Autonomic dysfunction is very common in patients with dementia, and its presence might also help in differential diagnosis among dementia subtypes. Various central nervous system structures affected ...in Alzheimer's disease are also implicated in autonomic nervous system regulation, and it has been hypothesized that the deficit in central cholinergic function observed in Alzheimer's disease could likely lead to autonomic dysfunction. Several feasible tests can be used in clinical practice for the assessment of parasympathetic and sympathetic functions, especially in terms of cardiovascular autonomic modulation. In this review, we describe the different tests available and the evidence from the literature which indicate a definite presence of autonomic dysfunction in dementia at various degrees. Importantly, the recognition of dysautonomia, besides possibly being an early marker of dementia, would help prevent the disabling complications which increase the risk of morbidity, institutionalization, and mortality in these individuals.
Amyloid deposition within stenotic aortic valves (AVs) also appears frequent in the absence of cardiac amyloidosis, but its clinical and pathophysiological relevance has not been investigated. We ...will elucidate the rate of isolated AV amyloid deposition and its potential clinical and pathophysiological significance in aortic stenosis (AS). In 130 patients without systemic and/or cardiac amyloidosis, we collected the explanted AVs during cardiac surgery: 57 patients with calcific AS and 73 patients with AV insufficiency (41 with AV sclerosis and 32 without, who were used as controls). Amyloid deposition was found in 21 AS valves (37%), 4 sclerotic AVs (10%), and none of the controls. Patients with and without isolated AV amyloid deposition had similar clinical and echocardiographic characteristics and survival rates. Isolated AV amyloid deposition was associated with higher degrees of AV fibrosis (
= 0.0082) and calcification (
< 0.0001). Immunohistochemistry analysis suggested serum amyloid A1 (SAA1), in addition to transthyretin (TTR), as the protein possibly involved in AV amyloid deposition. Circulating SAA1 levels were within the normal range in all groups, and no difference was observed in AS patients with and without AV amyloid deposition. In vitro, AV interstitial cells (VICs) were stimulated with interleukin (IL)-1β which induced increased SAA1-mRNA both in the control VICs (+6.4 ± 0.5,
= 0.02) and the AS VICs (+7.6 ± 0.5,
= 0.008). In conclusion, isolated AV amyloid deposition is frequent in the context of AS, but it does not appear to have potential clinical relevance. Conversely, amyloid deposition within AV leaflets, probably promoted by local inflammation, could play a role in AS pathophysiology.
Left ventricular (LV) remodeling after ST-segment elevation myocardial infarction (STEMI) is explained only in part by the infarct size, and the inter-patient variability may be ascribed to different ...inflammatory response to myocardial injury. Epicardial adipose tissue (EAT) is a source of inflammatory mediators which directly modulates the myocardium. EAT increase is associated to several cardiovascular diseases; however, its response to myocardial injury is currently unknown. Among inflammatory mediators, IL-13 seems to play protective role in LV regeneration, but its variations after STEMI have not been described yet. Purpose: In the present study we analyzed the association between infarct-related changes of EAT and IL-13 in post-STEMI LV remodeling.
We enrolled 100 patients with STEMI undergoing primary angioplasty. At the enrolment (T0) and after 3 months (T1), we measured EAT thickness by echocardiography and circulating levels of IL-13 by ELISA.
At T1, the 60% of patients displayed increased EAT thickness (ΔEAT > 0). ΔEAT was directly associated to LV end-diastolic volume (
= 0.42;
= 0.014), LV end-systolic volume (
= 0.42;
= 0.013) and worse LV ejection fraction (LVEF) at T1 (
= -0.44;
= 0.0094), independently of the infarct size. In the overall population IL-13 levels significantly decreased at T1 (
= 0.0002). The ΔIL-13 was directly associated to ΔLVEF (
= 0.42;
= 0.017) and inversely related to ΔEAT (
= -0.51;
= 0.022), thus suggesting a protective role for IL-13.
The variability of STEMI-induced "inflammatory response" may be associated to the post-infarct LV remodeling. ΔEAT thickness and ΔIL-13 levels could be novel prognostic markers in STEMI patients.
Atrial Fibrillation (AF) is the most frequent cardiac arrhythmia and its prevalence increases with age. AF is strongly associated with an increased risk of stroke, heart failure and cardiovascular ...mortality. Among the risk factors associated with AF onset and severity, obesity and inflammation play a prominent role. Numerous recent evidence suggested a role of epicardial adipose tissue (EAT), the visceral fat depot of the heart, in the development of AF. Several potential arrhythmogenic mechanisms have been attributed to EAT, including myocardial inflammation, fibrosis, oxidative stress, and fat infiltration. EAT is a local source of inflammatory mediators which potentially contribute to atrial collagen deposition and fibrosis, the anatomical substrate for AF. Moreover, the close proximity between EAT and myocardium allows the EAT to penetrate and generate atrial myocardium fat infiltrates that can alter atrial electrophysiological properties. These observations support the hypothesis of a strong implication of EAT in structural and electrical atrial remodeling, which underlies AF onset and burden. The measure of EAT, through different imaging methods, such as echocardiography, computed tomography and cardiac magnetic resonance, has been proposed as a useful prognostic tool to predict the presence, severity and recurrence of AF. Furthermore, EAT is increasingly emerging as a promising potential therapeutic target. This review aims to summarize the recent evidence exploring the potential role of EAT in the pathogenesis of AF, the main mechanisms by which EAT can promote structural and electrical atrial remodeling and the potential therapeutic strategies targeting the cardiac visceral fat.
Human aging is a complex phenomenon characterized by a wide spectrum of biological changes which impact on behavioral and social aspects. Age-related changes are accompanied by a decline in ...biological function and increased vulnerability leading to frailty, thereby advanced age is identified among the major risk factors of the main chronic human diseases. Aging is characterized by a state of chronic low-grade inflammation, also referred as inflammaging. It recognizes a multifactorial pathogenesis with a prominent role of the innate immune system activation, resulting in tissue degeneration and contributing to adverse outcomes. It is widely recognized that inflammation plays a central role in the development and progression of numerous chronic and cardiovascular diseases. In particular, low-grade inflammation, through an increased risk of atherosclerosis and insulin resistance, promote cardiovascular diseases in the elderly. Low-grade inflammation is also promoted by visceral adiposity, whose accumulation is paralleled by an increased inflammatory status. Aging is associated to increase in epicardial adipose tissue (EAT), the visceral fat depot of the heart. Structural and functional changes in EAT have been shown to be associated with several heart diseases, including coronary artery disease, aortic stenosis, atrial fibrillation, and heart failure. EAT increase is associated with a greater production and secretion of pro-inflammatory mediators and neuro-hormones, so that thickened EAT can pathologically influence, in a paracrine and vasocrine manner, the structure and function of the heart and is associated to a worse cardiovascular outcome. In this review, we will discuss the evidence underlying the interplay between inflammaging, EAT accumulation and cardiovascular diseases. We will examine and discuss the importance of EAT quantification, its characteristics and changes with age and its clinical implication.
Interleukin-1beta (IL-1β) is crucially involved in the pathogenesis of coronary atherosclerotic diseases (CAD) and its inhibition has proven cardiovascular benefits. Epicardial adipose tissue (EAT) ...is a local source of inflammatory mediators which may negatively affect the surrounding coronary arteries. In the present study, we explored the relationship between serum and EAT levels of IL-1β and IL-1 receptor antagonist (IL-1ra) in patients with chronic coronary syndrome (CCS) and recent acute coronary syndrome (ACS).
We obtained EAT biopsies in 54 CCS (Group 1) and 33 ACS (Group 2) patients undergoing coronary artery bypass grafting. Serum and EAT levels of IL-1β and IL-1ra were measured in all patients. An immunophenotypic study was carried out on EAT biopsies and the CD86 events were studied as markers of M1 macrophages.
Circulating levels of IL-1β were significantly higher in the overall CAD population compared to a control group 7.64 pg/ml (6.86; 8.57) vs. 1.89 pg/ml (1.81; 2.29);
< 0.001. In contrast, no differences were observed for serum IL-1ra levels between CAD and controls. Comparable levels of serum IL-1β were found between Groups 1 and 2 7.6 pg/ml (6.9; 8.7) vs. 7.9 pg/ml (7.2; 8.6);
= 0.618. In contrast, significantly lower levels of serum IL-1ra were found in Group 2 compared to Group 1 274 pg/ml (220; 577) vs. 603 pg/ml (334; 1022);
= 0.035. No differences of EAT levels of IL-1β were found between Group 2 and Group 1 3.4 pg/ml (2.3; 8.4) vs. 2.4 pg/ml (1.9; 8.0);
= 0.176. In contrast, significantly lower EAT levels of IL-1ra were found in Group 2 compared to Group 1 101 pg/ml (40; 577) vs. 1344 pg/ml (155; 5327);
= 0.002. No correlation was found between EAT levels of IL-1β and CD86 and CD64 events.
The present study explores the levels of IL-1β and IL-1ra in the serum and in EAT of CCS and ACS patients. ACS seems to be associated to a loss of the counter-regulatory activity of IL-1ra against the pro-inflammatory effects related to IL-1β activation.
Cardiac amyloidosis (CA) has been recently recognized as a condition frequently associated with aortic stenosis (AS). The aim of this study was to evaluate: the main characteristics of patients with ...AS with and without CA, the impact of CA on patients with AS mortality, and the effect of different treatment strategies on outcomes of patients with AS with concomitant CA.
A detailed search related to CA in patients with AS and outcomes was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seventeen studies enrolling 1,988 subjects (1,658 AS alone and 330 AS with CA) were included in the qualitative and quantitative analysis of main patients with AS characteristics with and without CA, difference in mortality, and treatment strategy.
The prevalence of CA resulted in a mean of 15.4% and it was even higher in patients with AS over 80 years old (18.2%). Patients with the dual diagnosis were more often males, had lower body mass index (BMI), were more prone to have low flow, low gradient with reduced left ventricular ejection fraction AS phenotype, had higher E/A and E/e', and greater interventricular septum hypertrophy. Lower Sokolow-Lyon index, higher QRS duration, higher prevalence of right bundle branch block, higher levels of
-terminal pro-brain natriuretic peptide, and high-sensitivity troponin T were significantly associated with CA in patients with AS. Higher overall mortality in the 178 patients with AS + CA in comparison to 1,220 patients with AS alone was observed odds ratio (OR) 2.25,
= 0.004. Meta-regression analysis showed that younger age and diabetes were associated with overall mortality in patients with CS with CA (
-value -3.0,
= 0.003 and
-value 2.5,
= 0.013, respectively). Finally, patients who underwent surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) had a similar overall mortality risk, but lower than medication-treated only patients.
Results from our meta-analysis suggest that several specific clinical, electrocardiographic, and echocardiographic features can be considered "red flags" of CA in patients with AS. CA negatively affects the outcome of patients with AS. Patients with concomitant CA and AS benefit from SAVR or TAVI.
Epicardial adipose tissue (EAT) has been shown to be involved in the pathogenesis and progression of heart failure (HF). In this study we aimed to explore the predictive value of echocardiographic ...EAT thickness on prognosis of a selected population of HF patients.
The patient population included n. 69 consecutive patients with systolic HF referred to implantable cardioverter defibrillator (ICD) implantation for primary or secondary prevention. At the time of enrolment, echocardiographic EAT thickness was assessed in all patients along with demographic and clinical data. The study had a median follow-up time of 49.8 months. We assessed the prognostic predictive value of EAT thickness on a composite clinical and arrhythmic outcome including HF related deaths, new hospital admissions for HF worsening, and atrial and life threatening ventricular arrhythmic events. Clinical and arrhythmic outcomes were also evaluated separately.
At univariate analysis, EAT thickness significantly predicted all the three outcomes considered. Of interest, at multivariate analysis, after adjusting for known risk factor, EAT remained significantly associated to the composite HR 1.18 (1.09-1.28);
< 0.001, arrhythmic HR 1.14 (1.03-1.25);
= 0.008, and clinical HR 1.14 (1.03-1.27);
= 0.010 outcomes.
Echocardiographic assessment of EAT can predict outcome of HF patients and it is significantly associated with both arrhythmic and clinical events. These preliminary findings pave the way for future and larger studies aimed to definitively recognize the prognostic value of this novel risk marker in HF.
Background and aims:
Post-operative atrial fibrillation (POAF), defined as new-onset AF in the immediate period after surgery, is associated with poor adverse cardiovascular events and a higher risk ...of permanent AF. Mechanisms leading to POAF are not completely understood and epicardial adipose tissue (EAT) inflammation could be a potent trigger. Here, we aim at exploring the link between EAT-secreted interleukin (IL)-1β, atrial remodeling, and POAF in a population of coronary artery disease (CAD) patients.
Methods:
We collected EAT and atrial biopsies from 40 CAD patients undergoing cardiac surgery. Serum samples and EAT-conditioned media were screened for IL-1β and IL-1ra. Atrial fibrosis was evaluated at histology. The potential role of NLRP3 inflammasome activation in promoting fibrosis was explored
in vitro
by exposing human atrial fibroblasts to IL-1β and IL-18.
Results:
40% of patients developed POAF. Patients with and without POAF were homogeneous for clinical and echocardiographic parameters, including left atrial volume and EAT thickness. POAF was not associated with atrial fibrosis at histology. No significant difference was observed in serum IL-1β and IL-1ra levels between POAF and no-POAF patients. EAT-mediated IL-1β secretion and expression were significantly higher in the POAF group compared to the no-POAF group. The
in vitro
study showed that both IL-1β and IL-18 increase fibroblasts’ proliferation and collagen production. Moreover, the stimulated cells perpetuated inflammation and fibrosis by producing IL-1β and transforming growth factor (TGF)-β.
Conclusion:
EAT could exert a relevant role both in POAF occurrence and in atrial fibrotic remodeling.
Diabetes mellitus (DM) and Alzheimer’s disease (AD) are two highly prevalent conditions in the elderly population and major public health burden. In the past decades, a pathophysiological link ...between DM and AD has emerged and central nervous system insulin resistance might play a significant role as a common mechanism; however, other factors such as inflammation and oxidative stress seem to contribute to the shared pathophysiological link. Both preclinical and clinical studies have evaluated the possible neuroprotective mechanisms of different classes of antidiabetic medications in AD, with some promising results. Here, we review the evidence on the mechanisms of action of antidiabetic drugs and their potential use in AD.
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