-
1.
Hypolipaemic nutraceutics: red yeast rice and Armolipid, berberine and bergamot.
Kłosiewicz-Latoszek, L, Cybulska, B, Stoś, K, Tyszko, P
Annals of agricultural and environmental medicine : AAEM. 2021;(1):81-88
Abstract
INTRODUCTION Increased serum cholesterol levels constitute one of the main risk factors for cardiovascular diseases. Statins are a major method for reducing the levels which also lower the risk of cardiovascular events. However, these valuable drugs cannot be used in all patients who need them due to contraindications and intolerance. In such cases, help can be sought from nutraceutics that reduce the serum cholesterol concentration. Since there are numerous products of this type available at drugstores, registered as supplements, there seems to be a need to demonstrate their effectiveness in preventing cardiovascular diseases induced by atherosclerosis. In literature, increasingly more attention is drawn to red yeast rice, Armolipid, berberine and bergamot. BRIEF DESCRIPTION This article presents knowledge about these nutraceutics based on clinical studies and expert statements relating to their use. The results of clinical studies and metaanalyses have shown that nutraceutics with cholesterol lowering properties, red yeast rice and Armolipid are the most favourable for reducing cardiovascular events. However, the evidence of benefits of berberine and bergamot is not so conclusive. CONCLUSIONS Red yeast rice products and Armolipid may be used as an alternative treatment in statin intolerant patients, especially in combination with ezetimibe. These nutraceutics can be also considered, as an adjunct to diet therapy in primary prevention of cardiovascular diseases in patients with mild and moderate hypercholesterolaemia. The opinion of experts on berberine and bergamot is ambiguous.
-
2.
Meta-Analysis of Intensive Lipid-Lowering Therapy in Patients With Polyvascular Disease.
Alkhalil, M, Kuzemczak, M, Whitehead, N, Kavvouras, C, Džavík, V
Journal of the American Heart Association. 2021;(5):e017948
Abstract
Background Polyvascular atherosclerotic disease is associated with an increased risk of future cardiovascular events. Intensive lipid-lowering therapy (ILT) may mitigate this risk. The aims of this study-level meta-analysis were to examine the effects of ILT in patients with polyvascular disease and whether baseline low-density lipoprotein cholesterol (LDL-C) may determine the level of benefit. Methods and Results Electronic databases were searched through January 2020 to identify randomized controlled trials of treatments targeting upregulation of LDL-C receptors (ie, statins, ezetimibe, and PCSK9 [proprotein convertase subtilisin-kexin type 9] inhibitors). The primary end point was major adverse vascular events as defined by the included studies. A total of 94 362 patients (14 821 [18.6%] with polyvascular disease) from 7 studies were included. In patients with monovascular disease, ILT was associated with a 13% reduction in the primary end point (rate ratio [RR] 0.87; 95% CI, 0.81-0.93 [P=0.0002]) (absolute RR, 1.8%) compared with less ILT, while patients with polyvascular disease had 15% relative RR (0.85; 95% CI, 0.80-0.90 [P<0.00001]) (absolute RR, 6.5%) (P=0.66 for interaction). When factoring LDL-C, unlike patients with monovascular disease, the relative benefits of ILT, compared with less ILT, in patients with polyvascular disease were comparable with LDL-C >100 mg/dL (RR, 0.85; 95% CI, 0.80-0.90 [P<0.00001]) and LDL-C <100 mg/dL (RR, 0.88; 95% CI, 0.81-0.96 [P=0.003]) (P=0.23 for interaction). Conclusions Patients with polyvascular disease experienced comparable benefits to those with monovascular disease in response to ILT. The benefits of ILT in patients with polyvascular disease were not dependent on baseline LDL-C, challenging the approach of using LDL-C as a prerequisite to commence ILT for this high-risk subgroup.
-
3.
Nutraceutical Combinations in Hypercholesterolemia: Evidence from Randomized, Placebo-Controlled Clinical Trials.
Protic, O, Bonfigli, AR, Antonicelli, R
Nutrients. 2021;(9)
Abstract
There is an increasing number of nutraceutical combinations (NCs) on the market for hypercholesterolemia, although clinical trials to verify their safety and efficacy are scarce. We selected fourteen randomized, placebo-controlled clinical trials (RCTs) on different lipid-lowering NCs in hypercholesterolemic subjects. We described each compound's mechanism of action and efficacy in the mixtures and summarized the clinical trials settings and NCs safety and efficacy results. Almost all NCs resulted efficient against hypercholesterolemia; only one reported no changes. Interestingly, red yeast rice (RYR) was present in eleven mixtures. It is not clear whether the lipid-lowering efficacy of these combinations derives mainly from the RYR component monacolin K "natural statin" single effect. Up to now, few RCTs have verified the efficacy of every single compound vs. NCs to evaluate possible additive or synergistic effects, probably due to the complexity and the high resources request. In conclusion, to manage the arising nutraceutical tide against hypercholesterolemia, it could be helpful to increase the number and robustness of clinical studies to verify the efficacy and safety of the new NCs.
-
4.
Residual Cardiovascular Risk at Low LDL: Remnants, Lipoprotein(a), and Inflammation.
Hoogeveen, RC, Ballantyne, CM
Clinical chemistry. 2021;(1):143-153
-
-
Free full text
-
Abstract
BACKGROUND Current guidelines target low-density lipoprotein cholesterol (LDL-C) concentrations to reduce atherosclerotic cardiovascular disease (ASCVD) risk, and yet clinical trials demonstrate persistent residual ASCVD risk despite aggressive LDL-C lowering. CONTENT Non-LDL-C lipid parameters, most notably triglycerides, triglyceride-rich lipoproteins (TGRLs), and lipoprotein(a), and C-reactive protein as a measure of inflammation are increasingly recognized as associated with residual risk after LDL-C lowering. Eicosapentaenoic acid in statin-treated patients with high triglycerides reduced both triglycerides and ASCVD events. Reducing TGRLs is believed to have beneficial effects on inflammation and atherosclerosis. High lipoprotein(a) concentrations increase ASCVD risk even in individuals with LDL-C < 70 mg/dL. Although statins do not generally lower lipoprotein(a), proprotein convertase subtilisin/kexin type 9 inhibitors reduce lipoprotein(a) and cardiovascular outcomes, and newer approaches are in development. Persistent increases in C-reactive protein after intensive lipid therapy have been consistently associated with increased risk for ASCVD events. SUMMARY We review the evidence that biochemical assays to measure TGRLs, lipoprotein(a), and C-reactive protein are associated with residual risk in patients treated to low concentrations of LDL-C. Growing evidence supports a causal role for TGRLs, lipoprotein(a), and inflammation in ASCVD; novel therapies that target TGRLs, lipoprotein(a), and inflammation are in development to reduce residual ASCVD risk.
-
5.
Managing hyperlipidaemia in patients with COVID-19 and during its pandemic: An expert panel position statement from HEART UK.
Iqbal, Z, Ho, JH, Adam, S, France, M, Syed, A, Neely, D, Rees, A, Khatib, R, Cegla, J, Byrne, C, et al
Atherosclerosis. 2020;:126-136
-
-
Free full text
-
Abstract
The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes Coronavirus Disease 2019 (COVID-19) has resulted in a pandemic. SARS-CoV-2 is highly contagious and its severity highly variable. The fatality rate is unpredictable but is amplified by several factors including advancing age, atherosclerotic cardiovascular disease, diabetes mellitus, hypertension and obesity. A large proportion of patients with these conditions are treated with lipid lowering medication and questions regarding the safety of continuing lipid-lowering medication in patients infected with COVID-19 have arisen. Some have suggested they may exacerbate their condition. It is important to consider known interactions with lipid-lowering agents and with specific therapies for COVID-19. This statement aims to collate current evidence surrounding the safety of lipid-lowering medications in patients who have COVID-19. We offer a consensus view based on current knowledge and we rated the strength and level of evidence for these recommendations. Pubmed, Google scholar and Web of Science were searched extensively for articles using search terms: SARS-CoV-2, COVID-19, coronavirus, Lipids, Statin, Fibrates, Ezetimibe, PCSK9 monoclonal antibodies, nicotinic acid, bile acid sequestrants, nutraceuticals, red yeast rice, Omega-3-Fatty acids, Lomitapide, hypercholesterolaemia, dyslipidaemia and Volanesorsen. There is no evidence currently that lipid lowering therapy is unsafe in patients with COVID-19 infection. Lipid-lowering therapy should not be interrupted because of the pandemic or in patients at increased risk of COVID-19 infection. In patients with confirmed COVID-19, care should be taken to avoid drug interactions, between lipid-lowering medications and drugs that may be used to treat COVID-19, especially in patients with abnormalities in liver function tests.
-
6.
Recent advances in synthetic pharmacotherapies for dyslipidaemias.
Sirtori, CR, Yamashita, S, Greco, MF, Corsini, A, Watts, GF, Ruscica, M
European journal of preventive cardiology. 2020;(15):1576-1596
-
-
Free full text
-
Abstract
Despite the demonstrated benefits of statins and injectable biologics, there is a need for new and safe oral agents for addressing classical lipid targets, low-density lipoprotein cholesterol (LDL-C), triglycerides and high-density lipoprotein cholesterol (HDL-C). LDL-C is unquestionably causal in the development of atherogenesis and atherosclerotic cardiovascular disease, but new options are required to address triglyceride-rich lipoproteins and lipoprotein(a). For hypercholesterolaemia, pitavastatin provides a very low dose and potent statin that does not adversely affect glucose metabolism; bempedoic acid acts at a biochemical step preceding hydroxymethylglutaryl-CoA reductase and is not associated with muscular side effects. For hypertriglyceridaemia, pemafibrate displays a unique and selective agonist activity on peroxisomal proliferator activated receptor-α that does not elevate homocysteine or creatinine. Although omega-3 fatty acids supplementation is not effective in secondary prevention, high dose eicosapentaenoic ethyl ester can lead to a remarkable fall in first and recurrent events in high risk patients with hypertriglyceridaemia/low HDL-C. Gemcabene, a dicarboxylic acid regulating apolipoprotein B-100, is effective in reducing both cholesterol and triglycerides. Among cholesteryl ester transfer protein antagonists that elevate HDL-C, only anacetrapib reduces cardiovascular events. Probucol stimulates reverse cholesteryl ester transport, lowers LDL-C stabilizing plaques and may lower incidence of cardiovascular events. These agents, which act through novel mechanisms, afford good and potentially safe treatment choices that may increase adherence and the attainment of therapeutic targets.
-
7.
ω-3 and ω-6 Polyunsaturated Fatty Acids, Obesity and Cancer.
D'Angelo, S, Motti, ML, Meccariello, R
Nutrients. 2020;(9)
Abstract
Recently, nutraceutical bioactive compounds in foods have been discovered for their potential health benefits regarding the prevention of chronic disorders, such as cancer, and inflammatory, cardiovascular, and metabolic diseases. Dietary omega-3 polyunsaturated fatty acids (ω-3PUFAs), including alpha-linolenic acid, docosapentaenoic acid, and eicosapentaenoic acid, are mostly attractive. They are available for the customers worldwide from commonly used foods and/or as components of commercial food supplements. The anti-inflammatory and hypotriglyceridemic effects of these fatty acids are well known, whereas pro-inflammatory properties have been recognized in their dietary counterparts, the ω-6PUFAs. Both ω-3 and ω-6PUFAs contribute to the production of lipid mediators such as endocannabinoids that are notably involved in control of food intake, energy sensing, and food-related disorders. In this review, we present ω-3 and ω-6PUFAs and their derivatives, endocannabinoids; discuss the anti-obesity effects of ω-3PUFAs; their roles in inflammation and colorectal cancer development; and how their action can be co-preventative and co-therapeutic.
-
8.
Review article: the impact of liver-directed therapies on the atherogenic risk profile in non-alcoholic steatohepatitis.
Connelly, MA, Velez Rivera, J, Guyton, JR, Siddiqui, MS, Sanyal, AJ
Alimentary pharmacology & therapeutics. 2020;(4):619-636
-
-
Free full text
-
Abstract
BACKGROUND Patients with non-alcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease, are at higher risk of cardiovascular disease (CVD) and associated mortality. Therefore, it is important to understand how new therapies for non-alcoholic steatohepatitis (NASH) may impact CVD risk factors in these patients. AIMS To summarise the effects of drug therapies on lipid and lipoprotein levels in patients with NASH and provide insight into the potential mechanisms for the observed changes. METHODS PubMed searches of the literature were performed and results were compiled. RESULTS Recent clinical trials have highlighted the safety and efficacy of drug candidates for the treatment of NASH. Several agents have shown improvements in the histological features of NASH and liver function. Pioglitazone, a drug that is currently available for type 2 diabetes and may be useful for NASH, exhibits beneficial effects on lipids. However, agents such as farnesoid X receptor agonists, which are in development for NASH, may adversely affect circulating lipids and lipoproteins. CONCLUSIONS NASH is a multi-system disease with a disproportionate CVD burden. Current and future drugs for NASH have had variable impact on the atherogenic risk profile. Potential co-administration of a statin may help mitigate the negative impact of some of these therapies on lipid and lipoprotein levels.
-
9.
Increased cardiovascular risk associated with hyperlipoproteinemia (a) and the challenges of current and future therapeutic possibilities.
Fras, Z
Anatolian journal of cardiology. 2020;(2):60-69
Abstract
Population, genetic, and clinical studies demonstrated a causative and continuous, from other plasma lipoproteins independent relationship between elevated plasma lipoprotein (a) [Lp(a)] concentration and the development of cardiovascular disease (CVD), mainly those related to athe-rosclerotic CVD, and calcific aortic stenosis. Currently, a strong international consensus is still lacking regarding the single value which would be commonly used to define hyperlipoproteinemia (a). Its prevalence in the general population is estimated to be in the range of 10%-35% in accordance with the most commonly used threshold levels (>30 or >50 mg/dL). Since elevated Lp(a) can be of special importance in patients with some genetic disorders, as well as in individuals with otherwise controlled major risk factors, the identification and establishment of the proper therapeutic interventions that would lower Lp(a) levels and lead to CVD risk reduction could be very important. The majority of the classical lipid-lowering agents (statins, ezetimibe, and fibrates), as well as nutraceuticals (CoQ10 and garlic), appear to have no significant effect on its plasma levels, whereas for the drugs with the demonstrated Lp(a)-lowering effects (aspirin, niacin, and estrogens), their clinical efficacy in reducing cardiovascular (CV) events has not been unequivocally proven yet. Both Lp(a) apheresis and proprotein convertase subtilisin/kexin type 9 inhibitors can reduce the plasma Lp(a) by approximately 20%-30% on average, in parallel with much larger reduction of low-density lipoprotein cholesterol (up to 70%), what puts us in a difficulty to conclude about the true contribution of lowered Lp(a) to the reduction of CV events. The most recent advancement in the field is the introduction of the novel apolipoprotein (a) [apo(a)] antisense oligonucleotide therapy targeting apo(a), which has already proven itself as being very effective in decreasing plasma Lp(a) (by even >90%), but should be further tested in clinical trials. The aim of this review was to present some of the most important accessible scientific data, as well as dilemmas related to the currently and potentially in the near future more widely available therapeutic options for the management of hyperlipoproteinemia (a).
-
10.
Proanthocyanidins of Natural Origin: Molecular Mechanisms and Implications for Lipid Disorder and Aging-Associated Diseases.
Nie, Y, Stürzenbaum, SR
Advances in nutrition (Bethesda, Md.). 2019;(3):464-478
-
-
Free full text
-
Abstract
Proanthocyanidins are phytonutrients formed by oligomerization or polymerization of subunits catechin, epicatechin, and their gallic acid esters. Proanthocyanidins are a component of many plants and thus form an integral part of the human diet. Oligomeric proanthocyanidins are currently marketed as medicinal products that target vascular disorders and chronic pathological conditions, many of which are age-associated. Proanthocyanidins are also characterized by their effects on energy homeostasis. Not dissimilar to their chemically synthesized counterparts, naturally extracted proanthocyanidins act via inhibition of lipases, stimulation of energy expenditure, or suppression of appetite. Here we review the current knowledge-base and highlight challenges and future impacts regarding involvement of proanthocyanidins in global lipid metabolism, with a focus on the molecular mechanisms and pathological conditions that progress with aging.