***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 Background According to prior analyses , extended-release niacin/laropiprant ( ERN/LRPT ) consistently reduces low-density lipoprotein cholesterol ( LDL-C ) and triglycerides ( TG ) and increases high-density lipoprotein cholesterol ( HDL-C ) levels across a wide range of dyslipidemic patient subgroups . Objectives This analysis examined ERN/LRPT ’s consistency across four phase III , r and omized , double-blind trials in improving other lipid/lipoprotein parameters associated with cardiovascular risk , across several key dyslipidemic patient subgroups . Methods In three of the studies , the r and omized population included patients with primary hypercholesterolemia or mixed hyperlipidemia ; in the remaining study , the population included patients with type 2 diabetes mellitus . The lipid-altering consistency of ERN/LRPT ’s efficacy was evaluated versus the predefined comparator ( placebo or active control ) among key subgroups of sex , race ( White , non-White ) , region ( US , ex-US ) , baseline age ( < 65 years , ≥65 years ) , use of statin therapy ( yes , no ) , coronary heart disease ( yes , no ) , risk status ( low , multiple , high ) , and type of hyperlipidemia ( primary hypercholesterolemia , mixed dyslipidemia ) , as well as across baseline LDL-C , HDL-C , and TG levels . The consistency of the treatment effects on lipoprotein(a ) [ Lp(a ) ] , apolipoprotein B ( ApoB ) , non-HDL-C , ApoA1 , and ApoB/ApoA1 ratio was evaluated by examining treatment difference estimates of the percentage change from baseline with 95 % confidence intervals . Results Treatment with ERN/LRPT produced significantly greater improvements in Lp(a ) , ApoB , non-HDL-C , ApoA1 , and ApoB/ApoA1 ratio compared with placebo/active comparator in each study . These effects were generally consistent across key subgroups within each study . Conclusion ERN/LRPT  produced lipid-altering efficacy on the parameters evaluated in four controlled studies ; these effects were generally consistent across all examined subgroups . ERN/LRPT represents an effective and reliable therapeutic option for the treatment of dyslipidemia in a wide range of patient types . Clinical Trial Registration Registered as Clinical trials.gov NCT00269204 , NCT00269217 , NCT00479388 , and NCT00485758 The goal of this study was to determine , using analytic ultracentrifugation , the effect of nicotinic acid alone or nicotinic acid added to gemfibrozil on lipoprotein subclass distribution , including intermediate-density lipoprotein ( IDL ; low-density to very low density flotation rate [ S(f ) ] 12 to 20 ) ; low-density lipoprotein ( LDL ) subfractions LDL-I ( S(f ) 7 to 12 ) , LDL-II ( S(f ) 5 to 7 ) , LDL-III ( S(f ) 3 to 5 ) , and LDL-IV ( S(f ) 0 to 3 ) ; and high-density lipoprotein ( HDL ) subfractions HDL(2 ) ( high-density flotation rate 3.5 to 9.0 ) and HDL(3 ) ( high-density flotation rate 0 to 3.5 ) . Patients with combined hyperlipidemia were r and omized to nicotinic acid ( 1,500 mg/day ) plus placebo or nicotinic acid plus gemfibrozil ( 1,200 mg/d ) for 12 weeks . Baseline characteristics were similar between the 2 groups , and mean LDL cholesterol ( 180 + /- 33 mg/dl ) and triglycerides ( 310 + /- 126 mg/dl ) were typical for patients with combined hyperlipidemia . Treatment with nicotinic acid result ed in a reduction in dense LDL ( S(f ) 5 to 7 ; p = 0.02 ) , which was counterbalanced by an increase in buoyant LDL ( S(f ) 7 to 12 ; p = 0.03 ) that result ed in no significant LDL mass or LDL cholesterol change . IDL was reduced ( p = 0.005 ) and HDL(2 ) increased by 143 % ( p = 0.004 ) . The combination of nicotinic acid and gemfibrozil result ed in a further 17.8 % reduction in apolipoprotein B ( p = 0.06 ) , a further 33.8 % reduction in IDL ( p = 0.06 ) , and a greater reduction in the apolipoprotein B/apolipoprotein A-I ratio ( p = 0.02 ) . The combination of nicotinic acid and gemfibrozil reduced atherogenic by IDL 71 % , dense LDL-III by 52 % , and apolipoprotein B by 37 % and increased protective HDL(2 ) by 90 % . In conclusion , this investigation revealed that a combination of a fibric acid derivative and nicotinic acid offers greater improvement in detailed lipoprotein subclass distribution and apolipoprotein ratios than monotherapy Introduction : High-density lipoprotein ( HDL ) cholesterol is a well-established inverse risk factor for cardiovascular disease . The extent to which cardiovascular risk can be modified through changes in HDL , however , is less clear . We further examined the role of aggressive HDL raising therapy on cardiovascular outcomes in the 143 patients enrolled in the Armed Forces Regression Study ( AFREGS ) . Methods : Re analysis of the AFREGS population . Patients with stable coronary disease were r and omized to receive gemfibrozil , niacin , and cholestyramine in combination or matching placebos , on top of aggressive dietary and exercise modification for a 30-month period . Blood work was performed at baseline and repeated after 1 year of therapy . Results : Patients were divided into 3 groups based on their therapeutic response : no HDL increase , mild HDL increase , and large HDL increase ( % change in HDL ≤0 , ≤ the lower 2 tertiles of HDL increase , and > the upper tertile of HDL increase , respectively ) . A progressive decrease in cardiovascular events was noted across these groups ( 30.4 % , 19.4 % , and 3.2 % , respectively , P = .01 ) . Kaplan-Meier analysis according to percentage change in HDL demonstrated a similar improvement in event-free survival ( P = .01 ) . Proportional hazards modeling also demonstrated that increasing HDL predicted a lower hazard of cardiovascular events , even after adjusting for changes in low-density lipoprotein ( [ LDL ] P < .01 ) . For every 1 % increase in HDL achieved , a 2 % decrease in events was recognized . Conclusions : These data suggest that in a population of patients with stable atherosclerosis , the greater the percentage increase in HDL achieved , the greater the cardioprotective benefit . This further supports HDL raising as a beneficial therapeutic strategy Patients with combined hyperlipidemia and low high-density lipoprotein ( HDL ) cholesterol levels may benefit from combination therapy with a statin and niacin ; therefore , we assessed the efficacy and safety of rosuvastatin and extended-release ( ER ) niacin alone and in combination in 270 patients with this atherogenic dyslipidemia . Men and women > or = 18 years with fasting total cholesterol levels > or = 200 mg/dl , triglycerides 200 to 800 mg/dl , apolipoprotein B > or cf=110 mg/dl , and HDL cholesterol < 45 mg/dl were r and omized to 1 of 4 treatments in this 24-week , open-label , multicenter trial : rosuvastatin 10 to 40 mg ; ER niacin 0.5 to 2 g ; rosuvastatin 40 mg/ER niacin 0.5 to 1 g ; or rosuvastatin 10 mg/ER niacin 0.5 to 2 g. Percent changes from baseline in low-density lipoprotein ( LDL ) cholesterol , non-HDL cholesterol , and other lipid measurements at week 24 were determined by analysis of variance , with statistical testing performed separately between the rosuvastatin monotherapy group and each remaining treatment group . Daily doses of rosuvastatin 40 mg reduced LDL and non-HDL cholesterol significantly more than either ER niacin 2 g or rosuvastatin 10 mg/ER niacin 2 g ( -48 % vs -0.1 % and -36 % for LDL cholesterol and -49 % vs -11 % and -38 % for non-HDL cholesterol , respectively ; p < 0.01 for all comparisons ) ; no additional reduction in LDL or non-HDL cholesterol was observed with the combination of rosuvastatin 40 mg/ER niacin 1.0 g ( -42 % and -47 % ; p = NS ) . Triglyceride reductions ranged from -21 % ( ER niacin monotherapy ) to -39 % ( rosuvastatin 40 mg/ER niacin 1 g ) , but no observed differences were statistically significant . Compared with rosuvastatin alone , rosuvastatin 10 mg/ER niacin 2 g produced significantly greater increases in HDL cholesterol ( 11 % vs 24 % , p < 0.001 ) and apolipoprotein A-I ( 5 % vs 11 % , p < 0.017 ) . Similar increases in HDL cholesterol and apolipoprotein A-I were noted between the monotherapy groups . Over 24 weeks , rosuvastatin alone was better tolerated than either ER niacin alone or the combinations of rosuvastatin and ER niacin Aims Niacin has potentially favourable effects on lipids , but its effect on cardiovascular outcomes is uncertain . HPS2-THRIVE is a large r and omized trial assessing the effects of extended release ( ER ) niacin in patients at high risk of vascular events . Methods and results Prior to r and omization , 42 424 patients with occlusive arterial disease were given simvastatin 40 mg plus , if required , ezetimibe 10 mg daily to st and ardize their low-density lipoprotein (LDL)-lowering therapy . The ability to remain compliant with ER niacin 2 g plus laropiprant 40 mg daily ( ERN/LRPT ) for ∼1 month was then assessed in 38 369 patients and about one-third were excluded ( mainly due to niacin side effects ) . A total of 25 673 patients were r and omized between ERN/LRPT daily vs. placebo and were followed for a median of 3.9 years . By the end of the study , 25 % of participants allocated ERN/LRPT vs. 17 % allocated placebo had stopped their study treatment . The most common medical reasons for stopping ERN/LRPT were related to skin , gastrointestinal , diab 
    Output:
    
Moderate- to high- quality evidence suggests that niacin does not reduce mortality , cardiovascular mortality , non-cardiovascular mortality , the number of fatal or non-fatal myocardial infa rct ions , nor the number of fatal or non-fatal strokes but is associated with side effects .
Benefits from niacin therapy in the prevention of cardiovascular disease events are unlikely