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      Assessment of Atherosclerosis in Peripheral and Central Circulation in Adult β Thalassemia Intermedia Patients by Color Doppler Ultrasound: Egyptian Experience

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          Abstract

          Background: Atherosclerosis has been extensively studied in thalassemia major (TM) and sickle cell disease but not yet in β thalassemia intermedia (TI). Previous studies concerned with TM were performed in children. TI patients usually live longer and, thus, are more prone to complications of atherosclerosis. Aim: In our study, we applied color Doppler for the determination of arterial conduit and flow velocities in β TI patients. Methods: For central circulation, we measured right and left middle cerebral arteries (MCAs) and basilar artery (BA) mean flow velocity (MFV), pulsatility index (PI), and peak systolic velocity (PSV) as well as carotid intimal media thickness, and to assess peripheral circulation, we studied ankle/brachial index and posterior and anterior tibial arteries’ (ATA, PTA) pressure and PSV. This was applied for 30 adult TI patients and 20 age-, sex-, and ethnic group-matched controls. Results: Transcranial Doppler findings among cases and controls showed that the MFV, PSV of MCAs, and PSV, PI, and MFV of the BA were statistically higher in cases than controls. A comparison between splenectomized and nonsplenectomized patients showed that total leukocyte count, platelet count, lactate dehydrogenase, ferritin, PSV and MFV of the left MCA were all statistically higher in splenectomized cases. Differences between males and females with TI with respect to laboratory and Doppler findings were all statistically insignificant except for intima media thickness, PTA pressure, ATA pressure, and PSV. Conclusion: More than one parameter should be applied to assess atherosclerosis in TI. There is evidence of an increased risk of central ischemia rather than peripheral ischemia in these patients.

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          Sensitivity and specificity of the ankle-brachial index to predict future cardiovascular outcomes: a systematic review.

          The ankle-brachial index is the ratio of the ankle and the brachial systolic blood pressure and is used to assess individuals with peripheral arterial disease. An ankle-brachial index <0.90 suggests the presence of peripheral arterial disease and is a marker of cardiovascular risk. The objective of this review is to determine the sensitivity and specificity of an ankle-brachial index <0.90 to predict future cardiovascular events, including coronary heart disease, stroke, and death. We conducted a systematic review of the literature and included studies that used an ankle-brachial index cutoff between 0.80 and 0.90 to classify patients with or without peripheral arterial disease, followed patients prospectively, and recorded cardiovascular outcomes (ie, myocardial infarction, stroke, or mortality). Data were combined using a random-effects model meta-analysis to determine the sensitivity, specificity, relative risks, and likelihood ratios of a low ankle-brachial index to predict future cardiovascular disease. A total of 22 studies were identified, 13 were excluded, and 9 studies were included in the meta-analysis. The sensitivity and specificity of a low ankle-brachial index to predict incident coronary heart diseases were 16.5% and 92.7%, for incident stroke were 16.0% and 92.2%, and for cardiovascular mortality were 41.0% and 87.9%, respectively. The corresponding positive likelihood ratios were 2.53 (95% CI, 1.45 to 4.40) for coronary heart disease, 2.45 (95% CI, 1.76 to 3.41) for stroke, and 5.61 (95% CI, 3.45 to 9.13) for cardiovascular death. The specificity of a low ankle-brachial index to predict future cardiovascular outcomes is high, but its sensitivity is low. The ankle-brachial index should become part of the vascular risk assessment among selected individuals.
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            Iron chelation improves endothelial function in patients with coronary artery disease.

            Some epidemiological studies have shown that increased iron stores are associated with increased cardiovascular events. Redox-active iron may contribute to lipid peroxidation, endothelial cell activation, and generation of reactive oxygen species (especially hydroxyl radical, via Fenton chemistry). Increased oxidative stress is associated with impaired action of endothelium-derived nitric oxide in patients with atherosclerosis. To test the hypothesis that reducing vascular iron stores would reverse endothelial dysfunction, we examined the effects of the iron chelator deferoxamine (500 mg intra-arterially over 1 hour) on vasomotor function in forearm resistance vessels of patients with coronary artery disease by venous occlusion plethysmography. Patients with coronary artery disease had impaired endothelium-dependent vasodilation in response to methacholine compared with healthy control subjects (P<0.001). Deferoxamine infusion decreased serum iron levels (P<0.001). Deferoxamine improved the blood flow response to methacholine in patients with coronary artery disease (P<0.01 by 2-way repeated-measures ANOVA) but had no effect on the response to sodium nitroprusside. In normal volunteers, deferoxamine had no effect on the response to methacholine. The nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine abolished augmentation of the methacholine response associated with deferoxamine. The hydroxyl radical scavenger mannitol had no effect on the methacholine response. Deferoxamine improved nitric oxide-mediated, endothelium-dependent vasodilation in patients with coronary artery disease. These results suggest that iron availability contributes to impaired nitric oxide action in atherosclerosis.
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              Microvesicles in haemoglobinopathies offer insights into mechanisms of hypercoagulability, haemolysis and the effects of therapy.

              Levels of circulating red blood cell (RBC)-derived vesicles are increased in sickle cell anaemia (SCA) and thalassaemia intermedia (TI) but the mechanisms, effects and controlling factors may differ. This study found that levels of vesicles and intravascular haemolysis were linked as shown by the correlation between levels of vesicles and plasma Hb. Vesicle levels were 6-fold greater in SCA and 4-fold greater in TI than in controls. The proportion of plasma Hb within vesicles was increased in SCA and TI with a significantly higher proportion in TI. We examined whether subpopulations of RBC expressing phosphatidylserine (PS) were a source of PS(+) vesicles and observed a significant association. Thrombin generation was promoted by the vesicles in which 40-50% expressed PS. In TI, markers of thrombin generation were significantly related to PS(+) RBC. Splenectomy in TI had significant effects including greater increases in vesicle levels, plasma Hb, PS(+) RBCs and thrombin generation markers than in unsplenectomised patients. In hydroxycarbamide (HC)-treated SCA patients these measures were decreased compared with untreated controls. The relationship between vesicle levels and plasma Hb suggests a mechanism linking vesiculation to haemolysis and consequently nitric oxide (NO) bioavailability and suggests a means by which HC treatment improves NO bioavailability.
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                Author and article information

                Journal
                JVR
                J Vasc Res
                10.1159/issn.1018-1172
                Journal of Vascular Research
                S. Karger AG
                1018-1172
                1423-0135
                2020
                July 2020
                12 May 2020
                : 57
                : 4
                : 206-212
                Affiliations
                [_a] aVascular Medicine Unit, Internal Medicine Department, Kasr Al Ainy Faculty of Medicine, Cairo University, Cairo, Egypt
                [_b] bClinical Hematology Unit, Internal Medicine Department, Kasr Al Ainy Faculty of Medicine, Cairo University, Cairo, Egypt
                [_c] cArmy Force Faculty of Medicine, Cairo, Egypt
                Author notes
                *Noha M. El Husseiny, Kasr Al Ainy Faculty of Medicine, Cairo University, Kasr Al Ainy Street, Cairo 11111 (Egypt), Noha_el_husseiny77@yahoo.com
                Author information
                https://orcid.org/0000-0002-5061-9536
                https://orcid.org/0000-0002-6806-3505
                Article
                506518 J Vasc Res 2020;57:206–212
                10.1159/000506518
                32396894
                7b86dc6c-2ece-49df-bf1a-e3c9aa215264
                © 2020 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 26 September 2019
                : 13 February 2020
                Page count
                Figures: 2, Tables: 5, Pages: 7
                Categories
                Research Article

                General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
                Stroke,Transcranial Doppler,Thalassemia intermedia,Thrombosis

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