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Abstract Aims We report the results of a real‐world study based on heart failure (HF) patients' continuous remote monitoring strategy using the CardioMEMS system to assess the impact of this device on healthcare outcomes, costs, and patients' management and quality of life. Methods and results We enrolled seven patients (69.00 ± 4.88 years; 71.43% men) with HF, implanted with CardioMEMS, and daily remote monitored to optimize both tailored adjustments of home therapy and/or hospital infusions of levosimendan. We recorded clinical, pharmacological, biochemical, and echocardiographic parameters and data on hospitalizations, emergency room access, visits, and costs. Following the implantation of CardioMEMS, we observed a 50% reduction in the total number of hospitalizations and a 68.7% reduction in the number of days in the hospital. Accordingly, improved patient quality of life was recorded with EQ‐5D (pre 58.57 ± 10.29 vs. 1 year post 84.29 ± 19.02, P = 0.008). Echocardiographic data show a statistically significant improvement in both systolic pulmonary artery pressure (47.86 ± 8.67 vs. 35.14 ± 9.34, P = 0.022) and E/e′ (19.33 ± 5.04 vs. 12.58 ± 3.53, P = 0.023). The Quantikine® HS High‐Sensitivity Kit determined elevated interleukin‐6 values at enrolment in all patients, with a statistically significant reduction after 6 months (P = 0.0211). From an economic point of view, the net savings, including the cost of CardioMEMS, were on average €1580 per patient during the entire period of observation, while the analysis performed 12 months after the implant vs. 12 months before showed a net saving of €860 per patient. The ad hoc analysis performed on the levosimendan infusions resulted in 315 days of hospital avoidance and a saving of €205 158 for the seven patients enrolled during the observation period. Conclusions This innovative strategy prevents unplanned access to the hospital and contributes to the efficient use of healthcare facilities, human resources, and costs.

Background: Cardiovascular diseases (CVDs) are associated with very high rates of re-hospitalization and mortality worldwide, so the complexity of these pathologies requires frequent access to hospital facilities. The guidelines also emphasize the importance of cardiac rehabilitation (CR) programs, which have demonstrated a favorable effect on outcomes, and cardiac telerehabilitation (CTR) could represent an innovative healthcare delivery model. The aim of our review is to study how technologies used in rehabilitation have changed over time and also to understand what types of rehabilitation programs have been used in telerehabilitation. Methods: We searched randomized controlled trials (RCTs) in three electronic databases, PubMed, Web of Science, and Scopus, from January 2015 to January 2024, using relevant keywords. Initially, 502 articles were found, and 79 duplicates were identified and eliminated with EndNote. Results: In total, 16 RCTs fulfilled the pre-defined criteria, which were analyzed in our systematic review. The results showed that after CTR, there was a significant improvement in main outcome measures, as well as in relation to technological advances. Conclusions: Moreover, compared to center-based rehabilitation, CTR can offer further advantages, with better cost-effectiveness, the breakdown of geographical barriers, and the improvement of access to treatment for the female population, which is traditionally more socially committed.

Chronic kidney disease (CKD) is a global health issue with a rising prevalence, affecting 697.5 million people worldwide. It imposes a substantial burden, contributing to 35.8 million disability-adjusted life years (DALYs) and 1.2 million deaths in 2017. The mortality rate for CKD has increased by 41.5% between 1990 and 2017, positioning it as a significant cause of global mortality. CKD is associated with diverse health complications, impacting cardiovascular, neurological, nutritional, and endocrine aspects. One prominent complication is CKD–mineral and bone disorder (MBD), a complex condition involving dysregulation of bone turnover, mineralization, and strength, accompanied by soft tissue and vascular calcification. Alterations in mineral metabolism, including calcium, phosphate, parathyroid hormone (PTH), vitamin D, fibroblast growth factor-23 (FGF-23), and Klotho, play pivotal roles in CKD-MBD. These disturbances, observed early in CKD, contribute to the progression of bone disorders and renal osteodystrophy (ROD). Vascular calcification (VC) is a key component of CKD-MBD, accelerated by CKD. The pathophysiology involves complex processes in vascular smooth muscle cells and the formation of calciprotein particles (CPP). VC is closely linked to cardiovascular events and mortality, emphasizing its prognostic significance. Various serum markers and imaging techniques, including lateral plain X-ray, Kauppila Score, Adragao Score, and pulse wave velocity, aid in VC detection. Additionally, pQCT provides valuable information on arterial calcifications, offering an advantage over traditional scoring systems. CKD poses a substantial global health burden, and its complications, including CKD-MBD and VC, significantly contribute to morbidity and mortality. Understanding the intricate relationships between mineral metabolism, bone disorders, and vascular calcification is crucial for effective diagnosis and therapeutic interventions.

High glucose–induced endothelial dysfunction is an important pathological feature of diabetic vasculopathy. While genome-wide studies have identified an association between type 2 diabetes mellitus (T2DM) and increased expression of a C2 calcium-dependent domain containing 4B (C2CD4B), no study has yet explored the possible direct effect of C2CD4B on vascular function. Vascular reactivity studies were conducted using a pressure myograph, and nitric oxide and oxidative stress were assessed through difluorofluorescein diacetate and dihydroethidium, respectively. We demonstrate that high glucose upregulated both mRNA and protein expression of C2CD4B in mice mesenteric arteries in a time-dependent manner. Notably, the inhibition of C2CD4B expression by genetic knockdown efficiently prevented hyperglycemia–induced oxidative stress, endothelial dysfunction, and loss of nitric oxide (NO) bioavailability. Recombinant C2CD4B evoked endothelial dysfunction of mice mesenteric arteries, an effect associated with increased reactive oxygen species (ROS) and decreased NO production. In isolated human umbilical vein endothelial cells (HUVECs), C2CD4B increased phosphorylation of endothelial nitric oxide synthase (eNOS) at the inhibitory site Thr495 and reduced eNOS dimerization. Pharmacological inhibitors of phosphoinositide 3-kinase (PI3K), Akt, and PKCα effectively attenuated oxidative stress, NO reduction, impairment of endothelial function, and eNOS uncoupling induced by C2CD4B. These data demonstrate, for the first time, that C2CD4B exerts a direct effect on vascular endothelium via a phosphoinositide 3-kinase (PI3K)/Akt/PKCα–signaling pathway, providing a new perspective on C2CD4B as a promising therapeutic target for the prevention of oxidative stress in diabetes–induced endothelial dysfunction.

Obesity is a growing public health epidemic worldwide and is implicated in slowing improved life expectancy and increasing cardiovascular (CV) risk; indeed, several obesity-related mechanisms drive structural, functional, humoral, and hemodynamic heart alterations. On the other hand, obesity may indirectly cause CV disease, mediated through different obesity-associated comorbidities. Diet and physical activity are key points in preventing CV disease and reducing CV risk; however, these strategies alone are not always sufficient, so other approaches, such as pharmacological treatments and bariatric surgery, must support them. Moreover, these strategies are associated with improved CV risk factors and effectively reduce the incidence of death and CV events such as myocardial infarction and stroke; consequently, an individualized care plan with a multidisciplinary approach is recommended. More precisely, this review explores several interventions (diet, physical activity, pharmacological and surgical treatments) to address CV risk in obese patients and emphasizes the importance of adherence to treatments.

Sacubitril/valsartan (Sac/Val) reduces mortality in patients with heart failure with reduced ejection fraction (HFrEF) compared to enalapril. However, its effects on functional capacity remain uncertain; consequently, we sought to compare Sac/Val vs. standard medical therapy, in terms of effects on prognostically significant CPET parameters, in HFrEF patients during a long follow-up period. We conducted a single-center, observational study in an HF clinic; specifically, we retrospectively identified that 12 patients switched to Sac/Val and 13 patients that managed with standard, optimal medical therapy (control group). At each visit, baseline, and follow-up (median time: 16 months; IQ range: 11.5–22), we collected demographic information, medical history, vital signs, cardiopulmonary exercise testing, standard laboratory data, pharmacological treatment information, and echocardiographic parameters. The study’s primary end-point was the change from baseline in peak VO2 (adjusted to body weight). We did not observe significant differences between the two study groups at baseline. Similarly, we did not observe any significant differences during the follow-up in mean values of peak VO2 corrected for body weight: Sac/Val baseline: 12.2 ± 4.6 and FU: 12.7 ± 3.3 vs. control group: 13.1 ± 4.2 and 13.0 ± 4.2 mL/kg/min; p = 0.49. No significant treatment differences were observed for changes in VE/VCO2 slope: Sac/Val baseline: 35.4 ± 7.4 and FU: 37.2 ± 13.1 vs. control group: 34.6 ± 9.1 and 34.0 ± 7.3; p = 0.49. In conclusion, after a median follow-up period of 16 months, there was no significant benefit of Sac/Val on peak VO2 and other measures of CPET compared with standard optimal therapy in patients with HFrEF.

Arterial hypertension (AH) is a progressive issue that grows in importance with the increased average age of the world population. The potential role of artificial intelligence (AI) in its prevention and treatment is firmly recognized. Indeed, AI application allows personalized medicine and tailored treatment for each patient. Specifically, this article reviews the benefits of AI in AH management, pointing out diagnostic and therapeutic improvements without ignoring the limitations of this innovative scientific approach. Consequently, we conducted a detailed search on AI applications in AH: the articles (quantitative and qualitative) reviewed in this paper were obtained by searching journal databases such as PubMed and subject-specific professional websites, including Google Scholar. The search terms included artificial intelligence, artificial neural network, deep learning, machine learning, big data, arterial hypertension, blood pressure, blood pressure measurement, cardiovascular disease, and personalized medicine. Specifically, AI-based systems could help continuously monitor BP using wearable technologies; in particular, BP can be estimated from a photoplethysmograph (PPG) signal obtained from a smartphone or a smartwatch using DL. Furthermore, thanks to ML algorithms, it is possible to identify new hypertension genes for the early diagnosis of AH and the prevention of complications. Moreover, integrating AI with omics-based technologies will lead to the definition of the trajectory of the hypertensive patient and the use of the most appropriate drug. However, AI is not free from technical issues and biases, such as over/underfitting, the “black-box” nature of many ML algorithms, and patient data privacy. In conclusion, AI-based systems will change clinical practice for AH by identifying patient trajectories for new, personalized care plans and predicting patients’ risks and necessary therapy adjustments due to changes in disease progression and/or therapy response.

Cardiovascular diseases (CVDs) are the leading cause of death and illness in Europe and worldwide, responsible for a staggering 47% of deaths in Europe. Over the past few years, there has been increasing evidence pointing to bioactive sphingolipids as drivers of CVDs. Among them, most studies place emphasis on the cardiovascular effect of ceramides and sphingosine-1-phosphate (S1P), reporting correlation between their aberrant expression and CVD risk factors. In experimental in vivo models, pharmacological inhibition of de novo ceramide synthesis averts the development of diabetes, atherosclerosis, hypertension and heart failure. In humans, levels of circulating sphingolipids have been suggested as prognostic indicators for a broad spectrum of diseases. This article provides a comprehensive review of sphingolipids’ contribution to cardiovascular, cerebrovascular and metabolic diseases, focusing on the latest experimental and clinical findings. Cumulatively, these studies indicate that monitoring sphingolipid level alterations could allow for better assessment of cardiovascular disease progression and/or severity, and also suggest them as a potential target for future therapeutic intervention. Some approaches may include the down-regulation of specific sphingolipid species levels in the circulation, by inhibiting critical enzymes that catalyze ceramide metabolism, such as ceramidases, sphingomyelinases and sphingosine kinases. Therefore, manipulation of the sphingolipid pathway may be a promising strategy for the treatment of cardio- and cerebrovascular diseases.

Omega-3 fatty acids have been shown to exert several beneficial effects in the prevention of cardiovascular and cerebrovascular diseases. The objective of the present study was to analyze the effects of a novel high-load omega-3 lysine complex, AvailOm®, its related constituents and a novel mixture of AvailOm® with specific vasoactive anthocyanins on vascular function in mice resistance artery. Pressure myograph was used to perform vascular reactivity studies. Nitric oxide and oxidative stress were assessed by difluorofluorescein diacetate and dihydroethidium, respectively. Increasing doses of AvailOm® exerted a dose-response vasorelaxation via AMPK-eNOS-mediated signaling. Omega-3 Ethyl Ester was identified as the main bioactive derivative of AvailOm®, being capable of inducing vasorelaxant action to the same extent of entire product. The combination of AvailOm® with a mix of potent vasoactive anthocyanins (C3-glu + DP3-glu + Mal3-glu + Mal3-gal + PEO3-gal), strongly protected mesenteric arteries from vascular dysfunction and oxidative stress evoked by oxidized-LDL. These data demonstrate for the first time the direct effects of AvailOm® on resistance arteries. The evidence that the combination of specific vasoactive anthocyanins and AvailOm® further enhanced the vasculoprotective properties of these compounds, may offer new promising perspectives for preventing the onset of cardiovascular and cerebrovascular events.

Background High blood pressure (BP) has long been recognized as a major health threat and, particularly, a major risk factor for stroke, cardiovascular disease, and end‐organ damage. However, the identification of a novel, alternative, integrative approach for the control of BP and cardiovascular protection is still needed. Methods and Results Sixty‐nine uncontrolled hypertension patients, aged 40 to 68 years, on antihypertensive medication were enrolled in 2 double‐blind studies. Forty‐five were randomized to placebo or a new nutraceutical combination named AkP05, and BP, endothelial function, and circulating nitric oxide were assessed before and at the end of 4 weeks of treatment. Twenty‐four patients were randomized to diuretic or AkP05 for 4 weeks and underwent a cardiopulmonary exercise test to evaluate the effects of AkP05 on functional capacity of the cardiovascular, pulmonary, and muscular systems. Vascular and molecular studies were undertaken on mice to characterize the action of the single compounds contained in the AkP05 nutraceutical combination. AkP05 supplementation reduced BP, improved endothelial function, and increased nitric oxide release; cardiopulmonary exercise test revealed that AkP05 increased maximum O2 uptake, stress tolerance, and maximal power output. In mice, AkP05 reduced BP and improved endothelial function, evoking increased nitric oxide release through the PKCα/Akt/endothelial nitric oxide synthase pathway and reducing reactive oxygen species production via NADPH‐oxidase inhibition. These effects were mediated by synergism of the single compounds of AkP05. Conclusions This is the first study reporting positive effects of a nutraceutical combination on the vasculature and exercise tolerance in treated hypertensive patients. Our findings suggest that AkP05 may be used as an adjunct for the improvement of cardiovascular protection and to better control BP in uncontrolled hypertension.

Latent Mycobacterium tuberculosis infection (LTBI) and active tuberculosis in prisoners are higher than the general population and are two public health concerns, especially in low- and middle-income countries. We conducted a cross-sectional study to determine the prevalence and the factors associated with LTBI among the inmate population detained in three Southern Italian penitentiaries. Tuberculin intradermal reaction skin test was performed on the inmates who agreed to participate in the study. In case of positivity, the QuantiFERON-TB test was performed. In those positive to QuantiFERON, chest X-ray films were performed, and treatment initiated. A total of 381 inmates accepted to participate. The prevalence of LTBI was 4.2%. In the analysis, LTBI was associated with no self-reported contact with active tuberculosis patients within the prisons, and 10% of subjects admitted the use of inhaled drugs. No HIV coinfections were found. No cases of active symptomatic tuberculosis were identified during the study period. Our results confirm that incarceration increases the risk of tuberculous infection. Non-EU nationality and a history of drug addiction appear to be major risk factors for tuberculosis infection in the penitentiary setting. Reinforcing tuberculosis control is essential to prevent its transmission in prisons.

Vitamin D is the first item of drug expenditure for the treatment of osteoporosis. Its deficiency is a condition that affects not only older individuals but also young people. Recently, the scientific community has focused its attention on the possible role of vitamin D in the development of several chronic diseases such as cardiovascular and metabolic diseases. This review aims to highlight the possible role of vitamin D in cardiovascular and metabolic diseases. In particular, here we examine (1) the role of vitamin D in diabetes mellitus, metabolic syndrome, and obesity, and its influence on insulin secretion; (2) its role in atherosclerosis, in which chronic vitamin D deficiency, lower than 20 ng/mL (50 nmol/L), has emerged among the new risk factors; (3) the role of vitamin D in essential hypertension, in which low plasma levels of vitamin D have been associated with both an increase in the prevalence of hypertension and diastolic hypertension; (4) the role of vitamin D in peripheral arteriopathies and aneurysmal pathology, reporting that patients with peripheral artery diseases had lower vitamin D values than non-suffering PAD controls; (5) the genetic and epigenetic role of vitamin D, highlighting its transcriptional regulation capacity; and (6) the role of vitamin D in cardiac remodeling and disease. Despite the many observational studies and meta-analyses supporting the critical role of vitamin D in cardiovascular physiopathology, clinical trials designed to evaluate the specific role of vitamin D in cardiovascular disease are scarce. The characterization of the importance of vitamin D as a marker of pathology should represent a future research challenge.

Many studies have shown that resveratrol has a lot of therapeutic effects on liver disorders. Its administration can significantly increase the survival rate after liver transplantation, reduce fat deposition and ischemia-induced necrosis and apoptosis in Wistar rats. Resveratrol can provide Liver protection against chemical, cholestatic, and alcohol-mediated damage. It can improve glucose metabolism and lipid profile, reduce liver fibrosis, and steatosis. Additionally, it is capable of altering the fatty acid composition of the liver cells. Resveratrol may be a potential treatment option for the management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant, and calorie-restricting effects. There are also studies that have evaluated the effect of resveratrol on lipid and liver enzyme profiles among patients with metabolic syndrome (MetS) and related disorders. Based on the extent of liver disease worldwide and the need to find new treatment possibilities, this review critically examines current in vitro and in vivo preclinical studies and human clinical studies related to liver protection.

Recent scientific literature has investigated the cardiovascular implications of COVID-19. The mechanisms of cardiovascular damage seem to involve the protein angiotensin-converting enzyme 2 (ACE2), to which severe acute respiratory syndrome (SARS) coronavirus-2 (CoV-2) binds to penetrate cells and other mechanisms, most of which are still under study. Cardiovascular sequelae of COVID-19 include heart failure, cardiomyopathy, acute coronary syndrome, arrhythmias, and venous thromboembolism. This article aims to collect scientific evidence by exploiting PubMed, Scopus, and Pedro databases to highlight the cardiovascular complications of COVID-19 and to define the physiotherapy treatment recommended for these patients. Exercise training (ET), an important part of cardiac rehabilitation, is a powerful tool in physiotherapy, capable of inducing significant changes in the cardiovascular system and functional in the recovery of endothelial dysfunction and for the containment of thromboembolic complications. In conclusion, due to the wide variety of possible exercise programs that can be obtained by combining intensity, duration, and speed in various ways, and by adjusting the program based on continuous patient monitoring, exercise training is well suited to the treatment of post-COVID patients with an impaired cardiovascular system of various degrees.

Aging can be seen as process characterized by accumulation of oxidative stress induced damage. Oxidative stress derives from different endogenous and exogenous processes, all of which ultimately lead to progressive loss in tissue and organ structure and functions. The oxidative stress theory of aging expresses itself in age-related diseases. Aging is in fact a primary risk factor for many diseases and in particular for cardiovascular diseases and its derived morbidity and mortality. Here we highlight the role of oxidative stress in age-related cardiovascular aging and diseases. We take into consideration the molecular mechanisms, the structural and functional alterations, and the diseases accompanied to the cardiovascular aging process.

Cardiovascular diseases (CVDs) such as hypertension, atherosclerosis, myocardial infarction, and diabetes are a significant public health problem worldwide. Although several novel pharmacological treatments to reduce the progression of CVDs have been discovered during the last 20 years, the better way to contain the onset of CVDs remains prevention. In this regard, nutraceuticals seem to own a great potential in maintaining human health, exerting important protective cardiovascular effects. In the last years, there has been increased focus on identifying natural compounds with cardiovascular health-promoting effects and also to characterize the molecular mechanisms involved. Although many review articles have focused on the individual natural compound impact on cardiovascular diseases, the aim of this manuscript was to examine the role of the most studied nutraceuticals, such as resveratrol, cocoa, quercetin, curcumin, brassica, berberine and Spirulina platensis, on different CVDs.

Diabetes mellitus is a common disease that affects 3–5% of the general population in Italy. In some countries of northern Europe or in North America, it can even affect 6–8% of the population. Of great concern is that the number of cases of diabetes is constantly increasing, probably due to the increase in obesity and the sedentary nature of the population. According to the World Health Organization, in the year 2030 there will be 360 million people with diabetes, compared to 170 million in 2000. This has important repercussions on the lives of patients and their families, and on health systems that offer assistance to patients. In this review, we try to describe in an organized way the pathophysiological continuity between diabetes mellitus, endothelial dysfunction, and platelet hyperaggregation, highlighting the main molecular mechanisms involved and the interconnections.

A growing number of evidences report that aging represents the major risk factor for the development of cardio and cerebrovascular diseases. Understanding Aging from a genetic, biochemical and physiological point of view could be helpful to design a better medical approach and to elaborate the best therapeutic strategy to adopt, without neglecting all the risk factors associated with advanced age. Of course, the better way should always be understanding risk-to-benefit ratio, maintenance of independence and reduction of symptoms. Although improvements in treatment of cardiovascular diseases in the elderly population have increased the survival rate, several studies are needed to understand the best management option to improve therapeutic outcomes. The aim of this review is to give a 360° panorama on what goes on in the fragile ecosystem of elderly, why it happens and what we can do, right now, with the tools at our disposal to slow down aging, until new discoveries on aging, cardio and cerebrovascular diseases are at hand.