Cardiovascular Benefits Research Articles

Advances in SGLT2 Inhibitors for Type 2 Diabetes Management

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have emerged as a significant class of medications for the management of type 2 diabetes mellitus, offering improved glycemic control and cardiovascular benefits. This review focuses on the development of various SGLT2 inhibitors, highlighting their chemical structures, pharmacological properties, and therapeutic potential. Methods: A comprehensive literature review was conducted, summarizing the synthesis and biological evaluation of multiple SGLT2 inhibitors, including novel compounds derived from C-aryl glucoside scaffolds, C-glucosides, and 5α-carba-β-D-glucopyranose derivatives. Studies utilized various techniques, such as click chemistry, Friedel-Crafts alkylation, and pharmacokinetic assessments, to evaluate the efficacy and selectivity of these inhibitors. Results: Several promising compounds were identified, including compound 1 (GCC5694A) with an IC50 of 0.460 nM against SGLT2 and strong selectivity for SGLT1, and compound 26, which exhibited an IC50 of 4.47 nM, surpassing dapagliflozin. Novel derivatives, such as compound 22 (IC50 = 47 nM) and compound 27, demonstrated significant inhibitory effects and selectivity profiles. Pharmacokinetic studies revealed compounds like compound 28 had enhanced half-lives compared to established drugs like sergliflozin. Additionally, compounds such as the nitric oxide-releasing dapagliflozin derivative exhibited dual anti-diabetic and anti-thrombotic properties. Conclusion: The ongoing development of SGLT2 inhibitors demonstrates substantial advancements in therapeutic options for type 2 diabetes. The structural modifications and novel compounds explored in this review highlight the potential for improved efficacy and safety profiles, suggesting that these new agents could play a vital role in diabetes management and warrant further clinical investigation.

Estrategia terapéutica en el paciente diabético (I). Empoderamiento del paciente y educación. Objetivos terapéuticos. Estilo de vida, alimentación y control de los factores de riesgo cardiovascular. Sistemas de control glucémico

Managing type 2 diabetes (DM2) requires a multifactorial approach. The foundation of treatment is lifestyle modification and diabetes education. Patients must be involved in decision making and be given tools to help them manage their disease. The four basic pillars of DM2 management are: a) glycemic control; b) blood pressure management; c) lipid management; and d) use of drugs with proven cardiovascular and renal benefits. In terms of lifestyle, it is recommended to combine a diet that contributes to weight maintenance and glycemic control as well as the incorporation of regular moderate physical activity (at least 150minutes per week). Cholesterol and blood pressure targets should be individualized for each patient with DM2 based on the presence of cardiovascular disease or cardiovascular risk. Smoking cessation is recommended. There are two main glycemic control systems: blood glucose monitoring (capillary glycemia) and continuous glucose monitoring.

EMMY trial: What we know and what we need to know

ABSTRACT SGLT-2 inhibitors are a class of antidiabetic drugs with additional cardiovascular benefits. Though initially developed for glycemic control, subsequent studies in the heart failure (HF) population also demonstrated positive outcomes. Currently, they are approved for use in HF with both reduced and preserved ejection fraction. More recently, encouraging data have emerged on acute HF. Following an episode of acute myocardial infarction, patients are also at high risk for developing HF and experiencing recurrent events despite optimal therapy. The PARADISE MI study failed to demonstrate any benefits of ARNI in this scenario. The EMMY trial explored the role of SGLT-2i in >450 odds patients with acute MI. At 26 weeks SGLT-2i (empagliflozin) use led to a higher fall in NT-pro-BNP levels compared to standard treatment. There was additional improvement in left ventricular echocardiographic parameters with empagliflozin too. However, it was a small trial, had a short follow-up and there were no clinical endpoints. But none the least, it attested to the safety of SGLT-2i in the post-MI scenario. Because the primary care physician frequently encounters patients in the post-MI scenario, the manuscript provides insights into their practice. Based on contemporary evidence, the universal use of SGLT-2 inhibitors in patients following acute MI is not warranted. A further role of these drugs in post-MI HF will be clarified in ongoing trials.

Integrating molecular and cellular components of endothelial shear stress mechanotransduction.

The lining of blood vessels is constantly exposed to mechanical forces exerted by blood flow against the endothelium. Endothelial cells detect these tangential forces (i.e., shear stress), initiating a host of intracellular signaling cascades that regulate vascular physiology. Thus, vascular health is tethered to the endothelial cells' capacity to transduce shear stress. Indeed, the mechanotransduction of shear stress underlies a variety of cardiovascular benefits, including some of those associated with increased physical activity. However, endothelial mechanotransduction is impaired in aging and disease states such as obesity and type 2 diabetes, precipitating the development of vascular disease. Understanding endothelial mechanotransduction of shear stress, and the molecular and cellular mechanisms by which this process becomes defective, is critical for the identification and development of novel therapeutic targets against cardiovascular disease. In this review, we detail the primary mechanosensitive structures that have been implicated in detecting shear stress, including junctional proteins such as platelet endothelial cell adhesion molecule-1 (PECAM-1), the extracellular glycocalyx and its components, and ion channels such as piezo1. We delineate which molecules are truly mechanosensitive and which may simply be indispensable for the downstream transmission of force. Furthermore, we discuss how these mechanosensors interact with other cellular structures, such as the cytoskeleton and membrane lipid rafts, which are implicated in translating shear forces to biochemical signals. Based on findings to date, we also seek to integrate these cellular and molecular mechanisms with a view of deciphering endothelial mechanotransduction of shear stress, a tenet of vascular physiology.

Relationship Between Renin, Aldosterone, Aldosterone-to-Renin Ratio and Arterial Stiffness and Left Ventricular Mass Index in Young Adults.

Primary aldosteronism, characterized by renin-independent aldosterone production, is associated with adverse cardiovascular remodeling and outcomes. Elevated cardiovascular risk is observed even in subclinical forms of primary aldosteronism according to studies conducted primarily in middle-aged and elderly populations. This study aimed to assess whether early changes in primary aldosteronism biomarkers during young adulthood are associated with arterial stiffness and left ventricular mass index (LVMI) before the onset of overt disease. The Raine Study is a longitudinal, population-based cohort study in Western Australia that enrolled women during pregnancy. We analyzed the data from the offspring of these women at 17 (2006-2009) and 27 (2016-2018) years of age. Participants with elevated high-sensitivity C-reactive protein (>10 mg/L) and female participants who were on oral contraception were excluded. Pulse wave velocity and aortic augmentation index were measured by SphygmoCor Pulse Wave System at both ages, and aortic distensibility and LVMI were measured by cardiac magnetic resonance imaging at 27 years. Multivariable linear regression was used to examine the relationship between plasma renin, aldosterone, or aldosterone-to-renin ratio and arterial stiffness and LVMI. Mediation analysis was used to test the role of systolic blood pressure. This study included 859 participants at 17 (38.0% female) and 758 participants at 27 (33.2% female) years of age. Females had lower renin concentration at both 17 (20.7 mU/L versus 25.7 mU/L; P<0.001) and 27 (12.0 mU/L versus 15.4 mU/L; P<0.001) years of age; hence, the aldosterone-to-renin ratio was significantly higher at both 17 (18.2 versus 13.5; P<0.001) and 27 (21.0 versus 15.6; P<0.001) years of age in females compared with males. At 27 years of age, a significant association was detected between aldosterone and LVMI in males (β=0.009 [95% CI, 0.001-0.017]; P=0.027) and between aldosterone-to-renin ratio and LVMI in females (β=0.098 [95% CI, 0.001-0.196]; P=0.050) independently of systolic blood pressure and other confounders. No association was found between primary aldosteronism biomarkers and measures of arterial stiffness (pulse wave velocity, aortic augmentation index, and aortic distensibility) at either age. Aldosterone concentration and aldosterone-to-renin ratio were positively associated with the LVMI in young males and females, respectively, independently of systolic blood pressure. Long-term follow-up is required to determine whether the relationship persists over time, and clinical trials are needed to assess the cardiovascular benefits of early interventions to block aldosterone.

Publication bias in pharmacogenetics of statin-associated muscle symptoms, an umbrella review with a meta-epidemiological study

Background and aimsStatin-associated muscle symptoms (SAMS) are a major cause of treatment discontinuation. Clinical Pharmacogenetics Implementation Consortium (CPIC) recommend dose adjustment for statin treatment according to known SLCO1B1 genotype to reduce SAMS. We hypothesized that the association between SLCO1B1 genotype and SAMS is misestimated because of publication bias. MethodsWe searched published systematic reviews on the association between SLCO1B1 genotype and SAMS. To assessed publication bias, we used funnel plot visual inspection, Egger’s test, and the Bayes Factor (BFPublication-bias) from Robust Bayesian Meta-Analysis (RoBMA). We compared the odds ratios (ORUncorrected) from meta-analyses before and after correcting for publication bias using trim-and-fill (ORTrim&Fill) and RoBMA (ORRoBMA) methods. ResultsWe included 8 cohort and 11 case-control studies, totaling 62 OR of three SLCO1B1 genotypes and six statin drugs. In the primary analysis, the funnel plot was suggestive of publication bias, confirmed by Egger’s test (p=0.001) and RoBMA (BFPublication-bias=18). Correcting the estimate for publication bias resulted in loss of the association, from a significant ORUncorrected (1.31 95%CI [1.13–1.53]) to corrected ORs suggesting no difference: ORTrim&Fill (1.07 95%CI [0.89–1.30]) and ORRoBMA (1.02 95%CI [1.00–1.33]). This suggested that publication bias overestimated the association by 18% and 23%, respectively. Similar results were found for genotype rs4149056, simvastatin and atorvastatin. ConclusionsThe effect of the SLCO1B1 genotype on the risk of developing SAMS is overestimated in the published literature, especially rs4149056. This could lead prescribers to incorrectly decreasing statin doses or even avoiding statin use, leading to a loss of the potential cardiovascular benefit of statins.

Protocolo terapéutico de la diabetes mellitus tipo 2 con obesidad y riesgo cardiovascular

The management of type 2 diabetes mellitus (DM2) with obesity and cardiovascular risk is a growing challenge due to the high prevalence of both conditions. This protocol describes therapeutic recommendations based on glycemic control and the cardiovascular benefits of certain drugs. Two classes of drugs with weight and cardiometabolic efficacy stand out: glucagon-like peptide-1 agonists (GLP-1a) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i). This document suggests the joint use of both to reduce cardiovascular risk and promote weight loss. It also describes the role of metabolic surgery as an effective option for the management of DM2 and obesity, as it significantly improves glycemic outcomes and reduces cardiovascular risk. Continuous follow-up is recommended to adjust treatment according to the patient's clinical response and to avoid therapeutic inertia.

Geriatric Pharmacotherapy Case Series: Medications for Diabetes-A Focus on Secondary Stroke Prevention.

This report addresses evidence for efficacy of diabetes medications with a focus on stroke risk reduction. The cardiovascular benefits of SGLT-2 inhibitors and GLP-1 receptor agonists have been well-established; however, clinical trials to date have examined composite cardiovascular endpoints that include, but do not specifically focus on, stroke. The purpose of this case review is to examine the evidence for the various diabetes medications in reducing the risk for stroke. This literature review was inspired by a patient seen in a geriatric day hospital program with diabetes and a history of multiple strokes. Our goal was to select a diabetes management regimen that would provide both glycemic control and stroke risk reduction. As diabetes and cerebrovascular disease commonly coexist and are important contributors to morbidity and mortality in older individuals, appropriate management must incorporate both current evidence as well as consideration for patient-specific factors that may influence the treatment plan. This patient case illustrates the importance of both.

Chronic cannabidiol treatment induces cardiovascular improvement in renovascular hypertensive rats.

Cannabidiol (CBD) is increasingly studied for its therapeutic potential in neurodegenerative diseases. Previous research on acute CBD administration has demonstrated cardiovascular benefits in hypertensive rats, including reduced mean blood pressure and oxidative stress. To investigate the long-term cardiovascular effects of chronic CBD treatment in renovascular hypertension induced by the 2-kidney-1-clip (2K1C) model. Male Wistar rats (180-200 g, 8 weeks old) underwent 2K1C or SHAM surgery. Six weeks later, rats received chronic CBD treatment (20 mg/kg, twice daily for 14 days). A combination of ex vivo, in vitro, and in vivo methods was used to assess CBD's cardiovascular effects in 2K1C hypertensive rats. Chronic CBD treatment significantly reduced blood pressure and the depressor response to hexamethonium (a ganglionic blocker). It also normalized variability in low-frequency (LF) power and LF/high-frequency (HF) ratio. CBD enhanced vasodilation and reduced vasoconstriction in the mesenteric artery of 2K1C rats, accompanied by decreased expression of aortic reactive oxygen species (ROS). Our findings suggest that chronic CBD treatment exerts antihypertensive effects by improving baroreflex sensitivity and vascular function while decreasing arterial ROS levels and sympathetic nerve activity. These results underscore CBD's potential therapeutic role in managing cardiovascular complications associated with renovascular hypertension.

Therapeutic Potential of Momordicine I from Momordica charantia: Cardiovascular Benefits and Mechanisms.

Momordica charantia (bitter melon), a traditional medicinal plant, has been demonstrated to have potential in managing diabetes, gastrointestinal problems, and infections. Among its bioactive compounds, momordicine I, a cucurbitane-type triterpenoid, has attracted attention due to its substantial biological activities. Preclinical studies have indicated that momordicine I possesses antihypertensive, anti-inflammatory, antihypertrophic, antifibrotic, and antioxidative properties, indicating its potential as a therapeutic agent for cardiovascular diseases. Its mechanisms of action include modulating insulin signaling, inhibiting inflammatory pathways, and inducing apoptosis in cancer cells. The proposed mechanistic pathways through which momordicine I exerts its cardiovascular benefits are via the modulation of nitric oxide, angiotensin-converting enzymes, phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt), oxidative stress, apoptosis and inflammatory pathways. Furthermore, the anti-inflammatory effects of momordicine I are pivotal. Momordicine I might reduce inflammation through the following mechanisms: inhibiting pro-inflammatory cytokines, reducing adhesion molecules expression, suppressing NF-κB activation, modulating the Nrf2 pathway and suppressing c-Met/STAT3 pathway. However, its therapeutic use requires the careful consideration of potential side effects, contraindications, and drug interactions. Future research should focus on elucidating the precise mechanisms of momordicine I, validating its efficacy and safety through clinical trials, and exploring its pharmacokinetics. If proven effective, momordicine I could considerably affect clinical cardiology by acting as a novel adjunct or alternative therapy for cardiovascular diseases. To date, no review article has been published on the role of bitter-melon bioactive metabolites in cardiovascular prevention and therapy. The present work constitutes a comprehensive, up-to-date review of the literature, which highlights the promising therapeutic potential of momordicine I on the cardiovascular system and discusses future research recommendations.

The role of flozins in managing cardiovascular risk in patients with type 2 diabetes - narrative review

Introduction. Cardiovascular disease is a leading cause of morbidity and mortality among patients with type 2 diabetes mellitus. The emergence of flozins, a class of sodium-glucose co-transporter-2 inhibitors, has introduced a novel therapeutic avenue with potential cardiovascular benefits beyond glycemic control. Objective. This review aims to synthesize current evidence on the role of flozins in managing cardiovascular risk among patients with T2DM, examining their efficacy, safety profile, and mechanisms of action. Review methods. A comprehensive literature search was conducted using databases, covering studies published between 2015 and 2024. Clinical trials, meta-analyses, and observational studies evaluating the cardiovascular outcomes associated with flozins in T2DM patients were included. Brief description of the state of knowledge. Research shows that flozins improve glycemic control and provide significant cardiovascular protection, reducing major adverse cardiovascular events, heart failure hospitalizations, and cardiovascular mortality in T2DM patients. These benefits are likely due to hemodynamic changes, enhanced cardiac function, and reduced inflammation and oxidative stress. Summary. Flozins represent a promising therapeutic option for reducing cardiovascular risk in T2DM patients. Their dual benefits on both metabolic and cardiovascular health position them as a cornerstone in the management of T2DM. Further research is needed to fully elucidate their long-term benefits and safety in diverse patient populations.

Empagliflozin alleviates obesity-related cardiac dysfunction via the activation of SIRT3-mediated autophagosome formation

BackgroundEmpagliflozin (EMPA) has demonstrated efficacy in providing cardiovascular benefits in metabolic diseases. However, the direct effect of EMPA on autophagy in obesity-related cardiac dysfunction remains unclear. Therefore, this study aimed to determine changes in cardiac autophagy during diet-induced obesity and clarify the exact mechanism by which EMPA regulates autophagic pathways.MethodsMale C57BL/6J mice were fed a 12-week high-fat diet (HFD) followed by 8 weeks of EMPA treatment. Body composition analysis and echocardiography were performed to evaluate metabolic alterations and cardiac function. Histological and immunofluorescence staining was used to evaluate potential enhancements in myocardial structure and biological function. Additionally, H9c2 cells were transfected with small interfering RNA targeting sirtuin 3 (SIRT3) and further treated with palmitic acid (PA) with or without EMPA. Autophagy-related targets were analyzed by western blotting and RT‒qPCR.ResultsEMPA administration effectively ameliorated metabolic disorders and cardiac diastolic dysfunction in HFD-fed mice. EMPA prevented obesity-induced myocardial hypertrophy, fibrosis, and inflammation through the activation of SIRT3-mediated autophagosome formation. The upregulation of SIRT3 triggered by EMPA promoted the initiation of autophagy by activating AMP-activated protein kinase (AMPK) and Beclin1. Furthermore, activated SIRT3 contributed to the elongation of autophagosomes through autophagy-related 4B cysteine peptidase (ATG4B) and autophagy-related 5 (ATG5).ConclusionsEMPA promotes SIRT3-mediated autophagosome formation to alleviate damage to the cardiac structure and function of obese mice. Activated SIRT3 initiates autophagy through AMPK/Beclin1 and further stimulates elongation of the autophagosome membrane via ATG4B/ATG5. These results provide a new explanation for the cardioprotective benefits of EMPA in obesity.

Exploration of the regional effects of colchicine in the LoDoCo2 trial

The Low Dose Colchicine 2 (LoDoCo2) trial randomized 5,522 patients with chronic coronary disease to colchicine 0.5mg daily or placebo in a 1:1 ratio and demonstrated the cardiovascular benefits of colchicine. In the trial, which was conducted in Australia and The Netherlands, a prespecified subgroup analysis suggested a difference in magnitude of treatment effect of colchicine by region (Australia: HR 0.51; 95% CI 0.39-0.67 vs The Netherlands: HR 0.92; 95% CI 0.71-1.20). The aim of this study was to explore possible explanations for the apparent difference in magnitude of treatment effect of colchicine by region in the LoDoCo2 trial. The analysis explored potential determinants of variations in the magnitude of effectiveness of colchicine treatment across the regions. This included investigating differences in investigational product, clinical characteristics, concurrent medical therapies and the duration of follow-up using a range of statistical techniques, including sub-group, landmark and effect modification analyses. No differences were found in the colchicine product used in each region. Despite minor differences observed in baseline clinical characteristics and concomitant therapies, the effect modifier analyses demonstrated that these factors did not explain the difference in magnitude of treatment effect of colchicine by region. Randomization in Australia began more than two years before The Netherlands, with shorter duration of follow-up in The Netherlands compared to Australia. In a landmark analysis, over the period when more than 90% of patients in each region had been followed, the effects of colchicine were similar (Australia hazard ratio [HR] 0.58 95% CI 0.34-0.97 vs The Netherlands HR 0.67 95% CI 0.47-0.96). After examining several plausible explanations for the observed differences in the magnitude of treatment effect of colchicine between regions in the LoDoCo2 trial could be due to the differences in duration of follow-up but a substantial portion of the differences remain unexplained. https://www.anzctr.org.au/ACTRN12614000093684.

Glucose-Lowering Drugs with Proven Cardiovascular Benefit Following Acute Coronary Syndrome in Patients with Type 2 Diabetes: Treatment Gaps and Outcomes.

Background: Real-world data on the implementation and prognostic impact of glucose-lowering drugs with proven cardiovascular benefits in patients with type 2 diabetes (T2D) following acute coronary syndrome (ACS) are limited. We investigated the utilization and treatment patterns of sodium-glucose contrasporter-2 inhibitors (SGLT2Is) and glucagon-like peptide-1 recepto-agonists (GLP1RAs) in patients with T2D experiencing ACS and analyzed their association with mortality and major adverse cardiovascular events (MACEs) including recurrent ACS, acute revascularization, heart failure, or ischemic stroke. Methods: We carried out a retrospective analysis of 9756 patients with T2D from a nationwide healthcare organization in Israel who were hospitalized with ACS between 01/2019 and 01/2022. Drug prescriptions were estimated pre-hospitalization, 90 days, and 1 year following hospitalization. The association between SGLT2I and/or GLP1RA treatment with MACE and mortality was investigated using a time-dependent Cox regression analysis with multivariable adjustment. Results: The prescription rates (pre-hospitalization, 90 days, and 1 year post-hospitalization) of GLP1RAs were 13%, 13.2%, and 18%, and those of SGLT2Is were 23.9%, 33.6%, and 42.7%, respectively. At 1 year, 13.9% of patients were prescribed both treatments. The use of SGLT2Is and/or GLP1RAs was higher in younger age groups and increased from 2019 to 2021 (38.1% to 59.2%). The adjusted hazard ratio for the association of pre- or post-hospitalization SGLT2I and/or GLP1RA treatment with mortality and MACE was 0.724 (0.654-0.801) and 0.974 (0.909-1.043), respectively. Conclusions: In the real-world practice of treating patients with T2D experiencing ACS, the implementation of SGLT2Is, particularly GLP1RAs, was suboptimal when prescribed both early and 1 year following hospitalization, emphasizing the need to improve medical care. Treatment with SGLT2Is and/or GLP1RAs was associated with a favorable impact on mortality but not MACE.

A Clinicians Guide to Recommending Common Cholesterol-Lowering Dietary Supplements.

The US dietary supplement (DS) market has expanded exponentially since 1994, with an estimated 50,000-80,000 individual products currently available. Many DS claim cholesterol or cardiovascular benefits. Overall, well-designed randomized controlled trials (RCTs) with DS are lacking, while studies with favorable results are commonly performed outside of the USA, resulting in inconsistent findings. The expansion of the DS market has limited the ability of the Food and Drug Administration to regulate and prevent substandard products. Eicosapentaenoic acid and docosahexaenoic acid are components of DS fish oil. Recent RCTs utilizing prescription fish oil have provided mixed findings and small but significant safety concerns. Hence, the role of DS fish oil is limited and no longer recommended by major cardiovascular guidelines. Concerns have also been observed from RCTs utilizing prescription niacin, resulting in a negligible role for DS niacin in lipid management. Red yeast rice has demonstrated significant low-density lipoprotein cholesterol (LDL-C) reductions in studies performed worldwide, including the USA. However, quality concerns and inconsistent study results have been reported on multiple occasions. Other common DS have produced modest reductions in LDL-C and may provide other cardiometabolic benefits, including garlic, phytosterols, psyllium, and berberine. Yet inconsistent study results and quality concerns continue to be reported for most. Nonetheless, there is a need for alternative therapies that can safely and effectively reduce cardiovascular risk. However, until DS routinely match label claims and are free of contaminants, the agents have a limited role in clinical practice.

The Comparison of the Effectiveness of Dapagliflozin and Empagliflozin in the Prevention of Cardiovascular Outcomes in Patients With Type 2 Diabetes: A Network Meta-Analysis.

Type 2 diabetes mellitus (T2DM) is a significant risk factor for cardiovascular diseases, prompting research into treatments that can mitigate this risk. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, particularly dapagliflozin and empagliflozin, have shown promising cardiovascular benefits in T2DM patients. This meta-analysis aimed to directly compare the cardiovascular outcomes of these two drugs. To achieve this, we conducted a comprehensive literature search across multiple databases up to August 5, 2024, including both randomized controlled trials (RCTs) and observational studies. The primary outcomes of interest were major adverse cardiovascular events (MACE), atrial fibrillation (AF), cardiovascular mortality, myocardial infarction (MI), and hospitalization for heart failure (HF). Twelve studies met the inclusion criteria for this meta-analysis. The pooled analysis revealed several key findings. Notably, dapagliflozin demonstrated superior efficacy in preventing atrial fibrillation compared to empagliflozin. However, no significant differences were observed between the two drugs in terms of MACE, cardiovascular mortality, hospitalization for heart failure (HHF), or myocardial infarction. When compared to placebo, both dapagliflozin and empagliflozin showed greater effectiveness in preventing adverse cardiovascular outcomes in T2DM patients.These results reinforce the cardiovascular benefits of both dapagliflozin and empagliflozin in patients with T2DM. The comparable efficacy in most outcomes suggests that clinicians have flexibility in prescribing either of these SGLT2 inhibitors. However, the lower risk of atrial fibrillation associated with dapagliflozin may be a crucial factor in treatment decisions, especially for patients with a history of or at high risk for atrial fibrillation.

The Use of Horse and Donkey Meat to Enhance the Quality of the Traditional Meat Product (Kaddid): Analysis of Physico-Chemical Traits.

The aim of this study was to evaluate the use of horse and donkey meat in the production of kaddid-a traditional dish typically not made with these meats-from a physical and chemical perspective. The results showed that both meats exhibit similar water retention during cooking, contributing to comparable tenderness and juiciness, with no significant differences in pH values, indicating similar quality (p > 0.05). However, their amino acid profiles differ: horse meat contains lower levels of glutamate (p < 0.05), methionine (p < 0.01), isoleucine (p < 0.05), and leucine (p < 0.05), but higher levels of proline (p < 0.05), histidine (p < 0.01), and lysine (p < 0.001) compared to donkey meat. Both meats provide essential amino acids. Horse meat is richer in saturated and monounsaturated fatty acids (32.44% and 39.58%, respectively), while donkey meat has a higher content of polyunsaturated fatty acids (31.51%), with a more favorable PUFA/SFA ratio, suggesting better cardiovascular health benefits. In terms of dried meat, donkey kaddid has a higher protein (17.45 g/100 g) and lower fat content (2.1 g/100 g) compared to horse kaddid (16.7 g/100 g, and 3.5 g/100 g, respectively) (p < 0.05). These findings inform consumer choices and production practices, promoting the use of horse and donkey meat for kaddid production.

Cardiovascular and Metabolic Benefits of Extra Virgin Olive Oil Phenolic Compounds: Mechanistic Insights from In Vivo Studies.

Extra virgin olive oil (EVOO) represents a significant source of monounsaturated fatty acids (MUFA) and vitamin E, but it is also considered a functional food, due to the content of peculiar bioactive molecules, such as phenolic compounds, being able to modulate various processes related to aging and the most common metabolic and degenerative diseases. A lot of experimental research has focused on some of these components, but in most cases, the studies were performed in vitro testing compounds at non-physiological concentrations and achieving results that cannot easily be translated in vivo. Recent clinical studies demonstrated that in vivo these compounds are able to regulate physiological functions and prevent several pathological events including metabolic and cardiovascular diseases (CVDs), which represent the main causes of death worldwide. This review aims to sum up the major evidence on the beneficial effects of EVOO phenolic compounds in vivo on these pathologies, describing and evaluating the efficacy in relation to the mechanisms of diseases of the whole phenolic fraction and some of its specific components.

Heart failure with preserved ejection fraction and atrial fibrillation: catheter ablation vs. standard medical therapy - a systematic review and meta-analysis.

The latest guidelines advocate for catheter ablation (CA) over standard medical therapy (SMT) for managing atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (HFrEF). However, significant knowledge gaps exist regarding the effectiveness of CA vs. SMT in patients with heart failure with preserved ejection fraction (HFpEF). PubMed, Scopus, and Embase until February 2024 were systematically searched. Given the limited number of randomized studies, propensity score-matched observational studies comparing CA with SMT in AF patients with HFpEF were also included. The primary outcome was a composite endpoint of all-cause mortality and HF hospitalization. Eight studies that enrolled 17,717 SMT and 2537 CA patients were included. CA was associated with a significantly lower risk of the composite endpoint of all-cause mortality and HF hospitalization (HR 0.61; 95% CI, 0.43-0.85). The risk of HF hospitalization (HR 0.44; 95% CI, 0.23-0.83), cardiovascular mortality (HR 0.43; 95% CI, 0.22-0.84), and AF recurrence (HR 0.53; 95% CI, 0.39-0.73) were also lower in the CA group. CA demonstrated significant cardiovascular morbidity and mortality benefits compared to SMT in the HFpEF population.

Unexplored Opportunities of Utilizing Food Waste in Food Product Development for Cardiovascular Health.

Global food production leads to substantial amounts of agricultural and food waste that contribute to climate change and hinder international efforts to end food insecurity and poverty. Food waste is a rich source of vitamins, minerals, fibers, phenolic compounds, lipids, and bioactive peptides. These compounds can be used to create food products that help reduce heart disease risk and promote sustainability. This review examines the potential cardiovascular benefits of nutrients found in different food waste categories (such as fruits and vegetables, cereal, dairy, meat and poultry, and seafood), focusing on animal and clinical evidence, and giving examples of functional food products in each category. Current evidence suggests that consuming fruit and vegetable pomace, cereal bran, and whey protein may lower the risk of cardiovascular disease, particularly in individuals who are at risk. This is due to improved lipid profile, reduced blood pressure and increased flow-mediated dilation, enhanced glucose and insulin regulation, decreased inflammation, as well as reduced platelet aggregation and improved endothelial function. However, the intervention studies are limited, including a low number of participants and of short duration. Food waste has great potential to be utilized as cardioprotective products. Longer-term intervention studies are necessary to substantiate the health claims of food by-products. Technological advances are needed to improve the stability and bioavailability of bioactive compounds. Implementing safety assessments and regulatory frameworks for functional food derived from food waste is crucial. This is essential for maximizing the potential of food waste, reducing carbon footprint, and improving human health.