title: Efficacy and Tolerability of a Nutraceutical Combination (Red Yeast Rice, Policosanols, and Berberine) in Patients with Low-Moderate Risk Hypercholesterolemia: A Double-Blind, Placebo-Controlled Study Is Hyperglycemia a Cardiovascular Risk Factor? Eulipidemic effects of berberine administered alone or in combination with other natural cholesterol-lowering agents. A single-blind clinical investigation. Administration of natural astaxanthin increases serum HDL-cholesterol and adiponectin in subjects with mild hyperlipidemia. Clinical evidence of efficacy of red yeast rice and berberine in a large controlled study versus diet Effects of Poly-Bioactive Compounds on Lipid Profile and Body Weight in a Moderately Hypercholesterolemic Population with Low Cardiovascular Disease Risk: A Multicenter Randomized Trial Long-term effects of nutraceuticals (berberine, red yeast rice, policosanol) in elderly hypercholesterolemic patients Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. Usefulness of Nutraceuticals (Armolipid Plus) Versus Ezetimibe and Combination in Statin-Intolerant Patients With Dyslipidemia With Coronary Heart Disease. Positive Effects of Astaxanthin on Lipid Profiles and Oxidative Stress in Overweight Subjects A dose-finding trial of the effect of long-term folic acid intervention: implications for food fortification policy. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. Glycated hemoglobin measurement and prediction of cardiovascular disease. Effects of Armolipid Plus on small dense LDL particles in a sample of patients affected by familial combined hyperlipidemia Effects of a nutraceutical combination (berberine, red yeast rice and policosanols) on lipid levels and endothelial function randomized, double-blind, placebo-controlled study.
abstract: Background Statins are at the forefront of strategies to manage hypercholesterolemia . However 10 % to 15 % of patients are intolerant to any statin drugs , even at low daily doses and almost one-third of statin users discontinue therapy within 1 year . Some nutraceuticals are prescribed as lipid-lowering substances , but doubts remain about their efficacy and tolerability . Objectives We aim ed to investigate the efficacy and the safety of a nutraceutical combination consisting mainly of 200 mg red yeast rice extract ( equivalent to 3 mg monacolins ) , 500 mg berberine , and 10 mg policosanols ( MBP-NC ) in patients with low-moderate risk hypercholesterolemia . Methods In this single centre , r and omized , double-blind , placebo-controlled study 60 consecutive out patients ( 29 men and 31 women ; age range = 18–60 years ) , with newly diagnosed primary hypercholesterolemia not previously treated , after a run-in period of 3 weeks on a stable hypolipidic diet , were r and omized to receive a pill of MBP-NC ( n = 30 ) or placebo ( n = 30 ) once a day after dinner , in addition to the hypolipidic diet . The efficacy and the tolerability of the proposed nutraceutical treatment were fully assessed after 4 , 12 , and 24 weeks of treatment . Results In the MBP-NC group both total cholesterol and LDL-C already showed a significant reduction at Week 4 ( –30.3 % ± 33.9 % and –29.4 % ± 35.3 % , respectively ) that remained substantially unchanged at Week 12 ( –26.7 % ± 33.1 % and –25.6 % ± 31.5 % , respectively ) and at Week 24 ( –24.6 % ± 32.1 % and –23.7 % ± 32.6 % , respectively ) . The between-groups differences were significant at all time points for both total cholesterol and LDL-C. There were no significant changes in HDL-C , fasting glucose , and triglyceride serum levels in either group . MBP-NC  was also safe and well tolerated . Conclusions In patients with low- to moderate-risk hypercholesterolemia  a nutraceutical combination in association with a hypolipidic diet  significantly reduced total cholesterol and LDL-C levels and may favor the reaching the recommended cholesterol targets . Clinical Trials.gov identifier : NCT02078167 Patients with diabetes show an increased vascular morbidity and mortality that reduces their life expectancy by ~5–15 years ( depending on the age at diagnosis ) ( 1 ) . There is convincing evidence from epidemiological and pathophysiological studies that hyperglycemia per se is largely responsible for the harmful effects of the disease . As recently shown by clinical trials , treatment of this condition may reduce cardiovascular events and mortality , and several therapies should be considered : initiating early and individualized treatment and avoiding hypoglycemia . As shown in the Multiple Risk Factor Intervention Trial , at any given level of major cardiovascular risk factors , diabetes is associated with an odds ratio of 2–4 for cardiovascular mortality compared with nondiabetic subjects ( 2 ) . These results were confirmed by the European Prospect i ve Investigation of Cancer and Nutrition ( EPIC Norfolk ) study ( 3 ) and a recent analysis of the Atherosclerosis Risk in Communities ( ARIC ) study ( 4 ) . Furthermore , a recently published 18-year follow-up study from Finl and demonstrated a similar impact of type 1 and type 2 diabetes on cardiovascular mortality . The adjusted hazard ratios compared with age-matched subjects without diabetes were 5.2 and 4.9 for type 1 and type 2 diabetes , respectively ( 5 ) . Thus , today evidence exists on long-term follow-up population -based studies in patients with type 1 and type 2 diabetes . This evidence clearly suggests that hyperglycemia is a key risk factor not only for diabetes-related disease , but also for cardiovascular and all-cause mortality . On the basis of these long-term observations , one can assume an increment of cardiovascular disease per increase of 1 unit ( % ) A1C of ~18 % ( 6 ) . As shown in numerous prospect i ve studies , the deleterious effects of dysglycemia ( fasting and postpr and ial hyperglycemia ) develop before diabetes is diagnosed . In the Glucose Tolerance in Acute Myocardial Infa rct ion study of patients with acute coronary syndrome  , abnormal glucose tolerance was the strongest independent Berberine ( BERB ) and a combination ( COMB ) of berberine ( CAS 2086 - 83 - 1 ) with policosanol ( CAS 557 - 61 - 9 ) , red yeast extract ( containing monacolin , CAS 557 - 61 - 9 ) , folic acid and astaxanthin were orally administered daily for 4 weeks to 40 subjects with moderate dyslipidemias divided in two parallel groups each of 20 subjects .  Total cholesterol ( TC ) , LDL , HDL , Non HDL , ApoB , ApoA , Lp(a ) and triglycerides ( TG ) were measured before and at the end of treatments . BERB and COMB significantly reduced TC ( respectively by 16 % and 20 % ) , LDL ( by 20 % and 25 % ) , ApoB ( by 15 % and 29 % ) and TG ( by 22 % and 26 % ) , and increased HDL ( by 6.6 % and 5.1 % ) . Adverse events or impairments of liver transaminases or of CPK were not observed . In conclusion , food supplements containing natural products such as berberine , policosanol , red yeast extracts , folic acid and astaxanthin could be a useful support to diet and life style changes to correct dyslipidemias and to reduce cardiovascular risk in subjects with moderate mixed dyslipidemias BACKGROUND Astaxanthin has been reported to improve dyslipidemia and metabolic syndrome in animals , but such effects in humans are not well known . METHODS Placebo-controlled astaxanthin administration at doses of 0 , 6 , 12 , 18 mg/day for 12 weeks was r and omly allocated to 61 non-obese subjects with fasting serum triglyceride of 120 - 200mg/dl and without diabetes and hypertension , aged 25 - 60 years . RESULTS In before and after tests , body mass index ( BMI ) and LDL-cholesterol were unaffected at all doses , however , triglyceride decreased , while HDL-cholesterol increased significantly . Multiple comparison tests showed that 12 and 18 mg/day doses significantly reduced triglyceride , and 6 and 12 mg doses significantly increased HDL-cholesterol . Serum adiponectin was increased by astaxanthin ( 12 and 18 mg/day ) , and changes of adiponectin correlated positively with HDL-cholesterol changes independent of age and BMI . CONCLUSIONS This first-ever r and omized , placebo-controlled human study suggests that astaxanthin consumption ameliorates triglyceride and HDL-cholesterol in correlation with increased adiponectin in humans Efficacy of a new patented proprietary combination of natural nutraceuticals ( PN ) containing natural hypolipidemic as red yeast , policosanol and berberine was tested in a large study on dyslipidemic patients in clinical practice . A parallel , controlled , r and omized , multicenter study was design ed . After 2 weeks on a stable dietary regimen , the patients were r and omized to PN 1 tablet/day associated with diet ( PN + D ) or diet alone ( D ) for 16 weeks . Entry criteria were : Tot-Chol > 200 mg/dL or LDL-Chol > 150 mg/dL without a clear indication for statins , or plasma triglycerides > 150 mg/dL.  Lipid pattern and CV parameters were evaluated at baseline and monthly . 1,751 patients were enrolled in 248 Italian units , 933 patients on PN + D and 818 on D. The baseline lipid values were : Tot-Chol 255.4 versus 243.1 mg/dL , LDL-Chol 170.1 versus 162.2 mg/dL , HDL-Chol 50.0 versus 48.8 mg/dL , and TG 190.5 versus 184.4 mg/dL. PN constantly and significantly improved lipid parameters versus D group : at 16 weeks −19.1 versus −9.4 % for Tot-Chol ( p < 0.001 ) , −23.5 versus −10.8 % for LDL-Chol ( p < 0.001 ) , + 11.6 versus + 4.0 % for HDL-Chol ( p < 0.001 ) , −17.9 versus −11.3 % for TG ( p < 0.001 ) . In conclusions , PN plus diet allows an effective improvement of blood lipids with a significant reduction of global CV risk , suggesting a role for PN in CHD prevention A dietary supplement ( AP , Armolipid Plus ) that combines red yeast rice extract , policosanol , berberine , folic acid , coenzyme Q10 and asthaxantine can have beneficial effects on cardiovascular disease ( CVD ) biomarkers . The aim of this study was to assess whether the intake of AP , in combination with dietary recommendations , reduces serum low density lipoprotein cholesterol ( LDL-c ) concentrations and other CVD biomarkers in patients with hypercholesterolemia . Eligible patients were recruited from the outpatient clinics of six Spanish hospitals Hospital Virgen del Rocío ( Sevilla ) ; Hospital San Jorge ( Huesca ) ; Hospital San Pedro ( Logroño ) ; Hospital Gregorio Marañón ( Madrid ) , Hospital la Fe ( Valencia ) and Hospital Universitari Sant Joan ( Reus ) as recruiting and coordinating center . 102 participants ( mean age ± SD ; 50.91±11.61 ; 32 men ) with low CVD , with mild-to-moderately elevated LDL-c ( between 3.35 mmol/L and 4.88 mmol/L ) without hypolipemic therapy were r and omized in a double-blind , parallel , controlled , multicenter trial commencing January 2012 and ending December 2012 . Among the exclusion criteria were any concomitant chronic disease , triglycerides ( TG ) > 3.97 mmol/L , pregnant or lactating , and history of CVD . At 12 weeks , compared to placebo , AP reduced LDL-c by −6.9 % , apolipoprotein ( Apo ) B-100 by −6.6 % and total cholesterol/HDL-c ratio by −5.5 % , the ApoB/ApoA1 ratio by −8.6 % , while increasing ApoA1 by + 2.5 % ( p<0.05 ) . AP consumption was associated with modest mean weight loss of −0.93 kg ( 95%CI : -1.74 to -0.12 ; P = 0.02 ) compared with control group while dietary composition remained unchanged in the AP group . The AP product was well tolerated . In conclusion , AP , combined with dietary recommendations , reduced LDL-c levels as well as total cholesterol/HDL-c and ApoB/ApoA1 ratios , while increasing Apo A1 , all of which are improvements in CVD risk indicators . AP is a product which could benefit patients having moderate hyperlipidemia and excess body weight . Trial Registration Clinical Trials.gov Introduction Statins are at the forefront of strategies to manage dyslipidemia , although they are not always well tolerated . At 6–7 months after the drug was supplied , discontinuation rates averaged 30 % . Alternate agents to statins have been studied . Some nutraceuticals demonstrated an efficacy in reducing cholesterol concentrations . However , there are no data regarding the use of nutraceuticals in elderly dyslipidemic patients . The purpose of this study was to examine the efficacy , safety , and tolerability of a nutraceutical-based protocol in elderly hypercholesterolemic patients previously intolerant to statins . Methods This study was performed as a r and omized , prospect i ve , parallel group , single-blind study . Patients were included in the study if they had high total cholesterolemia , high low-density lipoprotein cholesterol ( LDL-C ) , > 75 years of age , statin-intolerant , and were refusing other pharmaceutical treatments for hypercholesterolemia . At the baseline visit , eligible patients were r and omized to either nutraceutical-combined pill ( containing berberine 500 mg , policosanol 10 mg , red yeast rice 200 mg , folic acid 0.2 mg , coenzyme Q10 2.0 mg , and astaxanthin 0.5 mg ) or placebo , and the first dose was dispensed . The efficacy , safety , and tolerability of the proposed treatment were fully assessed after 3 , 6 , and 12 months of treatment . Results Out of 106 consecutive patients screened , 80 eligible patients were r and omized to receive either nutraceutical-combined pill ( 40 patients ) or placebo ( 40 patients ) . No patients were lost and no deaths occurred during the follow-up . There was a statistically significant reduction in total cholesterolemia ( −20 % ) , LDL-C ( −31 % ) , and insulin resistance ( −10 % ) with nutraceutical treatment . No significant changes were detected for plasma high-density lipoprotein cholesterol ( HDL-C ) . Furthermore , no statistical differences were found between baseline and end- study safety parameters . Medication compliance and tolerability were high . Conclusion In this study the authors have demonstrated that combined nutraceuticals significantly reduce cholesterolemia and achieved acceptable plasma LDL-C levels in elderly hypercholesterolemic patients who were previously statin-intolerant .  Combined nutraceuticals is also safe and well tolerated in these patients BACKGROUND Statin therapy reduces low-density lipoprotein ( LDL ) cholesterol levels and the risk of cardiovascular events , but whether the addition of ezetimibe , a nonstatin drug that reduces intestinal cholesterol absorption , can reduce the rate of cardiovascular events further is not known . METHODS We conducted a double-blind , r and omized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter ( 1.3 to 2.6 mmol per liter ) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter ( 1.3 to 3.2 mmol per liter ) if they were not receiving lipid-lowering therapy .  The combination of simvastatin ( 40 mg ) and ezetimibe ( 10 mg ) ( simvastatin-ezetimibe ) was compared with simvastatin ( 40 mg ) and placebo ( simvastatin monotherapy ) . The primary end point was a composite of cardiovascular death , nonfatal myocardial infa rct ion , unstable angina requiring rehospitalization , coronary revascularization ( ≥30 days after r and omization ) , or nonfatal stroke . The median follow-up was 6 years . RESULTS The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter ( 1.4 mmol per liter ) in the simvastatin-ezetimibe group , as compared with 69.5 mg per deciliter ( 1.8 mmol per liter ) in the simvastatin-monotherapy group ( P<0.001 ) . The Kaplan-Meier event rate for the primary end point at 7 years was 32.7 % in the simvastatin-ezetimibe group , as compared with 34.7 % in the simvastatin-monotherapy group ( absolute risk difference , 2.0 percentage points ; hazard ratio , 0.936 ; 95 % confidence interval , 0.89 to 0.99 ; P=0.016 ) . Rates of prespecified muscle , gallbladder , and hepatic adverse effects and cancer were similar in the two groups . CONCLUSIONS When added to statin therapy , ezetimibe result ed in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes . Moreover , lowering LDL cholesterol to levels below previous targets provided additional benefit . ( Funded by Merck ; IMPROVE-IT Clinical Trials.gov number , NCT00202878 . ) Statins are extensively used to treat dyslipidemia , but , because of their low tolerability profile , they are discontinued in a significant proportion of patients . Ezetimibe and nutraceuticals have been introduced as alternative therapies and have proved to be effective and well tolerated . A single-blind , single-center , r and omized , prospect i ve , and parallel group trial comparing a combination of nutraceuticals ( red yeast rice , policosanol , berberine , folic acid , coenzyme Q10 and astaxanthin ) , called Armolipid Plus , and ezetimibe for 3 months in terms of efficacy and tolerability . Patients who did not achieve their therapeutic target ( low-density lipoprotein cholesterol < 100 mg/dl ) could add the alternative treatment on top of r and omized treatment for another 12 months : 100 patients who are dyslipidemic with ischemic heart disease treated with percutaneous coronary intervention were enrolled ( ezetimibe n = 50 , nutraceutical n = 50 ) . Efficacy ( lipid profile ) and tolerability ( adverse events , transaminases , and creatine kinase ) were assessed after 3 and 12 months . After 3 months , 14 patients in the nutraceutical group achieved their therapeutic target , whereas none of the patients in the ezetimibe group did . At 1-year follow-up , 58 patients ( 72.5 % ) of the combined therapy group ( n = 86 ) and 14 ( 100 % ) of the nutraceutical group reached the therapeutic goal . No patients experienced important undesirable effects . In conclusion , nutraceuticals alone or in combination with ezetimibe are well tolerated and improve the lipid profile in statin-intolerant patients with coronary heart disease . Further studies are needed to assess long-term effects of nutraceuticals on mortality Astaxanthin , a carotenoid , has antioxidant activity as well as many positive effects , such as anticancer and anti-inflammatory effects . We performed a r and omized , double-blind , placebo-controlled study to investigate the effects of astaxanthin on lipid profiles and oxidative stress in overweight and obese adults in Korea . In total , 27 subjects with body mass index > 25.0 kg/m2 were enrolled and r and omly assigned into two groups administered astaxanthin or placebo capsules for 12 weeks . Total cholesterol , triglycerides , high density lipoprotein ( HDL ) cholesterol , low density lipoprotein ( LDL ) cholesterol , apolipoprotein A1 ( ApoA1 ) , and apolipoprotein B ( ApoB ) were measured before and after intervention . Malondialdehyde ( MDA ) , isoprostane ( ISP ) , superoxide dismutase ( SOD ) , and total antioxidant capacity ( TAC ) , as oxidative stress biomarkers , were measured at baseline and at 4 , 8 , and 12 weeks after intervention . LDL cholesterol and ApoB were significantly lower after treatment with astaxanthin , compared with the start of administration , whereas none of the lipid profiles was changed in the placebo group . At the baseline , all four biomarkers were not significantly different between the two groups . Compared with the placebo group , MDA and ISP were significantly lower , but TAC was significantly higher in the astaxanthin group at 12 weeks . These results suggest that supplementary astaxanthin has positive effects by improving the LDL cholesterol , ApoB , and oxidative stress biomarkers BACKGROUND The lowest dose of folic acid required to achieve effective reductions in homocysteine is controversial but important for food fortification policy given recent concerns about the potential adverse effects of overexposure to this vitamin . OBJECTIVE We compared the effectiveness of 0.2 mg folic acid/d with that of 0.4 and 0.8 mg/d at lowering homocysteine concentrations over a 6-mo period . DESIGN A r and omized dose-finding trial with folic acid was conducted . Of 203 participants screened , 101 patients with ischemic heart disease and 71 healthy volunteers completed the study . Participants were r and omly assigned to receive placebo or folic acid at doses of 0.2 , 0.4 , or 0.8 mg/d for 26 wk ; sub sample s of patients with ischemic heart disease were also examined at 6 or 12 wk . RESULTS Participants with higher baseline homocysteine concentrations had the greatest reductions in homocysteine in response to folic acid doses of 0.2 mg ( -20.6 % ) , 0.4 mg ( -20.7 % ) , and 0.8 mg ( -27.8 % ) ; in those with lower baseline homocysteine concentrations , the responses were -8.2 % , -8.9 % , and -8.3 % , respectively . No significant differences in homocysteine responses to the different doses were observed . In the patient group sample d at intervals during the intervention , the maximal homocysteine response appeared to be achieved by 6 wk in the 0.8-mg/d group and by 12 wk in the 0.4-mg/d group . However , the homocysteine response was suboptimal in the 0.2-mg/d group at both 6 and 12 wk compared with that at 26 wk . CONCLUSIONS A folic acid dose as low as 0.2 mg/d can , if administered for 6 mo , effectively lower homocysteine concentrations . Higher doses may not be necessary because they result in no further significant lowering , whereas doses even lower than 0.2 mg/d may be effective in the longer term . Previous trials probably overestimated the folic acid dose required because of a treatment duration that was too short . This trial was registered at clinical trials.gov as IS RCT N45296887 CONTEXT Recent r and omized trials among patients with preexisting cardiovascular disease ( CVD ) have failed to support benefits of B-vitamin supplementation on cardiovascular risk . Observational data suggest benefits may be greater among women , yet women have been underrepresented in published r and omized trials . OBJECTIVE To test whether a combination of folic acid , vitamin B6 , and vitamin B12 lowers risk of CVD among high-risk women with and without CVD . DESIGN , SETTING , AND PARTICIPANTS Within an ongoing r and omized trial of antioxidant vitamins , 5442 women who were US health professionals aged 42 years or older , with either a history of CVD or 3 or more coronary risk factors , were enrolled in a r and omized , double-blind , placebo-controlled trial to receive a combination pill containing folic acid , vitamin B6 , and vitamin B12 or a matching placebo , and were treated for 7.3 years from April 1998 through July 2005 . INTERVENTION Daily intake of a combination pill of 2.5 mg of folic acid , 50 mg of vitamin B6 , and 1 mg of vitamin B12 . MAIN OUTCOME MEASURES A composite outcome of myocardial infa rct ion , stroke , coronary revascularization , or CVD mortality . RESULTS Compared with placebo , a total of 796 women experienced a confirmed CVD event ( 406 in the active group and 390 in the placebo group ) . Patients receiving active vitamin treatment had similar risk for the composite CVD primary end point ( 226.9/10,000 person-years vs 219.2/10,000 person-years for the active vs placebo group ; relative risk [ RR ] , 1.03 ; 95 % confidence interval [ CI ] , 0.90 - 1.19 ; P = .65 ) , as well as for the secondary outcomes including myocardial infa rct ion ( 34.5/10,000 person-years vs 39.5/10,000 person-years ; RR , 0.87 ; 95 % CI , 0.63 - 1.22 ; P = .42 ) , stroke ( 41.9/10,000 person-years vs 36.8/10,000 person-years ; RR , 1.14 ; 95 % CI , 0.82 - 1.57 ; P = .44 ) , and CVD mortality ( 50.3/10,000 person-years vs 49.6/10,000 person-years ; RR , 1.01 ; 95 % CI , 0.76 - 1.35 ; P = .93 ) . In a blood sub study , geometric mean plasma homocysteine level was decreased by 18.5 % ( 95 % CI , 12.5%-24.1 % ; P < .001 ) in the active group ( n = 150 ) over that observed in the placebo group ( n = 150 ) , for a difference of 2.27 micromol/L ( 95 % CI , 1.54 - 2.96 micromol/L ) . CONCLUSION After 7.3 years of treatment and follow-up , a combination pill of folic acid , vitamin B6 , and vitamin B12 did not reduce a combined end point of total cardiovascular events among high-risk women , despite significant homocysteine lowering . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000541 IMPORTANCE The value of measuring levels of glycated hemoglobin ( HbA1c ) for the prediction of first cardiovascular events is uncertain . OBJECTIVE To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease ( CVD ) risk . DESIGN , SETTING , AND PARTICIPANTS Analysis of individual-participant data available from 73 prospect i ve studies involving 294,998 participants without a known history of diabetes mellitus or CVD at the baseline assessment . MAIN OUTCOMES AND MEASURES Measures of risk discrimination for CVD outcomes ( eg , C-index ) and reclassification ( eg , net reclassification improvement ) of participants across predicted 10-year risk categories of low ( < 5 % ) , intermediate ( 5 % to < 7.5 % ) , and high ( ≥ 7.5 % ) risk . RESULTS During a median follow-up of 9.9 ( interquartile range , 7.6 - 13.2 ) years , 20,840 incident fatal and nonfatal CVD outcomes ( 13,237 coronary heart disease and 7603 stroke outcomes ) were recorded . In analyses adjusted for several conventional cardiovascular risk factors , there was an approximately J-shaped association between HbA1c values and CVD risk . The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate , but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein . The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 ( 95 % CI , 0.7350 to 0.7517 ) . The addition of information on HbA1c was associated with a C-index change of 0.0018 ( 0.0003 to 0.0033 ) and a net reclassification improvement of 0.42 ( -0.63 to 1.48 ) for the categories of predicted 10-year CVD risk . The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting , r and om , or postload plasma glucose levels . CONCLUSIONS AND RELEVANCE In a study of individuals without known CVD or diabetes , additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk Abstract Aim : The aim of this study was to test small dense LDL changes with Armolipid Plus treatment in patients with familial combined hyperlipidemia ( FCHL ) . Methods : After 4 weeks , 30 patients with FCHL were included in an 8-week , r and omized , double-blind study and were taking , in addition to the st and ard diet , either placebo or Armolipid Plus . Results : The placebo group showed no statistically significant differences in the studied parameters ; instead , in the Armolipid Plus group , statistically significant reduction differences were detected in BMI ( p = 0.010 ) , LDL score ( p = 0.035 ) and an increase in mean LDL particle diameter ( p = 0.040 ) . Conclusion : The combination of a st and ard diet with Armolipid Plus is able to reduce LDL score and increase LDL particle diameter in a group of FCHL after 8 weeks of treatment BACKGROUND AND AIMS Some nutraceuticals are prescribed as lipid-lowering substances . However , doubts remain about their efficacy . We evaluated the effects of a nutraceutical combination ( NC ) , consisting of 500 mg berberine , 200 mg red yeast rice and 10 mg policosanols , on cholesterol levels and endothelial function in patients with hypercholesterolemia . METHODS AND RESULTS In this single centre , r and omized , double-blind , placebo-controlled study , 50 hypercholesterolemic patients ( 26 males and 24 females , mean age 55±7 years , total cholesterol 6.55±0.75 mmol/l , BMI 28±3.5 ) were r and omized to 6 weeks of treatment with a daily oral dose of NC  ( 25 patients ) or placebo  ( 25 patients ) . In a subsequent open-label extension of 4 weeks , the whole sample received NC . The main outcome measure was decrease total cholesterol ( C ) levels in the NC arm . Secondary outcome measures were decreased low-density lipoprotein cholesterol ( LDL-C ) and triglyceride levels , and improved endothelial-dependent flow-mediated dilation ( FMD ) and insulin sensitivity in relation to NC . Evaluation of absolute changes from baseline showed significant reductions in NC versus placebo for C and LDL-C ( C : -1.14±0.88 and -0.03±0.78 mmol/l , p<0.001 ; LDL-C : -1.06±0.75 and -00.4±0.54 mmol/l , p<0.001 ) , and a significant improvement of FMD ( 3±4 % and 0±3 % respectively , p<0.05 ) . After the extension phase , triglyceride levels decreased significantly from 1.57±0.77 to 1.26±0.63 mmol/l , p<0.05 and insulin sensitivity improved in a patient subgroup with insulin resistance at baseline ( HOMA : from 3.3±0.4 to 2.5±1.3 , p<0.05 ) . No adverse effect was reported . CONCLUSIONS This NC reduces cholesterol levels . The reduction is associated with improved endothelial function and insulin sensitivity
target: NComb-induced amelioration of lipid profile was not affected by duration of supplementation nor by baseline lipid levels ; conversely , a greater glucose-lowering effect of NComb was found with higher baseline glucose levels and longer duration s of supplementation .
  In conclusion , the present results suggest that NComb supplementation is associated with improvement of lipid and glucose profile .
  Short-term beneficial effects of NComb supplementation appear to be maintained in the long term
background: Dyslipidemia and hyperglycemia are associated with an increased risk of  ischemic cardiovascular disease .
  Positive effects of a nutraceutical combination comprising red yeast rice , berberine , policosanol , astaxanthin , coenzyme Q10 and folic acid ( NComb ) on plasma lipid and glucose levels have been reported in some but not all clinical trials .
  To address this inconsistency , we tried to estimate the size of lipid- and glucose-lowering effects of NComb through a systematic review and meta- analysis of r and omized controlled trials .