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The Treatment Adherence Perception Questionnaire (TAPQ) is a new, brief self-report instrument for assessing patient perceptions and attitudes regarding their own adherence to medical treatment plans. It includes 3 distinct scales: Perceived Behavior, Perceived Benefit, and Perceived Burden. In contrast with existing measures, the TAPQ was expected to have a clear factor structure; have good discrimination; and assess distinct types of perception, each of which has different patterns of association with interpersonal, personality, motivational, and emotional variables. Foundational work on the TAPQ (with 891 patients) included 5 quantitative scale development studies and 1 qualitative study. The present report focuses on results from a final validation study using 450 patients recruited via market research panels to complete online questionnaires. This study included a general medical sample and a sample of people with either diabetes or hypertension. A confirmatory factor analysis specifying strict measurement invariance across these groups produced a good fit. Analysis with item-response theory suggested that the scales on the TAPQ provide good discrimination across a wide range of experience levels. The 3 scales on the TAPQ each had distinct patterns of association with criterion variables regarding conscientiousness, health behavior, motivation, affect, type of diagnosis, and interpersonal communication with health-care professionals. These effects could not be explained by another existing measure of adherence or by a measure of response bias. (PsycINFO Database Record (c) 2020 APA, all rights reserved). [ABSTRACT FROM AUTHOR]

The Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion on the safety of monacolins in red yeast rice (RYR) and to provide advice on a dietary intake of monacolins that does not give rise to concerns about harmful effects to health. The Panel reviewed the scientific evidences available as well as the information provided by interested parties in response of a public 'Call for data' launched by EFSA. The Panel considered that monacolin K in lactone form is identical to lovastatin, the active ingredient of several medicinal products authorised for the treatment of hypercholesterolaemia in the EU. On the basis of the information available, the Panel concluded that intake of monacolins from RYR via food supplements, could lead to estimated exposure to monacolin K within the range of the therapeutic doses of lovastatin. The Panel considered that the available information on the adverse effects reported in humans were judged to be sufficient to conclude that monacolins from RYR when used as food supplements were of significant safety concern at the use level of 10 mg/day. The Panel further considered that individual cases of severe adverse reactions have been reported for monacolins from RYR at intake levels as low as 3 mg/day. The Panel concluded that exposure to monacolin K from RYR could lead to severe adverse effects on musculoskeletal system, including rhabdomyolysis, and on the liver. In the reported cases, the product contained other ingredients in addition to RYR. However, these reported effects in particular musculoskeletal effects, have both occurred after ingestion of monacolin K and lovastatin independently. On the basis of the information available and several uncertainties highlighted in this opinion, the Panel was unable to identify a dietary intake of monacolins from RYR that does not give rise to concerns about harmful effects to health, for the general population, and as appropriate, for vulnerable subgroups of the population. [ABSTRACT FROM AUTHOR]

Physical exercise increase is confirmed as a fundamental treatment for hypercholesterolemia patients, but the effect on the arterial stiffness and oxidative stress is still unclear. 74 hypercholesterolemia patients were divided into 2 groups. The exercise group received dietary recommendations and a 3-month exercise program, prescribed according to their first cardiopulmonary exercise tests(CPET), while the control group only received dietary recommendations. All patients underwent blood tests, CPET and brachial-ankle pulse wave velocity (baPWV) studies at enrollment and at 3 months' follow-up. At the end of 3 months, there was no change in total cholesterol (TC) level in either group. However, in the exercise group, we found maximal exercise parameters increased and baPWV values declined. Meanwhile, there were significant changes in the level of malondialdehyde, 8-isoprostane-F2α and superoxide dis-mutase. Moreover, the change of baPWV was positively correlated with the change of 8-isoprostane-F2α (r = 0.36, P < 0.01). In the control group, no change in baPWV or oxidative bio-marker was observed. Our findings suggested that regular aerobic exercise could lessen arterial stiffness in hypercholesterolemia patients, even in the context of no obvious TC decrease. During this process, favorable adjustment in oxidative stress might be an important pathway, which remains to be further explored. [ABSTRACT FROM AUTHOR]

Aims: The aims of the present study were, firstly, to evaluate long‐term trends in the occurrence and treatment of cardiovascular disease (CVD) risk factors and the occurrence of CVD events in children with type 1 diabetes mellitus (T1DM) and, secondly, to assess the determinants of undertreatment of CVD risk factors. Methods: A retrospective cohort study was conducted in 3728 children (<19 years of age) with T1DM and up to 5 age‐ and gender‐matched diabetes‐free children (reference cohort) (n = 18 513) using data from the Clinical Practice Research Datalink (CPRD). Results: Compared with diabetes‐free subjects, children with T1DM had significantly higher annual prevalence rates of CVD risk factors and cardiovascular (CV) medication use 20 years after the onset of diabetes (index date): hypertension: 35.2% vs. 11.4%, P < 0.001; hypercholesterolaemia: 66.7% vs. 7.14%, P < 0.001; and CV medication use: 37.0% vs. 3.6%, P < 0.001. The significant differences between prevalence rates in the two cohorts started from 1 year before the index date. Furthermore, 50% of the children in the T1DM cohort with hypertension and 53% with hypercholesterolaemia remained untreated with CV drugs for a period of 2–5 years during the 20‐year follow‐up. Age was the only determinant associated with undertreated hypertension in the T1DM cohort. Conclusions: Children with T1DM had substantially higher prevalence rates of hypertension and hypercholesterolaemia from 1 year before up to 20 years after the onset of diabetes compared with nondiabetics. There is a substantial undertreatment of CVD risk factors with CV drugs. In children with T1DM, screening for CVD risk factors and adequate treatment are of the utmost importance to prevent CVD later in life. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To develop a conceptual model that provides a comprehensive understanding of the structures and processes underpinning patient enablement and satisfaction in general practice nurse consultations. Background: Current evidence regarding patient satisfaction and enablement arising from general practice nursing care is either quantitative or qualitative. To date, no studies have integrated the results of mixed methods research to provide a deeper understanding of processes that facilitate their achievement. Design: A concurrent mixed methods study. Methods: Our 2013–2014 concurrent mixed methods study comprised a quantitative study that analysed variables identified in interviews with general practice nurses, patients and practice managers with data from a cross‐sectional survey of 678 patients receiving nursing care in 21 general practices; and a qualitative study that used a grounded theory approach to in‐depth interviews with nurses and patients from these same practices. Using joint displays, we compared and integrated the results of the multilevel analyses and the grounded theory model derived from these studies. Findings: We conceptualized a model—‘developing a positive patient experience with nurses in general practice’—in which time, continuity of care, nursing scope of practice and autonomy, and patients’ health conditions provide platforms for the processes of triggering healthcare partnerships and tailoring care in nurse consultations. Conclusion: This model builds on previous evidence describing processes and characteristics that optimize the quality of care in general practice nurse consultations. It provides a practical tool to inform education and training for general practice nurses and other clinicians. [ABSTRACT FROM AUTHOR]

Study Design: Clinical trial study. Purpose: The aim of this study was to evaluate the effect of atorvastatin on sensory and motor function in patients with acute spinal cord injury. Overview of Literature: The prevalence and incidence of traumatic spinal cord injury are increasing. Statins are well established for use in hypercholesterolemia as well as during anti-inflammatory events. Methods: This clinical trial study included 60 patients with acute spinal cord injury. These were randomly divided into two groups: the case group which received atorvastatin and also underwent surgical therapy and the control group which only underwent surgical therapy. Results: The severity of spinal cord lesions was evaluated based on the Frankel grade at three periods; this showed no significant difference between the two groups. Comparisons of the levels of pain between the groups based on a Visual Analog Scale system showed no significant difference at the three periods. Conclusions: We observed no improvement at the 3- and 6-month follow-up in patients who were administered atorvastatin. However, a comparison of the two groups based on pain severity demonstrated a significant difference, suggesting that atorvastatin had a positive effect on patients with spinal cord injury. [ABSTRACT FROM AUTHOR]

Context:Clausena anisum-olens(Blanco) Merr. (Rutaceae) is a medicinal shrub which has been reported to have various pharmacological uses. No study regarding the effects ofC. anisum-olenson cholesterol-lowering has been reported. Objective:The effects of the ethanol extract ofC. anisum-olensleaves on the cholesterol level of hypercholesterolemic rats were evaluated. Materials and methods:Acute oral toxicity of the extract (175, 550 and 2000 mg/kg) was determined using female Sprague-Dawley rats, as described in OECD 425 Main test guidelines. The lipid-lowering assay utilized 30 male Sprague-Dawley rats divided into five groups (A–E). Triton X-100 was administered to induce hypercholesterolemia. After hypercholesterolemia induction, oral treatment of Atorvastatin and crude ethanol extract was given daily to the treatment groups for 14 days. The total cholesterol, triglycerides, HDL and LDL were determined before induction, after induction, after first week of treatment and after second week of treatment. Results:Acute oral toxicity showed the crude extract is nontoxic up to 2000 mg/kg. The lipid-lowering assay indicated reduction of serum cholesterol (87.21 ± 5.10 mg/dL), triglycerides (58.09 ± 4.10 mg/dL) and LDL (27.82 ± 4.11 mg/dL) for 200 mg/kw extract. Reduction in serum cholesterol (74.72 ± 3.64 mg/dL), triglycerides (52.79 ± 2.98 mg/dL) and LDL (12.06 ± 5.51 mg/dL) were observed for 400 mg/kg group. The result is comparable to Atorvastatin, which showed serum cholesterol (80.90 ± 9.72 mg/dL), triglycerides (55.94 ± 7.19 mg/dL) and LDL (22.09 ± 7.60 mg/dL) reduction. Discussion and conclusion:The crude extract ofC. anisum-olensproved to be useful in lowering of cholesterol. [ABSTRACT FROM AUTHOR]

Introduction: Significant advancements in the treatment of hypercholesterolemia have recently been achieved. However, a considerable level of residual cardiovascular risk still affects patients' outcomes. Atherogenic dyslipidemia is one of the major constituents of residual risk. Fibrates, PPAR alpha agonists, which modify lipid profile and have numerous pleiotropic effects, seem to be drugs of choice in patients with atherogenic dyslipidemia. These drugs are effective both in monotherapy and combined therapy with statins. Areas covered: A review of clinical trials and experimental studies on fibrates and their use in the treatment of lipid disorders has been performed. Expert commentary: Fibrates are an effective and safe group of drugs to treat patients with atherogenic dyslipidemia. In this particular population of patients, they improve cardiovascular outcomes. Benefits of fibrate treatment extend beyond the impact of lipid profile. Significant improvements in carbohydrate metabolism, adipokines levels, thrombosis and inflammation were also noted. [ABSTRACT FROM AUTHOR]

Objective To explore the hypoglycaemic and hypocholesterolemic potential of conventional and supercritical extracts of black cumin. Methods Purposely, rat modelling was carried out for 2 months by designing three studies i.e. study I (normal rats), study II (hyperglycaemic rats) and study III (hypercholesterolemic rats). Each study was further divided into three groups based on diet i.e. control, functional diet (contained extract of black cumin prepared by using conventional solvent) and nutraceutical diet (contained extract of black cumin prepared by supercritical fluid extraction system). Results During whole trial, an abating trend was observed in the level of serum cholesterol with maximum reduction (12.8%) in nutraceutical group of study III. Low density lipoprotein and triglyceride level was also lowered maximum in study III as 17.1% and 11.6%, respectively. Whereas, highest decline in glucose level was in nutraceutical group of study II as 11.2%. Conclusions Inclusion of black cumin extracts in diet significantly lowers the occurrence of hyperglycaemia and hypercholesterolaemia. Furthermore, hypoglycaemic and hypocholesterolemic potential of nutraceutical diet is more prominent as compared to functional diet. [ABSTRACT FROM AUTHOR]

Background: Phytosterols and red yeast rice are largely studied cholesterol-lowering nutraceuticals, respectively inhibiting the bowel absorption and liver synthesis of cholesterol. Our aim was to test the effect on lipid profile of phytosterols, red yeast rice and their association. Methods: We performed a three parallel arms, double blind, clinical trial randomizing 90 moderately hypercholesterolemic subjects to treatment with phytosterols 800 mg (group 1), red yeast rice standardized to contain 5 mg monacolins from Monascus purpureus (group 2), or both combined nutraceuticals (group 3). Results: After 8 weeks of treatment, in group 1 no significant variation of lipid parameters has been detected. In group 2 a significant reduction (p < 0.001) of LDL-Cholesterol (-20.5% vs. baseline) and Apolipoprotein B (-14.4% vs. baseline) as it occurred in group 3 (LDL-Cholesterol vs. baseline: -27.0%, Apolipoprotein B vs. baseline: -19.0%) (P < 0.001). LDL-Cholesterol and Apolipoprotein B changes were significantly different comparing group 2 with group 1 (P < 0.05), and group 3 with group 1 (P < 0.05). LDL-Cholesterol change was also significantly higher in group 3 than in group 2 (P < 0.05). Conclusion: The association of phytosterol and red yeast rice seems to have additive cholesterol lowering effect, reaching a clinically significant LDL-Cholesterol reduction in mildly hypercholesterolemic patients. Trial registration: ClinicalTrial.gov ID: NCT02603276, Registered 27/08/2015. [ABSTRACT FROM AUTHOR]

Background: Hypercholesterolemia is one of the main risk factors for cardiovascular disease. The first line treatment for hypercholesterolemia is statin therapy. When the expected low-density lipoprotein cholesterol (LDL-C) concentration is not achieved, the pharmacotherapy may be extended by combining the statin with the cholesterol absorption inhibitor ezetimibe.Methods/design: The study is designed as a randomized, open-label, single-center, crossover study evaluating the effectiveness of combined therapy with rosuvastatin and ezetimibe for hypercholesterolemia. The study is planned to include 200 patients with hypercholesterolemia ineffectively treated with statins for at least 6 weeks. After enrollment participants are randomized into one of two arms receiving rosuvastatin and ezetimibe. In the first arm the study drug is administered in the morning (8:00 am) for 6 weeks and then in the evening for the next 6 weeks; in the second arm the study drug is administered at first in the evening (8:00 pm) for the first 6 weeks and then in the morning for the following 6 weeks. In order to minimize non-adherence to the treatment, all patients will receive the study drug free of charge. The primary outcome of the study is change in LDL-C at 6 and 12 weeks of the treatment, depending on the time of day of study drug administration. The secondary endpoints include change in total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoproteins ApoB and Apo AI, non-HDL cholesterol, small, dense (sd)-LDL cholesterol, lipoprotein(a), glucose, glycated hemoglobin, high-sensitivity C-reactive protein, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, and creatine kinase at 6 and 12 weeks of the study drug treatment, as well as assessment of plasma fluorescence using stationary and time-resolved fluorescence spectroscopy at baseline and at 6 and 12 weeks of the therapy.Discussion: The RosEze trial is expected to demonstrate whether there is a significant difference in the effectiveness of the lipid-lowering therapy in reducing the concentration of cholesterol when the medications are taken in the morning compared with the evening time of day.Trial Registration: ClinicalTrials.gov, NCT02772640 . Registered on 28 March 2016. [ABSTRACT FROM AUTHOR]

Growing attention is now being given to the possible preventive/alternative ways to avoid illness onset. Changes in lifestyle and food habits are taking over from the conventional pharmaceutical-based approach, especially for chronic pathologies. Nutraceuticals have been proposed as key tools for the prevention and cure of some pathological conditions. This is leading research to develop new formulations based on these pharma-foods addressed in a specific way to prevent and cure health issues, which, in turn, will have an effect on therapy-related costs sustained by any National Health Organization. According to existing regulations, nutraceuticals cannot be categorized as either food or drugs but, by definition, often inhabit a grey area in between the two, being assimilated into food supplements, notwithstanding the beneficial properties that they can provide for some pathological conditions. A nutraceuticals-based approach for health management, in particular for some pathological conditions, has resulted in a worldwide growing 'nutraceutical' revolution. An outstanding example is the approach to the 'metabolic syndrome', which includes overweight, obesity and cardiovascular-related diseases, causing a sort of cascade of chronic health conditions, which is becoming a norm in modern life. Hypercholesterolaemia is one of these. It represents an example of a pathology that can be linked to both a poor lifestyle and dietary habits. The nutraceutical approach to hypercholesterolaemia is described in the present review as a possible alternative to the conventional drug-based therapy.Linked Articles: This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. [ABSTRACT FROM AUTHOR]

As part of its single technology appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of evolocumab (Amgen) to submit evidence on the clinical and cost effectiveness of evolocumab. The appraisal assessed evolocumab as monotherapy or in combination with a statin with or without ezetimibe, or in combination with ezetimibe (without statin therapy), in adult patients with primary hypercholesterolaemia (which includes mixed dyslipidaemia), for whom statins do not provide optimal control of their low-density lipoprotein cholesterol (LDL-C) levels and/or for whom statins are contraindicated or not tolerated. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based on the company's submission to NICE. The evidence was derived mainly from four randomised controlled trials comparing evolocumab with either ezetimibe or placebo in adults with primary familial or non-familial hypercholesterolaemia, who were either able to take statins or who were statin intolerant. The clinical-effectiveness review found that evolocumab is efficacious at lowering LDL-C but that there was uncertainty regarding its impact on cardiovascular disease (CVD) outcomes. In response to the ERG's critique of the submitted health economic model, the company submitted an amended model, which also included a patient access scheme (PAS). Based on this, the deterministic incremental cost-effectiveness ratios (ICERs) for evolocumab against ezetimibe were above £74,000 and £45,000 per quality-adjusted life-year (QALY) gained within the non-familial primary and secondary prevention populations, respectively, whilst the ICER within the heterozygous familial hypercholesterolaemia (HeFH) population was approximately £23,000 per QALY gained. The final determination was that evolocumab would be a clinically and cost-effective use of UK NHS resource in certain patient subgroups. [ABSTRACT FROM AUTHOR]

Statins are efficient cholesterol-lowering medicines utilized worldwide. However, 10% of patients suffer from adverse effects specially related to skeletal muscle function. Pro- or anti-oxidant effects of statins have been reported. Here we hypothesized that statins induce muscle mitochondrial oxidative stress leading to mitochondrial permeability transition (MPT) which may explain statin muscle toxicity. Thus, our aims were to investigate the effects of statin chronic treatment on muscle mitochondrial respiration rates, MPT and redox state indicators in the context of hypercholesterolemia. For this purpose, we studied muscle biopsies of the hypercholesterolemic LDL receptor knockout mice (LDLr-/-) treated with pravastatin during 3 months. Plantaris, but not soleus muscle of treated mice showed significant inhibition of respiration rates induced by ADP (-14%), oligomycin (-20%) or FCCP (-40%). Inhibitions of respiratory rates were sensitive to EGTA (Ca2+ chelator), cyclosporin A (MPT inhibitor), ruthenium red (inhibitor of mitochondria Ca2+ uptake) and coenzyme Q10 (antioxidant), indicating that pravastatin treatment favors Ca2+ induced MPT. Diet supplementation with creatine (antioxidant) also protected treated mice against pravastatin sensitization to Ca2+ induced MPT. Among several antioxidant enzymes analyzed, only catalase activity was increased by 30% in plantaris muscle of pravastatin treated mice. Oxidized lipids, but not proteins biomarkers were identified in treated LDLr-/- plantaris muscle. Taken together, the present results suggest that chronic pravastatin administration to a model of familial hypercholesterolemia promotes mitochondrial dysfunctions in plantaris muscle that can be counteracted by antioxidants administered either in vitro (CoQ10) or in vivo (creatine). Therefore, we propose that inhibition of muscle mitochondrial respiration by pravastatin leads to an oxidative stress that, in the presence of calcium, opens the permeability transition pore. This mitochondrial oxidative stress caused by statin treatment also signals for cellular antioxidant system responses such as catalase upregulation. These results suggest that the detrimental effects of statins on muscle mitochondria could be prevented by co-administration of a safe antioxidant such as creatine or CoQ10. [ABSTRACT FROM AUTHOR]

Objective : The aim of this study was to explore co-crystallization to enhance the solubility of simvastatin (SV) as a drug of choice for hypercholesterolemia using saccharin (Sacch) as co-former. Methods: Molecular modeling of sacch against SV has been conducted by in silico using auto dock 4.2. Preparation of co-crystal has carried out by solvent evaporation (SE) using an equimolar ratio of SV and Sacch. Co-crystal of SV-Sacch was evaluated by the saturated solubility test and intrinsic dissolution test. Afterward, the co-crystal was characterized by infrared spectrophotometry (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), binary phase diagram and stability studies in storage condition 400C and relative humidity (RH) 75% for three months. Results: In silico studies showed that the interaction of SV against sacch has hydrogen bonding as molecular synthon. Evaluations of solubility and intrinsic dissolution have shown an increased in rate properties significantly of co-crystal as compared to pure SV and its physical mixer (PM). Characterizations of a co-crystal SV: sacch (1: 1) has indicated the formation of different new solid crystal phase as compared to SV, sacch, and its PM, and stable for 400C and RH 75% in 3 months. Conclusion: Co-crystallization has been used to increase the solubility and dissolution rate of simvastatin and all characterization has shown the formation of co-crystal SV: sacch (1: 1). [ABSTRACT FROM AUTHOR]

OBJECTIVE Cholestyramine ( CHO), as a bile acid sequestering exchange resin, has been widely used to treat hypercholesterolemia. The aim of this study was to explore how CHO regulated serum cholesterol amounts and bile acid levels in animal models. METHODS New Zealand White rabbits were randomly assigned to the control (given distilled water) and CHO-treated (given CHO solution 1 g/kg per day for 2 weeks) groups. To assess bile acid pool size, bile fistulas were constructed in five rabbits in each group. Serum cholesterol levels and biliary and fecal bile outputs were determined. Liver cholesterol 7α-hydroxylase ( CYP7A1), small heterodimer partner ( SHP), bile salt export pump ( BSEP), ileal bile acid-binding protein ( IBABP) and LDL receptor ( LDL-R) m RNA expressions were assessed by real-time polymerase chain reaction. CYP7A1 activity was also determined. RESULTS CHO treatment decreased serum cholesterol levels by 12.1%. Although CHO did not change the bile acid pool size and biliary bile acid output, it significantly increased fecal bile acid output. Interestingly, CHO also significantly increased the expression and activity of CYP7A1, as well as IBABP and LDL-R m RNA expressions, but decreased hepatic SHP and BSEP gene expressions. CONCLUSION CHO markedly alters bile acid and cholesterol amounts in rabbit intestinal and liver tissues, downregulating genes responsible for cholesterol homeostasis. [ABSTRACT FROM AUTHOR]

Background and aims High plasma LDL-cholesterol (LDL-C) and platelet responses have major pathogenic roles in atherothrombosis. Thus, statins and anti-platelet drugs constitute mainstays in cardiovascular prevention/treatment. However, the role of platelet tissue factor-dependent procoagulant activity (TF-PCA) has remained unexplored in hypercholesterolemia. We aimed to study platelet TF-PCA and its relationship with membrane cholesterol in vitro and in 45 hypercholesterolemic patients (HC-patients) (LDL-C >3.37 mmol/L, 130 mg/dL) and 37 control subjects (LDL-C <3.37 mmol/L). The effect of 1-month administration of 80 mg/day atorvastatin (n = 21) and 20 mg/day rosuvastatin (n = 24) was compared. Methods Platelet TF-PCA was induced by GPIbα activation with VWF-ristocetin. Results Cholesterol-enriched platelets in vitro had augmented aggregation/secretion and platelet FXa generation (1.65-fold increase, p = 0.01). HC-patients had 1.5-, 2.3- and 2.5-fold increases in platelet cholesterol, TF protein and activity, respectively; their platelets had neither hyper-aggregation nor endogenous thrombin generation (ETP). Rosuvastatin, but not atorvastatin, normalized platelet cholesterol, TF protein and FXa generation. It also increased slightly the plasma HDL-C levels, which correlated negatively with TF-PCA. Conclusions Platelets from HC-patients were not hyper-responsive to low concentrations of classical agonists and had normal PRP-ETP, before and after statin administration. However, washed platelets from HC-patients had increased membrane cholesterol, TF protein and TF-PCA. The platelet TF-dependent PCA was specifically expressed after VWF-induced GPIbα activation. Rosuvastatin, but not atorvastatin treatment, normalized the membrane cholesterol, TF protein and TF-PCA in HC-patients, possibly unveiling a new pleiotropic effect of rosuvastatin. Modulation of platelet TF-PCA may become a novel target to prevent/treat atherothrombosis without increasing bleeding risks. [ABSTRACT FROM AUTHOR]

The article presents a recommendation statement from the U.S. Preventive Services Task Force on screening for lipid disorders in children and adolescents. Topics discussed include the benefits of early detection and treatment of the disease, screening tests, and dyslipidemia treatment. The use of statins in children with familial hypercholesterolemia is also discussed.

ABSTRACT Hypercholesterolemia is a common condition and is a risk factor for tendon rupture, specifically in the supraspinatus tendon. In the clinic, statins are commonly prescribed to lower cholesterol, but little information is available examining the effect of statin treatment on the musculoskeletal system. Therefore, the objective of this study was to determine the biomechanical and histological effects of statin treatment in a diet-induced hypercholesterolemia model. We hypothesized that hypercholesterolemic rats treated with statins would have improved tendon biomechanical and histological properties compared to hypercholesterolemic rats not receiving daily statin treatment. Thirty adult male Sprague-Dawley rats ate either high-cholesterol (HC) diet ( n = 20) or normal chow (CTL, n = 10). After 6 months, a subset of HC rats began daily oral simvastatin dosing (HC+S) at 20 mg/kg. All rats were sacrificed after a total of 9 months (3 months of statin treatment) and evaluated for histology and mechanics. For mechanics, at the insertion region, HC+S group had increased tendon cross-sectional area decreased and modulus. No differences were noted in mechanical properties at the midsubstance. For histology, no differences were noted in the insertion region. In the midsubstance region, HC+S group had more spindle shaped cells. Our results suggest that 3 months of simvastatin treatment in a diet-induced hypercholesterolemia rat model alters some tendon mechanical and histological properties, although a strong conclusion in support of improved parameters cannot be drawn. Therefore, we conclude that simvastatin treatment does not negatively affect tendon properties. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2009-2015, 2016. [ABSTRACT FROM AUTHOR]

Background: Child-parent screening for familial hypercholesterolemia has been proposed to identify persons at high risk for inherited premature cardiovascular disease. We assessed the efficacy and feasibility of such screening in primary care practice.Methods: We obtained capillary blood samples to measure cholesterol levels and to test for familial hypercholesterolemia mutations in 10,095 children 1 to 2 years of age during routine immunization visits. Children were considered to have positive screening results for familial hypercholesterolemia if their cholesterol level was elevated and they had either a familial hypercholesterolemia mutation or a repeat elevated cholesterol level 3 months later. A parent of each child with a positive screening result for familial hypercholesterolemia was considered to have a positive screening result for familial hypercholesterolemia if he or she had the same mutation as the child or, if no mutations were identified, had the higher cholesterol level of the two parents.Results: The use of a prespecified cholesterol cutoff value of 1.53 multiples of the median (MoM, corresponding to a percentile of 99.2) identified 28 children who had positive screening results for familial hypercholesterolemia (0.3% of the 10,095 children; 95% confidence interval [CI], 0.2 to 0.4), including 20 with a familial hypercholesterolemia mutation and 8 with a repeat cholesterol level of at least 1.53 MoM. A total of 17 children who had a cholesterol level of less than 1.53 MoM also had a familial hypercholesterolemia mutation. The overall mutation prevalence was 1 in 273 children (37 in 10,095; 95% CI, 1 in 198 to 1 in 388). The use of an initial cholesterol cutoff value of 1.35 MoM (95th percentile) plus a mutation, or two cholesterol values of at least 1.50 MoM (99th percentile), identified 40 children who had positive screening results for familial hypercholesterolemia (0.4% of the 10,095 children, including 32 children who had a familial hypercholesterolemia mutation and 8 who did not have the mutation) and 40 parents who had positive screening results for familial hypercholesterolemia.Conclusions: Child-parent screening was feasible in primary care practices at routine child immunization visits. For every 1000 children screened, 8 persons (4 children and 4 parents) were identified as having positive screening results for familial hypercholesterolemia and were consequently at high risk for cardiovascular disease. (Funded by the Medical Research Council.). [ABSTRACT FROM AUTHOR]

Background: To investigate the relationship between oxysterols and mild cognitive impairment (MCI) in a matched case–control study. Methods: The plasma levels of four oxysterols, 27–hydroxycholesterol (27–OHC), 24S–hydroxycholesterol (24S–OHC), 7α–hydroxycholesterol (7α–OHC) and 7β–hydroxycholesterol (7β–OHC), were analyzed by High Performance Liquid Chromatography–Mass Spectrometry (HPLC–MS) and compared between 70 MCI patients and 140 matched controls with normal cognition. The odds ratio (OR) was calculated using logistic analyses to assess the association between oxysterols and MCI. Results: Compared with controls with normal cognition, plasma level of 27–OHC was significantly higher in MCI patients. Logistic analyses suggested high plasma level of 27–OHC was significantly associated with MCI even after multivariate adjustment (OR = 2.86, 95 % CI: 1.52 ∼ 5.37). Conclusions: Our findings suggested that the increased plasma level of 27-OHC was associated with MCI, suggesting high plasma levels of 27-OHC may pay an important role in the development of MCI. [ABSTRACT FROM AUTHOR]

The health benefits of raw garlic intake has been extensively studied, but little is known about the biological effects of aged garlic consumption. A randomized, placebo-controlled, parallel-arm, double-blinded trial involving 41 hypercholesterolemic individuals was conducted to simultaneously examine and compare the blood lipid lowering and antioxidant effects after acute and extended exposures to aged and raw garlic supplements (1080 mg daily). Aged and raw garlic did not affect blood lipid concentrations in these hypercholesterolemic participants after acute and 13-week supplementation. The plasma and urinary F2-isoprostanes concentrations were significantly decreased after 13 weeks of aged garlic treatment. Aged garlic supplementation over 13 weeks also significantly decreased serum lipid hydroperoxide concentration and myeloperoxidase activity. Raw garlic treatments did not affect the F2-isoprostanes concentrations in blood plasma and urine, and lipid hydroperoxides in blood sera. Acute effects on the measured parameters were absent for both garlic treatments. In separate in vitro experiments, aqueous methanolic extract of aged garlic inhibited F2-isoprostanes formation and myeloperoxidase activity in freshly isolated human neutrophils to a greater extent than the raw garlic extract and S-allylcysteine at equivalent dosing concentrations. The aged garlic preparation was found to contain significantly higher total phenolic and Sallylcysteine contents than the raw garlic precursor. Our data showed that supplementation with aged garlic, not its raw garlic precursor, reduced oxidative stress and alleviated lipid peroxidation, possibly via the inhibition of myeloperoxidase. The differential antioxidant actions of the aged and raw garlic may be related to their different total phenolic contents and, to a lesser extent, their S-allylcysteine contents. [ABSTRACT FROM AUTHOR]

This review reports the current situation with respect to therapeutic options (lifestyle and drugs) reducing the concentrations of atherogenic low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]). Three lipoprotein apheresis (LA) principles have been realized: precipitation, filtration, and adsorption. Available LA methods are herein described in detail -- major components, pumps, extracorporeal volume, treated volume, and anticoagulation. General features of all LA methods as well as pleotropic effects are elaborated. Indications for LA therapy are quoted: homozygous familial hypercholesterolemia (HCH), severe HCH, and isolated elevation of Lp(a) and progress of atherosclerotic disease. A major focus is on the evidence of the effect of LA on cardiovascular outcome data, and the most important publications are cited in this context. The best studies have been performed in patients with elevated Lp(a) in whom cardiovascular events were reduced by more than 80%. Major adverse effects and contraindications are listed. The impact of an LA therapy on patient quality of life and the requirements they have to fulfill are also highlighted. Finally, the future role of LA in treating high-risk patients with high LDL-C and/or high Lp(a) is discussed. It is probable that the significance of LA for treating patients with elevated LDL-C will decrease (with the exception of homozygous familial HCH) due to the application of PCSK9 inhibitors. The antisense oligonucleotide against apolipoprotein(a) could replace LA in patients with high Lp(a), provided positive outcome data are generated. [ABSTRACT FROM AUTHOR]

Background Ezetimibe added to statin therapy further reduces LDL-C and clinical atherosclerotic cardiovascular disease compared to statin alone. However, the number of effective and safe oral agents for patients not at LDL-C goal is limited. In prior clinical trials, gemcabene reduced LDL-C and was generally well-tolerated in nearly 900 patients treated for up to 12 weeks. Objective To evaluate the LDL-C lowering and safety of gemcabene as add-on to stable statin therapy in hypercholesterolemic patients. Methods This was an 8-week, double-blind, placebo-controlled, randomized, phase 2 study in men and postmenopausal women ≥18 and ≤65 years of age with LDL-C ≥130 mg/dL (3.4 mmol/L) while on low-intensity to high-intensity stable statin (the majority on moderate intensity) therapy. Sixty-six patients were randomized 1:1:1 to gemcabene 300 mg, 900 mg, or placebo QD. Results Gemcabene 300 mg and 900 mg produced a mean percent change in LDL-C of −23.4 ± 4.7% ( P = .005) and −27.7 ± 4.3% ( P < .001), respectively, vs −6.2 ± 4.3% for placebo. The median percent change in CRP was −26.1% ( P = .196) and −53.9% ( P < .001) for gemcabene 300 mg and 900 mg, respectively, vs −11.1% for placebo. Gemcabene 300 mg and 900 mg were well-tolerated with no significant difference in AEs compared to placebo. Conclusions Gemcabene as add-on to stable statin therapy demonstrated additional dose-dependent and statistically significant reductions in LDL-C of >20% and CRP >40% compared to placebo. The results support gemcabene-continued development for patients requiring LDL-C lowering beyond that provided by background statin therapy. [ABSTRACT FROM AUTHOR]

Simvastatin (SIM) and lovastatin (LOV) are two important active pharmaceutical ingredients from statin class, prescribed in the treatment of hypercholesterolemia. Our study presents the results obtained by our research group regarding the decomposition of SIM and LOV in oxidative atmosphere, by employing three isoconversional methods, namely Friedman, Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa. The results obtained by Friedman method suggested a multistep degradation, while the ones obtained by Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa suggested a single-step degradation. In order to validate the results, we used the NPK method, which allowed a concrete separation and nature of processes that contributed to the degradation of both statins. NPK method showed that both SIM and LOV are degraded by contribution of two distinctive chemical processes, and the mean values of activation energies are also reported. [ABSTRACT FROM AUTHOR]

Lipoprotein apheresis is used to treat patients with familial hypercholesterolemia (FH). The aim of the present study is to clarify the lipoprotein apheresis procedure performed by cascade filtration (CF) or double filtration plasmapheresis (DFPP) on pediatric patients in terms of side effects, laboratory results and cardiovascular follow-up. Data of ten pediatric patients were analyzed retrospectively. The average age of the patients was 12.1 ± 3.4 years. Percentage of long term reduction of low density lipoprotein cholesterol was 62.35 ± 7.19% (n = 3) for CF and 63.66 ± 6.63% (n = 3) for CF plus DFPP, 64.79 ± 8.29% (n = 7) for DFPP. Cardiovascular disease was not detected in thirty percent of the patients. Lesions remained stable in fifty percent of patients with heart valve lesions. Valvular lesions worsened in twenty percent of patients. Lipoprotein apheresis can be used effectively and successfully in pediatric patients as well as adults for homozygous FH. [ABSTRACT FROM AUTHOR]

Statins are used daily by a large and increasing number of individuals worldwide. They were initially designed as 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) inhibitors to treat patients with hypercholesterolemia. Recent studies on HCV chronically infected individuals have suggested that their use in vivo in combination with PEG-IFN and ribavirin favor the sustained viral response (SVR). Herein, we describe the effects of a set of statins on HCV entry and on HCV key entry factors in vitro . Our results suggest that all tested statins exert a proviral effect through the upregulation of LDLR. Interestingly, at higher concentration, we also provide evidence of a yet unknown competing antiviral effect of statins (except for pravastatin) through the downregulation of CLDN-1. Importantly, this work enlightens the blunt proviral effect of pravastatin at the entry step of HCV in vitro . [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome is an increasingly prevalent problem, not only in industrialized developed countries, but in developing countries as well. The modern healthcare to reduce the dysfunction of metabolic syndrome is burdened with great problems of unsafe medicines and certain degree of side effects. Medicinal plants and derived component products are becoming increasingly popular in modern society as natural alternatives to synthetic multiple drugs for the treatment of hypercholesterolemia and hypertriglyceridemia. The present research work was carried out to evaluate the zedoary (Curcuma zedoaria Roscoe.) herbal tea (ZHT) for antihypercholestrolemic and antilipidemic perspectives in discerning consumers. Methods: Zedoary rhizome dried powder (ZRDP) after proximate composition analysis was used to prepared ZHT samples as T1 (500 mg ZRDP), T2 (1 g ZRDP) and T3 (1.5 g ZRDP) in 200 mL boiling water for 5 minutes, respectively. ZHT samples were characterized for total phenolic compounds (TPC), DPPH inhibition, total flavonoids, color tonality (L*, a* and b* value), pH, acidity, total soluble solids (TSS) and sensory acceptance. Thirty mild– hypercholestrolemic male human volunteers were randomly allocated to three groups (G1, G2 and G3) and each group consisting of 1o mild–hypercholestrolemic male human subjects. The volunteers were assigned ZHT samples for consecutive two months. The blood drawn for day 0, day 30 and day 60 after an overnight 12 h fast was analyzed for serum parameters such as total cholesterol (TC), high–density lipoprotein cholesterol (HDL–cholesterol), low–density lipoprotein cholesterol (LDL–cholesterol) and triglycerides (TG) concentration. Results: The ZRDP possessed abundantly the crude protein (13.5 ± 0.68 %), total dietary fiber (21.86 ± 0.71 %), acid detergent fiber (13.22 ± 0.44 %), neutral detergent fiber (18.68 ± 0.53 %) and mineral contents. Highest TPC, DPPH inhibition and total flavonoids values were observed 9.74 ± 0.64 (mg GAE/g DW), 47.28 ± 1.62 (%) and 17.12 ± 0.75 (QE mg/g), respectively in T3. L* value was significantly (p ≤ 0.05) low for T3 samples. In contrast, a* value and b* value was significantly (p ≤ 0.05) higher for T3 when compared with T1 and T2. T3 samples showed lower pH (5.13 ± 0.13) and higher acidity (0.25 ± 0.08) values than T1 (5.64 ± 0.25, 0.17 ± 0.05) and T2 (5.42 ± 0.21, 0.21 ± 0.06), respectively. Similarly, an increasing trend in TSS contents was observed. Sensory scores assigned to color, flavor, aroma and overall acceptability attributes varied in a quite narrow range for all ZHT samples. The lowest evaluation scores were recorded for T3 samples. The G3 showed the more reduction in body weight and BMI during efficacy study as compared to G1 and G2. The decrease in serum TC for G1, G2 and G3 on day 60 was observed 9 %, 14 % and 17 %, respectively when compared with reference value at day 0. The consumption of T3 resulted in significant increase (6.8 %) of HDL-cholesterol after two months. A trend in decrease of serum LDL–cholesterol (5.6 %) and TG (12.5 %) was also observed after consumption of T3 at day 60. Conclusions: The results of the present study conclude that the strong phenolic contents and radical scavenging activity of zedoary rhizome have protective role against hypercholesterolemic and lipidemic conditions. [ABSTRACT FROM AUTHOR]

Objective. To investigate vascular endothelial function (VEF) responses to a single low-density lipoprotein (LDL) apheresis session in hypercholesterolemic patients undergoing chronic treatment. Methods. We measured brachial artery flow-mediated dilation (FMD), plasma lipids, vitamin E (α- and γ-tocopherol), markers of oxidative/nitrative stress (malondialdehyde (MDA) and nitro-γ-tocopherol (NGT)), and regulators of NO metabolism (arginine (ARG) and asymmetric dimethylarginine (ADMA)) prior to (Pre) and immediately following (Post) LDL apheresis and at 1, 3, 7, and 14 d Post in 5 hypercholesterolemic patients (52 ± 11 y). Results. Relative to Pre, total cholesterol (7.8±1.5 mmol/L) and LDL-cholesterol (6.2±1.2 mmol/L) were 61% and 70% lower (P<0.01), respectively, at Post and returned to Pre levels at 14 d. Brachial FMD responses (6.9 ± 3.6%) and plasma MDA, ARG, and ADMA concentrations were unaffected by LDL apheresis. Plasma α-tocopherol, γ-tocopherol, and NGT concentrations were 52–69% lower at Post (P<0.01), and α-tocopherol remained 36% lower at 1 d whereas NGT remained 41% lower at d 3. Conclusions. Acute cholesterol reduction by LDL apheresis does not alter VEF, oxidative stress, or NO homeostasis in patients treated chronically for hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Simvastatin is one of the most frequently prescribed statins because of its efficacy in the treatment of hypercholesterolemia, reducing cardiovascular risk and related mortality. Determination of its side effects on different tissues is mandatory to improve safe use of this drug. In the present study, the effects of simvastatin on molecular composition and structure of healthy rat livers were investigated by Fourier transform infrared and Raman imaging. Simvastatin-treated groups received 50 mg/kg/day simvastatin for 30 days. The ratio of the area and/or intensity of the bands assigned to lipids, proteins, and nucleic acids were calculated to get information about the drug-induced changes in tissues. Loss of unsaturation, accumulation of end products of lipid peroxidation, and alterations in lipid-to-protein ratio were observed in the treated group. Protein secondary structure studies revealed significant decrease in a-helix and increase in random coil, while native ß-sheet decreases and aggregated ß-sheet increases in treated group implying simvastatin-induced protein denaturation. Moreover, groups were successfully discriminated using principal component analysis. Consequently, highdose simvastatin treatment induces hepatic lipid peroxidation and changes in molecular content and protein secondary structure, implying the risk of liver disorders in drug therapy. [ABSTRACT FROM AUTHOR]

Glucans are present in fungi, plants, algae, and bacteria. β-Glucan, one of the major cell wall components of Saccharomyces cerevisiae, has been found to enhance immune functions. Glucans are glucose polymers with an α- or β-type glycosidic chain. The role of (1→3)-β-D-glucan is in the maintenance of yeast cell wall shape and rigidity. Studies reveal that soluble glucans can lower total cholesterol and LDL levels in patients with hypercholesterolemia. The important benefit of β-glucan is to improve the immune system and to decrease cholesterol levels in the blood. Several studies have reported the benefits of β-glucan as: antiseptic, antioxidant, anti-aging, immune system activators, protection against radiation, anti-inflammatory, anti-diabetic, anti-cholesterol etc. In this research S. cerevisiae was cultured in yeast extract-peptone-glucose (YPG) broth medium to produce beta-glucan. Cells were harvested at the stationary phase, washed, and disrupted by means of sonication method. The obtained cell walls were used to prepare alkali-soluble β-glucan (glucan-S1). In this regard, 2% sodium hydroxide (NaOH) and 3% acetic acid were used in alkaline-acid extraction, respectively. Potential use of beta-glucan extract as an anticholesterol agent was tested using Sprague dawley strain rats. The experiments were divided into eight groups with four replicates: Group I (normal control), group II (fed with cholesterol without beta-glucan), group III (fed with cholesterol + atorvastatin), group IV (fed with cholesterol + β-glucan standard), group V-VIII (fed of cholesterol + β-glucan of S. cerevisiae with each dose of 10, 20, 30, and 40 mg / BW. Rats were fed with cholesterol for 14 days, except for group I. Analysis of blood was carried out to determine total cholesterol, triglycerides, and malondialdehyde. The results showed that beta-glucan crude obtained from S. cerevisiae cultures was 6.890g.L-1. Beta-glucan extract of S. cerevisiae can reduce total cholesterol approaching normal values at doses of 10 mg of 32.79 % (blood plasma) and 33.71 % (in the liver). The extract was capable of reducing triglyceride levels in a dose of 10 mg of beta-glucan 64.43 % (blood plasma) and at a dose 30 mg of beta-glucan 19.45 % (liver). Beta-glucan treatment at a dose of 40 mg can reduce MDA levels of 45.22 % (blood plasma) and 42.64 % (liver). [ABSTRACT FROM AUTHOR]

Atherosclerosis and hypertension can potentially progess into dangerous cardiovascular diseases such as myocardial infarction and stroke. Statins are widely used to lower cholesterol levels while antihypertensive agents such as captopril are widely prescribed to treat high blood pressure. Curcumin, a phenolic compound isolated from Curcuma domestics, has been proven effective for a broad spectrum of diseases, including hypertension and hypercholesterolemia. Therefore, curcumin is quite promising as an alternative therapeutic compound. Our previous studies have proven a significant increase in physical properties, bioavailability, and stability of curcumin when encapsulated in a nanoemulsion. The purpose of this study was to assess the ability of the nanoemulsion in enhancing curcumin activity as a antihypertensive and antihypercholesterolemic agent. The formulation and preparation method of the curcumin nanoemulsion have been developed in our previous study. Physical characterization was performed, including measurement of droplet size, polidispersity index, zeta potential, entrapment efficiency, and loading capacity. Antihypertensive activity of curcumin was evaluated by determining Angiotensin Converting Enzyme (ACE) inhibition in vitro. A substrate for ACE, hippuryl-L-histidyl-L-leucine was allowed to react with ACE, resulting in hippuric acid formation as the product. The degree of ACE inhibition by curcumin was represented by the amount of hippuric acid formed. Antihypercholesterolemic activity of curcumin was studied using the HMG-CoA reductase assay equipped with a 96-well UV plate. This assay was based on the spectrophotometric measurement of the decrease in absorbance which represents the oxidation of NADPH by the catalytic subunit of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) in the presence of the substrate HMG-CoA. Curcumin is known to have no significant difference in inhibiting ACE compared to Captopril, but when it was incorporated in the self-nanoemulsifying carrier, it slightly increased the inhibitory effect on ACE. In contrast, the effect of curcumin in reducing cholesterol based on the HMGR assay was more pronounced. Curcumin encapsulated in a nanoemulsion showed significant cholesterol-lowering activity compared to a standard drug, pravastatin. Therefore, we conclude that curcumin does not show ACE inhibitory effects, but has potential use as an alternative therapeutic compound to treat hyperlipidaemia. Curcumin encapsulated in a nanoemulsion increased not only the HMGR inhibition, but also ACE inhibition of curcumin. These effects are suggested to be the result of improved solubility in the nanoemulsion system. [ABSTRACT FROM AUTHOR]

Simvastatin is a drug which is widely used in the treatment of hypercholesterolemia, but it is practically insoluble in water and is not well absorbed via gastrointestinal tract. Therefore, introducing effective methods to improve its dissolution rate that may result in increased bioavailability is very important. Particle size reduction is one of the physical methods which are used to improve the dissolution rate of drugs in aqueous media. Amongst the several methods which have been used for particle size reduction, the use of supercritical fluid technology has some special advantages. In this study, the simvastatin nanoparticles (47 nm), were formed using supercritical trifluoromethane and showed a significant improvement in terms of dissolution rate. The effects of extraction temperature and pressure and spray distance on particle size were analyzed. Characterization tests included X-ray diffraction (XRD), Fourier Transform Infrared Analysis (FTIR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), and Dynamic Light Scattering (DLS). Response surface methodology (RSM) was used for experimental design and process optimization and it was found that the best results can be obtained at 10 MPa, 50 °C, and 7 cm. [ABSTRACT FROM AUTHOR]

Background: Ethanolic extract of licorice root has been shown to reduce low-density lipoprotein (LDL) oxidation in atherosclerotic mice and in both hypercholesterolemic and normal lipidemic humans. Objective: This study examined the effect of licorice-root extract on carotid intima-media thickness (CIMT) in individuals with hypercholesterolemia. Design: Individuals with hypercholesterolemia (total cholesterol ≥6.18 mmol/L [240 mg/dL]) and without significant stenosis were randomly allocated to two groups: an experimental group that consumed 0.2 g/day of ethanolic extract of licorice root for 12 months, and a control group that received a placebo. Results: Of 110 eligible participants, 94 (41-80 years old) completed the study. A significant CIMT decrease from 0.92 ± 0.25 mm to 0.84 ± 0.21 mm was observed in the experimental group compared with an increase from 0.85 ± 0.17 mm to 0.88 ± 0.19 mm in the control group. Mean plasma total cholesterol levels and LDL cholesterol decreased, at the range baseline to 1 year, from 284 ± 32 mg/dl to 262 ± 25 mg/dl and from 183 ± 8.5 mg/dl to 174 ± 9.1 mg/dl, respectively, for the experimental group (p <0.001) and from 291 ± 35 to 289 ± 31 mg/dl and from 177.6 ± 10.7 to 179.3 ± 9.6 (p =0.08), respectively, for the control group. Mean high-density lipoprotein (HDL) did not change significantly in either group. In the experimental group, systolic blood pressure decreased from 138 ± 12 mmHg to 125 ± 13 mmHg after 1 year (p =0.01) and increased from 136 ± 15 mmHg to 137 ± 13 mmHg in the control group. Diastolic blood pressure decreased from 92 ± 9 mmHg to 84 ± 10 mmHg (p =0.01) in the experimental group and increased from 89 ± 11 mmHg to 90 ± 8 mmHg in the control group. Conclusion: Following 1 year of licorice consumption, mean CIMT, total cholesterol, LDL levels, and blood pressure were decreased. This suggests that licorice may attenuate the development of atherosclerosis and of related cardiovascular diseases. [ABSTRACT FROM AUTHOR]

This study evaluates in vitro hypocholesterolemic and antioxidant potential of Calotropis procera root extracts and its diterpenoid rich fraction. In vitro hypocholesterolemic activity was determined by measuring cholesterol concentration in the normal and hypercholesterolemic human red blood cells (hRBCs) after incubating with the test extracts (1, 10 and 100 µg/mL) for 24 h. The bioactivity guided fractionation of crude acetone root extract yielded a fraction with EC 50 63.03±1.10 µg/mL in relation to ascorbic acid standard (EC 50 39.95±1.25 µg/mL). In case of isolated erythrocytes of diseased donors, the purified fraction reduced the membrane cholesterol up to 1.62±0.22 µmole CH/mL (52%), whereas it was 1.01±0.75 µmole CH/mL (35%) in case of quercetin standard. The whole blood, when incubated with purified fraction and quercetin standard at 10 µg/mL for 24 h, it showed significant decrease in the cholesterol level of hRBCs of both, healthy ( P <0.001) as well as diseased ( P <0.05) donors. GC-HRMS analysis of the bioactive diterpenoid rich fraction revealed cyclic diterpenoids – Phenol, 2,4 bis (1,1-dimethylethyl) ester and 1,2 benzedenedicarboxylic acid, bis(2-methylpropyl) ester. In conclusion, C. procera root extract and its diterpenoid rich fraction exhibited potential hypocholesterolemic effect possibly by inhibiting membrane cholesterol synthesis and improving antioxidant levels in hypercholesterolemic hRBCs. [ABSTRACT FROM AUTHOR]

Pecan shell decoction has been used to treat diabetes and obesity-related diseases. In this study, the effects of a pecan shell aqueous extract (PSAE) were evaluated in diabetic and hypercholesterolemic Wistar rats, analyzing clinical signs and biochemical as well as genotoxic and mutagenic parameters, to assess its safe use and efficacy. Diabetes mellitus and hypercholesterolemia were induced with streptozotocin (STZ) and tyloxapol, respectively. Animals were orally administered PSAE (100 mg/kg body weight, b.w.) for 28 days. Biochemical analyses and genotoxicity were evaluated in blood samples and mutagenicity was evaluated in bone marrow. PSAE treatment decreased the blood glucose level and stabilized clinical signs of diabetes in diabetic rats. PSAE diminished the increase in total cholesterol and triglyceride levels in hypercholesterolemic rats. The urea levels were higher in diabetic rats than in treated ones; however, creatinine values were the same in all groups. Elevated transaminase levels were suggestive of liver injuries in diabetic rats, and were not altered by PSAE treatment. PSAE did not show genotoxic or mutagenic activities in diabetic and hypercholesterolemic rats, indicating its safe use at 100 mg/kg b.w. not only in healthy rats but also in rats with induced metabolic alterations. The findings on PSAE's efficacy may indicate that its successful and popular use is in accordance with our results. Thus, PSAE might be a potential candidate for medical purposes as a complementary treatment of diabetes and hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Statins are widely used in the treatment of hypercholesterolemia and are efficient in the prevention of cardiovascular disease. Molecular mechanisms explaining statin-induced impairment in insulin secretion remain largely unknown. In the current study, we show that simvastatin decreased glucose-stimulated insulin secretion in mouse pancreatic MIN6 β-cells by 59% and 79% (p<0.01) at glucose concentration of 5.5 mmol/l and 16.7 mmol/l, respectively, compared to control, whereas pravastatin did not impair insulin secretion. Simvastatin induced decrease in insulin secretion occurred through multiple targets. In addition to its established effects on ATP-sensitive potassium channels (p = 0.004) and voltage-gated calcium channels (p = 0.004), simvastatin suppressed insulin secretion stimulated by muscarinic M3 or GPR40 receptor agonists (Tak875 by 33%, p = 0.002; GW9508 by 77%, p = 0.01) at glucose level of 5.5 mmol/l, and inhibited calcium release from the endoplasmic reticulum. Impaired insulin secretion caused by simvastatin treatment were efficiently restored by GPR119 or GLP-1 receptor stimulation and by direct activation of cAMP-dependent signaling pathways with forskolin. The effects of simvastatin treatment on insulin secretion were not affected by the presence of hyperglycemia. Our observation of the opposite effects of simvastatin and pravastatin on glucose-stimulated insulin secretion is in agreement with previous reports showing that simvastatin, but not pravastatin, was associated with increased risk of incident diabetes. [ABSTRACT FROM AUTHOR]

The article presents a case study of an 84 years old woman who was admitted to the hospital due to continuous central chest pain with breathing movements. Topics discussed include diagnosing patient with hypothyroidism, starting levothyroxine and statin therapy for hypercholesterolemia and weakness of the proximal muscles determined after physical examination.

Familial hypercholesterolaemia (FH) is an autosomal inherited disorder characterized by markedly elevated LDL-cholesterol (LDL-C) levels and an increased risk of premature atherosclerotic cardiovascular disease. Although FH is one of the most common genetic disorders, this disorder remains mostly undetected and its management is often suboptimal. High-intensity statins are standard treatment for patients with FH, but LDL-C levels in most patients treated with statin monotherapy remain above those recommended by guidelines. Combination therapy to lower LDL-C levels further-such as treatment with statins plus ezetimibe-has been successful, and combination of apheresis with high-intensity statin treatment is used in patients with homozygous FH and in those with heterozygous FH who are statin-refractory. Mipomersen, an inhibitor of apolipoprotein B-100 synthesis, and lomitapide, a microsomal triglyceride transfer protein inhibitor, reduce LDL-C levels further when added to high-intensity statin treatment in homozygous FH, but both have important adverse effects, such as increasing liver fat content. At present, PCSK9 inhibition (with alirocumab or evolocumab) is well tolerated and reduces LDL-C levels considerably in patients receiving the maximally tolerated statin treatment, and seems the most promising emerging treatment option. Nevertheless, data from outcome trials with hard end points for PCSK9 inhibitors, mipomersen, and lomitapide are still needed before these therapies become standard for patients with FH. [ABSTRACT FROM AUTHOR]

The ability of pharmacological agents to target both “classical” risk factors and inflammation may be key for successful outcomes in the prevention and treatment of atherogenesis. Among the promising drugs interfering with cholesterol metabolism, we investigated whether methyl beta-cyclodextrin (KLEPTOSE® CRYSMEB) could positively impact on atherogenesis, lipid profile and atherosclerotic plaque inflammation in ApoE −/− mice. Eleven-week old ApoE −/− mice were fed either a normal diet (N.D.) or a high-cholesterol diet (H.D.), resulting in different levels of hypercholesterolemia. KLEPTOSE® CRYSMEB (40 mg/kg) or vehicle was intraperitoneally administrated 3 times per week in the last 16 weeks before euthanasia in mice under N.D. and in the last 11 weeks under H.D. Treatment with KLEPTOSE® CRYSMEB reduced triglyceride serum levels in both atherogenesis mouse models. In H.D. mice, treatment with KLEPTOSE® CRYSMEB increased HDL-cholesterol levels and reduced free fatty acids and spleen weight. In both mouse models, treatment with KLEPTOSE® CRYSMEB reduced atherosclerotic plaque size in thoraco-abdominal aortas and intraplaque T lymphocyte content, but did not induce relevant improvements in other histological parameters of vulnerability (macrophage, neutrophil, MMP-9 and collagen content). Conversely and more markedly in H.D. mice, treatment with KLEPTOSE® CRYSMEB was associated with a reduction in genetic markers of Th1-mediated immune response. In vitro, KLEPTOSE® CRYSMEB dose-dependently abrogated Th1 proliferation and IFNγ release. In conclusion, treatment with KLEPTOSE® CRYSMEB reduced atherosclerotic plaque size by improving triglyceride serum levels and Th1-mediated response. These results indicate this drug as a potential tool for blocking atheroprogression associated with different severity degrees of hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Background: Goal attainment of guideline-recommended low-density lipoprotein cholesterol (LDL-C) is suboptimal. Little is known about how patient factors influence physicians' treatment decision-making in hypercholesterolemia. We examined physicians' treatment recommendations in high-risk patients whose LDL-C remained uncontrolled despite statin monotherapy. Methods: Physicians completed a questionnaire prior to randomization into period I of a two-period randomized controlled trial evaluating LDL-C goal attainment in patients whose LDL-C remained ≥100 mg/dL after 5 weeks' treatment with atorvastatin 10 mg/day (NCT01154036). Physicians' treatment recommendations were surveyed for two hypothetical and one real scenario: (1) LDL-C presumed near goal (between 100-105 mg/dL), (2) LDL-C presumed far from goal (~120 mg/dL), and (3) observed baseline LDL-C of enrolled patients. Prognostic factors considered during decision-making were identified by regression analysis. Observed lipid outcomes at the end of period I (following 6 weeks' treatment with ezetimibe 10 mg plus atorvastatin 10 mg, atorvastatin 20 mg, or rosuvastatin 10 mg) were compared with estimated LDL-C outcomes for physicians' treatment recommendations after 6 weeks (based on individual patients' pre-randomization LDL-C and expected incremental change). Results: Questionnaires were completed for 1,534 patients. No change in therapy, or double atorvastatin dose, were frequently recommended, even when LDL-C was far from goal (6.5% and 52.2% of patients, respectively). Double atorvastatin dose was commonly recommended in all scenarios (43-52% of patients). More intensive LDL-C-lowering regimens were recommended infrequently e.g. double atorvastatin dose and add ezetimibe only <12% in all scenarios. Overall, cardiovascular risk factors and desire to achieve a more aggressive LDL-C goal were prominent factors in decision-making for treatment. Comparison of observed and estimated LDL-C levels showed that physicians tended to overestimate the effectiveness of their recommendations. Conclusions: This study provides insight into physicians' perspectives on clinical management of hypercholesterolemia and highlights a gap in knowledge translation from guidelines to clinical practice. The need for lower LDL-C and cardiovascular risk were key drivers in clinical decision-making, but physicians' treatment choices were more conservative than guideline recommendations, potentially resulting in poorer LDL-C reduction. When compared with actual outcomes, projected LDL-C control was better if physicians used more comprehensive strategies rather than simply doubling the statin dose. Trial registration: Clinicaltrials.gov: NCT01154036 [ABSTRACT FROM AUTHOR]

Background: Recent evidence points to an increased incidence of new-onset diabetes and a negative impact on glucose parameters with statin use. This study examined the safety of ezetimibe vs placebo for change from baseline to week 24 in HbA1c (primary endpoint), glycoalbumin, and fasting plasma glucose (secondary endpoints) in Japanese subjects with type 2 diabetes and hypercholesterolemia. Methods: This was a randomized, double-blind, placebo-controlled, parallel-group, multi-site trial. Adults with type 2 diabetes and hypercholesterolemia whose LDL-C measured <140 mg/dl (subjects receiving lipid-lowering drugs) or <160 mg/dl (subjects not receiving lipid-lowering drugs) at the start of the screening phase, were randomized after a 5-week wash-out period to ezetimibe 10 mg or placebo (1:1) for 24 weeks. Changes in HbA1c, glycoalbumin and fasting plasma glucose from baseline to week 24 were evaluated. The non-inferiority margin was set at 0.5% for HbA1c. Results: Overall, 152 subjects were randomized (75 to ezetimibe and 77 to placebo). From baseline to 24 weeks, HbA1c significantly increased in both the ezetimibe and placebo groups (between-treatment difference 0.08 [95% CI: -0.07 to 0.23]). Ezetimibe was statistically non-inferior to placebo. At 24 weeks, the mean change from baseline in glycoalbumin levels (between-treatment differences 0.00 [95% CI: -0.47, 0.47]) and fasting plasma glucose (between-treatment differences -4.8 [95% CI: -12.1, 2.1]) were similar in both treatment groups. Conclusions: These results suggest that ezetimibe 10 mg does not result in dysregulation of glucose metabolism in Japanese patients with type 2 diabetes and hypercholesterolemia over 24 weeks of treatment. Trial registration: ClinicalTrials.gov identifier NCT01611883. [ABSTRACT FROM AUTHOR]

This paper is an effort to review all the most important studies and guidelines in the topics of lipid, blood pressure and kidney published in 2014. Irrespective of advances, the options for improving simultaneous hypercholesterolemia and hypertension management (as well as its complication – chronic kidney disease) remain a problem. Recommending hypolidemic, hypotensive and kidney disease drugs to obtain therapy targets in cardiovascular, diabetic, elderly and kidney disease (=high risk) patients might strengthen risk factor control, improve compliance and the therapy efficacy, and in the consequence reduce the risk of cardiovascular events and mortality rate. That is why the authors have decided to summary and discuss the recent scientific achievements in the field of lipid, blood pressure and kidney. [ABSTRACT FROM AUTHOR]

Aims Statins are competitive inhibitors of HMGCoA reductase and are commonly used as antihypercholesterolemic agents. Experimental studies clearly demonstrate the beneficial effects of statins on bone. Tocotrienols have also been shown to have anti-osteoporotic effects on the skeletal system. This study was conducted to observe the effect of a combination of delta-tocotrienol and lovastatin on structural bone histomorphometry and bone biomechanical strength in a postmenopausal rat model at clinically tolerable doses, and to compare it with the effect of delta-tocotrienol or lovastatin. Main methods Forty-eight female Sprague Dawley rats were randomly divided into six groups: baseline control; sham-operated control; ovariectomised control; ovariectomised + 11 mg/kg lovastatin; ovariectomised + 60 mg/kg delta-tocotrienol and ovariectomised + 60 mg/kg delta-tocotrienol + 11 mg/kg lovastatin. These treatments were given via oral gavage daily for eight weeks. After sacrificing the rats, the left and right femurs were dissected and processed for bone histomorphometric analysis and a bone biomechanical test, respectively. Key findings Delta-tocotrienol in combination with lovastatin significantly improved the trabecular volume, trabecular number, trabecular thickness and trabecular separation; and it significantly increased bone strength in oestrogen-deficient rats. Delta-tocotrienol alone enhanced bone formation and maintained bone strength in ovariectomised rats. Delta-tocotrienol plus lovastatin treatment promoted better trabecular volume and trabecular number and received higher load than delta-tocotrienol alone. Lovastatin alone was not effective. Significance Thus, the combination of delta-tocotrienol and lovastatin has the potential to be used for anti-osteoporotic therapy in postmenopausal women. [ABSTRACT FROM AUTHOR]

Free circulating extracellular DNA, plasma activities of matrix metalloproteinases in hypothyroid rats, and ultrastructural changes in the myocardium were studied under conditions of experimental hypercholesterolemia. For suppression of thyroid function, the animals received antithyroid drug mercazolyl under conditions of cholesterol diet. Hypercholesterolemia in hypothyroid rats (thyroxine concentration 2-fold below the normal) was paralleled by a pronounced increase of the concentration of free circulating extracellular DNA and total matrix metalloproteinases 2 and 7 activity. These changes were associated with lytic and destructive changes in cardiomyocytes and blood capillary endotheliocytes. Changes in the cardiomyocyte and endotheliocyte ultrastructure were more pronounced in hypothyroid rats. [ABSTRACT FROM AUTHOR]

The authors discuss how the development of monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) serine protease advances the treatment of familial and other types of hypercholesterolemia. Topics addressed include the enhanced intraheptic cycling of the low-density lipoprotein (LDL) receptor, the effects of the monoclonal antibodies alirocumab and evolocumab, PCSK9 inhibitors' putative mechanism of action, and reductions in plasma lipoprotein concentrations.

Purslane (Portulaca oleracea L.) is a widely extended plant in Cuban fields and its use for alimentary and medicinal purposes is well known. Traditionally it has been employed as diuretic, antihelmintic, anti-inflammatory, etc. It is reported that Portulaca oleracea L. can reduce atherosclerosis after prolonged hypercholesterolemia due to the presence of phytosterols which are able to inhibit the intestinal absorption of cholesterol. In this work, a method by High Performance Liquid Chromatography (HPLC) for qualitative and quantitative analysis of stigmasterol and β-sitosterol in Portulaca oleracea L. powder was developed. A Lichrospher RP-18 (5 μm) 125 X 4 mm chromatographic column (reversed phase); isocratic operation mode and UV detection at a wavelength of 208 nm were set. The developed method was validated for the quality control of the mentioned plant powders by means of the following parameters: linearity, precision, accuracy, specificity and detection / quantification limits, as described in international standards. The developed and validated technique allowed the simultaneous determination of stigmasterol and β-sitosterol in Portulaca oleracea L. powders. A 0,243 % (dry base) of stigmasterol and 0,815 % (dry base) of β-sitosterol were obtained from quantitative analysis. The HPLC method was reliable and could be employed as a quality control method. [ABSTRACT FROM AUTHOR]

The current study focused on testing the hypolipidemic activity of two doses of barley bran on hypercholesterolemic male rats. Twenty-four male albino rats weighing 180-200 gm were divided into four groups. The first group (G1) was the negative control, the second group (G2) was the positive control group fed 2% cholesterol in the diet, and rats of the third and the fourth groups were fed 2% cholesterol and were cosupplemented with 5% and 10% barley bran, respectively, for 8 weeks. The hypercholesterolemic rats of (G2) showed an increase in lipid profile, liver enzymes, lactate dehydrogenase, creatine kinase-MB, and lipid peroxide and a decrease in antioxidant enzymes, whereas kidney function, fasting blood sugar, glycated hemoglobin total protein, and total bilirubin were not significantly affected compared with the negative control group in G1. Moreover, histology of heart, liver, and kidney of G2 rats showed histopathological changes compared with the negative control. Administration of the two doses of barley bran in G3 and G4 to the hypercholesterolemic rats ameliorated the level of lipids, liver enzymes, lactate dehydrogenase, and creatine kinase-MB. In addition, the histology of heart, liver, and kidney tissues nearly restored the normal state as in G1. [ABSTRACT FROM AUTHOR]

The histologic spectrum of gastrointestinal stromal tumor (GIST) is wide, but as far as we are aware, a specific intraneoplastic vasculopathy has not been described in it. This is the first report of foam cell vasculopathy in a GIST. This combination of lesions arose in a 66-year-old obese woman in treatment for hypothyroidism, hypercholesterolemia and hypertension. The patient presented a 7 cm GIST, located in the anterior wall of the stomach, which histologically showed vessels of varying sizes with striking intimal foam cell infiltration, occasional fibrinoid necrosis, hyalinization, and marked luminal narrowing or occlusion. There was a transmural lymphocytic infiltrate predominantly involving the small vessels. As a consequence of the vasculopathy, extensive tumor areas showed cellular hydropic swelling and microcyst formation. No changes of vasculopathy were observed in non-tumor vessels. The foam cell vasculopathy we have documented was a diffuse process within the GIST, and can be considered an exceptional type of intratumor necrotizing vasculitis. [ABSTRACT FROM AUTHOR]