Cholesterol Absorption Inhibitor Research Articles

Use of cholesterol-lowering medications in relation to risk of primary liver cancer in the Clinical Practice Research Datalink.

Although the relation between statin use and liver cancer risk has been extensively examined, few studies have examined other cholesterol-lowering medications in relation to liver cancer risk. The authors examined five classes of nonstatin medications and liver cancer risk. A nested case-control including 3719 cases and 14,876 matched controls was conducted within the Clinical Practice Research Datalink. Additional matches on type 2 diabetes and chronic liver disease were also implemented. The medications examined included cholesterol absorption inhibitors, bile acid sequestrants, fibrates, niacin, and omega-3 fatty acids. Conditional logistic regression estimated odds ratios and 95% confidence intervals. Cholesterol absorption inhibitor use was associated with reduced liver cancer risk in the overall analysis (odds ratio, 0.69; 95% confidence interval, 0.50-0.96) and in analyses based on type 2 diabetes and chronic liver disease status. Although bile acid sequestrant use was associated with increased liver cancer risk in the overall analysis (odds ratio, 5.31; 95% confidence interval, 3.534-7.97), the results of the analyses based on type 2 diabetes and chronic liver disease status were inconsistent. No associations were observed for the other medications. Cholesterol absorption inhibitors may be associated with reduced liver cancer risk. Whether bile acid sequestrant use was associated with increased risk was only partially supported in the current study.

Ezetimibe use and mortality after myocardial infarction: A nationwide cohort study

BackgroundThe inhibition of intestinal cholesterol absorption by ezetimibe improves outcomes after myocardial infarction (MI), yet real-world data on ezetimibe is scarce. We studied the usage of ezetimibe and association with outcome after MI. MethodsConsecutive MI patients in Finland (2010–2018) were retrospectively studied (N = 57,505; 65 % men; mean age 69 years). The study data were collected from national registries. The median follow-up was 4.5 (IQR 2.8–7.1) years. Between-group differences were adjusted for using multivariable regression. Ezetimibe use was studied with competing risk analyses. ResultsThe cumulative incidence of ezetimibe use was 3.7 % at 90 days, 13.4 % at 5 years, and 19.8 % at 10 years. Younger age was one of the strongest predictors of ezetimibe use (adj.sHR 6.67; CI 5.88–7.69 for patients aged <60 vs ≥80 years). Women were more likely to use ezetimibe during follow-up than men. The average proportion of patients using ezetimibe during follow-up was 6.8 %. (11.7 % at 10 years). Ezetimibe was discontinued by 43.6 % of patients during follow-up. Patients with early ezetimibe therapy after MI had lower all-cause mortality during follow-up (33.6% vs 45.1 %; adj.HR 0.77; CI 0.69–0.86; P < 0.0001). Early ezetimibe use was associated with lower mortality irrespective of sex, age, atrial fibrillation, diabetes, heart failure, malignancy, revascularization, or statin use. Ongoing ezetimibe therapy during follow-up was associated with lower mortality in a time-dependent analysis (adj.HR 0.53; CI 0.48–0.59; P < 0.0001). ConclusionsEzetimibe is associated with a lower risk of death after MI, yet its therapeutic use is limited, and discontinuation is frequent.

Eutectic mixtures containing the active pharmaceutical ingredient ezetimibe: Phase diagrams, solid state characterization and dissolution profiles

Cardiovascular disease represents the leading cause of death worldwide, according to the World Health Organization (WHO) report. One of the treatment strategies is the use of the drug ezetimibe (EZT). This drug is a cholesterol absorption inhibitor with low aqueous solubility, which affects its therapeutic efficacy. The purpose of this paper was to obtain eutectic materials of EZT with methylparaben (MPB), salicylic acid (SCA) and nicotinamide (NTM) coformers, and to study their phase diagrams, dissolution properties and hygroscopicity to assess possible enhancements. Phase and Tamman diagrams were constructed using differential scanning calorimetry (DSC) results. The eutectic materials were characterized by powder X-ray diffraction (PXRD) and polarized light optical microscopy (OM). The hygroscopicity of the materials was assessed at different relative humidities (RH) through dynamic vapor sorption (DVS). The dissolution study was conducted with the materials in powder form, with paddle dissolution, rotating at 50 rpm, in 900 mL of aqueous buffer solution at pH 6.8 and 37 °C. The phase diagrams demonstrated that EZT formed eutectic systems with eutectic molar fractions of 0.59, 0.67 and 0.69 for EZT-SCA, EZT-NTM and EZT-MPB, respectively. The three eutectic materials are characterized as microcrystalline conglomerates of their components. In terms of the hygroscopic behavior of EZT at different RHs, eutectic materials demonstrated lower susceptibility to monohydrate formation compared to the anhydrous form. In dissolution studies, EZT-SCA and EZT-MPB solubilized EZT in amounts 22 % higher than the pure drug in 15 min. On the other hand, EZT-NTM eutectic suppressed the dissolution of EZT down to 56 % at the same time. The results indicated the possibility of obtaining materials with enhanced properties using eutectic mixtures, with improved dissolution rates and hygroscopic stability.

Management of a patient at very high cardiovascular risk with myositis during high-intensity statin therapy

The main purpose of this article is to translate the existing experience of successful optimization of lipid-lowering treatment in a patient with a very high cardiovascular risk and a long history of dyslipidemia, cerebral atherosclerosis and myositis, which developed on a high-intensity statin therapy regimen. Using the example of a 56-year-old patient observed in the lipid center of the city of Kemerovo, it was shown that the combination of pitavastatin in the maximum tolerated dose of 2 mg and the cholesterol absorption inhibitor ezetimibe 10 mg can not only be effective in achieving target values of low-density lipoprotein cholesterol (1.4 mmol/l) after undergoing carotid revascularization, but also safe for registered muscle symptoms that arose during a high-intensity statin therapy regimen. It was demonstrated that, against the background of high adherence to the selected treatment and low-cholesterol diet, and maintenance of regular physical activity, the patient completely disappeared both muscle pain and muscle weakness, and there was no clinical or instrumental progression of cerebral stenosis. The article provides current data on the prevalence of muscle symptoms when taking statins in real practice and in randomized clinical trials, discusses existing predisposing factors and potential mechanisms of occurrence, describes variants of clinical manifestations and tentative diagnostic search criteria. In addition, recommendations on the tactics of managing patients with their development at various cardiovascular risks have been systematized. An expert classification system for statin-associated muscle symptoms is demonstrated. Also presented is the routing of patients with side effects developing during statin therapy, adopted in the city of Kemerovo.

A new indication for bempedoic acid (Nexletol).

The oral adenosine triphosphate-citrate lyase (ACL) inhibitor bempedoic acid was approved by the FDA in 2020 for use alone (Nexletol – Esperion) and in a fixed-dose combination with the cholesterol absorption inhibitor ezetimibe (Nexlizet) as an adjunct to maximally tolerated statin therapy in adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional LDL-cholesterol (LDL-C) lowering.

Cholesterol Absorption Inhibition by Some Nutraceuticals.

Hyperlipidemia, characterized by elevated levels of lipids in the blood, represents a major risk factor for cardiovascular diseases, a leading cause of morbidity and mortality worldwide. Conventional pharmacological interventions have been effective in managing hyperlipidemia, but concerns about side effects and long-term use have prompted interest in alternative approaches, particularly the use of nutraceuticals. This comprehensive review aims to summarize and critically evaluate the current body of knowledge surrounding the role of nutraceuticals in the management of hyperlipidemia. We provide an overview of the different classes of nutraceuticals, including plant sterols, omega-3 fatty acids, soluble fiber, antioxidants, and various herbal extracts, which have been investigated for their lipid-lowering properties. The mechanisms of action of these nutraceuticals are discussed, highlighting their ability to modulate lipid metabolism, reduce oxidative stress, and promote cardiovascular health. Furthermore, we review the results of clinical trials and epidemiological studies that have assessed the efficacy of nutraceutical interventions in lowering cholesterol levels, improving lipid profiles, and reducing the risk of cardiovascular events. In addition to their lipid-lowering effects, we examine the safety profile, dosage recommendations, and potential interactions of nutraceuticals with conventional lipid-lowering medications. We also address the importance of patient adherence to dietary and lifestyle modifications in conjunction with nutraceutical supplementation. While nutraceuticals offer a promising avenue for managing hyperlipidemia, we emphasize the need for further research to establish evidence-based guidelines for their use in clinical practice. Challenges related to standardization, quality control, and regulatory considerations are also discussed. In conclusion, this comprehensive review provides valuable insights into the potential of nutraceuticals as adjunctive or alternative therapies for managing hyperlipidemia. While further research is needed, the accumulating evidence suggests that nutraceuticals can play a valuable role in promoting cardiovascular health and reducing the burden of hyperlipidemia- related diseases.

A Promising Functional Food for Diabetes Prevention, Antioxidation, and Anti-inflammation of Green Coffee Bean Extract

Functional foods and nutrition have become increasingly popular in preventing and reducing the incidence of diabetes. Green coffee bean extract (GCBE) has received much interest because of the evidence that coffee consumption reduces the risk of diabetes and many inflammatory diseases. This study was designed to investigate the phytochemicals contained in GCBE and their antioxidant, anti-diabetic, and anti-inflammatory efficacies. GCBE phytochemicals were analyzed using high-performance liquid chromatography (HPLC). This analysis demonstrated that chlorogenic acid was the predominant component of GCBE, followed by caffeine and caffeic acid. The antioxidant capacity of GCBE was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2’-azinobis 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays, demonstrating significant scavenging capacity with IC50 values of 2.96 ± 1.04 and 7.63 ± 1.03 µg/mL, respectively. The anti-hyperlipidemic efficacy of GCBE was observed through inhibiting cholesterol absorption (by increasing micelle sizes and decreasing cholesterol solubility), lipid digestion, and pancreatic lipase activity in vitro. The investigations revealed that GCBE possessed anti-hyperlipidemic properties by inhibiting cholesterol absorption, lipid digestion, and pancreatic lipase activity. Specifically, GCBE increased micelle particle sizes by ~6.5-fold, decreased cholesterol solubility by 2-fold, and reduced pancreatic lipase activity by 25%. Additionally, the in vitroanti-hyperglycemic activity of GCBE was evaluated by inhibition of α-amylase and α-glucosidase capacity. GCBE demonstrated anti-hyperglycemic activity by inhibiting α-amylase activity (32.80 ± 7.06% inhibition), while α-glucosidase activity remained unaffected. The anti-inflammatory potential of GCBE was evaluated by mRNA regulation using RT-PCR analysis. This analysis revealed that GCBE attenuated mRNA expression of COX-2, TNF-α, IL-1b, and IL-6 in LPS-induced RAW264.7 cells. GCBE’s antioxidant, anti-hyperlipidemic, and anti-hyperglycemic efficacies and its molecular mechanisms in modulating the inflammation pathway found in the present study highlight its potential as a supplement in functional foods or beverages. Doi: 10.28991/HEF-2024-05-01-08 Full Text: PDF

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.

Treatment of Ezetimibe lowers total and low-density lipoprotein cholesterol in hypercholesterolemic dogs with hyperadorenocorticism.

Ezetimibe is a cholesterol absorption inhibitor that blocks the intestinal absorption of both biliary and dietary cholesterol, thereby lowering primarily low density lipoprotein-cholesterol (LDL-chol) in human studies. This study aimed to investigate the effects of ezetimibe on dyslipidemia control in nine dogs with hypercholesterolemia. Changes in total cholesterol (T-chol) and each lipoprotein fractions were evaluated at 0, 2, and 4 months following initiation of ezetimibe treatment. A significant decrease in T-chol was observed, and a mean T-chol concentration below 400 mg/dL was achieved at 2 and 4 months. Furthermore, a significant decrease in LDL-chol was observed (-53.3% and -64.3% at 2 and 4 months, respectively). Taken together, treatment of ezetimibe could lower LDL-chol levels in dogs with hypercholesterolemia.

The Effect of Traditional Jamu with Polyphenol-Rich Mixture Content on Cholesterol Levels in the Elderly with Coronary Heart Disease

Introduction: The aging process can impact the cardiovascular system in both structural and physiological ways, which can lead to atherosclerosis and an increased risk of coronary heart disease. While pharmacological interventions for CHD exist, they may come with unwanted side effects. As an alternative, many individuals turn to complementary medicine, including traditional herbal remedies. Among these remedies is a polyphenol-rich mixture (PRM) that has been shown to lower cholesterol levels and inhibit cholesterol absorption. Consequently, this study seeks to explore the efficacy of traditional herbal medicine containing PRM in reducing cholesterol levels in older adults with CHD. Methods: Design research uses quasi-experiment with two groups pre-test and post-test, the number of samples is 55 older adults with CHD, divided into 28 older adults consuming traditional herbal medicine and 27 older adults’ control. The researcher used an Accu-check to check the cholesterol level and analysed using a t-test. Results: The results showed that the decrease in mean cholesterol levels before and after the intervention period in the herbal medicine group (d = 50.50) was significantly greater than the mean score in the control group (d = -1.44) with p &lt;.001. Conclusion: Older adults with coronary heart disease could benefit from traditional Jamu containing polyphenol-rich mixture by reducing cholesterol levels. This could be used as complementary medicine in nursing.

Ezetimibe inhibits triple-negative breast cancer proliferation and promotes cell cycle arrest by targeting the PDGFR/AKT pathway

Cholesterol levels were strongly associated with tumor progression and metastasis. Targeted cholesterol metabolism has broad prospects in tumor treatment. Ezetimibe, the only FDA-approved inhibitor of cholesterol absorption, has been reported to be able to inhibit angiogenesis in liver cancer. However, the efficacy and specific mechanisms of Ezetimibe in the treatment of Triple-Negative Breast Cancer (TNBC)have not been reported. Our research shows Ezetimibe inhibits TNBC cell proliferation and blocks the cell cycle in the G1 phase. Mechanistically, Ezetimibe inhibits the activation of PDGFRβ/AKT pathway, thereby promoting cell cycle arrest and inhibiting cell proliferation. By overexpressing PDGFRβ in TNBC cells, we found that PDGFRβ significantly reduced the inhibitory effect of Ezetimibe on TNBC cell proliferation and the cell cycle. Similarly, SC79, an AKT agonist, can reduce the proliferation inhibitory and cycle-blocking effects of Ezetimibe on TNBC cells. Furthermore, the AKT inhibitor MK2206 enhanced the inhibitory effect of Ezetimibe on the cell cycle and proliferation ability of TNBC cells overexpressing PDGFRβ. In xenograft tumor models, we also found that Ezetimibe inhibited TNBC growth, an effect that can be blocked by overexpression of PDGFR or activation of AKT. In summary, we have demonstrated that EZ inhibits the PDGFR/AKT pathway, thereby halting TNBC cycle progression and tumor growth.

Expanding the therapeutic landscape: ezetimibe as non-statin therapy for dyslipidemia.

Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), and statins are the primary therapeutic options for reducing low-density lipoprotein cholesterol (LDL-C) levels. However, it can be challenging to achieve optimal LDL-C goals with statin monotherapy. Ezetimibe, a cholesterol absorption inhibitor, offers a potential non-statin therapy to optimize LDL-C management. Key clinical trials, such as IMPROVE-IT and RACING, have demonstrated that the addition of ezetimibe to statin therapy leads to further decreases in LDL-C or significant decreases in major adverse cardiovascular events (MACEs), particularly in patients with high ASCVD risk. Subsequent meta-analyses and clinical trials have further supported the beneficial effect of ezetimibe, suggesting additive decreases in LDL-C and MACEs, as well as pleiotropic effects. This review provides a comprehensive analysis of the clinical implications of ezetimibe for managing dyslipidemia; it also evaluates the available evidence that supports the role of ezetimibe as an adjunct non-statin therapy for long-term use. However, the long-term pleiotropic effects of ezetimibe remain controversial because of limited clinical data. Therefore, additional research is needed to clarify its potential benefits beyond LDL-C reduction. Nonetheless, an understanding of the role of ezetimibe in dyslipidemia management will help clinicians to develop effective treatment strategies.

Bioactive Functions of Lipids in the Milk Fat Globule Membrane: A Comprehensive Review.

The milk fat globule membrane (MFGM) is a complex tri-layer membrane that wraps droplets of lipids in milk. In recent years, it has attracted widespread attention due to its excellent bioactive functions and nutritional value. MFGM contains a diverse array of bioactive lipids, including cholesterol, phospholipids, and sphingolipids, which play pivotal roles in mediating the bioactivity of the MFGM. We sequentially summarize the main lipid types in the MFGM in this comprehensive review and outline the characterization methods used to employ them. In this comprehensive review, we sequentially describe the types of major lipids found in the MFGM and outline the characterization methods employed to study them. Additionally, we compare the structural disparities among glycerophospholipids, sphingolipids, and gangliosides, while introducing the formation of lipid rafts facilitated by cholesterol. The focus of this review revolves around an extensive evaluation of the current research on lipid isolates from the MFGM, as well as products containing MFGM lipids, with respect to their impact on human health. Notably, we emphasize the clinical trials encompassing a large number of participants. The summarized bioactive functions of MFGM lipids encompass the regulation of human growth and development, influence on intestinal health, inhibition of cholesterol absorption, enhancement of exercise capacity, and anticancer effects. By offering a comprehensive overview, the aim of this review is to provide valuable insights into the diverse biologically active functions exhibited by lipids in the MFGM.

KAJIANPUSTAKA: HIPERKOLESTEROLEMIADAN PENANGGULANGANNYA DENGAN MENGGUNAKANBERBAGAI SENYAWA BIOAKTIF

Hypercholesterolemia is characterized by levels of total cholesterol and low-density lipoprotein (LDL) above normal. Hypercholesterolemia is a major risk factor for cardiovascular disease. This study was aimed to explore and analyze various bioactive compounds to manage hypercholesterolemia. Efforts to overcome the condition of hypercholesterolemia are to reduce the consumption of a diet rich in cholesterol and calories, and consuming contemporary hypercholesterolemic drugs such as statins, as well as by regulating the body’s cholesterol metabolism with various antihypercholesterolemic bioactive compounds. Various findings of antihypercholesterolemic bioactive compounds have various sources and effects on cholesterol profiles. Bioactive compounds can be classified according to their mechanism of hypocholesterolemic action, which are inhibition of cholesterol absorption, inhibition of cholesterol biosynthesis, increased cholesterol excretion, increased cholesterol reverse transport, and increased cholesterol catabolism. Several bioactive compounds are involved in a dual mechanism. The development of these various bioactive compounds can be used as an alternative treatment for hypercholesterolemia since contemporary medicines have proven to have many side effects.

Ezetimibe Induces Vasodilation in Rat Mesenteric Resistance Arteries through Inhibition of Extracellular Ca2+ Influx.

Ezetimibe is a lipid-lowering agent that selectively inhibits cholesterol absorption by binding to the Niemann-Pick C1-like 1 (NPC1L1) protein. Although it is well known that administration of ezetimibe in hypercholesterolemia patients reduces the risk of cardiovascular events through attenuation of atherosclerosis, studies on the direct effect of ezetimibe on vascular function are not sufficient. The aim of the present study was to investigate the vascular effects of ezetimibe in rat mesenteric arteries. In the present study, 12-week-old male Sprague Dawley rats were used. After the rats were sacrificed, the second branches of the mesenteric arteries were isolated and cut into 2-3 mm segments and mounted in a multi-wire myography system to measure isometric tension. Ezetimibe reduced vasoconstriction induced by U46619 (500 nM) in endothelium-intact and endothelium-denuded arteries. Ezetimibe-induced vasodilation was not affected by the endothelial nitric oxide synthase (eNOS) inhibitor Nω-Nitro-L-arginine (L-NNA, 300 μM) or the non-selective potassium channel blocker, tetraethylammonium (TEA, 10 mM). Moreover, ezetimibe also completely blocked the contraction induced by an increase in external calcium concentration. Ezetimibe significantly reduced vascular contraction induced by L-type Ca2+ channel activator (Bay K 8644, 30 nM). Treatment with ezetimibe decreased the phosphorylation level of 20 kDa myosin light chain (MLC20) in vascular smooth muscle cells. In the present study, we found that ezetimibe has a significant vasodilatory effect in rat mesenteric resistance arteries. These results suggest that ezetimibe may have beneficial cardiovascular effects beyond its cholesterol-lowering properties.

Physiologically based pharmacokinetic modeling to characterize enterohepatic recirculation and predict food effect on the pharmacokinetics of hyzetimibe

Background and ObjectiveHyzetimibe is a cholesterol absorption inhibitor indicated for the treatment of hypercholesterolemia. This study aims to describe the multiple-peak pharmacokinetics (PK) of hyzetimibe and its active metabolite M1 through physiologically-based pharmacokinetic (PBPK) modeling, and to compare the model predictions of a virtual food effect study with the results of a clinical food effect study. MethodsThe plasma concentration data used for PBPK modeling were obtained from a single-dose, two-period crossover bioequivalence study in the fasted state. Advanced Compartmental Absorption and Transit model was used for absorption. Enterohepatic recirculation process was modeled by changing the gut physiological state from fasted to fed at meal time. Based on the established PBPK models, a virtual food effect study was simulated. A clinical food effect study was used for model external validation. ResultsPK profiles of hyzetimibe and M1 under fasting condition could be well described by the PBPK model, and the errors of Cmax, AUC0-∞, and AUC0-t were within the two-fold range. Simulated geometric mean ratios (GMRs, fed/fasted) showed that a high-fat breakfast slightly affected the PK of hyzetimibe, expressed as increased Cmax of hyzetimibe (130.6%). Simulated GMRs and 90% confidence intervals of AUC were within the preset bioequivalent range. The results of the simulated virtual food effect trial were consistent with those of the clinical food effect trial. ConclusionsThe established PBPK model could describe the concentration-time profiles of hyzetimibe and M1 well with good prediction performance. A fully mechanistic model of enterohepatic recirculation warrants further investigation.

Wind of change – PCSK9 inhibitors in hypolipidemic treatment. The Polish perspective

Introduction and aim. Cardiovascular diseases are the main cause of mortality in the world. One of the alterable risk factors of ischaemic heart disease is dyslipidemia. Discovery and usage of a new group of drugs - PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors lead to a decrease of LDL-C (low-density lipoprotein cholesterol) levels in patients who are resistant to standard hypolipidemic therapy. The aim of this paper is to introduce PCSK9 inhibitors and describe their usage in medicine. &#x0D; Material and methods. A review of the available literature was performed by searching the PubMed and GoogleScholar databases using the following key words: PCSK9 inhibitors; alirocumab; evolocumab; inclisiran. &#x0D; Analysis of the literature. According to the European Society of Cardiology guidelines for dyslipidemias from year 2019, the main aim of dyslipidemia treatment is LDL-C reduction to target values depending on patient risk levels. It may be achieved in 2 ways, namely, by lifestyle modification or by pharmacological treatment with statins, fibrates and cholesterol absorption inhibitors. However, a therapy with PCSK9 inhibitors may be considered the most effective in certain groups of patients. Evolocumab and alirocumab are 2 representatives of those new drugs, which are allowed for use in 3 scenarios – in patients with familial hypercholesterolemia, in those with high risk of cardiovascular incident, and in those with statin intolerance. The major advantage of the aforementioned drugs is their safety. Since 2021 inclisiran (the first drug in siRNA class) is available for use as a new type of PCSK9 blocker. &#x0D; Conclusion. PCSK9 inhibitors can be life-saving for patients with a high risk of cardiovascular incidents associated with an elevated level of LDL-C. They reduce LDL-C more efficiently and have fewer side effects in comparison with the other hypolipidemic drugs. Therefore, PCSK9 inhibitors play a very important role in the lipid-lowering treatment.

2023 China Guidelines for Lipid Management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of China guidelines for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "China Guidelines for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with CVD risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

2023 Chinese guideline for lipid management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of Chinese guideline for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "Chinese guideline for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with cardiovascular disease (CVD) risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

The modulatory effects on enterohepatic cholesterol metabolism of novel cholesterol-lowering peptides from gastrointestinal digestion of Xuanwei ham

The aim of this study was to investigate the effects and mechanism of in vitro protein digestive products of Xuanwei ham with different ripening periods on cholesterol metabolism and hypercholesterolemia. The results showed that compared with other gastrointestinal digestion (GID) groups, the GID group of Xuanwei ham with 3-year ripening period (XWH3-GID) inhibited the expression of Niemann-Pick C1-like 1 (NPC1L1) and acetyl-CoA acetyltransferase 2 (ACAT2) through hepatocyte nuclear factor 1-alpha (HNF-1α), which in turn effectively inhibited cholesterol absorption in Caco-2 cell monolayers. Following absorption by Caco-2 cell monolayers, the XWH3-GID group suppressed the expression and secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) via HNF-1α, which enhanced the protein expression and fluorescence intensity of low density lipoprotein receptor (LDLR) on the HepG2 cell membrane, and thus promoted the uptake of low density lipoprotein (LDL). Importantly, three novel peptides (LFP, PKF and VPFP) derived from titin were identified after intestinal epithelial transport in the XWH3-GID group, which could exert cholesterol-lowering effects through inhibiting intestinal cholesterol absorption and promoting peripheral hepatic LDL uptake, and effectively ameliorate western diet-induced hypercholesterolemia in ApoE-/- mice. These results suggest that Xuanwei ham with 3-year ripening period can be used as a source of cholesterol-lowering peptides and has potential to intervene in hypercholesterolemia.