Low-density Lipoprotein Cholesterol In Adults Research Articles

Cognitive function with evolocumab in pediatric heterozygous familial hypercholesterolemia

Evolocumab is a fully human monoclonal antibody inhibitor of PCSK9 approved for lowering low-density lipoprotein cholesterol in adults and pediatric patients with familial hypercholesterolemia (FH). The cognitive safety of evolocumab has been established in adults but has not yet been described in pediatric patients. To determine the effects of evolocumab on cognitive function in pediatric heterozygous FH. Cognitive function was assessed during a 24-week, randomized, double-blind, placebo-controlled study (HAUSER-RCT) evaluating the efficacy, safety, and tolerability of 24 weeks of monthly subcutaneous injections of evolocumab in pediatric patients with FH. Cognitive safety endpoints included changes from baseline to week 24 in test scores in domains of psychomotor function, attention, visual learning, and executive function. Between-group differences in age-standardized mean test score changes were analyzed using analysis of covariance models and point estimates with 95% confidence interval (CI). Magnitudes of difference between treatment groups (Cohen's d) and reliable change indices were calculated for each cognitive function test. At week 24, changes from baseline in age-standardized cognitive test scores were similar between the treatment groups. Differences (95% CI) between the evolocumab and placebo groups in mean test score changes for the Groton Maze Learning, One-Card Learning, Identification, and Detection tests were 0.1 (-0.2, 0.4), -0.1 (-0.5, 0.4), 0.3 (0.0, 0.7), 0.3 (-0.1, 0.8), respectively. For all tests, abnormal and clinically important cognitive decline occurred with lesser frequency in the evolocumab group. In pediatric patients with FH, 24-week treatment with evolocumab did not negatively influence cognition. This study was funded and designed by Amgen.

Pooled Patient-Level Analysis of Inclisiran Trials in Patients With Familial Hypercholesterolemia or Atherosclerosis

BackgroundInclisiran is a double-stranded small interfering RNA that suppresses proprotein convertase subtilisin–kexin type 9 (PCSK9) translation in the liver, leading to sustained reductions in low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipoproteins with twice-yearly dosing. ObjectivesThe purpose of this study was to conduct a patient-level pooled analysis from 3 phase 3 studies of inclisiran. MethodsParticipants with heterozygous familial hypercholesterolemia (ORION-9 [Trial to Evaluate the Effect of Inclisiran Treatment on Low Density Lipoprotein Cholesterol (LDL-C) in Subjects With Heterozygous Familial Hypercholesterolemia (HeFH)]), atherosclerotic cardiovascular disease (ASCVD) (ORION-10 [Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol]), or ASCVD and ASCVD risk equivalents (ORION-11 [Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol]) taking maximally tolerated statin therapy, with or without other LDL-C–lowering agents, were randomly assigned in a 1:1 ratio to receive either inclisiran or placebo, administered by subcutaneous injection on day 1, day 90, and every 6 months thereafter for 540 days. The coprimary endpoints were the placebo-corrected percentage change in LDL-C level from baseline to day 510 and the time-adjusted percentage change in LDL-C level from baseline after day 90 to day 540. Levels of other atherogenic lipoproteins and treatment-emergent adverse events were also assessed. ResultsA total of 3,660 participants (n = 482, n = 1,561, and n = 1,617 from ORION-9, -10, and -11, respectively) underwent randomization. The placebo-corrected change in LDL-C with inclisiran at day 510 was −50.7% (95% confidence interval: −52.9% to −48.4%; p < 0.0001). The corresponding time-adjusted change in LDL-C was −50.5% (95% confidence interval: −52.1% to −48.9%; p < 0.0001). Safety was similar in both groups. Treatment-emergent adverse events at the injection site were more frequent with inclisiran than placebo (5.0% vs. 0.7%), but were predominantly mild, and none were severe or persistent. Liver and kidney function tests, creatine kinase values, and platelet counts did not differ between groups. ConclusionsThese pooled safety and efficacy data show that inclisiran, given twice yearly in addition to maximally tolerated statin therapy with or without other LDL-C lowering agents, is an effective, safe, and well-tolerated treatment to lower LDL-C in adults with heterozygous familial hypercholesterolemia, ASCVD, or ASCVD risk equivalents.

Effects of long-term excessive iodine intake on blood lipids in Chinese adults: a cross-sectional study.

The aim of this study was to evaluate the effects of long-term excessive iodine intake on blood lipids in adults. Three counties from Dezhou city and Liaocheng city in the Shandong province of China were selected as survey locations. Three to five villages were selected from each county and then categorized by the iodine concentration detected in the groundwater into Low (<10 µg/L), Medium (10-150 µg/L), High (150-300 µg/L), and Excessive (>300 µg/L) groups. A self-reported questionnaire was completed by each subject to provide demographic characteristics. Body height, weight, and blood pressure were recorded by trained staff. Blood lipids were measured. A total of 2156 subjects were recruited for the final analysis. The serum triglyceride (TRIG) was significantly higher in the Excessive group than in the other three groups (P < 0.05). Total cholesterol (TCHOL) and low-density lipoprotein-cholesterol (LDL-C) showed downward trends with the increases in the water iodine concentration. A statistical significance of the crude correlation coefficient was detected between the water iodine concentration and the TRIG, TCHOL, or LDL-C (P < 0.05). A significant correlation was also noted between the water iodine concentration and TCHOL or LDL-C after adjustment for covariates. High iodine concentration was a significant protective factor for TCHOL and LDL-C in adults, whereas elevated BMI and advancing age were risk factors for both variables. An association was identified between iodine excess and low TCHOL or LDL-C. In areas with excessive iodine, iodine intake should be considered in studies examining the factors that influence blood lipids.

Efficacy, safety, and tolerability of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia: Rationale and design of the HAUSER-RCT study

Evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9, is safe and effective in reducing low-density lipoprotein cholesterol in adults with familial hypercholesterolemia. A dedicated study, HAUSER-RCT, is being conducted to examine the efficacy and safety of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia (HeFH). To present the rationale and design of the HAUSER-RCT study. The HAUSER-RCT study is a double-blind, randomized, multicenter, placebo-controlled study designed to characterize the efficacy, safety, and tolerability of evolocumab treatment as an add-on to diet and lipid-lowering therapy, including a stable, optimized dose of statin, in pediatric patients aged 10 to 17years with HeFH. Approximately, 150 patients will be randomized in a 2:1 ratio to receive 24weeks of monthly evolocumab or placebo. The study will include approximately 51 sites located in North America, South America, Europe, South Africa, Australia, and New Zealand. The primary efficacy endpoint is the percent change in low-density lipoprotein cholesterol from baseline to week 24. A key secondary efficacy endpoint is the percent change in other lipid parameters from baseline to week 24. Other assessments include Tanner staging, carotid intima-media thickness, and cognitive tests. At the end of the study, consenting patients can participate in an 18-month open-label extension study (HAUSER-OLE). The study is ongoing and the results will be communicated at the end of the study. The HAUSER-RCT study, the largest randomized, placebo-controlled study with proprotein convertase subtilisin/kexin type 9 inhibitors being conducted in the pediatric HeFH population, aims to provide efficacy, safety, and tolerability data of evolocumab as an add-on therapy in these patients.

Clinical outcomes to exercise training in type 1 diabetes: A systematic review and meta-analysis

AimsTo establish the relationship between exercise training and clinical outcomes in people with type I diabetes. MethodsStudies were identified through a MEDLINE search strategy, Cochrane Controlled Trials Registry, CINAHL, SPORTDiscus and Science Citation Index. The search strategy included a mix of key concepts related to trials of exercise training in people with type 1 diabetes; glycaemic control. Searches were limited to prospective randomized or controlled trials of exercise training in humans with type 1 diabetes lasting 12 weeks or more. ResultsIn exercised adults there were significant improvements in body mass Mean Difference (MD): −2.20 kg, 95% Confidence Interval (CI) −3.79–0.61, p = .007; body mass index (BMI) MD: −0.39 kg/m2, 95% CI −0.75–0.02, p = .04; Peak VO2 MD: 4.08 ml/kg/min, 95% CI −2.18–5.98, p < .0001; and, low-density lipoprotein cholesterol (LDL) MD: −0.21 mmol/L, 95% CI −0.33–0.08, p = .002. In exercised children there were significant improvements in insulin dose MD: −0.23 IU/kg, 95% CI −0.37–0.09, p = .002; waist circumference MD: −5.40 cm, 95% CI −8.45 to −2.35, p = .0005; LDL MD: −0.31 mmol/L, 95% CI −0.55 to −0.06, p = .02; and, triglycerides MD: −0.21 mmol/L, 95% CI −0.42 to −0.01, p = .04. There were no significant changes in glycosylated haemoglobin (HbA1C%), fasting blood glucose, resting heart rate, resting systolic blood pressure or high density lipoproteins in either group. ConclusionsExercise training improves some markers of type 1 diabetes severity; particularly body mass, BMI, Peak VO2 and LDL in adults and insulin dose, waist circumference, LDL and triglycerides in children.

Krill oil supplementation lowers serum triglycerides without increasing low-density lipoprotein cholesterol in adults with borderline high or high triglyceride levels

The aim of the study was to explore the effects of 12 weeks daily krill oil supplementation on fasting serum triglyceride (TG) and lipoprotein particle levels in subjects whose habitual fish intake is low and who have borderline high or high fasting serum TG levels (150–499 mg/dL). We hypothesized that Krill oil lowers serum TG levels in subjects with borderline high or high fasting TG levels. To test our hypothesis 300 male and female subjects were included in a double-blind, randomized, multi-center, placebo-controlled study with five treatment groups: placebo (olive oil) or 0.5, 1, 2, or 4 g/day of krill oil. Serum lipids were measured after an overnight fast at baseline, 6 and 12 weeks. Due to a high intra-individual variability in TG levels, data from all subjects in the four krill oil groups were pooled to increase statistical power, and a general time- and dose-independent one-way analysis of variance was performed to assess efficacy. Relative to subjects in the placebo group, those administered krill oil had a statistically significant calculated reduction in serum TG levels of 10.2%. Moreover, LDL-C levels were not increased in the krill oil groups relative to the placebo group. The outcome of the pooled analysis suggests that krill oil is effective in reducing a cardiovascular risk factor. However, owing to the individual fluctuations of TG concentrations measured, a study with more individual measurements per treatment group is needed to increase the confidence of these findings.

Phytosterols for dyslipidemia

The efficacy and safety of phytosterols for the management of dyslipidemia are reviewed. Phytosterols have been evaluated in over 40 clinical trials. The incorporation of 2 g of phytosterols daily into margarine, mayonnaise, orange juice, olive oil, low-fat milk, yogurt, and tablets is associated with significant reductions in low-density-lipoprotein (LDL) cholesterol from baseline over 1-12 months in adults with normal or high cholesterol, in children, and in patients with type 2 diabetes mellitus. Phytosterol dosages of 1.6-3 g daily have been shown to reduce LDL cholesterol by 4.1-15% versus placebo within the first month of therapy. One meta-analysis found mean reductions of 10-11%, but results vary. Several placebo-controlled trials found that the addition of phytosterols to statin therapy was associated with reductions of 7-20% in LDL cholesterol for up to 1.5 years. Overall, phytosterols are useful for reducing LDL cholesterol in patients who cannot reach their treatment goal by diet alone or who are taking maximum tolerated doses of statins. These products offer an alternative to statins in patients who cannot take statins or whose statin dosage is restricted because of potential drug interactions or concomitant diseases. Commonly reported adverse effects are primarily gastrointestinal in nature. Phytosterol therapy produces an average 10-11% reduction in LDL cholesterol concentration, but it is unknown whether this effect persists beyond two years. Phytosterol products are well tolerated and have few drug interactions, but their long-term safety has not been established. Current evidence is sufficient to recommend phytosterols for lowering LDL cholesterol in adults.

Almond Consumption and Cardiovascular Risk Factors in Adults with Prediabetes

Objective: The authors tested the hypothesis that in adults with prediabetes, an almond-enriched American Diabetes Association (ADA) diet improves measures of insulin sensitivity and other cardiovascular risk factors compared with an ADA nut-free diet.Methods: Design: Randomized parallel-group trial. Setting: Outpatient dietary counseling and blood analysis. Subjects: Sixty-five adult participants with prediabetes. Intervention: Sixteen weeks of dietary modification featuring an ADA diet containing 20% of energy from almonds (approximately 2 oz per day). Measures of Outcome: Outcomes included fasting glucose, insulin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, TC:HDL-C, and HbA1c, which were measured at weeks 0, 8, and 16. Body weight, body mass index (BMI), waist circumference, blood pressure, and nutrient intake were measured at weeks 0, 4, 8, 12, and 16.Results: The almond-enriched intervention group exhibited greater reductions in insulin (−1.78 µU/ml vs. +1.47 µU/ml, p = 0.002), homeostasis model analysis for insulin resistance (−0.48 vs. +0.30, p = 0.007), and homeostasis model analysis for beta-cell function (−13.2 vs. +22.3, p = 0.001) compared with the nut-free control group. Clinically significant declines in LDL-C were found in the almond-enriched intervention group (−12.4 mg/dl vs. −0.4 mg/dl) as compared with the nut-free control group. No changes were observed in BMI (−0.4 vs. −0.7 kg/m2, p = 0.191), systolic blood pressure (−4.4 mm Hg vs. −3.5 mm Hg, p = 0.773), or for the other measured cardiovascular risk factors.Conclusions: An ADA diet consisting of 20% of calories as almonds over a 16-week period is effective in improving markers of insulin sensitivity and yields clinically significant improvements in LDL-C in adults with prediabetes.

Whole-Grain Ready-to-Eat Oat Cereal, as Part of a Dietary Program for Weight Loss, Reduces Low-Density Lipoprotein Cholesterol in Adults with Overweight and Obesity More than a Dietary Program Including Low-Fiber Control Foods

Objective Weight loss and consumption of viscous fibers both lower low-density lipoprotein (LDL) cholesterol levels. We evaluated whether or not a whole-grain, ready-to-eat (RTE) oat cereal containing viscous fiber, as part of a dietary program for weight loss, lowers LDL cholesterol levels and improves other cardiovascular disease risk markers more than a dietary program alone. Design Randomized, parallel-arm, controlled trial. Subjects/setting Free-living, overweight and obese adults (N=204, body mass index 25 to 45) with baseline LDL cholesterol levels 130 to 200 mg/dL (3.4 to 5.2 mmol/L) were randomized; 144 were included in the main analysis of participants who completed the trial without significant protocol violations. Intervention Two portions per day of whole-grain RTE oat cereal (3 g/day oat b-glucan) or energy-matched low-fiber foods (control), as part of a reduced energy (∼500 kcal/day deficit) dietary program that encouraged limiting consumption of foods high in energy and fat, portion control, and regular physical activity. Main outcome measures Fasting lipoprotein levels, waist circumference, triceps skinfold thickness, and body weight were measured at baseline and weeks 4, 8, 10, and 12. Results LDL cholesterol level was reduced significantly more with whole-grain RTE oat cereal vs control (−8.7±1.0 vs −4.3±1.1%, P=0.005). Total cholesterol (−5.4±0.8 vs −2.9±0.9%, P=0.038) and non–high-density lipoprotein-cholesterol (−6.3±1.0 vs −3.3±1.1%, P=0.046) were also lowered significantly more with whole-grain RTE oat cereal, whereas high-density lipoprotein and triglyceride responses did not differ between groups. Weight loss was not different between groups (−2.2±0.3 vs −1.7±0.3 kg, P=0.325), but waist circumference decreased more (−3.3±0.4 vs −1.9±0.4 cm, P=0.012) with whole-grain RTE oat cereal. Larger reductions in LDL, total, and non–high-density lipoprotein cholesterol levels and waist circumference were evident as early as week 4 in the whole-grain RTE oat cereal group. Conclusions Consumption of a whole-grain RTE oat cereal as part of a dietary program for weight loss had favorable effects on fasting lipid levels and waist circumference.

Effects of aerobic exercise on lipids and lipoproteins in adults with type 2 diabetes: A meta-analysis of randomized-controlled trials

To conduct a meta-analysis of randomized-controlled trials in order to examine the effects of 8 weeks or more of aerobic exercise on lipids and lipoproteins in adults with Type 2 diabetes. Studies were included if total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), ratio of TC to HDL-C (TC/HDL-C), triglycerides (TG), or all of the above, were assessed. A secondary outcome was glycosylated haemoglobin (HbA1). Seven studies representing 220 men and women (112 exercise, 108 control) were available for pooling. Using a random-effects model, a statistically significant reduction of about 5% was found for LDL-C, whereas no statistically significant improvements were found for TC, HDL-C, TC/HDL-C or TG. A trend for a statistically significant reduction in HbA1 was also found. Although our overall results suggest that aerobic exercise lowers LDL-C in adults with Type 2 diabetes, additional randomized-controlled trials are needed on this topic.