Search

Background Cardiovascular diseases are the leading cause of mortality, morbidity, and disability in the world, especially in the older adults. A relevant proportion of patients admitted to Cardiac Rehabilitation (CR) may suffer from frailty, a complex geriatric syndrome with multifactorial aetiology. Aims The hypothesis underlying the study is that frailty complicates the management of older patients undergoing CR. The main objective is, therefore, to determine the relationship between frailty and CR outcomes in hospitalized older adults. Methods The participants have been recruited among patients aged ≥ 65 years admitted at the hospital for CR. A Comprehensive Geriatric Assessment (CGA)-based Frailty Index (FI) was created following a standard procedure. The outcome was measured as the ratio between 6-min walk test (6MWT) distance at the end of CR and normal predicted values for a healthy adult of same age and gender, according to reference equations. Results The study population consisted of 559 elderly patients, 387 males (69.2%), with age of 72 (69–76) years. The most frequent diagnosis at admission was ischaemic heart disease (231, 41.5%) and overall 6MWT ratio was 0.62 ± 0.21. At the multivariable regression analysis, gender, diagnosis and FI were significantly and independently associated with 6MWT ratio (p ≤ 0.0001, p ≤ 0.001 and p ≤ 0.0001, respectively), while no significant association emerged for age. Conclusion FI resulted independently correlated to 6MWT ratio in a population of older patients undergoing in-hospital CR programs. Frailty is a multifactorial geriatric syndrome whose assessment is essential for prognostic evaluation of older patients, also in CR clinical setting.

Aims: Limited data are available regarding cardiac expression of molecules involved in heart failure (HF) pathophysiology. The majority of the studies have focused on end-stage HF with reduced ejection fraction (HFrEF) without comparison with healthy subjects, while no data are available with regard to HF with preserved ejection fraction (HFpEF). HFpEF is a condition whose multiple pathophysiological mechanisms are still not fully defined, with many proposed hypotheses remaining speculative due to limited access to human heart tissue. This study aimed at evaluating cardiac expression levels of key genes of interest in human biopsy samples from patients affected with HFrEF and HFpEF in order to possibly point out distinct phenotypes. Methods and results: Total RNA was extracted from left ventricular cardiac biopsies collected from stable patients with HFrEF (n=6) and HFpEF (n=7) and healthy subjects (n=9) undergoing elective cardiac surgery for valvular replacement, mitral valvuloplasty, aortic surgery, or coronary artery bypass. Real-time PCR was performed to evaluate the mRNA expression levels of genes involved in somatotropic axis regulation [IGF-1, IGF-1 receptor (IGF-1R), and GH receptor (GHR)], in adrenergic signalling (GRK2, GRK5, ADRB1, and ADRB2), in myocardial calcium handling (SERCA2), and in TNF-α. Patients with HFrEF and HFpEF showed reduced serum IGF-1 circulating levels when compared with controls (102±35.6, 138±11.5, and 160±13.2ng/mL, P&nbsp

Background Findings from the T.O.S.CA. Registry recently reported that patients with concomitant chronic heart failure (CHF) and impairment of insulin axis (either insulin resistance—IR or diabetes mellitus—T2D) display increased morbidity and mortality. However, little information is available on the relative impact of IR and T2D on cardiac structure and function, cardiopulmonary performance, and their longitudinal changes in CHF. Methods Patients enrolled in the T.O.S.CA. Registry performed echocardiography and cardiopulmonary exercise test at baseline and at a patient-average follow-up of 36 months. Patients were divided into three groups based on the degree of insulin impairment: euglycemic without IR (EU), euglycemic with IR (IR), and T2D. Results Compared with EU and IR, T2D was associated with increased filling pressures (E/e′ratio: 15.9 ± 8.9, 12.0 ± 6.5, and 14.5 ± 8.1 respectively, p 2) in TD2 vs EU and IR patients was recorded (respectively, 15.8 ± 3.8 ml/Kg/min, 18.4 ± 4.3 ml/Kg/min and 16.5 ± 4.3 ml/Kg/min, p 2 in the T2D group (+ 13% increase in RV dimension, − 21% decline in TAPSE/PAPS ratio and − 20% decrease in peak VO2). Conclusion The higher risk of death and CV hospitalizations exhibited by HF-T2D patients in the T.O.S.CA. Registry is associated with progressive RV ventricular dysfunction and exercise impairment when compared to euglycemic CHF patients, supporting the pivotal importance of hyperglycaemia and right chambers in HF prognosis. Trial registration ClinicalTrials.gov identifier: NCT023358017

Background The correct use of personal protective equipment (PPE) during the Covid-19 pandemic is mandatory to minimize the contagion risk. The current study aimed to evaluate quality information of YouTube™ videos on PPE use during the pandemic. Materials and methods Using Google™ Trend tool, the frequency of worldwide YouTube™ and Google™ searches for "donning and doffing" was examined. We queried YouTube™ with terms related to donning and doffing of PPE. Validated quality information assessment tools were used. Results From the 1st December 2019 to the 31st January 2021, according to YouTube™ and Google™ searches, both peaks occurred in April 2020 (69.5 and 72.0%,respectively). Of all videos, 144 were eligible for the analyses. According to misinformation tool, 90 (62.5%) videos contained inaccuracies. The median DISCERN Section 1 ranged from 3 to 5. The median DISCERN Section 3 was 4. According to Global Quality Score, 8.3% (n=12), 14.6% (n=21), 22.9% (n=33), 30.6% (n=44) and 23.6% (n=34) were classified as poor, partially poor, moderate, partially good and excellent quality videos, respectively. Conclusions Nowadays, YouTube™ may be recommended as a reliable source of information. Nevertheless, a not negligible number of videos contained inaccuracies. Future authors should improve videos contents to provide more complete information.

Heart failure (HF) is a growing public health burden, with high prevalence and mortality rates. A proportion of patients with HF have a normal ventricular ejection fraction (EF), referred to as HF with preserved EF (HFpEF), as opposed to patients with HF with reduced ejection fraction (HFrEF). HFpEF currently accounts for about 50% of all HF patients, and its prevalence is rising. Angiopoietins (ANGPTs), vascular endothelial growth factors (VEGFs) and secretory phospholipases A2 (sPLA2s) are proinflammatory mediators and key regulators of endothelial cells.

BACKGROUND: Despite severe acute respiratory syndrome (SARS)-Coronavirus (CoV-2) primarily targeting the lungs, the heart represents another critical virus target. Thus, the identification of SARS-CoV-2 disease of 2019 (COVID-19)-associated biomarkers would be beneficial to stratify prognosis and the risk of developing cardiac complications. Aldosterone and galectin-3 promote fibrosis and inflammation and are considered a prognostic biomarker of lung and adverse cardiac remodeling. Here, we tested whether galectin-3 and aldosterone levels can predict adverse cardiac outcomes in COVID-19 patients. METHODS: To this aim, we assessed galectin-3 and aldosterone serum levels in 51 patients diagnosed with COVID-19, using a population of 19 healthy subjects as controls. In in-vitro studies, we employed 3T3 fibroblasts to assess the potential roles of aldosterone and galectin-3 in fibroblast activation. RESULTS: Serum galectin-3 levels were more elevated in COVID-19 patients than healthy controls and correlated with COVID-19 severity classification and cardiac troponin-I (cTnI) serum levels. Furthermore, we observed an augmented secretion of aldosterone in COVID-19 patients. This adrenal hormone is a direct stimulator of galectin-3 secretion; therefore, we surmised that this axis could perpetrate fibrosis and adverse remodeling in these subjects. Thus, we stimulated fibroblasts with 10% of serum from COVID-19 patients. This challenge markedly rose the expression of smooth muscle alpha (α)-2 actin (ACTA2), a myofibroblast marker. CONCLUSIONS: Our study suggests that COVID-19 can affect cardiac structure and function by triggering aldosterone and galectin-3 release that may serve as prognostic and therapeutic biomarkers while monitoring the course of cardiac complications in patients suffering from COVID-19.

Although in heart failure (HF) there is a strict correlation between heart and kidney, no data are available on the potential relationship in HF between renal dysfunction (RD) and the impaired sympathetic innervation. Aim of the present study was to assess the relationship between RD and cardiac sympathetic innervation in HF patients with reduced ejection fraction. Two hundred and sixty-three patients with mild-to-severe HF underwent iodine-123 meta-iodobenzylguanidine myocardial scintigraphy to assess sympathetic innervation, evaluating early and late heart-to-mediastinum (H/M) ratios and washout rate. In all patients, glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was assessed. A direct association was found between EPI-eGFR and late H/M (r = .215; P

Background: Given the potential risk of unhealthy weight management, the monitoring of body composition in athletes is advised. However, limited data reveal how body composition measurements can benefit athlete health and, in particular, respiratory function. The aim of this study is to evaluate the impact of body composition on pulmonary function in a population of adult athletes. Methods: Data from 435 competitive adult athletes regarding body compositions parameters and spirometry are retrospectively analyzed. Results: Our study population consists of 335 males and 100 female athletes. Muscle mass and fat-free mass are significantly and positively associated with forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) in the male and female population, while waist-to-height ratio is negatively associated with FEV1, FVC, and FEV1/FVC in the male population. In multivariable analysis, muscle mass and fat-free mass show significant association with FEV1 and FVC in both males and females (p < 0.05), and waist-to-height ratio is significantly and inversely associated with FEV1 and FVC in males (p < 0.05). Conclusions: Fat-free mass and muscle mass are positively and independently associated with FEV1 and FVC in athletes of both genders, and waist-to-height ratio is inversely associated with FEV1 and FVC only among male athletes. These findings suggest that body composition in athletes may be helpful in monitoring respiratory function.

Background: Limited evidence exists regarding adverse modifications affecting cardiovascular and pulmonary function in physical active adults affected by COVID-19, especially in athletic populations. We aimed to describe the clinical presentation of COVID-19 in a cohort of competitive athletes, as well as spirometry and echocardiography findings and cardio-respiratory performance during exercise. Methods: Twenty-four competitive athletes with COVID-19 were recruited for this study after ending self-isolation and confirmation of negative laboratory results. All athletes underwent clinical evaluation, spirometry, echocardiography and cardiopulmonary exercise testing (CPET). These data were compared to a group of healthy control athletes. Results: Anosmia was the most frequent symptom present in 70.83% patients, followed by myalgia, fatigue and ageusia. The most frequent persisting symptoms were anosmia 11 (45.83%) and ageusia 8 (33.33%). Compared to controls, COVID-19 patients presented lower FEV1%: 97.5 (91.5–108) vs. 109 (106–116) p = 0.007. Peak Oxygen Uptake (VO2) in COVID-19 patients was 50.1 (47.7–51.65) vs. 49 (44.2–52.6) in controls (p = 0.618). Conclusions: Reduced exercise capacity was not identified and pulmonary and cardiovascular function are not impaired during early recovery phase in a population of physical active adults except FEV1 reduction.

Infective endocarditis (IE) is an inflammatory disease usually caused by bacteria entering the bloodstream and settling in the heart lining valves or blood vessels. Despite modern antimicrobial and surgical treatments, IE continues to cause substantial morbidity and mortality. Thus, primary prevention and enhanced diagnosis remain the most important strategies to fight this disease. In this regard, it is worth noting that for over 50 years, oral microbiota has been considered one of the significant risk factors for IE. Indeed, among the disparate recommendations from the American heart association and the European Society of Cardiology, there are good oral hygiene and prophylaxis for high-risk patients undergoing dental procedures. Thus, significant interest has grown in the role of oral microbiota and it continues to be a subject of research interest, especially if we consider that antimicrobial treatments can generate drug-resistant mutant bacteria, becoming a severe social problem. This review will describe the current knowledge about the relationship between oral microbiota, dental procedures, and IE. Further, it will discuss current methods used to prevent IE cases that originate from oral pathogens and how these should be focused on improving oral hygiene, which remains the significant persuasible way to prevent bacteremia and systemic disorders.

Aims Recent evidence supports the occurrence of multiple hormonal and metabolic deficiency syndrome (MHDS) in chronic heart failure (CHF). However, no large observational study has unequivocally demonstrated its impact on CHF progression and outcome. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Treatment in Heart Failure) Registry has been specifically designed to test the hypothesis that MHDS affects morbidity and mortality in CHF patients. Methods and Results The T.O.S.CA. Registry is a prospective, multicentre, observational study involving 19 Italian centres. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydropianoandrosterone sulfate, insulin resistance, and the presence of diabetes were evaluated. A MHDS was defined as the presence of ≥2 hormone deficiencies (HDs). Primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Four hundred and eighty heart failure patients with ejection fraction ≤45% were enrolled. MHDS or diabetes was diagnosed in 372 patients (77.5%). A total of 271 events (97 deaths and 174 cardiovascular hospitalizations) were recorded, 41% in NO-MHDS and 62% in MHDS (P Conclusion MHDS is common in CHF and independently associated with increased all-cause mortality and cardiovascular hospitalization, representing a promising therapeutic target. Trial registration ClinicalTrials.gov identifier: NCT023358017

Along with epidemiologic transitions of the global population, the burden of aortic stenosis (AS) is rapidly increasing and transcatheter aortic valve replacement (TAVR) has quickly spread; indeed, it is nowadays also employed in treating patients with AS at intermediate operative risk. Nonetheless, the less invasive interventional strategy still carries relevant issues concerning post-procedural optimal antithrombotic strategy, given the current indications provided by guidelines are not completely supported by evidence-based data. Geriatric patients suffer from high bleeding and thromboembolic risks, whose balance is particularly subtle due to the presence of concomitant conditions, such as atrial fibrillation and chronic kidney disease, that make the post-TAVR antithrombotic management particularly insidious. This scenario is further complicated by the lack of specific evidence regarding the ‘real-life’ complex conditions typical of the geriatric syndromes, thus, the management of such a heterogeneous population, ranging from healthy ageing to frailty, is far from being defined. The aim of the present review is to summarize the critical points and the most updated evidence regarding the post-TAVR antithrombotic approach in the geriatric population, with a specific focus on the most frequent clinical settings.

Introduction Heart failure (HF) is frequently associated with comorbidities. 123I-metaiodobenzylguanidine (123I-mIBG) imaging constitutes an effective tool to measure cardiac adrenergic innervation and to improve prognostic stratification in HF patients, including the risk of major arrhythmic events. Although comorbidities have been individually associated with reduced cardiac adrenergic innervation, thus suggesting increased arrhythmic risk, very comorbid HF patients seem to be less likely to experience fatal arrhythmias. We evaluated the impact of the number of comorbidities on cardiac adrenergic innervation, assessed through 123I-mIBG imaging, in patients with systolic HF. Methods Patients with systolic HF underwent clinical examination, transthoracic echocardiography and cardiac 123I-mIBG scintigraphy. The presence of 7 comorbidities/conditions (smoking, chronic obstructive pulmonary disease, diabetes mellitus, peripheral artery disease, atrial fibrillation, chronic ischemic heart disease and chronic kidney disease) was documented in the overall study population. Results The study population consisted of 269 HF patients with a mean age of 66±11 years, a left ventricular ejection fraction (LVEF) of 31±7%, and 153 (57%) patients presented ≥3 comorbidities. Highly comorbid patients presented a reduced late heart to mediastinum (H/M) ratio, while no significant differences emerged in terms of early H/M ratio and washout rate. Multiple regression analysis revealed that the number of comorbidities was not associated with mIBG parameters of cardiac denervation, which were correlated with age, body mass index and LVEF. Conclusion In systolic HF patients, the number of comorbidities is not associated with alterations in cardiac adrenergic innervation. These results are consistent with the observation that very comorbid HF patients suffer lower risk of sudden cardiac death.

Background: A link between diabetes mellitus (DM) and Parkinson’s disease (PD) have been proposed but evidence are sparse and inconsistent. Objective: Perform a systematic review of all evidence that link DM and PD characterising the prevalence of DM in PD patients, the risk of developing PD in DM patients and the influence of DM on PD severity and progression. Methods: MEDLINE, Scopus, and Cochrane Library from inception to June 30, 2021 were searched. Studies reporting prevalence, incidence, severity and disease progression of DM and PD were included. Prevalence of DM in PD and incidence of PD in DM patients, and characteristics of PD. Results: A total of 21 studies (n = 11,396) included data on DM prevalence in PD patients, 12 studies (n = 17,797,221) included data on incidence of PD in DM patients, and 10 studies (n = 2,482) included data on DM impact on PD severity and disease progression. The prevalence of DM in PD patients was 10.02 %, (95%C.I. 7.88 –12.16), DM patients showed a higher risk of developing PD (OR: 1.34 95%CI 1.26–1.43 p

Background: Heart Failure (HF), a leading cause of morbidity and mortality, represents a relevant trigger for the development of frailty in the elderly. Inflammation has been reported to play an important role in HF and frailty pathophysiology. Galectin-3 (Gal-3), whose levels increase with aging, exerts a relevant activity in the processes of cardiac inflammation and fibrosis. The aim of the present study was to investigate the potential of Galectin-3 to serve as a biomarker of frailty in HF patients. Methods: 128 consecutive patients aged 65 and older with the diagnosis of systolic HF underwent a frailty assessment and blood sample collection for serum Gal-3 detection. A multivariable regression analysis and decision curve analysis (DCA) were used to identify significant predictors of frailty. Results: Frailty was present in 42.2% of patients. Age: Odds Ratio (OR) = 3.29, 95% Confidence Interval CI (CI) = 1.03&ndash, 10.55, Cumulative Illness Rating Scale Comorbidity Index (CIRS-CI): OR = 1.85, 95% CI = 1.03&ndash, 3.32, C-Reactive phase Protein (CRP) OR = 3.73, 95% CI = 1.24&ndash, 11.22, N-terminal-pro-Brain Natriuretic Peptide (NT-proBNP): OR = 2.39, 95% CI = 1.21&ndash, 4.72 and Gal-3: OR = 5.64, 95% CI = 1.97&ndash, 16.22 resulted in being significantly and independently associated with frailty. The DCA demonstrated that the addition of Gal-3 in the prognostic model resulted in an improved clinical &lsquo, net&rsquo, benefit. Conclusions: Circulating levels of Gal-3 are independently associated with frailty in elderly patients with systolic HF.

Klara Komici,1 Dino F Vitale,2 Dario Leosco,1 Angela Mancini,1 Graziamaria Corbi,3 Leonardo Bencivenga,1 Alessandro Mezzani,4 Bruno Trimarco,5 Carmine Morisco,5 Nicola Ferrara,1,2 Giuseppe Rengo1,2 1Division of Geriatrics, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy; 2Cardiac Rehabilitation Division, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Telese Terme (BN), Telese Terme, Italy; 3Department of Medicine and Health Sciences, University of Molise Campobasso, Campobasso, Italy; 4Cardiac Rehabilitation Division, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Veruno, Veruno, Italy; 5Division of Cardiology, Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy Objectives: To assess pressure injury (PI) incidence among patients hospitalized for acute myocardial infarction (AMI) in an intensive coronary care unit (ICCU) and to detect the impact of specific risk factors on the development of PI in this clinical setting.Patients and methods: Prospective cohort study in ICCU setting. Patients admitted for AMI: patients mean age 67.5±11.5 years (n=165). Norton Scale, Mini Nutritional Assessment (MNA), demographic, clinical and biochemical data collected at the time of ICCU admission have been tested in a logistic model to assess the odds ratios (ORs) of PI risk development. The jackknifed area under the receiver operating characteristic curve (AUC) and the decision curve analysis have been employed to assess the additive predictive value of a factor.Results: Twenty-seven (16.3%) patients developed PIs. An increased PI risk was associated with advanced age (OR =2.5 every 10-year increase; 95% CI =1.1–5.7), while probability of PI development was reduced in patients with higher left ventricular ejection fraction (LVEF) (OR =0.4 every 5% increase; 95% CI =0.24–0.66), MNA score (OR =0.65 every unit change; 95% CI =0.44–0.95) and Norton Scale score (OR =0.7 every unit change; 95% CI =0.57–0.88). The AUC and the decision curve analysis showed that LVEF inclusion improved the discrimination power and the clinical net benefit of the final model.Conclusion: Age, LVEF, Norton Scale and MNA scores have a strong and independent clinical value as predictors of in-hospital PI development in patients with AMI. This finding has the potential to improve the clinical management of patients admitted in ICCU. Keywords: pressure injury, Mini Nutritional Assessment, Norton Scale, acute myocardial systolic dysfunction

Purpose To assess the impact of body mass index (BMI) on cardiac adrenergic derangement, measured by iodine-123 metaiodobenzylguanidine (123I-mIBG) imaging in heart failure (HF) patients.Overweight and obesity represent relevant health issues, and augmented sympathetic tone has been described in patients with increased BMI. An extensive literature supports that HFdependent cardiac denervation, measured through mIBG parameters, is an independent predictor of cardiovascular outcomes and mortality. However, the influence of BMI on cardiac mIBG uptake has not been largely investigated. Methods We prospectively enrolled patients with systolic HF, collecting demographic, clinical, echocardiographic data, and mIBG imaging parameters. In order to detect the factors associated with mIBG parameters, a model building strategy, based on the Multivariable Fractional Polynomial algorithm, has been employed. Results We studied 249 patients with systolic HF, mean age of 66.4 ± 10.6 years, and mean left ventricular ejection fraction (LVEF) of 30.7%± 6.4, undergoing cardiac 123I-mIBG imaging to assess HF severity and prognosis. Seventy-eight patients (31.3%) presented a BMI ≥ 30 kg/m2 and obese patients showed a significant reduction in early heart to mediastinum (H/M) ratio (1.66 ± 0.19 vs. 1.75 ± 0.26; p = 0.008) and a trend to reduction in washout rate (33.6 ± 18.3 vs. 38.1 ± 20.1; p = 0.092) compared with patients with BMI < 30 kg/m2.Multiple regression analysis revealed that BMI, age, and LVEF were significantly correlated with early and late H/M ratios. Conclusions Results of the present study indicate thatBMI, together with LVEF and age, is independently correlated with cardiac mIBG uptake in HF patients.

Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly population, representing a global public health priority. Despite a large improvement in understanding the pathogenesis of AD, the etiology of this disorder remains still unclear, and no current treatment is able to prevent, slow, or stop its progression. Thus, there is a keen interest in the identification and modification of the risk factors and novel molecular mechanisms associated with the development and progression of AD. In this context, it is worth noting that several findings support the existence of a direct link between neuronal and non-neuronal inflammation/infection and AD progression. Importantly, recent studies are now supporting the existence of a direct relationship between periodontitis, a chronic inflammatory oral disease, and AD. The mechanisms underlying the association remain to be fully elucidated, however, it is generally accepted, although not confirmed, that oral pathogens can penetrate the bloodstream, inducing a low-grade systemic inflammation that negatively affects brain function. Indeed, a recent report demonstrated that oral pathogens and their toxic proteins infect the brain of AD patients. For instance, when AD progresses from the early to the more advanced stages, patients could no longer be able to adequately adhere to proper oral hygiene practices, thus leading to oral dysbiosis that, in turn, fuels infection, such as periodontitis. Therefore, in this review, we will provide an update on the emerging (preclinical and clinical) evidence that supports the relationship existing between periodontitis and AD. More in detail, we will discuss data attesting that periodontitis and AD share common risk factors and a similar hyper-inflammatory phenotype.

Atrial fibrillation (AF) represents the most common arrhythmia worldwide and its prevalence exponentially increases with age. It is related to increased risk of ischemic stroke or systemic embolism, which determines a significant burden of morbidity and mortality, as widely documented in the literature. AF also constitutes a risk factor for other less investigated conditions, such as heart failure, pulmonary embolism, impairment in physical performance, reduced quality of life, development of disability, mood disorders and cognitive impairment up to dementia. In the elderly population, the management of AF and its complications is particularly complex due to the heterogeneity of the ageing process, the lack of specific evidence-based recommendations, as well as the high grade of comorbidity and disability characterizing the over 65 years aged people. In the present review, we aim to summarize the pieces of the most updated evidence on AF complications beyond stoke, mainly focusing on the elderly population.

Periodontitis is a chronic inflammatory disease, initiated by the presence of a bacterial biofilm, called dental plaque, which affects both the periodontal ligaments and bone surrounding teeth. In the last decades, several lines of evidence have supported the existence of a relationship between periodontitis and systemic health. For instance, as periodontitis acts within the same chronic inflammatory model seen in cardiovascular disease (CVD), or other disorders, such as diabetes, several studies have suggested the existence of a bi-directional link between periodontal health and these pathologies. For instance, people with diabetes are more susceptible to infections and are more likely to suffer from periodontitis than people without this syndrome. Analogously, it is now evident that cardiac disorders are worsened by periodontitis, both experimentally and in humans. For all these reasons, it is very plausible that preventing periodontitis has an impact on the onset or progression of CVD and diabetes. On these grounds, in this review, we have provided an updated account on the current knowledge concerning periodontal disease and the adverse effects exerted on the cardiovascular system health and diabetes, informing readers on the most recent preclinical studies and epidemiological evidence.

The adrenergic system has an important role in normal central nervous system function as well as in brain disease. The locus coeruleus, the main source of norepinephrine in brain, is involved in the regulation of learning and memory, reinforcement of sleep-wake cycle and synaptic plasticity. In Alzheimer's disease, locus coeruleus degeneration is observed early in the course of the disease, years before the onset of clinical cognitive signs, with neurofibrillary detected at the stage of mild cognitive impairment, preceding amyloid deposition. Thus, in the last years, a great interest has grown in evaluating the possibility of central adrenergic system modulation as a therapeutic tool in Alzheimer's disease. However, evidences do not show univocal results, with some studies suggesting that adrenergic stimulation might be beneficial in Alzheimer's Disease and some others favoring adrenergic blockade. In this review, we summarize data from both hypothesis and describe the pathophysiological role of the adrenergic system in neurodegeneration.

Purpose Sympathetic nervous system (SNS) hyperactivity is a salient characteristic of chronic heart failure (HF) and contributes to the progression of the disease. Iodine-123 meta-iodobenzylguanidine (123I-mIBG) imaging has been successfully used to assess cardiac SNS activity in HF patients and to predict prognosis. Importantly, SNS hyperactivity characterizes also physiological ageing, and there is conflicting evidence on cardiac 123I-mIBG uptake in healthy elderly subjects compared to adults. However, little data are available on the impact of ageing on cardiac sympathetic nerve activity assessed by 123I-mIBG scintigraphy, in patients with HF. Methods and results We studied 180 HF patients (age = 66.1 ± 10.5 years [yrs]), left ventricular ejection fraction (LVEF = 30.6 ± 6.3 %) undergoing cardiac 123I-mIBG imaging. Early and late heart to mediastinum (H/M) ratios and washout rate were calculated in all patients. Demographic, clinical, and echocardiographic data were also collected. Our study population consisted of 53 patients aged >75 years (age = 77.7 ± 4.0 year), 67 patients aged 62–72 years (age = 67.9 ± 3.2 years) and 60 patients aged ≤61 year (age = 53.9 ± 5.6 years). In elderly patients, both early and late H/M ratios were significantly lower compared to younger patients (p < 0.05). By multivariate analysis, H/M ratios (both early and late) and washout rate were significantly correlated with LVEF and age. Conclusions Our data indicate that, in a population of HF patients, there is an independent age-related effect on cardiac SNS innervation assessed by 123I-mIBG imaging. This finding suggests that cardiac 123I-mIBG uptake in patients with HF might be affected by patient age.

Background: Malnutrition is a frequent condition in the elderly, and is associated with prolonged hospitalization and increased mortality. However, the impacts of malnutrition among elderly patients with acute myocardial infarction have not been clarified yet. Methods and Results: We enrolled 174 patients aged 65 years and over, admitted with the diagnosis of acute myocardial infarction (AMI), who underwent evaluation of nutritional status by Mini Nutritional Assessment (MNA) and evaluation of mortality risk by GRACE Score 2.0. All-cause mortality was the outcome considered for this study. Over a mean follow-up of 24.5 &plusmn, 18.2 months, 43 deaths have been registered (24.3%). Non-survivors were more likely to be older, with worse glomerular filtration rate, lower systolic blood pressure, lower albumin and MNA score, higher prevalence of Killip classification III-IV grade, and higher Troponin I levels. Multivariate Cox proportional analysis revealed that GRACE Score and MNA showed a significant and independent impact on mortality, (HR = 1.76, 95%, CI = 1.34&ndash, 2.32, and HR = 0.56, 95% CI = 0.42&ndash, 0.73, respectively). Moreover, the clinical decision curve revealed a higher clinical net benefit when the MNA was included, compared to the partial models without MNA. Conclusion: Nutritional status is an independent predictor of long-term mortality among elderly patients with AMI. MNA score in elderly patients with AMI may help prognostic stratification and identification of patients with, or at risk of, malnutrition in order to apply interventions to improve nutritional status, and maybe survival in this population.

Diabetes mellitus (DM) and heart failure (HF) are frequent comorbidities among elderly patients. HF, a leading cause of mortality and morbidity worldwide, is characterized by sympathetic nervous system hyperactivity. The prevalence of diabetes mellitus (DM) is rapidly growing and the risk of developing HF is higher among DM patients. DM is responsible for several macro- and micro-angiopathies that contribute to the development of coronary artery disease (CAD), peripheral artery disease, retinopathy, neuropathy and diabetic nephropathy (DN) as well. Independently of CAD, chronic kidney disease (CKD) and DM increase the risk of HF. Individuals with diabetic nephropathy are likely to present a distinct pathological condition, defined as diabetic cardiomyopathy, even in the absence of hypertension or CAD, whose pathogenesis is only partially known. However, several hypotheses have been proposed to explain the mechanism of diabetic cardiomyopathy: increased oxidative stress, altered substrate metabolism, mitochondrial dysfunction, activation of renin-angiotensin-aldosterone system (RAAS), insulin resistance, and autonomic dysfunction. In this review, we will focus on the involvement of sympathetic system hyperactivity in the diabetic nephropathy.

Hyperaldosteronism alters cardiac function, inducing adverse left ventricle (LV) remodeling either via increased fibrosis deposition, mitochondrial dysfunction, or both. These harmful effects are due, at least in part, to the activation of the G protein-coupled receptor kinase 2 (GRK2). In this context, we have previously reported that this kinase dysregulates both β-adrenergic receptor (βAR) and insulin (Ins) signaling. Yet, whether aldosterone modulates cardiac Ins sensitivity and βAR function remains untested. Nor is it clear whether GRK2 has a role in this modulation, downstream of aldosterone. Here, we show in vitro, in 3T3 cells, that aldosterone impaired insulin signaling, increasing the negative phosphorylation of insulin receptor substrate 1 (ser307pIRS1) and reducing the activity of Akt. Similarly, aldosterone prevented the activation of extracellular signal-regulated kinase (ERK) and the production of cyclic adenosine 3',5'-monophosphate (cAMP) in response to the β1/β2AR agonist, isoproterenol. Of note, all of these effects were sizably reduced in the presence of GRK2-inhibitor CMPD101. Next, in wild-type (WT) mice undergoing chronic infusion of aldosterone, we observed a marked GRK2 upregulation that was paralleled by a substantial β1AR downregulation and augmented ser307pIRS1 levels. Importantly, in keeping with the current in vitro data, we found that aldosterone effects were wholly abolished in cardiac-specific GRK2-knockout mice. Finally, in WT mice that underwent 4-week myocardial infarction (MI), we observed a substantial deterioration of cardiac function and increased LV dilation and fibrosis deposition. At the molecular level, these effects were associated with a significant upregulation of cardiac GRK2 protein expression, along with a marked β1AR downregulation and increased ser307pIRS1 levels. Treating MI mice with spironolactone prevented adverse aldosterone effects, blocking GRK2 upregulation, and thus leading to a marked reduction in cardiac ser307pIRS1 levels while rescuing β1AR expression. Our study reveals that GRK2 activity is a critical player downstream of the aldosterone signaling pathway; therefore, inhibiting this kinase is an attractive strategy to prevent the cardiac structural disarray and dysfunction that accompany any clinical condition accompanied by hyperaldosteronism.

Aldosterone (Aldo) has been intensively studied for years since its isolation by Simpson and Tait in the 1950s. Interestingly, although most early research around Aldo's actions focused primarily on its interaction with the kidney, it was soon evident that this hormone is able to exert unexplained extra-renal effects, on various target organs including the heart. Importantly, over the course of the last decade a number of studies in pre-clinical models (in vitro and in vivo) and in humans have clearly demonstrated that Aldo, following the interaction with its receptor, the mineralocorticoid receptor (MR), is able to activate specific intracellular genomic and non-genomic pathways thus, regulating the homeostasis of the entire cardiovascular system. In this regard, Aldo has been shown to influence the function and growth of different type of cells including cardiomyocytes, fibroblasts and vascular cells (vascular smooth muscle cells and endothelial cells). Importantly, when present at high levels, Aldo have been associated with the onset of disparate cardiovascular disorders including heart failure (HF). For this reason, several pre-clinical study and clinical trials have been designed in order to test the effects of Aldo antagonism in HF patients. In this chapter, we will guide the readers through the current knowledge around Aldo activity in cardiovascular system and the relevant therapies acting in blocking the noxious Aldo/MR signaling pathway.

Heart failure (HF) is a complex clinical syndrome, with high prevalence in the elderly. The World Heath Organization (WHO) predicts that by 2050 the population aged over 80 years will account around 400 million, reflecting that HF will still represent a major public health concern. Improved management of cardiovascular diseases and HF, together with the increased life expectancy explains, at least in part, the high prevalence of HF especially in the elderly. Beside the canonical therapy for HF failure, including angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers and aldosterone antagonists, new potential and promising therapies, such as sacubitril/valsartan, iron deficiency treatment and serelaxine, are emerging also in elderly HF patients. In this review we focus on the classical recommended HF therapy and the possible application of new trends in elderly.

Purpose: Klinefelter syndrome (KS), the most frequent chromosomic abnormality in males, is associated with hypergonadotropic hypogonadism and an increased risk of cardiovascular diseases (CVD). The mechanisms involved in increasing risk of cardiovascular morbidity and mortality are not completely understood. This review summarises the current understandings of the complex relationship between KS, metabolic syndrome and cardiovascular risk in order to plan future studies and improve current strategies to reduce mortality in this high-risk population. Methods: We searched PubMed, Web of Science, and Scopus for manuscripts published prior to November 2017 using key words "Klinefelter syndrome" AND "insulin resistance" OR "metabolic syndrome" OR "diabetes mellitus" OR "cardiovascular disease" OR "testosterone". Manuscripts were collated, studied and carried forward for discussion where appropriate. Results: Insulin resistance, metabolic syndrome, and type 2 diabetes are more frequently diagnosed in KS than in the general population; however, the contribution of hypogonadism to metabolic derangement is highly controversial. Whether this dangerous combination of risk factors fully explains the CVD burden of KS patients remains unclear. In addition, testosterone replacement therapy only exerts a marginal action on the CVD system. Conclusion: Since fat accumulation and distribution seem to play a relevant role in triggering metabolic abnormalities, an early diagnosis and a tailored intervention strategy with drugs aimed at targeting excessive visceral fat deposition appear necessary in patients with KS.

Background: Caloric restriction (CR) has been described to have cardioprotective effects and improve functional outcomes in animal models and humans. Chronic ischemic heart failure (HF) is associated with reduced cardiac sympathetic innervation, dysfunctional β-adrenergic receptor signaling, and decreased cardiac inotropic reserve. We tested the effects of a long-term CR diet, started late after myocardial infarction on cardiac function, sympathetic innervation, and β-adrenergic receptor responsiveness in a rat model of postischemic HF. Methods and Results: Adult male rats were randomly assigned to myocardial infarction or sham operation and 4 weeks later were further randomized to a 1-year CR or normal diet. One year of CR resulted in a significant reduction in body weight, heart weight, and heart weight/tibia length ratio when compared with normal diet in HF groups. At the end of the study period, echocardiography and histology revealed that HF animals under the CR diet had ameliorated left ventricular remodeling compared with HF rats fed with normal diet. Invasive hemodynamic showed a significant improvement of cardiac inotropic reserve in CR HF rats compared with HF-normal diet animals. Importantly, CR dietary regimen was associated with a significant increase of cardiac sympathetic innervation and with normalized cardiac β-adrenergic receptor levels in HF rats when compared with HF rats on the standard diet. Conclusions: We demonstrate, for the first time, that chronic CR, when started after HF established, can ameliorate cardiac dysfunction and improve inotropic reserve. At the molecular level, we find that chronic CR diet significantly improves sympathetic cardiac innervation and β-adrenergic receptor levels in failing myocardium.

The mineralocorticoid hormone aldosterone (Aldo) has been intensively studied for its ability to influence both the physiology and pathophysiology of the cardiovascular system. Indeed, although research on Aldo actions for decades has mainly focused on its effects in the kidney, several lines of evidence have now demonstrated that this hormone exerts disparate extrarenal adverse effects, especially in the circulatory system. Accordingly, in the last lusters, a number of studies in preclinical models (in vitroandin vivo) and in humans have established that Aldo, following the interaction with its receptor—the mineralocorticoid receptor (MR)—is able to activate specific intracellular genomic and nongenomic pathways, thus regulating the homeostasis of the cardiovascular system. Importantly, through this mechanism of action, this hormone becomes a crucial regulator of the function and growth of different types of cells, including fibroblasts, cardiomyocytes, and vascular cells. For this main reason, it is plausible that when Aldo is present at high levels in the blood, it profoundly modifies the physiology of these cells, therefore being at the foundation of several cardiovascular disorders, such as heart failure (HF). On these grounds, in this review, we will provide an updated account on the current knowledge concerning Aldo activity in the cardiovascular system and the most recent preclinical studies and clinical trials designed to test better approaches able to counter the hyperactivity of the Aldo/MR signaling pathway in the setting of cardiovascular diseases.

G protein-coupled receptor (GPCR) kinase-2 (GRK2) is a regulator of GPCRs, in particular β-adrenergic receptors (ARs), and as demonstrated by decades of investigation, it has a pivotal role in the development and progression of cardiovascular disease, like heart failure (HF). Indeed elevated levels and activity of this kinase are able to promote the dysfunction of both cardiac and adrenal α- and β-ARs and to dysregulate other protective signaling pathway, such as sphingosine 1-phospate and insulin. Moreover, recent discoveries suggest that GRK2 can signal independently from GPCRs, in a 'non-canonical' manner, via interaction with non-GPCR molecule or via its mitochondrial localization. Areas covered: Based on this premise, GRK2 inhibition or its genetic deletion has been tested in several disparate animal models of cardiovascular disease, showing to protect the heart from adverse remodeling and dysfunction. Expert opinion: HF is one of the leading cause of death worldwide with enormous health care costs. For this reason, the identification of new therapeutic targets like GRK2 and strategies such as its inhibition represents a new hope in the fight against HF development and progression. Herein, we will update the readers about the 'state-of-art' of GRK2 inhibition as a potent therapeutic strategy in HF.

Anticoagulation is superior to dual antiplatelet therapy (DAPT) in the prevention of thromboembolic events in patients with atrial fibrillation (AF), otherwise the prevention of ischemic risk and stent thrombosis after percutaneous coronary intervention (PCI) is warranted by DAPT. The coexistence of conditions requiring combined antithrombotic therapies is becoming an increasing relevant clinical problem, whose therapeutic management has long been found in the medical experience rather than in guidelines and consensus. Recently, updates in guidelines and relevant studies have been published in order to better clarify the best management of combined antithrombotic therapy. In the present review, we have analyzed the recent literature, underlining the progresses and the residual limits of the most up-to-date evidence on the management of patients requiring dual or triple antithrombotic therapy, due to coexisting AF and coronary artery disease. An in-depth overview is also focused on the management of antithrombotic therapy in the elderly patient, which represents an even more complex challenge for the clinician. This is due to the high prevalence, among over 65 years aged people, of conditions requiring association of antiplatelet and anticoagulant drugs, the numerous comorbidities, the higher risk of complications, such as bleedings, and the lack of specific evidence, especially for the frail elderly. Nowadays, triple therapy [oral anticoagulation (OAC) plus dual antiplatelet agents] for the shortest possible time should be the treatment for AF patients undergoing PCI, whereas dual therapy (single antiplatelet plus OAC) may be preferred for patients at high bleeding risk.

The sphingosine kinases 1 and 2 (SphK1 and 2) catalyze the phosphorylation of the lipid, sphingosine, generating the signal transmitter, sphingosine 1-phosphate (S1P). The activation of such kinases and the subsequent S1P generation and secretion in the blood serum of mammals represent a major checkpoint in many cellular signaling cascades. In fact, activating the SphK/S1P system is critical for cell motility and proliferation, cytoskeletal organization, cell growth, survival and response to stress. In the cardiovascular system, the physiological effects of S1P intervene through the binding and activation of a family of five highly-selective G protein-coupled receptors (GPCRs), called S1PR1–5. Importantly, SphK/S1P signal is present on both vascular and myocardial cells. S1P is a well-recognized survival factor in many tissues. Therefore, it is not surprising that the last two decades have seen a flourishing of interest and investigative efforts directed to obtain additional mechanistic insights into the signaling, as well as the biological activity of this phospholipid, and of its receptors, especially in the cardiovascular system. Here, we will provide an up-to-date account on the structure and function of sphingosine kinases, discussing the generation, release, and function of S1P. Keeping the bull's eye on the cardiovascular system, we will review the structure and signaling cascades and biological actions emanating from the stimulation of different S1P receptors. We will end this article with a summary of the most recent, experimental and clinical observations targeting S1PRs and SphKs as possible new therapeutic avenues for cardiovascular disorders, such as heart failure.