Low-density Lipoprotein Reduction Research Articles

MODIFICATION OF GUT BACTERIAL BILE SALT HYDROLASE ACTIVITY AND CARDIOVASCULAR RISK: A RANDOMIZED STUDY

Introduction: secretion of bacterial bile salt hydrolase (BSH) is one of the main mechanisms by which gut microbiota play role in cholesterol metabolism. There are limiting and controversial data regarding the clear effect of gut BSH activity correction on modification of serum cholesterol and cardiovascular risk (CVR). Aim of investigation was to evaluate the relationship between modification of the gut bacterial BSH relative activity (RA) by probiotic L. plantarum and serum cholesterol with CVR levels. Methods: the study was conducted as open, comparative, randomized, parallel and included 26 almost healthy participants (healthy control group) and 77 patients with dyslipidemia and without anamnesis of major cardiovascular events, that were divided in two groups: main treatment group (n=41) received combination therapy (capsules with Lactobacillus plantarum in the amount of 2*109 CFU one time a day and tablets simvastatin 20 mg one time a day) and control treatment group (n=36) received monotherapy (simvastatin 20 mg one time a day) during 12 weeks. Before and after 12 weeks of treatment the assessment of total RA of gut BSH, lipid profile and CVR level according to 5 risk scores were performed. Results: at baseline the RA of BSH was higher in healthy adults comparing to participants with dyslipidemia (p<0,001); after 12 weeks of treatment there wasn`t difference between healthy control and only main treatment groups (р=0,45). It was found that with increasing of RA of gut bacterial BSH, the risk of failure of treatment efficacy endpoints achievement (³20% reduction of values) decreased regarding: total cholesterol (TC) (p=0,0306), OR=0,00133 (95% CI; 3,28*10-6-0,538); low-density lipoproteins (LDL) (p<0,001), OR=5,65*10-14(95% CI; 6,38*10-20-5*10-8); CVR level according to Framingham score (р=0,0035), OR=4,09*10-5(95% CI; 4,66*10-8-0,0359); CVR level according to 2013 ACC/AHA algorithm (р=0,0135), OR=3,8*10-4(95% CI; 7,34*10-7-0,197); CVR level according to PROCAM score (p=0,00125), OR=8,38*10-6 (95%; CI; 6,93*10-9-0,0101). Conclusions: additional supplementation with BSH-producing bacteria L. plantarum was more effective in increasing of BSH activity compared to simvastatin monotherapy. Increasing of BSH RA by L. plantarum was associated with higher chances to achieve treatment efficacy goals regarding reduction of TC, LDL and CVR levels according to Framingham, 2013 ACC/AHA algorithm and PROCAM scores.

Effects of 2 Types of Resistance Training Models on Obese Adolescents' Body Composition, Cardiometabolic Risk, and Physical Fitness.

Magnani Branco, BH, Carvalho, IZ, Garcia de Oliveira, H, Fanhani, AP, Machado dos Santos, MC, Pestillo de Oliveira, L, Macente, SB, and Nelson, NJ. Effects of 2 types of resistance training models on obese adolescents' body composition, cardiometabolic risk, and physical fitness. J Strength Cond Res 34(9): 2672-2682, 2020-The main objective of this study was to investigate the effects of 2 types of resistance training (RT) models in conjunction with interdisciplinary interventions by other health professionals to reduce the body fat and cardiometabolic risk of obese adolescents while improving their general health-related physical fitness. The 12-week analyses involved 18 male adolescents who were split into 2 groups (weight lifting: n = 9 and functional: n = 9), with equalization according to the primary muscle group (whenever possible), the effort:pause ratio, and intensity. The results showed reductions in fat mass and body fat, as well as in waist and hip circumferences (p < 0.05) after the intervention period. However, no significant differences were observed in terms of the body mass, body mass index, neck circumference, systolic and diastolic blood pressures, and for lean mass (p > 0.05) after the respective period. Maximal isometric strength, abdominal strength resistance, flexibility, and maximal oxygen consumption all produced significant increases after the interventions (p < 0.05). There were reductions in low-density lipoproteins and triglyceride levels after the intervention period (p < 0.05). For fasting glycemia, high-density lipoproteins, and alanine aminotransferase, no differences were observed (p > 0.05). In addition, no differences were observed in rating of perceived recovery, internal training load, or caloric intake (p > 0.05). With the results presented, it is concluded that both RT methods were effective at reducing both fat mass and body fat, thus improving health-related physical fitness components and decreasing cardiometabolic risk.

Effect of pumpkin seed oil on cholesterol fractions and systolic/diastolic blood pressure

Abstract Pumpkin seed oil (PSO) is high in unsaturated fatty acids and plant sterols, which have numerous cardiovascular benefits. The study explores the hypothesis by investigating effects of consumption of 1000 mg of PSO on total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), systolic (SBP) and diastolic (DBP) blood pressure ((BP). PSO has high oxidative stability and contains favorable essential fatty acids profile along with sterols and tocopherols. One hundred and twenty-seven participants 39 to 63 years old, with varying degree of one or multiple medical conditions including dyslipidemia, hypertension, diabetes and obesity were randomly selected and assigned among case and control groups. Both groups were biochemically, anthropometrically and clinically assessed pre and post intervention. Group 1 (cases) (n=63) was administered 1000 mg of PSO along with recommendations for healthy diet and lifestyle whereas Group 2 (controls) (n=64), was only provided with dietary and lifestyle changes. Analysis of cases baseline and endpoint data revealed advantageous effect of intervention. Cases data showed a significant reduction in endpoint LDL and DBP values along with a likewise significant increase in HDL cholesterol. Experiment results revealed PSO possessed hypolipidemic and anti-hypertensive activity as it lowered DBP and LDL and increased HDL levels.

Comprehensive lipidomics in apoM-/- mice reveals an overall state of metabolic distress and attenuated hepatic lipid secretion into the circulation

Apolipoprotein M (apoM) participates in both high-density lipoprotein and cholesterol metabolism. Little is known about how apoM affects lipid composition of the liver and serum. In this study, we systemically investigated the effects of apoM on liver and plasma lipidomes and how apoM participates in lipid cycling, via apoM knockout in mice and the human SMMC-7721 cell line. We used integrated mass spectrometry-based lipidomics approaches to semiquantify more than 600 lipid species from various lipid classes, which include free fatty acids, glycerolipids, phospholipids, sphingolipids, glycosphingolipids, cholesterol, and cholesteryl esters (CEs), in apoM-/- mouse. Hepatic accumulation of neutral lipids, including CEs, triacylglycerols, and diacylglycerols, was observed in apoM-/- mice; while serum lipidomic analyses showed that, in contrast to the liver, the overall levels of CEs and saturated/monounsaturated fatty acids were markedly diminished. Furthermore, the level of ApoB-100 was dramatically increased in the liver, whereas significant reductions in both ApoB-100 and low-density lipoprotein (LDL) cholesterol were observed in the serum of apoM-/- mice, which indicated attenuated hepatic LDL secretion into the circulation. Lipid profiles and proinflammatory cytokine levels indicated that apoM-/- leads to hepatic steatosis and an overall state of metabolic distress. Taken together, these results revealed that apoM knockout leads to hepatic steatosis, impaired lipid secretion, and an overall state of metabolic distress.

Losing Weight after Menopause with Minimal Aerobic Training and Mediterranean Diet.

Objective: It is a common belief that menopausal women have greater difficulty losing weight. The aim of this study was to assess the efficacy of a Mediterranean diet (MD) to promote weight loss in postmenopausal women. All participants were prescribed a hypocaloric traditional MD, tailored to the individual. Subjects were asked not to begin any kind of physical activity. Body composition was measured at the beginning and after 8 weeks of treatment. In total, 89 women (age 52.8 ± 4.5 years, BMI 30.0 ± 5.2 kg/m2, fat mass 31.6 ± 10.5 kg) were divided into two groups: the first group consisted of fertile women over 45 years of age, the second group consisted of those diagnosed as menopausal. All women had an improvement in body composition (fat mass −2.3 ± 2.1 kg, p < 0.001; protein −0.1 ± 0.7 kg, p = 0.190) and blood pressure values. No differences were found between the two groups except for a higher reduction of low-density lipoprotein in the menopausal group (p = 0.035). A positive significant correlation between plant to animal protein ratio and fat-free mass variation was found in the menopausal group. These data suggest that a high adherence to a traditional MD would enable menopausal women to lose fat mass and maintain muscle mass with no significant difference to younger women. Fat mass reduction provides menopausal women with improved cardiovascular and metabolic risk factors.

What Change in Body Mass Index Is Required to Improve Cardiovascular Outcomes in Childhood and Adolescent Obesity through Lifestyle Interventions: A Meta-Regression

Background: Using meta-regression, this article aims at establishing the minimum change in BMI-standard deviation score (SDS) needed to improve lipid profiles and blood pressure in children and adolescents with obesity, to aid future trials and guidelines. Methods: Studies with participants involved in lifestyle interventions, aged 4-19 years, with a diagnosis of obesity according to defined BMI thresholds, were considered for inclusion in a large systematic review. Interventions had to report pre- and post-intervention (or mean change in) BMI-SDS, plus either systolic blood pressure (SBP), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and/or triglycerides (TGs). Random-effects meta-regression quantified the relationship between mean change in BMI-SDS and mean change in cardiovascular outcomes. Results: Seventy-one papers reported various cardiovascular measurements and mean change in BMI-SDS. Fifty-four, 59, 46, and 54 studies were analyzed, reporting a change in SBP, HDL, LDL, and TG, respectively. Reduction in mean BMI-SDS was significantly related to improvements in SBP, LDL, TG, and HDL (p < 0.05); BMI-SDS reductions of 1, 1.2, and 0.7 ensured a mean reduction of SBP, LDL, and TG, respectively, although an equivalent value for HDL improvement was indeterminate. Conclusion: Reductions in mean BMI-SDS of >1, >1.2, or >0.7 are likely to reduce SBP, LDL, and TG, respectively. Further studies are needed to clarify the optimal duration, intensity, and setting for interventions. Consistency is required regarding derived BMI values to facilitate future systematic reviews and meta-analyses.

The Impact of Lipoprotein Apheresis on Oxidative Stress Biomarkers and High-Density Lipoprotein Subfractions.

Lipoprotein apheresis (LA) treatment results in a substantial reduction of low-density lipoprotein- (LDL-) cholesterol and lipoprotein(a) concentrations, which consequently decreases the rate of cardiovascular events. The additional benefit of LA may be associated with its impact on the composition and quality of high-density lipoprotein (HDL) particles, inflammation, and oxidative stress condition. To verify the effects of LA procedure, the current study is aimed at analyzing the effect of a single apheresis procedure with direct hemadsorption (DALI) and cascade filtration (MONET) on oxidative stress markers and HDL-related parameters. The study included eleven patients with familial hypercholesterolemia and hyperlipoproteinemia(a) treated with regular LA (DALI or MONET). We investigated the pre- and postapheresis concentration of the lipid-related oxidative stress markers 8-isoPGF2, oxLDL, TBARS, and PON-1. We also tracked potential changes in the main HDL apolipoproteins (ApoA-I, ApoA-II) and cholesterol contained in HDL subfractions. A single session of LA with DALI or MONET techniques resulted in a similar reduction of lipid-related oxidative stress markers. Concentrations of 8-isoPGF2 and TBARS were reduced by ~60% and ~30%, respectively. LA resulted in a 67% decrease in oxLDL levels along with a ~19% reduction in the oxLDL/ApoB ratio. Concentrations of HDL cholesterol, ApoA-I, ApoA-II, and PON-1 activity were also reduced by LA sessions, with more noticeable effects seen in the MONET technique. The quantitative proportions between HDL2 and HDL3 cholesterol did not change significantly by both methods. In conclusion, LA treatment with MONET or DALI system has a small nonselective effect on lowering HDL particles without any changes in the protein composition of these particles. Significant reduction in the level of oxidative stress parameters and less oxidation of LDL particles may provide an additional benefit of LA therapy.

MODIFICATION OF GUT BACTERIAL BILE SALT HYDROLASE ACTIVITY AND CARDIOVASCULAR RISK: A RANDOMIZED STUDY

Introduction: secretion of bacterial bile salt hydrolase (BSH) is one of the main mechanisms by which gut microbiota play role in cholesterol metabolism. There are limiting and controversial data regarding the clear effect of gut BSH activity correction on modification of serum cholesterol and cardiovascular risk (CVR). Aim of investigation was to evaluate the relationship between modification of the gut bacterial BSH relative activity (RA) by probiotic L. plantarum and serum cholesterol with CVR levels. Methods: the study was conducted as open, comparative, randomized, parallel and included 26 almost healthy participants (healthy control group) and 77 patients with dyslipidemia and without anamnesis of major cardiovascular events, that were divided in two groups: main treatment group (n=41) received combination therapy (capsules with Lactobacillus plantarum in the amount of 2*109 CFU one time a day and tablets simvastatin 20 mg one time a day) and control treatment group (n=36) received monotherapy (simvastatin 20 mg one time a day) during 12 weeks. Before and after 12 weeks of treatment the assessment of total RA of gut BSH, lipid profile and CVR level according to 5 risk scores were performed. Results: at baseline the RA of BSH was higher in healthy adults comparing to participants with dyslipidemia (p&lt;0,001); after 12 weeks of treatment there wasn`t difference between healthy control and only main treatment groups (р=0,45). It was found that with increasing of RA of gut bacterial BSH, the risk of failure of treatment efficacy endpoints achievement (≥20% reduction of values) decreased regarding: total cholesterol (TC) (p=0,0306), OR=0,00133 (95% CI; 3,28*10-6-0,538); low-density lipoproteins (LDL) (p&lt;0,001), OR=5,65*10-14(95% CI; 6,38*10-20-5*10-8); CVR level according to Framingham score (р=0,0035), OR=4,09*10-5(95% CI; 4,66*10-8-0,0359); CVR level according to 2013 ACC/AHA algorithm (р=0,0135), OR=3,8*10-4(95% CI; 7,34*10-7-0,197); CVR level according to PROCAM score (p=0,00125), OR=8,38*10-6 (95%; CI; 6,93*10-9-0,0101). Conclusions: additional supplementation with BSH-producing bacteria L. plantarum was more effective in increasing of BSH activity compared to simvastatin monotherapy. Increasing of BSH RA by L. plantarum was associated with higher chances to achieve treatment efficacy goals regarding reduction of TC, LDL and CVR levels according to Framingham, 2013 ACC/AHA algorithm and PROCAM scores.

Local Condiment, Iru, Obtained from the Fermentation of Parkia biglobosa Seed Substantially Reduced the Serum Cholesterol Level of Wister Rats.

Hypercholesterolaemia is one of the risk factors in coronary heart disease. Hence, this research was designed to investigate the effect of iru on cholesterol levels in hypercholesterolaemic rats. The fermented condiment iru was produced naturally and with starter cultures of Lactobacillus plantarum, Bacillus subtilis, and Leuconostoc sp.. The hypercholesterolaemic rats were fed a diet supplemented with iru for 28 days, and total cholesterol, triglyceride (TG), high density lipoproteins (HDL), and low density lipoproteins (LDL) were determined before and after feeding. Cholesterol levels in hypercholesterolaemic rats (100.80 mg/dL) were reduced to 56.99∼80.21 mg/dL after feeding with iru supplementation while rats not placed on the iru diet had cholesterol levels of 119 mg/dL. There were also significant reductions (P<0.05) in serum TG (78.77∼32.57 mg/dL) and LDL (28.43∼6.63 mg/dL) levels in rats fed the iru diet compared with the control (63.36 mg/dL). Higher and significantly different (P<0.05) HDL was found in rats fed with iru fermented with L. plantarum (44.01 mg/dL) while the least was found in the untreated group (28.93 mg/dL). The results from this study suggest that supplementing the diet with iru obtained by the fermentation of Parkia biglobosa seeds may significantly reduce cholesterol level in the blood stream.

Effect of atorvastatin and metformin combination therapy in type 2 diabetic dyslipidemias

Background: Dyslipidaemia is a major risk factor for cardiovascular complications in patients with type 2 diabetes mellitus and affects 10-73% of this population. In type 2 diabetes mellitus, increased efflux of free fatty acids from adipose tissue and impaired insulin mediated skeletal muscle uptake of free fatty acids, increases fatty acid flux to the liver and also decreased glucose utilization in muscle that leads to acute elevation of free fatty acids. Lipid profile which is altered in diabetes state is one of the significant factors in development of cardiovascular diseases. The derangements seen in serum lipid profile includes: increased total cholesterol (TC), triglycerides (TG) and low-density lipoprotein (LDL) and decreased high-density lipoprotein cholesterol (HDL) concentration. Hence with the aforementioned views the present study had been planned to evaluate the effect of atorvastatin and metformin combination therapy in type 2 diabetic dyslipidemias.Methods: Study design, observational prospective study, with duration of 4-5 months and sample size of 30 patients with type 2 diabetes mellitus are taken with mild to moderate dyslipidemias. The study subjects received combination therapy of metformin 500 mg/day along with atorvastatin 20mg/day, there effect is seen on serum lipid profile and fasting blood glucose levels (FBS).Results: There was a significant mean decrease in TC, LDL , TG , FBS by 31.7 mg/dl (p&lt;0.05), 28.5 mg/dl (p value &lt;0.05), 19.5 mg/dl (p&lt;0.05), 9.13 mg/dl (p&lt;0.05) respectively and rise in HDL by 1.7 mg/dl (p&lt;0.05) ), no significant decrease in VLDL (p&gt;0.05).Conclusions: Combination of atorvastatin and metformin was effective in reduction of TC, LDL, TG and FBS and elevation of HDL levels in type-2 diabetic dyslipidemias.

Long-term effects of one-anastomosis gastric bypass on liver histopathology in NAFLD cases: a prospective study.

Weight reduction can effectively improve nonalcoholic fatty liver disease (NAFLD), which is a constant companion of severe obesity. This study aimed to determine the effect of one-anastomosis gastric bypass (OAGB) on pathological liver changes in severely obese cases with NAFLD. The present prospective research comprised 67 subjects with morbid obesity scheduled for OAGB during the period from February 2015 to August 2018. Clinical, biological, and histologic data were evaluated pre and 15months postoperatively. Fifteen months after surgery, a considerable reduction was noted in the grades of fat deposition, liver cell ballooning, and lobular inflammatory changes, in addition to the total NAS score. Fifteen months after surgery, nonalcoholic steatohepatitis (NASH) disappeared in 42% of the patients. A significant regression of fibrosis stage occurred after surgery in 79.1% of patients (p < 0.001). After surgery, patients had substantial reductions in aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, HbA1c, total cholesterol, and Low-density lipoprotein (p < 0.001, for all comparisons). Diabetes mellitus, hypertension, and dyslipidemia resolved in 54%, 59%, and 69% of the patients, respectively. OAGB resolved NASH from nearly 42% of patients and reduced the histological features of NAFLD 15months after surgery. Bariatric procedures might be adopted as a therapeutic modality in severely obese cases with NAFLD after the failure of lifestyle modifications.

The Effects of Islamic Fasting on Blood Biochemical Parameters in Morbidly Obese Patients Undergone Bariatric Surgery

Morbidly obese patients who have undergone Roux-en-Y gastric bypass are prone to alterations in lipid, glucose, and serum electrolyte profiles. The changes in these factors were investigated after Islamic fasting vs. non-fasting in bariatric surgery patients. This case-control study was conducted on patients who had undergone bariatric surgery 6 to 12 months before. Two groups of participants (case group: Islamic fasting; control group: no fasting) were compared in terms of their blood biochemical parameters. Blood samples were collected 2 weeks before and 2 weeks after the fasting period of Ramadan. None of the participants showed any known complications. The mean age of the participants was 38.4 ± 8.2 years. The two groups were similar in terms of age and sex (P > 0.05 for both). The comparison of these factors after the fasting period showed a significant reduction in blood cholesterol (P = 0.003), low-density lipoprotein (P = 0.016), and total protein (P = 0.022) in the case group compared with those in the controls. Other parameters, including fasting blood glucose, blood urea nitrogen, creatinine, triglyceride, high-density lipid, very low-density lipoprotein, albumin, calcium, phosphor, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin, showed no significant differences after fasting in this study (P > 0.05). Islamic fasting does not have detrimental effects on blood chemistry parameters in patients who have had Roux-en-Y gastric bypass.

The Effect of Dietary Nitrate and Vitamin C on Endothelial Function and Oxidative Stress Biomarkers

Abstract Objectives Examine the effects of concentrated beetroot juice (CBJ) supplementation with and without vitamin C on markers of endothelial function (reactive hyperemia index (RHI) and blood biomarkers) and lipid profiles. Methods Subjects 50 to 70 years of age with low density lipoprotein (LDL) &amp;gt; 130 mg/dL and RHI ≤ 2 were enrolled in this randomized crossover double-blind study. Two 4-week interventions were separated by a 2-week washout. Subjects were assigned to daily CBJ (70 mls) with 1000 mg of vitamin C (NC) or CBJ with matched placebo (N), then switched to alternate treatment. At baseline and 4-weeks, RHI was measured using EndoPAT. Secondary outcomes included the sum of plasma NO metabolites (NO2 + NO3 = NOx), oxidized LDL (oxLDL), and serum lipids. Paired t-tests were used to compare differences between treatments. Results Eighteen of 23 subjects completed all study visits (7 male, 11 females). No significant treatment differences were observed in RHI change (N: 0.21 ± 0.46; NC: 0.20 ± 0.67; P &amp;gt; 0.05). NC subjects with baseline RHI of &amp;lt; 1.67 (mean = 1.23; n = 8) had greater improvements in RHI compared to subjects with RHI scores &amp;gt; 1.67 (mean = 1.75; n = 8; P = 0.02). Compared to N, NC resulted in a significant increase in plasma NOx (N: 94.2 ± 15.5 μmol/L; NC: 128.7 ± 29.1 μmol/L; P = 0.01). NC treatment reduced oxLDL/NOx ratio compared to N (N: −3.97 ± 2.8 U/L; NC: −4.29 ± 3.1 U/L; P = 0.02). NC elicited significant reductions in LDL (N: 2.2 ± 2; NC: −10.7 ± 23; P = 0.049), and triglycerides (N: 14.6 ± 43; NC: −43.7 ± 45; P = 0.03) with no change in serum high density lipoprotein. Conclusions NC appears effective at improving RHI in subjects with evidence of endothelial dysfunction. Four weeks of NC enriched the NO pool and promoted favorable changes in oxLDL/NOx ratio and blood lipids in subjects with hypercholesterolemia. These preliminary findings highlight a novel supplementation strategy that may reduce the progression of atherosclerotic disease and deserves further attention in studies using flow mediated dilation methods. Funding Sources Thornton Scholarship funds, College of Health Sciences, University of Kentucky.

The Effects of Magnesium Supplementation on Lipid Profile Among Type 2 Diabetes Patients: a Systematic Review and Meta-analysis of Randomized Controlled Trials.

We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effects of magnesium (Mg) supplementation on the lipid profile in type 2 diabetes (T2DM) patients. Web of Science, Scopus, PubMed, and Embase databases were searched to infinity until 30 January 2020. Weighted mean differences (WMD) were pooled using a random-effects model. Heterogeneity, sensitivity analysis, and publication bias were reported using standard methods. The pooled analysis of 12 randomized controlled trial s indicated that Mg administration led to significant reduction of serum low-density lipoprotein (LDL) levels (p = 0.006). However, our results revealed that Mg supplementation did not have any effect on triglycerides (TG), total cholesterol (TC), and high-density lipoprotein (HDL) serum concentrations among T2DM patients in comparison with the control group. Subgroup analysis based on duration of study suggested that more than 12weeks of Mg supplementation significantly decreased the serum TC levels (p = 0.002). Subgroup analysis comparing the dose of intervention indicated that Mg supplementation less than 300mg significantly decreased the serum LDL concentrations (p < 0.001), while more than 300mg of Mg supplementation significantly increased the serum HDL levels (p = 0.026). In a subgroup analysis comparing the type of intervention, it displayed that inorganic Mg supplementation decreased the LDL (p < 0.001) and TC (p = 0.003) levels, while organic Mg supplementation showed no difference. Mg supplementation has a beneficial effect on lowering LDL level in T2DM patients. However, we have to note that any research performed so far is not sufficient for making robust guidelines to use Mg supplementation in clinical practice.

Effects of supervised exercise training on lipid profile of children and adolescents: Systematic review, meta-analysis and meta-regression

Summary Objectives The aim of the present study was to conduct a systematic review and meta-analysis evaluating the effects of supervised exercise on total cholesterol and low-density lipoprotein adaptations in children and adolescents. Additionally, we aimed to know the possible moderators of exercise effects. News Eligible studies that evaluated the effect of supervised exercise on the total cholesterol and low-density lipoprotein levels of children or adolescents (aged between 2 and 17 years) were searched on EMBASE, MEDLINE, Cochrane and Scopus databases up to June 2017. Random effect was used and the effect size was calculated by using the standardized mean difference with a 95% confidence interval. Exercise promotes reduction in total cholesterol (effect size: −0.67; 95% confidence interval: −1.12, −0.22; P = 0.003) and low-density lipoprotein (effect size: −1.13; 95% confidence interval: −1.66, −0.59; P Conclusion Supervised exercise is efficient in reducing total cholesterol and low-density lipoprotein levels of children and adolescents. For total cholesterol and low-density lipoprotein outcomes, the longer the follow-up, lower the reductions found. Greater decreases in low-density lipoprotein were associated with older age of adolescents.

Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol

BackgroundInclisiran inhibits hepatic synthesis of proprotein convertase subtilisin–kexin type 9. Previous studies suggest that inclisiran might provide sustained reductions in low-density lipoprotein (LDL) cholesterol levels with infrequent dosing.MethodsWe enrolled patients with atherosclerotic cardiovascular disease (ORION-10 trial) and patients with atherosclerotic cardiovascular disease or an atherosclerotic cardiovascular disease risk equivalent (ORION-11 trial) who had elevated LDL cholesterol levels despite receiving statin therapy at the maximum tolerated dose. Patients were randomly assigned in a 1:1 ratio to receive either inclisiran (284 mg) or placebo, administered by subcutaneous injection on day 1, day 90, and every 6 months thereafter over a period of 540 days. The coprimary end points in each trial were the placebo-corrected percentage change in LDL cholesterol level from baseline to day 510 and the time-adjusted percentage change in LDL cholesterol level from baseline after day 90 and up to day 540.ResultsA total of 1561 and 1617 patients underwent randomization in the ORION-10 and ORION-11 trials, respectively. Mean (±SD) LDL cholesterol levels at baseline were 104.7±38.3 mg per deciliter (2.71±0.99 mmol per liter) and 105.5±39.1 mg per deciliter (2.73±1.01 mmol per liter), respectively. At day 510, inclisiran reduced LDL cholesterol levels by 52.3% (95% confidence interval [CI], 48.8 to 55.7) in the ORION-10 trial and by 49.9% (95% CI, 46.6 to 53.1) in the ORION-11 trial, with corresponding time-adjusted reductions of 53.8% (95% CI, 51.3 to 56.2) and 49.2% (95% CI, 46.8 to 51.6) (P<0.001 for all comparisons vs. placebo). Adverse events were generally similar in the inclisiran and placebo groups in each trial, although injection-site adverse events were more frequent with inclisiran than with placebo (2.6% vs. 0.9% in the ORION-10 trial and 4.7% vs. 0.5% in the ORION-11 trial); such reactions were generally mild, and none were severe or persistent.ConclusionsReductions in LDL cholesterol levels of approximately 50% were obtained with inclisiran, administered subcutaneously every 6 months. More injection-site adverse events occurred with inclisiran than with placebo. (Funded by the Medicines Company; ORION-10 and ORION-11 ClinicalTrials.gov numbers, NCT03399370 and NCT03400800.)

Assessment of the Efficacy of Lowering LDL Cholesterol with Rosuvastatin 10 mg in Four Korean Statin Benefit Groups as per ACC/AHA Guidelines (NewStaR4G).

The American College of Cardiology and American Heart Association (ACC/AHA) guidelines identified four statin benefit groups on the basis of atherosclerotic cardiovascular disease risk reduction and proposed statin therapy by evidence-based intensity. Although these guidelines used randomized controlled trials with hard outcomes as exclusive evidence for its recommendations, a limited number of studies conducted in Asian countries makes its application of treatment strategy, intensity, and statin doses uncertain in these population. This prospective, multicenter study aimed to evaluate the efficacy of rosuvastatin 10 mg in the four statin benefit groups requiring high- or moderate-intensity statin therapy according to the ACC/AHA guidelines in the Korean population. The primary endpoint was percentage reduction in low-density lipoprotein (LDL) cholesterol. Secondary endpoints were percentage reduction in other lipids and achievement of ≥50% reduction in LDL cholesterol. Rosuvastatin 10 mg lowered LDL cholesterol by 61.4 mg/dL, a 44.9% decrease from baseline after eight weeks. Reduction of LDL cholesterol ≥50% was achieved in 46.3% of patients. Rosuvastatin 10 mg was generally well tolerated. In the Korean population, rosuvastatin 10 mg was favorable and tolerant in lowering LDL cholesterol in the four statin benefit groups requiring high- or moderate-intensity statin therapy according to the ACC/AHA guidelines.

Argon plasma coagulation alone versus argon plasma coagulation plus full-thickness endoscopic suturing to treat weight regain after Roux-en-Y gastric bypass: a prospective randomized trial (with videos)

A significant number of patients regain weight after Roux-en-Y gastric bypass. Ablation with argon plasma coagulation (APC) plus endoscopic full-thickness suturing (FTS-APC) and ablation alone have been reported for treating weight regain when associated with gastrojejunostomy (GJ) dilation. However, comparative controlled data are still lacking. This was a pilot single-center open-label randomized trial comparing the effectiveness and safety of APC alone versus FTS-APC for transoral outlet reduction. Patients with at least 20% weight regain from the nadir, and GJ≥15mm were considered eligible. The primary outcome was percentage total weight loss (%TWL) at 12 months. Secondary outcomes were the incidence of adverse events, amelioration of metabolic laboratory parameters, and improvement in quality of life and eating behavior. Forty patients meeting the eligibility criteria were enrolled from October 2017 to July 2018. Technical and clinical success rates were similar between the groups. At 12 months, the mean %TWL was 8.3% ± 5.5% in the APC alone group versus 7.5% ± 7.7% in the FTS-APC group (P= .71). The pre-revisional % solid gastric retention at 1 hour positively correlated with the probability of achieving≥10% TWL at 12 months. Both groups experienced significant reductions in low-density lipoprotein and triglyceride levels at 12 months, and improvement in eating behavior and quality of life at 3 months. There were 2 cases of stenoses (1 from each group), which were successfully treated with endoscopic balloon dilation. APC alone is similar to FTS-APC in terms of technical and clinical outcomes within 1 year of follow-up. (Clinical trial registration number: NCT03094936.).

Effect of CETP inhibition with evacetrapib in patients with diabetes mellitus enrolled in the ACCELERATE trial

BackgroundHigh-density lipoprotein (HDL) levels are inversely associated with cardiovascular risk. Cholesteryl ester transfer protein inhibition with evacetrapib results in a marked increase in HDL and reduction in low-density lipoprotein (LDL)...

Triglycerides and Cardiovascular Outcomes-Can We REDUCE-IT ?

The causal linkage between triglycerides and coronary artery disease has been controversial. Most of the trials hitherto have shown marginal or no beneficial effects of reduction of triglycerides (with fibrates) on top of low-density lipoprotein (LDL) reduction. But a significant residual cardiovascular risk remains even after use of high dose of statins. Omega-3 fatty acids have been shown to reduce triglyceride levels and some old trials have shown the benefits of fish oils in reducing cardiovascular events. However, barring a few trials most of the large trials of omega-3 fatty acids are negative. Recently, few large trials have been conducted to see the effects of high dose omega-3 fatty acids on cardiovascular outcomes and some of them have shown promising results on top of LDL reduction.