels of asymmetric dimethylarginine , an endogenous inhibitor of nitric oxide . Conclusions —Antioxidant therapy with vitamins C and E restores endothelial function in hyperlipidemic children . Early detection and treatment of endothelial dysfunction in high-risk children may retard the progression of atherosclerosis Background We previously reported in a placebo-controlled study that extended-release niacin slowed the progression of carotid atherosclerosis when added to statin monotherapy . This analysis examines the relationship between glycemic status and the effects of niacin on common carotid intima-media thickness ( CIMT ) and HDL cholesterol . Methods Post-hoc , subgroup analysis of ARBITER 2 , a r and omized , placebo-controlled trial of once-daily extended-release niacin ( 1000 mg ) added to background statin therapy in 167 patients ( mean age 67 years ) with known coronary heart disease . The primary analysis was a comparison of the primary endpoint , the change in CIMT , between participants with either normal glycemic status , diabetes mellitus ( DM ) or the metabolic syndrome ( MS ) . Results Baseline cardiovascular risk variables were significantly worse in those with abnormal glycemic status , particularly among subjects with MS . Niacin increased HDL-C to a similar degree ( ∼20 % ) across normals , DM and MS . Placebo-treated patients had the greatest CIMT progression , regardless of glycemic status . The lowest progression rate was observed in niacin treated patients with normal glycemic status . Among all niacin treated subjects , there was a significant linear relationship between change in CIMT and change in HDL-C ( r = −0.16 ; p = 0.05 ) , which was of similar magnitude in subgroups with normal glycemic status ( r 
    Output:
    
Meta-regression indicated no association between niacin-induced changes in FMD and changes in plasma HDL-cholesterol , low-density lipoprotein-cholesterol or triglycerides .
None of the included studies could find any significant effect of niacin on nitroglycerin-mediated dilation .
In conclusion , treatment with niacin improves endothelial function