Anti-cytokine therapy for prevention of atherosclerosis

Abstract Background Currently a chronic inflammation is considered to be the one of the most important reasons of the atherosclerosis progression. A huge amount of researches over the past few decades are devoted to study the various mechanisms of inflammation in the development of atherosclerotic lesions. Purpose To review current capabilities of anti-inflammatory therapy for the prevention and treatment of atherosclerosis and its clinical manifestations. Methods Appropriate articles on inflammatory cytokines in atherosclerosis and anti-inflammatory prevention of atherosclerosis were searched in PubMed Database from their respective inceptions until October 2015. Sections “The role of infl…

GLP-1 receptor agonists and reduction of cardiometabolic risk: Potential underlying mechanisms

Type 2 diabetes mellitus (T2DM) is a metabolic condition with an elevated impact on cardiovascular (CV) risk. The innovative therapeutic approaches for T2DM - incretin-based therapies (IBTs), including glucagon-like peptide 1 (GLP-1) receptor agonists, have become popular and more widely used in recent years. The available scientific data from clinical studies and clinical practice highlights their beyond glucose-lowering effects, which is achieved without any increase in hypoglycaemia. The former effects include reduction in body weight, lipids, blood pressure, inflammatory markers, oxidative stress, endothelial dysfunction, and subclinical atherosclerosis, thus reducing and potentially pr…

LE VESCICOLE EXTRACELLULARI VEGETALI PER LO SVILUPPO DI NUOVI NUTRACEUTICI: STUDIO PRE-CLINICO E CLINICO DELLE PROPRIETÀ BIOLOGICHE DELLE VESCICOLE ISOLATE DA SUCCO DI LIMONE

Razionale dello studio: Le vescicole extracellulari (EVs) sono strutture lipoproteiche rilasciate dalle cellule animali e vegetali, che veicolano sostanze bioattive tra cui lipidi, proteine, acidi nucleici e altri metaboliti, rendendole più stabili e biodisponibili. EVs isolate da semi, foglie e frutti di svariate specie vegetali presentano attività anti-tumorale, anti-infiammatoria ed anti-ossidante. Metodi e Risultati: Il nostro gruppo di ricerca si occupa da anni della caratterizzazione strutturale e funzionale delle EVs da succo di limone (LEVs). Le LEVs esercitano effetti antinfiammatori sia in vitro, su linee di macrofagi murini, che ex vivo, su linfociti T, attraverso l’inibizione de…

Anti-inflammatory properties of an aldehydes-enriched fraction of grapefruit essential oil

Chronic inflammation is linked to the development of numerous diseases and is accompanied by increased cytokine secretion. Macrophages provide a first line of defense against pathogens that under inflammatory stimuli release pro-inflammatory cytokines. The essential oil (EO) fractions obtained from Citrus spp. rich in different compounds have gained the attention of both researchers and users during the last decades. In particular, grapefruit (Citrus paradisi) peel is rich in phenolics and flavonoids with several health benefits, including anti-inflammatory actions. Additionally, its EO consists of a large number of compounds such as monoterpenes, sesquiterpenes, alcohols, aldehydes, esters…

Use of Combination Statin and Bile Acid Sequestrant Therapy to Treat Dyslipidemia

Lipid management guidelines promulgated around the world continue to emphasize the need to reduce serum levels of low-density lipoprotein cholesterol (LDL-C) in order to reduce risk for acute cardiovascular events in both the primary and secondary prevention settings [1–3]. There is growing consensus that when it comes to LDL-C management, lower is better with no apparent lower limit that is discernible from current evidence, i.e., there is greater and greater benefit as LDL-C decreases with no apparent loss in safety [4–8]. Dyslipidemia and coronary artery disease (CAD) are widely prevalent throughout the world. Considerable effort continues to be focused on expanding the appropriate use o…

Nutraceuticals as Lipid-Lowering Treatment in Pregnancy and Their Effects on the Metabolic Syndrome.

Maternal nutrition and lifestyle before and during pregnancy influence both mother and offspring’s health and can be correlated with the metabolic syndrome in later life. Findings from animal and human studies indicate that nutrition during pregnancy has an important role in microbiological, metabolic, physiologic and immunologic development and homeostasis. A low nutritional intake in early pregnancy may represent a risk for adverse effects during pregnancy as well as on birth outcome. It seems that dietary supplementation with probiotics in perinatal period may represent safe and practical approach in dealing with the most common adverse pregnancy outcomes such as obesity and gestational …

Clinical anatomic, immunomorphologic and molecular anatomic data suggest interplay of thyroidal molecules, autoantibodies and Hsp60 in Hashimoto’s disease

Hsp60 is, typically, a mitochondrial protein, but it also occurs in the cytosol, vesicles, and plasma membrane, and in the intercellular space and biological fluids, e.g., blood. Changes in the levels and distribution of Hsp60 are linked to several pathologies, including cancer and chronic inflammatory and autoimmune disorders. What is the histopathological pattern of Hsp60 in the thyroid of Hashimoto’s patients? Are there indications of a pathogenic role of Hsp60 that may make Hashimoto’s thyroiditis a chaperonopathy? Experiments reported here provide information regarding those questions. We found by various immunomorphological techniques increased levels of Hsp60 in the thyroid from HT p…

Effects of obesity and estradiol on Na+/K+-ATPase and their relevance to cardiovascular diseases

Obesity is associated with aberrant sodium/potassium-ATPase (Na+/K+-ATPase) activity, apparently linked to hyperglycemic hyperinsulinemia, which may repress or inactivate the enzyme. The reduction of Na+/K+-ATPase activity in cardiac tissue induces myocyte death and cardiac dysfunction, leading to the development of myocardial dilation in animal models; this has also been documented in patients with heart failure (HF). During several pathological situations (cardiac insufficiency and HF) and in experimental models (obesity), the heart becomes more sensitive to the effect of cardiac glycosides, due to a decrease in Na+/K+-ATPase levels. The primary female sex steroid estradiol has long been …

An overview of statin-induced myopathy and perspectives for the future

Introduction: Statins remain the most commonly prescribed lipid-lowering drug class for the treatment of atherosclerotic cardiovascular disease. Their well-recognized side effects are known as statin-associated muscle symptom (SAMS). Some advances in this field have been made in recent years, but the understanding of the mechanisms has lagged. Investigating the specific role of the anti-HMGCR autoantibody, pharmacokinetic genetic variants, characterization of the known phenotypes of statin toxicity, in relation to clinical markers of disease, is of high importance. Areas covered: We summarized currently available findings (on PubMed) related to SAMS and discussed the therapeutic approaches,…

Peroxisome Proliferator-Activated Receptors and Atherosclerosis

The peroxisome proliferator-activated receptors (PPARs) represent the family of 3 nuclear receptor isoforms-PPARα, -γ, and -δ/β, which are encoded by different genes. As lipid sensors, they are primarily involved in regulation of lipid metabolism and subsequently in inflammation and atherosclerosis. Atherosclerosis considers accumulation of the cells and extracellular matrix in the vessel wall leading to the formation of atherosclerotic plaque, atherothrombosis, and other vascular complications. Besides existence of natural ligands for PPARs, their more potent synthetic ligands are fibrates and thiazolidindiones. Future investigations should now focus on the mechanisms of PPARs activation, …

Liraglutide Improved Cardiometabolic Parameters More in Obese than in Non-obese Patients with Type 2 Diabetes: A Real-World 18-Month Prospective Study.

Introduction The glucagon-like peptide-1 agonist (GLP1-RA) liraglutide is currently approved for the treatment of both obesity and type 2 diabetes (T2DM). We investigated whether the effect of this agent on cardiometabolic parameters in subjects with T2DM varied in relation to the concomitant presence of obesity. Methods One hundred thirty-five subjects (78 men and 57 women; age: 62 +/- 10 years) naive to incretin-based therapies were treated with low-dose liraglutide (1.2 mg/day) as an add-on to metformin for 18 months. Patients were divided into two subgroups based on their body-mass index (BMI): (a) obese (BMI >= 30) and (b) non-obese (BMI < 30). Clinical and laboratory analyses we…

Gestational diabetes and the metabolic syndrome: Can obesity and small, dense low density lipoproteins be key mediators of this association?

Gestational diabetes mellitus (GDM) represents a condition of glucose intolerance with first appearance or recognition at the time of a pregnancy, associated with an inadequate pancreatic response to the advanced insulin resistance of the later stages of pregnancy, and accompanied by enhancing β-cell mass and secretion of insulin. Women who had GDM exhibit a higher risk for later advent of type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). Additionally, previous GDM has been proposed as independently correlated with higher risk for development of atherosclerosis in a healthy population, similar to the metabolic syndrome (MetS) and independently of the presence of established…

Inclisiran: a small interfering RNA strategy targeting PCSK9 to treat hypercholesterolemia

Introduction: Inclisiran is a novel posttranscriptional gene silencing therapy that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis by RNA interference and has a potent, dose-dependent, durable effect in lowering LDL-C, and therefore is an effective drug to treat dyslipidemia, reducing the risk for acute cardiovascular (CV) events. It is safe and well-tolerated. Areas covered: This paper aims to review the mechanism of action of inclisiran while evaluating its efficacy and safety in the treatment of dyslipidemia from data of the clinical trials in the ORION program. Expert opinion: Data from the clinical trials in the ORION program demonstrated efficacy and safety o…

Gli effetti extraglicemici di liraglutide: Focus sui marker cardiometabolici

The purpose of innovative therapeutic approaches for type 2 diabetes mellitus is to customize the antidiabetic treatment to each patient's need, in order to intensify glucose-lowering effects without hypoglycemia, reduce adverse events, and prevent cardiovascular events. Glucagon-like peptide 1 (GLP-1) analogues are effective drugs in the treatment of type 2 diabetes, and they also seem to have beneficial effects on several risk factors for cardiovascular disease, leading to cardiovascular risk reduction independent of hypoglycemic effects. Among these new drugs, liraglutide, a GLP-1 analogue with a homology of 97% to native GLP-1, exerts an effect on body weight, lipid parameters, blood pr…

Effects of Liraglutide on Carotid Intima-Media Thickness in Patients with Type-2 Diabetes and Non-Alcoholic Fatty Liver Disease: An 8-Month Prospective Pilot Study

Serological, immunomorphological and bioinformatics analyses suggest Hsp60 is involved in Hashimoto’s thyroiditis pathogenesis.

ETC-1002: A future option for lipid disorders?

ETC-1002 is a new investigational low density lipoprotein cholesterol (LDL-C)-lowering agent (Esperion Therapeutics, Inc.). ETC-1002 is a dicarboxylic acid derivative with a novel mechanism of action targeting two hepatic enzymes - adenosine triphosphate-citrate lyase (ACL) and adenosine monophosphate-activated protein kinase (AMPK), inhibiting sterol and fatty acid synthesis and promoting mitochondrial long-chain fatty acid oxidation. This agent is currently in phase II clinical research. Available data report that ETC-1002 significantly decreased LDL-C levels (up to 32%) in both patients with normal and elevated baseline levels of triglycerides. Such beneficial effect is superior to curre…

Periodontitis, blood lipids and lipoproteins

Periodontitis, one of the most common chronic infections in adults, is characterized by the accumulation of dental plaque and infection by gram-negative pathogens bacteria, which further lead to the destruction of periodontal tissues. A relationship between chronic periodontitis and abnormalities in lipid and/or lipoprotein metabolism is not well understood yet. Periodontitis is associated with elevated pro-atherogenic plasma-lipids, including small dense LDL, while oxidized LDL may act as inflammatory stimulant in periodontitis. Periodontal pathogens may directly modify lipoprotein, including protective characteristics of HDL and contribute to development of metabolic syndrome, Type 2 diab…

Psoriasis and acute coronary syndrome risk

Statins and new-onset diabetes

Statins are highly efficacious lipid modifying agents that reduce the risk for cardiovascular (CV) events in both primary and secondary prevention settings. However, statins affect molecular mechanisms which adversely impact on insulin sensitivity and β-cell function, thereby increasing risk for new onset diabetes mellitus (NOD). Defining the mechanisms involved is the focus of considerable current investigation. The statins reduce the risk for CV events in normoglycemic patients as well as in those with diabetes mellitus (DM) and their benefits outweigh the risk of inducing NOD. We review the clinical evidence for NOD with statin treatment, as well as the potential mechanisms involved. Our…

A Nutraceutical Containing Chlorogenic Acid and Luteolin Improves Cardiometabolic Parameters in Subjects with Pre-Obesity: A 6-Month Randomized, Double-Blind, Placebo-Controlled Study

Pre-obesity is a condition that predisposes to the risk of developing obesity, cardiovascular diseases (CVD), and diabetes. Our previous study demonstrated that a Cynara cardunculus (L.) based nutraceutical named Altilix® (Bionap, Italy), containing chlorogenic acid and luteolin extracts, was able to improve several hepatic and cardio-metabolic parameters. Given this background, we conducted a post-hoc analysis of the Altilix® study in order to analyze the supplement’s effects in the subgroup of pre-obesity subjects on anthropometry (weight and waist circumference), glucose metabolism (HbA1C, HOMA-IR, and HOMA-β), lipid profile (total cholesterol, triglycerides, LDL-chole…

Nutraceuticals in Lipid-Lowering Treatment

Lipid-lowering drugs may cause adverse effects and, although lipid targets may be achieved, a substantial residual cardiovascular (CV) risk remains. Treatment with agents mimicking proteins present in the body, such as incretin-based therapies, provided promising results. However, in order to improve lipids and CV risk, lifestyle measures remain important. Some researchers focused on nutraceuticals that may beneficially affect metabolic parameters and minimize CV risk. Chitosan, a dietary fiber, can regulate lipids with benefit on anthropometric parameters. The beneficial properties of dietary supplements (such as green tea extract, prebiotics, plant sterols, and stanols) on plasma lipids,…

The dissociation of the Hsp60/pro-Caspase-3 complex by bis(pyridyl)oxadiazole copper complex (CubipyOXA) leads to cell death in NCI-H292 cancer cells

Abstract Cell survival and proliferation are central to carcinogenesis, involving various mechanisms among which those that impede apoptosis are important. In this, the role of the molecular chaperone Hsp60 is unclear since it has been reported that it can be both, pro- or anti-apoptotic. A solution to this riddle is crucial to the development of anti-cancer therapies targeting Hsp60. We addressed this question using a tumor cell line, NCI-H292, and [Cu(3,5-bis(2′-pyridyl)-1,2,4-oxadiazole) 2 (H 2 O) 2 ](ClO 4 ) 2 , CubipyOXA , a copper-containing compound with cytotoxic properties. We treated cells with various doses of the compound and measured cell viability; apoptosis indicators; and le…

Serum low density lipoprotein subclasses in asthma

Summary Background The levels of serum low-density lipoproteins (LDL) have been implicated in the inflammatory cascade in a murine model of asthma. Recent findings suggest that LDL may modulate the inflammatory state of the asthmatic airways in humans. Objective We explored whether LDL subclasses are associated with the occurrence and severity of asthma. Methods 24 asthmatics (M/F: 11/13) and 24 healthy individuals, with normal BMI and absence of metabolic syndrome, matched for age and gender. Serum concentrations of LDL subclasses were distributed as seven bands (LDL-1 and -2 defined as large, least pro-inflammatory LDL, and LDL-3 to −7 defined as small, most pro-inflammatory LDL), using t…

A novel copper compound, CuNV110, induces apoptosis in tumor cells by dissociation of the Hsp60- pro-caspase 3 complex

The biological activity of CuNV1110, a novel copper chemical compound, has been recently studied on cancer cells and it has been showed that it reduces the cell viability, in a dose and time dependent manner, and induces cell apoptosis. In this study we evaluated the possible mechanisms by which CuNV1110 induces cell apoptosis. In particular we looked at its effects on Hsp60 levels and caspase 3 activation. We used an in vitro model of a pulmonary mucoepidermoid carcinoma (NCI-H292 cells). We found that CuNV1110 reduces the cell viability and induces cell apoptosis in a dose/time dependent manner. Then, we found that Hsp60 levels decrease with the increasing concentrations of CuNV110; by co…

Nutraceuticals as an Important Part of Combination Therapy in Dyslipidaemia

Several risk factors such as abnormality of lipid metabolism (e.g. high levels of low-density lipoprotein cholesterol (LDL-C), elevated triglycerides and low levels of high-density lipoprotein cholesterol (HDL-C)) play a central role in the aetiology of cardiovascular disease (CVD). Nutraceutical combination together with a cholesterol- lowering action, when associated with suitable lifestyle, should furnish an alternative to pharmacotherapy in patients reporting statin-intolerance and in subjects at low cardiovascular risk. The present review is focused on nutraceuticals and their synergetic combinations demonstrating a beneficial effect in the management of dyslipidaemia. Several nutraceu…

CuNV1110 induces dissociation of the Hsp60-pro-caspase 3 complex and activation of apoptosis in tumor cells

Drug Evaluation: The Combination of Fenofibrate and Simvastatin for the Treatment of Dyslipidemia: When and for Whom?

Simvastatin and fenofibrate are the most frequently co-prescribed drugs for the treatment of dyslipidemia, manifesting beneficial effects on non-lipid parameters as well. The combination of these two drugs has been shown to increase success in the management of combined hyperlipidemia. Their different mechanism of action allows for the targeting of two types of lipid abnormalities: increased cholesterol and atherogenic dyslipidemia. Clinical studies have demonstrated that statin and fibrate combination therapy is effective in improving multiple lipid abnormalities, that may further decrease overall cardiovascular (CV) risk of patients with combined dyslipidemia. However, the clinical use of…

LDL and HDL subfractions, dysfunctional HDL: treatment options.

Low-density lipoproteins (LDL) are considered as important risk factors for cardiovascular diseases (CVD), while highdensity lipoproteins (HDL) are well recognized for their putative role in reverse cholesterol transport and other atheroprotective functions. Both LDL and HDL are heterogeneous in nature, including various subfractions depending on the method of isolation (≥ 7 LDL and 10 HDL subspecies, respectively). While it is established that small, dense LDL (sdLDL) have atherogenic potential, the role of different HDL subfractions is still largely unclear. The majority of clinical studies suggest an atheroprotective role of larger HDL particles, although recent work has highlighted the…

IMPROVE-IT: what have we learned?

Purpose of review: Recent studies and dyslipidemia treatment guidelines indicate that combination lipid-lowering therapy is frequently needed and its use has increased in recent years. Ezetimibe and simvastatin as a fixed dose is an efficacious treatment choice based on positive results of the recent IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). In this review, we discuss recent controversies surrounding ezetimibe and provide clinical perspective on the results of the IMPROVE-IT study. Recent findings: IMPROVE-IT is the first trial that demonstrates a significant clinical benefit of a nonstatin hypolipidemic agent (ezetimibe) used in combination with sta…

An evaluation of RVX-208 for the treatment of atherosclerosis

Introduction: RVX-208 is a first-in-class, orally active, novel small molecule in development by Resverlogix Corporation (Calgary, AB, Canada). It acts through an epigenetic mechanism by inhibiting the bromodomain and extraterminal (BET) family of proteins, increasing apolipoprotein A-I (apoA-I) and targeting high-density lipoprotein (HDL) metabolism, including generating of nascent HDL and increased larger HDL particles, resulting in the stimulation of reverse cholesterol transport. RVX-208 also has a beneficial effect on inflammatory factors known to be involved in atherosclerosis and plaque stability. New therapeutic strategies are needed for patients with atherosclerosis.Areas covered: …

The efficacy and safety of dipeptidyl peptidase-4 inhibitors compared to other oral glucose-lowering medications in the treatment of type 2 diabetes

ABSTRACT Introduction The dipeptidyl peptidase-4 inhibitors (DPP-4is), which belong to the class of incretin-based medications, are recommended as second or third-line therapies in guidelines for the management of type 2 diabetes mellitus. They have a favorable drug tolerability and safety profile compared to other glucose-lowering agents. Objective This review discusses data concerning the use of DPP-4is and their cardiovascular profile, and gives an updated comparison with the other oral glucose-lowering medications with regards to safety and efficacy. Currently available original studies, abstracts, reviews articles, systematic reviews and meta-analyses were included in the review. Discu…

Can the effects of gender, menopause and ageing on lipid levels be differentiated?

The menopause, as well as ageing in both genders, can influence cardiovascular disease (CVD) risk1. An atherogenic lipoprotein profile, including small dense low density lipoprotein (sdLDL) particles, can be present even in normolipidaemic healthy young individuals (about 6%)2. If confirmed by larger studies, it will be necessary to consider different risk stratifications for those with atherogenic normolipidaemia and those with non-atherogenic hypercholesterolaemia. Furthermore, other changes associated with the menopause (increase in lipoprotein (a) [Lp(a)] levels, central obesity, endothelial dysfunction and systemic inflammation) may contribute to pro-atherogenic changes, while ethnicit…

Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel

Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has focused on statin-associated muscle symptoms (SAMS), and avoided the use of the term 'statin intolerance'. Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10 - 15% of patients. In clinical practice, statin intolerance limits effecti…

Effects of Aging and Diet on Cardioprotection and Cardiometabolic Risk Markers.

The prevalence of several diseases increases by age, including cardiovascular diseases, which are the leading cause of morbidity and mortality worldwide. Aging, as a complex process characterized by senescence, triggers various pathways, such as oxidative stress, systemic inflammation, metabolism dysfunction, telomere shortening, mitochondrial dysfunction and deregulated autophagy. A better understanding of the mechanisms underlying senescence may lead to the development of new therapeutic targets and strategies for age-related pathologies and extend the healthy lifespan. Modulating lifestyle risk factors and adopting healthy dietary patterns remain significant tools in delaying the aging …

A meta-analysis of the role of statins on renal outcomes in patients with chronic kidney disease. Is the duration of therapy important?

article i nfo Introduction: The efficacy of statin treatment in chronic kidney disease (CKD) patients remains controversial. Therefore, we performed a meta-analysis to investigate whether statins modulate renal function in patients with CKD. Methods: Data from Scopus, PubMed, Web of Science, and the Cochrane Central Register of randomized controlled trials for years 1966-December 2012 were searched for appropriate studies. Results: Twenty trials with 6452 CKD subjects randomized to receive either statin or placebo were included. Statin therapy significantly influenced high sensitivity C-reactive protein levels in patients on or off dialysis (−0.28 mg/dl, 95%CI: −0.93 to −0.37; p b 0.05 and …

Adipokines and lipoproteins: modulation by antihyperglycemic and hypolipidemic agents.

Adipose tissue is an endocrine organ that secretes a number of hormones and metabolically active substances that impact energy metabolism and insulin sensitivity. These inflammatory markers are collectively referred to as adipocytokines, or adipokines. Adipose tissue's functional capacity and metabolic activity vary among individuals, thus partly explaining the incomplete overlap between obesity and the metabolic syndrome. The functional failure of adipose tissues results in changed energy delivery and impaired glucose consumption, triggering self-regulatory mechanisms to maintain homeostasis. Antihyperglycemic, hypolipidemic, antiobesity, and angiotensin II receptor blocker drugs influence…

Small, dense LDL: An update

Purpose of review In this review, we summarize the latest findings on small, dense LDL (sdLDL) atherogenic particles, including their associations with other biomarkers. Recent findings Increased sdLDL levels have been reported not only in different metabolic disorders such as diabetes, obesity and metabolic syndrome, but also in patients with rheumatoid and psoriatic arthritis as well as hypothyroidism. A wide range of lipid-lowering, as well as other drug classes, including novel antidiabetic agents and nutraceuticals, exert favourable effects on these atherogenic particles. The 'gold standard' methodology for the assessment of sdLDL has not been established yet. However, the association …

Effects of statins on lipid profile in chronic kidney disease patients: a meta-analysis of randomized controlled trials

The available data on statin effects in chronic kidney disease (CKD) patients are still conflicting. We investigated the impact of short- and long-term statin therapy on lipid profiles in CKD patients requiring or not requiring dialysis.Data from Scopus, PubMed, Web of Science, and the Cochrane Library from 1966 to May 2012 were searched for studies that investigated this effect. We included all randomized controlled clinical trials that investigated the impact of statin therapy on lipids and lipoproteins.The final analysis included 16 trials with 3594 subjects. In CKD patients, statin therapy significantly reduced total cholesterol (TC), triglycerides (TG) and low-density lipoprotein chole…

Lifestyle recommendations for the prevention and management of metabolic syndrome: an international panel recommendation.

The importance of metabolic syndrome (MetS) lies in its associated risk of cardiovascular disease and type 2 diabetes, as well as other harmful conditions such as nonalcoholic fatty liver disease. In this report, the available scientific evidence on the associations between lifestyle changes and MetS and its components is reviewed to derive recommendations for MetS prevention and management. Weight loss through an energy-restricted diet together with increased energy expenditure through physical activity contribute to the prevention and treatment of MetS. A Mediterranean-type diet, with or without energy restriction, is an effective treatment component. This dietary pattern should be built …

Natural approaches in metabolic syndrome management

Metabolic syndrome (MetS) is characterized as a group of cardiometabolic risk factors that raise the risk for heart disease and other health problems, such as diabetes mellitus and stroke. Treatment strategies include pharmacologic interventions and supplementary (or "alternative") treatments. Nutraceuticals are derived from food sources (isolated nutrients, dietary supplements and herbal products) that are purported to provide health benefits, in addition to providing basic nutritional value. Nutraceuticals are claimed to prevent chronic diseases, improve health, delay the aging process, increase life expectancy, and support the structure and function of the body. The study of the benefici…

PPAR Agonists, Atherogenic Dyslipidemia and Cardiovascular Risk.

Peroxisome proliferator-activated receptors (PPAR) are implicated in the pathology of several metabolic diseases including obesity, diabetes, and atherosclerosis. PPAR agonists exert multiple lipid modifying actions which are beneficial to the prevention of atherosclerosis. Such benefits in lipid lowering actions include improvements in atherogenic dyslipidemia that seems to be particularly expressed in individuals at higher cardiovascular (CV) risk. In addition, the favorable effects of PPAR agonists on different cardio-metabolic parameters are established in several metabolic conditions, such as diabetes mellitus, insulin resistance, and heightened systemic inflammation. The goal of this …

Nutraceuticals Supporting Body Weight Loss

It is known that obesity has reached epidemic proportions and its management is of high clinical importance. In this chapter we will discuss recent data about the role of nutraceuticals and functional foods in obesity and body weight management, including the mechanisms responsible for their favorable effects. In addition, the impact of healthy dietary patterns on weight loss will be addressed. Apart from influencing the imbalance between energy intake and output, nutraceuticals may prevent and/or decrease the development of oxidative stress and inflammation in obesity, as well as favorably influence other cardiovascular disease risk factors, thereby limiting obesity-related complications. …

Lipoprotein Subfractions in Metabolic Syndrome and Obesity: Clinical Significance and Therapeutic Approaches

Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS) are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in t…

Altilix® Supplement Containing Chlorogenic Acid and Luteolin Improved Hepatic and Cardiometabolic Parameters in Subjects with Metabolic Syndrome: A 6 Month Randomized, Double-Blind, Placebo-Controlled Study

The objective was to evaluate the effects of 6 months of supplementation with Altilix&reg

Gut Microbiota, Obesity and Bariatric Surgery: Current Knowledge and Future Perspectives.

Background::There is an urgent need for a better understanding and management of obesity and obesity- associated diseases. It is known that obesity is associated with structural and functional changes in the microbiome.Methods::The purpose of this review is to present current evidence from animal and human studies, demonstrating the effects and the potential efficacy of microbiota modulation in improving obesity and associated metabolic dysfunctions.Results::This review discusses possible mechanisms linking gut microbiota dysbiosis and obesity, since there is a dual interaction between the two of them. Furthermore, comments on bariatric surgery, as a favourable model to understand the under…

The effect of bergamot on dyslipidemia

Abstract Background Statins are the most common used lipid lowering drugs but they may cause adverse effects and despite their well-established therapeutic benefits residual cardiovascular (CV) risk remains. The use of other lipid lowering drugs and nutraceuticals alone or as add-on lipid-modifying therapy can be an option in such cases. Several studies have reported health-related properties of the Citrus fruits, among which bergamot (Citrus bergamia Risso) differs from others by particularly high content of certain compounds. Purpose This narrative review summarizes the current evidence on the effects of bergamot on lipid parameters based on studies involving animals and humans. Main evid…

Novel anti-obesity drugs and plasma lipids

Obesity is a health problem of global, epidemic proportions and a major risk factor for chronic diseases resulting in accelerated morbidity and mortality. Dyslipidemia with a predominance of small dense LDL, impaired functionality of HDL particles, and increased serum levels of remnant particles due to impaired clearance of triglyceriderich lipoproteins significantly heightens cardiovascular events in obese subjects. Pharmacotherapy in combination with lifestyle modification is the primary approach to reduce obesity-related cardiovascular risk. Although there are several potential anti-obesity drugs, orlistat is the only agent that remains available in the market. Lorcaserin and Qsymia ® , …

Emerging approaches for the treatment of hypertriglyceridemia.

Hypertriglyceridemia is frequent in diabetic and obese subjects, who are at increased risk for cardiovascular diseases (CVD). Increased triglycerides (TG) are a hallmark of atherogenic dyslipidemia, representing a marker of atherogenic small dense low-density lipoproteins (sdlDL). Importantly, non-fasting/postprandial TG measurements tend to be emphasized in clinical practice for the prediction of CVD, and TG-lowering agents (primarily fibrates) have a beneficial effect on atherogenic dyslipidemia, reducing TG-rich particles and ultimately lowering the production of sdlDL. The combination of omega-3 fatty acids and statins is also recommended, and widely used in clinical practice for subjec…

Effects of Chitosan on Plasma Lipids and Lipoproteins

Chitosan can favorably modulate plasma lipids, but the available data are not conclusive. We evaluated the effect of chitosan on plasma lipids and lipoproteins in 28 patients with plasma triglyceride levels >150 mg/dL (mean age: 63 ± 12 years), not taking other lipid-lowering agents. All patients received a chitosan derived from fungal mycelium (Xantonet, Bromatech, Italy) at a fixed dose of 125 mg/d in addition to their current medications for 4 months. Polyacrylamide gel electrophoresis was used to measure low-density lipoprotein (LDL) subclasses. After treatment, total cholesterol reduced by 8%, LDL cholesterol by 2%, and triglycerides by 19%, with a concomitant 14% increase in high-…

Nutraceuticals as Lipid-Lowering Treatment in Pregnancy and Their Effects on the Metabolic Syndrome.

Maternal nutrition and lifestyle before and during pregnancy influence both mother and offspring's health and can be correlated with the metabolic syndrome in later life. Findings from animal and human studies indicate that nutrition during pregnancy has an important role in microbiological, metabolic, physiologic and immunologic development and homeostasis. A low nutritional intake in early pregnancy may represent a risk for adverse effects during pregnancy as well as on birth outcome. It seems that dietary supplementation with probiotics in perinatal period may represent safe and practical approach in dealing with the most common adverse pregnancy outcomes such as obesity and gestational …

Liraglutide Reduces Oxidative Stress And Restores Heme Oxygenase-1 and Ghrelin Levels in Patients with Type 2 Diabetes: A Prospective Pilot Study

Abstract Context: Liraglutide is a glucagon-like peptide-1 analog and glucose-lowering agent whose effects on cardiovascular risk markers have not been fully elucidated. Objective: We evaluated the effect of liraglutide on markers of oxidative stress, heme oxygenase-1 (HO-1), and plasma ghrelin levels in patients with type-2 diabetes mellitus (T2DM). Design and Setting: A prospective pilot study of 2 months' duration has been performed at the Unit of Diabetes and Cardiovascular Prevention at University of Palermo, Italy. Patients and Intervention(s): Twenty subjects with T2DM (10 men and 10 women; mean age: 57 ± 13 y) were treated with liraglutide sc (0.6 mg/d for 2 wk, followed by 1.2 mg/d…

GLP-1 receptor agonists, carotid atherosclerosis and retinopathy

It is known that diabetes is associated with the development of premature atherosclerosis and microvascular complications and consequently increased cardiovascular (CV) morbidity and mortality. In ...

Intensive LDL-cholesterol lowering therapy and neurocognitive function

The key lipid-lowering target is to achieve guideline-recommended low-density lipoprotein cholesterol (LDL-C) levels, usually by using statins. The new treatment strategies for lipid-lowering therapy include using proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors as an exciting approach to reduce residual risk of cardiovascular diseases (CVD). However, concerns about possible adverse effects, including neurocognitive disorders, were issued by the Food and Drug Administration (FDA). The current disputable evidence does not allow definite conclusions as to whether statins contribute to, or cause, clinically meaningful cognitive impairment. Some evidence indicates a high rate of…

Low- and high-density lipoprotein subclasses in subjects with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with increased cardiometabolic risk. Although dyslipidemia represents a key factor in this disease, its impact on serum levels of distinct lipoprotein subfractions is largely unknown.OBJECTIVE: To assess the full low-density lipoprotein (LDL) and high-density lipoprotein (I-EDL) profiles in patients with NAFLD.METHODS: Seven LDL and 10 HDL subfractions were assessed by gel electrophoresis (Lipoprint, Quantimetrix Corporation, USA) in men with biopsy proven NAFLD (simple steatosis [n = 17, age, 34 7 years] and nonalcoholic steatohepatitis [NASH; n = 24, age, 32 +/- 6 years]). Exclusion criteria included robust alcohol consump…

Adipokines and Lipoproteins: Modulation by Antihyperglycemic and Hypolipidemic Agents

Abstract Adipose tissue is an endocrine organ that secretes a number of hormones and metabolically active substances that impact energy metabolism and insulin sensitivity. These inflammatory markers are collectively referred to as adipocytokines, or adipokines. Adipose tissue's functional capacity and metabolic activity vary among individuals, thus partly explaining the incomplete overlap between obesity and the metabolic syndrome. The functional failure of adipose tissues results in changed energy delivery and impaired glucose consumption, triggering self-regulatory mechanisms to maintain homeostasis. Antihyperglycemic, hypolipidemic, antiobesity, and angiotensin II receptor blocker drugs …

Liraglutide Increases Serum Levels of MicroRNA-27b, -130a and -210 in Patients with Type 2 Diabetes Mellitus: A Novel Epigenetic Effect

Liraglutide has shown favourable effects on several cardiometabolic risk factors, beyond glucose control. MicroRNAs (miRNAs) regulate gene expression, resulting in post-transcriptional modifications of cell response and function. Specific miRNAs, including miRNA-27b, miRNA-130a, and miRNA-210, play a role in cardiometabolic disease. We aimed to determine the effect of liraglutide on the serum levels of miRNA-27b, miRNA-130a and miRNA-210. Twenty-five subjects with type-2 diabetes mellitus (T2DM), na&iuml

Should low high-density lipoprotein cholesterol (HDL-C) be treated?

The first observations linking a low serum level of HDL-C to increased risk for cardiovascular disease were made over 50 years ago. High serum levels of HDL-C appear to protect against the development of atherosclerotic disease, while low serum levels of this lipoprotein are among the most important predictors of atherosclerotic disease in both men and women and people of all racial and ethnic groups throughout the world. It has long been assumed that therapeutic interventions targeted at raising HDL-C levels would lower risk for such cardiovascular events as myocardial infarction, ischemic stroke, and death. Even after five decades of intensive investigation, evidence to support this assum…

The role of fibrate treatment in dyslipidemia: an overview.

Dyslipidemia, and especially atherogenic dyslipidemia, a combination of small low-density lipoproteins cholesterol (LDL-C), decreased high-density lipoprotein cholesterol (HDL-C) and increased triglyceride (TG) concentrations, represents a major cardiovascular (CV) risk factor. Nuclear receptor peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of lipid metabolism; PPAR ligands are used to treat dyslipidemias. Fibrates have a major impact on TG metabolism as well as on modulating LDL size and subclasses. Fibrates target atherogenic dyslipidemia by increasing plasma HDL-C concentrations and decreasing small dense LDL (sdLDL) particles and TGs, thus contributin…

Weight loss programmes using low carbohydrate diets to control the cardiovascular risk in adolescents (Review).

Cardiovascular risk (CVR) is a broad term that includes traditional factors like hypertension, hyper lipidemia, abdominal obesity, hyperinsulinemia or overt type 2 diabetes mellitus (T2DM), and emerging ones such as hypothyroidism or inflammatory diseases. In epidemiologic studies, all of these factors are associated with atherogenesis and have complex interactions between them. They have in common an increased prevalence in the general population beginning in childhood, and are correlated with endothelial damage as demonstrated by echocardiographic modifications of the left ventricle or carotid intima-media thickness. Adolescence is a transition period where behavioural eating patterns dev…

SUBFRACTIONS AND SUBPOPULATIONS OF HDL: AN UPDATE

High-density lipoproteins (HDL) are classified as atheroprotective because they are involved in transport of cholesterol to the liver, known as "reverse cholesterol transport (RCT)" exerting antioxidant and anti-inflammatory activities. There is also evidence for cytoprotective, vasodilatory, antithrombotic, and anti-infectious activities for these lipoproteins. HDLs are known by structural, metabolic and biologic heterogeneity. Thus, different methods are able to distinguish several subclasses of HDL. Different separation techniques appear to support different HDL fractions as being atheroprotective or related with lower cardiovascular (CV) risk. However, HDL particles are not always prote…

Uric Acid Metabolism in Pre-hypertension and the Metabolic Syndrome

In humans uric acid (UA) is the end product of degradation of purines. The handling of UA by the renal system is a complex process which is not fully understood. To date, several urate transporters in the renal proximal tubule have been identified. Among them, urate transporter 1 (URAT1) and a glucose transporter 9 (GLUT9) are considered of greater importance, as potential targets for treatment of hyperuricemia and the potential associated cardio-metabolic risk. Therefore, the recognition of the metabolic pathway of UA and elucidation of occurrence of hyperuricemia may provide important insights about the relationship between UA, pre-hypertension (preHT) and the metabolic syndrome (MetS). W…

Incretins, Pregnancy, and Gestational Diabetes

The number of pregnant women affected by gestational diabetes mellitus (GDM) is increasing among Caucasians, and East Asians. GDM also increases the risk for later advent of type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease in both women and their offspring. The underlying mechanism of GDM is not fully elucidated. Incretins such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), have been suggested to have a role in maternal metabolism and weight as well as fetal growth. These hormones might be implicated in mechanisms that compensate for the increment in glycemia and insulin resistance seen during pregnancy, while other factors, such a…

The effects of liraglutide on glucose, inflammatory markers and lipoprotein metabolism: current knowledge and future perspectives.

Glucagon-like peptide-1 is an incretin secreted in response to nutrient ingestion. Derangements in the incretin system may contribute to the onset and progression of hyperglycemia in Type 2 diabetes. Liraglutide is a long-acting human glucagon-like peptide-1-receptor agonist suitable for once-daily administration. Blood glucose- and weightreducing effects, improvements in pancreatic b-cell function and a low risk of hypoglycemic events have been demonstrated with this agent. There is a trend towards improvement in the proinflammatory milieu. Liraglutide also appears to have beneficial effects on plasma lipids and lipoproteins in the form of a reduction in total cholesterol, triglycerides an…

Nutraceuticals and Lipid Management

Scientific data support the effectiveness of reducing total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in preventing atherosclerotic disease cardiovascular disease (ASCVD) events. Current guidelines suggest the use of innovative nutritional strategies in lipid management based on consumption of nutraceuticals and functional foods. Nutraceuticals are products isolated or purified from foods (generally sold in medicinal forms), while a functional food is similar in appearance to, or may be, a conventional food. Both nutritional components promote health, lead to better well-being, and reduce risk of cardiovascular disease, possibly by affecting plasma lipid levels. The m…

Exosomal Heat Shock Proteins as New Players in Tumour Cell-to-cell Communication

Exosomes have recently been proposed as novel elements in the study of intercellular communication in normal and pathological conditions. The biomolecular composition of exosomes reflects the specialized functions of the original cells. Heat shock proteins (Hsps) are a group of chaperone proteins with diverse biological roles. In recent years, many studies have focused on the extracellular roles played by Hsps that appear to be involved in cancer development and immune system stimulation. Hsps localized on the surface of exosomes, secreted by normal and tumour cells, could be key players in intercellular cross-talk, particularly during the course of different diseases, such as cancer. Exoso…

Effect of a Natural Supplement Containing Curcuma Longa, Guggul, and Chlorogenic Acid in Patients With Metabolic Syndrome

The impact of a natural supplement (Kepar; Rikrea, Italy), containing several plant extracts such as curcuma longa, silymarin, guggul, chlorogenic acid, and inulin, was evaluated in 78 patients with metabolic syndrome (MetS; 45 men; age: 62 ± 9 years). Kepar at a dose of 2 pills/d was given for 4 months as add-on therapy to the ongoing treatment, maintained at fixed doses for the entire study. Anthropometric variables, plasma lipids, glucose parameters, and oxidative stress were measured at baseline and after 4 months. We found significant reductions in body weight (from 81.1 ± 13.5 to 79.4 ± 12.5 kg, P < .0001), body mass index (from 29.6 [23.7] to 29.3 [21.9] kg/m2, P = .001), and wai…

Liraglutide Reduces Carotid Intima-Media Thickness by Reducing Small Dense Low-Density Lipoproteins in a Real-World Setting of Patients with Type 2 Diabetes: A Novel Anti-Atherogenic Effect

Introduction: Liraglutide has several non-glycemic effects, including those on plasma lipids and lipoproteins, contributing to its cardiovascular benefit; however, the exact underlying mechanisms remain unclear. We investigated a novel anti-atherogenic effect of liraglutide in a real-world prospective study on patients with type 2 diabetes (T2DM). Methods: Sixty-two patients with T2DM (31 men, 31 women; mean age ± standard deviation 61 ± 9 years) naïve to incretin-based therapies were treated with liraglutide (1.2 mg/day) as add-on therapy to metformin (1500–3000 mg/day) for 4 months. Laboratory analyses included the assessment of lipoprotein subclass profile by gel electrophoresis (Lipopri…

Resistin: An Inflammatory Cytokine. Role in Cardiovascular Diseases, Diabetes and the Metabolic Syndrome

Resistin is an adipocyte- and monocyte-derived cytokine which has been implicated in the modulation of insulin action, energy, glucose and lipid homeostasis. Resistin has been associated with insulin resistance and many of its known complications. As a molecular link between metabolic signals, inflammation, and vascular dysfunction, resistin can be proposed as playing a significant role in the heightened inflammatory state induced by metabolic stress linked to excessive caloric intake, thus contributing to the risk for metabolic syndrome (MetS), type 2 diabetes (T2DM), and cardiovascular diseases (CVD). In this review, we highlighted the role of resistin, as an inflammatory cytokine, in the…

Cardiovascular outcomes trials with incretin-based medications: a critical review of data available on GLP-1 receptor agonists and DPP-4 inhibitors

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors are so called “incretin-based therapies” (IBTs) that represent innovative therapeutic approaches and are commonly used in clinical practice for the treatment of type 2 diabetes mellitus (T2DM). The cardiovascular outcome trials (CVOTs) have provided useful information that has helped to shape changes in clinical practice guidelines for the management of T2DM. At the same time, the mechanisms that may explain the nonglycemic and cardiovascular (CV) benefits of these medications are still being explored. A summary of the main findings from CVOTs performed to-date with particular emphasis on vari…

Statin treatment in the elderly: how much do we know?

Choosing an ideal pharmacotherapeutic strategy for dyslipidemia in children.

Dyslipdiemia can manifest at a young age, and it is a risk factor for atherosclerotic cardiovascular disease (ASCVD), the principal cause of mortality in developed nations. Therefore, treating it a...

Liraglutide improves carotid intima-media thickness in patients with type 2 diabetes and non-alcoholic fatty liver disease: An 8-month prospective pilot study

Objective: To explore the effects of the glucagon-like peptide-1 receptor analogue liraglutide on subclinical atherosclerosis in diabetic subjects with non-alcoholic fatty liver disease (NAFLD).Research design and methods: In this 8-month prospective study, 29 subjects with type 2 diabetes (T2DM) and NAFLD (16 men and 13 women, mean age: 61 ± 10 years) were matched for age and gender with 29 subjects with T2DM without NAFLD (16 men and 13 women, mean age: 61 ± 8 years). Liraglutide 0.6 mg/day for 2 weeks, followed by 1.2 mg/day, was given in addition to metformin.Main outcome measures: Anthropometric variables, glucometabolic parameters and carotid intima-media thickness (IMT) using B-mode …

Liraglutide improves metabolic parameters and carotid intima-media thickness in diabetic patients with the metabolic syndrome: an 18-month prospective study

Abstract Background Liraglutide, a GLP-1 analogue, exerts several beneficial non-glycemic effects in patients with type-2 diabetes (T2DM), such as those on body weight, blood pressure, plasma lipids and inflammation markers. However, the effects of liraglutide on cardiovascular (CV) risk markers in subjects with the metabolic syndrome (MetS) are still largely unknown. We herein explored its effects on various cardio-metabolic risk markers of the MetS in subjects with T2DM. Methods We performed an 18-month prospective, real-world study. All subjects had T2DM and the MetS based on the AHA/NHLBI criteria. Subjects with a history of a major CV event were excluded. One hundred-twenty-one subject…

Incretin-Based Therapies, Glucometabolic Health and Endovascular Inflammation

Incretin peptides are a group of gastrointestinal hormones that play a prominent role in the regulation of glucose metabolism. Incretin-based therapies (IBTs) have recently emerged as an important treatment option for patients with type 2 diabetes mellitus (T2DM). These pharmaceutical agents may be specially well suited for patients who are overweight or obese with primarily post-meal glucose peaks, and in whom traditional first-line oral agents have failed to maintain adequate glycemic control. There are 2 classes of IBTs: the dipeptidyl peptidase-4 (DPP-4) inhibitors and the glucagon-like peptide 1 (GLP-1) receptor agonists. The ultimate effect of both types of agents is to augment GLP-1 …

Preliminary Results of CitraVes™ Effects on Low Density Lipoprotein Cholesterol and Waist Circumference in Healthy Subjects after 12 Weeks: A Pilot Open-Label Study

Appropriate monitoring and control of modifiable risk factors, such as the level of low-density lipoprotein cholesterol (LDL-C) and other types of dyslipidemia, have an important role in the prevention of cardiovascular diseases (CVD). Recently, various nutraceuticals with lipid-lowering effects have gained attention. In addition to the plant-derived bioactive compounds, recent studies suggested that plant cells are able to release small lipoproteic structures named extracellular vesicles (EVs). The interaction between EVs and mammalian cells could lead to beneficial effects through anti-inflammatory and antioxidant activities. The present study aimed to assess the safety of the new patente…

Management of Statin Intolerance in 2018: Still More Questions Than Answers.

Statin therapy is generally well tolerated and very effective in the prevention and treatment of cardiovascular disease, regardless of cholesterol levels; however, it can be associated with various adverse events (myalgia, myopathy, rhabdomyolysis, and diabetes mellitus, among others). Patients frequently discontinue statin therapy without medical advice because of perceived side effects and consequently increase their risk for cardiovascular events. In patients with statin intolerance, it may be advisable to change the dose, switch to a different statin, or try an alternate-day regimen. If intolerance is associated with all statins—even at the lowest dose—non-statin drugs and certain nutra…

Nutraceuticals and Cardiovascular Disease

Cardiovascular disease (CVD) remains the primary cause of mortality worldwide, taking an estimated 17.9 million lives each year. Among several cardiometabolic risk factors, dyslipidemia, and especially high low-density lipoprotein cholesterol (LDL-C) levels, are associated with the development and progression of atherosclerosis and its clinical sequelae. Recent studies have shown promising results for nutraceutical compounds on various CVD risk factors and complications. In addition to looking at individual nutrients or foods, dietary pattern have also emerged as a complementary approach to examine the relationship between the overall diet and the risk for CVD. The Mediterranean Diet (MedDi…

Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel

Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has focused on statin-associated muscle symptoms (SAMS), and avoided the use of the term ‘statin intolerance’. Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10 – 15% of patients.In clinical practice, statin intolerance limits effectiv…

Pasta Supplemented with Opuntia ficus-indica Extract Improves Metabolic Parameters and Reduces Atherogenic Small Dense Low-Density Lipoproteins in Patients with Risk Factors for the Metabolic Syndrome: A Four-Week Intervention Study

Food supplementation with Opuntia ficus-indica (OFI) has been associated with a significant reduction in total cholesterol, body fat, hyperglycemia and blood pressure. Since OFI may also have antioxidant and anti-atherogenic properties, we hypothesized that its supplementation might reduce atherogenic lipoproteins, including small, dense low-density lipoproteins (sdLDL). Forty-nine patients (13 men and 36 women, mean age: 56 &plusmn

Exenatide once-weekly improves metabolic parameters, endothelial dysfunction and carotid intima-media thickness in patients with type-2 diabetes: An 8-month prospective study.

AIM: To evaluate the effect of exenatide long acting release (LAR) on carotid intima-media thickness (IMT) and endothelial function in patients with type 2 diabetes mellitus. METHODS: Sixty subjects with type 2 diabetes mellitus were treated with exenatide LAR as add-on to stable doses of metformin for 8 months in an open label study. Anthropometric variables, lipid profile and glycemic parameters were assessed by routine analysis. Carotid IMT by Doppler ultrasound and endothelial function by flow-mediated dilation of the brachial artery were also assessed. RESULTS: Exenatide significantly improved fasting glycaemia (from 8.8 ± 2.8 to 7.3 ± 2.2 mmol/L, p < 0.0001), HbA1c (from 8.0 ± 0.4 …

Position paper Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel

Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has focused on statin associated muscle symptoms (SAMS), and avoided the use of the term 'statin intolerance'. Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10-15% of patients. In clinical practice, statin intolerance limits effective…

Emerging therapies for raising high-density lipoprotein cholesterol (HDL-C) and augmenting HDL particle functionality.

High-density lipoprotein (HDL) particles are highly complex polymolecular aggregates capable of performing a remarkable range of atheroprotective functions. Considerable research is being performed throughout the world to develop novel pharmacologic approaches to: (1) promote apoprotein A-I and HDL particle biosynthesis; (2) augment capacity for reverse cholesterol transport so as to reduce risk for the development and progression of atherosclerotic disease; and (3) modulate the functionality of HDL particles in order to increase their capacity to antagonize oxidation, inflammation, thrombosis, endothelial dysfunction, insulin resistance, and other processes that participate in arterial wal…

Bergamot reduces plasma lipids, atherogenic small dense LDL, and subclinical atherosclerosis in subjects with moderate hypercholesterolemia: A 6 months prospective study

Background: Some patients experience statin-induced side effects or prefer nutraceutical approaches for the treatment of dyslipidemia. This has led to a search for alternative therapeutic approaches for dyslipidemia management. In recent studies Citrus bergamia (known as Bergamot) juice was able to reduce serum levels of lipids. Such benefit may be attributed to high amounts of flavonoids contained in Bergamot fruit juice (neoeriocitrin, neohesperidin, naringin). The aim of the present study was to fully investigate the effects of a Bergamot extract on cardio-metabolic parameters, including plasma lipids, atherogenic lipoproteins and subclinical atherosclerosis. Methods: Eighty subjects (42…

Serum lipoproteins are not associated with the severity of asthma

Abstract Background Asthma is a chronic inflammatory disorder of the bronchi with a complicated and largely unknown pathogenesis . In this context, an emerging role is attributed to the apolipoproteins which serve as structural components of plasma lipoproteins . Low density lipoproteins (LDL) may be involved in the inflammatory pathways of the asthmatic airways; in particular, small dense LDL (sdLDL) particles were associated with increased oxidative susceptibility compared to medium and large sized LDL. In our previous study, we found a positive correlation between forced expiratory volume 1 s (FEV 1) % predicted and larger LDL particles (LDL-1), and an inverse correlation between FEV1% p…

Daily Use of Extra Virgin Olive Oil with High Oleocanthal Concentration Reduced Body Weight, Waist Circumference, Alanine Transaminase, Inflammatory Cytokines and Hepatic Steatosis in Subjects with the Metabolic Syndrome: A 2-Month Intervention Study

Extra virgin olive oil (EVOO) intake is associated with reduced cardiovascular risk, and its phenolic compound oleocanthal (OC) has anti-oxidant and anti-inflammatory properties. The cardiometabolic effects of EVOO with a high OC concentration have not been fully elucidated. We administered EVOO with a high OC concentration daily to 23 subjects with the metabolic syndrome (MetS) and hepatic steatosis (15 men and 8 women, age: 60 &plusmn

Elevated blood Hsp60, its structural similarities and cross-reactivity with thyroid molecules, and its presence on the plasma membrane of oncocytes point to the chaperonin as an immunopathogenic factor in Hashimoto's thyroiditis.

The role Hsp60 might play in various inflammatory and autoimmune diseases is under investigation, but little information exists pertaining to Hashimoto’s thyroiditis (HT). With the aim to fill this gap, in the present work, we directed our attention to Hsp60 participation in HT pathogenesis. We found Hsp60 levels increased in the blood of HT patients compared to controls. The chaperonin was immunolocalized in thyroid tissue specimens from patients with HT, both in thyrocytes and oncocytes (Hurthle cells) with higher levels compared to controls (goiter). In oncocytes, we found Hsp60 not only in the cytoplasm but also on the plasma membrane, as shown by double immunofluorescence performed on …

The Role of Nutraceuticals in Statin Intolerant Patients.

Abstract Statins are the most common drugs administered for patients with cardiovascular disease. However, due to statin-associated muscle symptoms, adherence to statin therapy is challenging in clinical practice. Certain nutraceuticals, such as red yeast rice, bergamot, berberine, artichoke, soluble fiber, and plant sterols and stanols alone or in combination with each other, as well as with ezetimibe, might be considered as an alternative or add-on therapy to statins, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. These nutraceuticals could exert significant lipid-lowering activ…

LIPOPROTEIN SUBCLASS DISTRIBUTION IN DIFFERENT CLINICAL PATTERNS AND THEIR VARIATION AFTER THERAPY

Liraglutide Reduces Carotid Intima-Media Thickness by Reducing Small Dense Low-Density Lipoproteins in a Real-World Setting of Patients With Type 2 Diabetes: A Novel Anti-Atherogenic Effect

Article full text The article associated with this page has been accepted for online publication and is in the final stages of production. The link to the full text will be made available on this page in the next few days. The above summary slide represents the opinions of the authors. For a full list of declarations, including funding and author disclosure statements, please see the full text online (see “read the peer-reviewed publication” opposite). © The authors, CC-BY-NC 2020.

Effects of Liraglutide on Metabolic Parameters and Carotid Intima-Media Thickness in Patients with The Metabolic Syndrome: A 12-Month Prospective Pilot Study

Recent research indicates that therapy with the GLP-1 agonist liraglutide in patients with type 2 diabetes mellitus (T2DM) seems to have beneficial actions on blood pressure, lipids, and the atherosclerotic process, which may be independent of its effect on glucose metabolism. However, the effects of liraglutide in subjects with the metabolic syndrome (MetS) are largely unknown. Forty-nine subjects with the MetS (24 men and 25 women, age 65±10 yrs) diagnosed by the AHA/NHLBI criteria were included in a 12-month prospective study. All subjects had T2DM, were naïve to incretin-based therapies, and treated with metformin only. Liraglutide was added at a dose of 0.6 mg subcutaneously daily for …

Liraglutide improves carotid intima-media thickness in patients with type-2 diabetes and non-alcoholic fatty liver disease: an 8-month prospective pilot study

Background and Aims: It has been shown in the last years that GLP-1 analogues, such as liraglutide, have several anti-atherogenic properties beyond their effects on glucose metabolism, including that on subclinical atherosclerosis. Yet, the effects of liraglutide in subjects with non-alcoholic fatty liver disease (NAFLD) are largely unknown. Materials and Methods: We included in a 8-month prospective study 29 subjects with type-2 diabetes and NAFLD (16 men and 13 women, mean age: 61±10 years), who were matched for age and gender with another group of 29 subjects with type-2 diabetes (T2DM) but without NAFLD (16 men and 13 women, mean age: 61±8 years). The diagnosis of NAFLD was based on ult…