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Coronary artery disease is the major complication and leading cause of death among patients with diabetes mellitus. Oxidative stress and dyslipidemia plays an important role in the pathogenesis and the occurrence of complications in diabetic populations. Policosanol is a mixture of high molecular weight primary aliphatic alcohols isolated and purified from sugar cane wax. The objective of this randomized, double-blinded and placebo-controlled pilot study was to investigate the effect of policosanol treatment on lipid profile and plasma oxidative variables in diabetic patients with hypercholesterolemia. Thirty diabetic patients of both sexes, aged 50 to 70 years were enrolled in the study. Fifteen patients were treated with policosanol (10 mg/day) and 15 with placebo for 12 weeks. Changes in low-density lipoprotein cholesterol (LDL-C) values were considered the primary efficacy variable. Plasma oxidative markers were considered secondary efficacy variables. Baseline characteristics were well matched in both groups. After 12 weeks, policosanol produced significant reductions of LDL-C and total cholesterol, and increased highdensity lipoprotein-cholesterol. Policosanol significantly decreased serum malondialdehyde and increased the plasma total antioxidant capacity. There were no significant changes in any of the variables in the placebo group. Treatments were safe and well tolerated. No patient withdrew from the study. It is concluded that policosanol treatment favorably modified lipid profile and plasma oxidative variables in diabetic patients. Further studies should expand more data on the effects of policosanol treatment in diabetic patients. [ABSTRACT FROM AUTHOR]

Aims To elucidate the effects of intensive LDL-C lowering treatment with a standard dose of statin and ezetimibe in patients with dyslipidaemia and high risk of coronary events, targeting LDL-C less than 70 mg/dL (1.8 mmol/L), compared with standard LDL-C lowering lipid monotherapy targeting less than 100 mg/dL (2.6 mmol/L). Methods and results The HIJ-PROPER study is a prospective, randomized, open-label trial to assess whether intensive LDL-C lowering with standard-dose pitavastatin plus ezetimibe reduces cardiovascular events more than standard LDL-C lowering with pitavastatin monotherapy in patients with acute coronary syndrome (ACS) and dyslipidaemia. Patients were randomized to intensive lowering (target LDL-C < 70mg/dL [1.8mmol/L]; pitavastatin plus ezetimibe) or standard lowering (target LDL-C 90 mg/dL to 100 mg/dL [2.3-2.6mmol/L]; pitavastatin monotherapy). The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, and ischaemiadriven revascularization. Between January 2010 and April 2013, 1734 patients were enroled at 19 hospitals in Japan. Patients were followed for at least 36months. Median follow-up was 3.86 years. Mean follow-up LDL-C was 65.1mg/dL (1.68mmol/L) for pitavastatin plus ezetimibe and 84.6 mg/dL (2.19mmol/L) for pitavastatin monotherapy. LDL-C lowering with statin plus ezetimibe did not reduce primary endpoint occurrence in comparison with standard statin monotherapy (283/864, 32.8% vs. 316/857, 36.9%; HR 0.89, 95% CI 0.76-1.04, P = 0.152). In, ACS patients with higher cholesterol absorption, represented by elevated pre-treatment sitosterol, was associated with significantly lower incidence of the primary endpoint in the statin plus ezetimibe group (HR 0.71, 95% CI 0.56-0.91). Conclusion Although intensive lowering with standard pitavastatin plus ezetimibe showed no more cardiovascular benefit than standard pitavastatin monotherapy in ACS patients with dyslipidaemia, statin plus ezetimibe may be more effective than statin monotherapy in patients with higher cholesterol absorption; further confirmation is needed. [ABSTRACT FROM AUTHOR]

Suboptimal drug adherence represents a major challenge to effective primary and secondary prevention of cardiovascular disease. While adherence is influenced by multiple considerations, polypharmacy and dosing frequency appear to be rate-limiting factors in patient satisfaction and subsequent adherence. The cardiovascular and metabolic therapeutic areas have recently benefited from a number of advances in drug therapy, in particular protease proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and incretin-based therapies, respectively. These drugs are administered subcutaneously and offer efficacious treatment options with reduced dosing frequency. Whilst patients with diabetes and diabetologists are well initiated to injectable therapies, the cardiovascular therapeutic arena has traditionally been dominated by oral agents. It is therefore important to examine the practical aspects of treating patients with these new lipid-lowering agents, to ensure they are optimally deployed in everyday clinical practice. [ABSTRACT FROM AUTHOR]

Background In contrast to current guidelines in Western countries, moderate reduction of low-density lipoprotein cholesterol (LDL-C) is recommended for Japanese patients with atherosclerotic cardiovascular disease and dyslipidemia even in secondary prevention. HIJ-PROPER (Heart Institute of Japan-PRoper level of lipid lOwering with Pitavastatin and Ezetimibe in acute coRonary syndrome) is a prospective, randomized, open-label, blinded endpoint multicenter trial designed to assess whether closely controlled LDL-C lowering with a standard statin dose plus ezetimibe, targeting LDL-C of <70 mg/dL, would reduce cardiovascular events more than standard statin monotherapy targeting LDL-C of <100 mg/dL as per the Japan Atherosclerotic Society guideline in patients with acute coronary syndrome (ACS) and dyslipidemia. Methods We recruited patients with ACS and dyslipidemia who had undergone coronary angiography. Participants are randomly allocated to either intensive LDL-C lowering treatment (target LDL-C of <70 mg/dL; pitavastatin plus ezetimibe) or standard LDL-C lowering treatment (target LDL-C of 90–100 mg/dL; pitavastatin monotherapy). The primary endpoint is a composite of total death, non-fatal myocardial infarction (MI), non-fatal stroke, unstable angina, and any ischemia-driven revascularization. Patients will be followed for a minimum of 3 years. Results Between January 2010 and April 2013, 1734 patients were enrolled from 19 hospitals in Japan with a mean age of 65.6 years; 75.5% were men and 83.3% were statin-naïve. The qualifying ACS was an acute MI in 61.5%. This study is expected to report its findings in August 2016. Conclusion HIJ-PROPER will determine whether targeting LDL-C of <70 mg/dL with pitavastatin plus ezetimibe can improve cardiovascular outcomes in Japanese patients with ACS and dyslipidemia in comparison to targeting LDL-C of 90–100 mg/dL with standard pitavastatin monotherapy. Trial registration UMIN000002742. [ABSTRACT FROM AUTHOR]

Naringenin is a natural flavonoid that is widely distributed in citrus fruits and pharmacologically demonstrated to licit lipid-lowering activity. However, the clinical relevance of naringenin is limited due to its poor water solubility and inefficient absorption. In this study, we designed and developed naringenin-zein-sodium caseinate-galactosylated chitosan nanoparticles (GC-NPs) for hepatocyte-specific targeting, with naringenin-zein-sodium caseinate-chitosan nanoparticles (CS-NPs) as a control. Electrostatic adsorption was the primary binding mode in the GC-NPs and CS-NPs. Moreover, the particle size and zeta potential of GC-NPs were larger than those of CS-NPs and both types of nanoparticles had similar encapsulation rates. In vitro study experiments demonstrated that GC-NPs aggregated inside and outside of the cell membrane and significantly inhibited total triglyceride and cholesterol levels in oleic acid-induced HepG2 cells (p < 0.05). In high-fat diet-fed C57BL/6J mice, GC-NPs administration visibly improved the body weight, total cholesterol, and triglyceride content in the serum and liver, and high-density lipoprotein cholesterol levels improved, which corresponded to liver histological results. Additionally, in vitro and in vivo assays demonstrated that GC-NPs exhibited higher lipid-lowering activity than CS-NPs and naringenin monomers. These results suggest that GC-NPs are effective for oral delivery of naringenin in lipid-lowering therapies. [Display omitted] • Galactose was substituted onto chitosan to achieve liver targeting. • Naringenin supplementation attenuated HFD-induced liver lipid accumulation. • GC-NPs loaded with naringenin exhibit better lipid-lowering effect. [ABSTRACT FROM AUTHOR]

[Display omitted] • Nemopilema nomurai peptides (NNPs) were prepared by papain enzymolysis and proved to have lipid-lowering effect in 3 T3-L1 cell. • NNPs could induce synergistic remodeling in 3 T3-L1 metabolic networks to prevent the accumulation of lipid, and inhibit adipogenesis by down-regulating energy metabolism. Jellyfish peptides are of significant interest, due to their potential application as a source of bioactive peptides in pharmaceutical domains. Here, we investigated the action of Nemopilema nomurai peptides (NNPs) on lipids reduction in 3 T3-L1 adipocytes. We demonstrated for the first time that NNPs prepared by papain enzymolysis were able to reduce lipid accumulation in 3 T3-L1cells. Differentially expressed metabolites among control group, MDI group, GW9662 treatment group, and NNPs treatment group were identified using non-targeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. A total of 105 differentially expressed metabolites were identified between MDI group and NNPs treatment group. These metabolites were predominantly enriched in amino acid, carbohydrate and lipid metabolism. Metabolomics analysis indicated that NNPs leads to imbalance of lipid, which represent as down-regulated glycerolipid and glycerophospholipid, up-regulated sphingolipid metabolism and sphingolipid signaling pathway. Additionally, ATP level was significantly decreased in TCA cycle and oxidative phosphorylation pathway, which correlated with glucagon signaling pathway and fatty acid synthesis. The lipid-lowering activity of NNPs may associate with lipid and energy-related metabolism in 3 T3-T1 cell. ATP may be a potential biomarker for lipid-lowering, with a fold change of 0.534. [ABSTRACT FROM AUTHOR]

Context: Chia seeds are touted as a healthy food capable of providing a beneficial effect on high-density lipoprotein (HDL) cholesterol. Similar claims have been made for oats in various forms, claiming that they improve cholesterol or are in some way "heart healthy.", Objective:  This study aims to demonstrate the effect of daily consumption of chia seeds, if any, on HDL cholesterol levels and compare this to the effects of oats on HDL levels., Methods:  This pilot study is a randomized controlled trial performed at an academic primary care center. Participation was voluntary, and all participants provided written consent prior to enrollment. There were no exclusion criteria other than that participants must be adults and willing to come in to get their cholesterol profiles checked at the beginning and end of the study. The participants consumed their assigned breakfast in a standard serving size for a month with blood draws and weights recorded before and after the diet. The patients' cholesterol profiles were also compared with their weights. To standardize the delivery of chia seeds, the group consuming chia seeds mixed them with oatmeal. The three meal groups consisted of Cheerios (red group), oatmeal (white group), and oatmeal with chia seeds (blue group). Initially, there were a total of 11 subjects, three in the red group, four in the white group, and four in the blue group. Two subjects were lost to follow-up, one each from the red and white groups. Statistical analysis including one-way analysis was done with the means, Wilcoxon/Kruskal-Wallis, and one-way analysis tests., Results:  The results showed a similar weight gain pattern between the three groups, with an average of 2.8 lbs gained in the red group, 2.4 lbs gained in the white group, and 2.6 lbs gained in the blue group. The average HDL levels decreased by 1.00 mg/dL in the red group (standard deviation (SD) 2.82843), increased by 2.00 mg/dL in the white group (SD 8.88819), and increased by 5.75 mg/dL in the blue group (SD 8.01561). The HDL:total cholesterol ratios decreased by 0.00748 in the red group (SD 0.002660), an average of 0.04053 in the white group (SD 0.028138), and an average of 0.01614 in the blue group (SD 0.023808)., Conclusion:  The results suggest that both chia seeds and oatmeal may be good dietary sources to naturally increase HDL cholesterol, more substantially so with the diet including chia seeds, but may or may not improve total cholesterol:HDL ratios. The effect of weight gain is unclear, as all groups gained weight similarly. Hence, further study is warranted., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Dickens et al.)

Background: The impact of the stepwise implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) treatment algorithm on low-density lipoprotein cholesterol (LDL-C) goal attainment was simulated in patients from the DA VINCI study., Methods: Monte Carlo simulation was used to evaluate treatment optimisation scenarios, based on a patient's risk category: statin intensification (step 1), addition of ezetimibe (step 2), and addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (step 3). Residual cardiovascular risk and predicted relative and absolute risk reduction (RRR and ARR) in cardiovascular events were assessed., Findings: In DA VINCI, 2482 patients did not achieve their 2019 ESC/EAS LDL-C goals and were included in the simulation. In patients without atherosclerotic cardiovascular disease (ASCVD) ( n  = 962), 27.0% ( n  = 259) and 57.0% ( n  = 548 ) are likely to achieve their LDL-C goals at step 1 and step 2, respectively. Of those at very high risk without ASCVD ( n  = 74), 88.1% ( n  = 65) are likely to achieve their LDL-C goals at step 3. In patients with ASCVD ( n  = 1520), 12.0% ( n  = 183), 42.1% ( n  = 641) and 93.2% ( n  = 1416) are likely to achieve their LDL-C goals at steps 1, 2 and 3, respectively. In patients with and without ASCVD, treatment optimisation may result in mean simulated RRR of 24.0% and 17.7%, respectively, and ARR of 8.1% and 2.6%, respectively., Interpretation: Most patients at high cardiovascular risk are unlikely to achieve LDL-C goals through statin optimisation and ezetimibe, and will require a PCSK9 inhibitor, leading to greater reduction in cardiovascular risk., Funding: Amgen., Competing Interests: JB has received speaker fees from Amgen and research grant support from AstraZeneca. SB is an employee of Amgen Ltd and holds stock in Amgen. GV is an employee of Amgen (Europe) GmbH and holds stock in Amgen. ALC has received research grant(s)/support from Amgen, Eli Lilly, Menarini, Mylan, Sanofi, and Sanofi-Regeneron; and has served as a consultant for or received fees from Aegerion, Akcea, Amgen, Amryt, AstraZeneca, Daiichi Sankyo, Esperion, Genzyme, Ionis Pharmaceuticals, Kowa, Medco, Menarini, MSD, Mylan, Novartis, Recordati, Regeneron, and Sanofi. NP has received consultancy fees and financial support for research projects from Amgen and Pfizer, and financial support for arranging and speaking at educational meetings from Amgen, MSD and Pfizer. He holds no stocks and shares in any such companies. NP is supported by the National Institute for Health Research Senior Investigator Awards, Biomedical Research Centre funding, and the British Heart Foundation Research Centre Excellence Award. He has received financial support from several pharmaceutical companies which manufacture lipid lowering agents, for consultancy fees (Pfizer and Amgen), research projects and staff (Pfizer and Amgen) and for arranging and speaking at educational meetings (MSD, Amgen and Pfizer). He holds no stocks and shares in any such companies. AJV-V has participated, or is currently participating, in research grants to Imperial College London from Amgen, Daiichi Sankyo, MSD, Pfizer, Regeneron, and Sanofi-Aventis; has received personal fees for consulting from Bayer and Regeneron; and has received fees for lectures from Akcea, Amgen, Mylan and Ferrer; all outside the submitted work. KKR reports grants from Amgen, Daiichi Sankyo, MSD, Pfizer, Regeneron and Sanofi; and has received personal fees from Abbott, Amarin, Amgen, AstraZeneca, Bayer, Beren Therapeutics, Biologix Pharma, Boehringer Ingelheim, Cargene, CSL Behring, CRISPR, Eli Lilly Esperion, Kowa, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Resverlogix, Sanofi, Silence Therapeutics, SCRIBE Therapeutics, Vaxxinity and Viatris., (© 2023 The Author(s).)

Background: To assess the causal role of lipid traits and lipid-lowering agents in inflammatory bowel disease (IBD)., Methods: Univariable mendelian randomization (MR) and multivariable MR (MVMR) analyses were conducted to evaluate the causal association between low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and IBD. Drug-targeted MR analyzed the effects of lipid-lowering drugs on IBD, and network MR was used to analyze potential mediation effects., Results: The levels of HDL-C had an inverse relationship with the risk of Crohn's disease (CD, OR: 0.85, 95% CI: 0.73-0.98, P = 0.024). In MVMR, the inverse relationships were found in all three outcomes. Drug-targeted MR analyses showed that with one-SD LDL-C decrease predicted by variants at or near proprotein convertase subtilisin/kexin type 9 ( PCSK9) , the OR values of people diagnosed with IBD, ulcerative colitis (UC) and CD were 1.75 (95%CI: 1.13-2.69, P = 0.011), 2.1 (95%CI: 1.28-3.42, P = 0.003) and 2.24 (95%CI: 1.11-4.5, P = 0.024), respectively. With one-SD LDL-C decrease predicted by variants at or near cholesteryl ester transfer protein (CETP) , the OR value of people diagnosed with CD was 0.12 (95%CI: 0.03-0.51, P = 0.004). Network-MR showed that HDL-C mediated the causal pathway from variants at or near CETP to CD., Conclusion: Our study suggested a causal association between HDL-C and IBD, UC and CD. Genetically proxied inhibition of PCSK9 increased the risk of IBD, UC and CD, while inhibition of CETP decreased the risk of CD. Further studies are needed to clarify the long-term effect of lipid-lowering drugs on the gastrointestinal disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tao, Yu, Dong, Liu, Peng and Chen.)

At present, most of the research on coix seed polyphenols (CSPs) focuses on the separation, purification, structure analysis, and biological functions of specific components, and few studies have considered the overall bioavailability and the metabolites that play a role after digestion and absorption and their biological functional activities. In this study, we constructed a MKN28 and Caco-2 cell monolayer continuous transport model (MCTM) to study the bioavailability of CSPs in the digestion and absorption stages of the stomach and small intestine. Using this model, we innovatively divided CSPs into easy-to-digest and hard-to-digest polyphenols and studied their intracellular lipid-lowering function and their influence on human intestinal flora. Transwell experiments showed that ferulic acid, rutin, naringin, arbutin, and syringetin had high transmembrane transport efficiency, especially syringetin. The methylation reaction in the monolayer membrane of Caco-2 cells may be the reason for the higher transport rate of syringetin. Further experiments showed that CPL reduced TG accumulation by more than 50% during 3T3-L1 differentiation and promoted the transformation of adipocytes into brown cells ( p < 0.05). Finally, in vitro fermentation experiments showed that CSP&#95;AP can increase the abundance of Lactobacillus and Bifidobacterium of human gut microbiota at the genus level ( p < 0.05).

Hyperlipidemia is a key risk factor in inducing fatty liver, hypertension, atherosclerosis and cerebrovascular diseases. Previous studies have verified that polysaccharides from fruiting bodies (PEPE) of Pleurotus eryngii (king oyster mushroom) are capable of decreasing the lipid content. In this study, the P. eryngii polysaccharide is obtained by solid-state fermentation (PESF) using lignocellulosic wastes, corn-cobs and wheat bran. The high-performance liquid chromatography (HPLC) assays indicate that PESF has a similar composition to that of PEPE. Meanwhile, PESF has no detectable toxicity and is able to significantly inhibit foam-cell formation in murine macrophage cells (RAW264.7) induced by oxidized low-density lipoprotein. Further verification indicates that PESF has lipid-lowering effects during the lipid absorption phase in a zebrafish hyperlipidemia model. Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.

A gene-silencing platform (miQURE) has been developed and successfully used to deliver therapeutic microRNA (miRNA) to the brain, reducing levels of neurodegenerative disease-causing proteins/RNAs via RNA interference and improving the disease phenotype in animal models. This study evaluates the use of miQURE technology to deliver therapeutic miRNA for liver-specific indications. Angiopoietin-like 3 ( ANGPTL3 ) was selected as the target mRNA because it is produced in the liver and because loss-of-function ANGPTL3 mutations and/or pharmacological inhibition of ANGPTL3 protein lowers lipid levels and reduces cardiovascular risk. Overall, 14 candidate miRNA constructs were tested in vitro , the most potent of which ( miAngE ) was further evaluated in mice. rAAV5- miAngE led to dose-dependent (≤-77%) decreases in Angptl3 mRNA in WT mice with ≤-90% reductions in plasma ANGPTL3 protein. In dyslipidemic APOE∗3-Leiden.CETP mice, AAV5- miAngE significantly reduced cholesterol and triglyceride levels vs. vehicle and scrambled ( miSCR ) controls when administrated alone, with greater reductions when co-administered with lipid-lowering therapy (atorvastatin). A significant decrease in total atherosclerotic lesion area (-58% vs. miSCR ) was observed in AAV5- miAngE -treated dyslipidemic mice, which corresponded with the maintenance of a non-diseased plaque phenotype and reduced lesion severity. These results support the development of this technology for liver-directed indications., Competing Interests: V.Z. and Y.P.L. are uniQure employees, hold uniQure stocks, and are inventors on the corresponding patent application. A.V., J.M.P.L., L.P., C.V.T., H.W., T.V.Z., K.V.R., M.G., T.G., and E.E. are uniQure employees and hold uniQure stocks. E.J.P., N.K., H.M.G.P., and G.S. are employees of TNO and were employees of TNO during the time this work was conducted., (© 2023 The Author(s).)

Aim: This online interactive survey investigated lipid-lowering approaches of French cardiologists in high- and very high-cardiovascular risk patients with hypercholesterolemia. Materials & methods: Physicians assessed three hypothetical patients at three clinic visits, and selected the patients' cardiovascular risk category, target low-density lipoprotein cholesterol (LDL-C) and treatment. Results: A total of 162 physicians completed 480 risk assessments; 58% of assessments correctly categorized the hypothetical patients. Most physicians chose the correct LDL-C target for one of the very high-risk patients, but higher-than-recommended targets were selected for the other very high-risk patient and the high-risk patient. Statins were the most commonly chosen treatment. Conclusion: French cardiologists often underestimate cardiovascular risk in patients with hypercholesterolemia, select a higher-than-recommended LDL-C target and prescribe less intensive treatment than that recommended by guidelines.

Introduction: Cardiovascular disease (CVD) leads to 1 in 4 premature deaths with higher likelihood in the most deprived population1 . Consistent data demonstrated efficacy of statins in CVD prevention and mortality reduction through modifying lipid profile1,2. NICE:CG181 recommends high-intensity statin, namely atorvastatin 20mg daily in type 2 diabetes (T2DM) with high risk of developing CVD1, whilst the European Society of Cardiology suggests LDL-C target below 1.4mmol/L, the lower the better 2. In contrast, 30% of patients in Hastings Primary Care Network (PCN) are prescribed sub-optimal statin therapy3 with scope to promote medicine optimisation through modification of CVD risk factor in one of the England’s most deprived areas. Aim: Lowering patient’s CVD risk through optimising statin therapy and improving practice’s compliance with NICE:CG181. Methods: NHS Health Research Authority Decision tool was followed, ethics approval was not required. Statin prescribing data were obtained through OpenPrescribing database. This pilot study focused on the prescribing of simvastatin at one surgery within the PCN where patients were identified using the surgery medical information system with the inclusion clinical codes of: “T2DM”, “QRISK2>10%”, “latest LDL-C>1.4mmol/L” and “current simvastatin 10/20/40mg prescription”. Systematic review of patient medical records was followed, including medical history, latest lipid profile and liver function, allergies, history of statin intolerance, previous lipid therapy and frailty status determined using the electronic frailty index, Rockwood score and medical notes. Patients with heterozygous familial hypercholesterolaemia diagnosis, confirmed statin intolerance and moderately-to-severely frail were excluded. Patients were contacted to exercise shared decision-making. Once intervention agreed, prescription was initiated for prescriber authorisation. Blood test 3 months post-intervention monitored for liver function and lipid profile. Results: Search in February 2022 identified 44 patients with 39 suitable for intervention after exclusion. Thirty-six contactable patients were all switched to high intensity statin. Thirty-four were switched to atorvastatin 20 mg whilst two with prior atorvastatin intolerance were switched to rosuvastatin 10 mg. At baseline, 32 patients (88%) had cholesterol profile done within a year as per NICE:CG181. Three-month post-intervention blood tests were completed for 21, with 15 pending; 33% (7/21) had a reduction of LDL-C. In February 2022, 28.9% of the practice’s statin prescriptions were of low and medium intensity and was reduced to 25.6% post intervention. Discussion/Conclusion: All contactable patients had statin therapy optimised after exercising shared decision-making with improvement of prescribing compliance to NICE:CG181 demonstrated in this practice. Findings were inconclusive whether the intensification of statin therapy demonstrated cholesterol lowering effect in this cohort. Study limitations due to small sample size, currency of baseline profile at time of intervention and patient compliance not measured. Raised LDL-C observed could have been influenced by lifestyle changes such as poor diet and lack of exercise1 . The limitations of this study will be reviewed for future roll out across Hastings PCN. Further exploration of therapy compliance, lifestyle education and the barriers to regular blood test would facilitate such medicine optimisation intervention. In conclusion, patients prescribed with suboptimal lipid therapy should be reviewed and managed through healthy lifestyle recommendations and aggressive pharmacological intervention. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the pharmaceutical care for patients with cerebral infarction complicated with hypothyroidism in lipid-lowering drug treatment by clinical pharmacists. METHODS: Through participating in the treatment process, the clinical pharmacists analyzed the possible causes of the elevated creatine kinase, and put forward recommendations for lipid-lowering drug treatment programs. RESULTS: The clinical pharmacists believed that the elevated creatine kinase was concerned with statins and/or hypothyroidism, and suggested the clinicians to stop using atorvastatin calcium and changed by other lipid-lowering drugs such as bile acid sequestrants or nicotinic acid, so as to reduce the total cholesterol and low density lipoprotein cholesterin; in addition, statin-related drugs can be used till the thyroid function and creatine kinase values back to normal. CONCLUSIONS: Through analyzing the causes of the patient's elevated creatine kinase, the clinical pharmacists recommend the clinicians to adjust lipid-lowering therapy to avoid the occurrence of adverse drug reactions. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Although Cuphea carthagenensis (Jacq.) J. F. Macbr. is used in Brazilian folk medicine in the treatment of atherosclerosis and circulatory disorders, no study evaluating these effects has been conducted. The aim of this study was to evaluate the possible hypolipemiant and antiatherogenic activity of the ethanol soluble fraction obtained from C. carthagenensis (ES-CC) in an experimental atherosclerosis model using New Zealand (NZ) rabbits undergoing cholesterol-rich diet (CRD). Material and methods Dyslipidemia and atherogenesis were induced by administration of standard commercial diet increased of 1% cholesterol (CRD) for 8 weeks. ES-CC was orally administered at doses of 10, 30 and 100 mg/kg, once daily for four weeks, starting from the 4th week of CRD diet. Body weight measurements were weekly carried out from the beginning of experiments for 8 weeks. Serum levels of triglyceride (TG), total cholesterol (TC) and their fractions (LDL-C, VLDL-C and HDL-C) were measured at the beginning of experiments and at weeks four and eight. After euthanasia of rabbits, aorta segments (aortic arc, thoracic, abdominal and iliac segments) were macroscopically and microscopically evaluated and the intima and media layers of the arteries were measured. Additionally, the antioxidant activity of ES-CC and its influence on the functioning of hepatic antioxidant enzymes were also determined. Results CRD induced dyslipidemia and major structural changes in the aortic wall. In addition, an increase in lipid peroxidation and a reduction of hepatic glutathione and serum nitrite levels were observed. Treatment with ES-CC was able to prevent the increase in TC, LDL-C, VLDL-C levels and triglycerides and promoted an increase in HDL-C levels in NZ rabbits. These effects were accompanied by a significant reduction in oxidative stress and modulation of the catalase and superoxide dismutase function. Moreover, the intima and media layers of the arterial segments were significantly reduced by ES-CC treatment. Conclusions This study demonstrated that ES-CC reduces serum lipids and hepatic oxidative stress when orally administered to NZ rabbits. In addition, it was able to prevent the development of CRD-induced atherosclerosis. [ABSTRACT FROM AUTHOR]

Berberine (BBR) is an isoquinoline plant alkaloid endowed with several pharmacological activities, including anti-microbial, glucose- and cholesterol-lowering, anti-tumoral and immunomodulatory properties. The main mechanism by which BBR exerts a protective role in atherosclerosis relates to its cholesterol-lowering activity. BBR significantly increases hepatic low density lipoprotein receptor (LDLR) expression and reduces the expression and secretion of the LDLR modulator proprotein convertase subtilisin/kexin type 9 (PCSK9). In addition to this, several other atheroprotective effects have been ascribed to BBR, including anti-inflammatory and anti-oxidant properties, inhibition of vascular smooth muscle cell proliferation and improvement of endothelial dysfunction. BBR also increases glucose utilization in adipocytes and myocytes, while decreases glucose absorption in intestinal cells, resulting in a net hypoglycemic effect. In hypercholesterolemic animals, BBR significantly decreases LDL-C and total cholesterol (TC) levels and reduces aortic lesions, an effect similar to that of statins. In diabetic animals, BBR significantly reduces glucose levels, improves glucose tolerance, reduces body weight gain and adipose tissue mass. Several clinical studies have also tested the efficacy of BBR in humans. In hypercholesterolemic subjects, BBR induces a significant reduction of TC, triglycerides and LDL-C levels and a significant increase of HDL-C levels, without major adverse effects. BBR also reduces glycemia and plasma cholesterol in diabetic patients, improves lipid and glucose profile and decreases body mass index and waist circumference in subjects with metabolic syndrome. These findings, together with the good tolerability, suggest that BBR administration might be considered a potential therapeutic approach for the treatment of hypercholesterolemia or diabetes. Given the level of evidence available to date well-designed randomized controlled trials to test safety and efficacy of BBR are warranted. [ABSTRACT FROM AUTHOR]

Monacolin K (MK), also known as lovastatin (LOV), is a secondary metabolite synthesized by Monascus in the later stage of fermentation and is the main component of functional red yeast rice (RYR). The structure of MK is similar to 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), and it can competitively bind to 3-hydroxy-3- methylglutaryl coenzyme A reductase (HMGCR), thus reducing the level of blood lipids. MK can affect the expression of MAPK, PI3K/AKT, and NF-κB pathway, prepare conjugates with other compounds, and enhance the sensitivity of cancer cells to chemotherapeutic drugs so as to induce apoptosis of acute myeloid leukemia, prostate cancer, breast cancer, lung cancer, gastric cancer, and liver cancer. Combined with the synthetic route of MK, this paper summarizes the latest lipid-lowering and anticancer mechanism of MK, and provides a reference for the application of MK in medicine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Utilization of lipid-lowering agents has been associated with improved long-term outcomes in acute coronary syndrome (ACS) patients. However, updated data regarding local use and outcomes was lacking.Methods: We retrospectively reviewed 696 hospitalized patients in the local ACS registry of Prince of Wales Hospital during 1 January 2008 to 31 December 2009 with data retrieved using computerized clinical records of all patients.Results: Among the 402 MI patients included, 104 (25.9 %) were not prescribed with statins at discharge. Percutaneous coronary intervention (PCI) not performed or planned during hospitalization (OR: 0.324, p = 0.001) and latest lower LDL-C level before discharge (OR: 0.221 for an increment of 1 mmol/L, p = 0.009) were significant independent predictors of the absence of statin prescriptions at discharge. A significantly lower all-cause mortality rate (14.4 % vs 51.7 %, p < 0.001), fewer total hospitalizations (p < 0.001) and fewer hospitalizations due to cardiovascular problems (p < 0.001) were observed in patients discharged with statins. LDL-C goal attainment of < 2.6 mmol/L resulted in a significant reduction in mortality (10.8 % vs 24.2 %, p = 0.001), but not for goal attainment of < 1.8 mmol/L. Significant difference in survival existed only when LDL-C cut-off values were above 2.4 mmol/L.Conclusions: This study revealed the under-utilization of statin therapy in eligible MI patients at discharge and unsatisfactory percentages of LDL-C goal attainment, and also reassured the role of low LDL-C reduction to < 2.6 mmol/L in the management of MI. However, the current study did not show that the lower LDL-C reduction improved survival of ACS patients. Further research should be conducted to assess the necessity of aggressive LDL-C reduction to < 1.8 mmol/L in local patients. [ABSTRACT FROM AUTHOR]

Background: Yindan Xinnaotong capsule has been used for treating cardio-cerebrovascular diseases for several decades in China. Exercise training can protect against the development of atherosclerosis. The aim of the present study is to evaluate the joint effect of YXC and exercise on atherosclerosis in rats. Methods: A combined method involving low shear stress and a high-fat diet was used to establish the atherosclerosis model in rats. Partial ligation of the left common carotid artery was performed, and then the rats were divided into 9 treatment groups according to a 3 x 3 factorial design with two factors and three levels for each factor, swimming of 0, 0.5,1 h daily and YXC administration of 0,1, 2 g/kg p.o. daily. Next the interventions of swimming and YXC were executed for 8 weeks. After that, blood samples were collected to determine blood viscosity, plasma viscosity, haematocrit (HCT), fibrinogen (FIB), blood lipid profile (including total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C)), nitric oxide (NO), 6-keto- prostaglandin (PG) F1α, endothelin (ET) and thromboxane (TX) B2. The common carotid arteries of the rats were harvested to examine pathological changes, wall thickness and circumference, and the expression of SM22α was assayed via immune-histochemistry. Results: The early pathological changes were observed. The joint effects of YXC and swimming showed significant changes in the examined parameters: (1) decreases in plasma viscosity, blood viscosity and FIB; (2) increases in NO and 6-keto-PGF1α; (3) decreases in ET and TXB2; and (4) decreases in LDL-C and TG. The combination of 2 g/kg YXC and 1 h of swimming led to synergistic decreases in LDL-C and TG. The interactive effect between YXC and swimming was obvious in decreasing wall thickness. Swimming alone was able to up-regulate the expression of SM22α. Conclusions: In conclusion, this study indicates that the combination of YXC and swimming may prevent atherosclerosis through a synergistic effect between YXC and swimming in improving blood circulation, hemorheological parameters, blood lipids levels and the vascular endothelium in rats. The vascular remodeling may be contributed to the prevention effects on AS by up-regulating SM22α. [ABSTRACT FROM AUTHOR]

Aims To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy. Methods and results A planned interim analysis of an ongoing, open-label extension trial in patients (n = 141) with familial HC receiving a subcutaneous injection of 200 mg mipomersen weekly plus maximally tolerated lipid-lowering therapy for up to 104 weeks. The mean changes in low-density lipoprotein cholesterol (LDL-C) from baseline to weeks 26 (n = 130), 52 (n = 111), 76 (n = 66), and 104 (n = 53) were −28, −27, −27, and −28%; and in apolipoprotein B −29, −28, −30, and −31%, respectively. Reductions in total cholesterol, non-high-density lipoprotein-cholesterol, and lipoprotein(a) were comparable with decreases in LDL-C and apolipoprotein B levels. Mean high-density lipoprotein cholesterol increased from baseline by 7 and 6% at weeks 26 and 52, respectively. The long-term safety profile of mipomersen was similar to that reported in the associated randomized placebo-controlled Phase 3 trials. Adverse events included injection site reactions and flu-like symptoms. There was an incremental increase in the median liver fat during the initial 6–12 months that appeared to diminish with continued mipomersen exposure beyond 1 year and returned towards baseline 24 weeks after last drug dose suggestive of adaptation. The median alanine aminotransferase level showed a similar trend over time. Conclusion Long-term treatment with mipomersen for up to 104 weeks provided sustained reductions in all atherosclerotic lipoproteins measured and a safety profile consistent with prior controlled trials in these high-risk patient populations. Clinicaltrials.gov NCT00694109. [ABSTRACT FROM PUBLISHER]

Obesity accompanied with metabolic disorder is often complicated with a strong link of dyslipidemia and insulin resistance, whose indicator is the excess accumulation of triglycerides (TG) in cells. Consideration the idea of lipid-lowering and improving insulin resistance, 34 novel compounds by combination the xanthine scaffold with the chain of Rosiglitazone have been synthesized. Among them, several compounds showed efficiency on reducing TG in 3T3-L1 adipoctyes, and 11c exhibited the most optimal capacity in lipid-lowering and improving obese clinical symptoms in DIO mice. Furthermore, the hydrochloride of 11c ( 11c · HCl ) showed excellent bioavailability, 58.94%, over 2 folds than that (28.03%) of 11c , and the anti-obesity effect of 11c · HCl at 50 mg/kg dose was better than that of Metformin at 150 mg/kg dose in DIO mice, almost reversed HFD to a normal level. Thus, 11c · HCl might be a potent and orally available anti-obesity agent via alleviating the obese clinical symptoms, body fat, improving serum parameters and insulin resistance and TG clearance in liver. [ABSTRACT FROM AUTHOR]

Previous studies have found that the protein in barley extract fermented by Lactiplantibacillus plantarum dy-1 has the ability to inhibit lipid accumulation. However, the isolation, purification, and structural identification of the protein with lipid-lowering activity were still needed. In the present study, barley protein fermented by L. plantarum dy-1 with the optimal lipid-lowering ability was isolated and purified in three steps: using ammonium sulfate precipitation, anion-exchange chromatography, and size-exclusion chromatography. Combined with the model of HepG2 cells induced by oleic acid, the results showed that the pure protein LFBEP-C1 had the best lipid-lowering potential. Furthermore, our research found that LFBEP-C1 enriched the content of hydrophobic amino acids in LFBEP-C1. Ultraviolet spectroscopy analysis indicated that the glycosidic bond in LFBEP-C1 was an O-type glycosidic bond. The FTIR and circular dichroism spectra indicated that α-helix and random coil were the main secondary structures of LFBEP-C1. Mass spectrometry determined the theoretical molecular weight of LFBEP-C1 as 48 kDa, and its amino acid coverage was 63%. These findings suggest that the protein LFBEP-C1 with the best lipid-lowering activity was isolated and purified, and its structural characteristics were identified.

Background: Polymorphisms of the apolipoprotein E (APOE) gene are related to the efficacy of statin therapy. The biological functions of the APOE subtypes determine the metabolism of blood plasma lipids and the progression of atherosclerosis. This study aimed to explore the impact of APOE gene polymorphisms on the effect of atorvastatin on lipid regulation and plaque stabilization., Methods: The study was a prospective cohort study that consecutively included patients with acute ischemic stroke (AIS) in the Department of Neurology, Shanghai Tenth People's Hospital, from December 2018 to December 2019. The patients were divided into E2, E3, and E4 groups according to their APOE genotype. Atorvastatin (20 mg) was administrated to all patients. Changes in blood lipid levels over 3 months and plaque size and stability over 12 months were analyzed., Results: We enrolled 253 consecutive patients with AIS, of whom, 136 had carotid atherosclerotic plaques. Two patients with genotype E2/E4 were excluded. There were 30 patients in the E2 group (12.0%), 191 patients in the E3 group (76.0%), and 30 patients in the E4 group (12.0%). The lowest percentage reduction in low-density lipoprotein cholesterol (LDL-C) was observed in the E4 group (41.2%), while the highest percentage reduction was observed in the E2 group (17.6%). The plaques in the E2 group showed slower progression, while those in the E4 group showed more rapid progression., Conclusion: APOE gene polymorphisms affect the biological functions of atorvastatin. Compared to the ε3 or ε4 allele, the ε2 allele exerted a greater lipid-lowering effect on LDL-C levels, enhanced the ability of atorvastatin to stabilize carotid artery plaques, and slowed carotid artery plaque progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bi, Zhou, Lu, Fu, Wang, Wang and Wang.)

Introduction: Patients with severe mental illness (SMI) have a high risk for diabetes, dyslipidemia, and other components of metabolic syndrome. Patients with these metabolic comorbidities and cardiac risk factors should receive not only antipsychotics but also medications aiming to reduce cardiovascular risk. Therefore, many patients may be exposed to clinically relevant drug-drug interactions., Areas Covered: This narrative review summarizes data regarding the known or potential drug-drug interactions between antipsychotics and medications treating metabolic syndrome components, except for hypertension, which has been summarized elsewhere. A literature search in PubMed and Scopus up to 7/31/2021 was performed regarding interactions between antipsychotics and drugs used to treat metabolic syndrome components, aiming to inform clinicians' choice of medication for patients with SMI and cardiometabolic risk factors in need of pharmacologic interventions., Expert Opinion: The cytochrome P450 system and, to a lesser extent, the P-glycoprotein transporter is involved in the pharmacokinetic interactions between antipsychotics and some statins or saxagliptin. Regarding pharmacodynamic interactions, the available information is based mostly on small studies, and for newer classes, like PCSK9 inhibitors or SGLT2 inhibitors, data are still lacking. However, there is sufficient information to guide clinicians in the process of selecting safer antipsychotic-cardiometabolic risk reduction drug combinations.

[Display omitted] • S. cerevisiae and L. plantarum sequentially fermented dealcoholized apple juice has the effect of reducing fat and regulating fatty liver. • Long-term consumption of low-alcohol cider under high-fat diet can aggravate fatty liver and inflammation of the body. • S. cerevisiae and L. plantarum sequentially fermented dealcoholized apple juice reduce inflammation by regulating the LPS/LBP/CD14/TLR4 signaling pathway. • Genes MBOAT7 , TMC4 , CYP2E1 and CYP7A1 have potential mechanisms for lipid accumulation and fatty liver regulation. • S. cerevisiae and L. plantarum sequentially fermented dealcoholized apple juice enrich the gut microbial abundance and short-chain fatty acid content. Low-alcohol beverages damage the liver, whereas dealcoholized apple juice sequentially fermented by Saccharomyces cerevisiae and Lactobacillus plantarum is a promising dietary intervention for hyperlipidaemia as a functional non-alcoholic beverage that lowers lipid levels and regulates fatty liver. However, their mechanisms of action have not been identified. In this study, we found that low-alcohol cider exacerbated inflammation in mice on a high-fat diet, up-regulate fatty liver CYP2E1 gene, and inhibit the expression of MBOAT7 and TMC4. Apple juice traditionally fermented by S. cerevisiae and then dealcoholized, followed by sequential fermentation by L. plantarum , can improve obesity and fatty liver, reduce the production of liver cholesterol and fat accumulation, and promote the production of short-chain fatty acids. Our research demonstrates that the lipopolysaccharide/lipopolysaccharide-binding protein/cluster of differentiation 14 protein/Toll-like receptor 4 protein signaling pathway affects the occurrence of obesity and inflammation in mice, and the expression of CYP7A1 inhibits the production of lipids. Further research reveals that L. plantarum sequentially fermented dealcoholized apple juice not only regulate and restore the intestinal flora, but also change the ratio of Firmicutes -to- Bacteroides , and decreased endotoxin-bearing Proteobacteria levels. Together, this functional product may be a potential dietary strategy to interfere with hyperlipidemia and obesity-related metabolic disorders. [ABSTRACT FROM AUTHOR]

Abstract: Background: Current guidelines recommend intensive low-density lipoprotein (LDL) cholesterol lowering with statins, with a target of 70mg/dL (1.81mmol/L) LDL cholesterol for those with a very high risk of coronary artery events. However, there is no multicenter study assessing the effect of intensive lipid-lowering therapy with statins on acute coronary syndrome (ACS) in a Chinese population with low baseline LDL cholesterol levels. Methods and results: Patients (n =1355) with ACS were treated with a moderate dose of statin (atorvastatin 10 mg/d, or equivalent dose of other statins, n =675) or with an intensive dose of statin (atorvastatin, 20 or 40mg/d, or equivalent dose of other statins, n =680) for 2 years. The primary end points were cardiac death, non-fatal acute myocardial infarction (MI), revascularization, ischemic stroke and documented unstable angina or severe heart failure requiring emergency hospitalization. Baseline lipid levels were nearly identical in both groups with a mean LDL cholesterol level of 2.7mmol/L (103mg/dL). At 3 months, LDL cholesterol levels declined 20.2% in the moderate dose statin group and 26.6% in the intensive statin group, respectively (P <0.001). In a 2-year follow-up, a primary end point event occurred in 20 patients in the moderate dose statin group and in 28 patients in the intensive statin group. There was no significant between-group difference in the primary outcome (hazard ratio, 1.39; 95% confidence interval [CI], 0.78–2.46; P =0.245). Conclusions: For ACS patients with a relatively low baseline LDL cholesterol level who received optimized current medication and interventional therapy, the incremental LDL cholesterol reduction of 6.4% achieved by double-dose statin did not bring significant clinical effectiveness. [Copyright &y& Elsevier]

Aims: Elevated body mass index (BMI) is an important cause of cardiovascular disease (CVD). The population-level impact of pharmacologic strategies to mitigate the risk of CVD conferred by the metabolic consequences of an elevated BMI is not well described., Methods and Results: We conducted an analysis of 145 986 participants (mean age 50 years, 58% women) from 21 high-, middle-, and low-income countries in the Prospective Urban and Rural Epidemiology study who had no history of cancer, ischaemic heart disease, heart failure, or stroke. We evaluated whether the hazards of CVD (myocardial infarction, stroke, heart failure, or cardiovascular death) differed among those taking a cardiovascular medication (n = 29 174; including blood pressure-lowering, blood glucose-lowering, cholesterol-lowering, or anti-thrombotic medications) vs. those not taking a cardiovascular medication (n = 116 812) during 10.2 years of follow-up. Cox proportional hazard models with the community as a shared frailty were constructed by adjusting age, sex, education, geographic region, physical activity, tobacco, and alcohol use. We observed 7928 (5.4%) CVD events and 9863 (6.8%) deaths. Cardiovascular medication use was associated with different hazards of CVD (interaction P &lt; 0.0001) and death (interaction P = 0.0020) as compared with no cardiovascular medication use. Among those not taking a cardiovascular medication, as compared with those with BMI 20 to &lt;25 kg/m2, the hazard ratio (HR) [95% confidence interval (95% CI)] for CVD were, respectively, 1.14 (1.06-1.23); 1.45 (1.30-1.61); and 1.53 (1.28-1.82) among those with BMI 25 to &lt;30 kg/m2; 30 to &lt;35 kg/m2; and ≥35 kg/m2. However, among those taking a cardiovascular medication, the HR (95% CI) for CVD were, respectively, 0.79 (0.72-0.87); 0.90 (0.79-1.01); and 1.14 (0.98-1.33). Among those not taking a cardiovascular medication, the respective HR (95% CI) for death were 0.93 (0.87-1.00); 1.03 (0.93-1.15); and 1.44 (1.24-1.67) among those with BMI 25 to &lt;30 kg/m2; 30 to &lt;35 kg/m2; and ≥35 kg/m2. However, among those taking a cardiovascular medication, the respective HR (95% CI) for death were 0.77 (0.69-0.84); 0.88 (0.78-0.99); and 1.12 (0.96-1.30). Blood pressure-lowering medications accounted for the largest population attributable benefit of cardiovascular medications., Conclusion: To the extent that CVD risk among those with an elevated BMI is related to hypertension, diabetes, and an elevated thrombotic milieu, targeting these pathways pharmacologically may represent an important complementary means of reducing the CVD burden caused by an elevated BMI., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Dyslipidemias are disorders of plasma levels of lipids, such as elevated levels of total cholesterol and triglyceride, that are associated with various human diseases including cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). Statins are the first-line drugs for treatment of dyslipidemia. However, a substantial proportion of patients cannot reach the recommended LDL-c level even with the highest tolerated doses of statins, and there is no available drug specifically for NAFLD therapy. Sea cucumbers are one of the widely distributed invertebrates, and are an important resource of food and medicine. Sea cucumbers have many valuable nutrients including saponins, fatty acids, phospholipids, cerebrosides, sulfated polysaccharides, as well as proteins and peptides. In recent years, these natural products derived from sea cucumbers have attracted attentions for treatment of CVD and NAFLD because of their lipid-lowering effect and low toxicity. However, the hypolipidemic mechanisms of action and the structure-activity relationship of these bioactive components have not been well-documented in literature. This review article summarizes the signaling pathways and the potential structure-activity relationship of sea cucumber-derived bioactive compounds including saponins, lipids, carbohydrates as well as peptides and proteins. This article will provide information useful for the development of sea cucumber-derived lipid-lowering compounds as well as for investigation of hypolipidemic compounds that are derived from other natural resources., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Shen, Yin and Guo.)

The saponins in different parts of Gynostemma pentaphyllum were analyzed via UPLC-Q-TOF-MS~E. A total of 46 saponins were identified, and the underground part had 26 saponins more than the aboveground part, most of which were trisaccharide saponins. The rat model of hyperlipidemia was established with high-fat diet. This study explored the lipid-lowering activity of total saponins in the underground part of G. pentaphyllum, so as to provide a theoretical basis for the comprehensive utilization of the underground part of G. pentaphyllum. A total of 99 healthy SD rats were randomly assigned into a blank group, a model group, a positive drug group, an aboveground total saponins group, and low-, medium-, and high-dose underground total saponins groups. Except the blank group, the other groups were fed with high-fat diet for 6 weeks. Then, the blood was collected from the orbital cavity to determine whether the modeling was successful according to the serum levels of total cholesterol(TC) and triglyceride(TG). After intragastric administration of the corresponding agents for 30 continuous days, the physical state of the rats were observed, and the body weight and liver specific gravity were measured. Furthermore, the levels of TC, TG, low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), alanine transaminase(ALT), aspartate transaminase(AST), bilirubin, and total bile acids in serum, as well as the levels of superoxide dismutase(SOD), malondialdehyde(MDA), peroxidase proliferator-activated receptor(PPAR-γ) in the liver tissue, were determined. The pathological changes of liver was observed via HE staining. The results showed that the aboveground total saponins and medium-and high-dose underground total saponins can treat hepatocyte steatosis, lower TC, TG, LDL-C, ALT, AST, total bilirubin, MDA, and PPAR-γ levels, and increase HDL-C and SOD levels in the model rats. The effect tended to be more obvious with the increase in dosage. Therefore, the total saponins in the underground part of G. pentaphyllum have good pharmacological effect of reducing blood lipid, which provides a theoretical basis for the comprehensive utilization of the underground part of G. pentaphyllum.

Abstract: Ethnopharmacological relevance: Atherosclerosis (AS) can result in severe cardiovascular diseases. Early indications of AS include disorders in lipid metabolism, inflammatory responses, and endothelial dysfunction. Statins are the preferred drugs for stabilizing atherosclerotic plaques because of their lipid-lowering, anti-inflammation and endothelial-protection activities. However, they can exhibit side effects and are effective in only one-third of patients. Many natural products (especially traditional Chinese medicines (TCMs)) possessing similar lipid-lowering, anti-inflammation and antioxidant activities are of interest in many studies exploring new AS drug therapy. The widely distributed hawthorn is used to prevent and cure heart disease not only in China but also in the United States and several European countries. For example, the fruit of Crataegus pinnatifida Bge. and Crataegus pinnatifida Bge. var. major N.E.Br. (a commonly used hawthorn fruit in China) is used in combination with other TCMs to treat AS. Studies have also shown that the water extracts of these two hawthorn fruits are effective against hyperlipidemia by lowering lipid levels, reducing endothelial dysfunction, and inhibiting inflammation. The aim of the study is to investigate the effect and possible mechanisms of the aqueous extract of Crataegus pinnatifida var. major on AS rats. Materials and methods: The fruit of Crataegus pinnatifida var. major was extracted with 70% ethanol; the ethanol extract was chromatographed on a D101 macroporous resin to obtain a sugar-free aqueous extract (AECP). Atherosclerotic rats were fed a high-fat diet and injected with vitamin D3 and ovalbumin. Rats were divided into five groups: normal, model, model plus simvastatin, model plus low-dose AECP, and model plus high-dose AECP. AECP and simvastatin were administered (via the intragastric route) to AECP groups and the simvastatin group. For normal and model groups, water was given for 4 weeks. After 12 weeks, levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) in blood were measured by an automatic biochemistry analyzer. Serum concentrations of interleukin (IL)-1β, IL-8, nitric oxide (NO), endothelin (ET), 6-keto-prostaglandin F1α (6-keto-PGF1α) and thromboxane B2 (TXB2) were determined by radioimmunoassay (RIA). Serum concentrations of C-reactive protein (CRP) and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA). Pathological changes in arteries were observed using an optical microscope and the intima-media thickness (IMT) calculated. Cholesterol deposition was evaluated by filipin staining. Chemical ingredients in AECP were analyzed by qualitative and quantitative means by high-performance liquid chromatography (HPLC). Results: AECP significantly reduced the levels of TC, TG and LDL-C but increased HDL-C levels. It also decreased the concentrations of CRP, IL-1β, IL-8 and IL-18. AECP increased levels of ET and TXB2 but increased 6-keto-PGF1α levels. Histopathological examination showed that AECP inhibited pathological changes in the arteries of AS rats and reduced IMT. Chemical analysis suggested that the main components of AECP were chlorogenic acid, procyanidin B2, (−)-epicatechin, rutin and isoquercitrin. Conclusions: These data suggest that AECP can inhibit AS progression in high-fat-diet-fed rats. Possible mechanisms of action include improvement of lipid metabolism, decrease in inflammatory cytokine responses, and protection of the endothelium. [Copyright &y& Elsevier]

Abstract: Objective: This study attempts to identify a structure among patient-related factors that could predict treatment adherence in statin patients, especially with regards to the necessity-concern framework. Methods: 414 Swedish patients using statins completed a questionnaire about their health, treatment, locus of control, perception of necessity-concern and adherence. The data were handled using a structural equation modeling approach. Results: Patients that reported high perceptions of necessity to treatment seemed to adhere well, and side effects appear to affect adherence negatively. Disease burden, cardiovascular disease experience and high locus of control seem to have mediating effects on adherence. Conclusion: This study provides support for the hypothesis that health- and treatment-related factors, as well as locus of control factors, are indirectly associated with treatment adherence via their association with mediating factor necessity. Practice implications: This study highlights the importance of considering patients’ beliefs about medications, disease burden, experience of cardiovascular events and locus of control as these factors are associated with adherence behavior to statin treatment. This study also emphasizes more generally the importance of an approach targeting necessity and concern when communicating with and treating patients with lipid-lowering medication. [Copyright &y& Elsevier]

Statins are highly effective drugs prescribed to millions of people to lower LDL-cholesterol and decrease cardiovascular risk. The benefits of statin therapy seen in randomized clinical trials will only be replicated in real-life if patients adhere to the prescribed treatment regimen. But, about half of patients discontinue statin therapy within the first year, and adherence decreases with time. Patient, physician and healthcare system-related factors play a role in this problem. Recent studies have focused more on the patients' perspectives on non-adherence. Adverse events are cited as the most common cause of statin discontinuation; thus, the healthcare provider must be willing to ally and dialogue with patients to address concerns and assess the risks and benefits of continued statin therapy. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is still the leading cause of death globally, and atherosclerosis is the main pathological basis of CVDs. Low-density lipoprotein cholesterol (LDL-C) is a strong causal factor of atherosclerosis. However, the first-line lipid-lowering drugs, statins, only reduce approximately 30% of the CVD risk. Of note, atherosclerotic CVD (ASCVD) cannot be eliminated in a great number of patients even their LDL-C levels meet the recommended clinical goals. Previously, whether the elevated plasma level of triglyceride is causally associated with ASCVD has been controversial. Recent genetic and epidemiological studies have demonstrated that triglyceride and triglyceride-rich lipoprotein (TGRL) are the main causal risk factors of the residual ASCVD. TGRLs and their metabolites can promote atherosclerosis via modulating inflammation, oxidative stress, and formation of foam cells. In this article, we will make a short review of TG and TGRL metabolism, display evidence of association between TG and ASCVD, summarize the atherogenic factors of TGRLs and their metabolites, and discuss the current findings and advances in TG-lowering therapies. This review provides information useful for the researchers in the field of CVD as well as for pharmacologists and clinicians., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Yin, Qiao and Guo.)

Bile acids, the endogenous steroid nucleus containing signaling molecules, are responsible for the regulation of multiple metabolic processes, including lipoprotein and glucose metabolism to maintain homeostasis. Within our body, they are directly produced from their immediate precursors, cholesterol C (low-density lipoprotein C, LDL-C), through the enzymatic catabolic process mediated by 7-α-hydroxylase (CYP7A1). Bile acid sequestrants (BASs) or amphiphilic resins that are nonabsorbable to the human body (being complex high molecular weight polymers/electrolytes) are one of the classes of drugs used to treat hypercholesterolemia (a high plasma cholesterol level) or dyslipidemia (lipid abnormalities in the body); thus, they have been used clinically for more than 50 years with strong safety profiles as demonstrated by the Lipid Research Council-Cardiovascular Primary Prevention Trial (LRC-CPPT). They reduce plasma LDL-C and can slightly increase high-density lipoprotein C (HDL-C) levels, whereas many of the recent clinical studies have demonstrated that they can reduce glucose levels in patients with type 2 diabetes mellitus (T2DM). However, due to higher daily dosage requirements, lower efficacy in LDL-C reduction, and concomitant drug malabsorption, research to develop an "ideal" BAS from sustainable or natural sources with better LDL-C lowering efficacy and glucose regulations and lower side effects is being pursued. This Review discusses some recent developments and their corresponding efficacies as bile removal or LDL-C reduction of natural biopolymer (polysaccharide)-based compounds.