Fiorella Devito

Inflammatory bowel disease, liver diseases and endothelial function: is there a linkage?

Atherosclerosis is a systemic inflammatory disease able to deeply worsen the outcome of patients because of its serious clinical consequences. The complex inflammatory background underlining such a disease makes atherosclerosis linked to several systemic inflammatory conditions able to impair endothelial function and morphology. Inflammatory bowel diseases are a group of gastrointestinal diseases including Crohns disease and ulcerative colitis, that is, syndromes characterized by changes in mucosal immunity and gastrointestinal physiology, which could negatively influence the vascular endothelial function and structure. Hepatitis (i.e. inflammatory diseases of the liver mainly due to viral infections) and nonalcoholic fatty liver disease could be aligned to inflammatory bowel disease in such an induction of atherosclerosis disease. Many studies tried to point out the relationship between bowel and liver inflammatory diseases and early vascular changes, considered the first step for atherosclerosis development. The aim of such a narrative review is to explain the relationship between inflammatory bowel disease, hepatitis and nonalcoholic fatty liver disease and their role in increasing cardiovascular risk profile due to early impairment in vascular function and morphology.

Survival Benefits of Invasive Versus Conservative Strategies in Heart Failure in Patients With Reduced Ejection Fraction and Coronary Artery Disease: A Meta-Analysis.

Background— Heart failure with reduced ejection fraction caused by ischemic heart disease is associated with increased morbidity and mortality. It remains unclear whether revascularization by either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) carries benefits or risks in this group of stable patients compared with medical treatment. Methods and Results— We performed a meta-analysis of available studies comparing different methods of revascularization (PCI or CABG) against each other or medical treatment in patients with coronary artery disease and left ventricular ejection fraction ⩽40%. The primary outcome was all-cause mortality; myocardial infarction, revascularization, and stroke were also analyzed. Twenty-one studies involving a total of 16 191 patients were included. Compared with medical treatment, there was a significant mortality reduction with CABG (hazard ratio, 0.66; 95% confidence interval, 0.61–0.72; P<0.001) and PCI (hazard ratio, 0.73; 95% confidence interval, 0.62–0.85; P<0.001). When compared with PCI, CABG still showed a survival benefit (hazard ratio, 0.82; 95% confidence interval, 0.75–0.90; P<0.001). Conclusions— The present meta-analysis indicates that revascularization strategies are superior to medical treatment in improving survival in patients with ischemic heart disease and reduced ejection fraction. Between the 2 revascularization strategies, CABG seems more favorable compared with PCI in this particular clinical setting.

From proprotein convertase subtilisin/kexin type 9 to its inhibition: state-of-the-art and clinical implications

Statins are recommended as first-line therapy for patients with hypercholesterolaemia. A sizable proportion of patients, however, does not reach therapeutic goals, is statin intolerant, or, despite optimal statin therapy, is at high risk of ischaemic events. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a major role in lipid metabolism and several comorbidities. Monoclonal antibodies targeting PCSK9 are a new lipid-lowering approach with the potential to improve clinical outcomes in patients with dyslipidaemia. In this review, we discuss current experimental and clinical evidence of the role of PCSK9 and its inhibition on lipid metabolism and several pathologic conditions with a focus on clinical outcomes. A state-of-the-art analysis of current clinical evidence and future directions on PCSK9 and its inhibition is provided.

Endothelial Dysfunction Correlates with Liver Fibrosis in Chronic HCV Infection

Background. Hepatitis C virus (HCV) infection can exert proatherogenic activities due to its direct action on vessel walls and/or via the chronic inflammatory process involving the liver. Aims. To clarify the role of HCV in atherosclerosis development in monoinfected HCV patients at different degrees of liver fibrosis and with no risk factors for coronary artery disease. Methods. Forty-five patients were included. Clinical, serological, and anthropometric parameters, liver fibrosis (transient liver elastometry (fibroscan) and aspartate aminotransferase to platelet ratio index (APRI)), carotid intima-media thickness (c-IMT), and brachial artery flow-mediated vasodilatation (FMD) were assessed. Patients were divided into 3 tertiles according to fibroscan values. Results. Patients in the third tertile (fibroscan value >11.5 KPa) showed FMD values were significantly lower than second and first tertiles (4.7 ± 1.7% versus 7.1 ± 2.8%, p = 0.03). FMD values were inversely related to liver elastomeric values. c-IMT values were normal. The risk for endothelial dysfunction development in the third tertile (p = 0.02) was 6.9 higher than the first tertile. A fibroscan value >11.5 KPa had a positive predictive power equal to 79% for endothelial dysfunction. Conclusions. HCV advanced liver fibrosis promotes atherosclerosis by inducing endothelial dysfunction independently of common cardiovascular risk factors.

Pulmonary hypertension in thyroid diseases.

The influence of thyroid hormones on cardiovascular system is well established. Thyroid diseases can effectively enhance the alteration on cardiovascular system by influencing chronotropic and inotropic actions of the heart; altering the strength and the speed of contraction, the speed of relaxation, the duration of the potential of action, and the duration of the refractory period and atrio-ventricular conduction time; modulating circulation and peripheral vascular beds. One of the more intriguing insights in the connection between thyroid diseases and cardiovascular alterations is related to the evaluation of the influence of thyroid hormones on pulmonary vascular beds. Literature reported several studies regarding the association between both hypothyroidism and hyperthyroidism and the occurrence of increased vascular pulmonary arterial pressure. Nevertheless, the pathogenetic mechanisms able to explain such relationship are not fully understood. Many doubts still persist in the comprehension of the mechanisms of pulmonary hypertension in thyroid diseases. The aim of this review was to provide possible explanation about the possible interaction between pulmonary vascular beds and thyroid function in order to evaluate the possibility of novel perspectives in the general management of patients suffering from thyroid and cardiovascular diseases.

Endothelial function and cardiovascular risk in patients with inflammatory bowel disease in remission phase

To the editorUlcerative colitis (UC) and Crohn’s disease (CD)are the main chronic inflammatory disorders ofdigestive tract (inflammatory bowel disease [IBD])[1]. There is evidence that patients with IBD are atincreased thrombotic risk compared to generalpopulation since it has been demonstrated that IBDare associated with subclinical atherosclerosis,endothelial dysfunction and increased carotidintima-media thickness [2,3]. Intestinal vessels mayshow a microvascular endothelial dysfunction in IBD,which correlates to intestinal activity. In a previousstudy [4], we demonstrated that subjects sufferingfrom IBD in an active phase show an endothelialdysfunction, measured by brachial flow-mediateddilatation (FMD). Therefore, we report here resultsabout the endothelial function assessed by FMD in agroup of IBD patients in remission phase.A total of 58 (men/female: 30/28, mean age 43.95 ±15.15 years) patients with IBD, 29 CD and 29 UC,were recruited. Forty healthy controls matched forgender and age were enrolled. Diagnosis was basedon standard clinical, endoscopic and histologicalcriteria. Disease activity was assessed according toHarvey–Bradshaw index (HBI) for CD and GlobalDisease activity index (Mayo) for UC.Mean HBI was 1.57 ± 1.23, range 0–4, while DAIwas constantly 0 points, except for two patients whohad Mayo 1 (0.07 ± 0.26). C-reactive protein (CRP)anderythrocytesedimentationrate(ESR)werewithinnormalvaluesbothinIBDandcontrols(TableI).IBDpatients were under medical treatment (salicylatesand/orazathioprine).Physicalexamination,laboratoryinvestigations,electrocardiography,ambulatorybloodpressure monitoring, ultrasound examination of thecarotid arteries (Intima-Media thickness [IMT]) andbrachialarteryFMDwereperformed,accordingtotheprotocol of our previous experience [4–6].Comparisons between groups were analyzed usingStudent’s t test for independent samples, ANOVAplus Neuman–Keuls. Frequencies were comparedusing chi-squared or Fisher’s exact test. ThePearson’s coefficient of correlation (R) was calcu-lated. Multiple regression analysis was then appliedto evaluate independent associations and confound-ing parameters.As reported in Table I, cases and controls were notsignificantly different, except for triglycerides levels

Evaluation of body composition with bioimpedence. A comparison between athletic and non-athletic children

Abstract Purpose: Conventional Bioelectrical Impedance Analysis (BIA) or Bioelectrical Impedance Vector Analysis (BIVA) can provide direct evaluations of body composition. The purpose of this study was to evaluate lean and fat mass (FM), and hydration of children involved in daily competitive sports. Methods: 190 non-athletic [8.2–10.5 years] and 29 competitive children [8.0–10.5 years] were enrolled. They were evaluated: at baseline (t0), 6 months (t1) and one year (t2). Anthropometric, BIA and BIVA, lean and FM, and hydration evaluations were performed. Results: Resistance (R/h) and reactance (Xc/h) were lower at t0 in competitive individuals when compared to controls. Xc/h (+3.28) significantly increases in competitive when compared to non-competitive individuals (+0.66, p for difference: 0.011), while phase angle (PA) was lower at t0 (5.72 vs. 6.17, p < .001) and after 6 months (p = .001). Total body water adjusted for height (TBW/h) significantly increased only in non-athletes (+0.50 ± 0.13, p < .001) between t0 and t1. At t1, extracellular water (ECW) significantly decreased (p = .026) in the two groups: −0.45 ± 0.19% in non-competitive, −1.63 ± 0.49% in competitive subjects, while intracellular water (ICW) increased. At one-year follow-up (t2), there were no statistically significant differences in R/h, Xc/h and PA in competitive individuals when compared to baseline and t1. Furthermore, we observed at t2 that hours/week of training, age, male gender and body mass index can influence FFM/h and FM/h in both competitive and non-competitive subjects. In particular, a direct correlation was for hours/week and FFM/h, inverse for hours/week and FM/h. Conclusions: Body mass index does not allow evaluating differences in lean body mass and FM between athletes and non-athletes. BIA and BIVA can give more reliable details about body composition differences in competitive adolescents and non-competitive, outlining a progressive decline in ECW and increase in ICW without affecting TBW composition of athletes.

ST2L Transmembrane Receptor Expression: An Immunochemical Study on Endarterectomy Samples

Background ST2 (suppression of tumorigenity) has been described as a receptor for the interleukin-33, a member of the IL-1 family of cytokines. It is associated to coronary artery disease, all-causes mortality and cardiovascular mortality. Aims The present study was designed to assess the immunohistochemical expression of the ST2 receptor (ST2L/Il-1R) in atherosclerotic plaques of formalin fixed paraffin-embedded internal carotid arteries of patients with and without cerebro-vascular symptoms. Methods and Results The study involved 41 cases (23 asymptomatic and 18 symptomatic). All the clinical and morphological parameters examined were uniformly distributed between the two groups, with a mild predominance of degree of calcification in asymptomatic cases (p = 0.01). ST2L expression was found to be more evident as a membrane pattern in macrophages when observing carotid atherosclerotic plaques of symptomatic patients, rather than in asymptomatic patients’ plaques (77.7% vs 39.1%; p = 0.015), and its expression was particularly remarkable in VI type plaque (AHA). Significantly, ST2L was marked by the endothelium of neoangiogenetic vessels on the shoulder region of the plaque, but not (apart from a few cases) in the endothelium covering the residual lumen of the vessel. Conclusions The ST2L immunohistochemical expression was for the first time investigated in a large number of human carotid atherosclerotic plaques, as for its pattern of distribution in the different plaque cell populations. Furthermore, ST2L was particularly remarkable on macrophages, as a membrane pattern, of symptomatic patients’ plaque. Considering our data, we hypothesize that ST2L/IL33 axis could drive the mechanism of plaque development and eventually rupture.

Focus on alirocumab: A PCSK9 antibody to treat hypercholesterolemia

Statin treatment represents the gold standard in the reduction of low-density lipoprotein cholesterol and cardiovascular risk. Although statin therapy is generally well tolerated, some patients fail to achieve the target level of low-density lipoprotein cholesterol or discontinue the treatment for the occurrence of adverse events. In recent years new lipid-modifying agents have been studied to overcome these limitations and to reduce low-density lipoprotein cholesterol plasma levels. Alirocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9, thereby preventing its interaction with low density lipoprotein receptors. Several trials have been conducted in the last few years to evaluate long-term effects of this new molecule on low-density lipoprotein cholesterol levels and cardiovascular risk.

Bioresorbable vascular scaffolds: design, clinical trials, and current applications.

In recent years, bioresorbable vascular scaffolds (BVS) have been introduced into clinical practice. The main advantage of BVS is that they overcome the problem of the foreign body in the treated artery. BVS, once placed into narrowed coronary vessels, behave like a conventional drug-eluting stent, but a device that disappears over time can preserve the anatomy and physiology of the treated vessel. The progression of stenosis after stenting has been attributed, at least in part, to inflammation around metallic struts, that, however, disappears gradually when using BVS. BVS have proven to be effective and safe as drug-eluting stents; in fact, the rate of adverse cardiovascular events and scaffold thrombosis in patients is low. The aim of this review article is to provide a comprehensive and updated description of the status of the art on BVS, highlighting the current evidence and future perspectives of this technology.