Cholesterol-lowering Efficacy Research Articles

Comparative Efficacy of Colchicine and Intensive Low-density Lipoprotein Cholesterol Lowering in Patients with Atherosclerotic Diseases receiving Statins: A Network Meta-analysis of Randomized Controlled Trials.

Adding intensive low-density lipoprotein cholesterol (LDL-C)-lowering agents or colchicine to statin has been shown to result in additional cardiovascular benefits for patients with atherosclerotic cardiovascular diseases (ASCVD). We aimed to compare the efficacy and safety of these supplementary agents in patients with ASCVD receiving statin. We performed a systematic review and frequentist network meta-analysis of randomized controlled trials. The primary efficacy endpoint was the main adverse cardiovascular event (MACE), and the secondary efficacy endpoints were myocardial infarct, stroke, coronary revascularization, cardiovascular death, and all-cause mortality, respectively. The safety endpoints were treatment discontinuation and non-cardiovascular death. We obtained estimates for efficacy outcomes and safety endpoints and presented these estimates as risk ratio (RR) with 95% confidence intervals. We ranked the comparative efficacy and safety of all drugs with P-scores. Seventeen trials totaling 85,823 participants treated with colchicine (5926 participants), intensive LDL-C lowering (37,854 participants) via proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, Niemann-Pick C1-like 1 protein (NPC1L1) inhibitor or ATP citrate lyase (ACL) inhibitor, or statin alone (42,043 participants) were included. Colchicine was associated with a greater reduction in the risk of MACE (RR 0.72, 0.69-0.91), stroke (RR 0.55, 0.33-0.92), and coronary revascularization (RR 0.73, 0.60-0.90) compared with NPC1L1 inhibitor, and it provided a larger reduction in the risk of MACE (RR 0.79, 0.69-0.91) compared to PCSK9 inhibitor. However, colchicine was associated with increased risk of non-cardiovascular death compared with NPC1L1 inhibitor (RR 1.48, 1.04-2.10) and PCSK9 inhibitor (RR 1.57, 1.08-2.27). Although no regimen prolonged survival, colchicine had worse performance on non-cardiovascular death and all-cause mortality. In patients with ASCVD receiving statin, colchicine seems to be more effective than intensive LDL-C-lowering therapy with PCSK9 inhibitor or NPC1L1 inhibitor for cardiovascular prevention. However, using colchicine as an alternative to intensive LDL-C-lowering therapy may need to be weighed against the cardiovascular benefits and the potential harms of higher non-cardiovascular death. PROSPERO Identifier: CRD42023441385.

Discovery of Novel 11-Membered Templates as Squalene Synthase Inhibitors.

Squalene synthase is one of the most promising pharmaceutical targets to treat hyperlipidemia. Inhibition of the squalene synthase causes a decrease in the hepatic cholesterol concentration. We have already reported the design and synthesis of highly potent benzhydrol-type squalene inhibitors. Although these templates showed unique and potent cyclic active conformations via intramolecular hydrogen bonds, the in vivo cholesterol-lowering efficacy was insufficient. We attempted to improve their potential as an orally active medicine. In our medicinal chemistry effort, cyclized 11-membered ring templates were acquired. The novel series of compounds exhibited potent squalene synthase inhibitory activity, and one of the derivatives, isomer A-(1S, 3R)-14i, showed plasma lipid-lowering efficacy in hamster and marmoset repeated-dose studies. Our findings provide valuable insights into the design and development of novel and unique 11-membered ring-type highly potent squalene synthase inhibitors.

The profile of cholesterol metabolism does not interfere with the cholesterol-lowering efficacy of phytostanol esters

Increasing evidence suggests that high cholesterol absorption efficiency enhances the risk of atherosclerotic cardiovascular diseases. It is not known whether inhibiting cholesterol absorption has different metabolic effects in high- vs. low cholesterol absorbers. We evaluated the effects of phytostanol esters on serum lipids and cholesterol metabolism in a post hoc study of three randomized, double-blind, controlled trials. The participants were classified into low (n=20) and high (n=21) cholesterol absorbers by median cholesterol absorption efficiency based on the plasma cholesterol absorption marker cholestanol at baseline. The participants consumed mayonnaise or margarine without or with phytostanol esters for six to nine weeks without other changes in the diet or lifestyle. Serum cholesterol, cholestanol, lathosterol, and faecal neutral sterols and bile acids were analysed by gas-liquid chromatography. According to power calculations, the size of the study population (n=41) was appropriate. During the control period, cholesterol synthesis, and faecal neutral sterols and bile acids were lower in high- vs. low absorbers (p<0.05 for all). Phytostanol esters reduced low-density lipoprotein cholesterol by 10-13% in both groups, and directly measured cholesterol absorption efficiency by 41±7% in low- and 47±5% in high absorbers (p<0.001 for all) without side effects. Cholesterol synthesis and faecal neutral sterols (p<0.01) increased in both groups, more markedly in the high vs. low absorbers (p<0.01). Low cholesterol absorption combined with high faecal neutral sterol excretion are components of reverse cholesterol transport. Thus, high- vs. low absorbers had a more disadvantageous metabolic profile at baseline. In both groups, phytostanol esters induced favourable changes in serum, lipoprotein, and metabolic variables known to help in prevention of the development of atherosclerotic cardiovascular diseases.

Sex Differences in Cardiovascular Outcomes and Cholesterol-Lowering Efficacy of PCSK9 Inhibitors: Systematic Review and Meta-Analysis

BackgroundGuideline-recommended low-density lipoprotein cholesterol (LDL-C) thresholds are often not achieved in women. The proprotein convertase subtilisin/kexin type-9 inhibitor (PCSK9i) monoclonal antibodies can help further reduce LDL-C and major adverse cardiovascular events (MACE) although differences in efficacy by sex and type are less understood. ObjectivesThe authors sought to determine if there are differences in the efficacy of LDL-C lowering and reduction in the risk of MACE by sex and type of PCSK9i. MethodsA comprehensive literature search was done through October 17, 2022, for published trials comparing PCSK9i vs control. Outcomes assessed were LDL-C reduction and incidence of MACE following the use of PCSK9i vs placebo, stratified by sex and type of PCSK9i used. ResultsWe identified 16 trials with 54,996 adults, and 15,143 (27.5%) of them were female. PCSK9i significantly reduced MACE compared to placebo in both women (HR: 0.86, 95% CI: 0.74-0.97, P < 0.001) and men (HR: 0.85, 95% CI: 0.79-0.91, P < 0.001) with no significant sex difference (MD −0.01, 95% CI: −0.14 to −0.13, P = 0.930). PCSK9i also significantly reduced LDL-C levels in both sexes at 12 weeks (females: MD −62.57, 95% CI: −70.24 to −54.91, P < 0.001; males: MD −66.19, 95% CI: −72.03 to −60.34, P < 0.001) and 24 weeks (females: MD −47.52, 95% CI: −52.94 to −42.09, P < 0.001; males: MD −54.07, 95% CI: −59.46 to −48.68, P < 0.001). Significant sex difference was seen in the LDL reduction of PCSK9i for both 12 weeks (males vs females: MD −4.55, 95% CI: −7.34 to −1.75, P < 0.01) and 24 weeks (males vs females: MD −7.11, 95% CI: −9.99 to −4.23, P < 0.001). ConclusionsThe use of PCSK9i results in significant LDL-C and MACE reduction in both males and females. While there is no significant sex difference in MACE reduction, LDL-C reduction is greater in males than in females. Our data support the equal use of PCSK9i in all eligible patients, regardless of sex.

A virus-like particle-based bivalent PCSK9 vaccine lowers LDL-cholesterol levels in non-human primates

Elevated low-density lipoprotein cholesterol (LDL-C) is an important risk factor in the development of atherosclerotic cardiovascular disease (ASCVD). Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9), a negative regulator of LDL-C metabolism, have emerged as promising approaches for reducing elevated LDL-C levels. Here, we evaluated the cholesterol-lowering efficacy of virus-like particle (VLP) based vaccines that target epitopes found within the LDL receptor (LDL-R) binding domain of PCSK9. In both mice and non-human primates, a bivalent VLP vaccine targeting two distinct epitopes on PCSK9 elicited strong and durable antibody responses and lowered cholesterol levels. In macaques, a VLP vaccine targeting a single PCSK9 epitope was only effective at lowering LDL-C levels in combination with statins, whereas immunization with the bivalent vaccine lowered LDL-C without requiring statin co-administration. These data highlight the efficacy of an alternative, vaccine-based approach for lowering LDL-C.

Lipid lowering effects and safety of evolocumab in Chinese patients at very high cardiovascular risk: a single-center study.

Lipid lowering effects and safety of evolocumab in Chinese patients at very high cardiovascular risk: a single-center study.

Co-Amorphous Formation of Simvastatin-Ezetimibe: Enhanced Physical Stability, Bioavailability and Cholesterol-Lowering Effects in LDLr-/-Mice.

Hypercholesterolemia is one of the independent risk factors for the development of cardiovascular diseases such as atherosclerosis. The treatment of hypercholesterolemia is of great significance to reduce clinical cardiovascular events and patient mortality. Simvastatin (SIM) and ezetimibe (EZE) are commonly used clinically as cholesterol-lowering drugs; however, their treatment efficacy is severely affected by their poor water solubility and low bioavailability. In this study, SIM and EZE were made into a co-amorphous system to improve their dissolution, oral bioavailability, storage stability, and cholesterol-lowering effects. The SIM-EZE co-amorphous solids (CO) were prepared successfully using the melt-quenched technique, and the physicochemical properties of CO were characterized accordingly, which exhibited improved physical stability and faster dissolution release profiles than their physical mixture (PM). In the pharmacokinetic study, the SIM-EZE CO or PM was given once by oral gavage, and mouse blood samples were collected retro-orbitally at multiple time points to determine the plasma drug concentrations. In the pharmacodynamic study, low-density lipoprotein receptor-deficient (LDLr−/−) mice were fed with a high-fat diet (HFD) for two weeks to establish a mouse model of hypercholesterolemia. Using PM as a control, we investigated the regulation of CO on plasma lipid levels in mice. Furthermore, the mice feces were collected to determine the cholesterol contents. Besides, the effect of EZE on the NPC1L1 mRNA expression level in the mouse intestines was also investigated. The pharmacokinetics results showed that the SIM-EZE CO has improved bioavailability compared to the PM. The pharmacodynamic studies showed that SIM-EZE CO significantly increased the cholesterol-lowering effects of the drugs compared to their PM. The total cholesterol excretion in the mouse feces and inhibitory effect on NCP1L1 gene expression in the mouse intestines after being given the SIM-EZE CO were more dramatic than the PM. Our study shows that the SIM-EZE CO prepared by the melt-quenched method can significantly improve the stability, bioavailability, and cholesterol-lowering efficacy with excellent development potential as a new drug formulation.

Meta-analysis of randomized controlled trials examining the safety and efficacy of bempedoic acid

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Bempedoic acid (BA), an inhibitor of ATP citrate lyase, has emerged as a new therapy for patients with dyslipidemia. The objective of this study was to perform a meta-analysis of BA's safety and cholesterol lowering efficacy. Methods A meta-analysis was performed using RCTs testing the safety and efficacy of BA versus placebo. The primary analysis calculated the odds ratio (OR) and 95% confidence interval (CI) of any adverse events, muscular-related AEs including myopathy, muscle weakness, and myalgias, as well as serious AEs as self-defined by the individual RCT. Additionally, we evaluated the mean difference (MD) and CI of low density lipoprotein-cholesterol (LDL-C), non-high density lipoprotein-cholesterol (non-HDL-C), total cholesterol (TC), and apolipoprotein B (ApoB) at 12 weeks, as well as LDL-C at 24 weeks of BA use as compared to placebo. Results Four RCTs were identified comparing BA to placebo. There was no increased risk of any AE [OR 1.04; 95%CI 0.89, 1.22], serious AE [OR 1.07; 95%CI 0.87, 1.34], or muscular-related AE [OR 1.25; 95%CI 0.98, 1.58] with BA use compared to placebo. BA resulted in a significant reduction in LDL-C [MD -21.06; 95%CI -24.49, -17.62], TC [MD -16.02; 95%CI -19.09, -12.93], non-HDL-C [MD -17.84; 95%CI -21.34, -14.34], and ApoB [MD -14.19; 95%CI -17.18, -11.21] at 12 weeks, and LDL-C at 24 weeks [MD -16.42; 95%CI -18.15, -14.69] compared to placebo. Conclusion In this meta-analysis testing BA versus placebo, BA significantly reduced levels of LDL-C, TC, non-HDL-C, and ApoB at 12 weeks and LDL-C at 24 weeks, and was not associated with an increased risk of any AE, muscular-related AE or serious AE. Further studies with longer time of follow up are needed to confirm the safety and long term cholesterol effects of BA.

The cholesterol lowering efficacy of Lactobacillus plantarum ECGC 13110402 in hypercholesterolemic adults: a double-blind, randomized, placebo controlled, pilot human intervention study

• L. plantarum ECGC 13110402 supports the reduction of multiple cholesterol biomarkers. • L. plantarum ECGC 13110402 has high bile salt hydrolase activity. • L. plantarum ECGC 13110402 is a well-tolerated and safe probiotic strain. • L. plantarum ECGC 13110402 improves the lipid profiles of dyslipidaemic patients. Lactobacillus plantarum ECGC13110402 is a probiotic, selected for its high bile salt hydrolase and cholesterol reducing activity. This parallel, double-blind, placebo-controlled, randomized pilot study, investigated the cholesterol reducing capacity of L. plantarum ECGC13110402 in 16 hypercholesterolemic adults. Participants ingested 4 ×10 9 CFU encapsulated ECGC13110402 (active; n=8) or placebo (n=8), once daily, over 6 weeks, followed by a 3-week washout. Fasting blood samples were collected for blood lipid, liver function, and vitamin D analysis. After 6 weeks of L. plantarum ECGC 13110402 daily intake, biologically and statistically significant reductions were noted in TC by an average 34.6% (p=0.001), LDL-C by 28.4% (p=0.03), non-HDL-C by 17.6% (p=0.001) and apoB by 28.6% (p=0.008) compared to the placebo. No changes were observed in liver function biomarkers and vitamin D and no adverse effects were noted throughout the study. The findings of this study suggest that L. plantarum ECGC 13110402 can safely improve lipid profiles in dyslipidaemic individuals.

Prostate cancer prognosis after initiation of androgen deprivation therapy among statin users. A population-based cohort study

PurposeStatins’ cholesterol-lowering efficacy is well-known. Recent epidemiological studies have found that inhibition of cholesterol synthesis may have beneficial effects on prostate cancer (PCa) patients, especially patients treated with androgen deprivation therapy (ADT). We evaluated statins’ effect on prostate cancer prognosis among patients treated with ADT.Materials and methodsOur study population consisted of 8253 PCa patients detected among the study population of the Finnish randomized study of screening for prostate cancer. These were limited to 4428 men who initiated ADT during the follow-up. Cox proportional regression model adjusted for tumor clinical characteristics and comorbidities was used to estimate hazard ratios for risk of PSA relapse after ADT initiation and prostate cancer death.ResultsDuring the median follow-up of 6.3 years after the ADT initiation, there were 834 PCa deaths and 1565 PSA relapses in a study cohort. Statin use after ADT was associated with a decreased risk of PSA relapse (HR 0.73, 95% CI 0.65–0.82) and prostate cancer death (HR 0.82; 95% CI 0.69–0.96). In contrast, statin use defined with a one-year lag (HR 0.89, 95% CI 0.76–1.04), statin use before ADT initiation (HR 1.12, 95% CI 0.96–1.31), and use in the first year on ADT (HR 1.02, 95% CI 0.85–1.24) were not associated with prostate cancer death, without dose dependency.ConclusionStatin use after initiation of ADT, but not before, was associated with improved prostate cancer prognosis.

Evaluation of Cholesterol Lowering Efficacy and Antibacterial Potential of Probiotics: An In vitro Study

Background and Objectives: Probiotics are nonpathogenic and beneficial viable microorganisms that exhibit potential health welfare for human beings. Probiotics are found in various food products. They also occur as natural microflora in the intestine of mammals. Main goal of this study was to isolate probiotics conferring antibacterial activity and cholesterol lowering ability from different fruits. Materials and Method: Present research reveals the usefulness of probiotics, in which twenty one bacterial cultures were isolated from different fruit samples including figs, coconut water and grapes. These strains were explored for their antibacterial and cholesterol reduction ability by conducting in vitro experiments. Results and Discussion: Among twenty one isolates, nine probiotic cultures FgC2, FgC7, FgC14, G2C5, G1C, GrC18 and StCW showed maximum antibacterial activity against different human clinical pathogens. This suggests that these microbes produce inhibitory metabolites which are extracellular and diffusible. For cholesterol assimilation assay, six strains FgC2, FgC7, FgC12, FgC13, GrC7 and GrC18 presented remarkable cholesterol lowering efficacy (up to 98%) when grown in the presence of bile salts. Only potential probiotic cultures were identified and characterized as lactic acid bacteria (LAB), on the basis of Bergey’s Manual of Determinative Bacteriology. Conclusion: Thus, this study is helpful to exploit the bioactive and therapeutic potential of beneficial microorganisms so that they can be utilized in the generation of functional food and other health promoting products.

Bempedoic Acid in the Treatment of Patients with Dyslipidemias and Statin Intolerance.

An elevated plasma low-density lipoprotein cholesterol (LDL-C) level is a well-established atherosclerotic cardiovascular disease (ACSVD) risk factor. Randomized studies with statins (alone or in combination with other lipid-lowering drugs) have demonstrated their clinical efficacy in lowering LDL-C. Several classes of new, non-statin agents have been successfully studied and used (e.g., ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 [i-PSCK9]). However, many high ACSVD risk patients remain at a high residual cardiovascular risk, with at least 10% being statin intolerant. Bempedoic acid (ETC-1002) is a new inhibitor of cholesterol synthesis that targets ATP citrate lyase (ACL). Importantly, ETC-1002 is only converted into an active form in the liver and is free of muscle side effects.Area Covered: Mechanism of action of ETC-1002, clinical pharmacology, completed clinical studies with bempedoic acid, lipid-lowering efficacy/safety issues, and recent meta-analyses of trials with ETC-1002.Expert Opinion: ETC-1002 has been extensively studied in phase I-III clinical studies in over 4000 individuals from different patient populations (statin intolerance, familial hypercholesterolemia, and high ACSVD risk patients), ETC-1002 has been demonstrated to have moderate cholesterol-lowering efficacy and a good safety profile at a dose of 180mg/day as a monotherapy and in combination with statins and ezetimibe. The ongoing study CLEAR Outcomes, with composite cardiovascular endpoints, will elucidate the role of bempedoic acid in the management of high ACSVD risk and statin-intolerant patients with hypercholesterolemia. Long-term safety data on bempedoic acid are needed to fully establish this agent in evidence-informed guidelines for managing of patients with dyslipidemias.

Global review of heart health claims for oat beta-glucan products.

Coronary heart disease (CHD) is the leading cause of death globally. Consumption of whole grains and cereal fiber, as part of a healthy diet, can lower the risk of CHD. Health claims on food products are effective in helping consumers select healthful diets. The US Food and Drug Administration was the first to approve a health claim, in 1997, between beta-glucan soluble fiber from whole oats, oat bran, and whole oat flour and reduced risk of CHD. Only a few countries have approved similar claims. Since 1997, a significant amount of additional evidence has been published on the relationship between oat beta-glucan and CHD. To assist other jurisdictions in potentially utilizing this claim, the full extent of data that supports this claim (ie, the evidence utilized by the US Food and Drug Administration to substantiate the claim, as well as the results of 49 clinical trials published since 1997) are reviewed here. The complexities involved in authoring evidence-based health claims, including the impact of processing on beta-glucan cholesterol-lowering efficacy in approving eligible beta-glucan products, are also discussed.

A Pilot Study to Assess Food Safety and Potential Cholesterol-Lowering Efficacy of Antrodia cinnamomea Solid-State Cultivated Mycelium in Healthy Adults.

Antrodia cinnamomea is a Taiwanese medicinal mushroom with multiple pharmacological activities. Antrodia cinnamomea solid-state cultivated mycelium (LAC) exerts health-related effects in animal and cell models, but clinical data is limited. This study aimed to determine the safety and effects of LAC on human physiological functions. In an open-label, single-arm study, 32 healthy men and women ingested LAC capsules for three months. The subjects were monitored during the study and one month after the study end-point. LAC consumption did not significantly change fasting blood glucose, blood pressure, and triglyceride levels or liver and renal function indices. No adverse events occurred during the trial. Moreover, a significant change from baseline in total cholesterol levels was observed; men and women had decreases of 5.7% and 5.3%, respectively. Based on these, the ingestion of LAC-capsule has a considerable degree of safety and has the potential to reduce total cholesterol in healthy adults.

Use of Plant Sterol and Stanol Fortified Foods in Clinical Practice.

Plant sterols and stanols (PS) are natural, non-nutritive molecules that play a structural role in plant membranes similar to that of cholesterol in animal membranes and abound in seeds and derived oils. PS exert their physical effect of interference with micellar solubilization of cholesterol within the intestinal lumen and are marginally absorbed by enterocytes, with negiglible increases in circulating levels. The physiological role of PS in plants and their natural origin and non-systemic action, together with their cholesterol-lowering effect, make them an attractive option as non-pharmacological agents for the management of hypercholesterolemia. Recent meta-analyses have summarized the results of >100 controlled clinical trials and have firmly established that the consumption of PS-supplemented foods in different formats at doses of 2-3 g per day results in LDL-cholesterol reductions of 9-12%. PS are both effective and safe cholesterol-lowering agents and have many clinical applications: adjuncts to a healthy diet, treatment of common hypercholesterolemia, combination therapy with statins and other lipid-lowering drugs, and treatment of metabolic syndrome and diabetes. The cholesterol-lowering efficacy is similar in all clinical situations. PS are also useful agents for treatment of hypercholesterolemic children who are not yet candidates to statins or receive low-doses of these agents. In the setting of statin treatment, the average LDL-cholesterol reduction obtained with PS is equivalent to up- titrating twice the statin dose. However, information is still scarce on the efficacy of PS as an add-on therapy to ezetimibe, fibrates, omega- 3 fatty acids, or bile acid binding resins. The consistent scientific evidence on the cholesterollowering efficacy and safety of functional foods supplemented with PS has led several national and international scientific societies to endorse their use for the non-pharmacologic treatment of hypercholesterolemia as adjuncts to a healthy diet. There is, however, a lack of clinical trials of PS with outcomes on cardiovascular events.

Lunasin Improves the LDL-C Lowering Efficacy of Simvastatin via Inhibiting PCSK9 Expression in Hepatocytes and ApoE-/- Mice.

Statins are the most popular therapeutic drugs to lower plasma low density lipoprotein cholesterol (LDL-C) synthesis by competitively inhibiting hydroxyl-3-methyl-glutaryl-CoA (HMG-CoA) reductase and up-regulating the hepatic low density lipoprotein receptor (LDLR). However, the concomitant up-regulation of proprotein convertase subtilisin/kexin type 9 (PCSK9) by statin attenuates its cholesterol lowering efficacy. Lunasin, a soybean derived 43-amino acid polypeptide, has been previously shown to functionally enhance LDL uptake via down-regulating PCSK9 and up-regulating LDLR in hepatocytes and mice. Herein, we investigated the LDL-C lowering efficacy of simvastatin combined with lunasin. In HepG2 cells, after co-treatment with 1 μM simvastatin and 5 μM lunasin for 24 h, the up-regulation of PCSK9 by simvastatin was effectively counteracted by lunasin via down-regulating hepatocyte nuclear factor 1α (HNF-1α), and the functional LDL uptake was additively enhanced. Additionally, after combined therapy with simvastatin and lunasin for four weeks, ApoE−/− mice had significantly lower PCSK9 and higher LDLR levels in hepatic tissues and remarkably reduced plasma concentrations of total cholesterol (TC) and LDL-C, as compared to each monotherapy. Conclusively, lunasin significantly improved the LDL-C lowering efficacy of simvastatin by counteracting simvastatin induced elevation of PCSK9 in hepatocytes and ApoE−/− mice. Simvastatin combined with lunasin could be a novel regimen for hypercholesterolemia treatment.

Phytosterol compositions of enriched products influence their cholesterol-lowering efficacy: a meta-analysis of randomized controlled trials.

The composition of phytosterol (PS) formulations used to enrich food and supplements are typically different due to varying natural sources. Sitosterol and it's hydrogenated form: sitostanol are the major PSs in most of these formulations. This review aimed to investigate whether the proportion of sitosterol plus sitostanol in a PS formulation is a determinant of the hypocholesterolaemic effect of PS products. If the amount of sitosterol plus sitostanol in a PS composition is ≥80%, the product is considered to be high in sitosterol plus sitostanol, otherwise the product is considered to be low in sitosterol plus sitostanol. We conducted a meta-analysis on the cholesterol-lowering potential of PS products that were high or low in sitosterol plus sitostanol. Databases including PubMed, EMBASE, and Cochrane Library were searched, and published RCTs investigating the efficacy of dietary PSs intervention (≥1.5 g/d) on blood lipid profile improvement were selected. After strict screening and quality assessment, a total of 51 RCTs were included. As expected, PSs with all compositions significantly reduced LDL-C (p < 0.00001), while the LDL-C lowering effect associated with the high sitosterol plus sitostanol group was significantly greater than that of the low sitosterol plus sitostanol group (p = 0.002). PSs also significantly reduced TG (p = 0.009) without affecting HDL-C. Thus, the composition might affect the hypocholesterolaemic effect of PS products. PS products with higher sitosterol plus sitostanol proportions might have superior cholesterol-lowering potential than those with lower sitosterol plus sitostanol proportions.

New agents to reduce cholesterol levels: implications for nephrologists.

Statins and ezetimibe effectively reduce the burden of cardiovascular (CV) disease in patients with chronic kidney disease (CKD). Unfortunately, many subjects still die or have CV events despite cholesterol-lowering therapy. This is particularly true in patients with more advanced CKD. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that induces the degradation of the low-density lipoprotein receptor by targeting it for lysosomal destruction. Its inhibition causes a dramatic fall in cholesterol levels on top of maximized statin therapy. This goal is obtained with different therapeutic approaches, spanning from monoclonal antibodies to non sense oligonucleotides and silencing RNA (siRNA). Two human, monoclonal antibodies are approved for clinical use; they are still very expensive. Both agents significantly lower cholesterol levels. Evolocumab and alirocumab reduce significantly the risk for CV disease without relevant safety issues. Inclisiran is an siRNA molecule that produces PCSK9-specific RNA silencing. Data from a Phase II study showed significant cholesterol-lowering efficacy. The experience accumulated so far is limited in the CKD population. PCSK9 inhibition also has the potential to reduce the burden of CV in this subset by obtaining a much greater decrease in serum cholesterol compared with statin therapy or ezetimibe. Doubts exist that this approach will improve the outcome of dialysis patients, in whom vascular calcifications predominate.

Functional Probiotic Assessment and In Vivo Cholesterol-Lowering Efficacy of Weissella sp. Associated with Arid Lands Living-Hosts.

The research and the selection of novel probiotic strains from novel niches are receiving increased attention on their proclaimed health benefits to both humans and animals. This study aimed to evaluate the functional properties of Weissella strains from arid land living-hosts and to select strains with cholesterol-lowering property in vitro and in vivo, for use as probiotics. They were assessed for acid and bile tolerance, antibiotic susceptibility, membrane properties, antibacterial activity, antiadhesive effect against pathogens to host cell lines, and cholesterol assimilation in vitro. Our results showed that the majority of strains revealed resistance to gastrointestinal conditions. All the strains were nonhemolytic and sensitive to most of the tested antibiotics. They also exhibited high rates of autoaggregation and some of them showed high coaggregation with selected pathogens and high adhesion ability to two different cell lines (Caco-2 and MIM/PPk). Particularly, W. halotolerans F99, from camel feces, presented a broad antibacterial spectrum against pathogens, reduced Enterococcus faecalis and Escherichia coli adhesion to Caco-2 cells, and was found to reduce, in vitro, the cholesterol level by 49 %. Moreover, W. halotolerans F99 was evaluated for the carbohydrate utilization as well as the serum lipid metabolism effect in Wistar rats fed a high-cholesterol diet. W. halotolerans F99 showed an interesting growth on different plant-derivative oligosaccharides as sole carbon sources. Compared with rats fed a high-fat (HF) diet without Weissella administration, total serum cholesterol, low-density lipoprotein cholesterol, and triglycerides levels were significantly (p<0.001) reduced in W. halotolerans F99-treated HF rats, with no significant change in high-density lipoprotein cholesterol HDL-C levels. On the basis of these results, this is the first study to report that W. halotolerans F99, from camel feces, can be developed as cholesterol-reducing probiotic strain. Further studies may reveal their potential and possible biotechnological and probiotic applications.

Newer evidences and recommendations in lipidology

The correlation between cholesterol and risk reduction is unique: no J curve is seen even at extreme low levels. According to PRECISE-IVUS, the effect of intensive cholesterol lowering on plaque regression is more pronounced post-myocardial infarction syndrome than in chronic coronary disease. The importance of LDL-C lowering with ezetimibe in IMPROVE-IT (1.4 mmol/L compared to 1.8 mmol/L in the statin monotherapy arm) is expressed in several international guidelines and the indication spectrum of combination cholesterol lowering has broadened and strengthened. There is a strong evidence that myalgia during statin treatment is generally not caused by statins and it is not related to type or dose of the drug. With patience, the majority of patients can be made to become statin takers even with good quality of life; for those who cannot, ezetimibe monotherapy can be an alternative. Even though intensive cholesterol lowering is safe, avoiding statin myopathy should be emphasized. Despite the outstanding efficacy and safety of cholesterol lowering, Hungarian statin sales have decreased recently, in which driven dilettante public climate around the products may be of utmost importance. Everyone of us should counteract this according to the possibilities. Orv Hetil. 2018; 159(32): 1303-1309.