World Health Organization recommends adjusting the salt intake as a part of the nine global targets to reduce premature mortality from non-communicable chronic diseases as priority and most cost-effective intervention. In 2006. the main aim of the Croatian Action on Salt and Health was to decrease salt intake for 16% because of its critical intake and consequences on human health. We have organized educative activities for increasing awareness on salt harmfulness, defined food categories of prime interest, collaborate with industries and determine salt intake (24h urine-sodium excretion). It was determined that the proportion of salt in ready-to-eat baked bread should not exceed 1.4%. In the period 2014 –2022, salt in the semi-white bread was reduced 14%, in bakery 22% and in largest meat industry in Croatia 25%. Awareness of the harmfulness of salt on health increased from 65.3% in 2008 to 96.9% in 2023 and salt intake was reduced 15.9%-1.8 grams/day (22.8% men, 11.7% women). In last 18 years a significant decrease in salt intake was achieved in Croatia, awareness of its harmfulness increased, collaboration with food industry established and regulatory documents launched. However, salt intake is still very high underlying the need for continuation of efforts and even stronger activities.

Cardiovascular diseases (CVDs) a leading cause of mortality worldwide. Therefore, there is in-creasing interest in dietary interventions to reduce risk factors associated with these conditions. Cherries and berries are rich sources of bioactive compounds and have attracted attention for their potential cardiovascular benefits. This review summarizes the current research on the effects of cherries and berries consumption on cardiovascular health, including in vivo studies and clinical trials. These red fruits are rich in phenolic compounds, such as anthocyanins and flavonoids, which have multiple bioactive properties. These properties include antioxidant, anti-inflammatory, and vasodilatory effects. Studies suggest that regular consumption of these fruits may reducing in-flammation and oxidative stress, leading to lower blood pressure, improved lipid profiles, and enhanced endothelial function. However, interpreting findings and establishing optimal dosages is challenge due to the variability in fruit composition, processing methods, and study design. Despite these limitations, the evidence highlights the potential of cherries and berries as components of preventive strategies against CVD. Further research is needed to maximize their health benefits and improve clinical practice.

It has been proposed that procedures which up-regulate mitochondrial biogenesis and autophagy by replacing damaged mitochondria with healthy ones, may prevent the development of several heart diseases. A member of serine and threonine kinases, AMPK, could play essential roles in the autophagy and/or mitophagy. AMPK is widely distributed in various cells, which might play diverse regulatory roles in different tissues and/or organs. In fact, changes in the kinase function of AMPK due to alteration of activity have been linked with diverse pathologies including cardiac disorders. AMPK can regulate mitochondrial biogenesis via PGC1α signaling and also improve oxidative mitochondrial metabolism through inhibition of mTOR pathway, which may also modulate the autophagy/mitophagy through ULK1 and/or TGF-β signaling. Therefore, the modulation of AMPK in autophagy/mitophagy pathway might be considered as a therapeutic tactic for several cardiac disorders. As kinases are amongst the most controllable proteins, in general, the design of small molecules targeting kinases might be an eye-catching avenue to modulate the cardiac function. Some analyses of the molecular biology underlying mitophagy suggests that nutraceuticals and/or drugs including specific AMPK modulator as well as physical exercise and/or dietary restriction that could modulate AMPK may be useful against several heart diseases. In particular, some nutraceutical regimens may have encouraging potential for controlling some of cardiac disorders.

BACKGROUND AND AIMS: Cardiovascular disease and colorectal cancer (CRC) are significant health problems and share some risk factors. The aim of our study was to develop and validate a predictive score for advanced colorectal neoplasia (CRN) based on risk factors for cardiovascular disease and CRC. MATERIALS AND METHODS: A cross-sectional study comprising a derivation cohort and an external validation cohort of 1049 and 308 patients respectively. A prediction score for advanced CRN (CRNAS: Colorectal Neoplasia Advanced Score) was developed from a logistic regression model, comprising sex, age, first-degree family history for CRC, systolic and diastolic blood pressure, total cholesterol, HDL-cholesterol, body mass index, diabetes, smoking, and antihypertensive treatment. Other cardiovascular risk scores (Framingham-Wilson, REGICOR, SCORE and FRESCO) were also used to predict the risk of advanced CRN. The discriminatory capacity of each score was evaluated using the area under the curve (AUC). RESULTS: CRN were found in 379 subjects from the derivation cohort (36%) including 228 patients (22%) with an advanced CRN. Male sex, age, diabetes, and smoking were identified as independent risk factors for advanced CRN. The newly created score (CRNAS), showed an AUC of 0.68 (95% CI: 0.64-0.73) for advanced CRN, which was better than cardiovascular risk scores (p

Background: Both hypertension and carotid atherosclerosis are independent risk factors for cardiovascular disease. Understanding their combined impact could enhance risk assessment and management strategies. Hypothesis: We hypothesized that the synergistic effects of hypertension and carotid plaques would increase the risk of both cardiovascular events and all-cause mortality. Methods: A follow-up study was conducted at the Preventive Cardiology department of Vilnius University Hospital Santaros klinikos between 2012 and 2021. The study recruited participants aged 40-60 who did not have overt CVD and were part of the Lithuanian High Cardiovascular Risk primary preventive program. The study collected demographic and clinical data, including an ultrasound assessment of carotid plaque. The participants were monitored for 4-10 years for CVD events and all-cause mortality. Results: Among 6,138 participants, 954 (16%) experienced cardiovascular disease (CVD) events. The presence of carotid plaque on both sides was significantly associated with CVD events, myocardial infarction, and all-cause mortality. However, the combination of hypertension and carotid plaque did not significantly increase the risk for CVD events, stroke, or all-cause mortality. Conclusion: The combination of hypertension and carotid plaque did not significantly increase the risk of CVD events or all-cause mortality. CV events depend on the spread of the atherosclerosis process in the carotid vessels.

Background and Objectives: High job strain is worsening the outcome in coronary artery disease, CAD. Severe dissatisfaction on workplace, imbalance between high demands , and low rewards, are affecting the quality of life, and diminishing the duration of life, especially in CAD patients. Our study included two samples : CAD patients (experimental group), and without CAD patients, but with traditional risk factors (control group). The main objective of the study was the role played by high sensitivity C reactive protein, hs CRP, and microalbuminuria, as mediators of job strain and CAD relationship. Secondary objectives were the following: identification of the most vulnerable patients( with significant job strain) and intervention towards this category, for cardiovascular events prevention (primary or secondary). Materials and Methods: The utilized methods were the following : clinical exam; electrocardiogram; echocardiogram; non contrast enhanced computed chest tomography; laboratory findings ( lipid profile, glycemia, hs CRP, microalbuminuria); type D scale, DS 14; depression questionnaire, PHQ-9; and satisfaction with work scale, SWWS. Results: The highest values for hs CRP and microalbuminuria were noticed in patients with the lowest Likert score, for both samples CAD, and without CAD patients. The highest job strain was noticed in females. More than half of CAD patients ,with low Likert scores, revealed myocardial infarction. Conclusions: Microalbuminuria and hs CRP were statistical significant in the study as intercessors, in job strain and CAD relationship. The most vulnerable patients for vascular events were females, in both groups : CAD and “CAD waiting desk”. In CAD sample, the vascular vulnerability was also increased by high job strain.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

Prolylcarboxypeptidase (PRCP, PCP, Lysosomal Pro-X-carboxypeptidase, Angiotensinase C) controls angiotensin - and kinin- induced cell signaling. Elevation of PRCP appear to be activated in chronic inflammatory diseases (cardiovascular disease (CVD), diabetes) in proportion to severity. Vascular endothelial cell senescence and mitochondrial dysfunction have consistently been shown in models of CVD in aging. The cellular senescence, a driver of age-related dysfunction, can differentially alter the expression of lysosomal enzymes due to lysosomal membrane permeability. There is a lack of data demostrating the effect of age-related dysfunction on the expression and function of PRCP. To explore the changes in PRCP, PRCP-dependent prekallikrein (PK) pathway was charcterized in early – and late-passage human pulmonary artery endothelial cells (HPAECs). Detailed kinetic analysis of cells treated with high molecular weight kininogen (HK), a precursor of bradykinin (BK), and PK revealed a mechansim by which senescent HPAECs activate the generation of kallikrein upon the assembly of the HK-PK complex on HPAECs in parallel with an upregulation of PRCP and endothelial nitric oxide (NO) synthase (eNOS) and NO formation. The NO production and expression of both PRCP and eNOS increased in early-passage HPAECs while decreased in late-passage HPAECs. Low activity of PRCP in late passage HPAECs was associated with rapid decreased telomerase reverse transcriptase mRNA levels. We also found that, with an increase in the passage number of HPAECs, reduced PRCP altered respiration rate. These results indicated that aging dysregulates PRCP protein expression, and further studies will shed light into the complexity of PRCP-dependent signling pathway in aging.

The prevalence of Noncommunicable Diseases (NCDs) in South Africa is increasing annually, with the burden projected to escalate by 2030. Devastatingly, factors such as lifestyle changes, urbani- sation, and an aging population significantly contribute to a rising burden of Cardiovascular disease (CVDs), diabetes, and cancer which directly impact the mortality and morbidity rates seen in South Africa. Recognising this, the South African government has seen the need for emphasis on developing policies and interventions tar- geting physical inactivity to prevent and manage NCD, particularly cost-free and easy to administer training protocols. However, phys- ical inactivity remains a significant issue, leading to various health concerns in rural communities, including injuries and Fetal Alcohol Spectrum Disorders (FASD). Despite effort to promote physical ac- tivity, the prevalence of NCDs continues to rise, necessitating target- ed interventions to ensure equitable healthcare among South African citizens. On the Contrast, preservation and promotion of traditional games is vital as they offer indigenous populations accessible and culturally relevant means to maintain health and wellness. In this regard, it is important to recognize the importance of preserving and promoting traditional games as they potentially serve as a method for indigenous people to maintain their health and wellness in a way that is accessible and culturally relevant to them. These games have gained popularity in South Africa, with initiatives underway to show- case them globally fostering cultural exchange. Further, revitalizing and conserving these games can cultivate a culture of health and wellbeing in South Africa.

Risk stratification for malignant ventricular arrhythmias and sudden cardiac death is a daunting task for physicians in daily practice. Multiparametric mapping sequences obtained via cardio-vascular magnetic resonance imaging can improve the risk for malignant ventricular arrhythmias by unveiling the presence of pathophysiological pro-arrhythmogenic processes. However, their employment in clinical practice is still restricted. The present review explores the current evidence supporting the association between mapping abnormalities and the risk of ventricular arrhyth-mias in several cardiovascular diseases. The key message is that further clinical studies are needed to test the additional value of mapping techniques beyond conventional cardiovascular magnetic resonance imaging for selecting patients eligible for an implantable cardioverter defibrillator.

Background and Objectives: In this current state, Type 2 Diabetes Mellitus (T2DM) is more prevalent in the population, and metformin is used as a first-line medication for treating it. There was up surge in the utilization of alternative therapies in the management of diabetes. Especially in diabetes, Herbal medicines are considered safe and reliable by majority of the population. Aim: The purpose of this research is aimed to estimate the safety and efficacy of Polyherbal Metabolite Compounds (PHMC) capsules in adults with T2DM. Materials and Methods: In this study, 60 T2DM patients aged 18-60 years were randomly assigned to Groups A (30) receiving Metformin 500 mg twice a day after food and Group B (30) receiving PHMC capsule 500 mg twice a day after food in a prospective, randomized and open-label clinical study. The in-silico simulation study was performed to selected plants major compounds on target protein Insulin-like Growth Factor-1 (1K3A). Result: The PHMC is found to be safe and effective in the management of T2DM. The FBS, PPBS and HbA1c were significantly lowered (p

Fractional flow reserve (FFR) is well recognized as a gold standard measure for the estimation of functional coronary stenosis. Technological progressions in image processing have empowered the reconstruction of three-dimensional models of the coronary arteries via both non-invasive imaging modalities, such as Coronary Computed Tomography Angiography (CCTA), and invasive coronary angiography or intravascular imaging. The application of computational fluid dynamics (CFD) techniques to coronary 3D anatomical models allows the virtual evaluation of the hemodynamic significance of a coronary lesion with high diagnostic accuracy in comparison to the invasive FFR using pressure wires. These opportunities providing hemodynamic information based on anatomy have given rise to a new era of functional angiography and coronary imaging. However, further validations are needed to overcome several scientific and computational challenges before these methods are applied in everyday clinical practice. This review aims to present all the data on the studies and methodologies that have been presented for the virtual estimation of FFR, and the diagnostic execution of the virtual tools for the hemodynamic assessment of coronary lesions compared to the invasive FFR.

Atherosclerosis, a complex metabolic-immune disease characterized by a chronic inflammation driven by the buildup of lipid-rich plaques within arterial walls, has emerged as a pivotal factor in the intricate interplay between cancer and cardiovascular disease. This bidirectional relationship, marked by shared risk factors and pathophysiological mechanisms, underscores the need for a comprehensive understanding of how these two formidable health challenges intersect and influence each other. Cancer and its treatments can contribute to the progression of atherosclerosis while atherosclerosis with its inflammatory microenvironment can exert profound effects on cancer development and outcomes. Both cancer and cardiovascular disease involve intricate interactions between general and personal exposomes. In this review we want to summarize the state-of-the-art of translational data and try to show how oncologic studies on cardiotoxicity can broaden our knowledge of crucial pathways in cardiovascular biology with a positive impact on precision cardiology and cardioncology.

We aimed to evaluate the association between daily dietary calcium intake and the risk of cardiovascular disease (CVD) in postmenopausal women using data from the Korean National Health and Nutrition Examination Survey (KNHANES). This cross-sectional study included 12,348 women aged 45–70 years who had reached natural menopause. They were classified into three groups according to daily dietary calcium intake: < 400 mg, 400–800 mg, and >800 mg. The risks of CVD, stroke, angina, and myocardial infarction were assessed in each group. Further, we performed subgroup analysis according to the post-menopause duration (≤10 vs. >10 postmenopausal years). We performed logistic regression analysis with adjustment for age, menopausal age, income, urban area, education, insulin use, body mass index, hypertension, diabetes mellitus, dyslipidemia, high alcohol intake, smoking, exercise, oral contraceptive use, and hormonal therapy use. Calcium intake level was not significantly associated with the risk of CVD in the total population and the ≤10 postmenopausal years subgroup. However, in the >10 postmenopausal years subgroup, daily calcium intake >800 mg was associated with significantly decreased risks of all CVD (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.11–0.64), stroke (OR, 0.06; 95% CI, 0.01–0.42), and myocardial infarction (OR, 0.27; 95% CI, 0.11–0.64). Our findings suggest that a dietary calcium intake of >800 mg/day decreases the risk of CVD events in women who have been menopausal for >10 years.

Pregnancy is a complex biological process which is associated with significant metabolic and hemodynamic changes of the maternal body which allow a normal fetal growth. The inability to adapt to these changes can affect the cardiovascular health. During pregnancy, women may experience mood swings, anxiety and emotional ambivalence. These symptoms can lead to stress and have a negative impact on the mental well-being of expectant mothers. It is crucial to know the aspects that can influence the development of cardiovascular problems among pregnant women in order to manage these cases properly. The current narrative review explores and summarizes the evidence regarding the impact of stress and anxiety on cardiovascular health in pregnant women. Understanding the physiological adaptations that the body undergoes throughout pregnancy is crucial for educating and supporting individuals as well as healthcare professionals. This enables them to recognize any risk factors or pathological conditions that may exacerbate pregnant women's health. In order to reduce maternal morbidity and mortality from cardiovascular disease, a psychological and cardiovascular risk factor screening that is done either before or during pregnancy may be able to identify situations that call for particular medical and/or psychological therapies.

Background: Autonomic balance measurement (ABM) is a valuable tool in clinical practice for assessing the functioning of the autonomic nervous system (ANS), which controls involuntary bodily functions. Here we summarize the current understanding of the utility of autonomic balance measurement in clinical practice. Methods: A narrative review of relevant literature was conducted, focusing on studies investigating the use of autonomic balance measures in various clinical settings. Results: ABM holds potential benefits in clinical practice, including aiding in diagnosing autonomic dysfunction, monitoring treatment efficacy, and predicting potential health complications. ABM can be crucial for diagnosing various conditions, including cardiovascular diseases (Heart failure, arrhythmias, and hypertension), neurological disorders (Parkinson's disease, Alzheimer's disease, and diabetic neuropathy), in sports medicine athletes can undergo ABM to optimize training regimens, enhance performance, assessing the impact of training stress, preventing overtraining, and promoting overall well-being and probably to assess potential health risks, in metabolic syndromes ABM can aid in the early detection of autonomic neuropathy, a diabetes-related complication, allowing for timely intervention and better management of the disease, and psychiatric disorders (Anxiety, depression, and post-traumatic stress disorder). In addition, ABM can be helpful in monitoring of treatment efficacy, by tracking changes in autonomic balance, clinicians can assess if treatments for conditions impacting the autonomic nervous system are effective. ABM can also be helpful in predicting outcomes by facilitating early recognition of future health complications in certain populations. However, limitations exist, including non-specificity, variability in measurements, and limited evidence for routine use in specific clinical settings. Conclusion: Incorporating autonomic balance measurement into routine clinical assessments provides a more comprehensive understanding of a patient's health. It complements traditional diagnostic methods, offering additional insights into the body's regulatory mechanisms. While autonomic balance measurement offers potential benefits, careful interpretation and consideration of its limitations are crucial for its effective use in clinical practice. ABM remains a valuable and versatile tool in clinical practice for a deeper understanding of the autonomic nervous system, enabling early detection, targeted interventions, and improved management of various medical conditions across different specialties.

Insulin resistance/hyperinsulinemia as an independent risk factor for the development and worsening of HFpEF. Serafino Fazio MD¹, Valentina Mercurio MD, PhD2, Valeria Fazio MD3, Antonio Ruvolo MD⁴, Flora Affuso MD, PhD⁵. Authors’ Affiliation: ¹ Department of Internal Medicine (retired Professor). Federico II University, Via Sergio Pansini 5. 80135 Naples, Italy. 2 Department of Translational Medical Sciences. Federico II University. Via Sergio Pasini 5. 80135 Naples, Italy. ³ UOC Medicina Interna, Azienda Ospedaliera di Caserta, 81100 Caserta, Italy, ⁴ UOC Cardiologia AORN dei colli PO CTO, Viale Colli Aminei 21, 80100 Naples, Italy. ⁵ Independent researcher, Viale Raffaello 74, 80129 Naples, Italy. Abstract Heart failure (HF) has become a subject of continuous interest since it has been declared new pandemic in 1997 because of the exponential increase in hospitalizations for HF in the latest years. HF is the final state to which all heart diseases of different etiologies lead if not adequately treated, therefore it is highly prevalent worldwide, with a progressive increase with age, reaching a prevalence of 10% in subjects over the age of 65 years. It should also be underlined that lately, while the prevalence of HF with left ventricular reduced ejection fraction (HFrEF) is slowly decreasing, the incidence of HF with left ventricular preserved ejection fraction (HFpEF) is progressively increasing. In deed, among patients consecutively hospitalized for HF between 1987 and 2001 in a study from the Mayo Clinic Hospitals in Olmsted County, Minnesota, prevalence of HFpEF increased from 38% to 54%. HFpEF is typically characterized by concentric remodeling of the left ventricle (LV) with impaired diastolic function and increased filling pressures. Over the years, also the prevalence of insulin resistance/hyperinsulinemia in the general adult population has progressively increased, primarily due to lifestyle changes, particularly in developed and developing countries, with a range that globally ranges between 15.5% and 46.5%. Notably, insulin resistance (IR)/hyperinsulinemia (Hyperins) is present in up to 60% of patients with HF and is significantly higher in subjects with HfpEF. In the scientific literature it has been well highlighted that the increased circulating levels of insulin are associated with conditions of insulin resistance are responsible for progressive cardiovascular alterations over the years. In the setting of HFpEF, insulin stimulates the concentric remodeling of the left ventricle with associated diastolic dysfunction, which, coincidentally. Unfortunately, IR/Hyperins, despite being a well-known cardiovascular risk factor, is still not screened in the general population and is not treated as promptly as it should be, and this could at least in part concur in the progressive increase in prevalence of HFpEF in the general adult population. The aim of this manuscript was to review scientific literature that support a pathophysiologic connection between IR/Hyperins and HFpEF to stimulate the scientific community towards the identification of hyperinsulinemia associated with insulin resistance as an independent cardiovascular risk factor in development and worsening of HF, believing that its adequate screening in the general population and appropriate treatment could reduce the prevalence of HFpEF and improve its progression.

Abstract Cholesterol has ruled the history of atherosclerotic cardiovascular diseases (CVD) for decades, and the transport of cholesterol by lipoproteins has become a cornerstone of our view of etiology of the disease. Discovery of the lipoprotein-specific transport of lipid oxidation products (LOP) has opened a new and exciting area in research of CVD by revealing strong connections between atherogenic LOP, lipoprotein transport functions and CVD. This review goes through the evidence in support of the lipoprotein-specific LOP transport and speculates of possible consequences of the proposed role of lipoprotein LOP transport as a risk factor. Association of lipoprotein LOP with known risk factors of CVD are largely parallel with those of cholesterol, and due to the common transport and cellular intake mechanisms the elucidation of independent effects of either cholesterol or LOP is difficult. Yet, unlike cholesterol, LOP can directly initiate and boost atherogenic processes. It therefore appears inevitable that increasing knowledge of the lipoprotein-specific LOP transport will affect the present view of the role of cholesterol in aetiology and as a risk factor of CVD.

The most frequent cause of cardiac failure globally is ischemic heart disease, with chemothera-py-related cardiovascular side effects emerging as the second most frequent cause. Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT pro-longation, torsades de pointes, pericardial effusion and hypotension, as well as chronic conditions, such as hypertension, systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovas-cular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovas-cular side effect continues even after the causative medication is stopped, it is referred to as cardi-otoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even with very low medication dosages, and can show up as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome and myocardi-tis caused by cancer therapy.

Mediterranean Diet (MD), rich in minimally processed plant foods and in monounsaturated fats, but low in saturated fats, meat and dairy products, represents one of the most studied diets for cardiovascular health. It has been shown, from both observational and randomized controlled trials, that MD reduces body weight, improves cardiovascular disease surrogates such as waist-to-hip ratio, lipids, and inflammation markers, and even prevents the development of fatal and non-fatal cardiovascular disease, diabetes, obesity, and other diseases. However, it is unclear whether it offers cardiovascular benefits from its individual components or as a whole. Furthermore, limitations in the methodology of studies and meta-analyses have raised some concerns on its potential cardiovascular benefits. MD is also associated with characteristic changes in the intestinal microbiota, mediated through its constituents. These include increased growth of species producing short-chain fatty acids, such as Clostridium leptum and Eubacterium rectale, increased growth of Bifidobacteria, Bacteroides and Faecalibacterium prausnitzii species, and reduced growth of Firmicutes and Blautia species. Such changes are known to be favorably associated with inflammation, oxidative status, and overall metabolic health. This review will focus on the effects of MD on cardiovascular health through its action on gut microbioma.

Delve into the dynamic realms of neuroscience, neurology, and psychiatry with this groundbreaking editorial, unveiling the intricate mechanisms of brain function and dysfunction. Explore the latest advancements in molecular biology, genetics, epigenetics, pharmacology, and neuroimaging that are revolutionizing our understanding of neurological and psychiatric disorders. Uncover the challenges and gaps in translating cutting-edge research into practical clinical applications, aiming to enhance the lives of patients and their families. Discover the pivotal role of neuroplasticity in reshaping the brain's adaptability throughout life, alongside the promising potential of non-invasive brain stimulation techniques like transcranial magnetic stimulation and transcranial direct current stimulation. Embark on a journey of innovation and collaboration as researchers and clinicians strive to bridge the gap between bench and bedside, offering hope for improved diagnosis, prevention, and treatment of complex neurological and psychiatric conditions. Join us in this exploration of transformative ideas and novel interventions that hold the key to a brighter future for individuals and society.

Background: Coronavirus disease 2019 (COVID-19) caused several cardiovascular complications, including acute myocardial infarction(AMI) in infected patients. Our study aims to understand the overall trends of AMI among COVID-19 patients during the first two years of the pandemic and the disparities and outcomes between the first and second years. Methods: Our retrospective analysis via the 2020 and 2021 National Inpatient Sample(NIS) for hospitalizations between April 2020 and December 2021 analyzed adults with a primary diagnosis of COVID-19 who experienced events of AMI. We compared month-to-month events of AMI and mortality of AMI patients with COVID-19, patient characteristics, and outcomes between the 2020 and 2021 AMI samples. Results: There were 2,541,992 COVID-19 patients, with 3.55% experiencing AMI. The highest rate of AMI was in December 2021 (4.35%). No statistical differences in trends of AMI mortality were noted over the 21 months. AMI cases in 2021 had higher odds of undergoing PCI (aOR 1.627, p

The association between normal-range triglycerides and diabetes mortality remains unclear. This cohort study aimed to elucidate this relationship by examining 19,010 US adult participants with fasting serum triglycerides below 150 mg/dL. Cox proportional hazards models were employed to estimate mortality hazard ratios (HRs) and 95% confidence intervals (CIs). Participants were followed up for a mean of 15.3 years, during which 342 diabetes deaths were recorded. A 1-natural-log-unit increase in triglycerides was associated with a 57% higher risk of diabetes mortality (adjusted HR, 1.57; 95% CI, 1.04–2.38). Comparable results were obtained when triglycerides were analyzed in quartiles. Receiver operating characteristic curve analysis identified an optimal triglyceride cutoff of 94.5 mg/dL for diabetes mortality; individuals with triglyceride levels above this threshold faced a greater risk of diabetes mortality (adjusted HR, 1.43; 95% CI, 1.12–1.83). Further investigation revealed a positive association between normal triglyceride levels and all-cause mortality, though no association was observed between normal triglycerides and mortality from hypertension or cardiovascular disease. In conclusion, elevated triglycerides within the normal range were associated with an increased risk of diabetes mortality. Individuals with triglyceride levels of 95 mg/dL or higher may require vigilant monitoring for diabetes and its associated complications.

Space exploration is an arduous journey, with future explorations extending in duration, increasing the risk for common space-related health issues such as bone density loss due to microgravity, impaired gut microbiota, cardiovascular ailments, and exposure to cosmic radiation. These ailments can be addressed using medicinal plants. Enhancing their efficacy entails employing gene editing to target specific secondary metabolite pathways associated with therapeutic properties. Moreover, gene editing can combine multiple medicinal properties from various plants, culminating in a singular 'superplant' with enhanced therapeutic benefits. This review discusses the current usage of medicinal plants in promoting human health during space travel, the application of gene editing technology in modifying medicinal plants and presents a vision for the utilization of gene-edited medicinal plants in space to mitigate the risk of various space-related health issues.

Background: Although the link between environmental lead exposure and several patterns of cardiovascular disease (CVD) has been reported, its association with silent myocardial infarc-tion (SMI) has not been explored. We aimed to assess the association between blood lead levels (BLL) and risk of SMI. Methods: This analysis included 7283 (mean age 56.1±2.52 years, 52.5% women) participants from the Third National Health and Nutrition Examination Survey who were free of clinical CVD. Ascertainment of BLL done using graphite furnace atomic absorption spectrophotometry. SMI defined as ECG evidence of MI without history of MI. Multivariable lo-gistic regression analysis was used to examine the association between SMI and BLL. Results: SMI was detected in 120 participants corresponding to an unweighted prevalence of 1.65%. Par-ticipants with higher levels of BLL had higher prevalence of SMI (0.4%, 0.9%, and 2.4% across BLL tertiles; p-value

Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) has proven to be effective in reducing the rate of recurrence and disease as secondary prevention (evidence-based intervention) in patients who have suffered from myocardial infarction (MI). CR is a multidisciplinary path in which the patient is followed pharmacologically, from a psychological, nutritional, nursing and physiotherapy point of view. Post-MI patients present a reduction in the performance of the diaphragm muscle, the main inspiratory muscle, and this condition can become a risk factor for further relapses or for the onset of heart failure. Despite the solidity of the international guidelines for CR, the latter are lacking in specifically indicating an evaluation and training path regarding the inspiratory muscles in post-MI patients who have not undergone cardiac surgery. The article reviews the information on the adaptation of the diaphragm post-MI and highlights the need for clearer indications for a rehabilitation process that gives importance to the diaphragm.

Background: Cardiovascular diseases (CVDs) are a rising global burden. Preventative strategies such as Cardiac Rehabilitation (CR) have shown a marked reduction of disease burden. Despite this, CR is underutilized worldwide. This study aims to identify the barriers to CR among patients diagnosed with CVD. Methods: A scoping review of the literature was conducted following the Joanna Briggs Institute (JBI) guidelines. Three major databases including CINAHL, PubMed, EBSCOhost and Scopus were used to obtain studies published between 2010 and 2023. Search terms such as “Cardiac rehab*”, “Barrier*”, “Cardiovascular”, “Disease” And “diagnosis*” Were utilized in order to obtain subject-specific studies relevant to the research question. Results: From the initial 2098 studies only 14 were included in the final analysis, consisting of both qualitative and quantitative designs. The thematic analysis included “healthcare system-related factors”, “Socioeconomic factors”, and “individual characteristics”. Healthcare system-related factors were mostly related to poor availability of CR programs, lack of proper referral strategies, inadequate knowledge of CR provider and inter-provider communication issues, and lack of alternative methods of CR delivery. Socioeconomic barriers were lack of education, longer distance to CR facilities, high cost of care, unemployment, and poor income status. Identified individual characteristics were female gender, older age, and comorbidities. Conclusion: Lack of resources, poor access, educational attainment, and high cost of care were some of the barriers to CR, particularly in low and middle-income countries (LMICs). Health policymakers and healthcare providers should implement strategies incorporating issues identified in this scoping review. Systematic reviews may be required to confirm these findings.

Leukemia, contributing to 3% of all cancer cases in the United States, presents a significant challenge in treatment due to its diverse subtypes, each dis-playing unique genetic and molecular abnormalities. The aggressive growth of ab-normal blood cells compromises immune function and poses challenges in developing effective therapeutic approaches. Unlike solid tumors, surgical resection is not an option, limiting treatment strategies to chemotherapy, immunotherapy, and radiation therapy, which may be nonspecific and lead to organ damage and toxicity. Anthracyclines, widely used in hematological tumors, face limitations due to severe cardiotoxicity, causing progressive cardiomyopathy and, in severe cases, congestive heart failure. Heart failure incidence is significantly higher in cancer patients treated with anthracyclines over 5, 10, and 15 years. Early detection of left ventricular dysfunction and cardiotoxicity is crucial to mitigate progression to congestive heart failure (CHF) in this population. Recent research by Bayrón-Marrero et al. reveals that lower levels of plasma soluble TREM-Like Transcript-1 (s-TLT-1), a platelet-specific receptor, correlate with left ven-tricular dysfunction in cardiovascular disease patients. Those with s-TLT-1 levels ex-ceeding 544 pg/mL exhibit a significant association with congestive heart failure. These findings suggest the potential use of s-TLT-1 as a diagnostic screening tool for early detection and treatment of anthracycline-induced CHF in leukemia patients.

The normal ageing process significantly affects resistance arteries, leading to various biological and physiological consequences. Systolic hypertension is a common occurrence in ageing individuals, accompanied by increased large artery stiffening, heightened pulsatility, small artery remodeling, and damage to critical microvascular structures. Starting from young adulthood, there is a progressive elevation in mean arterial pressure, supported by clinical and epidemiological evidence as well as findings from animal models. The myogenic response, a protective mechanism for the microcirculation, may face disruptions during ageing. Dysregulation of calcium entry channels (T-type, L-type, TRP channels), dysfunction in intracellular calcium storage and extrusion mechanisms, altered expression of potassium channels, and a change in smooth muscle calcium sensitization may contribute to age-related dysregulation of myogenic tone. Flow-mediated vasodilatation, a hallmark of endothelial function, is compromised in ageing. This result of endothelial dysfunction is related to oxidative stress, lower nitric oxide bioavailability and a low-grade inflammatory response, further exacerbating vascular dysfunction. Resistance artery remodeling in ageing emerges as a hypertrophic response of the vessel wall, often seen in conjunction with outward remodeling (in normotension), but can also present as inward hypertrophic remodeling (in hypertension). The remodeling process involves oxidative stress, inflammation, reorganization of extracellular matrix fiber proteins and actin cytoskeletal components. Reactive oxygen species (ROS) signaling and chronic low-grade inflammation, often referred to as "inflammaging”, play substantial roles in age-related vascular dysfunction. Due to its role in regulation of vascular tone as well as structural proteins, the RhoA/Rho-kinase pathway becomes a new target in age-related vascular dysfunction and associated diseases. Understanding the intricate interplay of these factors is crucial for developing targeted interventions to mitigate the consequences of ageing on resistance arteries and enhance overall vascular health.

Introduction: Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Objectives: To confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and study their correlation with various disease parameters. Methods: Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients’ data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Correlations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. Results: AGEs levels in SLE patients were significantly higher than in HC (p<0.001). We found statistically significant positive correlation with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL6 and oral ulcers. We also found a negative statistically significant correlation with current positivity of anti-nuclear and anti-Ro60 antibodies. Conclusions: AGEs seem to have a role in LES pathophysiology, becoming a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher AGEs levels.

The prevalence and incidence of obesity and the comorbidities linked to it are increasing in the world population. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems, as well as regulate the expression of multiple genes and, therefore, proteins involved in starvation-satiety processes, activation of brown adipose tissue, increased lipolysis, decreased lipogenesis, and inflammation, beneficial changes in metabolism and improved insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of the bioactive compound.

Atrial fibrillation (AF), a complex cardiac arrhythmia, necessitates a shift in management paradigms, emphasizing an integrative approach that incorporates lifestyle modifications. Investigations into the role of interleukins and inflammatory mediators are underway, exploring their potential as diagnostic markers and predictors of cardiovascular events in AF. Despite the identification of biomarkers related to cardiac remodeling, their predictive ability for post-cardioversion outcomes remains controversial. Computational models are being developed to understand proarrhythmic contributions and identify anti-AF targets. Addressing the rising global incidence of AF, linked to stroke and heart failure, presents a critical health challenge. As risk factors like obesity prevail, AF becomes a pervasive public health concern, expected to double in prevalence over the next 50 years. The impact on mortality and morbidity, especially through hospitalizations, underscores the need for early detection and effective clinical management. Identifying individuals at increased AF risk becomes crucial for screening and prevention strategies. Lifestyle modifications, including weight management and physical activity, emerge as influential factors in AF management, offering the potential to alleviate symptoms and modify disease progression. The paper concludes by emphasizing the need for safer antiarrhythmic therapies based on AF mechanisms, promising improvement in global AF management. The multifaceted nature of AF etiology requires a broader perspective beyond traditional medical interventions, acknowledging the importance of integrated care to address this significant public health challenge.

Abstract Background: Metabolic syndrome (MetS) is a complex disorder characterized by insulin resistance (IR), central obesity, atherogenic dyslipidemia and higher glucose levels. It increases the risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), imposing an economic burden on the healthcare system. However, the historical origins of MetS as well as the development and evolution of its definitions have not been conclusively documented in the literature. Aim: This study seeks to enhance the understanding of the developmental trends of MetS during the preceding two decades, placing particular emphasis on the definition, diagnosis and prevalence. Methods: An extensive search was performed from 1920 to 2023 across prominent scientific research engines, including Scopus, PubMed, MDPI, and others. Results: Despite advancements, many aspects of MetS remain inadequately understood. As the understanding of the nature and pathophysiology of MetS progresses, the development and refinement of its diagnostic criteria, and assessment and treatment guidelines will continue. Additionally, there exists significant variation in the global prevalence of metabolic syndrome, ranging from 14 to 39%. This prevalence is projected to increase due to the adoption of less healthy dietary patterns and sedentary lifestyles. The observed disparities in metabolic syndrome prevalence can be attributed to multiple factors, including demographic characteristics. Furthermore, the lack of a standardized definition across studies also contributes to the variation in reported prevalence rates. Conclusion: Further studies focusing on the standardization of the MetS definition across different research are crucial. The establishment of consistent criteria would enhance the reliability and validity of research findings, enabling more meaningful comparisons and interpretations.

Hypertension is one of the most common primary cardiometabolic diseases and is a major contributor to cardiac mortality and morbidity. Furthermore, cardiac risk factors such as obesity and sedentary lifestyle are often seen in hypertensive patients. Regular exercise acts against these risk factors and improves the overall health of an individual. High-intensity interval training appears to do so in a more efficient way. We used a systematic literature review (SLR) approach to provide an overview of the present literature highlighting the cardiovascular advantages of HIIT in hypertensive individuals. We reviewed 4004 articles from reputable journals published between 2013 and August 14, 2023, focusing on 7 selected papers for in-depth analysis. This systematic review revealed the protective effects of HIIT against cardiac complications in hypertension. All the reviewed articles showed a decrease in blood pressure and many other risk variables of cardiovascular diseases. However, guidelines for this exercise are needed for maximum benefits. Therefore, further research on HIIT is necessary to fully harness its potential.

Background. IgA nephropathy (IgAN) is associated with chronic inflammation. Platelet-related parameters, such as platelet (PLT) count, platelet-to-albumin ratio (PAR) and platelet-to-lymphocyte ratio (PLR), were examined as potential prognostic indicators for renal and cardiovascular (CV) outcomes in IgAN. Methods. 150 IgAN patients were devided into two groups based on the cut-off value of PAR. All-cause mortality, major CV events and end-stage renal disease were the primary combined endpoints. Secondary endpoints, such as CV or renal endpoints, were also analyzed separately. Results. The patient’s mean age was 43.7 ± 13.5 years, and the follow-up time was 124 ± 67 months. The K-M curve showed that PLR, PAR and PLT were strongly associated with primary combined (p = 0.002, p = 0.004, p = 0.001) and renal outcomes (p < 0.001, p < 0.001, p < 0.001), but not with CV outcomes in IgAN. However, when combined with left ventricular hypertrophy (LVH) or metabolic syndrome (MetS) PAR was found to be a significant predictor of both primary (p < 0.001, p < 0.001) and secondary outcomes (p = 0.001 and p = 0.038; p = 0.001 and p = 0.015). Additionally, PLR correlated with microalbuminuria (r = -0.165, p = 0.033) and LVH (r = -0.178, p = 0.025), while PLT correlated with eGFR (r = 0.158, p = 0.040). Conclusion. Elevated PAR and PLR may predict progression to end-stage kidney disease, but in combination with LVH and MetS, they showed CV events also in IgAN. The determination of PAR and PLR can be useful and cost-effective parameters for assessing both cardiovascular and renal risks in CKD.

It is unknown whether postprandial plasma glucose measured from blood taken between 4 and 7.9 h (PPG4-7.9h) is associated with mortality from hypertension, diabetes, or cardiovascular disease (CVD). This study aimed to investigate these associations in 4,896 US adults who attended the third National Health and Nutrition Examination Survey. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of PPG4-7.9h for mortality. This cohort was followed up for 106,300 person-years (mean follow-up, 21.7 years). A 1-natural-log-unit increase in PPG4-7.9h was associated with a higher risk of mortality from hypertension (HR, 3.50; 95% CI, 2.34-5.24), diabetes (HR, 11.7; 95% CI, 6.85-20.0), and CVD (HR, 2.76; 95% CI, 2.08-3.68) after adjustment for all the tested confounders except hemoglobin A1c (HbA1c). After further adjustment for HbA1c, PPG4-7.9h remained positively associated with mortality from hypertension (HR, 2.15; 95% CI, 1.13-4.08) and CVD (HR, 1.62; 95% CI, 1.05-2.51), but was no longer associated with diabetes mortality. Subgroup analyses showed that similar results were obtained in the sub-cohort of participants without a prior diagnosis of myocardial infarction or stroke. In conclusion, PPG4-7.9h predicts mortality from hypertension and CVD independent of HbA1c.

Clopidogrel, a prescription drug to reduce ischemic events in cardiovascular patients, has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients as a predictive risk biomarker of poor responders and disease severity in this population. Thirty-six patients on clopidogrel (cases; divided into poor and normal responders) were enrolled along with 11 cardiovascular patients with no clopidogrel indications (positive control) and 13 healthy volunteers (negative control). Residual on-treatment platelet function (PRU), PON1 abundance by western blotting, and PON1 activity by enzymatic assays were measured. PON1 genotyping and computational haplotype phasing were performed for two genetic loci (rs662 and rs854560). No statistical differences in mean relative PON1 abundance were found among the groups (p&gt; 0.05). However, a significantly lower enzymatic activity was found in poor responders (10.57 6.79 µU/mL) when compared to controls (22.66 8.30 µU/mL and 22.21 9.66 µU/mL; p= 0.004). PON1 activity among carriers of the most prevalent PON1 haplotype (AA|AA) was significantly lower than in wild-types (7.90 µU/mL vs 22.03 µU/mL; p= 0.005). Our findings suggested that PON1 is a potential biomarker of cardiovascular disease severity in Caribbean Hispanics.

Novel genetic risk markers have helped to advance the field of cardiovascular epidemiology and refine our current understanding and risk stratification paradigms. Discovery and analysis of variants can help to tailor prognostication and management. However, populations underrepresented in cardiovascular epidemiology and cardiogenetics research may experience inequities in care if prediction tools are not applicable to them clinically. Therefore, the purpose of this article is to outline the barriers that underrepresented populations can face in participating in genetics research, describe current efforts to diversify cardiogenetics research, and outline strategies that researchers in cardiovascular epidemiology can implement to include underrepresented populations. Mistrust, a lack of diverse research teams, improper use of sensitive biodata, and constraints of genetic analyses are all barriers for including diverse populations in genetics studies. Current work is beginning to address the paucity of ethnically diverse genetics research and has already begun to shed light on the potential benefits of including underrepresented and diverse populations. Reducing barriers for individuals, utilizing community-driven research processes, adopting novel recruitment strategies, and pushing for organizational support for diverse genetics research are key steps that clinicians and researchers can take to develop equitable risk stratification tools and improve patient care.

Myotonic dystrophy is a hereditary disorder with systemic involvement. The Italian Neuro-Cardiology Network (INCN-RNC) is a unique collaborative experience involving neurology units combined with cardio-arrhythmology units. The INCN facilitates the creation of integrated neuro-cardiac teams in Neuromuscular Disease Centers for the management of cardiovascular involvement in the treatment of MD1.

Background and Aim: Serum alkaline phosphatase (ALP) activity has been associated with ath-erosclerotic cardiovascular disease (ASCVD). We aimed to investigate the association of ALP with ASCVD in patients with dyslipidemia. Methods: Retrospective cohort study including consecutive adults with dyslipidemia followed-up for ≥3 years (from 1999 to 2022) in the outpatient Lipid Clinic of Ioannina University General Hospital, Greece. The primary endpoint was the association between baseline ALP and incident ASCVD after adjusting for traditional risk factors (i.e. sex, age, hypertension, diabetes, smoking, dyslipidemia), baseline ASCVD and lipid-lowering treatment. ALP levels were stratified by ter-tiles as follows: low:<67 U/L, middle: 67-79 U/L, high: ≥79 U/L. Results: Overall, 1178 subjects were included; 44% were males and their median age was 57 years (range 49-65). During a 6-year median follow-up (interquartile range IQR: 4-9), 78 new ASCVD events (6.6%) occurred. A statistically significant association between baseline ALP levels and incident ASCVD was demonstrated (Odds Ratio, OR: 6.99, 95% Confidence Interval, CI: 2.29-21.03, p=0.001). Subjects in the highest ALP tertile had the highest odds for ASCVD when compared with those in the lowest tertile (OR: 2.35; 95% CI: 1.24-4.41, p=0.008). Conclusions: The present study demonstrated that ALP is associated with ASCVD development in patients with dyslipidemia.

Endothelial function is regulated by a myriad of complex pathways. In our previous study, the expression of miR-378a-3p was shown to inhibit endothelial autophagy and impair endothelial function. However, the mechanism underlying the effect of miR-378a-3p in endothelial cells remains to be elucidated. By employing an in silico approach, Protein Disulfide Isomerase 4 (PDIA-4) was identified as a target of miR-378-3p; however, its’ role in endothelial cells is not known. We here report that endothelial cell-specific loss of PDIA-4 leads to impaired autophagic flux accompanied by loss of endothelial function and apoptosis. Endothelial cell-specific loss of PDIA-4 also induced marked changes in endothelial cells’ architecture, accompanied with the loss of endothelial markers and gain of mesenchymal markers consistent with endothelial-to-mesenchymal transition (EndMT). Loss of PDIA-4 activates TGF-signaling, and inhibition of TGF-signaling inhibits EndMT in PDIA-4 silenced endothelial cells in vitro. Our findings help elucidate the role of PDIA-4 in endothelial autophagy and endothelial function and provide a potential target to modulate and/or limit autophagy and EndMT in (patho-)physiological conditions.

Cardiovascular comorbidity is a common companion of psoriasis and psoriatic arthritis (PsA). Recently, a significant link has been found between the HLA-Cw6 allele and a better cardiometabolic profile in these patients. We aimed to check this finding in our setting. Cross-sectional observational study (n: 572 psoriasis patients, 30% with PsA). Different study variables were collected in detail, as well as classic cardiometabolic risk factors. The distribution of the HLA-Cw6 allele and the IFIH1/MDA5 gene variants previously linked to disease risk was determined in the study cohort and stratified according to the cardiometabolic comorbidity. Linear and logistic regression models were constructed to analyze these associations. The study cohort included 309 men and 263 women, mean age 46.7 years (SD 14.5), mean disease duration 19.4 years (SD 14.8). We confirmed the known association between HLA-Cw6 and type I psoriasis (familial, severe, early onset). Psoriasis severity (OR: 2.14), female sex (OR: 1.63), and the IFIH1/MDA5 rs1990760 TT genotype (OR: 1.62) were significantly related to PsA, while HLA-Cw6 resulted protective (OR: 0.65). HLA-Cw6 carriers showed lower waist perimeter, lower BMI, and lower risk of both hypertension (OR: 0.52, p<0.001) and diabetes (OR: 0.36, p<0.001), but these findings were no longer apparent upon adjusted regression models. No IFIH1/MDA5 gene variant was associated with any cardiometabolic risk factor. The influence of HLA-Cw6 on the cardiometabolic risk profile of psoriatic patients seems to be explained by other factors (age, sex, duration of the disease or arthritis) and not by this biomarker itself.

New technologies have resulted in a better understanding of blood and lymphatic vascular heterogeneity at the cellular and molecular levels. Meanwhile, we still need to learn more about the heterogeneity of the cardiovascular and lymphatic systems between different species at the anatomical and functional levels. Even the deceptively simple question of the functions of fish lymphatic vessels has yet to be conclusively answered. The most common interpretation assumes a similar dual setup of the vasculature in zebrafish and mammals: on the one hand, there is the cardiovascular, circulatory system, and on the other hand, the lymphatic vascular system, in which the unidirectional flow is derived from surplus interstitial fluid and returned into the cardiovascular system. A competing interpretation questions the identity of the lymphatic vessels in fish as at least some of them receive their flow from arteries via specialised anastomoses, neither requiring an interstitial source for the lymphatic flow nor stipulating unidirectionality. In this alternative view, the “fish lymphatics” are a specialised subcompartment of the cardiovascular system, called the “secondary vascular system” (SVS). Many of the contradictions found in the literature appear to stem from the fact that the SVS develops in part or its entirety from an embryonic lymphatic vascular system by transdifferentiation. Future research needs to establish the extent of embryonic transdifferentiation of lymphatics into SVS blood vessels. Similarly, more insight is needed into the molecular regulation of vascular development in fish. Most fish do feature more than the five VEGF genes and three VEGF receptor genes that we know from mice or humans, and the relative tolerance of fish to whole genome and gene duplications could underlie the evolutionary diversification of the vasculature. This review discusses the key elements of the fish lymphatics versus the SVS and attempts to draw a picture coherent with the existing data, including the phylogenetic knowledge.

Arrhythmogenic cardiomyopathy is a primary genetic disease caused by mutations of the desmosome genes. Ever since the introduction of new imaging criteria, like cardiovascular magnetic resonance, the diagnosis of arrhythmogenic cardiomyopathy is more challenging as left ventricular or biventricular variants may cause resemblance with other cardiomyopathies or myocarditis. Not only this, but they may also share an acute phase that might determine even more confusion and misdiagnosis which can influence prognosis and outcome. In this case report we present a 31-year-old patient with multiple clinical pictures: acute chest pain, new onset of heart failure and arrhythmia symptoms which determined a dynamic change in clinical diagnosis and management, ultimately taking into consideration arrhythmogenic cardiomyopathy. Through the article we try to emerge and explain common pathophysiological pathways shared by arrhythmogenic cardiomyopathy and other clinical entities with a special focus on inflammation. The final question remains: “If there is more than one heart disorder that eventually will lead to the same clinical picture, one could not but wonder if arrhythmogenic cardiomyopathy is rather a syndrome than a specific condition?”

Cornelian cherry (Cornus mas L.) fruits, abundant in iridoids and anthocyanins, are natural products with proven beneficial impact on the functions of the cardiovascular system and the liver. The aim of this study is to stipulate and compare whether and to what extent two different doses of resin-purified cornelian cherry extract (10 mg/kg b.w. or 50 mg/kg b.w.) applied in a cholesterol-rich diet rabbit model affect the levels of ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, CCAAT/enhancer binding protein α, sterol regulatory ele-ment-binding protein 1c, fatty acid synthase, endothelial lipase, carnitine palmitoyltransferase 1A, and adiponectin receptor 2 in liver tissue; lipoprotein lipase, visceral adipose tissue-derived serine protease inhibitor, and retinol-binding protein 4 in visceral adipose tissue; resistive index of com-mon carotid arteries and aortas, and histopathological changes in CCAs. Obtained outcomes are referred to the results of our previous works. Moreover, our study, to our knowledge, test the in-fluence of Cornus derivative on CPT1A, AdipoR2, RBP4, LIPG, and vaspin for the first time, with a relevant outcome for the first three. Oral administration of the cornelian cherry extract decreased the SREBP-1c and C/EBPα in both doses. The dose of 10 mg/kg b.w. increased ABCA1 and de-creased FAS, CPT1A, and RBP4, and the dose of 50 mg/kg b.w. enhanced ABCG1 and AdipoR2. Mitigation in atheromatous changes in rabbits’ CCAs was also observed. The beneficial results confirm that cornelian cherry fruit extract may constitute a potentially effective product in the prevention and treatment of obesity-related disorders.

Petroselinum crispum (Mill.) Fuss (Apiaceae), popularly known as parsley, is a ubiquitous aromatic herb used for culinary and medicinal purposes worldwide. Besides the richness in nutrients, sev-eral bioactive secondary metabolites, especially the flavone apigenin and its glycosides, have been described in the species. Parsley has already been shown to have several health-promoting activi-ties, such as antithrombotic, antihypertensive, and hypolipidemic. The multiple studies conducted in animal models so far suggest the species is a potential source of cardioprotective agents. This review provides up to date information and perspectives on the potential of parsley and its bioac-tive compounds for the development of nutraceutical products and drugs for the promotion of cardiovascular health. It includes not only a discussion on reported bioactivities, but also the knowledge of supplements and food additives developed as innovative parsley-based products.

Background: COVID-19 was initially identified as a respiratory system disorder, but it has been discovered to interact with and influence the cardiovascular system. COVID-19-associated cardiovascular (CV) complications are common, resulting in high acute phase mortality and a large number of morbidities in the chronic phase, thus severely impacting patients' quality of life and health outcomes. Nevertheless, clinical, cellular, and molecular biological factors underlying the pathophysiology of cardiovascular complications associated with COVID-19 are poorly understood. Objective: This review investigates putative underlying clinical factors as well as cellular and molecular biological mechanisms by which COVID-19 leads to acute CV complications, including state-of-the-art genomic sequencing-based findings, assessing the long-term CV consequences of COVID-19, and aiming to shed light on developing strategies for differential diagnosis, risk prognostic stratification, prevention, and clinical management of CV sequlea in COVID-19 patients. Methods: For this purpose, a through review of literature and published data was carried out from first report of COVID-19 till October 2023 to find out a comprehensive account of clinical, cellular and molecular genetic factors underlying COVID-19-associated cardiovascular diseases. Results: We found that the relationship between COVID-19 and CV risk is complex and multifaceted. In addition to acute COVID-19 detertriuos effects, COVID-19 survivors may experience long-term CV effects. We provide a detailed account of the involvement of a large number of genomic alterations, microRNAs, and novel viral as well as host proteins in CVDs associated with COVID-19, which has helped identify some novel drug targets to treat COVID-19-related cardiovascular complications. Conclusions: The relationship between COVID-19 and CV risk is complex and multifaceted. While COVID-19 primarily affects the respiratory system, it can also significantly affect CV health. as compared to classical cardiovascular diseases, there are new clinical, cellular and molecular biological factors in CVDs related to COVID-19, that need specific diagnostic assays, prognostic stratification and treatment modules. Therefore, specail care is must taken to treat cardiovascular diseases associated with COVID-19.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent, debilitating and still enigmatic disease. There is a broad overlap in the symptomatology of ME/CFS and the Post-COVID Syndrome (PCS). A fraction of the PCS patients develops the full clinical picture of ME/CFS. New observations in microvessels and blood from patients suffering from PCS have appeared and include microclots and malformed pathological blood cells. Capillary blood flow is impaired not only by pathological blood components but also by prothrombotic changes in the vascular wall, endothelial dysfunction, and expression of adhesion molecules in the capillaries. These disturbances can finally cause a low capillary flow and even capillary stasis. A low cardiac stroke volume due to hypovolemia and the inability of the capacitance vessels to adequately constrict to deliver the necessary cardiac preload generate an unfavorable low precapillary perfusion pressure. Furthermore, a predominance of vasoconstrictor over vasodilator influences exists, in which sympathetic hyperactivity and endothelial dysfunction play a strong role, causing constriction of resistance vessels and of precapillary sphincters which leads to a fall in capillary pressure behind the sphincters. The interaction of these two precapillary cardiovascular mechanisms causing a low capillary perfusion pressure is hemodynamically highly unfavorable in the presence of a primary capillary stasis already caused by the pathological blood components and their interaction with the capillary wall, to severely impair organ perfusion. The detrimental coincidence of the microcirculatory with the precapillary cardiovascular disturbances may constitute the key disturbance of the Post-COVID-19 syndrome and finally lead to ME/CFS in pre-disposed patients because the interaction causes a particular kind of perfusion disturbance - capillary ischemia-reperfusion - which has a high potential of causing mitochondrial dysfunction by inducing sodium- and calcium-overload in skeletal muscles. The latter in turns worsens the vascular situation by the generation of reactive oxygen species to close a vicious cycle from which the patient can hardly escape.

Cerebrovascular diseases represent a significant mortality rate worldwide and constitute a major public health and economic challenge. Many African countries such as Cape Verde are going through an epidemiological transition from communicable to non-communicable diseases, demographic and socioeconomic changes and facing an increase in cerebrocardiovascular diseases associated with increased cardiovascular risk. The present study aimed to identify the prevalence of risk factors that predispose to cardiovascular diseases in adult individuals residing on the island of Santiago. Cross-sectional population-based study with individuals over 18 years of age, of both sexes. Data collection took place in October and November 2021, in all municipalities on the island of Santiago. Individuals with Cape Verdean nationality who stayed abroad for more than one year and who arrived on the island of Santiago less than 30 days ago and individuals with any type of disability that could prevent them from participating in the study were excluded from the study. The sample size was calculated based on the projection of the population of the island of Santiago for the year 2021, according to the appropriate epidemiological model. Sociodemographic data were obtained through the application of a questionnaire containing age, sex, race, weight, height, risk factors (presence of diabetes, dyslipidemia, heredity, physical activity, smoking habits, history of cerebrovascular events, control of weight and blood pressure). RESULTS: Study sample is predominantly female (54.8%), the age group with the largest number was 18-27 years (21%); 42.2% with BMI ≥ 25 kg/m2; 65.1% sedentary; Smoking 7.3% and alcoholism 14.4%; 6.5% with diagnosed heart disease; 19.9% with close family members with cardiac pathology; 2.7% had a stroke, 0.1% had a transient ischemic attack; 0.5% acute myocardial infarction; 23.5% had the periodic habit of assessing blood pressure; 32.6% hypertensive; 4.5% with diabetics. CONCLUSIONS: The study showed that there is a high prevalence of cerebrovascular risk factors on Santiago Island, especially in females. Smoking and alcoholism showed a relationship with males. BMI, physical inactivity, diabetes and dyslipidemia were shown to be related to sex. Hypertension and Diabetes revealed a significant relationship with age group. Alcoholism, smoking, hypercholesterolemia and hypertriglyceridemia maintained a significant relationship with the municipalities.

Topological data analysis (TDA) is a recent approach for analyzing and interpreting complex data sets, based on ideas a branch of mathematics called algebraic topology. TDA has proven useful to disentangle non-trivial data structure in a broad range of data analytics problems including the study of cardiovascular signals. This review aims to provide an overview of the application of TDA to cardiovascular signals and its potential to enhance the understanding of cardiovascular diseases and their treatment. We first introduce the concept of TDA and its key techniques, including persistent homology, Mapper, and multidimensional scaling. We then discuss the use of TDA in analyzing various cardiovascular signals, including electrocardiography, photoplethysmography, and arterial stiffness. We also discuss the potential of TDA to improve the diagnosis and prognosis of cardiovascular diseases, as well as its limitations and challenges. Finally, we outline future directions for the use of TDA in cardiovascular signal analysis and its potential impact on clinical practice. Overall, TDA has shown great promise as a powerful tool for the analysis of complex cardiovascular signals and may offer significant insights into the understanding and management of cardiovascular diseases.

Cardiovascular disease (CVD) accounts for nearly one-third of all global fatalities, establishing itself as a leading cause of death. To address this pressing issue, there is a growing demand for improved diagnostic methods and secure, non-invasive imaging techniques that can deliver precise insights into the progression of CVD. The success of personalized therapy for CVD depends on a couple of critical factors: accurate diagnosis and early detection. Therapeutic options for conditions like CVD, which develop over several decades, are highly specific to the individual's condition and the stage of the disease. In the field of biomedicine, nanotechnology has become increasingly prominent as a tool with diverse applications, including diagnostics, biosensing, and drug delivery. This review article offers an in-depth look at the most recent developments in the utilization of nanotechnology for detecting and managing prevalent cardiovascular diseases, providing valuable insights into this crucial area of healthcare research.

We conducted a monocentric observational study aimed at evaluating the pharmaceutical service provided at a Community Pharmacy (C.PH.) during pandemia in our Puglia Region in the period from 29.12.2021 to 12.03.2022 on 550 patients of various ages, sexes, and with concomitant diseases. We collected anamnestic data and any post-vaccination adverse reactions. Interviews with the integrated EQ5 method on evaluating the quality of the service offered and any therapy preference were also performed. As expected, the vaccines were reactogenic after the first dose in the patients with mild-moderate reactions with younger age and female gender as risk factors. Immune-allergic reactions of moderate-severe degree were observed in adult females. In the elderly, the vaccination procedure was well tolerated. Comirnaty showed a favorable O.R.<;1 vs other vaccines. No myocarditis and thromboembolic events in our population were observed. All treatments in May 2023 were correlated with a viremia trend, Paxlovid was prescribed in 3% of the patients in our center and in 1.46% in the Puglia Region with no effects in the hospitalization. It was distributed/dispensed by a novel on behalf of third parties distribution/dispensation (D.P.C.) protocol by the C.PH. The C.PH. resulted in a safe vaccination center providing appropriate patient inclusion during vaccination.

This review is focused on synephrine, the principal phytochemical found in bitter orange and other medicinal plants, and widely used as a dietary supplement for weight loss/body fat reduction. We examine different aspects of synephrine biology, delving into its established and potential molecular targets, as well as its mechanisms of action. We present an overview of the origin, chemical composition, receptors, and pharmacological properties of synephrine, including its anti-inflammatory and anti-cancer activity in various in vitro and animal models. Additionally, we conduct a comparative analysis of the molecular targets and effects of synephrine with those of its metabolite, selective glucocorticoid receptor agonist (SEGRA) Compound A (CpdA), which shares a similar chemical structure with synephrine. SEGRA, including CpdA, have been extensively studied as glucocorticoid receptor activators that have a better benefit/risk profile than glucocorticoids due to the reduced adverse effects. We discuss the potential of synephrine usage as a template for the synthesis of new generation of non-steroidal SEGRA. The review also provides insights into the safe pharmacological profile of synephrine.

Background and Objectives: The risk of developing cardiovascular diseases (CVD) in patients suffering from rheumatoid arthritis (RA) is two times higher compared to the general population. The objective of this retrospective study was to determine the type of cardiovascular complications that can appear in men vs. women with rheumatoid arth-ritis. Early diagnosis and initiation of therapeutic measures to reduce the progression rate of rheumatoid arthritis, while also maintaining an active lifestyle, are the most important problems in young patients. Materials and Methods: We included a number of 200 pa-tients, divided in 2 groups according to gender (124 women and 76 men) with rheumatoid arthritis, presenting various stages of disease concomitant with cardiovascular complications. We assessed traditional and non-traditional risk factors, electrocardio-graphic and echocardiographic findings in both groups. Results: All patients presented an atherogenic coefficient over two, indicating a significant risk of atherogenesis. Men had elevated levels of total cholesterol compared with women (≥ 200 mg/dL; 77.6% - men vs. 25.8% - women, p<0.001). The participants presented cardiac arrhythmias, especially in the active stage of RA. Women had an increased risk of atrial fibrillation by 2.308 times compared with men (p=0.020). One of the most important complications in young women was pulmonary arterial hypertension (p=0.007). Conclusion: However, in daily clinical practice, the screening for RA is poorly done. Thus, patients are often undiagnosed, while the risk factors are not assessed and RA patients continue to present an increased risk of developing CVD.

Magnesium alloy stents have been extensively studied in the field of biodegradable metal stents due to their exceptional biocompatibility, biodegradability and excellent biomechanical properties. Nevertheless, the specific in vivo service environment causes magnesium alloy stents to degrade rapidly and fail to provide sufficient support for certain time. This paper presents an overview of the development history and protection strategies for magnesium alloy stents. Alloying, optimizing stent structure and preparing protective coating have improved the corrosion resistance of magnesium alloy stents. Based on the corrosion mechanism of magnesium alloy stents, as well as their deformation during use and environmental characteristics, we present some novel solution strategies aiming at reducing the corrosion rate of magnesium alloys and enhancing the comprehensive performance of magnesium alloy stents. These strategies include adapting protective coatings for the deformation of the stents, preparing rapid endothelialization coatings to enhance the service environment of the stent, and constructing coatings with self-healing functions. It is hoped that this review can help to understand the development of magnesium alloy cardiovascular stents and solve the problems related to magnesium alloy stents in clinical applications at the early implantation stage.

We explored how dietary behaviors (sucrose, fructose, sodium, and potassium consumption) and endured psychological stress in young adult males and females impact the vascular aging index (VAI) and CVD risk by mid-life. Data were obtained from the Coronary Artery Risk Development in Young Adults Study, an ongoing longitudinal study. Included participants (n=2,656) had un-dergone carotid artery ultrasound at year 20 allowing VAIs to be calculated. Demographics, di-etary data and depression scores were obtained at baseline and year 20. Regression analyses were used to assess the predictors of VAI. Cox regression analyses were conducted to assess the risk of CVD, stroke and all-cause mortality. Predictors of vascular aging were found to be sex-specific. In females, CES-D scores at baseline were positively associated with VAI (B-weight=0.063, p=0.015). In males, sodium intake at year 20 positively predicted VAI (B-weight=0.145, p=0.003) and potassium intake inversely predicted VAI (B-weight=-0.160, p<0.001). BMI significantly predicted CVD, stroke, and death. Fructose consumption at year 20 was a significant predictor of CVD risk while having high blood pressure at baseline was signif-icantly associated with stroke risk. Our findings support the promotion of nutrient- specific be-havior changes to prevent vascular aging in early adulthood and CVD risk in mid-life.

SARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD patients at the time of hospital admission are still missing. Here, we investigated whether this prediction is achievable by prospectively analysing the blood immunophenotype of 94 participants, including 20 uninfected and 37 acutely SARS-CoV-2-infected CVD patients and 37 healthy donors, using a 36-colour spectral flow cytometry panel. Unsupervised data analysis revealed little differences between healthy donors and CVD patients, whereas the distribution of the cell populations changed dramatically in SARS-CoV-2-infected CVD patients. The latter had more mature NK cells, activated monocyte subsets, central memory CD4+ T cells, and plasmablasts but fewer dendritic cells, CD16+ monocytes, innate lymphoid cells, and CD8+ T cell subsets. Moreover, we identified an immune signature characterised by mucosal-associated invariant T (MAIT) cells, intermediate effector CD8+ T cells, and natural killer T (NKT) cells that is predictive for CVD patients with a severe course of COVID-19. Thus, intensified immunophenotype analyses can help identify patients at risk of severe COVID-19 at hospital admission, improving clinical outcomes through specific treatment.

The treatment of critically ill patients remains an evolving and controversial issue. Mechanical circulatory support through a percutaneous approach for the management of cardiogenic shock has taken place in recent years. The combined use of IABP and Impella 2.5 device may have a role to play for this group of patients. A simulation approach may help with a quantitative as-sessment of the achievable degree of assistance. In this paper, we analyse the interaction be-tween Impella 2.5 pump applied as LVAD and IABP using the numerical simulator of the cardi-ovascular system developed in our laboratory. Starting with pathological conditions reproduced using literature data, the simulations were performed setting different rotational speeds for the LVAD and driving the IABP in full mode (1:1) or partial mode (1:2, 1:3 and 1:4). The effects in-duced by drug administration during the assistance were simulated too. The haemodynamic pa-rameters under investigation were: mean aortic pressure, systolic and diastolic aortic pressure, mean pulmonary arterial pressure, mean left and right atrial pressure, cardiac output, cardiac index, left and right ventricular end-systolic volume, left ventricular end-diastolic volume and mean coronary blood flow. The energetic variables considered in the study were: left and right ventricular external work and left and right atrial pressure-volume area. The outcome of our simulations shows that the combined use of IABP and Impella 2.5 achieves adequate support in the acute phase of cardiogenic shock compared to each standalone device. This would allow fur-ther stabilisation and transfer to a transplant centre should escalation of treatment be required.

Numerous studies were published suggesting that troponin level is related to adverse outcomes in chronic cardiac and non-cardiac conditions. Our study investigated whether troponin levels gathered from an unselected blood sample taken during outpatient care are associated with adverse outcomes in a population with stable coronary artery disease. In a cohort of 949 patients with stable coronary artery disease, average age of 67.5 ± 9.5 years, 69.5% male, 52.1% diabetics, 51.6% with previous myocardial infarction, 57.9% with triple-vessel disease, 21.7% of patients encountered new events during an average period of monitoring of 2.07 ± 0.81 years. Troponin I/99th percentile categorized into tertiles emerged as an independent predictor of death and combined events risk (hazard ratio: 2.02 (1.13-3.60), p=0.017; 2.30 (1.37-3.88, p=0.002, respectively). A troponin ratio > 0.24 was able to identify 53.3% of patients at risk of death and heart failure hospitalization. In patients with stable coronary artery disease and adherent to treatment, troponin level is independently associated with death and heart failure hospitalization in a medium-term follow up.

In this observational study, we compared continuous physiological signals during an active stand test in adults aged 50 years and over, characterized as frail by three different criteria, using data from The Irish Longitudinal Study on Ageing (TILDA). Four independent groups were identified: those characterized as frail only by one of the frailty tools used (the physical Frailty Phenotype (FP), the 32-item Frailty Index (FI), or the Clinical Frailty Scale (CFS) classification tree), and a fourth group where participants were not characterized as frail by any of these tools. Continuous non-invasive physiological signals were collected during an active stand test: systolic (sBP) and diastolic (dBP) blood pressure, as well as heart rate (HR), using digital artery photoplethysmography. Additionally, frontal lobe cerebral oxygenation (Oxy), deoxygenation (Deoxy), and tissue saturation index (TSI) were also non-invasively measured using near-infrared spectroscopy (NIRS). The signals were visualized across frailty groups and statistically compared using one-dimensional statistical parametric mapping (SPM). A total of 1,124 participants (mean age 63.5 years, 50.2% women) were included: 23 were characterized as frail only by FP, 97 by FI, 38 by CFS, and 966 by none of these criteria. SPM analyses revealed that only the group characterized as frail by FI had significantly different signals (p<0.05) compared to the non-frail group. Specifically, they exhibited a lesser increase in HR between 5-15 seconds post-stand and larger deficits in sBP and dBP between 15-40 seconds post-stand, and possibly a lower Delta TSI at 20 seconds post-stand. In this comparison, the FI proved more adept at capturing distinct physiological responses to standing, likely due to its direct inclusion of cardiovascular morbidities in its definition.

Cardiac hypertrophy typically follows myocardial damage, a process known to involve members of the Krüppel-Like Factors (KLFs) which have pro-hypertrophic and anti-hypertrophic roles. Our study delved into the molecular mechanisms underlying KLFs-cardiac hypertrophy interplay post myocardial infraction. We induced myocardial dam-age in rats using isoproterenol. Total RNA was extracted from the left ventricle and Quantitative Real Time RT-PCR was conducted to assess the expression of KLFs, cardiac commitment genes, inflammatory markers, and certain conduction-related genes. We devel-oped a computational approach to construct a proteomic network centered on KLFs. Initial results revealed early expression (2-3 days post-induction) of KLF3, KLF4 and KLF6, followed by the subsequent expression of KLF11 and KLF15 (5-8 days after induction). In the maturation stage, KLF12 and KLF13 regulators were found upregulated. IL-6 was gradually found to be upregulated through. Interaction analysis revealed KLF3, KLF8 and KLF12 interacted with cardiac electrical functions. RT-PCR confirmed up-regulation in cardiac genes linked to electrical function and scar maturation. Our findings underscore the central role of KLFs during the modulation of the cardiac hypertrophic response. Dysregulation of KLF expression resulted in damaged myocardium, participating in the progression of abnormal hypertrophy, highlighting their potential as therapeutic targets for heart diseases.

(1) Background: Prevention of acute cardiovascular events in patients with cardiovascular diseases (CVDs) requires promoting health-protective behaviors (e.g., physical activity) and preventing health-compromising behaviors (sitting). Digital health interventions provide much potential. Based on multiple behavioral change theory, an intervention (reCardial app) was evaluated, and the following hypotheses were tested: H1: Health behaviors (physical activity, sitting) and disease self-management (self-care maintenance, self-care confidence) are closely interrelated. H2: Change in health behaviors and disease self-management indicators over time is more pronounced in reCardial app-users. H3: In the intervention group, changes in systolic and diastolic blood pressure indicate a positive trajectory. (2) Methods: A study with the design of a randomized controlled trial over 12 weeks was conducted. 40 CVD-patients were randomized equally to the Intervention Group (35% women; Mage=60.6years) and Control Group (45% women; Mage=61.5years). (3) Results: Findings support H1 with significant correlations between health behaviors (r=0.45-0.63**), and disease self-management (r=-0.32-0.54**), H2 with Eta²=0.21 (not statistically significant) and H3 partially with d=0.101 for systolic blood pressure but not regarding diastolic blood pressure. (4) Conclusions: Replications are needed with larger samples and more objective measures. The app can help prevent and manage CVD by means of promoting health-protective behaviors and preventing health-compromising behaviors. Taking different behaviors into account can increase intervention effects and with that support of users.

This mini-review examines the complex relationship between the gut microbiota and human health, with a special focus on its role in conditions such as inflammatory bowel disease (IBD) and cardiovascular disease (CVD). It explores how dietary patterns can affect the composition of the gut microbiota, thus contributing to the development of various diseases. The gut microbiota is crucial in the production of metabolites such as trimethylamine N-oxide (TMAO), which play a significant role in the development of both IBD and CVD. High levels of TMAO and other metabolites, such as phenylacetylglutamine, have been linked to an increased risk of CVD. The review highlights the potential of dietary interventions and therapies designed to modulate the gut microbiota in reducing these risks. Following a Mediterranean diet may offer cardiovascular protection, emphasizing the need for further research into the molecular mechanisms of diet-related changes in the microbiota.

Large epidemiological studies show U-shaped relationships between high-density lipoprotein cholesterol (HDL-C) levels and all-cause mortality in individuals without atherosclerotic cardiovascular diseases (ASCVD). Association in those with ASCVD by sex is unclear. We examined the association between HDL-C levels and 10-year all-cause mortality in subjects (≥40 years of age) with ASCVD using the 2010 National Health Insurance Service and the National Death Registry of Korea. We categorized HDL-C levels into three groups (low: <40 mg/dL for males, <50 mg/dL for females; high: 40-90 mg/dL for males, 50-90 mg/dL for females; extremely high: >90 mg/dL) and 10 mg/dL intervals. We conducted a sex-stratified and adjusted Cox proportional hazards analysis. Out of 1,711,548 individuals (54% female, mean age 61.4 years), 10-year mortality was observed in 218,252 (12.8%). Males had a higher mortality rate than females (16.2% vs 9.8%; P<0.001). When adjusting for age, body mass index, LDL-cholesterol, triglycerides, hypertension, diabetes, smoking, and alcohol consumption, the low and extremely high HDL-C groups had significantly higher hazard ratios for 10-year mortality compared to the high HDL-C group in males [1.183 (1.166-1.199), 1.359 (1.288-1.434)] and in females [1.153 (1.138-1.169), 1.095 (1.029-1.167)]. The frequency distribution bars for the 10-year mortality rate showed sex-specific nadirs of 50-59 mg/dL in males and 70-79 mg/dL in females. In this ASCVD cohort, the extremely high HDL-C (>90 mg/dL) group had 35.9% and 9.5% higher 10-year mortality risk than the high HDL-C group for males and females, respectively. There was a slightly U-shaped relationship between baseline HDL-C levels and 10-year mortality rate, with earlier inflection in males than in females.

This comprehensive review delves into the intricate relationship between Sodium-GlucoseCo-Transporter 2 (SGLT2) inhibitors and AF, highlighting the multifaceted actions of thesedrugs and their significant cardiovascular benefits. Mechanisms: SGLT2 inhibitors inducesubstantial hemodynamic changes, impacting blood pressure, adipose tissue function, andinflammation. They enhance glycemic control while potentially reducing oxidative stress andinflammation, and they modulate atrial electrophysiology, collectively contributing to the reductionof AF risk. Clinical Evidence: This review synthesizes a wealth of clinical evidence,drawing from observational studies and randomized controlled trials, consistently demonstratinga correlation between SGLT2 inhibitors, particularly dapagliflozin and empagliflozin, anda decreased risk of AF. This protective effect is most pronounced in patients with type 2 diabetesand heart failure, underscoring their potential as therapeutic agents for high-risk populations.Potential Benefits: SGLT2 inhibitors offer a spectrum of potential benefits, includingsubstantial reductions in AF risk, particularly in patients with type 2 diabetes and heart failure.These drugs have consistently demonstrated benefits in reducing heart failure hospitalizations,cardiovascular mortality, and stroke risk, which indirectly contribute to better AF management.Furthermore, SGLT2 inhibitors exhibit renoprotective properties by slowing theprogression of chronic kidney disease and reducing albuminuria, offering substantial benefitsfor AF patients with comorbid kidney disease. Metabolic improvements involving weight loss,blood pressure reduction, and favorable changes in lipid profiles contribute to enhanced cardiovascular health and reduced AF risk. Originally designed for diabetes management, thesemedications offer a holistic approach to AF risk reduction, particularly in patients with type 2diabetes and heart failure.

Objectives: The aim of our current study was to analyze whether the use of important measures of methodological quality and reporting of randomized clinical trials published in the field of cardiovascular disease research have changed over time. Further aim was to investigate whether there was an improvement over time in the ability of these trials to provide a good estimate of the true intervention effect. Methods We conducted two searches in the Cochrane Central Register of Controlled Trials (CENTAL) database to identify cardiovascular clinical research trials published in either 2012 or 2017. Randomized clinical trials (RCTs) trials in cardiovascular disease research with adult participants were eligible to be included. We randomly selected 250 RCTs for both publication year 2012 and 2017. Trial characteristics, data on measures of methodological quality and reporting were extracted and risk of bias for each trial was assessed. Results As compared to 2012 in 2017 there were significant improvements in the reporting of the presence of a data monitoring committee (42.0% in 2017 compared to 34.4% in 2012), and a positive tendency of registering cardiovascular disease research RCTs in clinical trial registries (83.6% in 2017 compared to 72.0% in 2012). On the other hand, we also observed that significantly fewer RCTs reported sample size calculation (60.4% in 2017 compared to 98.4% in 2012) in 2017 as compared to 2012. RCTs in 2017 were more likely to have low overall risk of bias ( RoB ) than in 2012 (29.2% in 2017compared to 21.2% in 2012). Conclusion: As compared to 2012 in 2017 there were significant improvement in some, but not all the important measures of methodological quality. Although more trials in the field of cardiovascular disease research had a lower overall RoB in 2017, the improvement over time was not consistently perceived in all RoB domains.

: For a long time, atherosclerosis has been regarded as a mere lipid deposit in the blood vessels. However, in the recent years a growing body of experimental and clinical evidence have highlighted the role of inflammation and immunity as a central mechanism of disease. Moreover, in the last decade the coming of next-generation sequencing and its application to large human population has broken the barrier between inflammation and cancer. Indeed, acquired mutation in key genes related to the control of hematopoiesis and myeloproliferation have paved the way to establish the new concept of clonal hematopoiesis of indeterminate potential. This phenomenon is being considered not such “indeterminate”, but as an emerging cardiovascular risk factor. Thus, this may explain the mechanisms of myeloproliferation and inflammation in atherosclerosis. And in a bidirectional journey, it has helped to explain the extremely high cardiovascular risk in cancer survivors, in particular in myeloprolfierative neoplasm patients. A deeper understanding of these mechanisms may pave the way for the future early diagnosis and potential preemptive treatments of the leading worldwide cause of death.

Cardiovascular diseases (CVD) are chronic diseases associated with a high risk of mortality and morbidity. Early detection of CVD is crucial to initiating timely interventions, such as appro- priate counseling and medication, which can effectively manage the condition and improve patient outcomes. Preventive measures should be implemented at the general public level, promoting a healthy lifestyle, and at the individual level, that is, in people with moderate to high risk of CVD or patients already diagnosed with CVD by addressing an unhealthy lifestyle. Personalized early diagnostic systems based on artificial intelligence (AI), ontologies, and other medical information processing systems may prove to be a great preventive measure. In this paper, we focus on the use of ontology-inspired database models in the diagnosis of cardiovascular disease, as well as their potential for use in web application development.

Nowadays, healthcare-associated infections (HAIs) represent a major global public health problem and the burden of these infections is high. In order to reduce the incidence of HAIs and to prevent the spread antibi-otics resistant organisms is mandatory to develop surveillance systems. We undertook a retrospective case-control study of all patients presenting HAIs admitted in Intensive Care Unit (ICU) in order to assess risk factors associated with death among patients with HAIs. Patients admitted to Intensive Care Unit who died were more likely to present an infection with a multidrug resistant bacteria, an infection with Acineto-bacter baumannii, and to suffer from acute myocardial infarction. Among the patients enrolled in the study, a higher probability of death was also observed in association with certain gram-negative pathogens: Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. The longer the patient remains admitted in ICU, the higher the risk of getting an infection that can often become fatal. Acquiring a noso-comial infection also increases the length of hospitalization which will lead to increased financial damage.

Introduction and objectives Obstructive sleep apnea (OSA) is defined as a cause of daytime sleepiness, as well as a clinical manifestation of sleep-disordered breathing. In the literature, there are numerous controversial studies regarding the etiology of this condition, but it is universally accepted that a significant role in its onset is played by the reduced activity of the upper airway muscles. Additionally, OSA has been associated with a series of comorbidities, such as type II diabetes, metabolic syndrome, cardiovascular and pulmonary conditions, as well as head and neck tumors, especially oropharyngeal and laryngeal tumors. The purpose of this review is to examine and demonstrate the prevalence of OSA in patients with associated pathologies, especially in patients with head and neck tumors, as well as the role of surgical and non-surgical therapeutic methods in improving the quality of life. Material and methods Taking into consideration the stated objective, a systematic analysis of the available literature was conducted, encompassing PubMed, Medline and Scopus databases. The evaluation was based on several keywords, including head and neck cancer, diabetes, diabetic, overlap syndrome, cardiovascular conditions, laryngeal neoplasm, radiotherapy, chemotherapy, as well as the concept of quality of life in laryngectomized patients and patients with OSA. Results Our results demonstrate the involvement of OSA in the presence of comorbidities and also, an increased incidence of OSA in patients with laryngeal cancer. It is important to note that surgical and post-surgical treatment can play a significant role in triggering OSA in these patients. Conclusions The clinician must recognize the increased prevalence of OSA in patients with head and neck cancer, as well as the coexistence of OSA with certain comorbidities. They should actively engage in early diagnosis and establish optimal treatment methods to improve the quality of life for patients with associated conditions such as head and neck tumors or cardiovascular pathology.

High hepcidin is linked to low-grade inflammation and lower iron levels. The consequence of testosterone replacement therapy (TRT) on inflammation and risk of cardiovascular disease (CVD) is undetermined. We investigate the effect of TRT on the inflammatory cardiovascular risk markers hepcidin-iron, fibroblast growth factor 23 (FGF23)-phosphate-klotho, and calprotectin pathways. Methods: A randomized, placebo-controlled, double-blinded study at an academic tertiary-care medical center. Interventions were testosterone gel (TRT, n=20) or placebo gel (n=19) for 24 weeks. We included 39 men (50─70 years) with type 2 diabetes (T2D) on metformin monotherapy with bioavailable testosterone levels <7.3 nmol/L. Body composition was assessed by DXA- and MRI-scans; main study outcomes were serum hepcidin-iron, FGF23, phosphate, klotho, and calprotectin. Results: Hepcidin levels decreased during TRT (β=-9.5 ng/mL, P<0.001), lean body mass (β=1.9 kg, P=0.001) increased, and total fat mass (β=-1.3 kg, P=0.009) decreased compared to placebo. Delta hepcidin was not associated with changes in lean body mass or fat mass. Iron and the pathways of FGF23-phosphate-klotho and calprotectin were unchanged during TRT. Conclusions: During TRT, the reduction in hepcidin was not associated with circulating iron levels, lean body mass, or fat mass; these findings suggested a direct anti-inflammatory effect of TRT and no indirect effect mediated through these factors.

1. Background: Cardiovascular diseases (CVDs) are India’s leading cause of mortality. This study aimed to recalibrate the original Framingham Risk Score (FRS) equations among adults in Kerala state. 2. Methods: Baseline survey data from the Kerala Diabetes Prevention Program were analyzed: 921 males and 567 females for lipid-based FRS scores and 1042 males and 646 females for BMI-based FRS scores. Recalibration of the original FRS scores was performed using local data on CVD risk factors and CVD mortality. 3. Results: Among males, the median 10-year CVD risk with the recalibrated lipid-based FRS score was 7.34 (IQR 4.33-12.42), compared with the original score of 8.88 (5.23-14.87) (p<0.001). For BMI-based FRS scores, the median 10-year CVD risk was 7.40 (4.27-11.83) with the recalibrated score, compared to 9.32 (5.40-14.80) for the original score (p<0.001). In females, the median 10-year CVD risk was 4.83 (2.90-8.36) with the recalibrated score, compared to 2.85 (IQR 1.71-4.98) with the original score (p<0.001). Similarly, the median 10-year CVD risk was 4.66 (2.74-8.81) with the recalibrated BMI-based FRS score, compared to 2.95 (1.72-5.61) with the original score (p<0.001). 4. Conclusions: Recalibrated FRS scores estimated a significantly lower 10-year CVD risk in males and a higher risk in females than the original FRS scores.

Objective: The objective of our study was to explore the potential benefits of combining moderate alcohol consumption with regular vigorous physical activity on HDL-cholesterol levels and its potential positive impact on cardiovascular health. Material and method: The study comprised two groups: group A (102 patients) who consumed 1 gram of alcohol per day, specifically red wine, and increased their exercise levels in addition to their standard medical treatment, and group B (108 patients) who adhered only to their standard medical treatment. The patients were monitored for a year, during which various clinical parameters were observed. Results:Our study showed that moderate alcohol consumption, particularly red wine, along with increased physical activity levels, was associated with enhancements in exercise tolerance and elevated levels of HDL-cholesterol. Our findings suggest the efficacy of the intervention in improving lipid profiles, with the group that consumed alcohol as part of their treatment scheme, generally experiencing more pronounced positive effects. Statistically significant differences between groups in terms of angina evolution, AMI recurrence, or arrhythmias evolution were not found. However, there were important differences in terms of EF improvement and quality of life, with the alcohol consuming group displaying greater improvements in both aspects. Conclusions:In conclusion, our study emphasizes the potential benefits of combining moderate alcohol consumption, specifically red wine, with increased physical activity levels for improving exercise tolerance and enhancing HDL-cholesterol levels. However, further research and clinical trials are essential to fully understand the mechanisms and optimize the integration of these lifestyle elements for improved cardiovascular health outcomes.

Methylglyoxal (MGO) is the major compound belonging to reactive carbonyl species (RCS) responsible for the generation of advanced glycation end products (AGEs). Its upregulation followed by deleterious effects at the cellular and systemic level is associated with metabolic disturbances (hyperglycemia/hyperinsulinemia/insulin resistance/hyperlipidemia/inflammatory processes/carbonyl stress/oxidative stress/hypoxia). Therefore, it is implicated in a variety of disorders including metabolic syndrome, diabetes mellitus and cardiovascular diseases. In this review an interplay between pathways leading to MGO generation and scavenging is addressed, in regard to this system’s impairment in pathology. The issues associated with mechanistic MGO involvement in pathological processes, as well as the discussion on its possible causative role in cardiometabolic diseases are enclosed. Finally, the main strategies aimed at MGO and its AGEs downregulation with respect to cardiometabolic disorders treatment are addressed. Potential glycation inhibitors and MGO scavengers are discussed, as well as the mechanisms of their action.

While it is well known that 98-99% of the human genome do not encode proteins, but are nevertheless transcriptionally active and give rise to a broad spectrum of noncoding RNAs (ncRNAs) with complex regulatory and structural functions, specific functions have so far been assigned to only a tiny fraction of all known transcripts. On the other hand, the striking observation of an overwhelmingly growing fraction of ncRNAs, in contrast to an only modest increase in the number of protein-coding genes, during evolution from simple organisms to humans, strongly suggests critical but so far essentially unexplored roles of the noncoding genome for human health and disease pathogenesis. Research into the vast realm of the noncoding genome during the past decades thus lead to a profoundly enhanced appreciation of the multi-level complexity of the human genome. Here, we address a few of the many huge remaining knowledge gaps and consider some newly emerging questions and concepts of research. We attempt to provide an up-to-date assessment of recent insights obtained by molecular and cell biological methods, and by the application of systems biology approaches. Specifically, we discuss current data regarding two questions: (1) By which mechanisms could evolutionary recent ncRNAs with critical regulatory functions in a broad spectrum of cell types (neural, immune, cardiovascular) constitute novel thera-peutic targets in human diseases ? (2) Since noncoding genome evolution is causally linked to brain evolution, and given the pro-found interactions between brain and immune system, could human-specific brain-expressed ncRNAs play a direct or indirect (immune-mediated) role in human diseases? Synergistic with the remarkable recent progress regarding delivery, efficacy, and safety of nu-cleic acid-based therapies, the ongoing large-scale exploration of the noncoding genome for human-specific therapeutic targets is encouraging to proceed with the development and clinical evaluation of novel therapeutic pathways suggested by these research fields.

Cardiovascular and cerebrovascular disease incidence has risen mainly due to poor control of preventable risk factors and still constitutes a significant financial and health burden worldwide. ChatGPT is an artificial intelligence language-based model developed by OpenAI. Due to the model’s unique cognitive capabilities beyond data processing and the production of high-quality text, there has been a surge of research interest concerning its role in the scientific community and contemporary clinical practice. To fully exploit ChatGPT's potential benefits and reduce its possi-ble misuse, extreme caution must be taken to ensure its implications ethically and equitably. In this article, we explore the language model's possible applications and limitations while empha-sizing its potential value for diagnosing, managing, and prognosis cardiovascular and cerebro-vascular disease.

Objective: The objective of our study was to explore the potential benefits of combining moderate alcohol consumption with regular vigorous physical activity on HDL-cholesterol levels and its potential positive impact on cardiovascular health. Material and method: The study comprised two groups: group A (102 patients) who consumed 1 gram of alcohol per day, specifically red wine, and increased their exercise levels in addition to their standard medical treatment, and group B (108 patients) who adhered only to their standard medical treatment. The patients were monitored for a year, during which various clinical parameters were observed. Results:Our study showed that moderate alcohol consumption, particularly red wine, along with increased physical activity levels, was associated with enhancements in exercise tolerance and elevated levels of HDL-cholesterol. Our findings suggest the efficacy of the intervention in improving lipid profiles, with the group that consumed alcohol as part of their treatment scheme, generally experiencing more pronounced positive effects. Statistically significant differences between groups in terms of angina evolution, AMI recurrence, or arrhythmias evolution were not found. However, there were important differences in terms of EF improvement and quality of life, with the alcohol consuming group displaying greater improvements in both aspects. Conclusions:In conclusion, our study emphasizes the potential benefits of combining moderate alcohol consumption, specifically red wine, with increased physical activity levels for improving exercise tolerance and enhancing HDL-cholesterol levels. However, further research and clinical trials are essential to fully understand the mechanisms and optimize the integration of these lifestyle elements for improved cardiovascular health outcomes.

Conducting computational stress-strain analysis using finite element methods (FEM) is a common approach when dealing with the complex geometries of atherosclerosis, which is a leading cause of global mortality and complex cardiovascular disease. The considerable expense linked to FEM analysis encourages the substitution of FEM with a considerably faster data-driven machine learning (ML) approach. This study investigated the potential of end-to-end deep learning tools as a more effective substitute for FEM in predicting stress-strain fields within 2D cross sections of arterial wall. We first proposed a U-Net based fully convolutional neural network (CNN) to predict the von Mises stress and strain distribution based on the spatial arrangement of calcification within arterial wall cross-sections. Further, we developed a conditional generative adversarial network (cGAN) to enhance, particularly from the perceptual perspective, the prediction accuracy of stress and strain field maps for arterial walls with various calcification quantities and spatial configurations. On top of U-Net and cGAN, we also proposed their ensemble approaches to further improve the prediction accuracy of field maps. Our dataset, consisting of input and output images, was generated by implementing boundary conditions and extracting stress-strain field maps. The trained U-Net models can accurately predict von Mises stress and strain fields, with structural similarity index scores (SSIM) of 0.854 and 0.830 and mean squared errors of 0.017 and 0.018 for stress and strain, respectively, on a reserved test set. Meanwhile, the cGAN models in a combination of ensemble and transfer learning techniques demonstrate high accuracy in predicting von Mises stress and strain fields, as evidenced by SSIM scores of 0.890 for stress and 0.803 for strain. Additionally, mean squared errors of 0.008 for stress and 0.017 for strain further support the model's performance on a designated test set. Overall, this study developed a surrogate model for finite element analysis, which can accurately and efficiently predict stress-strain fields of arterial walls regardless of complex geometries and boundary conditions.

Cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) are two of the four major chronic non-communicable diseases (NCDs), representing the leading cause of death worldwide. Several studies demonstrate that endothelial dysfunction (ED) plays a central role in the pathogenesis of these chronic diseases. Although it is well known that systemic chronic inflammation and oxidative stress are primarily involved in the development of ED, recent studies have shown that perivascular adipose tissue (PVAT) is implicated in its pathogenesis, also contributing to the progression of atherosclerosis and to insulin resistance (IR). In this review we describe the relationship between PVAT and ED, and we also analyse the role of PVAT in the pathogenesis of CVDs and T2DM, further assessing its potential therapeutic target with the aim of restoring normal ED and reducing global cardiovascular risk.

This study assessed the associations between host genetic variants and subgingival microbiota in patients with metabolic syndrome (MetS); 103 patients with MetS underwent medical and periodontal examinations and had blood and subgingival plaque samples taken. DNA was extracted and processed (assessing a panel of selected single nucleotide polymorphisms (SNPs) first (hypothesis-testing), and then expanding to a discovery phase. The subgingival plaque microbiome from these patients was profiled. Analysis of associations between host genetic and microbial factors was performed, stratified for periodontal diagnosis. Specific SNPs within RUNX2, CAMTA1 and VDR genes were associated with diversity metrics, with no genome-wide associations detected for periodontitis severity or Mets components at p&lt;10-7. Severe periodontitis was associated with pathogenetic genera and species. Some SNPs correlated with specific bacterial genera, as well as with microbial taxa, notably VDR (rs12717991) with Streptococcus mutans and RUNX2 (rs3749863) with Porphyromonas gingivalis. This is the first study exploring the role of host genotype variation in subgingival microbial dysbiosis in patients with MetS and periodontitis. In conclusion, variation in host genotypes may play a role in the dysregulated immune responses characterizing periodontitis and thus the oral microbiome, suggesting that systemic health-associated host traits further interact with oral health and microbiome.

Breast cancer and cardiovascular diseases (CVD) represent significant global health challenges, with CVD being the leading cause of mortality and breast cancer showing a complex pattern of incidence and mortality. We explore the intricate interplay between these two seemingly distinct medical conditions, shedding light on their shared risk factors and potential pathophysiological connections. A specific connection between hypertension (HTN), atrial fibrillation (AF), myocardial infarction (MI), and breast cancer was evaluated. HTN is explored in detail, emphasizing the role of aging, menopause, insulin resistance, and obesity as common factors linking HTN and breast cancer. Moreover, an attempt is made to identify the potential impact of antihypertensive medications and highlight the increased risk of breast cancer among those women, with a focus on potential mechanisms. A summary of key findings underscores the need for a multisystemic approach to understanding the relationship between CVD and breast cancer is also explored with a highlight for all the gaps in current research, such as the lack of clinical observational data on MI and breast cancer in humans and the need for studies specifically designed for breast cancer. This paper concludes that there should be a focus on potential clinical applications of further investigation in this field, including personalized prevention and screening strategies for women at risk. Overall, the authors attempt to provide a comprehensive overview of the intricate connections between breast cancer and cardiovascular diseases, emphasizing the importance of further research in this evolving field of cardio-oncology.

Neutrophils are the principal trouper of innate immune system. Activated neutrophils undergo a noble cell death termed NETosis and release a mesh-like structure called neutrophil extracellular traps (NETs) as a part of their defensive strategy against microbial pathogen attack. This web-like architecture includes a DNA backbone embedded with antimicrobial proteins like myeloperoxidase (MPO), neutrophil elastase (NE), histones etc. and deploys in the entrapment and clearance of encountered pathogens. Thus NETs play an inevitable beneficial role in the host's protection. However, recent accumulated evidence shows that dysregulated and enhanced NET formation has various pathological aspects including promotion of sepsis, pulmonary, cardiovascular, hepatic, nephrological, thrombotic, autoimmune, pregnancy, cancer diseases etc. and the list is increasing gradually. In this review, we summarize NETs mediated pathophysiology of different diseases, focus on some updated potential therapeutic approaches against NETs and share our future perspectives.

Coronavirus infection disease -2019 (COVID-19) was a global pandemic with high mortality and morbidity, that lead to an increased health burned all over the world. Although the virus affects mostly pulmonary tract, cardiovascular implications were often among COVID-19 positive patients, and are predictive for poor outcomes. Increased values of myocardial biomarkers such as Troponin I or NT-proBNP were proven to be risk factors for respiratory failure (26). Although the risk of acute coronary syndromes (ACS) was greater in acute-phase of COVID-19, there were lower rates of hospitalization for ACS, due to patient’s hesitation for presenting at the hospital (22). Hospitalized ACS patients with COVID-19 infection, had a prolonged symptom-to-first medical contact time, and longer door-to-balloon time. The mechanisms of myocardial injurie in COVID -19 patients are not still not clear, most often is incriminated: the down-regulation of ACE2 inhibitors, endothelial disfunction, pro-coagulant status, increased levels of pro-inflammatory cytokines. The aim of this paper is to evaluate the long-term outcomes of COVID-19 survivors that presented an acute myocardial infarction by reviewing existing data.

Obesity, characterized by the excessive accumulation of body fat, contributes to a multitude of physiological dysfunctions. This paper explores the complex relationship between obesity and various risk factors and complications, shedding light on critical health implications. Obesity triggers alterations in insulin, leptin, adiponectin, cytokines, and insulin-like growth factors, fostering conditions conducive to cancer initiation. Aberrations in nutrient-dependent intracellular signaling pathways, driven by the excess nutrition characteristic of obesity, contribute to the neoplastic transformation of cells. The Body Mass Index (BMI) correlates directly with adiposity, underlining its significance in cancer risk. Furthermore, insulin and insulin-like growth factors, notably IGF-2, play pivotal roles in this relationship. The expression of IR-A receptors is elevated in cancer. Obesity and cardiovascular diseases share a strong association. Obesity elevates the risk of fatal events like myocardial infarction. High cholesterol levels contribute to atherosclerosis in the aorta and coronary arteries. The severity of coronary artery disease is influenced by plaque formation characterized by calcium deposits. Obesity is also linked to hypertension and increased ventricular mass, exacerbating cardiovascular risks. Hypercholesterolemia and hypertension correlate with a high Body Mass Index (BMI). Obesity is intricately connected to insulin resistance, particularly evident in childhood obesity. It entails a gradual decline in insulin sensitivity, leading to elevated insulin levels in the bloodstream. Insulin resistance is a central factor in the development of Type 2 Diabetes Mellitus. Obesity also results in elevated triglyceride levels and reduced high-density lipoproteins, contributing to atherogenic dyslipidemia and a heightened risk of atherosclerosis. Additionally, obesity is associated with various other disorders, including epilepsy, depression, and neuropsychological problems. Beyond its physiological impact, obesity is associated with significant psychosocial challenges. Studies indicate that individuals with obesity face a higher risk of depressive symptoms, often related to overeating and unhealthy dietary patterns. The social withdrawal tendencies of obese individuals exacerbate these symptoms, with higher rates of depression observed in this group. OSA, a sleep disorder characterized by intermittent breathing cessation during sleep, is strongly correlated with obesity. Approximately 58% of obese individuals experience OSA, with higher Body Mass Index (BMI) associated with an increased risk. Weight reduction has been found to mitigate the severity of OSA and related arrhythmias. Continuous positive airway pressure (CPAP) therapy demonstrates effectiveness in reducing visceral fat accumulation and leptin levels. This comprehensive review underscores the intricate web of health implications associated with obesity, emphasizing the critical need for preventive measures and intervention strategies to address the multifaceted challenges posed by this global health concern.

Background: Galectin-3 (Gal-3) is a biomarker involved in a wide range of diseases including cardiac remodeling following acute myocardial infarction (AMI). Identification of prognostic markers in patients with AMI can guide strategies towards improved survival and the quality of life. Methods: Our study included 59 patients with AMI and preserved ejection fraction. We determined the Gal-3 plasma concentration within 24 hours of chest pain onset from aortic root, femoral/radial artery, coronary sinus and cubital vein. Major adverse cardiovascular events (MACE) were evaluated at six months follow-up. Results: MACE at six months post-AMI was recorded in 20 patients (34%). The Gal-3 plasma concentration from aortic root and the femoral/radial artery were independent predictors of MACE at six months follow-up after the first AMI (OR 1.228; 95%CI: 1.011-1.491; p=0.038; OR 3.438; 95%CI: 1.275-9.265; p=0.015). ROC analysis identifies the Gal-3 plasma concentration from aortic root as a better predictor of MACE or death (cut-off &gt;10.86 ng/ml; AUC 0.858; 95%CI: 0.744-0.973; p&lt;0.001) than Gal-3 plasma concentration from femoral/radial artery (cut-off &gt;10.18 ng/ml; AUC 0.742; 95%CI: 0.596-0.888; p=0.006). Conclusion: The Gal-3 plasma concentration in patients with AMI determined during coronary angiography, especially from the aortic root, within 24 hours after chest pain onset is a valuable biomarker of prognosis at six months follow-up.

Cardiovascular diseases (CVD) remain the leading cause of death across the globe, hence, establishing strategies to counteract CVD are imperative to reduce mortality and the burden on health systems. Dietary modification is an effective primary prevention strategy against CVD. Research regarding dietary supplementation has become increasingly popular. This review focuses on the current in vivo, in vitro, and epidemiological studies associated with that of omega-3 polyunsaturated fatty acids (n-3 PUFA) and polar lipids (PLs) and how they play a role against CVD. Furthermore, this review focuses on the results of several major clinical trials examining n-3 PUFA regarding both primary and secondary prevention of CVD. Notably, we place a lens on the REDUCE-IT and STRENGTH trials. Finally, supplementation of PLs has recently been suggested as a potential alternative avenue for the reduction of CVD incidence versus neutral forms of n-3 PUFA. However, the clinical evidence for this argument is currently rather limited. Therefore, we draw on the current literature to suggest future clinical trials for PL supplementation. We conclude that despite conflicting evidence, future human trials must be completed to confirm whether PL supplementation may be more effective than n-3 PUFA supplementation to reduce cardiovascular risk.

Background: The current review was conducted to determine the effectiveness of atenolol on all-cause mortality rate among Asian patients with chronic progressive diseases, mainly diabetes mellitus, primary hypertension, and coronary artery disease. Methods: We searched the COCHRANE, MEDLINE, TRIP, and EMBASE databases for published articles up to 31 March 2023. Studies that compared all-cause mortality rates among Asian patients who were on atenolol or other medications were included. Results: The review included 79603 Asian patients from three cohort studies. Out of the studied patients, 36046 were atenolol users and 43557 were non-atenolol users. The review revealed that atenolol users recorded lower all-cause mortality rates compared to non-users with a significant difference (OR= 0.57, CI= 0.44-0.75, P<0.001). The pooled estimate of the all-cause mortality rate was also lower among atenolol users (7.02%) compared to metoprolol tartrate users (13.15%) with a significant difference (OR= 0.50, CI= 0.47-0.53, p < 0.0001). Although the included studies were categorized as having a low risk of bias for most of the studied domains, significant heterogeneity was recorded across these studies (I2 =88%, P=0.001). Conclusion: This review found that atenolol when compared to a control or metoprolol tartrate, has a significant effect in reducing the all-cause mortality rate among Asian patients with chronic progressive disease.

Background: Cardiovascular disease (CVD) increases the risk of mortality and morbidity in patients with rheumatoid arthritis (RA). Patients with RA have a 50-60% increased risk for CVD compared with the general population. Cardiovascular risk is commonly meas-ured using the Systemic Coronary Risk Estimation 2 calculator modified for patients with RA. Traditional modifiable risk factors for CVD include arterial hypertension, dyslipidemia, insulin resistance, diabetes, cigarette smoking, and low physical activity. In this study, we analyzed the effects of smoking and the risk of CVD in patients with RA. Methods: This was a prospective, clinical, cohort study with an eight-year follow-up pe-riod. A total of 201 patients, 124 with RA (study group) and 77 with osteoarthritis (OA) (control group), were included in this study. However, only 137 patients (82 with RA and 55 with OA) completed the study. Fifty-eight patients (41 with RA and 17 with OA) died during the study period. We compared the prevalence of smoking and its association with the risk for CVD and RA. Results: The prevalence of smoking in the RA group was higher than that in the OA group (p<0.0001). Trends in the prevalence of smoking in both groups did not change signifi-cantly during the follow-up period. In the RA group, smoking was associated with the in-cidence of CVD in current smokers (p=0.028) and in patients with a history of smoking (p=0.016). These results suggest that smokers have an increased risk for RA. The trend of continued smoking in patients with RA may be attributed to attempts to reduce stress caused by RA symptoms. Conclusions: Previous studies have shown that current and former smokers with RA have more severe symptoms, more joint damage, and poorer response to therapy than those who have never smoked. However, the reason underlying the trend of continued cigarette smoking in patients with RA remains unclear. Further studies are needed to clarify the trend of continued smoking in patients with RA.

Selenoproteins are a group of proteins containing selenium in the form of selenocysteine (Sec, U) as the 21st amino acid coded in the genetic code. Their synthesis is dependent on dietary selenium uptake and a common set of cofactors. Selenoproteins accomplish diverse roles in the body and cell processes by acting, for example, as antioxidants, modulators of the immune function, detoxification agents for heavy metals, and other xenobiotics, key compounds in thyroid hormone metabolism. Although the functions of all this protein family are still unknown, several disorders in their structure, activity or expression have been described by researchers. They concluded that selenium or cofactors deficiency, on one hand, or the polymorphism in selenoproteins genes and synthesis, on the other hand, are involved in a large variety of pathological conditions, including type 2 diabetes, cardiovascular, muscular, oncological, hepatic, endocrine, immuno-inflammatory, neurodegenerative diseases. This review is focused on specific roles in medicine only of selenoproteins that are each named after an alphabet letter, less known than the rest of them, regarding their implications in patho-logical processes of several prevalent diseases and also in disease prevention.

Cardiovascular diseases (CVD) are prevalent and lead to high morbidity and mortality globally. Physiotherapists regularly interact with patients with or at risk of CVDs (pwCVDs). This study aimed to assess the nature of existing evidence, interventional approaches used, and the population groups included in physiotherapy-led health promotion (PLHP) for pwCVDs. The scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Medline, PubMed, Web of Science, Cochrane Central Register of Controlled Trials, CINAHL, and PEDro databases were searched from inception until June 2023. Two reviewers independently screened the titles, abstracts, full text and conducted data extraction. All conflicts were resolved with a third reviewer. A total of 4992 records were identified, of which 20 full-text articles were included in the review. The studies had varied populations, including those with stroke, coronary artery diseases, peripheral artery diseases, hypertension, diabetes, and multiple CVD risk factors. The interventions ranged from exercise and physical activity programs, dietary interventions, education, and counselling sessions with various supplementary approaches. Most interventions were short-term, with less than 12 months of follow-up. Interventions were personalised and patientcentred to promote adherence and health behaviour change. Among the included studies, 60% employed experimental designs, with the remainder using quasi-experimental designs. Although a wide range of PLHP strategies have been used for pwCVDs, exercise and physical activity were employed in 85% of included studies. Other components of health promotion, such as sleep, smoking, and alcohol abuse, should be investigated within PLHP.

Advances in cardiovascular therapies and cancer treatments result in longer patient survival. The coexistence of cancer and cardiovascular disease has been recognized as a complex clinical scenario. Beside cardiovascular disease, older people with cancer are at greater risk of experiencing multimorbidity and the geriatric syndromes such as frailty. In older people, the concurrent presence of cancer and cardiovascular disease increased the risk of mortality, and the presence of frailty can exacerbate their conditions and hinder the treatment effectiveness. Given the significant intersection among frailty, cardiovascular disease and cancer in older people, this paper aims to provide an overview of the current research in this field and identifies gaps in research to understand the burden and impact of frailty in these populations. While many studies have examined the prevalence and impact of frailty on adverse outcomes in patients with cancer or with cardiovascular disease, evidence of frailty in individuals with both conditions is lacking. There is no universally accepted definition of frailty, which leads to inconsistencies in identifying and measuring frailty in older adults with cardiovascular disease and cancer. The frailty index seems to be a preferred frailty definition in studies in patients with cancer, while the frailty phenotype seems to be more commonly used in cardiovascular research. However, differences in how the frailty index was categorised and in how patients were classified as ‘frail’ depending on the cut points may have negative effect on understanding the impact of frailty in the studied populations. This makes it challenging to compare findings across different studies and limits our understanding of the prevalence and impact of frailty in these populations. Addressing these research gaps will contribute to our understanding of the burden of frailty in older people with cardiovascular disease and cancer, and improved clinical care protocols in this vulnerable population.

The risk of developing cardiovascular diseases (CVD) in patients suffering from rheumatoid arthritis (RA) is 1.5 times higher compared to the general population. The objective of this retrospective study was to determine the type of cardiovascular complications that can appear in patients with rheumatoid arthritis. Reducing the cardiovascular risk, through an aggressive management of the traditional and non-traditional risk factors, is another objective of this study. Early diagnosis and initiation of therapeutic measures to reduce the progression rate of rheumatoid arthritis, while also maintaining an active lifestyle, are the most important problems in young patients. We included a number of 200 patients with rheumatoid arthritis, presenting various stages of disease, concomitant with cardiovascular complications. The incidence by gender was higher in women, while men presented a higher incidence of traditional and non-traditional cardiovascular risk factors. All the patients presented an atherogenic coefficient over 2, indicating a significant risk of atherogenesis. An increased incidence of coronary artery disease was found in men. The patients presented cardiac arrhythmias, especially in the active stage of the condition, while the incidence of atrial fibrillation was higher in women. The active stage of the disease was evaluated using inflammatory biomarkers (ESR, PCR). ESR is not a specific tool for diagnosing the disease, but its important role in monitoring the activity of RA should not be ignored. Moreover, ESR has a significant role in monitoring the evolution and determining the prognostic of congestive heart failure. A target treatment prescribed a target treatment to reduce inflammation and prevent exacerbations was prescribed for all patients. However, in daily clinical practice, the screening for RA is poorly done. Thus, patients are often undiagnosed, while the risk factors are not assessed. In conclusion, even nowadays, RA patients continue to present an increased risk of developing CVD.

Metabolic-dysfunction associated steatotic liver disease (MASLD) is a chronic liver disease that affects more than a quarter of the global population, and is increasing worldwide, due to the pandemic of obesity. Insulin resistance is closely associated with the development and progression of MASLD. Hepatic entry of increased fatty acids (FA) released from adipose tissue, increase in FA synthesis and reduced FA oxidation in the liver, and hepatic overproduction of triglyceride (TG)-rich lipoproteins may induce the development of MASLD. Since insulin resistance also induces atherosclerosis, the leading cause for death in MASLD patients is cardiovascular disease (CVD). Considering that the development of CVD determines the prognosis of MASLD patients, the ideal therapeutic interventions for MASLD should reduce body weight, improve coronary risk factors, in addition to an improvement in liver functiom. Lifestyle modification such as diet and exercise and surgical interventions such as bariatric surgery and intragastric balloons have shown to improve MASLD by reducing body weight. Sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to improve coronary risk factors and to suppress the occurrence of CVD. Both SGLT2i and GLP-1 have been reported to improve liver enzymes, hepatic steatosis and fibrosis. We recently reported that the selective peroxisome proliferator-activated receptor-alpha (PPARα) modulator, pemafibrate, improved liver function. PPARα agonists have multiple anti-atherogenic properties. Here, we consider the pathophysiology of MASLD and the mechanisms of action of such drugs, and consider whether such drugs and the combination therapy of such drugs could be the ideal treatments for MASLD.

The paper proposes an approach to determine the optimal number of medical specialists in the region. According to the author's theoretical model, in order to maximize public welfare, the marginal contribution of the last physician recruited to the growth of the public utility function should be equal to the marginal cost of attracting him and providing conditions for his work. To empirically assess the contribution of physicians to the number of lives saved, the CVD mortality rate is modeled using the instrumental variable method. On average, a 1% increase in the number of cardiologists is associated with a 0.6% decrease in cardiovascular mortality. At the level of provision with cardiologists in the amount of 1 per 100 thousand people, their marginal contribution to the number of lives saved is not less than 129 per 100 thousand people, with a further decrease by 5 people with the increase in the level of provision by 1 unit. The use of the obtained results will increase the validity of managerial decisions and in determining the optimal level of doctors when choosing between alternative possibilities of spending money on hiring doctors of different profiles or other expenses, especially in the case of limited resources.

Aims: Chronic coronary syndrome is associated with several risk factors, such as dyslipidemia and hypertension. AIP has been demonstrated to be a biochemical risk factor for coronary artery disease (CAD). This study aimed to determine whether AIP is an effective parameter for estimating obstructive CAD. Methods and Results: A total of 345 patients (mean age 62,2±10,3; 63% male) who underwent coronary angiography were included in this study. Obstructive CAD is defined as having one or more vessels with a stenosis of≥50%. Depending on the presence of obstructive CAD, all patients were divided into two groups. The AIP was significantly higher in the obstructive coronary artery group (AIP; 0,49±0,26 vs. 0,58±0,27, p=0,002). In univariate analysis, AIP was significantly associated with obstructive coronary artery disease [OD:3,74 (CI95% 1,62-8,64), P=0,020]. The AIP was further adjusted for confounding risk factors in three multivariate analysis models. Therefore, all three models showed a significant association. According to ROC analysis, 0.49 is the cut-off value for AIP, and a value above 0.49 indicates 50% coronary artery stenosis Conclusions: AIP may be used in the assessment of cardiovascular risk in patients with stable angina pectoris, and it may also be used to estimate obstructive CAD.

Endothelial cells are the crucial inner lining of blood vessels, pivotal in vascular homeostasis and integrity. However, these cells are perpetually subjected to a myriad of mechanical, chemical, and biological stresses that can compromise their plasma membranes. A sophisticated repair system involving key molecules, such as calcium, annexins, dysferlin, and MG53, is essential for maintaining endothelial viability. These components orchestrate complex mechanisms, including exocytosis and endocytosis, to repair membrane disruptions. Dysfunctions in this repair machinery, often exacerbated by aging, are linked to endothelial cell death, subsequently contributing to the onset of atherosclerosis and the progression of cardiovascular diseases (CVD) and stroke, major causes of mortality in the United States. Thus, identifying the core machinery for endothelial cell membrane repair is critically important for understanding the pathogenesis of CVD and stroke and developing novel therapeutic strategies for combating CVD and stroke. This review summarizes the recent advances in understanding the mechanisms of endothelial cell membrane repair. The future directions of this research area are also highlighted.

In the last decade, an increasing awareness was directed to the role of Vitamin D in non-skeletal and preventive roles for chronic diseases. Vitamin D is a key hormone involved in the regulation of calcium/phosphorous balance and it has been implicated in the pathogenesis of inflammation, insulin resistance and obesity. Cholecalciferol (Vitamin D3) and Ergocalciferol (Vitamin D2) are the main form of vitamin D: the active form (1,25-dihydroxyvitamin D) is the result of two hydroxylations that take place in liver, kidney, pancreas and immune cells. Some anti-inflammatory cytokines are produced at higher levels by vitamin D, while some pro-inflammatory cytokines are released at lower levels. Toll-Like Receptor (TLR) expression is increased and a pro-inflammatory state is also linked to low levels of vitamin D. Regardless of how it affects inflammation, various pathways suggest that vitamin D directly improves insulin sensitivity and secretion. The level of vitamin D in the body may change the ratio of pro- to anti-inflammatory cytokines, which would impact insulin action, lipid metabolism, and the development and function of adipose tissue. Many studies have demonstrated an inverse relationship between vitamin D concentrations and pro-inflammatory markers, insulin resistance, glucose intolerance, metabolic syndrome, obesity and cardiovascular disease. It's interesting to note that several long-term studies also revealed an inverse correlation between vitamin D level and the occurrence of diabetes mellitus. Vitamin D supplementation in people has controversial effects, in fact while some studies demonstrated improvements in insulin sensitivity, glucose and lipid metabolism, others revealed no significant effect on glycemic control and inflammation. The aim of this review is to provide insight into the molecular basis of the relationship between vitamin D, insulin-resistance, metabolic syndrome, type 1 and 2 diabetes, gestational diabetes, and cardiovascular diseases.

Telemedicine, telehealth, e-Health, and other related terms refer to the exchange of medical information or medical care from one site to another through electronic communication between a patient and healthcare provider. As telemedicine infrastructure has changed since the COVID-19 pandemic, this review provides an overview of telemedicine use and effectiveness in cardiology, with emphasis on the post-pandemic context. Pre-pandemic studies tend to report statistically insignificant or modest improvements in cardiovascular disease outcome from telemedicine use to usual care. By contrast, post-pandemic studies tend to report positive outcomes or comparable acceptance of telemedicine use to usual care. Today, telemedicine can effectively replace in person follow-ups to produce comparable (but not necessarily superior) outcomes in cardiovascular disease management. A major benefit of telemedicine is the significant reduction in follow-up time or time-to-intervention which may lead to earlier detection and prevention of adverse events. Nonetheless, there remain barriers to effective telemedicine implementation in the post-pandemic context. Providing accuracy and ease-of-use of telemedicine devices, ensuring adherence to remote rehabilitation procedures, and implementing widespread telemedicine infrastructure are such examples. Current knowledge gaps include the true economic cost of telemedicine infrastructure, feasibility of use in specific cardiology contexts, and sex/gender differences of health outcomes through telemedicine use. Future telemedicine developments will need to address these concerns to achieve widespread acceptance as the new standard of care.

A preventive effect for tea and its bio active components in cardiovascular health has been suggested by the results of several epidemiological studies, treatments utilizing randomized controlled trials, and mechanistic investigations. Therefore, scientific interest in green tea's ability to prevent cardiovascular diseases (CVDs) is growing. Green tea benefits for the metabolic syndrome, which includes diabetes and hypertension but may also raise cholesterol levels. Additionally, green tea reduces the mortality from any cause, arrhythmia, stroke, coronary heart disease, heart failure, and other conditions.

The analysis reported here is unique in that it is the first study of the original data from the Pfizer/BioNTech BNT162b2 mRNA vaccine clinical trial (CA4591001) to be carried out by a group unaffiliated with the trial sponsor. Our study is a forensic analysis of the 38 trial subjects who died between July 27, 2020, the start of Phase 2/3 of the clinical trial, and March 13, 2021, the data end date of their 6-Month Interim Report. Phase 2/3 of the trial involved 44,060 subjects who were equally distributed into two groups and received Dose 1 of either the BNT162b2 mRNA vaccinated or the Placebo control (0.9% normal saline). At Week 20, when the BNT162b2 mRNA vaccine received Emergency Use Authorization from the U.S. FDA, subjects in the placebo arm were given the option to be BNT162b2 vaccinated. All but a few accepted. Surprisingly, a comparison of the number of subject deaths per week during the 33 Weeks of this study found no significant difference between the number of deaths in the vaccinated versus placebo arms for the first 20 weeks of the trial, the placebo-controlled portion of the trial. After Week 20, as subjects in the Placebo were unblinded and vaccinated, deaths among this still unvaccinated cohort of this group slowed and eventually plateaued. Deaths in the BNT162b2 vaccinated subjects continued at the same rate. Our analysis revealed inconsistencies between the subject data listed in the 6-Month Interim Report and publications authored by Pfizer/BioNTech trial site administrators. Most importantly, we found evidence of an over 3.7-fold increase in number of deaths due to cardiovascular events in BNT162b2 vaccinated subjects compared to Placebo controls. This significant adverse event signal was not reported by Pfizer/BioNTech. Potential sources of these data inconsistencies are identified.