Hsp60 and heme oxygenase-1 (Hsp32) in acute myocardial infarction

Heat shock proteins (Hsps) are produced in response to various stressors, including ischemia-reperfusion, and they can exit cells and reach the blood. In this pilot study, we determined serum levels of Hsp60 and heme-oxygenase-1 (HO-1; also named Hsp32) in subjects with acute myocardial infarction (AMI) to assess their clinical significance and potential prognostic value. We also performed a bioinformatics analysis of the 2 molecules in search of structural clues on the mechanism of their release from cells. We studied 40 patients consecutively admitted for AMI (male:female patient ratio = 20:20, mean age: 64 ± 13 years) and 40 matched controls. A blood sample was drawn for biochemical anal…

The therapeutic modulation of atherogenic dyslipidemia and inflammatory markers in the metabolic syndrome: what is the clinical relevance?

The metabolic syndrome consists of a constellation of clinical and biochemical risk factors that cluster together and heighten the risk for atherogenesis, cardiovascular diseases, and diabetes. Established risk cardiovascular factors like hypertension, atherogenic dyslipidaemia, and glucose intolerance occur in the setting of insulin resistance and central adiposity, with genetic and environmental influences modulating the ultimate risk. Chronic insults to the endothelium take its toll in the form of silent as well as clinically evident cardiovascular events. The cellular and vascular accompaniments have shed some light into the underlying pathophysiology. Heightened, low-grade inflammatory…

Analysis of vitamin D levels in patients with and without statin-associated myalgia — A systematic review and meta-analysis of 7 studies with 2420 patients

article i nfo Introduction: VitaminD (vitD)deficiencymay beassociatedwith anincreased riskof statin-related symptomatic myalgia in statin-treated patients. The aim of this meta-analysis was to substantiate the role of serum vitamin D levels in statin-associated myalgia. Methods: The search included PUBMED, Cochrane Library, Scopus, and EMBASE from January 1, 1987 to April 1, 2014 to identify studies that investigated the impact of vit D levels in statin-treated subjects with and without myalgia. Two independent reviewers extracted data on study characteristics, methods and outcomes. Quantita- tive data synthesis was performed using a fixed-effect model. Results: The electronic search yielde…

Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review

The approval of once daily liraglutide, 3.0 mg, and once weekly semaglutide, 2.4 mg, for chronic weight management provides a novel effective strategy against obesity. The reliable models that might predict weight reducing potential at the individual level have not been identified yet. However, the coexistence of diabetes has been consistently related with less effective response than in people without this comorbidity. We aimed to review the efficacy of GLP-1 RAs approved for weight management in individuals with and without diabetes and discuss some potential mechanisms for consistently observed differences in efficacy between these two populations. The mean weight loss difference between…

Familial Hypercholesterolemia and Lipoprotein(a): A Gordian Knot in Cardiovascular Prevention

Familial hypercholesterolemia (FH) is the most frequent genetic disorder resulting in increased low-density lipoprotein cholesterol (LDL-C) levels from childhood, leading to premature atherosclerotic cardiovascular disease (ASCVD) if left untreated. FH diagnosis is based on clinical criteria and/or genetic testing and its prevalence is estimated as being up to 1:300,000-400,000 for the homozygous and similar to 1:200-300 for the heterozygous form. Apart from its late diagnosis, FH is also undertreated, despite the available lipid-lowering therapies. In addition, elevated lipoprotein(a) (Lp(a)) (>50 mg/dL; 120 nmol/L), mostly genetically determined, has been identified as an important car…

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…

Lipid levels in polycystic ovary syndrome: systematic review and meta-analysis.

Objective To quantify the magnitude and pattern of low-density lipoprotein (LDL) cholesterol and nonhigh-density lipoprotein (HDL) cholesterol levels in women with polycystic ovary syndrome (PCOS) versus control women. Design Systematic review and meta-analysis of lipid levels in published cross-sectional studies worldwide where PCOS women and controls were examined and sampled. Main Outcome Measure(s) Differences in plasma lipids (including triglycerides, HDL-cholesterol, LDL-cholesterol, and nonHDL-cholesterol) in PCOS versus control subjects were calculated. Comparisons were made with and without body mass index (BMI) matching. Result(s) Triglyceride levels were 26 mg/dL (95% confidence …

LDL size and subclasses in patients with abdominal aortic aneurysm

Abstract Since the type of dyslipidemia in patients with abdominal aortic aneurysm (AAA) is still insufficiently defined, we measured plasma lipids and analyzed LDL size and subclasses by gradient gel electrophoresis in 30 male patients (69±6 years, BMI: 27±3) with newly diagnosed AAA and in 26 age- and BMI-matched male healthy controls. Patients with AAA had lower HDL-cholesterol ( p p =.0002) and smaller LDL size ( p p =.0210) in relation to controls. Multivariate analysis also showed that small LDL size was independently associated with the presence of AAA ( p =.0350). Increased levels of small, dense LDL may therefore represent a common feature in patients with AAA.

Smoking and small, dense low-density lipoproteins.

Ezetimibe, cardiovascular risk and atherogenic dyslipidaemia.

Ezetimibe is a selective cholesterol absorption inhibitor with an excellent side-effect profile, able to reduce low-density lipoprotein (LDL) cholesterol by 15-25% from baseline in monotherapy and on top of statins and fibrates. Yet, it seems that ezetimibe produces quantitative rather than qualitative changes in LDL, with small net effects on atherogenic dyslipidaemia. This is supported by findings from the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) study on atherosclerosis progression, where the addition of ezetimibe to simvastatin in patients with heterozygous familial hypercholesterolaemia did not affect the mean change in carotid int…

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…

Metformin: Sex/Gender Differences in Its Uses and Effects-Narrative Review

Metformin (MTF) occupies a major and fundamental position in the therapeutic management of type 2 diabetes mellitus (T2DM). Gender differences in some effects and actions of MTF have been reported. Women are usually prescribed lower MTF doses compared to men and report more gastrointestinal side effects. The incidence of cardiovascular events in women on MTF has been found to be lower to that of men on MTF. Despite some promising results with MTF regarding pregnancy rates in women with PCOS, the management of gestational diabetes, cancer prevention or adjunctive cancer treatment and COVID-19, most robust meta-analyses have yet to confirm such beneficial effects.

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…

Lipid-lowering therapies and achievement of LDL-cholesterol targets.

Future perspectives of the pharmacological management of diabetic dyslipidemia

Introduction: Diabetic dyslipidemia is frequent among patients with type 2 diabetes mellitus (T2DM) and is characterized by an increase in triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), and small-dense (atherogenic) particles, and by a decrease in low high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo) A1 that are strongly related to insulin resistance. The increased flux of free fatty acids from adipose tissue to the liver aggravates hepatic insulin resistance and promotes all of aspects of the dyslipidemic state. Areas covered: Statins are the first-line agents for treatment while other lipid-lowering drugs (ezetimibe, fibrate and proprotein convertase…

Small, dense low-density lipoproteins (LDL) are predictors of cardio- and cerebro-vascular events in subjects with the metabolic syndrome

Summary Objective  Small, dense low-density lipoproteins (LDL) are a feature of the metabolic syndrome (MS) but their predictive role still remains to be established. We performed a 2-year follow-up study in 124 subjects with MS (63 ± 6 years), as defined by the American Heart Association/National Heart, Lung and Blood Institute guidelines, to assess clinical and biochemical predictors of cerebro- and cardio-vascular events. Methods and results  Beyond traditional cardiovascular risk factors, we measured LDL size and subclasses by gradient gel electrophoresis. Clinical events were registered in the 25% of subjects. At univariate analysis subjects with events had increased prevalence of elev…

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…

Low-density-lipoproteins size and cardiovascular prevention

Low-density lipoprotein (LDL) size appears to be an important predictor of cardiovascular events and progression of coronary artery disease, and the predominance of small, dense LDL has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III. Yet, other authors have suggested that LDL subclass measurement does not add independent information to that conferred generically by LDL concentration and other standard risk factors. Therefore, the debate continues as to whether to measure LDL particle size for cardiovascular prevention and, if so, in which categories of patients. Since the therapeutic modulation of distinct LDL …

Advances in pharmacological treatment of type 1 diabetes during pregnancy.

Introduction: In women with type 1 diabetes mellitus (T1DM), pregnancy is associated with a potential risk of maternal, foetal and neonatal outcomes. Stringent metabolic control is required to improve these outcomes. Areas covered: In this review, the authors summarise the current evidence from studies on the pharmacological therapy and on monitoring of T1DM during pregnancy. The authors also discuss the use of new technologies to improve therapeutic management and patient compliance. Expert opinion: Pre-conception counselling is essential in T1DM to minimise pregnancy risks. Pregnancy in T1DM is always considered a high-risk pregnancy. During pregnancy, the target haemoglobin A1C (HbA1c) i…

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,…

Cystatin C levels are decreased in acute myocardial infarction

Background: Cystatin C is the most abundant protease inhibitor in the plasma. Low plasma levels have been found in patients with aortic aneurysms and they seem correlated with the extension of the aortic lesions in early aneurysms detected by ultrasonography. Methods: In this study, plasma levels of cystatin C have been investigated in patients with acute myocardial infarction (AMI), unstable angina and controls. The effect on plasma levels of the G73A polymorphism of the CST3 gene has been also evaluated. Results: Patients with acute myocardial infarction showed significantly lower levels of cystatin C compared to unstable angina and controls, but levels were nearly normal in a week after …

“European Panel on Low Density Lipoprotein (LDL) Subclasses”: A Statement on the Pathophysiology, Atherogenicity and Clinical Significance of LDL Subclasses

Aim of the present Consensus Statement is to provide a comprehensive and up to-date document on the pathophysiology, atherogenicity and clinical significance of low density lipoproteins (LDL) subclasses. We sub-divided our Statement in 2 sections: section I discusses the pathophysiology, atherogenicity and measurement issues, while section II is focused on the effects of drugs and lifestlyle modifications. Suggestions for future research in the field are highlighted at the end of section II. Each section includes Conclusions.

Markers of inflammation are strong predictors of subclinical and clinical atherosclerosis in women with hypertension

Cardiovascular diseases in women still rises and remains their leading cause of death in most developed countries; yet we have less sex-specific data in women than in men as a result of lower enrollment in clinical trials and low rates of sex-specific reporting. The aim of our study was to evaluate in hypertensive postmenopausal women the potential predictive role of markers of inflammation, for example, fibrinogen and C-reactive protein (CRP), on subclinical and clinical atherosclerosis, beyond that of the other established cardiovascular risk factors. We studied 127 asymptomatic hypertensive postmenopausal women with different degrees of carotid intima–media thickness, as examined by the …

Non-glycemic effects of pioglitazone and incretin-based therapies.

Atherosclerosis and cardiovascular events are highly prevalent and represent the major cause of mortality in patients with type 2 diabetes. Therefore, there is significant interest in the non-glycemic properties of anti-diabetic agents, particularly on those that are effective on cardiovascular risk factors. Thiazolidinediones and incretin-based therapies (IBTs) represent some of the most recent treatment options approved for the management of type 2 diabetes; these agents have shown important glycemic effects, as well as a number of non-glycemic effects. The latter include those on body weight, inflammation, hypertension and dyslipidemia, thus impacting the different components of the meta…

Comparative effects of rosiglitazone and pioglitazone on fasting and postprandial low-density lipoprotein size and subclasses in patients with Type 2 diabetes

To assess the effects of pioglitazone and rosiglitazone on fasting and postprandial low-density lipoprotein (LDL) size and subclasses in patients with Type 2 diabetes.Nine Type 2 diabetic patients (age 61 +/- 10 years, body mass index 30 +/- 5 kg/m(2), glycosylated hemoglobin [HbA1c] 7.5 +/- 0.5%) were randomized in a crossover trial to rosiglitazone 4 mg b.i.d. or pioglitazone 45 mg/day for 12 weeks with an 8-week wash-out period. LDL size and subclasses were determined by non-denaturing polyacrylamide gradient gel electrophoresis. A standardized breakfast was served and variables were assessed after 3 and 6 h.HbA1c, insulin sensitivity (as assessed by the homeostasis model assessment) and…

Metabolic effect of berberine-silymarin association: A meta-analysis of randomized, double-blind, placebo-controlled clinical trials.

The aim of this study is to assess the impact of a combination of berberine and silymarin on serum lipids and fasting plasma glucose (FPG) through a systematic review of literature and meta-analysis of the available randomized, double-blind, placebo-controlled clinical trials (RCTs). A systematic literature search in SCOPUS, PubMed-Medline, ISI Web of Science, and Google Scholar databases was conducted up to October 2, 2018, in order to identify RCTs assessing changes in plasma concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and FPG during treatment with berberine and silymarin in combina…

The influence of atorvastatin on parameters of inflammation left ventricular function, hospitalizations and mortality in patients with dilated cardiomyopathy--5-year follow-up.

Background: We assessed the influence of atorvastatin on selected indicators of an inflammatory condition, left ventricular function, hospitalizations and mortality in patients with dilated cardiomyopathy (DCM). Methods. We included 68 DCM patients with left ventricular ejection fraction (LVEF) ≤40% treated optimally in a prospective, randomized study. They were observed for 5 years. Patients were divided into two groups: patients who were commenced on atorvastatin 40 mg daily for two months followed by an individually matched dose of 10 or 20 mg/day (group A), and patients who were treated according to current recommendations without statin therapy (group B). Results: After 5-year follow-u…

Ethnic differences in serum lipoproteins and their determinants in South African women.

The objective of the study was to characterize ethnic differences in lipid levels and low-density lipoprotein (LDL) particle size and subclasses in black and white South African women and to explore the associations with insulin sensitivity (S(I)), body composition, and lifestyle factors. Fasting serum lipids and LDL size and subclasses, body composition (dual-energy x-ray absorptiometry), and S(I) (frequently sampled intravenous glucose tolerance test) were measured in normal-weight (body mass index25 kg/m(2)) black (n = 15) and white (n = 15), and obese (body mass index30 kg/m(2)) black (n = 13) and white (n = 13) women. Normal-weight and obese black women had lower triglycerides (0.59 +/…

The clinical significance of the size of low-density-lipoproteins and the modulation of subclasses by fibrates

Beyond total low-density-lipoproteins (LDL) levels, increasing evidence suggests that the 'quality' of LDL exerts a great influence on the cardiovascular risk. Several studies have also shown that the therapeutic modulation of LDL size is of benefit in reducing the risk of cardiovascular events. Hypolipidaemic treatment is able to alter LDL subclass distribution but strong variations have been noticed among different agents. Fibrates have a major impact on triglyceride metabolism and in modulating LDL size and subclasses, but variations exist among the different molecules.A literature search (by Medline and Scopus) was performed using the following headings: 'small dense LDL', 'LDL size', '…

Family hystory, diabetes and extension of coronary atherosclerosis are strong predictors of adverse events after PTCA: a one year follow-up study

BACKGROUND AND AIM: In this study we addressed some open questions in patients with coronary artery disease (CAD). First, we analysed which of the traditional risk factors was associated with the spreading of coronary stenosis and second, we aimed to identify if any variable was predictive of post-percutaneous transluminal coronary angioplasty (PTCA) clinical events. METHODS AND RESULTS: We collected a consecutive series of patients with CAD (n=301) and in the subgroup of patients undergoing PTCA (n=135) we performed a prospective one-year follow-up study recording cardiovascular morbidity and total mortality. According to the extension of coronary atherosclerosis, we found a significant re…

Cilostazol and atherogenic dyslipidemia: a clinically relevant effect

Cilostazol is a reversible, selective inhibitor of PDE3A able to significantly improve walking distance in patients with intermittent claudication. However, beyond its antiplatelet and vasodilator properties, cilostazol seems to have significant effects on atherogenic dyslipidemia.The effects of cilostazol on plasma lipids, lipoproteins, apolipoproteins and postprandial lipemia are reviewed. A literature search (using Medline and Scopus) was performed up to 24 October 2010. The authors also manually reviewed the references of selected articles for any pertinent material.Cilostazol is able to significantly lower plasma triglyceride levels, with a concomitant increase in high-density lipoprot…

A systematic review and meta-analysis of the effect of statins on plasma asymmetric dimethylarginine concentrations.

AbstractThe impact of statin therapy on plasma asymmetric dimethylarginine (ADMA) levels has not been conclusively studied. Therefore the aim of the meta-analysis was to assess the effect of statins on circulating ADMA levels. We searched selected databases (up to August 2014) to identify randomized controlled trials (RCTs) that investigate the effect of statins on plasma ADMA concentrations. A weighted meta-regression (WMD) using unrestricted maximum likelihood model was performed to assess the impact of statin dose, duration of statin therapy and baseline ADMA concentrations as potential variables on the WMD between statin and placebo group. In total, 1134 participants in 9 selected RCTs …

Rational for statin use in psoriatic patients

Psoriasis represents a common skin disease which is clinically manifested by chronic cutaneous lesions. It has been observed that psoriasis is associated with an increased risk of cardiovascular diseases, which is contributed to the inappropriate lipid metabolism. Statins are commonly used in clinical practice to lower cholesterol concentration and, accordingly, decrease the individual risk of developing a cardiovascular episode. There have been reports that statin administration could also result in better management of psoriasis. The observed beneficial effects are contributed to the effects on lipid metabolism, including that in skin, as well as anti-inflammatory and immunomodulatory pro…

Endothelial dysfunction and carotid lesions are strong predictors of clinical events in patients with early stages of atherosclerosis: a 24-month follow-up study

Background The purpose of this study was to investigate whether the vasodilator response to brachial artery and the presence of carotid lesions may have a prognostic significance in patients with early stages of atherosclerosis. Methods and results Vascular echography was performed to analyze flow-mediated vasodilatation (FMD) at the brachial artery and intima–media thickness (IMT) of carotid arteries in 84 asymptomatic patients. At baseline, we evaluated all the established traditional cardiovascular risk factors. Transient ischemic attack, stroke, effort or unstable angina, acute myocardial infarction, peripheral arterial disease and cerebrovascular and cardiovascular death served as outc…

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…

Therapy with non-invasive ventilation in patients with obstructive sleep apnoea: effects on atherogenic lipoprotein phenotype.

Patients with obstructive sleep apnoea are at increased risk of atherosclerotic morbidity and mortality. Abnormalities in lipid metabolism that occur in response to chronic intermittent hypoxia in patients with sleep-disordered breathing may increase the cardiovascular risk in an already susceptible population. Atherogenic lipoprotein phenotype and small, dense LDL have an independent predictive role for future cardio- and cerebro-vascular events in patients with the metabolic syndrome. Therefore, testing the hypothesis that therapy of obstructive sleep apnoea may reduce atherogenic lipoprotein phenotype might have significant clinical implications. We suggest that abolition of obstructive …

Evaluation of the Possible Contribution of Antioxidants Administration in Metabolic Syndrome

The metabolic syndrome (MetS) is common, and its associated risk burdens of diabetes and cardiovascular disease (CVD) are a major public health problem. The hypothesis that main constituent parameters of the MetS share common pathophysiologic mechanisms provides a conceptual framework for the future research. Exercise and weight loss can prevent insulin resistance and reduce the risk of diseases associated with the MetS. Interrupting intracellular and extracellular reactive oxygen species (ROS) overproduction could also contribute to normalizing the activation of metabolic pathways leading to the onset of diabetes, endothelial dysfunction, and cardiovascular (CV) complications. On the other…

Effects of Coenzyme Q10 on Statin-Induced Myopathy

Abstract Objective To evaluate the efficacy of coenzyme Q10 (CoQ10) supplementation on statin-induced myopathy. Participants and Methods We searched the MEDLINE, Cochrane Library, Scopus, and EMBASE databases (November 1, 1987, to May 1, 2014) to identify randomized controlled trials investigating the impact of CoQ10 on muscle pain and plasma creatine kinase (CK) activity as 2 measures of statin-induced myalgia. Two independent reviewers extracted data on study characteristics, methods, and outcomes. Results We included 6 studies with 302 patients receiving statin therapy: 5 studies with 226 participants evaluated the effect of CoQ10 supplementation on plasma CK activity, and 5 studies (4 u…

Safety Evaluation of α-Lipoic Acid Supplementation: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Clinical Studies

Alpha-lipoic acid (ALA) is a natural short-chain fatty acid that has attracted great attention in recent years as an antioxidant molecule. However, some concerns have been recently raised regarding its safety profile. To address the issue, we aimed to assess ALA safety profile through a systematic review of the literature and a meta-analysis of the available randomized placebo-controlled clinical studies. The literature search included EMBASE, PubMed Medline, SCOPUS, Google Scholar, and ISI Web of Science by Clarivate databases up to 15th August 2020. Data were pooled from 71 clinical studies, comprising 155 treatment arms, which included 4749 subjects with 2558 subjects treated with ALA an…

An update on the role of markers of inflammation in atherosclerosis

In recent years, several studies have used the measurement of carotid intima-media thickness (IMT) as a marker of early atherosclerosis: IMT has been shown to correlate significantly with the presence of coronary artery disease (CAD) and to predict fatal and not fatal cerebro- and cardio-vascular events. These findings highlight the importance of recognizing and managing early stages of atherosclerosis for effective cardiovascular prevention. Beyond traditional established cardiovascular risk factors, inflammation has been shown to be crucial throughout atherosclerosis from endothelial dysfunction to plaque rupture and thrombosis. Several studies have shown the existence of a strong relatio…

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…

Liraglutide decreases carotid intima-media thickness in patients with type 2 diabetes: 8-month prospective pilot study.

Background Liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) analog, has several non- glycemic properties, but its effect on carotid intima-media thickness (IMT), a recognized marker of subclinical atherosclerosis, is still unknown. Methods A prospective study of 8 months duration in 64 patients with type-2 diabetes and no prior history of coronary artery disease evaluated whether adding liraglutide to metformin affects carotid IMT, measured by color doppler ultrasound. Results After 8 months, fasting glucose decreased by 2.1 mmol/l and HbA1c by 1.9% (p < 0.01 for all). Liraglutide reduced total-cholesterol and triglycerides by 10%, and LDL-cholesterol by 19%, whereas HDL-cholester…

Effects of statins on low-density-lipoproteins size: a new role in cardiovascular prevention ?

Cardiovascular diseases still represent the first cause of death in most of the industrialized countries. An effective prevention includes the treatment of a series of risk factors: smoking, hypertension, diabetes, obesity and dyslipidemia.1 Statins represent a class of cholesterol-lowering drugs as inhibitors of the hydroxymethylglutaryl-coenzyme A reductase enzyme which catalyzes one of the first steps of the cholesterol metabolic pathway. This class of drugs has been used in a very large number of patients, in both primary and secondary cardiovascular prevention, for its ability to reduce clinical events linked to atherosclerosis, including acute myocardial infarction, unstable angina, c…

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: …

High plasma levels of endothelin-1 enhance the predictive value of preclinical atherosclerosis for future cerebrovascular and cardiovascular events: a 20-year prospective study

BACKGROUND AND PURPOSE: Clinical and experimental evidence suggests that endothelin-1 (Et-1) plays a role in cardiac and vascular disease. In the present study, we investigated the prognostic significance of Et-1 for cerebrovascular and cardiovascular outcome, in a 20-year follow-up. METHODS: We studied 82 originally healthy individuals, referred to our Unit of Cardiovascular Prevention, to evaluate the presence of asymptomatic carotid lesions. We subdivided these individuals into two groups, according to the plasma values of Et-1 (respectively ≤ or >2.7 pg/ml). Traditional cardiovascular risk factors were investigated, and by carotid ultrasound examination, we distinguished between normal …

Reconnoitering the Role of Long-Noncoding RNAs in Hypertrophic Cardiomyopathy: A Descriptive Review

Hypertrophic cardiomyopathy (HCM) is the most common form of hereditary cardiomyopathy. It is characterized by an unexplained non-dilated hypertrophy of the left ventricle with a conserved or elevated ejection fraction. It is a genetically heterogeneous disease largely caused by variants of genes encoding for cardiac sarcomere proteins, including MYH7, MYBPC3, ACTC1, TPM1, MYL2, MYL3, TNNI3, and TNNT23. Preclinical evidence indicates that the enhanced calcium sensitivity of the myofilaments plays a key role in the pathophysiology of HCM. Notably, this is not always a direct consequence of sarcomeric variations but may also result from secondary mutation-driven alterations. Long non-coding R…

Effects of statins, fibrates, rosuvastatin, and ezetimibe beyond cholesterol: the modulation of LDL size and subclasses in high-risk patients.

Increasing evidence suggests that the quality-rather than just the quantity-of low-density lipoproteins (LDLs) exerts a great influence on cardiovascular risk. LDLs comprise multiple subclasses with discrete size and density, and different physicochemical composition, metabolic behaviors, and atherogenicity. Individuals generally cluster into 2 broad subgroups. Most have a predominance of large LDLs, and some have a higher proportion of small particles. Small, dense LDLs are good predictors of cardiovascular events and progression of coronary artery disease. Their predominance has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Tre…

Prevalence of dyslipidemia and associated risk factors in Turkish adults.

Background and Objectives Dyslipidemia is a modifiable major risk factor for coronary heart disease. The objective of this study was to determine the prevalence of dyslipidemia among Turkish adults and its associations with other cardiovascular risk factors. Methods This study included 4309 people ages 20 to 83 years old from 7 provinces of Turkey. People from the city centers, districts, and villages were selected by a stratified sampling method. Weight, height, and waist and hip circumferences were measured. Blood samples were obtained to determine glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides …

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 …

Molecular Endocrinology and Metabolism in 2021: What’s New

The last two years, despite the very serious COronaVIrus Disease-2019 (COVID-19) pandemic, have been quite productive in the field of molecular endocrinology and metabolism and our journal section has contributed extensively on that [...]

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 …

Nutritional characteristics of a rural Southern Italy population: the Ventimiglia di Sicilia Project.

Knowledge of alimentary habits among populations permits a better definition of appropriate public health interventions. We designed the epidemiological project "Ventimiglia di Sicilia" to characterize the risk profile in a rural village with low total cholesterol levels and low early cardiovascular mortality but with a large prevalence of overweight and obesity, which previously have been significantly associated with total mortality.488 individuals of age 20 to 69 years were included in the dietary survey conducted by a seven-day food record.Alimentary habits were characterized by high consumption of total and complex carbohydrates (respectively 52.5 +/- 7.6% and 46.6 +/- 8.2% of daily en…

Leukotriene receptor antagonists in monotherapy or in combination with antihistamines in the treatment of chronic urticaria: A systematic review

In vitro and in vivo clinical and experimental data have suggested that leukotrienes play a key role in inflammatory reactions of the skin. Antileukotriene drugs, ie, leukotriene receptor antagonists and synthesis inhibitors, are a class of anti-inflammatory drugs that have shown clinical efficacy in the management of asthma and in rhinitis with asthma. We searched MEDLINE database and carried out a manual search on journals specializing in allergy and dermatology for the use of antileukotriene drugs in urticaria. Montelukast might be effective in chronic urticaria associated with aspirin (ASA) or food additive hypersensitivity or with autoreactivity to intradermal serum injection (ASST) wh…

Lipoproteins and Cardiovascular Disease: An Update on the Clinical Significance of Atherogenic Small, Dense LDL and New Therapeutical Options

Dyslipidemia is a potent risk factor for the genesis and progression of cardiovascular disease (CVD), and both the concentration and type of low-density lipoproteins (LDL) augment this association. The small, dense LDL (sdLDL) subfraction is the subtype which is most strongly predictive of atherosclerosis and cardiovascular events. In addition to the traditionally available lipid-lowering treatment options, certain novel therapies have been shown to favorably impact sdLDL, among them the antidiabetic class of agents known as glucagon-like peptide 1 receptor agonists (GLP1-RAs). These drugs seem to alter the pathophysiologic mechanisms responsible for the formation and accumulation of athero…

The Role of Fructose as a Cardiovascular Risk Factor: An Update

There is increasing presence of fructose in food and drinks, and some evidence suggests that its higher consumption increases cardiovascular risk, although the mechanisms still remain not fully elucidated. Cardiovascular diseases (CVD) are still responsible for one-third of deaths worldwide, and therefore, their prevention should be assessed and managed comprehensively and not by the evaluation of individual risk factor components. Lifestyle risk factors for CVD include low degree of physical activity, high body mass index, alcohol consumption, smoking, and nutritional factors. Indeed, nutritional risk factors for CVD include unhealthy dietary behaviors, such as high intake of refined foods…

Undertreatment of dyslipidemia: from the Arabian Gulf to the USA. Time to solve this problem!

Undertreatment of dyslipideamia is a universal problem and reduces the efficasy of hypolipidaemic drugs to reduce cardiovascular event rates. The means to face this problem are available and should be utilized to optimize dyslipidaemia control and clinical outcomes.

Lipid triad or atherogenic lipoprotein phenotype: a role in cardiovascular prevention?

The term "lipid triad" or "atherogenic lipoprotein phenotype" has been introduced to describe a common form of dyslipidemia, characterized by three lipid abnormalities: increased plasma triglyceride levels, decreased HDL-cholesterol concentrations and the presence of small, dense LDL particles. It has been suggested that the clinical importance of the atherogenic lipoprotein phenotype probably exceeds that of LDL-cholesterol, because many more patients with coronary artery disease are found to have this trait than hypercholesterolaemia. There is a body of evidence that therapies effective against plasma HDL-cholesterol and triglycerides are associated with a strong reduction of cardiovascul…

Cardiometabolic Alterations in the Interplay of COVID-19 and Diabetes: Current Knowledge and Future Avenues

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19]) pandemic has raged for almost two years, with few signs of a sustained abatement or remission [...]

Association between COX-2 rs 6681231 genotype and interleukin-6 in periodontal connective tissue. A pilot study.

[Objectives] The aim of this pilot study was to investigate associations between IL-6 and COX-2 expression in gingival biopsies and both clinical diagnosis and genotypes in the IL-6 and COX-2 genes. [Design] A case-control study included 41 gingival biopsies obtained from Caucasian patients grouped according to clinical diagnosis of gingival health (n = 10), gingivitis (n = 15) or chronic periodontitis (n = 16). Immunohistochemistry analyses were performed to determine COX-2 expression in lamina propria, IL-6 expression in lamina propria and gingival epithelium and level of inflammatory cell infiltrate. Individual DNA was extracted and genotyped by real-time PCR for IL6 SNPs rs 2069827 and …

Atherosclerosis Development and Progression: The Role of Atherogenic Small, Dense LDL.

Atherosclerosis is responsible for large cardiovascular mortality in many countries globally. It has been shown over the last decades that the reduction of atherosclerotic progression is a critical factor for preventing future cardiovascular events. Low-density lipoproteins (LDL) have been successfully targeted, and their reduction is one of the key preventing measures in patients with atherosclerotic disease. LDL particles are pivotal for the formation and progression of atherosclerotic plaques; yet, they are quite heterogeneous, and smaller, denser LDL species are the most atherogenic. These particles have greater arterial entry and retention, higher susceptibility to oxidation, as well a…

The metabolic syndrome and HIV infection.

The metabolic syndrome (MetS), a cluster of risk factors for cardiovascular disease and type 2 diabetes, has become an important public health problem. Considerable differences in the prevalence of the MetS in human immunodeficiency virus (HIV)-infected subjects have been reported, as a consequence of several limitations regarding the diagnostic critera for MetS. New evidence suggests that the use of optimal waist cut-off points specific for the various ethnic populations could represent a step forward in overcoming these limitations. Also the use of specific cut-off points for measuring upper trunk fat as an adjunctive criterion of MetS in HIV patients with lipodystrophy could represent an…

Betatrophin Levels Are Related to the Early Histological Findings in Nonalcoholic Fatty Liver Disease

Betatrophin, a liver hormone, regulates glucose and lipid metabolism. We investigated the betatrophin levels in nonalcoholic fatty liver disease (NAFLD) and searched for any relationship with histological severity and metabolic parameters. Fifty males with NAFLD [Nonalcoholic Steatohepatitis (NASH) (n = 32)

Effects of Gestational Diabetes Mellitus on Cholesterol Metabolism in Women with High-Risk Pregnancies: Possible Implications for Neonatal Outcome

Metabolic disorders in pregnancy, particularly gestational diabetes mellitus (GDM), are associated with an increased risk for adverse pregnancy outcome and long-term cardiometabolic health of mother and child. This study analyzed changes of serum cholesterol synthesis and absorption markers during the course of high-risk pregnancies, with respect to the development of GDM. Possible associations of maternal lipid biomarkers with neonatal characteristics were also investigated. The study included 63 women with high risk for development of pregnancy complications. Size and proportions of small low-density (LDL) and high-density lipoprotein (HDL) particles were assessed across trimesters (T1&nd…

Statins and osteoporosis: Myth or reality?

Atorvastatin in stable angina patients lowers CCL2 and ICAM1 expression: Pleiotropic evidence from plasma mRNA analyses

Objective: Statin pleiotropy is still an evolving concept, and the lack of clarity on this subject is due at least in part to the lack of a definitive biomarker for statin pleiotropy. Using plasma mRNA analysis as a novel research tool for the non-invasive in vivo assessment of gene expression in vascular beds, we hypothesised that atorvastatin lowers the plasmamRNA level from statin pleiotropy-target genes, and the reduction is independent of the reduction of low-density lipoprotein cholesterol (LDL-C). Design and methods: Forty-four patients with stable angina received atorvastatin therapy (20 mg/day, 10 weeks). Plasma chemokine (C-C motif) ligand 2 (CCL2) and intercellular adhesion molec…

Gemfibrozil reduces small low-density lipoprotein more in normolipemic subjects classified as low-density lipoprotein pattern B compared with pattern A.

We tested the hypothesis that gemfibrozil has a differential effect on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclass distributions and postprandial lipemia that is different in subjects classified as having LDL subclass pattern A or LDL pattern B who do not have a classic lipid disorder. Forty-three normolipemic subjects were randomized to gemfibrozil (1,200 mg/day) or placebo for 12 weeks. Lipids and lipoproteins were determined by enzymatic methods. The mass concentrations of lipoproteins in plasma were determined by analytic ultracentrifugation and included the S(f) intervals: 20 to 400 (very LDL), 12 to 20 (intermediate-density lipoprotein), 0 to 12 (LDL), an…

New Lipid Modulating Drugs: The Role of Microsomal Transport Protein Inhibitors

Microsomal triglyceride transfer protein (MTP) is involved in the synthesis of very low density lipoprotein in the liver. Its deficiency results in abetalipoproteinemia. MTP inhibitors target the assembly and secretion of apolipoprotein B-containing lipoproteins. These agents may potentially play a role, alone or in combination, in the treatment of hypercholesterolemia or hypertriglyceridemia. Clinical applications of MTP inhibitors initially focused primarily on high-dose monotherapy in order to produce substantial reductions in LDL-cholesterol levels but these proved to induce significant hepatic steatosis and transaminase elevations. However, likely orphan indications for MTP inhibitors,…

Statin therapy and plasma coenzyme Q10 concentrations—A systematic review and meta-analysis of placebo-controlled trials

Statin therapy may lower plasma coenzyme Q10 (CoQ10) concentrations, but the evidence as to the significance of this effect is unclear. We assessed the impact of statin therapy on plasma CoQ10 concentrations through the meta-analysis of available RCTs. The literature search included selected databases up to April 30, 2015. The meta-analysis was performed using either a fixed-effects or random-effect model according to I(2) statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). The data from 8 placebo-controlled treatment arms suggested a significant reduction in plasma CoQ10 concentrations following treatment with statins (WMD: -0.44 μmol/…

Lack of efficacy of resveratrol on C-reactive protein and selected cardiovascular risk factors — Results from a systematic review and meta-analysis of randomized controlled trials

Introduction: Numerous studies have suggested that oral supplementation with resveratrol exerts cardioprotective effects, but evidence of the effects on C-reactive protein (CRP) plasma levels and other cardiovascular (CV) risk factors is inconclusive. Therefore, we performed a meta-analysis to evaluate the efficacy of resveratrol supplementation on plasma CRP concentrations and selected predictors of CV risk. Methods:The searchincludedPUBMED,Cochrane Library,Web ofScience,Scopus,andEMBASE(up toAugust31, 2014) to identify RCTs investigating the effects of resveratrol supplementation on selected CV risk factors. Quantitative data synthesis was performed using a random-effects model, with weig…

Accumulation of apoE-enriched triglyceride-rich lipoproteins in patients with coronary artery disease.

Triglycerides (TGs) are vehicled by multiple particles with different abilities to promote atherosclerosis. Among plasma TG-rich lipoproteins (TRLs), subspecies may or may not contain apolipoprotein E (apoE) molecules: in this study, we evaluated the relative contribution of apoE-rich and apoE-poor TRLs to coronary atherosclerosis. We selected a group of males with premature coronary artery disease (CAD) without any of the classical nonlipid risk factors and/or high plasma lipid levels and evaluated the plasma concentration of TRL subspecies in comparison with healthy controls. Patients with CAD and controls had total cholesterol and TG levels within the normal range (despite slightly, even…

Atherogenic lipoprotein phenotype and LDL size and subclasses in drug-naïve patients with early rheumatoid arthritis.

Abstract Objective : Subjects with rheumatoid arthritis (RA) have increased cardiovascular risk and may show atherogenic forms of dyslipidemia. The present study investigated whether patients with early RA, beyond alterations in plasma lipids, also show lower LDL size and altered LDL subclass distribution. Design and Methods We identified 25 subjects with RA (47±8 years, body mass index (BMI) 25±4kg/m 2 ) by the American College of Rheumatology diagnostic criteria, with a disease durations Results As compared to controls RA patients had higher plasma triglycerides (1.8±0.5 vs. 1.0±0.5mmol/L, p p =0.0027), while total- and LDL-cholesterol concentrations were similar. LDL particle size was lo…

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…

Association between metabolic syndrome and periodontitis: a systematic review and meta-analysis

Background: Several epidemiological studies have reported an association between metabolic syndrome (MetS) and periodontal diseases (PDs). The aim of this systematic review was to investigate the existence and magnitude of this association. Materials and Methods: A systematic search of the literature was conducted looking for casecontrol, cross-sectional, cohort studies and population surveys including patients with measures of MetS and PD. Ovid MEDLINE, EMBASE, LILACS, and Cochrane library databases were used for the search by 2 independent reviewers. A meta-analysis was conducted to investigate the association for coexistence of MetS and PD. Results: A total of 20 studies were included in…

When Periods Stop: Long-Term Consequences of PCOS

Update on the role of the atherogenic lipoprotein phenotype in cardiovascular prevention

Higher plasma triglyceride levels and decreased HDL-cholesterol concentrations are usually accompanied by the presence of small, dense LDL in the so-called lipid triad or ‘atherogenic lipoprotein phenotype’. This phenotype is highly atherogenic and its prevalence may suggest an even higher overall burden of atherosclerotic disease as compared with that associated with hypercholesterolemia. As stated by the National Cholesterol Education Program Adult Treatment Panel III, there is evidence suggesting each component of this lipid triad is individually atherogenic. However, the relative contribution of each component cannot be easily determined. Therefore, it has been suggested to consider th…

Size and subclasses of low-density lipoproteins in patients with obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) have proatherogenic dyslipidemia. We analyzed predictors of low-density lipoproteins' (LDLs) size in patients with OSA. In a cross-sectional study including 58 participants with OSA (30 without the metabolic syndrome [MetS] and 28 with MetS), we evaluated the size of LDL by gradient gel electrophoresis. Compared with patients without the MetS, those with MetS showed lower LDL size ( P = .007), due to a reduction in large LDL-I particles ( P = .002) and an increase in small, dense LDL-IIIA ( P = .048) and LDL-IIIB ( P = .037). The size of LDL correlated inversely with age ( r = −.268, P = .042) and serum triglycerides ( r = −.364, P = .005), and p…

Effects of lipid-lowering drugs on high-density lipoprotein subclasses in healthy men-a randomized trial.

Context and Objective Investigating the effects of lipid-lowering drugs on HDL subclasses has shown ambiguous results. This study assessed the effects of ezetimibe, simvastatin, and their combination on HDL subclass distribution. Design and Participants A single-center randomized parallel 3-group open-label study was performed in 72 healthy men free of cardiovascular disease with a baseline LDL-cholesterol of 111±30 mg/dl (2.9±0.8 mmol/l) and a baseline HDL-cholesterol of 64±15 mg/dl (1.7±0.4 mmol/l). They were treated with ezetimibe (10 mg/day, n = 24), simvastatin (40 mg/day, n = 24) or their combination (n = 24) for 14 days. Blood was drawn before and after the treatment period. HDL subc…

The differential effects of thiazolidindiones on atherogenic dyslipidemia in type 2 diabetes: what is the clinical significance?

Diabetic dyslipidemia is typically characterized by an increase in plasma triglycerides, a decrease in high-density lipoprotein cholesterol and a concomitant increase in atherogenic small dense low-density lipoproteins. Thiazolidindiones are able to lower the levels of fasting glucose and glycated hemoglobin significantly by improving insulin sensitivity, as well as improving some aspects of diabetic dyslipidemia: total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol tend to increase while triglycerides are generally decreased.This paper reviewed the effects of pioglitazone and rosiglitazone on atherogenic diabetic dyslipidemia, in particular on sma…

Obesity and HFpEF.

Heart failure with preserved ejection fraction (HFpEF) has represented a therapeutic challenge in recent decades [...]

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…

&amp;#x201C;European Panel On Low Density Lipoprotein (LDL) Subclasses&amp;#x201D;: A Statement on the Pathophysiology, Atherogenicity and Clinical Significance of LDL Subclasses: Executive Summary

The Role of the Metabolome and Non-Coding RNA on Pheochromocytomas and Paragangliomas: An Update.

Pheochromocytoma and paragangliomas (PPGL) are rare neuroendocrine tumors. In some patients they exhibit malignant behavior characterized by the presence of metastases, limiting treatment options and survival rates. Therapeutic options are limited to surgery, localized radiotherapy, and a few systemic therapies. However, in several recent studies, non-coding RNA molecules are gaining increasing attention as markers of malignancy for PPGL. The understanding of PPGL development molecular mechanisms has improved in the last years, with some of the epigenetic regulatory mechanisms such as DNA and histones methylation, being better understood than RNA-based mechanisms. Metabolome deregulation in…

Head-to-head comparison of statins versus fibrates in reducing plasma fibrinogen concentrations: A systematic review and meta-analysis

Several studies suggest differences between fibrates and statins in lowering plasma fibrinogen (Fib) concentrations, but the evidence is not definitive. Therefore, the aim of this meta-analysis of head-to-head randomized trials was to compare the efficacy of statins and fibrates on plasma Fib concentrations.The literature search included Medline, Scopus, and Web of Science up to February 1st, 2015, to identify head-to-head comparative randomized trials investigating the efficacy of fibrates vs statins on plasma Fib concentrations.In total 22 trials with 2762 participants were included to the meta-analysis. Random-effect meta-analysis suggested a significantly greater effect of fibrates vs s…

Novel therapeutical approaches to managing atherosclerotic risk

Atherosclerosis is a multifactorial vascular disease that leads to inflammation and stiffening of the arteries and decreases their elasticity due to the accumulation of calcium, small dense Low Density Lipoproteins (sdLDL), inflammatory cells, and fibrotic material. A review of studies pertaining to cardiometabolic risk factors, lipids alterations, hypolipidemic agents, nutraceuticals, hypoglycaemic drugs, atherosclerosis, endothelial dysfunction, and inflammation was performed. There are several therapeutic strategies including Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) inhibitors, inclisiran, bempedoic acid, Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RAs), and nutraceuticals t…

An update on the relationships between rheumatoid arthritis and atherosclerosis

Rheumatoid arthritis is a chronic inflammatory disease. Cardiovascular events are the most important cause of mortality and morbidity in patients with rheumatoid arthritis. Beyond the traditional cardiovascular risk factors, chronic systemic inflammation has been shown to be a crucial factor in atherosclerosis development and progression from endothelial dysfunction to plaque rupture and thrombosis. Many studies have shown that atherosclerosis is not a passive event like accumulation of lipids in the vessel walls; by contrast, it represents an active inflammation of the vessels. Inflammatory cells such as macrophages, monocytes and T cells play important roles in the development of both rhe…

High-Sensitivity C-Reactive Protein and Statin Initiation

The assessment of cardiovascular risk and treatment of cardiovascular diseases are major public health issues worldwide. Inflammation is now recognized as a key regulatory process that links multiple risk factors for atherosclerosis. The substantial number of patients having cardiovascular events lack commonly established risk factors. The utility of high-sensitivity C-reactive protein (hsCRP), a circulating biomarker related to inflammation, may provide additional information in risk prediction. This review will consider the impact of hsCRP level on initiation of statin therapy.

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 ® , …

Altilix

The objective was to evaluate the effects of 6 months of supplementation with Altilix®, containing chlorogenic acid and its derivatives, and luteolin and its derivatives, on cardiovascular risk and hepatic markers in subjects with metabolic syndrome (MetS). A randomized, double-blind, placebo-controlled study was performed in 100 subjects with MetS with a follow-up period of 6 months; 50 subjects were randomized to Altilix® (26 men and 24 women, mean age 63 ± 8 years) and the other 50 to placebo (28 men and 22 women, mean age 63 ± 11 years). Anthropometric, cardiometabolic, and hepatic parameters were assessed at baseline and at the end of follow-up. Carotid intima-media thickness and endot…

Low-density lipoproteins generated during an oral fat load in mild hypertriglyceridemic and healthy subjects are smaller, denser, and have an increased low-density lipoprotein receptor binding affinity.

Triglyceride-rich lipoproteins generated during the postprandial phase are atherogenic. Large very low-density lipoproteins (LDLs) or chylomicrons (CMs) are not as atherogenic as their remnants (Rem). Small and dense LDLs are associated with cardiovascular disease. Low-density lipoprotein size is partly under genetic control and is considered as a relatively stable LDL feature. In this article, we present data on retinyl palmitate kinetics correlated with the modification of LDL features in terms of size, density, and in vitro receptor binding affinity after an oral fat load. Six nondiabetic, hypertriglyceridemic (HTG) patients and 6 healthy controls were examined. Low-density lipoprotein s…

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 &gt;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-…

The Emerging Role of Dual GLP-1 and GIP Receptor Agonists in Glycemic Management and Cardiovascular Risk Reduction

The incretin pathway is a self-regulating feedback system connecting the gut with the brain, pancreas, and liver. Its predominant action is on the postprandial glucose levels, with extraglycemic effects on fat metabolism and endovascular function. Of the two main incretin hormones released with food ingestion, the actions of glucagon-like peptide-1 (GLP-1) have been exploited for therapeutic benefit. However, little attention has been paid to glucose-dependent insulinotropic polypeptide (GIP) until the recent experimental introduction of dual agonists, or "twincretins". Interestingly, simultaneous activation of both receptors is not only replicative of normal physiology, it seems to be an i…

Heat-shock protein 60 kDa and atherogenic dyslipidemia in patients with untreated mild periodontitis: a pilot study

Identification of predictors of cardiovascular risk can help in the prevention of pathologic episodes and the management of patients at all stages of illness. Here, we investigated the relationships between serum levels of Hsp60 and dyslipidemia in patients with periodontitis by performing a cross-sectional study of 22 patients with mild periodontitis without any prior treatment for it (i.e., drug naive) and 22 healthy controls, matched for age and body mass index (BMI). All subjects were evaluated for periodontal status, gingival inflammation, and oral hygiene. Levels of circulating Hsp60, C-reactive protein (CRP), and plasma lipids were measured, and small, dense low-density lipoproteins …

Current and emerging drugs for the treatment of atherosclerosis: the evidence to date

Introduction: Atherosclerosis can be considered a chronic inflammatory process that stands out as a dominant cause of cardiovascular disease (CVD). Since blood lipids are the leading risk factor for atherosclerosis development, lowering low-density lipoprotein cholesterol (LDL-C) and other apolipoprotein B-containing lipoproteins reduces the risk of future cardiovascular events. However, there has been significant progress in developing lipid-lowering drugs for aggressive management of dyslipidemia, the rates of CVD events remain unacceptably high, so there is great need to identify novel therapeutic pathways targeting the atherosclerosis process.Areas covered: We discussed the current guid…

Gender differences in the battle against COVID‐19: Impact of genetics, comorbidities, inflammation and lifestyle on differences in outcomes

Abstract It has been over six months now since the entire globe was struck by the new Coronavirus Disease 2019 (COVID‐19; aka severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2]), which has affected 215 nations. The medical and scientific communities continue to search for and study potential treatments for COVID‐19 as well as an effective vaccine. As of 21 June 2020, 11.4 million cases have been confirmed worldwide, with approximately 530,000 deaths. A large number of scientific papers have been produced, hundreds of thousands of patients have been hospitalized and studied, several treatments and vaccines are being tested in randomized clinical trials, social distancing regulation…

Statins, Fracture Risk, and Bone Remodeling: What Is True?

Besides the action on plasma lipid levels, statins show a series of ancillary effects defined as all of their vascular and nonvascular effects independent from the cholesterol reduction. It has been recently hypothesized that one of these ancillary effects could be the improvement of bone health, due to the interference with bone metabolism. This may potentially represent the rationale for statins' use in the treatment of osteoporosis, the most common disease of the bone. Both experimental observations and clinical studies on this topic generated a number of conflicting results; however, the largest randomized clinical trials, the Scandinavian Simvastatin Survival Study (4S), Long Term Inte…

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…

Nonalcoholic Fatty Liver Disease, Cardiovascular Risk, and Carotid Inflammation.

Nonalcoholic fatty liver disease (NAFLD) is defined by excessive triglycerides (TGs) accumulation in the liver (>5% of hepatocytes histologically) in the absence of alcohol excess. The NAFLD ranges from simple steatosis to steatohepatitis and cirrhosis. The NAFLD and nonalcoholic steatohepatitis (NASH) are now the number one cause of liver disease in Western countries. The prevalence of NAFLD is increasing but is underreported, and the epidemiology and demographic characteristics vary worldwide. The prevalence is increasing because of the rising occurrence of obesity and type 2 diabetes (T2DM); in fact, NAFLD is considered as the hepatic manifestation of metabolic syndrome (MetS). Nonalcoho…

Biosimilar and generic formulations of novel antidiabetic drugs: the role of liraglutide in clinical pharmacology of type 2 diabetes.

The clinical significance of small, dense low-density lipoproteins

Peak size of low-density lipoproteins (LDL) in humans does not show a normal, but a bimodal distribution and can be separated into two phenotypes, that differ in size, density, physicochemical composition, metabolic behavior, and atherogenicity. These phenotypes have been assigned as pattern A when larger, more buoyant LDL and pattern B when smaller, more dense LDL predominate. Small dense LDL correlates negatively with plasma HDL levels and positively with plasma triglyceride concentrations and is associated with the metabolic syndrome and increased risk for cardiovascular disease. LDL size seems to be an important predictor of cardiovascular events and progression of coronary heart diseas…

How should we manage atherogenic dyslipidemia in women with polycystic ovary syndrome?

Despite their young age, women with polycystic ovary syndrome (PCOS) have increased cardiovascular risk. Besides normal concentrations of low-density lipoprotein (LDL) cholesterol, dyslipidemia is very common and includes elevated triglyceride levels and low high-density lipoprotein cholesterol concentrations. Recent findings also showed that women with PCOS have qualitative LDL alterations, with increased levels of atherogenic small, dense LDL particles. Such lipid abnormalities constitute a common form of dyslipidemia, the so-called atherogenic lipoprotein phenotype (ALP), associated with a greater cardiovascular risk. Weight reduction and increased physical activity may constitute first-…

Glucose lowering and anti-atherogenic effects of incretin-based therapies: GLP-1 analogues and DPP-4-inhibitors

Type 2 diabetes is a chronic, progressive disease with a multi-faceted pathophysiology. Beyond the known defects of insulin resistance and beta-cell insufficiency, derangement of incretin hormones normally produced from the gut wall in response to food intake play an important role. In recent years, the 'incretin-based' therapies (IBTs) have been developed to address hyperglycemia through either mimicking the action of the endogenous incretin glucagon-like polypeptide (GLP-1) (GLP-1 receptor agonists) or by inhibiting the activity of the enzyme that degrades GLP-1 (the dipeptyl peptidase-4 inhibitors).We reviewed available evidence on the glucose lowering and anti-atherogenic effects of IBT…

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 …

Small, dense low-density-lipoproteins and the metabolic syndrome.

Small, dense low-density-lipoproteins (LDL) are associated with increased risk for cardiovascular diseases and diabetes mellitus and a reduction in LDL size has been reported in patients with coronary and non-coronary forms of atherosclerosis. LDL size has been accepted as an important predictor of cardiovascular events and progression of coronary artery disease as well as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III. Small, dense LDL, with elevated triglyceride levels and low HDL-cholesterol concentrations, constitute the 'atherogenic lipoprotein phenotype (ALP)', a form of atherogenic dyslipidemia that is a feature of type …

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…

Exploring the Role of Skeletal Muscle in Insulin Resistance: Lessons from Cultured Cells to Animal Models

Skeletal muscle is essential to maintain vital functions such as movement, breathing, and thermogenesis, and it is now recognized as an endocrine organ. Muscles release factors named myokines, which can regulate several physiological processes. Moreover, skeletal muscle is particularly important in maintaining body homeostasis, since it is responsible for more than 75% of all insulin-mediated glucose disposal. Alterations of skeletal muscle differentiation and function, with subsequent dysfunctional expression and secretion of myokines, play a key role in the pathogenesis of obesity, type 2 diabetes, and other metabolic diseases, finally leading to cardiometabolic complications. Hence, a de…

The role of macrophage colony-stimulating factor in patients with acute myocardial infarction: a pilot study.

We assessed whether macrophage colony-stimulating factor (M-CSF) levels are associated with left ventricular systolic dysfunction (LVSD) in patients with acute myocardial infarction (AMI). We studied 56 patients with AMI (mean age: 67 ± 12 years) and identified those with clinical (Killip class &gt;II) or echocardiographic signs (ejection fraction ≤45%) of LVSD. We evaluated the established cardiovascular risk factors and measured several cardiovascular biomarkers, including M-CSF. Serum M-CSF concentrations (pg/mL) were significantly increased in patients with both clinical and echocardiographic signs of LVSD (460 ± 265 vs 290 ± 210, P = .0103 and 493 ± 299 vs 287 ± 174, P = .0028, respec…

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…

The Evolving Role of Fetuin-A in Nonalcoholic Fatty Liver Disease: An Overview from Liver to the Heart

Nonalcoholic fatty liver disease (NAFLD) is strongly associated to the features of metabolic syndrome which can progress to cirrhosis, liver failure and hepatocellular carcinoma. However, the most common cause of mortality in people with NAFLD is not liver-related but stems from atherosclerotic cardiovascular disease (CVD). The prevalence of NAFLD is on the rise, mainly as a consequence of its close association with two major worldwide epidemics, obesity and type 2 diabetes (T2D). The exact pathogenesis of NAFLD and especially the mechanisms leading to disease progression and CVD have not been completely elucidated. Human fetuin-A (alpha-2-Heremans Schmid glycoprotein), a glycoprotein produ…

A Review of the Cardiovascular and Anti-Atherogenic Effects of Ghrelin

Ghrelin is a peptide hormone produced mainly in the stomach that has widespread tissue distribution and diverse hormonal, metabolic and cardiovascular activities. The circulating ghrelin concentration increases during fasting and decreases after food intake. Ghrelin secretion may thus be initiated by food intake and is possibly controlled by nutritional factors. Lean subjects have increased levels of circulating ghrelin compared with obese subjects. Recent reports show that low plasma ghrelin is associated with elevated fasting insulin levels, insulin resistance and type 2 diabetes mellitus. Factors involved in the regulation of ghrelin secretion have not yet been defined; however, it is as…

Recent Insights on Dark Chocolate Consumption and Cardiovascular Risk

Drug Induced Liver Injury (DILI) due to variability in monacolin K content in Red Yeast Rice (RYR): An expert opinion

Abstract Introduction Red yeast rice (RYR) is an effective cholesterol-lowering nutraceutical reversibly inhibiting 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase. As liver damage is a possible (albeit rare) side effect of HMG-CoA inhibitors, it make sense to focus on the tolerability of the liver to RYR extracts. The aim of this paper is to offer an expert opinion on the risk of liver damage by the use of RYR extract. Methods A review of the available literature has been carried out and critically reviewed by the authors. Results According to a large meta-analysis of 53 randomized clinical trials comprising 112 treatment arms, which included 8535 subjects with 4437 in the RYR arm and …

Long-term consequences of polycystic ovary syndrome on cardiovascular risk

Most available data suggest that the prevalence of cardiovascular diseases in women with polycystic ovary syndrome (PCOS) is smaller than expected based on risk calculations during fertile years; therefore, more studies are needed on long-term cardiovascular consequences. Evidence is accumulating that postmenopausal women with PCOS have an increased risk of cerebrovascular events and cardiovascular morbidity. These events are partially related to persisting hyperandrogenism but are mostly correlated with excessive body weight (mainly visceral obesity); this suggests that our best long-term strategy is to ensure that women with PCOS are informed about their high risk for metabolic and cardio…

Prediction of cardio- and cerebro-vascular events in patients with subclinical carotid atherosclerosis and low HDL-cholesterol.

Low HDL-cholesterol concentrations are associated with increased cardiovascular risk and recent evidences suggest that HDL may aggravate the atherosclerotic process promoting inflammation: HDL are anti-inflammatory in the absence of inflammation but can become proinflammatory in the presence of atherosclerosis. Yet, no data is available on the cardiovascular outcome in subjects with low HDL-cholesterol and early stages of atherosclerosis. Therefore, we included in a prospective 5-year follow-up study 150 subjects with low HDL-cholesterol concentrations and subclinical carotid atherosclerosis, as assessed by carotid colour doppler, evaluating at baseline all the established traditional cardi…

Diabetes and Colorectal Cancer Risk: A New Look at Molecular Mechanisms and Potential Role of Novel Antidiabetic Agents.

Epidemiological data have demonstrated a significant association between the presence of type 2 diabetes mellitus (T2DM) and the development of colorectal cancer (CRC). Chronic hyperglycemia, insulin resistance, oxidative stress, and inflammation, the processes inherent to T2DM, also play active roles in the onset and progression of CRC. Recently, small dense low-density lipoprotein (LDL) particles, a typical characteristic of diabetic dyslipidemia, emerged as another possible underlying link between T2DM and CRC. Growing evidence suggests that antidiabetic medications may have beneficial effects in CRC prevention. According to findings from a limited number of preclinical and clinical stud…

Clinical benefits of ezetimibe use: is absence of proof, proof of absence?

Doggrell reviewed the evidence regarding the clinical benefits of ezetimibe in the July issue of Expert Opinion on Pharmacotherapy [1]. The author concludes that since clinical outcome data are sti...

Androgen excess and cardiovascular risk.

Cardiovascular diseases represent the major cause of death in most of developed countries and ultimately kill as many men as women. Both genders are exposed to the same risk factors but their rates of cardiovascular morbidity and mortality are very different until old age. This represents a crucial point; in fact, only at age 75 and over cardiovascular rates of women approximate those of men. It has been suggested that differences in hormonal status and mainly in androgen levels may explain such gender disparity. Consistently with this hypothesis, it has been shown that women with polycystic ovary syndrome (PCOS) have elevated cardiovascular risk despite their young age. However, the possib…

Managing the Systemic Impact of Periodontitis

Periodontitis is a microbially driven host-mediated disease that leads to loss of periodontal attachment and bone. It is associated with elevation of systemic inflammatory markers and with the presence of systemic co-morbidities. Furthermore, periodontal treatment leads to a 24–48 h-long acute local and systemic inflammatory response. This systemic response might increase the burden of patients with compromised medical history and/or uncontrolled systemic diseases. The correlation between periodontitis and systemic diseases, the impact of periodontitis on the quality of life and public health, the effects of periodontal treatment on systemic health and disease, and the available methods to …

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…

Editorial (Thematic Issues: Managing the Cardiovascular Risk Associated with the Metabolic Syndrome)

Changes in immunohistochemical levels and subcellular localization after therapy and correlation and colocalization with CD68 suggest a pathogenetic role of Hsp60 in ulcerative colitis.

In an earlier work, the role of heat shock protein (Hsp60) in the pathogenesis of ulcerative colitis (UC) was suggested by its significant increase in the pathological mucosa parallel with an increase in inflammatory cells. More data in this direction are reported in this work. We analyzed by immunohistochemistry biopsies of colon tissue from 2 groups of patients with UC and treated with either 5-aminosalicylic acid (5-ASA) alone or in combination with a probiotic. We looked for inflammatory markers and Hsp60. Both the treatments were effective in reducing symptoms but the group treated with both 5-ASA and probiotics showed better clinical results. Amelioration of symptoms was associated wi…

Do we need better lipid tools for cardiovascular risk assessment ?

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…

Atherogenic lipoprotein phenotype and low-density lipoprotein size and subclasses in patients with growth hormone deficiency before and after short-term replacement therapy

Objective: Patients with growth hormone deficiency (GHD) have increased cardiovascular risk and may show elevated triglyceride and reduced high density lipoprotein (HDL) cholesterol concentrations, two lipid abnormalities usually accompanied by increased small dense LDL in the ‘atherogenic lipoprotein phenotype’ (ALP). In the present study, we directly investigated (1) whether hypopituitary patients with GHD have increased small dense LDL; (2) whether growth hormone replacement therapy (GHRT) beneficially impact on such particles; (3) the prevalence of ALP in GHD and GHRT patients. Design and methods: In 14 hypopituitary patients with GHD (44 ± 13 years, body mass index (BMI) 27 ± 3) before…

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…

The effects of ezetimibe on LDL-cholesterol: quantitative or qualitative changes ?

Ezetimibe represents the first of a new class of agents, the cholesterol absorption inhibitors, able to reduce low-density lipoproteins (LDL)-cholesterol by 15-25% from baseline in monotherapy and on top of statins and fibrates. To-date all the data regarding the efficacy of ezetimibe comes from the studies of its lipid-lowering power. Yet, recent findings from the ENHANCE study on atherosclerosis progression showed that the addition of ezetimibe to simvastatin in patients with heterozygous familial hypercholesterolemia did not affect the mean change in carotid intima-media thickness, although a significant reduction in LDL-cholesterol levels was present. Therefore, we cannot exclude that e…

Older age and markers of inflammation are strong predictors of clinical events in women with asymptomatic carotid lesions

OBJECTIVE: Limited information exists regarding the association between markers of inflammation, such as high-sensitivity C-reactive protein (hs-CRP) and fibrinogen, and adverse events in postmenopausal women with subclinical atherosclerosis. Therefore, we investigated the prognostic impact of traditional risk factors and inflammation on adverse cardiac events in women with asymptomatic carotid lesions. DESIGN: We studied 250 postmenopausal women who were free of cardiovascular disease. Traditional cardiovascular risk factors were investigated, and laboratory analysis included measurement of plasma lipids, fibrinogen, and hs-CRP. The early phases of carotid atherosclerosis were assessed by …

NLRP3 Inflammasome Biomarker-Could Be the New Tool for Improved Cardiometabolic Syndrome Outcome.

Metabolomics, the research area studying chemical processes involving metabolites, finds its utility in inflammasome biomarker discovery, thus representing a novel approach for cardiometabolic syndrome pathogeny acknowledgements. Metabolite biomarkers discovery is expected to improve the disease evolution and outcome. The activation of abundantly expressed NLRP3 inflammasome represents the background process of the diabetes mellitus disturbances like hyperglycemia and insulin resistance, as well as for myocardial cell death and fibrosis, all of them being features characteristic for cardiometabolic syndrome. Many molecules like troponins, brain natriuretic protein (BNP), ST2/IL-33, C-reacti…

Correlations between Diabetes Mellitus Self-Care Activities and Glycaemic Control in the Adult Population: A Cross-Sectional Study

Although it is well known that lifestyle changes can affect plasma glucose levels, there is little formal evidence for the sustained effectiveness of exercise and diet in diabetes mellitus (DM) management. Self-care in DM refers to the real-life application of the knowledge that the patient gained during the education programmes. The goals are to bring about changes in the patient&rsquo;s behaviour, thus improving glycaemic control. We evaluated the influence of DM self-care activities (SCA) on glycaemic control in a total of 159 patients with DM. Plasma glycated haemoglobin (HbA1c) levels were used to monitor glycaemic control, while SCA were assessed using the standardised Diabetes Self-M…

Long-Term Brain Disorders in Post Covid-19 Neurological Syndrome (PCNS) Patient

In the recent pandemic disease, called COVID-19, the role of neurologists and neurobiologists represents a chance to study key features of brain infection and deepen neurological manifestations of COVID-19 and other coronavirus infections. In fact, many studies suggest brain damage during infection and persistent neurological symptoms after COVID-19 infection. Reverse transcription PCR test, antibody tests, Computed Tomography (CT) of the lung, and Magnetic Resonance (MR) of the brain of the patient were periodically performed during this case report for eight months after infection. The aim of this article is to describe the prolonged neurological clinical consequences related to COVID-19.…

Statins decrease all-cause mortality only in CKD patients not requiring dialysis therapy--a meta-analysis of 11 randomized controlled trials involving 21,295 participants.

The available studies have reported the benefits of statins on all-cause and cardiovascular mortality in chronic kidney disease (CKD) patients. However studies in end-stage renal disease patients on dialysis yielded conflicting results. Therefore, we performed a meta-analysis and provide the most reliable trial data to date on the impact of statin therapy on cardiovascular events and death from all causes in CKD patients. Data from PubMed, Web of Science, Cochrane Library, and Scopus for the years 1966 to October 2012 were searched. The final meta-analysis included 11 randomized controlled trials involving 21,295 participants with CKD. Among them 6857 were on dialysis. The use of statins in…

Glucagon-Like Peptide 1 and Taste Perception: From Molecular Mechanisms to Potential Clinical Implications

Preclinical studies provided some important insights into the action of glucagon-like peptide 1 (GLP-1) in taste perception. This review examines the literature to uncover some molecular mechanisms and connections between GLP-1 and the gustatory coding. Local GLP-1 production in the taste bud cells, the expression of GLP-1 receptor on the adjacent nerves, a functional continuum in the perception of sweet chemicals from the gut to the tongue and an identification of GLP-1 induced signaling pathways in peripheral and central gustatory coding all strongly suggest that GLP-1 is involved in the taste perception, especially sweet. However, the impact of GLP-1 based therapies on gustatory coding i…

Mipomersen: a lipid-lowering agent with a novel mechanism of action

“...mipomersen is a ... valuable alternative to apheresis for patients with heterozygous familial hypercholesterolemia.”

The Effects of Statin Treatment on Serum Ferritin Levels: A Systematic Review and Meta-Analysis.

Background: Statins are the most widely used drugs for decreasing elevated serum LDL-cholesterol (LDL-C) and thus for the prevention of atherosclerotic cardiovascular disease (ASCVD), but they have also some pleiotropic effects, including anti-inflammatory properties. Atherosclerosis is a low-grade inflammatory disease, and elevated ferritin is considered to be one of the markers of inflammation. Since the results of studies on the effects of statins on serum ferritin levels are conflicting, this meta-analysis was performed. Methods: A literature search was performed using major electronic databases (MEDLINE/PubMed, Scopus, Embase, and ISI Web of Science) from inception up to 5 March 2022 t…

Plasma clearance of human low-density lipoprotein in human apolipoprotein B transgenic mice is related to particle diameter.

To test for intrinsic differences in metabolic properties of low-density lipoprotein (LDL) as a function of particle size, we examined the kinetic behavior of 6 human LDL fractions ranging in size from 251 to 265 A injected intravenously into human apolipoprotein (apo) B transgenic mice. A multicompartmental model was formulated and fitted to the data by standard nonlinear regression using the Simulation, Analysis and Modeling (SAAM II) program. Smaller sized LDL particles (251 to 257 A) demonstrated a significantly slower fractional catabolic rate (FCR) (0.050 +/- 0.045 h(-1)) compared with particles of larger size (262 to 265 A) (0.134 +/- -0.015 h(-1), P.03), and there was a significant …

Safety and benefit of incretin-based therapies in patients with type 2 diabetes: learnings and reflections

Reconnoitering the Therapeutic Role of Curcumin in Disease Prevention and Treatment: Lessons Learnt and Future Directions

Turmeric is a plant with a very long history of medicinal use across different cultures. Curcumin is the active part of turmeric, which has exhibited various beneficial physiological and pharmacological effects. This review aims to critically appraise the corpus of literature associated with the above pharmacological properties of curcumin, with a specific focus on antioxidant, anti-inflammatory, anticancer and antimicrobial properties. We have also reviewed the different extraction strategies currently in practice, highlighting the strengths and drawbacks of each technique. Further, our review also summarizes the clinical trials that have been conducted with curcumin, which will allow the …

Atherogenic lipoprotein phenotype and low-density lipoproteins size and subclasses in women with polycystic ovary syndrome.

Abstract Context: An altered lipid profile is common in polycystic ovary syndrome (PCOS) and is usually characterized by increased triglycerides and low high-density lipoprotein (HDL)-cholesterol levels. In the general population, these alterations are often associated with the increase of small low-density lipoproteins (LDLs) in the so-called “atherogenic lipoprotein phenotype” (ALP) that determines a further increase of cardiovascular risk. In this study, we evaluated the presence of ALP in the plasma of women with PCOS. Setting: Measurements and analysis of LDL size were performed at the Clinic of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital, Zurich. PCOS patients…

Effects of hypolipidemic and hypoglycemic agents on atherogenic small, dense LDL in Type 2 diabetes

Type 2 diabetes is associated with a cluster of inter-related plasma lipid and lipoprotein abnormalities, including reduced HDL-C, a predominance of small, dense LDL and elevated triglycerides. These abnormalities occur even in prediabetes, before blood sugars rise sufficiently in order to confirm a diagnosis of diabetes, and this transition phase incurs important cardiovascular risk. This is the rationale for paying attention to dyslipidemia through the use of the hypolipidemic, rather than hypoglycemic drugs only. A literature search (by Medline and Scopus) was performed. The authors also manually reviewed the references of selected articles for any pertinent material. Beyond the ‘quantit…

Postprandial metabolism: from research to clinical practice.

Over the last decade, the importance of postprandial metabolism has increased, given that it is the physiological state of humans in modern society. Moreover, postprandial lipemia is considered as a key player in the development of the most important cardiometabolic diseases. In this regard, postprandial lipemia has become more important, since it has been demonstrated that nonfasting triglycerides (TGs) are independent predictors of the risk of cardio vascular disease (CVD) [1,2]. Interestingly, the postprandial phase has been associated with increased inflammation and oxidation, which influences vascular function through a permanent endothelial aggression by atherogenic lipoprotein. TGs a…

Therapeutic modulation of lipoprotein-associated phospholipase A2 (Lp-PLA2)

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a calcium-independent phospholipase A2 that circulates in plasma in association with lipoprotein particles, whereas in atherosclerotic plaques it is co-localized with macrophages. Lp-PLA2 generates two proinflammatory mediators, lysophosphatidylcholine and oxidized nonesterified fatty acids, which play a role in the development of atherosclerotic lesions and formation of a necrotic core, leading to more vulnerable plaques. Epidemiologic studies demonstrate that increased circulating levels of Lp-PLA2 predict an increased risk of myocardial infarction, stroke and cardiovascular mortality. Furthermore, histologic examination of diseased hum…

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 &lt; .0001), body mass index (from 29.6 [23.7] to 29.3 [21.9] kg/m2, P = .001), and wai…

Prediction of vascular events in subjects with subclinical atherosclerosis and the metabolic syndrome: The role of markers of inflammation

AIM: The presence of the metabolic syndrome (MS) increases cardiovascular morbidity and mortality and we aimed to assess the outcome in subjects with the MS and subclinical atherosclerosis. METHODS: We followed-up for five years 339 Mediterranean subjects with asymptomatic carotid intima-media thickness >0.9 mm (men: 60%; age: 66±5 years), of whom 130 had the MS (men: 59%; age: 66±5 years), evaluating at baseline traditional cardiovascular risk factors (including male gender, older age, obesity, hypertension, diabetes, smoking, family history of cardiovascular diseases, dyslipidemia) and plasma levels of C-reactive protein and fibrinogen. RESULTS: Cardio- and cerebrovascular events were reg…

Effect of Bariatric Surgery on Intima Media Thickness: A Systematic Review and Meta-Analysis

Background: Obesity, and in particular extreme obesity, as a global health problem is an important risk factor for many diseases, including atherosclerotic cardiovascular disease (ACVD). Bariatric surgery might stop or slow atherogenesis by decreasing excessive weight in the early stages of atherogenesis, by suppressing low-grade systemic inflammation as well as by inhibiting oxidative stress and endothelial dysfunction. The aim of this meta-analysis was to provide an answer to whether bariatric surgery has a significant effect on intima-media thickness (IMT) which is a surrogate marker of early atherosclerosis and has a good correlation with atherosclerotic coronary heart disease. Methods:…

Incretin-Based Therapies Role in COVID-19 Era: Evolving Insights

The current coronavirus disease 2019 (COVID-19) pandemic has led the scientific community to breach new frontiers in the understanding of human physiology and disease pathogenesis. It has been hypothesized that the human dipeptidyl peptidase 4 (DPP4) enzyme receptor may be a functional target for the spike proteins of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Since DPP4-inhibitors are currently used for the treatment of patients with type-2 diabetes (T2DM), there is currently high interest in the possibility that these agents, or incretin-based therapies (IBTs) in general, may be of benefit against the new coronavirus infection. Diabetes is associated with increased COV…

A New Comorbidity in Periodontitis: Fusobacterium nucleatum and Colorectal Cancer

There is very recent and strong evidence relating Fusobacterium nucleatum to colorectal cancer. In this narrative review, we update the knowledge about gingival dysbiosis and the characteristics of Fusobacterium nucleatum as one of the main bacteria related to periodontitis. We provide data on microbiome, epidemiology, risk factors, prognosis, and treatment of colorectal cancer, one of the most frequent tumours diagnosed and whose incidence increases every year. We describe, from its recent origin, the relationship between this bacterium and this type of cancer and the knowledge and emerging mechanisms that scientific evidence reveals in an updated way. A diagram provided synthesizes the pa…

Impact of COVID-19 Pandemic on Disease Control Status and Quality of Life of Patients with Acromegaly.

Background and Objectives: Despite the best efforts of healthcare workers and the deployment of alternative healthcare delivery solutions through telemedicine, the pandemic has disrupted standard care for patients with chronic conditions. The long-lasting pandemic has also had a profound impact on the quality of life (QoL) of the majority of patients with chronic illnesses. The management of rare diseases has been particularly challenging. We aimed to evaluate the impacts that the long-lasting pandemic had on the disease control status and QoL in patients with acromegaly. Materials and Methods: Our prospective study included 34 patients from a national referral centre. The baseline SAGIT an…

The Therapeutic Role of SGLT-2 Inhibitors in Acute Heart Failure: From Pathophysiologic Mechanisms to Clinical Evidence with Pooled Analysis of Relevant Studies across Safety and Efficacy Endpoints of Interest

(1) Background: Sodium-glucose co-transporter-2 (SGLT-2) inhibitors constitute a novel drug class with remarkable cardiovascular benefits for patients with chronic heart failure (HF). Recently, this class has been utilized in acute HF as an additional treatment option to classic diuretics, which remain the cornerstone of treatment. (2) Methods: We attempted to identify those pathophysiologic mechanisms targeted by SGLT-2 inhibitors, which could be of benefit to patients with acute HF. We then conducted a comprehensive review of the literature within the PubMed database in order to identify relevant studies, both randomized controlled trials (RCTs) and observational studies, assessing the sa…

Alteration in Redox Status and Lipoprotein Profile in COVID-19 Patients with Mild, Moderate, and Severe Pneumonia

Background. Metabolic alterations, particularly disorders of lipoprotein metabolism in COVID-19, may affect the course and outcome of the disease. This study aims at evaluating the lipoprotein profile and redox status in SARS-CoV-2 infected patients with different pneumonia severity and their association with lethal outcomes. Methods. The prospective cohort study was performed on 98 COVID-19 patients with mild, moderate, and severe pneumonia. Lipid and inflammatory parameters, lipoprotein subclasses, and redox status biomarkers were determined at the study entry and after one week. Results. Compared to patients with mild and moderate pneumonia, severely ill patients had higher oxidised low-…

LDL size: does it matter?

The atherogenic lipoprotein phenotype is characterised by a moderate increase in plasma triglycerides, a decrease in high density lipoprotein cholesterol and the prevalence of smaller denser low density lipoprotein particles. The prevalence of this partially inheritable phenotype is approximately 30% and is a feature of the metabolic syndrome associated with an increased risk for cardiovascular events. The predominance of small dense LDL has been accepted as an emerging cardiovascular risk factor by the adult treatment panel (ATP) III.

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…

The predictive role of atherogenic dyslipidemia in subjects with non-coronary atherosclerosis

Abstract Background Recent findings have suggested that subjects with non-coronary atherosclerosis may show elevated prevalence of atherogenic dyslipidemia, including higher triglyceride levels, reduced HDL-cholesterol concentrations and increased levels of small, dense low-density lipoproteins (LDL). These three lipid abnormalities constitute the so-called “atherogenic-lipoprotein-phenotype” (ALP) but its predictive role in these patients still remains to be established. Methods We performed a 2-year follow-up study to assess clinical and biochemical predictors of cardiovascular events in 44 male patients (64 ± 5 years, BMI: 27 ± 3), 26 with peripheral arterial disease and 18 with abdomina…

Association of simvastatin and hyperlipidemia with periodontal status and bone metabolism markers.

Background: The objective of this study is to determine whether simvastatin consumption and hyperlipidemia are associated with a worse periodontal condition and specific bone activity biomarkers. Methods: This cross-sectional and analytic study includes 73 patients divided into three groups: 1) simvastatin-treated patients with hyperlipidemia (n = 29); 2) patients with hyperlipidemia treated by diet alone (n = 28); and 3) normolipidemic patients (controls, n = 16). The periodontal clinical variables of all participants were gathered, a blood sample was drawn from each to determine the lipid profile (total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein), se…

Differential apolipoprotein(a) isoform expression in heterozygosity is an independent contributor to lipoprotein(a) levels variability

Abstract Background and methods : Lipoprotein(a) [Lp(a)] levels represent an independent risk factor for cardio- and cerebrovascular diseases. Since lipoprotein(a) levels show a wide variability even in subjects with similar apolipoprotein(a) isoforms, we investigated the contribution of apolipoprotein(a) heterozygosity to lipoprotein(a) variance. Lipoprotein(a) levels, apolipoprotein(a) isoforms identification and expression, and the correlation with other lipo-apolipoprotein parameters have been investigated in 628 subjects >18 years of age. Results : In our study, 246 subjects were found heterozygous for apolipoprotein(a) isoforms. Lipoprotein(a) levels were higher in females. About 40% …

A practical method to determine the "atherogenic lipoprotein phenotype"

Oxidative stress and small, dense low-density lipoproteins: current and future perspectives

Small, dense low-density lipoproteins (LDLs) are more susceptible to oxidation than their larger, more buoyant counterparts and therefore the biological modification of these LDL particles may, in part, be responsible for their atherogenic properties. Kotani et al. found that at multiple regression analysis there was an independent and significant inverse correlation between the mean LDL particle size and the oxidative stress status; notably, the authors adjusted not only for the traditional cardiovascular risk factors, but also for drug treatments. Higher levels of small, dense LDL concentrations significantly contribute to atherosclerosis, and lipoprotein size and subfractions may refine …

Atherogenic lipoprotein phenotype and LDL size and subclasses in patients with peripheral arterial disease

The type of dyslipidemia in patients with peripheral arterial disease (PAD) is still ill defined. PAD patients often show elevated triglycerides and reduced HDL-cholesterol, two lipid abnormalities usually accompanied by decreased LDL size in the "atherogenic lipoprotein phenotype" (ALP). We investigated (1) whether PAD patients have lower LDL size, (2) altered LDL subclass distribution and (3) the prevalence of ALP. We measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis in 31 adults with intermittent claudication and 31 age-BMI-matched controls. Patients had higher prevalence of hypertension (p = .0132), smoking (p < .0020) and diabetes (p = .0024), with lowe…

Obesity and nonalcoholic fatty liver disease in type 1 diabetes mellitus patients

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Experimental and Emerging Free Fatty Acid Receptor Agonists for the Treatment of Type 2 Diabetes

The current management of Type 2 Diabetes Mellitus (T2DM) includes incretin-based treatments able to enhance insulin secretion and peripheral insulin sensitivity as well as improve body mass, inflammation, plasma lipids, blood pressure, and cardiovascular outcomes. Dietary Free Fatty Acids (FFA) regulate metabolic and anti-inflammatory processes through their action on incretins. Selective synthetic ligands for FFA1-4 receptors have been developed as potential treatments for T2DM. To comprehensively review the available evidence for the potential role of FFA receptor agonists in the treatment of T2DM, we performed an electronic database search assessing the association between FFAs, T2DM, i…

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...

The Role of Endothelium in COVID-19

The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), is causing a global pandemic. The virus primarily affects the upper and lower respiratory tracts and raises the risk of a variety of non-pulmonary consequences, the most severe and possibly fatal of which are cardiovascular problems. Data show that almost one-third of the patients with a moderate or severe form of COVID-19 had preexisting cardiovascular comorbidities such as diabetes mellitus, obesity, hypertension, heart failure, or coronary artery disease. SARS-CoV2 causes hyper inflammation, hypoxia, apoptosis, and a renin–angiotensin system imbalance …

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 …

The Role of Small, Dense Low-Density-Lipoproteins in Non-Coronary Forms of Atherosclerosis

Small, dense low density lipoproteins (LDL) are associated with increased risk for cardiovascular disease and seem to be an important predictor of cardiovascular events and progression of coronary artery disease. In addition, the predominance of small dense LDL has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III). Less data is available on the role of LDL size in the prevention of vascular diseases, including peripheral arterial disease, carotid artery disease and abdominal aortic aneurysm. The NCEP-ATP III stated that clinical non-coronary atherosclerosis carries a risk for coronary heart disease …

The effects of statins on blood pressure: current knowledge and future perspectives.

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 …

Evaluation of serum s-IgE/total IgE ratio in predicting clinical response to allergen-specific immunotherapy.

Background: To date, no predictive tests for the clinical response to allergen-specific immunotherapy (ASI) are available. Therefore an in vivo or in vitro test would be of great value. Objective: We sought to evaluate pretreatment parameters used in diagnosing allergic rhinitis and determining serum specific IgE (s-IgE) levels, serum total IgE (t-IgE) levels, and blood eosinophil counts and to identify whether can be used to predict clinical improvement in monosensitized patients with allergic rhinitis with or without asthma treated with immunotherapy. Methods:We analyzed 279 patients who had undergone 4 years of ASI administered either by means of the subcutaneous immunotherapy (76 patien…

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…

Heat Shock Protein-60 and Risk for Cardiovascular Disease

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. There is growing evidence that molecularchaperones, many of which are heat shock proteins HSPs, are involved in CVD pathogenesis. In this review we focus on HSP60,the human mitochondrial chaperone that also displays extramitochondrial and extracellular functions. HSP60 is typically cytoprotectivebut a number of stress conditions determine its conversion to a potentially toxic molecule for cells and tissues. We present illustrative examplesof specific subtypes of CVD where HSP60 is implicated in the initiation and/or progression of disease. The data not only indicatea pathogenic role for HSP60 but also its …

Anesthetics and Cerebral Protection in Patients Undergoing Carotid Endarterectomy

EREBRAL ISCHEMIA/HYPOXIA may occur in a vari-ety of perioperative circumstances. The main pathophy-siologic aspects involved in cerebral ischemia/reperfusion arecaused by adenosine triphosphate (ATP) consumption, theexcitotoxic actions of glutamate, changes in ionic homeostasis,and formation of free radicals (Fig 1). Outcomes from suchevents range from subclinical neurocognitive deficits to cata-strophic neurologic morbidity or death.

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

Novel Pharmaceutical and Nutraceutical-Based Approaches for Cardiovascular Diseases Prevention Targeting Atherogenic Small Dense LDL

Compelling evidence supports the causative link between increased levels of low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (CVD) development. For that reason, the principal aim of primary and secondary cardiovascular prevention is to reach and sustain recommended LDL-C goals. Although there is a considerable body of evidence that shows that lowering LDL-C levels is directly associated with CVD risk reduction, recent data shows that the majority of patients across Europe cannot achieve their LDL-C targets. In attempting to address this matter, a new overarching concept of a lipid-lowering approach, comprising of even more intensive, much earlier and lo…

Predictors of insulin resistance in patients with obesity: a pilot study.

We compared adipokines and inflammatory markers in obese insulin-sensitive (group A, n = 16) and insulin-resistant (group B, n = 48) patients divided according to homeostasis model assessment of insulin resistance (HOMA-IR). Serum levels of adiponectin, leptin, resistin, high-sensitivity C-reactive protein, interleukin 6, and tumor necrosis factor α were measured. Weight, height, waist (WC) and hip circumferences, waist to hip ratio , weight to height ratio, visceral adiposity index (VAI), and body adiposity index (BAI) were measured. The WC and VAI were significantly higher in group B (113.9 ± 11.1 vs 105.3 ± 9.8cm; P &lt; .01 and 2.3 ± 1.1 vs 1.6 ± 0.9; P &lt; .05, respectively), while s…

Treatment options for managing atherogenic dyslipidemia and fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries with up to 30% of the population affected. Since NAFLD is associated with an increased risk of cardiovascular (CV) disease, these patients should be stratified for CV risk factors, including atherogenic dyslipidemia, and managed accordingly. Lifestyle modifications represent an effective treatment for NAFLD, since most patients are overweight or obese. Also, promising, but not conclusive, results are available for current pharmacologic treatment. Drugs potentially effective against NAFLD include insulin sensitisers as well as fibrates and omega-3 polyunsaturated fatty acids, whil…

Advanced Glycation End Products: Do They Impair Bone Health in Diabetes?

AbstractIn diabetes mellitus (DM), there is increased formation and accumulation of advanced glycation end products (AGEs), which represent a heterogeneous class of molecules produced by non-enzymatic glycation of various molecules during long-term hyperglycaemia. Several studies have examined the role of AGEs in DM complications. Accumulating evidence suggests that AGEs affect bone metabolism. New knowledge indicates that they may play a role in bone disease among DM subjects. More data are now needed to clarify their role and to explore new AGEs-based therapeutic options for optimal bone health in DM.

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…

The role of GLP-1 receptor agonists during COVID-19 pandemia: a hypothetical molecular mechanism

ABSTRACT Introduction A number of anti-diabetic treatments have been favored during the continuing spread of the current SARS-CoV-2 pandemic. Glucagon like peptide-1 receptor agonists (GLP1-RAs) are a group of antidiabetic drugs, the glucose reducing effect of which is founded on augmenting glucose-dependent insulin secretion with concomitant reduction of glucagon secretion and delayed gastric emptying. Apart from their glucose lowering effects, GLP1-RAs also exert a plethora of pleiotropic activities in the form of anti-inflammatory, anti-thrombotic and anti-obesogenic properties, with beneficial cardiovascular and renal impact. All these make this class of drugs a preferred option for man…

Effect of hypolipidemic treatment on emerging risk factors in mixed dyslipidemia: a randomized pilot trial

Background The effects of different hypolipidemic treatment strategies on emerging atherosclerosis risk factors remain unknown. Materials and methods This is a prespecified analysis of a prospective, randomized, open-label, blinded end point (PROBE) study (ClinicalTrials.gov identifier: NCT01010516). Patients (n = 100) with mixed dyslipidaemia on a standard statin dose who had not achieved lipid targets were randomized to switch to the highest dose of rosuvastatin (40 mg/day) or to add-on-statin extended release nicotinic acid (ER-NA)/laropiprant (LRPT) or to add-on-statin micronized fenofibrate for a total of 3 months. Results Following 3 months of treatment, low-density lipoprotein (LDL) …

Challenges and Opportunities on Lipid Metabolism Disorders Diagnosis and Therapy: Novel Insights and Future Perspective

Dyslipidemia has been globally recognized, for almost seven decades, as one of the most important risk factors for the development and complications of atherosclerotic cardiovascular disease (ASCVD) [...]

The role of elevated growth hormone on the increased atherosclerosis in patients with acromegaly.

An Update on the Current and Emerging Use of Thiazolidinediones for Type 2 Diabetes.

Guidelines have increasingly stressed the concept that adequate glycemic control is required to prevent or decrease the macro- and microvascular complications of type 2 diabetes mellitus (T2DM). PPAR-gamma agonists (“glitazones”) are no longer prioritized due to their effects on heart failure. However, the association between these drugs and innovative therapies could be a valuable tool to attenuate the risk factors of the metabolic syndrome. Glitazones are used for the treatment of diabetes and associated comorbidities. There is substantial scientific evidence demonstrating the effect of glitazones at a cardiometabolic level, as well as on hematological and neurological pathologies that po…

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

Oxidative Stress and Inflammatory Biomarkers in Patients with Diabetic Foot

Background and Objectives: Diabetic foot (DF) development is driven by complex interactions of hyperglycemia, inflammation, and oxidative stress (OS). We aimed to investigate OS and inflammatory biomarkers in patients with DF and their potential to improve early diagnosis and management of DF. Materials and Methods: The prooxidant&ndash;antioxidant balance (PAB), superoxide dismutase (SOD), total oxidative status (TOS), total sulfhydryl groups (SHG), routine biochemical parameters, and complete blood count were determined in 42 patients with type-2 DM, of which 23 patients had DF, while 19 patients were without DF complications. The neutrophils-to-lymphocyte ratio (NLR) was evaluated as a b…

Statins in liver disease: not only prevention of cardiovascular events

Statins are lipid-lowering agents and one of the most pre-scribed drugs worldwide. Their main mechanism of action –inhibition of the mevalonate pathway through an effect on hydroxy-methylglutaryl CoA reductase, thus affecting the synthesis of cholesterol in the liver – makes this class of drugs pivotal in primary and secondary prevention of cardio-vascular risk, as extensively demonstrated in large prospective, randomized controlled trials. Along the years, we learned that the lower the better, and LDL-cholesterol targets have been progressively reduced to values ≤70 mg/dL for secondary prevention or in the presence of diabetes.

Cardiovascular effects of glucagon-like peptide-1 receptor agonist therapies in patients with type 1 diabetes

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 …

New Obesity Indices and Adipokines in Normotensive Patients and Patients With Hypertension

We compared the obesity parameters and selected adipokines—leptin, adiponectin, and resistin—in obese patients with hypertension and normotensive patients. A total of 67 nondiabetic obese outpatients were divided into 2 groups: A–hypertensive and B–normotensive. Serum levels of leptin, adiponectin, resistin, and insulin were measured. Weight, height, waist circumference, and hip circumference were measured to calculate waist-to-hip ratio (WHR), weight-to-height ratio, visceral adiposity index, and body adiposity index (BAI). Among patients with hypertension, significant positive correlations were observed between leptin and body mass index and BAI ( r = .31 and r = .63, respectively). In n…