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Background: While traditional medicine (TM) is employed by a significant portion of the global population for managing health issues, clinical guidelines and state recommendations often overlook this practice. The aim of this study was to describe the frequency of use of TM to control 3 metabolic risk factors (MRF): hypertension, hypercholesterolemia, and hyperglycaemia; and the sociodemographic, economic, and clinical characteristics associated with the use of TM. Methods: Cross-sectional descriptive study that analyses data obtained from a representative population survey in 2 health districts, one urban in the south of Quito and another in a forested rural area with diverse ethnic groups in Esmeraldas, Ecuador. We include 602 individuals with at least one MRF. We calculated the proportion of people reporting the regular use of TM (herbal or traditional remedy) to control their MRF and we assessed potential associations with sociodemographic, economic, and clinical characteristics with a multivariable logistic regression model. Results: In two very different sociocultural contexts in Ecuador we found that use of TM to control MRF was frequent (39.4% in Esmeraldas, 31.1% in Quito), frequently in combination with CM. There is a notable percentage of people, 33.9% in Esmeraldas and 39.0% in Quito, who did not take any treatment for their MRF, and the remainder used CM alone. In both settings, an individual's education lever was significantly associated with TM use. Whereas in Quito individuals with higher education more frequently treated their MRF with TM (aOR 2.04, 95% CI 1.03–3.90), in the rural, hard-to-reach context of Esmeraldas, it was more frequent among people with no formal schooling (aOR: 3.76; 95%CI 1.59–8.88), as well as those of younger age (aOR by year: 0.97; 95% CI 0.95–0.99) and afro ethnicity (aOR: 2.13; 95%CI 1.02–4.45). Conclusion: Traditional medicine is used by a significant proportion of the population in Ecuador, highlighting the need for a more accessible and intercultural healthcare approach. The health system should ensure access to the necessary information and resources for the management of their metabolic risk factors. [ABSTRACT FROM AUTHOR]

As the population ages, the demographic of adults aged 75 years and older in the U.S. is projected to grow to 45 million by 2050. Hypercholesterolemia is directly linked to atherosclerotic cardiovascular disease (ASCVD), which remains the leading cause of death in older adults. However, primary prevention of ASCVD through lipid-lowering agents remains unclear among older adults owing to limited involvement of older adults in current trials, lack of dedicated trials, and evidence primarily derived from secondary and retrospective analyses. Therefore, this article aims to (1) review key updates from the latest guidelines on treatment of hypercholesterolemia in older adults, (2) highlight limitations of the current ASCVD risk scores in the geriatric population, (3) present outcomes from key studies on the use of lipid-lowering agents and associated side effects, including a brief review of novel agents such as bempedoic acid, although very few adults over age 75 were included in these trial, and (4) finally, highlight upcoming dedicated trials of statins in older adults for the primary prevention of important geriatric outcomes as well as ASCVD. [ABSTRACT FROM AUTHOR]

• We present a novel approach to the adaptation of implementation recommendations from clinical guidelines into implementation strategies, using care of familial hypercholesterolaemia as an example. • We provide guidance on how implementation strategies can be tailored to local-contexts by key partners. • We draw upon existing programs in the literature to highlight how the application of this process is feasible. The International Atherosclerosis Society (IAS) published an evidence-informed guidance for familial hypercholesterolemia (FH) that provides both clinical and implementation recommendations. We reference examples of strategies from the literature to explore how these implementation recommendations can be tailored into implementation strategies at the local-level for stakeholders guided by a framework proposed by Sarkies and Jones. Four authors of the IAS guidance selected two published exemplar implementation recommendations for detection, management, and general implementation. Each recommendation was described as an implementation strategy using Proctor's guidance for specifying and reporting implementation strategies. It recommends reporting the actor (who), action (what), action-target (who is impacted), temporality (how often), and dose (how much) for each implementation strategy. Detection: A centralized cascade testing model, mobilized nurses (actor) to relative's homes, after the diagnosis of the proband (temporality), once (dose) to consent, obtain a blood sample and health information (action) on relatives (action-target). Management: A primary care initiative to improve FH management included an educational session (action) with clinicians (action-target), computer-based reminder message and message to patients to have their cholesterol screened once (dose) at a visit or outreach (temporality) by researchers (actor). General: A partnership between a statewide public pathology provider, local public hospital network, primary health network, government health ministry, and an academic university (actors) was established to implement a primary-tertiary shared care model (action) to improve the detection of FH (action-target). We demonstrate that implementation recommendations can be specified and reported for different local contexts with examples on monitoring, evaluation, and sustainability in practice. [ABSTRACT FROM AUTHOR]

Objective Colesevelam, a bile acid sequestrant approved for the treatment of hypercholesterolaemia, improves glycaemic control in type 2 diabetes. We hypothesised that single-dose colesevelam increases postprandial GLP-1 secretion, thus, reducing postprandial glucose excursions in individuals with type 2 diabetes. Further, we explored the effects of single-dose colesevelam on ultrasonography-assessed postprandial gallbladder motility, paracetamol absorption (proxy for gastric emptying), and circulating factors known to affect gallbladder motility. Methods In a randomised, double-blind, placebo-controlled crossover study, 12 individuals with type 2 diabetes (mean ± SD: age 61 ± 8.8 years; body mass index 29.8 ± 3.0 kg/m2) were subjected to 4 mixed meal tests on separate days; 2 with orally administered colesevelam (3.75 g) and 2 with placebo, with intravenous infusion of the GLP-1 receptor antagonist exendin(9-39)NH2 or saline. Results Single-dose colesevelam had no effect on postprandial concentrations of glucose (P =.786), C-peptide (P =.440), or GLP-1 (P =.729), and exendin(9-39)NH2 administration revealed no GLP-1-mediated effects of colesevelam. Colesevelam did not affect gallbladder emptying but abolished gallbladder refilling (P =.001), increased postprandial cholecystokinin (CCK) secretion (P =.010), and decreased postprandial serum concentrations of fibroblast growth factor 19 (FGF19) (P =.035) and bile acids (P =.043). Conclusion Single-dose colesevelam had no effect on postprandial GLP-1 responses or glucose tolerance but disrupted postprandial gallbladder refilling by increasing CCK secretion and reducing circulating concentrations of FGF19 and bile acids. These findings leave the antidiabetic actions of colesevelam unresolved but provide mechanistic insights into its effect on gallbladder motility. [ABSTRACT FROM AUTHOR]

The article reports on the analysis of the National Health and Nutritional Examination Survey (NHANES) data on the prevalence and degree of overlap of cardiac, renal, and metabolic (CRM) conditions in American adults. Among the CRM diseases are chronic kidney disease (CKD), diabetes, and cardiovascular disease (CVD). Also cited are the potential treatments like sodium-glucose cotransporter 2 (SGLT2) inhibitors.

Key content: Lipid and triglyceride levels increase in pregnancy and do not pose problems for most women. However, pregnancy‐specific factors and genetic aberrations, especially mutations, may result in supraphysiological hypercholesterolaemia (HC) and severe hypertriglyceridaemia (sHTG).HC and sHTG are associated with complications in pregnancy, including acute pancreatitis, hyperviscosity syndrome and pre‐eclampsia.Abnormally high levels of lipids and triglycerides also affect fetal growth and the onset of gestational diabetes.The clinical presentation and diagnosis of HC and sHTG are varied.Management options include lifestyle and dietary restriction/modification, omega‐3, bile‐acid sequestrants, fenofibrate, statins and plasmapheresis. Learning objectives: To understand the physiological changes that occur in lipids in pregnancy and how these are modulated.To appreciate the importance of severe HC and HTG in pregnancy, including their effects on maternal morbidity and mortality.To understand the various approaches to management and the importance of multidisciplinary management. Ethical issues: Should every woman be screened for HTG and HC during pregnancy?How safe are statins and other treatments for lipid disorders in pregnancy?Should women with very severe HTG be discouraged from getting pregnant? [ABSTRACT FROM AUTHOR]

Bile acid sequestrants (BASs) are non-systemic therapeutic agents used for the management of hypercholesterolemia. They are generally safe and not associated with serious systemic adverse effects. Usually, BASs are cationic polymeric gels that have the ability to bind bile salts in the small intestine and eliminate them by excretion of the non-absorbable polymer–bile salt complex. This review gives a general presentation of bile acids and the characteristics and mechanisms of action of BASs. The chemical structures and methods of synthesis are shown for commercial BASs of first- (cholestyramine, colextran, and colestipol) and second-generation (colesevelam and colestilan) and potential BASs. The latter are based on either synthetic polymers such as poly((meth)acrylates/acrylamides), poly(alkylamines), poly(allylamines) and vinyl benzyl amino polymers or biopolymers, such as cellulose, dextran, pullulan, methylan, and poly(cyclodextrins). A separate section is dedicated to molecular imprinting polymers (MIPs) because of their great selectivity and affinity for the template molecules used in the imprinting technique. Focus is given to the understanding of the relationships between the chemical structure of these cross-linked polymers and their potential to bind bile salts. The synthetic pathways used in obtaining BASs and their in vitro and in vivo hypolipidemic activities are also introduced. [ABSTRACT FROM AUTHOR]

Background: Unhealthy lifestyles and physical inactivity are among the contributing factors of hypercholesterolemia. This study assessed the prevalence, awareness of risk factors, and prevention and treatment of hypercholesterolemia among adults who visited Woldia referral hospital, Northeast Ethiopia. Methods: A cross-sectional survey was conducted among adults who visited Woldia referral hospital from May to August 2022. Data was collected using a structured questionnaire through a face-to-face interview and patient medical record review. Logistic regression analysis was employed to determine the association between hypercholesterolemia and other variables. A p-value at a 95% confidence level was statistically significant. Results: A total of 1180 eligible adults were included in the study. The magnitude of hypercholesterolemia was 26.4%. The majority of the respondents were aware of some risk factors, such as higher fat intake (82.3%), obesity (67.2%), and lack of adequate exercise (56.1%). However, the majority of the respondents were not aware that smoking, alcohol consumption, and age (86.8% for all) had cardiovascular risk. The majority of the respondents were aware that eating a limited amount of saturated fat (56.5%), maintaining a healthy weight (67.2%), and taking prescribed medications properly (86.8%) can prevent the risk of hypercholesterolemia. However, a larger proportion of respondents were unaware that smoking cessation (86.8%), exercise (55.3%), alcohol restriction (86.8%), and stress avoidance (75.3%) can prevent cardiovascular risks. Age (p = 0.036), smoking (p = 0.007), alcohol use (p = 0.013), fruit consumption (p = 0.019), saturated oil use (p = 0.031), level of physical activity (p < 0.001), and body mass index (p = 0.03) were significantly associated with hypercholesterolemia. Conclusion: This study concluded that more than one-fourth of adults had hypercholesterolemia. The majority of the respondents did not have an awareness of common cardiovascular risk factors and prevention and treatment techniques regarding unhealthy lifestyles and physical inactivity. [ABSTRACT FROM AUTHOR]

The escalating global burden of cardiovascular diseases (CVDs) is worrisome. The editorial emphasizes the critical role of individualized cardiovascular risk management, addressing controversies in cholesterol management and recognizing ethnicity-specific risk factors particularly considering genetic variations in Asian populations. It also delves into, creating awareness of hypertension and prevalent CVD including Ischaemic heart disease (IHD) and Heart failure (HF), their prevalence, and shifts in current management to tackle them. World Heart Day 2023, themed "Use Heart, Know Heart", emphasizes the significance of knowing our heart and heart health for a healthy life. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases, with an estimated 18.6 million deaths per year, are the leading cause of death worldwide. One of the major risk factors is elevated blood low-density lipoprotein cholesterol (LDL-C) secondary to multiple environmental and genetic factors. Genes involved in LDL-C metabolism are the targets of the most common treatment options. Advanced molecular techniques could pave the way for identifying novel targets in dyslipidemia therapies. The LIM domain and actin-binding 1 (LIMA1) gene binds to the NPC1L1 protein and facilitates its more efficient recycling to the plasma membrane. Inhibition of LIMA1 could disrupt cellular cholesterol hemostasis with a probable decrease in blood LDL-C levels. Objectives: The present study was designed to knock out exon 2 of the LIMA1 gene using lentiviruses as an in vitro model for reducing cholesterol absorption. Methods: A CRISPR/Cas9 system with dual guide RNAs (gRNAs) was designed to completely excise exon 2 of LIMA1. Two gRNAs (gRNA1 and gRNA2) were cloned in the LentiCRISPR v2 vector. LentiCRISPR viruses were produced in the HEK293T cell line to encode the CRISPR/Cas9 complex structure. HepG2 cell lines were transduced with two different LentiCRISPR viruses simultaneously. Results: Exon 2 deletion was detected by PCR, gel electrophoresis, and subsequent Sanger sequencing of the PCR product. Exon 2 deletion caused a frameshift mutation, and the subsequent production of nonfunctional transcripts led to gene knockout. The dual gRNA CRISPR/Cas9 system could be used in gene editing setups. Conclusions: The in vitro knockout model of LIMA1 could be considered as preliminary work to study the role and mechanism of action of the LIMA1 protein, along with its potential as a target for hypercholesterolemia therapy. [ABSTRACT FROM AUTHOR]

Background: Empirical evidence on the epidemiology of hypertension, diabetes and hypercholesterolemia is limited in many countries in Central and Eastern Europe. We aimed to estimate the prevalence, awareness, treatment and control of hypertension, diabetes and hypercholesterolemia in the Czech Republic, Russia, Poland and Lithuania, and to identify the risk factors for the three chronic conditions.Methods: We analysed cross-sectional data from the HAPIEE study, including adults aged 45-69 years in the Czech Republic, Russia, Poland and Lithuania, collected between 2002 and 2008 (total sample N = 30,882). Among prevalent cases, we estimated awareness, treatment, and control of hypertension, diabetes and hypercholesterolemia by gender and country. Multivariate logistic regression was applied to identify associated risk factors.Results: In each country among both men and women, we found high prevalence but low control of hypertension, diabetes, and hypercholesterolemia. Awareness rates of hypertension were the lowest in both men (61.40%) and women (69.21%) in the Czech Republic, while awareness rates of hypercholesterolemia were the highest in both men (46.51%) and women (51.20%) in Poland. Polish participants also had the highest rates of awareness (77.37% in men and 79.53% in women), treatment (71.99% in men and 74.87% in women) and control (30.98% in men and 38.08% in women) of diabetes. The common risk factors for the three chronic conditions were age, gender, education, obesity and alcohol consumption.Conclusions: Patterns of awareness, treatment and control rates of hypertension, diabetes and hypercholesterolemia differed by country. Efforts should be made in all four countries to control these conditions, including implementation of international guidelines in everyday practice to improve detection and effective management of these conditions. [ABSTRACT FROM AUTHOR]

Public health and individual health care are increasingly oriented towards managing risks. This 'surveillance medicine' does not target present illnesses but aims to prevent possible future conditions, greatly expanding the number of people implicated in medical interventions. In this paper, I interrogate the everyday experience of being at risk of illness. First, I suggest that we lack a comprehensive account of this experience, because current ways to characterise this phenomenon tend to equate risk with (chronic) illness and patient status. I then report a case study designed to avoid this starting point. I conducted interviews with laypersons with varying levels of elevated cholesterol, a common risk factor for cardiovascular diseases, who were recruited from a consumer panel in Finland in 2015. I found three elements that structure the health risk experience: the intangible nature of risk, the probabilistic character of risk estimates, and the ambivalent status of risk in terms of health and illness. While these findings overlap with previous literature in many ways, detaching health risk from illness foregrounds health management instead of patient behaviour. These findings call for caution in approaching health risk uncritically through illness categories or patient status, and I invite researchers to critically examine such elements in other cases and contexts. [ABSTRACT FROM AUTHOR]

High cholesterol is a preventable risk factor for heart disease. This study examines which aspects of patient-provider communication are associated with patient report of increased adherence to cholesterol management advice in a diverse, low-income patient population accessing the health care safety net, using the 2014 Health Center Patient Survey. Patient-provider communication measures included patient report of: how often a provider listened carefully, gave easy-to-understand information, knew important information about the patient's medical history, showed respect, and spent enough time with the patient. Outcome measures were patient report of following provider advice to eat fewer high fat or high cholesterol foods, manage weight, increase physical activity, or take prescribed medicine. In adjusted analyses, when patients perceived their provider always knew their medical history, patients were more likely to report taking prescribed medication (adjusted odds ratio [aOR]: 3.2; 95% confidence interval [CI]: 1.6, 6.6). Knowledge of medical history (aOR: 2.8, 95% CI: 1.4, 5.8), spending enough time (aOR: 2.3, 95% CI: 1.2, 4.4), and providing easily understandable information (aOR: 2.2, 95% CI: 1.0, 4.7) were significantly associated with report of following physical activity advice. Knowledge of medical history (aOR: 2.3, 95% CI: 1.0, 5.2) and providing easily understandable information (aOR: 3.3, 95% CI: 1.4, 7.9) were significantly associated with report of following weight management advice. This study indicates different components of patient-provider communication influence patient adherence to lifestyle modification advice and medication prescription. These results suggest a tailored approach to optimize the impact of patient-provider communication on cholesterol management advice adherence. [ABSTRACT FROM AUTHOR]

Garlic is a widely known and widely used plant. Due to its taste, it is used in the preparation of many dishes. Garlic is also used in the treatment of bacterial, viral, fungal and parasitic infections. There are many chemical compounds in garlic, but those responsible for its health-promoting effect include, first of all, those containing sulfur. These compounds are characterized by many mechanisms of action, such as antioxidant, cardioprotective and anti-inflammatory effects. Many mechanisms of action of organosulfur compounds influencing the regulation of blood pressure and lipid metabolism have been demonstrated. Many clinical studies and meta-analyses are assessing the effect of garlic on blood pressure and lipid profile in various groups of patients in the literature. This article aims to present the current knowledge on the influence of garlic on blood pressure and lipid metabolism. [ABSTRACT FROM AUTHOR]

Background: Hypercholesterolemia (plasma cholesterol concentration ≥5.2 mmol/L) is a risk factor for cardiovascular disease and stroke. Many different cholesterol self-tests are readily available at general stores, pharmacies and web shops. However, there is limited information on their analytical and diagnostic performance. Methods: We included 62 adult patients who required a lipid panel measurement (cholesterol, high-density lipoprotein (HDL), triglycerides and LDLcalc) for routine care. The performance of five different cholesterol self-tests, three quantitative meters (Roche Accutrend Plus, Mission 3-in-1 and Qucare) and two semi-quantitative strip tests (Veroval and Mylan MyTest), was assessed according to the manufacturers' protocol. Results: The average plasma cholesterol concentration was 5.2 ± 1.2 mmol/L. The mean absolute relative difference (MARD) of the five cholesterol self-tests ranged from 6 ± 5% (Accutrend Plus) to 20 ± 12% (Mylan Mytest). The Accutrend Plus cholesterol meter showed the best diagnostic performance with a 92% sensitivity and 89% specificity. The Qucare and Mission 3-in-1 are able to measure HDL concentrations and can thus provide a cholesterol:HDL ratio. The Passing-Bablok regression analyses for the ratio showed poor performance in both self-tests (Mission 3-in-1 : y = 1.62x–1.20; Qucare : y = 0.61x + 1.75). The Accutrend Plus is unable to measure the plasma high-density lipoprotein concentration. Conclusions/interpretation: The Accutrend Plus cholesterol meter (Roche) had excellent diagnostic and analytic performance. However, several of the commercially-available self-tests had considerably poor accuracy and diagnostic performance and therefore do not meet the required qualifications, potentially leading to erroneous results. Better regulation, standardization and harmonization of cholesterol self-tests is warranted. [ABSTRACT FROM AUTHOR]

Background: Familial hypercholesterolaemia (FH) is underdiagnosed in most countries. We report our first experience from a national pilot project of cascade screening in relatives of FH patients. Methodology: Participating specialists recruited consecutive index patients (IP) with Dutch Lipid Clinic Network (DLCN) score -6. After informed consent, the relatives were visited by the nurses to collect relevant clinical data and perform blood sampling for lipid profile measurement. FH diagnosis in the relatives was based on the DLCN and/or MEDPED FH (Make-Early-Diagnosis-to-Prevent-Early-Deaths-in-FH) criteria. Results: In a period of 18months, a total of 127 IP (90 with definite FH and 37 with probable FH) were enrolled in 15 centres. Out of the 270 relatives visited by the nurses, 105 were suspected of having FH: 31 with DCLN score >8, 33 with DLCN score 5-8 and 41 with MEDPED FH criteria. In a post-hoc analysis, another set of MEDPED FH criteria established in the Netherlands and adapted to Belgium allowed to detect FH in 51 additional relatives. Conclusion: In a country with no national FH screening program, our pilot project demonstrated that implementing a simple phenotypical FH cascade screening strategy using the collaboration of motivated specialists and two nurses, allowed to diagnose FH in 127 index patients and an additional 105 of their relatives over the two-year period. Newly developed MEDPED FH cut-offs, easily applicable by a nurse with a single blood sample, might further improve the sensitivity of detecting FH within families. [ABSTRACT FROM AUTHOR]

Dyslipidemia is one of the main risk factors for coronary heart disease (CHD). The E3 ubiquitin ligase which is encoded by the ring finger protein 145 (RNF145) gene is very important in the mediation of cholesterol synthesis and effectively treats hypercholesterolemia. Thus, the purpose of the present research is to investigate the connection between the polymorphism of the RNF145 gene and cholesterol levels in the populations in Xinjiang, China. A total of 1396 participants (Male: 628, Female: 768) were included in this study for genetic analysis of RNF145 gene, and we used the modified multiple connection detection response (iMLDR) technology to label two SNPs (rs17056583, rs12188266) of RNF145 genotyping. The relationship between the genotypes and the lipid profiles was analyzed with general linear model analysis after adjusting confounding variables. Through the analysis of the two SNPs in RNF145 gene, we discovered that both rs17056583 and rs12188266 were related to total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations (All P < 0.001). In addition, the association of rs17056583 and rs12188266 with lipid profiles concentrations is still statistically significant after multivariate adjustment of sex, age, smoking, obesity, drinking, diabetes, hypertension and lipid profiles. Meanwhile, we also found that rs17056583 was associated with high triglycerides concentrations before and after adjustment (All P < 0.001). Our study shows that both rs17056583 and rs12188266 SNPs of RNP145 gene are related to TC and LDL-C concentrations in Xinjiang population. [ABSTRACT FROM AUTHOR]

BackgroundEngagement in behaviors aimed at reducing the risk of developing dementia is a leading recommendation in most National Dementia Strategy programs.Objective: In an effort to advance knowledge regarding the implementation of this recommendation, the current study examined the perceptions and engagement of the adult population in Israel regarding behaviors aimed at reducing the risk of developing dementia, and its correlates.Methods: A cross-sectional survey was conducted among 502 Israeli adults aged 40 and over. Approximately half of the participants (51.2%) were female, and the majority (80.1%) were Jewish.Results: Overall, while the percentage of participants reporting that the examined activities were important for brain health was moderate, percentages reporting engaging in these behaviors were low. The most important correlate of engagement in health behaviors was participants' perceptions about the importance of these behaviors for their brain health. Increased age, being Jewish, and enhanced perceived susceptibility to develop dementia were also significantly associated with increased engagement in behaviors to reduce the risk of dementia.Conclusion: The results of this study emphasize the need to develop intervention programs aimed at promoting engagement in behaviors to reduce the risk of dementia development. These programs will benefit from assessing participants' perceived importance of these behaviors, and from identifying the needs of unique groups, such as older persons and those pertaining to ethno-cultural groups. [ABSTRACT FROM AUTHOR]

Accumulation of lipoprotein X (LpX) in blood can cause severe hypercholesterolemia and cutaneous xanthomas. Monocytes sensitively sense lipid changes in circulation and contribute to inflammation. However, how monocytes respond to LpX is undefined. We examined the phenotype of monocytes from a patient, who had LpX, severe hypercholesterolemia, and extensive cutaneous xanthomas, and effects of semiselective plasmapheresis therapy (SPPT). Fluorescence-activated cell sorting and adhesion assays were used to examine monocyte phenotype and ex vivo oxidized low-density lipoprotein uptake and adhesion in the patient before and after treatment with SPPT. Effects of plasma from the patient on the phenotype and adhesion of monocytes from a healthy participant were determined. SPPT improved hypercholesterolemia and cutaneous xanthomas. Before treatment, the patient had lower frequency of nonclassical monocytes but higher frequency of intermediate monocytes than the control participant. Before treatment, monocytes from the patient with LpX showed more intracellular lipid accumulation, alterations in several cell surface markers and intracellular cytokines, as well as enhanced oxidized low-density lipoprotein uptake and reduced adhesion compared with control. After SPPT, the phenotypes of monocytes from the patient with LpX were similar to control monocytes. Incubation with plasma from the patient before treatment as compared with plasma from the control participant or the patient after treatment increased CD11c expression and adhesion of monocytes from a healthy participant. LpX-induced hypercholesterolemia increased lipid accumulation and altered the phenotype of monocytes, which may contribute to cutaneous xanthoma development. Removal of LpX by SPPT reduced lipid accumulation and improved monocyte phenotype, likely contributing to xanthoma resolution. • Cutaneous xanthomas presented in a woman with lipoprotein X (LpX)-induced hypercholesterolemia. • LpX-induced hypercholesterolemia increased lipid accumulation in monocytes. • LpX-induced hypercholesterolemia altered phenotypes of circulating monocytes. • Removal of LpX by plasma exchange reduced size of the cutaneous xanthomas. • Removal of LpX by plasma exchange improved monocyte phenotypes. [ABSTRACT FROM AUTHOR]

Background/Aim: Lipid-lowering drugs have been suggested to affect neurocognitive function. This review aimed to give the latest evidence on the way these agents affect neurocognitive function based on clinical trials. Materials and Methods: A systematic search concerning original studies from 2015 to 2020 was performed through the databases PubMed, EMBASE and Cochrane, according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. The trials enrolled numerous patients and were conducted in different areas of the world. The terms used are cholesterol, lipid-lowering drugs, statins and cognitive function. Results: Eleven randomized trials met the inclusion criteria. The trials included patients suffering from cardiovascular conditions. In particular, patients with coronary heart disease, coronary heart disease risk equivalents and hypercholesterolemia were tested. The trials included evolocumab, alirocumab, statin, ezetimibe or placebo. Conclusion: Lipid-lowering drugs seem to have no significant effect on neurocognitive function, but further research specifically focused on this matter is needed. [ABSTRACT FROM AUTHOR]

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Background. Statins and exercise are recommended for managing hypercholesterolemia. However, statin types may vary in their interaction with exercise. We compared rosuvastatin versus atorvastatin combination with exercise on lipid profile and functional capacity. Methods. A retrospective cohort study using data from a 12-week cardiovascular rehabilitation program between 2014 and 2016. Statin use was determined through prescriptions, and the average exercise minutes/week were computed from exercise logs. The outcomes were changes in total cholesterol, low- and high-density lipoproteins (LDL and HDL), triglycerides, and functional capacity (6-minute walk test (6MWT)). Directed acyclic graphs were used to identify potential confounders, accounted for using multiple linear regression modeling. Results. The cohort included 282 patients from 106 atorvastatin and 176 rosuvastatin users. The average exercise minutes/week was 109.4 ± 66.1 among atorvastatin and 106.7 ± 49.1 among rosuvastatin users. Interaction models suggested that a higher number of exercise minutes/week were more favorable among atorvastatin users on total cholesterol and LDL (0.004, 95% CI: 0.001, 0.008 and 0.004, 95% CI: 0.001, 0.007, respectively) but did not reach significance for HDL and triglycerides. Rosuvastatin use was associated with greater increases in 6MWT; however, we observed no between-group differences in interaction estimates by the type of statin used. Conclusion. Rosuvastatin use could blunt the beneficial effect of exercise on LDL and total cholesterol compared to atorvastatin. No significant differences were observed in triglycerides, HDL, and functional capacity levels. Additional studies are warranted with randomized treatments and larger samples. Healthcare providers should continue prescribing statins alongside recommending exercise modalities, with a careful follow-up for rosuvastatin users. [ABSTRACT FROM AUTHOR]

Familial hypercholesterolaemia (FH) is caused by a major genetic defect in the low-density lipoprotein (LDL) clearance pathway. Characterised by LDL-cholesterol elevation from birth, FH confers a significant risk for premature coronary artery disease (CAD) if overlooked and untreated. With risk exposure beginning at birth, early detection and intervention is crucial for the prevention of CAD. Lowering LDL-cholesterol with lifestyle and statin therapy can reduce the risk of CAD. However, most individuals with FH will not reach guideline recommended LDL-cholesterol targets. FH has an estimated prevalence of approximately 1:250 in the community. Multiple strategies are required for screening, diagnosing and treating FH. Recent publications on FH provide new data for developing models of care, including new therapies. This review provides an overview of FH and outlines some recent advances in the care of FH for the prevention of CAD in affected families. The future care of FH in Australia should be developed within the context of the National Health Genomics Policy Framework. [ABSTRACT FROM AUTHOR]

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]

Objective: High cholesterol is a common condition in the United States, affecting nearly one third of adults, and is a leading precursor to coronary heart disease. This study investigates race/ethnic differences in treatment recommendations for patients with high cholesterol, including prescription medication and lifestyle changes such as eating less fat, losing weight, or exercising more. Design: Data were obtained from the 2005 to 2010 National Health and Nutrition Examination Survey (N = 4846), a representative sample of adults in the United States, and the 2005–2010 National Ambulatory Medical Care Survey (N = 12,113), a representative sample of patient visits in the United States. Logistic regression analyses were used to assess whether health professionals recommended lifestyle changes or medication prescriptions differently by patient race/ethnicity and age. Models adjusted for demographic characteristics, socioeconomic status, health behaviors, health care access/utilization, and comorbidities. Results: Non-Hispanic Black and Hispanic patients with high cholesterol were significantly and substantially more likely to receive recommendations for lifestyle changes compared to non-Hispanic White patients. These differences were exacerbated at younger ages and largely diminished for adults over the age of 65. These patterns were reflected in both datasets. However, non-Hispanic Black patients from the NHANES analysis were less likely than non-Hispanic White patients to receive medication prescriptions for high cholesterol, particularly at younger ages. There were no race/ethnic differences in odds of medication prescriptions for Hispanic patients compared to White patients. Conclusions: Results suggest widespread and pervasive race/ethnic differences in recommending lifestyle changes for patients with high cholesterol. Although lifestyle changes may lower cholesterol they are often less effective than prescription medication. Because differences in lifestyle recommendations were not reflected in prescription practices, results may indicate a form of discrimination within physician-patient interactions that could be addressed by increased provider education about most effective treatment practices. [ABSTRACT FROM AUTHOR]

Introduction: Exercise rehabilitation/training is integral in the prevention and management of chronic, lifestyle-related diseases. Poor long-term adherence to exercise by patients is a challenging problem for health professionals. Despite the evidence of appropriate supervision with improved exercise adherence, the supervision process is not adequately described in the literature. Further, the co-existing Technical and Cognitive Behavioral components of exercise supervision are commonly described separately. Methodology: The literature search included (a) reviewing the Technical Domain (TD) of exercise prescription; and (b) Cognitive Behavioral Domain (CBD) of exercise adoption and adherence. CB theories were selected based upon their scientific evidence base demonstrating efficacy in intervention trails. The FITTSBALL tool was developed combining TD and CBD identifying multiple interactions. The tool was applied to 3 case scenarios to demonstrate efficacy. Results: "FITTSBALL" combined the technical domain of "FITT" (Frequency, Intensity, Time, and Type of exercise) and the cognitive behavioral domain (combining five theories and additional constructs) explained by "SBALL" (Stage of change, Belief and Ability of the client, Limitations and Life satisfaction). The tool describes the exercise supervision process and its associations as a three dimensional "sphere" traveling in a particular trajectory. Case scenarios on exercise adoption, maintenance, and relapse are described. Discussion: The "FITTSBALL" tool developed and detailed in this article provides both a meaningful description of supervision and a logical, generic framework for exercise prescription, concentrating on adherence and behavior change. The tool could be used by all staff responsible for supervision. This approach describes how the technical "FITT" principle of prescribing exercise can coexist with a range of cognitive and behavioral theories that have been posited to describe approaches to encourage behavior change and support adherence to such changes. Many such approaches have been widely studied over recent decades using interventional trials. Conclusion: "FITTSBALL" is a logical, generic framework for exercise prescription, concentrating on adherence and behavior change. To the best of our knowledge, such a comprehensive and coherent tool has not been presented to date. Exercise training is integral in the management of chronic, lifestyle-related diseases, but long term adherence is a challenge. Exercise supervision improves adherence, but exercise supervision process is not adequately described in the literature. The tool "FITTSBALL" describes the supervision process and provides a logical, generic framework for exercise prescription and maintaining adherence to the behavior. The dynamic tool combines the traditional technical domain of "FITT" with the cognitive behavioral domain explained by "SBALL". [ABSTRACT FROM AUTHOR]

Background and Objective: Hypercholesterolemia is one of the major risk factor for atherosclerotic coronary heart disease, especially coronary heart disease. Most effective class of medications for prevention of cardiovascular events and LDL-C reduction are the statins. Approximately only one fourth of these high risk patients had achieved LDL-C levels <70 mg/dL with statins. Monoclonal antibody targeting PCSK9 is a novel class of drug used in the treatment of Hypercholesterolemia. Alirocumab is one such human monoclonal antibody directed against PCSK9. Binding of PCSK9 to the LDL-R on the hepatocytes promotes LDL-R degradation. Inhibition of PCSK9 binding to LDL-R leads to increased number of LDL-Rs to clear LDL, thus decreasing LDL-C levels. The purpose of this systematic study is to assess the safety and efficacy of Alirocumab in adults with hypercholesterolemia and Familial hypercholesterolemia. Materials and Methods: We searched Medline, PubMed Central database, Google scholar, EBSCO, Wiley library, conference proceedings and Clinical trials.gov registry through March 2017. Phase 3 randomized, controlled trials (RCTs) using Alirocumab in adults with hypercholesterolemia and Familial Hypercholesterolemia were selected. Results: In twelve RCTs comprising of 6019 patients included in the meta-analysis, significant favorable changes in LDL-C and HDL-C were found. Limitations: Results were derived from study level data rather than patient level data. Conclusions: Alirocumab substantially reduced the LDL-C level by over 50 %, increased the HDL-C level, and resulted in favorable changes in other lipids. [ABSTRACT FROM AUTHOR]

Background: The 2013 American College of Cardiology/American Heart Association guidelines for the treatment of blood cholesterol found little evidence to support the use of nonstatin lipid-modifying medications to reduce atherosclerotic cardiovascular disease (ASCVD) events. Since publication of these guidelines, multiple randomized controlled trials evaluating nonstatin lipid-modifying medications have been published.Methods: We performed a systematic review to assess the magnitude of benefit and/or harm from additional lipid-modifying therapies compared with statins alone in individuals with known ASCVD or at high risk of ASCVD. We included data from randomized controlled trials with a sample size of >1,000 patients and designed for follow-up >1 year. We performed a comprehensive literature search and identified 10 randomized controlled trials for intensive review, including trials evaluating ezetimibe, niacin, cholesterol-ester transfer protein inhibitors, and PCSK9 inhibitors. The prespecified primary outcome for this review was a composite of fatal cardiovascular events, nonfatal myocardial infarction, and nonfatal stroke.Results: The cardiovascular benefit of nonstatin lipid-modifying therapies varied significantly according to the class of medication. There was evidence for reduced ASCVD morbidity with ezetimibe and 2 PSCK9 inhibitors. Reduced ASCVD mortality rate was reported for 1 PCSK9 inhibitor. The use of ezetimibe/simvastatin versus simvastatin in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) reduced the primary outcome by 1.8% over 7 years (hazard ratio: 0.90; 95% CI: 0.84-0.96], 7-year number needed to treat: 56). The PSCK9 inhibitor evolocumab in the FOURIER study (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) decreased the primary outcome by 1.5% over 2.2 years (hazard ratio: 0.80; 95% CI: 0.73-0.88; 2.2=year number needed to treat: 67). In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab reduced the primary outcome by 1.6% over 2.8 years (hazard ratio: 0.86; 95% CI: 0.79-0.93; 2.8-year number needed to treat: 63). For ezetimibe and the PSCK9 inhibitors, rates of musculoskeletal, neurocognitive, gastrointestinal, or other adverse event risks did not differ between the treatment and control groups. For patients at high risk of ASCVD already on background statin therapy, there was minimal evidence for improved ASCVD risk or adverse events with cholesterol-ester transfer protein inhibitors. There was no evidence of benefit for the addition of niacin to statin therapy. Direct comparisons of the results of the 10 randomized controlled trials were limited by significant differences in sample size, duration of follow-up, and reported primary outcomes.Conclusions: In a systematic review of the evidence for adding nonstatin lipid-modifying therapies to statins to reduce ASCVD risk, we found evidence of benefit for ezetimibe and PCSK9 inhibitors but not for niacin or cholesterol-ester transfer protein inhibitors. [ABSTRACT FROM AUTHOR]

The management of hypercholesterolemia in older adults still represents a challenge in clinical medicine. The pathophysiological alterations of cholesterol metabolism associated with aging are still incompletely understood, even if epidemiological evidence suggests that serum cholesterol levels increase with ongoing age, possibly with a plateau after the age of 80 years. Age is also one of the main determinants of cardiovascular disease, according to all cardiovascular risk estimate tools. Cholesterol‐lowering treatment, therefore, would be expected to bring significant protection, even in these patients. Unfortunately, direct experimental evidence is extremely limited, particularly in the very old age strata of the population; a clinical benefit still seems to be present, but the risk for drug‐related adverse events is clearly higher. At any rate, at the present time, definite guidelines for the correct management of hypercholesterolemia in older patients are not available. Therefore, the decision whether or not a pharmacological treatment should be set up, and the choice of the drug, need to be tailored to the individual patient, and requires accurate clinical judgment. The specific aspects of frailty and disability, along with the actual age of the patients, have to be considered together, with a comprehensive assessment approach. The present review summarizes the evidence regarding the modifications of cholesterol metabolism in older patients, the impact of lipid‐lowering drugs on cardiovascular outcomes and focuses on the considerations that can help to define the most appropriate treatment strategy, in view of the individual functional profile. Geriatr Gerontol Int 2019; 19: 375–383. [ABSTRACT FROM AUTHOR]

Aims and objectives: To identify the key factors of adopting self‐care behaviours in the treatment of diabetes mellitus II, hypertension and hypercholesterolaemia when the three conditions appear simultaneously. Background: Diabetes, hypertension and hypercholesterolaemia are chronic health problems which often appear together. The correct monitoring of these pathologies when they concur simultaneously requires specific health management behaviours, to which a significant part of the population is unable of adhering, despite recommendations from professional healthcare workers. Design: A qualitative study using focus groups techniques was carried out. The elements related to the content were drafted following the recommendations of the Consolidated Criteria for Reporting Qualitative Research (COREQ checklist). Methods: Patients with simultaneous diabetes, hypertension and hypercholesterolaemia, as well as nursing professionals and family doctors who have treated patients at primary care centres, were the key sources of information. The methodology used to analyse the information was content analysis. Results: There were factors which can positively or negatively determine the adoption of the self‐management recommendations that healthcare professionals make to patients who simultaneously have diabetes, hypertension and hypercholesterolaemia. These factors were not only associated with the patient, but also with the health carers themselves and the healthcare system and policies in force. Conclusions: When health professionals provide recommendations for self‐care to people diagnosed with diabetes, hypertension and hypercholesterolaemia simultaneously, they should bear in mind not only the determinants of behaviour associated with the patient, but also those that are related to the health professionals themselves and with the healthcare system. The PRECEDE model could be a good tool to identify and design health education programs. Relevance to clinical practice: The knowledge of the determinants of health behaviour of patients with chronic diseases could improve adherence patients to health recommendations, avoid associated complications and increase their quality of life. [ABSTRACT FROM AUTHOR]

Given the high co-occurrence of age and hypercholesterolemia, there is a critical need for age-appropriate evidence for achieving normal cholesterol levels. The purpose of the current review was to map recent evidence (i.e., past 5 years) on hypercholesterolemia management in older adults and identify gaps in the evidence. Electronic searches in PubMed, CINAHL, and Scopus were conducted. Inclusion criteria were age 65 or older and lipid panel outcome. Exclusion criteria were a mixed age sample and familial hypercholesterolemia. An initial pool of 3,176 unique records resulted in 26 articles that met inclusion criteria. Arksey and O'Malley's scoping study framework was used. Sample sizes ranged from 12 to 1,010 (N = 8,509) adults ages 65 to 96. Evidence supports the use of exercise, diet, and statins in older adults. Laboratory, intervention, and methodological gaps were identified. Much remains to be examined in safely managing older adults with hypercholesterolemia, including determining time to behavior change in nonpharmacological interventions and contextual factors influencing adherence. [ABSTRACT FROM AUTHOR]

Background Tanjin is an herbal medicine made from the root of salvia miltiorrhiza. It is predominantly given to arteriosclerotic patients as a supplement to ameliorate the clinical symptoms of cardiovascular diseases. In China, tanjin is used frequently in combination treatment for hypercholesterolemia. Thus, there is a high probability of combination of tanjin and statins in these arteriosclerotic patients. This study investigated the interaction between tanjin and rosuvastatin. Methods We performed a randomized single-blind, two-period crossover clinical trial on six healthy male volunteers. Volunteers were administered rosuvastatin with placebo or a tanjin-containing drug randomly. The blood samples were collected before drug administration, and at 0.5, 1, 1.5, 2, 4, 8, and 12 hours after administration. Lymphocytes were isolated from blood samples before and 12 hours after drug administration to measure mRNA. As an animal experiment, an in situ intestinal injection with portal vein sampling model was used to examine the interaction between tanjin and rosuvastatin during the absorption phase. Rosuvastatin or rosuvastatin combined with tanjin solution was injected into the intestine. After injection, blood from the portal vein was collected and the concentration of rosuvastatin was measured by LC/MS/MS analysis. A portion of the intestine and liver from the rats was collected and stored at -80°C for mRNA measurement. Results In the clinical trial, co-administration of tanjin decreased the maximum plasma concentration (Cmax) of rosuvastatin by 26.85% compared with rosuvastatin alone, and also decreased the area under the plasma concentration-time curve of rosuvastatin from 0 to 12 h (AUC0-12) by 19.43%. The relative expression of BCRP and OATP mRNA in human lymphocytes was increased by co-administration of tanjin. In the animal experiment, co-administration of tanjin extract reduced the concentration of rosuvastatin to 84.4, 64.4, and 50.0% at 15, 30, and 45 minutes, respectively. The tanjin-containing drug had a similar effect to tanjin extract. Furthermore, tanjin significantly reduced the absorption of rosuvastatin and the inhibitory effects lasted for at least 24 hours. Tanjin increased the relative expression of BCRP mRNA in the intestine, but it did not change the expression of OATP. Moreover, the concentration of rosuvastatin in the portal vein and systemic blood was reduced. In the liver, tanjin increased both BCRP and OATP mRNA expression, which was consistent with the results from human lymphocytes. Conclusion The clinical trial and animal experiment revealed that tanjin can significantly reduce the absorption of rosuvastatin. This interaction occurred, at least, at the absorption phase in the small intestine due to the enhanced efflux transport. Thus, as tanjin and rosuvastatin were found to interact, their combination needs to be paid attention to. [ABSTRACT FROM AUTHOR]

Statins are widely used for the treatment of hypercholesterolemia. However, their inhibitory action on HMG-CoA reductase also results in the depletion of intermediate biosynthetic products, which importantly contribute to cell proliferation. The aim of the present study was to compare the effects of the individual commercially available statins on investigational breast cancer. Thus, in this study, biodegradable polymeric micelles as carrier of statins were prepared using biodegradable copolymers (PCL-PEG-PCL). These nanoparticles were prepared with two statins (atorvastatin and rosuvastatin) and drug loading, release, kinetic release, and anti-cancer activity of these drugs were studied. The triblock copolymer PCL-PEG-PCL was synthesized by a ring opening polymerization of e-caprolactone in the presence of PEG as the initiator and Sn(oct)2 as the catalyst. The synthesized copolymers and nanoparticles were characterized by FTIR, HNMR, GPC, DLS, and AFM analyses. The drug loading and release of drugs were studied by UV-Vis. Additionally, MTT assays on HFF-2 cell lines were performed for determination of biocompatibility of micelles. Finally, the anticancer activity of micelles was studied on MCF-7 breast cancer cell lines. The results showed that the average diameter of nanoparticles was less than 45 nm. The loading capacity of atorvastatin and rosuvastatin was 20.0 ± 1.01% and 13.21 ± 1.18%, respectively, and encapsulation efficiency of atorvastatin and rosuvastatin was 88.19 ± 1.11% and 69.32 ± 0.23%, respectively. The results showed strong and dose-dependent inhibition of cell (MCF-7line) growth by the nanoparticles compared with statins. The result of cell viability assay on the MCF-7 cell line verified that the bare nanoparticles showed little inherent cytotoxicity whereas the statins-loaded nanoparticles were cytotoxic. [ABSTRACT FROM AUTHOR]

The article presents a case study of an 11-year-old boy who was diagnosed with familial hypercholesterolemia (FH), a severe premature atherosclerosis. Topics discussed include the medical history, the diagnosis of the patient through electrocardiography and physical examination, and the success of the percutaneous coronary intervention (PCI).

Summary: Emerging scientific evidence suggests that the supplementation of probiotics may help to reduce/manage blood cholesterol levels in humans. We evaluated the in vitro cholesterol‐lowering activity of the probiotic strain Bacillus coagulansMTCC 5856. This probiotic de‐conjugated bile salts and liberated deoxycholic acid, confirming its bile salt hydrolase activity. Furthermore, B. coagulansMTCC 5856 also significantly (P < 0.05) reduced cholesterol levels in culture media under growing (48.42%), resting (live but suspended in buffer, 36.47%) and even heat‐killed (dead, 8.5%) conditions. Bacillus coagulansMTCC 5856 significantly reduced the cholesterol levels in cholesterol‐rich foods, such as egg yolk (39.79%), chicken liver (45.44%) and butter (49.51%), when incubated for 24 h in conditions mimicking the in vivo environment. Bacillus coagulansMTCC 5856 also produced significant (P < 0.05) amounts of propionic acid and butyric acid while fermenting cholesterol‐rich foods. The multitudinous ways by which B. coagulansMTCC 5856 reduces cholesterol levels endorses its application in functional food formulations and as a dietary ingredient for the management of hypercholesterolemia, potentially reducing the incidence of coronary heart disease and other related disabilities. The probiotic bacteria Bacillus coagulans MTCC 5856 exhibits in vitro cholesterol‐lowering activity via different mechanisms, including bile salt de‐conjugation, cholesterol removal, cholesterol binding to resting and dead cells and the production of short‐chain fatty acids. Further, B. coagulans MTCC 5856 helped remove cholesterol from cholesterol‐rich foods (egg yolk, liver and butter) under a hostile GI environment, thereby suggesting its ability to function in vivo. The findings reported in this study provide clear evidence of the effectiveness of the probiotic strain B. coagulans MTCC 5856 in the nutritional treatment of diet‐induced hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Abstract Aqueous and ethanol extracts prepared from leaves of Olea europaea L. were evaluated for in vitro antioxidant and in vivo hypocholesterolemic effect. The result of administration of O. europaea leaf extracts on serum total cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) in hypercholesterolaemic mice was evaluated. In addition, rutin and luteolin, reported to occur naturally in O. europaea leaves, were docked against HMG-CoA reductase, the rate-limiting enzyme in cholesterol metabolism. Mice treated with both extracts showed reduced total cholesterol (246.6 and 163.4 mg/dl, for mice groups treated with respective extracts) and LDL (150.16 and 81.28 mg/dl, for mice groups treated with respective extracts) levels as compared to the hypercholesterolaemic group (total cholesterol 253.00 mg/dl and LDL 160.00 mg/dl). Mice treated with aqueous extract (200 mg/kg body weight) showed significantly reduced triglyceride and VLDL levels as compared to the group treated with atorvastatine. HDL level of mice administered with O. europaea aqueous extract was comparable to the atorvastatine-treated group. The ethanol extract of O. europeae leaves was a potent antioxidant (IC 50 69.15 mg/ml, % inhibition 54.98, 82.63 mg ascorbic acid equivalent/g extract, 7.53 mol of Fe2+/g extract, and % inhibition 49.71, for the DPPH, β-carotene bleaching, total antioxidant capacity, FRAP, and ferric thiocyanate assays, respectively). Docking studies revealed that rutin showed higher binding affinity with HMG-CoA reductase as compared to luteolin. Data gathered from this study support the development of a prophylactic biomedicine from O. europaea leaves for the management of hypercholesterolemia and atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Alirocumab, a human monoclonal antibody, inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) to significantly reduce low-density lipoprotein cholesterol levels; pharmacokinetics (PK) are governed by non-linear, target-mediated drug disposition (TMDD).Objectives: We aimed to develop and qualify a population PK (PopPK) model to characterize the PK profile of alirocumab, evaluate the impact of covariates on alirocumab PK and on individual patient exposures, and estimate individual predicted concentrations for a subsequent PK/pharmacodynamic (PD) analysis.Methods: Data from 13 phase I-III trials of 2799 healthy volunteers or patients with hypercholesterolemia treated with intravenous or subcutaneous alirocumab (13,717 alirocumab concentrations) were included; a Michaelis-Menten approximation of the TMDD model was used to estimate PK parameters and exposures. The final model comprised two compartments with first-order absorption. Elimination from the central compartment was described by linear (CLL) and non-linear Michaelis-Menten clearance (Vm and Km). The model was validated using visual predictive check and bootstrap methods. Patient exposures to alirocumab were computed using individual PK parameters.Results: The PopPK model was well-qualified, with the majority of observed alirocumab concentrations in the 2.5th-97.5th predicted percentiles. Covariates responsible for interindividual variability were identified. Body weight and concomitant statin administration impacted CLL, whereas time-varying free PCSK9 concentrations and age affected Km and peripheral distribution volume (V3), respectively. No covariates were clinically meaningful, therefore no dose adjustments were needed.Conclusions: The model explained the between-subject variability, quantified the impact of covariates, and, finally, predicted alirocumab concentrations (subsequently used in a PopPK/PD model, see Part II) and individual exposures. [ABSTRACT FROM AUTHOR]

Background: Alirocumab, a human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly lowers low-density lipoprotein cholesterol levels.Objective: This analysis aimed to develop and qualify a population pharmacokinetic/pharmacodynamic model for alirocumab based on pooled data obtained from 13 phase I/II/III clinical trials.Methods: From a dataset of 2799 individuals (14,346 low-density lipoprotein-cholesterol values), individual pharmacokinetic parameters from the population pharmacokinetic model presented in Part I of this series were used to estimate alirocumab concentrations. As a second step, we then developed the current population pharmacokinetic/pharmacodynamic model using an indirect response model with a Hill coefficient, parameterized with increasing low-density lipoprotein cholesterol elimination, to relate alirocumab concentrations to low-density lipoprotein cholesterol values.Results: The population pharmacokinetic/pharmacodynamic model allowed the characterization of the pharmacokinetic/pharmacodynamic properties of alirocumab in the target population and estimation of individual low-density lipoprotein cholesterol levels and derived pharmacodynamic parameters (the maximum decrease in low-density lipoprotein cholesterol values from baseline and the difference between baseline low-density lipoprotein cholesterol and the pre-dose value before the next alirocumab dose). Significant parameter-covariate relationships were retained in the model, with a total of ten covariates (sex, age, weight, free baseline PCSK9, total time-varying PCSK9, concomitant statin administration, total baseline PCSK9, co-administration of high-dose statins, disease status) included in the final population pharmacokinetic/pharmacodynamic model to explain between-subject variability. Nevertheless, the high number of covariates included in the model did not have a clinically meaningful impact on model-derived pharmacodynamic parameters.Conclusions: This model successfully allowed the characterization of the population pharmacokinetic/pharmacodynamic properties of alirocumab in its target population and the estimation of individual low-density lipoprotein cholesterol levels. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A new series of small molecules have been identified as PCSK9 mRNA translation inhibitors. • Compounds 4d and 4g exhibit improved PCSK9 potency, ADME properties, and in vitro safety profiles when compared to earlier leads. • Small molecule PCSK9 inhibitors may be effective in the treatment of hypercholesterolemia. Abstract A series of N-(piperidin-3-yl)-N-(pyridin-2-yl)piperidine/piperazine-1-carboxamides were identified as small molecule PCSK9 mRNA translation inhibitors. Analogues from this new chemical series, such as 4d and 4g , exhibited improved PCSK9 potency, ADME properties, and in vitro safety profiles when compared to earlier lead structures. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases have been the major cause of mortality and morbidity all over the world accounting for more than 80% of the deaths from heart attacks and strokes. Hypercholesterolemia, an autosomal disorder of lipoprotein metabolism is one of the foremost causes of CVDs. An increased level of low-density lipoprotein cholesterol (LDL-C) in the plasma results in the rise of incidence rates in disease patients. Several conventional and combinational therapies have been proposed for lowering the LDL-C levels in the blood. These therapeutic agents are designed to target some crucial molecules that participates in the lipid metabolism such as apolipoprotein B, HMGCoA reductase, proprotein convertase subtilisin/kexin 9, etc. Although these therapies are effective but are associated with certain side effects. This article presents an overview on different conventional and nanotechnology-based approaches for the treatment and diagnosis of hypercholesterolemia. Numerous nanomaterial-based therapies including polymeric nanoparticles, cationic lipids, liposomes, dendrimers and inorganic nanoparticles have been discussed in lowering the cholesterol level along with recent advancement in diagnosis and imaging. [ABSTRACT FROM AUTHOR]

Statins are cholesterol-lowering drugs, commonly prescribed for the significant decline of high risks leading to arrhythmia and other cardiac issues. A study conducted reveals that 40% of population among the patients of cardiovascular, got arterial fibrillation with statins and 80% without statins that are mostly prescribed along with antihypertensive and if patient is diabetic, a regime of medicine is given for the management of all probable disorders and that sometimes may lead to undesired effects specifically regarding gastric. The present study is conducted to focus the root cause of digestive disorders as either medicine or condition. In present study the method adopted was cohort study and for the purpose prescription and history of case and control groups that were both hypercholestrimic and hypertensive but diabetic and non diabetic respectively. The study out comes reveal that 67% of case group reported the after effects of digestive disorders, however interestingly no such effects were observed from control group. Data analysis showed 0.24 risk ratio. The study outcomes helped to establish the idea that statins are not accountable for digestive disorders and the outcome nullify the delusion about that specific undesired effect of statins as that were only observed in diabetic patients since diabetes itself a metabolic and comorbid disorder blamed for aggravating the digestion. [ABSTRACT FROM AUTHOR]

The article describes the case of a 38-year-old man diagnosed with hypercholesterolemia and was treated with statins. Topics discussed include the involvement of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the regulation of cholesterol homeostasis, patient data during PCSK9 inhibitor treatment, and how an oxidized low density lipoprotein (LDL) marker level could be reduced.

Background. Beside the lipid-lowering effect, statins slow the progression of atherosclerosis by exerting anti-inflammatory and platelet inhibiting effects. We investigated whether platelet inhibition by simvastatin correlates with the statin effects on lipid lowering, inflammation, oxidative stress, and endothelial and platelet activation. Methods. In hypercholesterolemic patients allocated to diet (n=20) or a 2-month treatment with diet plus 40 mg simvastatin (n=25), we evaluated platelet aggregating responses to ADP, collagen, and arachidonic acid (AA), the effect of aspirin on AA-induced aggregation, pro- and anti-inflammatory and atherogenic mediators (IL-1β, -5, -6, -7, -8, -9, -10, -12, and -13, IFN-γ, IP-10, Eotaxin, and sRAGE), markers of endothelium (sE-selectin, VEGF, and MCP-1) and platelet activation (sP-selectin, sCD-40L, RANTES, and PDGF-bb), and oxidative stress (8-OH-2’-deoxyguanosine). Results. After treatment, beside the improvement of lipid profile, we observed the following: a reduction of platelet aggregation to ADP (p=0.0001), collagen (p=0.0001), AA (p=0.003); an increased antiaggregating effect of aspirin in the presence of AA (p=0.0001); a reduction of circulating levels of IL-6 (p=0.0034), IL-13 (p<0.0001), IFN-γ (p<0.0001), VEGF (p<0.0001), sE-selectin (p<0.0001), sCD-40L (p<0.0001), sP-selectin (p=0.003), and 8-OH-2’-deoxyguanosine (p<0.0001); an increase of IL-10 and sRAGEs (p=0.0001 for both). LDL-cholesterol levels (i) positively correlated with IL-6, IFN-γ, E-selectin, sCD-40L, 8-OH-2’-deoxyguanosine, platelet aggregation to ADP, collagen, AA, and aspirin IC-50 and (ii) negatively correlated with IL-10 and sRAGE. In multiple regression analyses, LDL-cholesterol was the strongest predictor for most parameters of platelet reactivity. Conclusion. In primary hypercholesterolemia, simvastatin treatment reduced platelet activation and subclinical inflammation and improved endothelial dysfunction. LDL-cholesterol levels were the major correlate of platelet reactivity; however, other effects of statins may contribute to reducing the progression of atherosclerosis. [ABSTRACT FROM AUTHOR]

Evolocumab is a PCSK9 inhibitor which is administered subcutaneously, and when added to statin therapy it has been shown to cause a significant incremental LDL-C reduction, leading to a reduction of cardiovascular risk. Evolocumab has a favorable side effect profile, and its self-administration at home appears to be safe and effective with the appropriate training and instructions from a health care provider. Current studies are showing encouraging results regarding adherence to evolocumab in real-life settings, and adherence rates to evolocumab appear to be better than those to statins. However, further larger studies are needed for a more definitive assessment of the short- and long-term patient adherence rates to evolocumab. In addition, reductions in the price of evolocumab may also be necessary to improve cost-effectiveness of the drug. [ABSTRACT FROM AUTHOR]

Abstract Background Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are established causal risk factors for cardiovascular disease (CVD). Lipoprotein apheresis is often required for treatment of patients with a high risk for CVD due to hypercholesterolemia and/or hyperlipoproteinemia(a). Aim To describe our experience with lipoprotein apheresis in patients with severe hypercholesterolemia or with hyperlipoproteinemia(a). Methods We retrospectively investigated patients treated with Lipoprotein apheresis using direct adsorption of lipoproteins (DALI) technique, between December 2008 and March 2018, in our center. Adverse events, acute and long term reductions in lipid parameters were analyzed. Results Between December 2008 and March 2018, a total of 950 treatments were performed in five patients, four with heterozygous familial hypercholesterolemia (HeFH), all on maximally tolerated cholesterol-lowering drug therapy and in one patient with hyperlipoproteinemia(a) and progressive CVD. In the four patients with HeFH we obtained mean acute reductions in LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) of 62.0 ± 7.8% and 60.4 ± 6.8%, respectively. Regarding long-term efficacy we achieved a mean reduction of 43.1% in LDL-C and of 41.2% in non-HDL-C. In the patient with hyperlipoproteinemia(a) we attained mean acute reductions of 60.4 ± 6.4% in Lp(a) and of 75.4 ± 7.3% in LDL-C per session and long term reductions in Lp(a) and LDL-C of 67.4% and 40.5%, respectively. Adverse events were recorded in only 1.2% of treatments. Conclusion Lipoprotein apheresis is an efficient and safe treatment in severely hypercholesterolemic patients who are refractory to conservative lipid-lowering therapy or with hyperlipoproteinemia(a) and progressive CVD. [ABSTRACT FROM AUTHOR]

Background and aims Induction of low-density lipoprotein receptor (LDLR) plays a significant role in reduction of plasma LDL-cholesterol (LDL-C) levels. Therefore, strategies that enhance the protein level of LDLR provide an attractive therapeutic target for the treatment of hypercholesterolemia. With this aim in mind, we concentrated our effort on studying the role of AKT kinase in regulation of LDLR levels and proceeded to examine the effect of MK-2206, an allosteric and highly selective AKT inhibitor, on LDLR expression. Methods Cultured human hepatoma cells were used to examine the effect of MK-2206 on the proteolytic processing of sterol regulatory element-binding protein-2 (SREBP-2), the expression of LDLR and cellular internalization of LDL. We also examined the effect of MK-2206 on LDLR levels in primary human hepatocytes. Results MK-2206 induced the proteolytic processing of SREBP-2, upregulated LDLR expression and stimulated LDL uptake. In contrast to statins, induction of LDLR levels by MK-2206 did not rely on 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibition. As a result, cotreatment of cells with MK-2206 and mevastatin potentiated the impact of mevastatin on LDLR. Importantly, MK-2206 stimulated the expression of LDLR by primary human hepatocytes. Conclusions MK-2206 is a novel LDLR-inducing agent that, either alone or in combination with statins, exerts a stimulating effect on cellular LDL uptake. [ABSTRACT FROM AUTHOR]

In familial hypercholesterolemia (FH), carriers profit from presymptomatic diagnosis and early treatment. Due to the autosomal dominant pattern of inheritance, first degree relatives of patients are at 50% risk. A program to identify healthy relatives at risk of premature cardiovascular problems, funded by the Netherlands government until 2014, raised questions on privacy and autonomy in view of the chosen active approach of family members. Several countries are building cascade screening programs inspired by Dutch experience, but meanwhile, the Netherlands' screening program itself is in transition. Insight in stakeholders' views on approaching family members is lacking. Literature and policy documents were studied, and stakeholders were interviewed on pros and cons of actively approaching healthy relatives. Sociotechnical analysis explored new roles and responsibilities, with uptake, privacy, autonomy, psychological burden, resources, and awareness as relevant themes. Stakeholders agree on the importance of early diagnosis and informing the family. Dutch healthcare typically focuses on cure, rather than prevention. Barriers to cascade screening are paying an own financial contribution, limited resources for informing relatives, and privacy regulation. To benefit from predictive, personalized, and preventive medicine, the roles and responsibilities of stakeholders in genetic testing as a preventive strategy, and informing family members, need to be carefully realigned. [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]