Search

Background and Aims: Vitamin D deficiency is a common cause of secondary hyperparathyroidism, particularly in elderly people. The aim of this study was to evaluate the associations of serum vitamin D and parathormone (PTH) concentrations with blood pressure values and hypertension-mediated target organ damage (HMOD), including left ventricular (LV) hypertrophy and carotid plaque (CP)., Methods and Results: We enrolled consecutive patients admitted to the Hypertension Center of Federico II University Hospital in Naples, Italy. All patients underwent carotid doppler ultrasound and echocardiography, measurement of vitamin D and PTH levels and main clinical and laboratory parameters. A total of 126 patients (mean age 54 years, 68% males) were enrolled. Pearson's correlation analysis indicated that PTH levels directly correlated with age, diabetes, dyslipidemia, hypertension, fasting glucose, and LV mass, and inversely with glomerular filtration rate, LDL cholesterol, and vitamin D. Vitamin D levels correlated inversely with PTH, diabetes and CP. Multivariate regression models indicated that an increased LV mass was associated with the presence of obesity (β = 0.342; P = 0.001). Maximal intima-media thickness was significantly associated with older age (β = 0.303; P = 0.033). Combined presence of low vitamin D/high PTH levels were associated with more than 4-fold increased risk of having CP in both univariate (OR = 4.77, p = 0.0001) and multivariate regression analysis (OR = 4.52, p = 0.014)., Conclusion: In a population at high cardiovascular risk, vitamin D and PTH levels were not directly associated with blood pressure values and HMOD. Secondary hyperparathyroidism due to vitamin D deficiency is associated with carotid atherosclerosis independently of other common cardiovascular risk factors., Competing Interests: Conflicts of interest The authors declare they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Heart Failure (HF) poses a challenge for our health systems, and early detection of Worsening HF (WHF), defined as a deterioration in symptoms and clinical and instrumental signs of HF, is vital to improving prognosis. Predicting WHF in a phase that is currently undiagnosable by physicians would enable prompt treatment of such events in patients at a higher risk of WHF. Although the role of Artificial Intelligence in cardiovascular diseases is becoming part of clinical practice, especially for diagnostic and prognostic purposes, its usage is often considered not completely reliable due to the incapacity of these models to provide a valid explanation about their output results. Physicians are often reluctant to make decisions based on unjustified results and see these models as black boxes. This study aims to develop a novel diagnostic model capable of predicting WHF while also providing an easy interpretation of the outcomes. We propose a threshold-based binary classifier built on a mathematical model derived from the Genetic Programming approach. This model clearly indicates that WHF is closely linked to creatinine, sPAP, and CAD, even though the relationship of these variables and WHF is almost complex. However, the proposed mathematical model allows for providing a 3D graphical representation, which medical staff can use to better understand the clinical situation of patients. Experiments conducted using retrospectively collected data from 519 patients treated at the HF Clinic of the University Hospital of Salerno have demonstrated the effectiveness of our model, surpassing the most commonly used machine learning algorithms. Indeed, the proposed GP-based classifier achieved a 96% average score for all considered evaluation metrics and fully supported the controls of medical staff. Our solution has the potential to impact clinical practice for HF by identifying patients at high risk of WHF and facilitating more rapid diagnosis, targeted treatment, and a reduction in hospitalizations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: We declare no conflicting interests.

In recent years, thanks to the advent of new classes of drugs (ARNI and SGLT2-i), the prognosis of patients suffering from heart failure with reduced ejection fraction (HFrEF) has gradually improved. Nonetheless, there is a residual risk that is not targeted by these therapies. Currently, it is recognized that vericiguat, an oral stimulator of soluble guanylate cyclase (sGC), can restore the NO-sGC-cGMP pathway, through stimulation and activation of sGC, aiming to increase cGMP levels with a reduction in heart failure-related oxidative stress and endothelial dysfunction. Even though the Victoria trial demonstrated that HFrEF patients in treatment with vericiguat showed a 10% reduction in the composite of cardiovascular mortality and rehospitalization for heart failure, statistically significantly reducing heart failure hospitalization, the international guidelines limit its use as a second-line drug for patients with worsening symptomatology despite optimized medical therapy. Furthermore, vericiguat has proved to be a valid therapeutic ally especially in those patients with comorbidities such that they cannot receive the classic four-pillar therapy of HF (in particular renal failure). In this review, the authors report on randomized clinical trials, substudies, and meta-analysis about vericiguat in HFrEF, emphasizing the strengths that would suggest the possible role of vericiguat as the fifth pillar of the HFrEF treatment, acknowledging that there are still gaps in the evidence that need to be clarified., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Ischemia with non-obstructive coronary artery (INOCA) is a common cause of hospital admissions, leading to negative outcomes and reduced quality of life. Central to its pathophysiology is endothelial dysfunction, which contributes to myocardial ischemia despite the absence of significant coronary artery blockage. Addressing endothelial dysfunction is essential in managing INOCA to alleviate symptoms and prevent cardiovascular events. Recent studies have identified diabetes mellitus (DM) as a significant factor exacerbating INOCA complications by promoting endothelial impairment and coronary microvascular dysfunction. MicroRNAs (miRNAs) have emerged as potential biomarkers and therapeutic targets in various biological processes, including endothelial dysfunction and cardiovascular diseases. However, research on miRNA biomarkers in INOCA patients is sparse. In this study, we examined a panel of circulating miRNAs involved in the regulation of endothelial function in INOCA patients with and without DM. We analyzed miRNA expression using RT-qPCR in a cohort of consecutive INOCA patients undergoing percutaneous coronary intervention. We detected a significant dysregulation of miR-363-5p and miR-92a-3p in INOCA patients with DM compared to those without DM, indicating their role as biomarkers for predicting and monitoring endothelial dysfunction in INOCA patients with DM., (© 2024. The Author(s).)

Cardiovascular disease (CVD) is the leading cause of morbimortality in Europe and worldwide. CVD imposes a heterogeneous spectrum of cardiac remodelling, depending on the insult nature, that is, pressure or volume overload, ischaemia, arrhythmias, infection, pathogenic gene variant, or cardiotoxicity. Moreover, the progression of CVD-induced remodelling is influenced by sex, age, genetic background and comorbidities, impacting patients' outcomes and prognosis. Cardiac reverse remodelling (RR) is defined as any normative improvement in cardiac geometry and function, driven by therapeutic interventions and rarely occurring spontaneously. While RR is the outcome desired for most CVD treatments, they often only slow/halt its progression or modify risk factors, calling for novel and more timely RR approaches. Interventions triggering RR depend on the myocardial insult and include drugs (renin-angiotensin-aldosterone system inhibitors, beta-blockers, diuretics and sodium-glucose cotransporter 2 inhibitors), devices (cardiac resynchronization therapy, ventricular assist devices), surgeries (valve replacement, coronary artery bypass graft), or physiological responses (deconditioning, postpartum). Subsequently, cardiac RR is inferred from the degree of normalization of left ventricular mass, ejection fraction and end-diastolic/end-systolic volumes, whose extent often correlates with patients' prognosis. However, strategies aimed at achieving sustained cardiac improvement, predictive models assessing the extent of RR, or even clinical endpoints that allow for distinguishing complete from incomplete RR or adverse remodelling objectively, remain limited and controversial. This scientific statement aims to define RR, clarify its underlying (patho)physiologic mechanisms and address (non)pharmacological options and promising strategies to promote RR, focusing on the left heart. We highlight the predictors of the extent of RR and review the prognostic significance/impact of incomplete RR/adverse remodelling. Lastly, we present an overview of RR animal models and potential future strategies under pre-clinical evaluation., (© 2024 European Society of Cardiology.)

Background: Prediabetes has garnered increasing attention due to its association with cardiovascular conditions, especially hypertension, which heightens the risk of prefrailty and frailty among older individuals., Methods: We screened elders with prefrail hypertension from March 2021 to January 2023. We assessed the correlation linking cognitive dysfunction (Montreal Cognitive Assessment score), insulin resistance (triglyceride-to-glucose index), and physical impairment (5-meter gait speed). Then, we measured the risk of developing frailty after a 1-year follow-up period, adjusting the outcome using multivariable Cox regression analysis. We also investigated the impact of administering 500 mg of metformin once daily to a subset of frail subjects for an additional 6 months., Results: We assessed the relationship between the triglyceride-to-glucose index and the Montreal Cognitive Assessment score, observing a significant correlation (r, 0.880; P <0.0001). Similarly, we analyzed the association between the triglyceride-to-glucose index and 5-meter gait speed, uncovering a significant link between insulin resistance and physical impairment (r, 0.809; P <0.0001). Prediabetes was found to significantly ( P <0.0001) elevate the risk of frailty development compared with individuals without prediabetes by the end of the 1-year follow-up, a finding confirmed via multivariable analysis with Cox regression. Furthermore, among the subgroup of subjects who developed frailty, those who received metformin exhibited a significant decrease in frailty levels ( P <0.0001)., Conclusions: Insulin resistance and prediabetes play substantial roles in the development of cognitive and physical impairments, highlighting their importance in managing hypertension, even before the onset of frank diabetes. Metformin, a well-established drug for the treatment of diabetes, has shown favorable effects in mitigating frailty., Competing Interests: Disclosures None.

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 factors, 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.

Background: Hypertension and chronic kidney disease (CKD) pose significant public health challenges, sharing intertwined pathophysiological mechanisms. Prediabetes is recognized as a precursor to diabetes and is often accompanied by cardiovascular comorbidities such as hypertension, elevating the risk of pre-frailty and frailty. Albuminuria is a hallmark of organ damage in hypertension amplifying the risk of pre-frailty, frailty, and cognitive decline in older adults. We explored the association between albuminuria and cognitive impairment in frail older adults with prediabetes and CKD, assessing cognitive levels based on estimated glomerular filtration rate (eGFR)., Methods: We conducted a study involving consecutive frail older patients with hypertension recruited from March 2021 to March 2023 at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, followed up after three months. Inclusion criteria comprised age over 65 years, prior diagnosis of hypertension without secondary causes, prediabetes, frailty status, Montreal Cognitive Assessment (MoCA) score < 26, and CKD with eGFR > 15 ml/min., Results: 237 patients completed the study. We examined the association between albuminuria and MoCA Score, revealing a significant inverse correlation (r: 0.8846; p < 0.0001). Subsequently, we compared MoCA Score based on eGFR, observing a significant difference (p < 0.0001). These findings were further supported by a multivariable regression analysis, with albuminuria as the dependent variable., Conclusions: Our study represents the pioneering effort to establish a significant correlation between albuminuria and eGFR with cognitive function in frail hypertensive older adults afflicted with prediabetes and CKD., (© 2024. The Author(s).)

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.

While chronic heart failure (CHF) treatment has considerably improved patient prognosis and survival, the therapeutic management of acute heart failure (AHF) has remained virtually unchanged in the last decades. This is partly due to the scarcity of pre-clinical models for the pathophysiological assessment and, consequently, the limited knowledge of molecular mechanisms involved in the different AHF phenotypes. This scientific statement outlines the different trajectories from acute to CHF originating from the interaction between aetiology, genetic and environmental factors, and comorbidities. Furthermore, we discuss the potential molecular targets capable of unveiling new therapeutic perspectives to improve the outcome of the acute phase and counteracting the evolution towards CHF., Competing Interests: Conflict of interest: T.T. received speaker fees and/or holds advisory board seats from Böhringer Ingelheim, Sanofi-Genzyme, Takeda, Novo-Nordisk, Amicus Therapeutics, KSILINK not related to the present article. T.T. filed and licensed patents about non-coding RNAs, and he is founder and shareholder of Cardior Pharmaceuticals (not related to this article). P.R. received travel support, speaker fees, honoraria from Novartis, Vifor, Böhringer, and Daiichi Sankyo (not related to this article). L.W.V.L. received Consultancy fees to UMCU from Abbott, Medtronic, Vifor, Novartis (not related to the present article). W.L. received honoraria from Bristol-Myers Squibb (MyoKardia), Merck, Sharp& Dohme (MSD, USA), and Servier, as well as a research grant from MSD (not related to the present article). J.B. received honoraria for lectures/consulting from Novartis, Vifor, Bayer, Pfizer, Boehringer Ingelheim, AstraZeneca, Cardior, CVRx, BMS, Amgen, Corvia, not related to the present article; and research support for the department from Zoll, CVRx, Abiomed, not related to the present article. C.G.T. reports Receipt of honoraria or consultation fees: VivaLyfe, Univers Formazione, Solaris, Myocardial Solutions; and is listed as an inventor of 2 patents related to HF. All other authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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 VO 2 (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 VO 2 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/VCO 2 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 VO 2 and other measures of CPET compared with standard optimal therapy in patients with HFrEF.

Prevention and effective treatment of cardiovascular disease are progressive issues that grow in tandem with the average age of the world population. Over recent decades, the potential role of artificial intelligence in cardiovascular medicine has been increasingly recognized because of the incredible amount of real-world data (RWD) regarding patient health status and healthcare delivery that can be collated from a variety of sources wherein patient information is routinely collected, including patient registries, clinical case reports, reimbursement claims and billing reports, medical devices, and electronic health records. Like any other (health) data, RWD can be analysed in accordance with high-quality research methods, and its analysis can deliver valuable patient-centric insights complementing the information obtained from conventional clinical trials. Artificial intelligence application on RWD has the potential to detect a patient's health trajectory leading to personalized medicine and tailored treatment. This article reviews the benefits of artificial intelligence in cardiovascular prevention and management, focusing on diagnostic and therapeutic improvements without neglecting the limitations of this new scientific approach., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

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.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to be a global challenge due to resulting morbidity and mortality. Cardiovascular (CV) involvement is a crucial complication in coronavirus disease 2019 (COVID-19), and no strategies are available to prevent or specifically address CV events in COVID-19 patients. The identification of molecular partners contributing to CV manifestations in COVID-19 patients is crucial for providing early biomarkers, prognostic predictors, and new therapeutic targets. The current report will focus on the role of microRNAs (miRNAs) in CV complications associated with COVID-19. Indeed, miRNAs have been proposed as valuable biomarkers and predictors of both cardiac and vascular damage occurring in SARS-CoV-2 infection. SIGNIFICANCE STATEMENT: It is essential to identify the molecular mediators of coronavirus disease 2019 (COVID-19) cardiovascular (CV) complications. This report focused on the role of microRNAs in CV complications associated with COVID-19, discussing their potential use as biomarkers, prognostic predictors, and therapeutic targets., (Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics.)

Purpose: Home blood pressure monitoring (HBPM) might be considered a valid alternative to ambulatory blood pressure monitoring (ABPM) for both the diagnosis and management of hypertension. Correct information on how to perform HBPM are crucial for its reliability. The aim of the present survey was to assess if hypertensive patients followed current recommendation on how to correctly perform HBPM measurements., Materials and Methods: The survey included 30 different items on how to perform the HBPM. It was developed by the 'Young Investigators' group of the Italian Society of Arterial Hypertension (SIIA) and it was administered during the office visit between May 2019 and December 2021., Results: A total of 643 hypertensive patients participated in the study. Main results show that, despite the rate of informed patients was relatively high (71% of the whole population), unacceptable number of patients did not follow indications on how to perform a correct HBPM. Patients who were informed on how to measure home BP had a significantly higher rate of correct position during measurement (78 vs. 22%, p  < 0.01), avoidance of talking and moving during measurement (68 vs. 32%, p  < 0.0001), and correct number and time interval between two measurements (85 vs. 15%, p  < 0.001). More accurate measurements of home BP were associated with less prevalence of carotid plaque., Conclusions: Correct performance for HBPM is low among patients treated in Italian hypertension centers. These findings shed light on the importance of correct HBPM measurements for the detection of accurate BP values for the proper management of hypertensive patients.

Dilated cardiomyopathy (DCM) is a complex disease affecting young adults. It is a pathological condition impairing myocardium activity that leads to heart failure and, in the most severe cases, transplantation, which is currently the only possible therapy for the disease. DCM can be attributed to many genetic determinants interacting with environmental factors, resulting in a highly variable phenotype. Due to this complexity, the early identification of causative gene mutations is an important goal to provide a genetic diagnosis, implement pre-symptomatic interventions, and predict prognosis. The advent of next-generation sequencing (NGS) has opened a new path for mutation screening, and exome sequencing provides a promising approach for identifying causal variants in known genes and novel disease-associated candidates. We analyzed the whole-exome sequencing (WES) of 15 patients affected by DCM without overloading (hypertension, valvular, or congenital heart disease) or chronic ischemic conditions. We identified 70 pathogenic or likely pathogenic variants and 1240 variants of uncertain clinical significance. Gene ontology enrichment analysis was performed to assess the potential connections between affected genes and biological or molecular function, identifying genes directly related to extracellular matrix organization, transcellular movement through the solute carrier and ATP-binding cassette transporter, and vitamin B12 metabolism. We found variants in genes implicated to a different extent in cardiac function that may represent new players in the complex genetic scenario of DCM.

Aims: The angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (Sac/Val) demonstrated to be superior to enalapril in reducing hospitalizations, cardiovascular and all-cause mortality in patients with ambulatory heart failure and reduced ejection fraction (HFrEF), in particular when it is maximally up-titrated. Unfortunately, the target dose is achieved in less than 50% of HFrEF patients, thus undermining the beneficial effects on the outcomes. In this study, we aimed to evaluate the role of Sac/Val and its titration dose on reverse cardiac remodelling and determine which echocardiographic index best predicts the up-titration success., Methods and Results: From January 2020 to June 2021, we retrospectively identified 95 patients (65.6 [59.1-72.8] years; 15.8% females) with chronic HFrEF who were prescribed Sac/Val from the HF Clinics of 5 Italian University Hospitals and evaluated the tolerability of Sac/Val high dose (the ability of the patient to achieve and stably tolerate the maximum dose) as the primary endpoint in the cohort. We used a multivariable logistic regression analysis, with a stepwise backward selection method, to determine the independent predictors of Sac/Val maximum dose tolerability, using, as candidate predictors, only variables with a P-value < 0.1 in the univariate analyses. Candidate predictors identified for the multivariable backward logistic regression analysis were age, sex, body mass index (BMI), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), dyslipidaemia, atrial fibrillation, systolic blood pressure (SBP), baseline tolerability of ACEi/ARBs maximum dose, left ventricle global longitudinal strain (LVgLS), LV ejection fraction (EF), tricuspid annulus plane systolic excursion (TAPSE), right ventricle (RV) fractional area change (FAC), RV global and free wall longitudinal strain (RVgLS and RV-FW-LS). After the multivariable analysis, only one categorical (ACEi/ARBs maximum dose at baseline) and three continuous (younger age, higher SBP, and higher TAPSE), resulted significantly associated with the study outcome variable with a strong discriminatory capacity (area under the curve 0.874, 95% confidence interval (CI) (0.794-0.954) to predict maximum Sac/Val dose tolerability., Conclusions: Our study is the first to analyse the potential role of echocardiography and, in particular, of RV dysfunction, measured by TAPSE, in predicting Sac/Val maximum dose tolerability. Therefore, patients with RV dysfunction (baseline TAPSE <16 mm, in our cohort) might benefit from a different strategy to titrate Sac/Val, such as starting from the lowest dose and/or waiting for a more extended period of observation before attempting with the higher doses., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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.

Though the acute effects of SARS-CoV-2 infection have been extensively reported, the long-term effects are less well described. Specifically, while clinicians endure to battle COVID-19, we also need to develop broad strategies to manage post-COVID-19 symptoms and encourage those affected to seek suitable care. This review addresses the possible involvement of the lung, heart and brain in post-viral syndromes and describes suggested management of post-COVID-19 syndrome. Post-COVID-19 respiratory manifestations comprise coughing and shortness of breath. Furthermore, arrhythmias, palpitations, hypotension, increased heart rate, venous thromboembolic diseases, myocarditis and acute heart failure are usual cardiovascular events. Among neurological manifestations, headache, peripheral neuropathy symptoms, memory issues, lack of concentration and sleep disorders are most commonly observed with varying frequencies. Finally, mental health issues affecting mental abilities and mood fluctuations, namely anxiety and depression, are frequently seen. Finally, long COVID is a complex syndrome with protracted heterogeneous symptoms, and patients who experience post-COVID-19 sequelae require personalized treatment as well as ongoing support.

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.

Insulin resistance (IRES) is a pathophysiological condition characterized by the reduced response to insulin of several tissues, including myocardial and skeletal muscle. IRES is associated with obesity, glucose intolerance, dyslipidemia, and hypertension, evolves toward type 2 diabetes, and increases the risk of developing cardiovascular diseases. Several studies designed to explore the mechanisms involved in IRES allowed the identification of a multitude of potential molecular targets. Among the most promising, G Protein Coupled Receptor Kinase type 2 (GRK2) appears to be a suitable one given its functional implications in many cellular processes. In this review, we will discuss the metabolic role of GRK2 in those conditions that are characterized by insulin resistance (diabetes, hypertension, heart failure), and the potentiality of its inhibition as a therapeutic strategy to revert both insulin resistance and its associated phenotypes.

Background: In the real world, medical practice is changing hand in hand with the development of new Artificial Intelligence (AI) systems and problems from different areas have been successfully solved using AI algorithms. Specifically, the use of AI techniques in setting up or building precision medicine is significant in terms of the accuracy of disease discovery and tailored treatment. Moreover, with the use of technology, clinical personnel can deliver a very much efficient healthcare service., Objective: This article reviews AI state-of-the-art in cardiovascular disease management, focusing on diagnostic and therapeutic improvements., Methods: To that end, we conducted a detailed PubMed search on AI application from distinct areas of cardiology: heart failure, arterial hypertension, atrial fibrillation, syncope and cardiovascular rehabilitation. Particularly, to assess the impact of these technologies in clinical decision-making, this research considers technical and medical aspects., Results: On one hand, some devices in heart failure, atrial fibrillation and cardiac rehabilitation represent an inexpensive, not invasive or not very invasive approach to long-term surveillance and management in these areas. On the other hand, the availability of large datasets (big data) is a useful tool to predict the development and outcome of many cardiovascular diseases. In summary, with this new guided therapy, the physician can supply prompt, individualised, and tailored treatment and the patients feel safe as they are continuously monitored, with a significant psychological effect., Conclusion: Soon, tailored patient care via telemonitoring can improve clinical practice because AI-based systems support cardiologists in daily medical activities, improving disease detection and treatment. However, the physician-patient relationship remains a pivotal step., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Serum uric acid (sUA) has been associated with cardiovascular risk. Although the recent mechanistic hypothesis poses the basis for the association between sUA and left ventricular mass index (LVMi), the issue remains poorly investigated in a clinical setup. Through a retrospective analysis of the database of the departmental Hypertension Clinic of University Hospital of Salerno Medical School, we identified 177 essential hypertensives (age 60.3 ± 13.3 years; 85 men), free from uric acid-modulating medications and severe chronic kidney disease, and whose sUA values, anthropometric, clinical, and echocardiographic data were available. In the studied cohort, the average duration of hypertension was 8.4 ± 7.1 years. LVMi associated with classical determinants, such as age, blood pressure, and kidney function, although after multivariate correction, only age remained significant. Also, sUA correlated positively with LVMi, as well as body size, metabolism, and kidney function. In a multivariate analysis, sUA confirmed the independent association with LVMi. Also, levels of sUA >5.6 mg/dl are associated with larger cardiac size. We confirmed our data in a replicate analysis performed in a larger population (1,379 hypertensives) from an independent clinic. Our results demonstrate that sUA increases with LVMi, and a cutoff of 5.6 mg/dl predict larger LV sizes. Our data suggest that hyperuricemia might help to stratify the risk of larger cardiac size in hypertensives., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Visco, Pascale, Virtuoso, Mongiello, Cinque, Gioia, Finelli, Mazzeo, Manzi, Morisco, Rozza, Izzo, Cerasuolo, Ciccarelli and Iaccarino.)

Food supply in the Mediterranean area has been recently modified by big retail distribution; for instance, industrial retail has favored shipments of groceries from regions that are intensive producers of mass food, generating a long supply chain (LSC) of food that opposes short supply chains (SSCs) that promote local food markets. However, the actual functional role of food retail and distribution in the determination of the risk of developing metabolic syndrome (MetS) has not been studied hitherto. The main aim of this study was to test the effects of food chain length on the prevalence of MetS in a population accustomed to the Mediterranean diet. We conducted an observational study in Southern Italy on individuals adhering to the Mediterranean diet. We examined a total of 407 subjects (41% females) with an average age of 56 ± 14.5 years (as standard deviation) and found that being on the Mediterranean diet with a SSC significantly reduces the prevalence of MetS compared with the LSC (SSC: 19.65%, LSC: 31.46%; p : 0.007). Our data indicate for the first time that the length of food supply chain plays a key role in determining the risk of MetS in a population adhering to the Mediterranean diet.

Difficult-to-control (DTC) hypertension represents a burden in real life that can be partially solved through identification of the characteristics of clinical patterns and tailoring antihypertensive strategies, including ICT-enabled integrated care (ICT-IC). In the quest for clinical predictors of DTC hypertension, we screened 482 hypertensive patients who were consecutively referred to the departmental hypertension clinic. Following a data quality check, patients were divided into controlled (C, 49.37%) and uncontrolled (UC, 50.63%) groups based on their systolic blood pressure (BP) at follow-up. We then performed statistical analysis on the demographic, clinical, laboratory, and ultrasound data and observed that older age, female sex, higher BP levels, and a family history of hypertension were predictors of DTC hypertension. We then developed a pilot service of ICT-IC, including weekly home visits by nurses and patient education on self-monitoring of BP, heart rate, body weight, and oxygen saturation using 3G-connected devices. Self-monitored data were transmitted to the hospital servers on the electronic chart of the patient for remote assessment by the hospital hypertension specialists. A total of 20 UC patients (M/F = 10/10; age: 72.04 ± 2.17 years) were enrolled to verify the efficacy of BP control without changes in medical treatment. After 1 month of the ICT-IC program, BP was reduced both at the office assessment (systolic BP (SBP): 162.40 ± 2.23 mm Hg, beginning of the program vs. 138.20 ± 4.26 mm Hg at 1 month, p < 0.01) and at home (SBP: 149.83 ± 3.44, beginning of the program vs. 134.16 ± 1.67 mm Hg at 1 month, p < 0.01). We concluded that DTC hypertension can be predicted based on the clinical characteristics at the first visit. For these patients, ICT-IC is a feasible therapeutic strategy to achieve BP control.

: 25-Hydroxyvitamin D insufficiency and increased cardiovascular risk (CVR) association is still debated. The vitamin D (VitD)-dependent parathyroid hormone (PTH) is considered as the possible actuator of VitD effects on CVR. To investigate the association of CVR, PTH and VitD, we carried out blood pressure measurements and blood samples and collected information on dietary habits, anamnestic, clinical and metabolic data of 451 participants in the Salerno area (Southern Italy) during the World Hypertension Day (17 May). CVR was calculated according to the Framingham CVR charts. The overall population mean age was 51.6 ± 0.7 years, and female sex was slightly prevalent (55%). VitD deficiency (<20 ng/ml) was most frequent (59.7%). In this population, VitD and CVR did not correlate. VitD and PTH inversely correlated (r = -0.265, P < 0.001) as expected. PTH was in direct correlation (r = 0.225, P < 0.001) with CVR. Elevated PTH (75 percentile; ≥49.5 pg/ml) levels identify a population with higher CVR (11.8 ± 0.5 vs. 8.5 ± 0.3, P < 0.001). In a multivariate analysis, both age and PTH correlate to CVR, but not VitD. In conclusion, VitD does not directly affect CVR in the overall population. Rather, increased PTH might be a better predictor of CVR.

The introduction of fixed combination of ACEi+CCB (Fixed) has significantly increased patients compliance and adherence to therapy. At the moment, however, there are no data suggesting the better control of once-daily fixed (Fixed) over free doses in separate administrations combination therapy in hypertensives. In a population of 39 consecutive outpatient patients referred to the departmental Hypertension clinic of the University Hospital of Salerno Medical School with the first diagnosis of arterial hypertension, we tested the hypothesis that the Fixed achieve a better control of blood pressure than the Free combination. Patients were randomized to either strategy and after 3 months patients underwent a clinical assessment to evaluate the antihypertensive effect. The two groups, matched for anthropometric and clinical parameters, received Amlodipine (5-10 mg/daily) and Perindopril (5-10 mg/daily). Perindopril and Amlodipine doses did not significantly differ between the two groups. After 3 months BP control was improved in both groups and BP targets were similarly reached in both groups (SBP; Fixed: 61.54%; Free 69.23%; n.s. DPB; Fixed: 80.77%; Free 84.62%; n.s.). The reduction in systolic blood pressure was similar in both groups (Fixed:7.64±2.49%; Free: 7.81±4.00%, n.s.), while the reduction of diastolic blood pressure was greater in the Fixed group (Fixed: 14.22±2.03%; Free: 4.92±5.00%, p<0.05). Although both strategies are effective in reducing BP, the use of Fixed dose has an advantage in the reduction of BP. The present study does not allow to identify the mechanisms of this difference, which can be assumed to be due to the pharmacokinetics of the drugs administered in once-daily fixed combination.