Browsing by Author "Rizzo, Manfredi (7202023733)"

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–T3), as well as concentrations of cholesterol synthesis (lathosterol, desmosterol) and absorption markers (campesterol, β-sitosterol). During the study, 15 women developed GDM, while 48 had no complications (non-GDM). As compared to the non-GDM group, women with GDM had significantly higher triglycerides in each trimester, while having a lower HDL-C level in T3. In addition, they had significantly lower levels of β-sitosterol in T3 (p < 0.05). Cholesterol synthesis markers increased across trimesters in both groups. A decrease in serum β-sitosterol levels during the course of pregnancies affected by GDM was observed. The prevalence of small-sized HDL decreased in non-GDM, while in the GDM group remained unchanged across trimesters. Newborn’s size in the non-GDM group was significantly higher (p < 0.01) and inversely associated with proportions of both small, dense LDL and HDL particles (p < 0.05) in maternal plasma in T1. In conclusion, high-risk pregnancies affected by GDM are characterized by altered cholesterol absorption and HDL maturation. Advanced lipid testing may indicate disturbed lipid homeostasis in GDM. © 2022 by the authors.

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–T3), as well as concentrations of cholesterol synthesis (lathosterol, desmosterol) and absorption markers (campesterol, β-sitosterol). During the study, 15 women developed GDM, while 48 had no complications (non-GDM). As compared to the non-GDM group, women with GDM had significantly higher triglycerides in each trimester, while having a lower HDL-C level in T3. In addition, they had significantly lower levels of β-sitosterol in T3 (p < 0.05). Cholesterol synthesis markers increased across trimesters in both groups. A decrease in serum β-sitosterol levels during the course of pregnancies affected by GDM was observed. The prevalence of small-sized HDL decreased in non-GDM, while in the GDM group remained unchanged across trimesters. Newborn’s size in the non-GDM group was significantly higher (p < 0.01) and inversely associated with proportions of both small, dense LDL and HDL particles (p < 0.05) in maternal plasma in T1. In conclusion, high-risk pregnancies affected by GDM are characterized by altered cholesterol absorption and HDL maturation. Advanced lipid testing may indicate disturbed lipid homeostasis in GDM. © 2022 by the authors.

Cardiovascular disease (CVD) is common cause of death in humans and its major underlying pathology is atherosclerosis. Atherosclerosis is a chronic inflammatory disease that predisposes to coronary artery disease (CAD), stroke and peripheral arterial disease, responsible for most of the cardiovascular morbidity and mortality. This inflammatory process, triggered by the presence of lipids in the vascular wall, and encompasses a complex interaction among inflammatory cells, vascular elements, and lipoproteins through the expression of several adhesion molecules and cytokines. Obesity is a risk factor for CVD but this association is not fully understood. Altered levels of obesity related peptides such as ghrelin may play an important role in this pathophysiology. Recent evidence indicates that ghrelin features several cardiovascular activities, including increased myocardial contractility, vasodilatation and protection from myocardial infarction. Recent data demonstrate that ghrelin can influence important key events in atherogenesis and thus they may play a role in atherosclerosis. In this review we present the latest data from recent animal and clinical studies which focus on a novel approach to ghrelin as a potential therapeutic agent in the treatment of a complex disease like atherosclerosis. Thus, ghrelin may become a new therapeutic target for the treatment of CVD. Further studies are necessary to investigate the potential mechanisms involved in the effects of ghrelin on the cardiovascular system. © 2012 by Nova Science Publishers, Inc. All rights reserved.

Growing interest in incretin-based therapies for diabetes mellitus has led to an increased evaluation of their potential effects on cancer development. This review aims to synthesize recent evidence regarding the relationship between incretin-based therapies and cancer risk. We conducted a comprehensive literature review focusing on studies investigating dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists in relation to various malignancies. Current findings suggest that while these therapies demonstrate potential benefits, including weight reduction and metabolic regulation, concerns remain regarding their long-term safety profile. Notably, some studies indicate an increased risk of thyroid and pancreatic cancers, while others report protective effects against prostate, colorectal, and breast cancers. Given the complexity of their effects, further long-term studies and post-marketing surveillance are warranted. This review highlights the need for careful clinical assessment when prescribing incretin-based therapies to patients who may be at increased risk of cancer. © 2025 by the authors.

[No abstract available]

In recent years, there has been growing interest in the possible use of nutraceuticals to improve and optimize dyslipidemia control and therapy. Based on the data from available studies, nutraceuticals might help patients obtain theraputic lipid goals and reduce cardiovascular residual risk. Some nutraceuticals have essential lipidlowering properties confirmed in studies; some might also have possible positive effects on nonlipid cardiovascular risk factors and have been shown to improve early markers of vascular health such as endothelial function and pulse wave velocity. However, the clinical evidence supporting the use of a single lipid-lowering nutraceutical or a combination of them is largely variable and, for many of the nutraceuticals, the evidence is very limited and, therefore, often debatable. The purpose of this position paper is to provide consensus-based recommendations for the optimal use of lipid-lowering nutraceuticals to manage dyslipidemia in patients who are still not on statin therapy, patients who are on statin or combination therapy but have not achieved lipid goals, and patients with statin intolerance. This statement is intended for physicians and other healthcare professionals engaged in the diagnosis and management of patients with lipid disorders, especially in the primary care setting. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved.

Background Body-mass index (BMI) and diabetes have increased worldwide, whereas global average blood pressure and cholesterol have decreased or remained unchanged in the past three decades. We quantified how much of the effects of BMI on coronary heart disease and stroke are mediated through blood pressure, cholesterol, and glucose, and how much is independent of these factors. Methods We pooled data from 97 prospective cohort studies that collectively enrolled 1·8 million participants between 1948 and 2005, and that included 57 161 coronary heart disease and 31 093 stroke events. For each cohort we excluded participants who were younger than 18 years, had a BMI of lower than 20 kg/m2, or who had a history of coronary heart disease or stroke. We estimated the hazard ratio (HR) of BMI on coronary heart disease and stroke with and without adjustment for all possible combinations of blood pressure, cholesterol, and glucose. We pooled HRs with a random-effects model and calculated the attenuation of excess risk after adjustment for mediators. Findings The HR for each 5 kg/m2 higher BMI was 1·27 (95% CI 1·23-1·31) for coronary heart disease and 1·18 (1·14-1·22) for stroke after adjustment for confounders. Additional adjustment for the three metabolic risk factors reduced the HRs to 1·15 (1·12-1·18) for coronary heart disease and 1·04 (1·01-1·08) for stroke, suggesting that 46% (95% CI 42-50) of the excess risk of BMI for coronary heart disease and 76% (65-91) for stroke is mediated by these factors. Blood pressure was the most important mediator, accounting for 31% (28-35) of the excess risk for coronary heart disease and 65% (56-75) for stroke. The percentage excess risks mediated by these three mediators did not differ significantly between Asian and western cohorts (North America, western Europe, Australia, and New Zealand). Both overweight (BMI ≥25 to <30 kg/m2) and obesity (BMI ≥30 kg/m2) were associated with a significantly increased risk of coronary heart disease and stroke, compared with normal weight (BMI ≥20 to <25 kg/m2), with 50% (44-58) of the excess risk of overweight and 44% (41-48) of the excess risk of obesity for coronary heart disease mediated by the selected three mediators. The percentages for stroke were 98% (69-155) for overweight and 69% (64-77) for obesity. Interpretation Interventions that reduce high blood pressure, cholesterol, and glucose might address about half of excess risk of coronary heart disease and three-quarters of excess risk of stroke associated with high BMI. Maintenance of optimum bodyweight is needed for the full benefits.

The increasing global incidence of obesity and type 2 diabetes mellitus (T2D) underscores the urgency of addressing these interconnected health challenges. Obesity enhances genetic and environmental influences on T2D, being not only a primary risk factor but also exacerbating its severity. The complex mechanisms linking obesity and T2D involve adiposity-driven changes in β-cell function, adipose tissue functioning, and multi-organ insulin resistance (IR). Early detection and tailored treatment of T2D and obesity are crucial to mitigate future complications. Moreover, personalized and early intensified therapy considering the presence of comorbidities can delay disease progression and diminish the risk of cardiorenal complications. Employing combination therapies and embracing a disease-modifying strategy are paramount. Clinical trials provide evidence confirming the efficacy and safety of glucagon-like peptide 1 receptor agonists (GLP-1 RAs). Their use is associated with substantial and durable body weight reduction, exceeding 15%, and improved glucose control which further translate into T2D prevention, possible disease remission, and improvement of cardiometabolic risk factors and associated complications. Therefore, on the basis of clinical experience and current evidence, the Eastern and Southern Europe Diabetes and Obesity Expert Group recommends a personalized, polymodal approach (comprising GLP-1 RAs) tailored to individual patient’s disease phenotype to optimize diabetes and obesity therapy. We also expect that the increasing availability of dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists will significantly contribute to the modern management of the cardiometabolic continuum. © The Author(s) 2024.

Non-alcoholic fatty liver disease (NAFLD), metabolic syndrome (MetS), and type 2 diabetes (T2DM) are metabolic disorders that belong to a highly prevalent disease cluster with a significant impact on public health worldwide. MetS is a complex condition characterized by metabolism perturbations that include glucose intolerance, insulin resistance, dyslipidaemia, associated pro-inflammatory state, and arterial hypertension. Because the components of MetS commonly co-occur, the management of these disorders cannot be considered separate issues. Thus NAFLD, recognized as a hepatic manifestation of MetS, is frequently associated with T2DM. This review analyses the underlying connections between these diseases and the risks associated with their co-occurrence. The effective management of NAFLD associated with MetS and T2DM involves an early diagnosis and optimal treatment of each condition leading to improvement in glycaemic and lipid regulation, liver steatosis, and arterial hypertension. The net effect of such treatment is the prevention of atherosclerotic cardiovascular diseases and liver fibrosis. © 2022 Termedia & Banach.

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 musclerelated. 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 treatment of patients at risk of, or with, cardiovascular disease. Knowledge of the most common adverse effects of statin therapy that might cause statin intolerance and the clear definition of this phenomenon is crucial to effectively treat patients with lipid disorders. Therefore, the aim of this position paper was to suggest a unified definition of statin intolerance, and to complement the recent EAS statement on SAMS, where the pathophysiology, diagnosis and the management were comprehensively presented. Copyright © 2015 Termedia & Banach.

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 treatment of patients at risk of, or with, cardiovascular disease. Knowledge of the most common adverse effects of statin therapy that might cause statin intolerance and the clear definition of this phenomenon is crucial to effectively treat patients with lipid disorders. Therefore, the aim of this position paper was to suggest a unified definition of statin intolerance, and to complement the recent EAS statement on SAMS, where the pathophysiology, diagnosis and the management were comprehensively presented. © 2015 Informa UK, Ltd.

Proteins play a crucial role in metabolism, in maintaining fluid and acid-base balance and antibody synthesis. Dietary proteins are important nutrients and are classified into: 1) animal proteins (meat, fish, poultry, eggs and dairy), and, 2) plant proteins (legumes, nuts and soy). Dietary modification is one of the most important lifestyle changes that has been shown to significantly decrease the risk of cardiovascular (CV) disease (CVD) by attenuating related risk factors. The CVD burden is reduced by optimum diet through replacement of unprocessed meat with low saturated fat, animal proteins and plant proteins. In view of the available evidence, it has become acceptable to emphasize the role of optimum nutrition to maintain arterial and CV health. Such healthy diets are thought to increase satiety, facilitate weight loss, and improve CV risk. Different studies have compared the benefits of omnivorous and vegetarian diets. Animal protein related risk has been suggested to be greater with red or processed meat over and above poultry, fish and nuts, which carry a lower risk for CVD. In contrast, others have shown no association of red meat intake with CVD. The aim of this expert opinion recommendation was to elucidate the different impact of animal vs vegetable protein on modifying cardiometabolic risk factors. Many observational and interventional studies confirmed that increasing protein intake, especially plant-based proteins and certain animal-based proteins (poultry, fish, unprocessed red meat low in saturated fats and low-fat dairy products) have a positive effect in modifying cardiometabolic risk factors. Red meat intake correlates with increased CVD risk, mainly because of its non-protein ingredients (saturated fats). However, the way red meat is cooked and preserved matters. Thus, it is recommended to substitute red meat with poultry or fish in order to lower CVD risk. Specific amino acids have favourable results in modifying major risk factors for CVD, such as hypertension. Apart from meat, other animal-source proteins, like those found in dairy products (especially whey protein) are inversely correlated to hypertension, obesity and insulin resistance. © 2020 The Author(s)

Proteins play a crucial role in metabolism, in maintaining fluid and acid-base balance and antibody synthesis. Dietary proteins are important nutrients and are classified into: 1) animal proteins (meat, fish, poultry, eggs and dairy), and, 2) plant proteins (legumes, nuts and soy). Dietary modification is one of the most important lifestyle changes that has been shown to significantly decrease the risk of cardiovascular (CV) disease (CVD) by attenuating related risk factors. The CVD burden is reduced by optimum diet through replacement of unprocessed meat with low saturated fat, animal proteins and plant proteins. In view of the available evidence, it has become acceptable to emphasize the role of optimum nutrition to maintain arterial and CV health. Such healthy diets are thought to increase satiety, facilitate weight loss, and improve CV risk. Different studies have compared the benefits of omnivorous and vegetarian diets. Animal protein related risk has been suggested to be greater with red or processed meat over and above poultry, fish and nuts, which carry a lower risk for CVD. In contrast, others have shown no association of red meat intake with CVD. The aim of this expert opinion recommendation was to elucidate the different impact of animal vs vegetable protein on modifying cardiometabolic risk factors. Many observational and interventional studies confirmed that increasing protein intake, especially plant-based proteins and certain animal-based proteins (poultry, fish, unprocessed red meat low in saturated fats and low-fat dairy products) have a positive effect in modifying cardiometabolic risk factors. Red meat intake correlates with increased CVD risk, mainly because of its non-protein ingredients (saturated fats). However, the way red meat is cooked and preserved matters. Thus, it is recommended to substitute red meat with poultry or fish in order to lower CVD risk. Specific amino acids have favourable results in modifying major risk factors for CVD, such as hypertension. Apart from meat, other animal-source proteins, like those found in dairy products (especially whey protein) are inversely correlated to hypertension, obesity and insulin resistance. © 2020 The Author(s)

Cardiometabolic diseases (CMD) are a direct consequence of modern living and contribute to the development of multisystem diseases such as cardiovascular diseases and diabetes mellitus (DM). CMD has reached epidemic proportions worldwide. A sodium pump (Na+/K+-ATPase) is found in most eukaryotic cells’ membrane and controls many essential cellular functions directly or indirectly. This ion transporter and its isoforms are important in the pathogenesis of some pathological processes, including CMD. The structure and function of Na+/K+-ATPase, its expression and distribution in tissues, and its interactions with known ligands such as cardiotonic steroids and other suspected endogenous regulators are discussed in this review. In addition, we reviewed recent literature data related to the involvement of Na+/K+-ATPase activity dysfunction in CMD, focusing on the Na+/K+-ATPase as a potential therapeutic target in CMD. Copyright © 2023 Obradovic, Sudar-Milovanovic, Gluvic, Banjac, Rizzo and Isenovic.

Statins are the most common drugs administered for patients with cardiovascular disease. However, due to statin-associated muscle symptoms, adherence to statin therapy is challenging in clinical practice. Certain nutraceuticals, such as red yeast rice, bergamot, berberine, artichoke, soluble fiber, and plant sterols and stanols alone or in combination with each other, as well as with ezetimibe, might be considered as an alternative or add-on therapy to statins, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. These nutraceuticals could exert significant lipid-lowering activity and might present multiple non–lipid-lowering actions, including improvement of endothelial dysfunction and arterial stiffness, as well as anti-inflammatory and antioxidative properties. The aim of this expert opinion paper is to provide the first attempt at recommendation on the management of statin intolerance through the use of nutraceuticals with particular attention on those with effective low-density lipoprotein cholesterol reduction. © 2018 American College of Cardiology Foundation