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      Plasma Desmosine and Abdominal Aortic Aneurysm Disease

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          Abstract

          Background

          It is recognized that factors beyond aortic size are important in predicting outcome in abdominal aortic aneurysm (AAA) disease. AAA is characterized by the breakdown of elastin within the aortic tunica media, leading to aortic dilatation and rupture. The aim of this study was to investigate the association of plasma desmosine (pDES), an elastin‐specific degradation product, with disease severity and clinical outcome in patients with AAA.

          Methods and Results

          We measured pDES and serum biomarker concentrations in 507 patients with AAAs (94% men; mean age, 72.4±6.1 years; mean AAA diameter, 48±8 mm) and 162 control subjects (100% men; mean age, 71.5±4.4 years) from 2 observational cohort studies. In the longitudinal cohort study (n=239), we explored the incremental prognostic value of pDES on AAA events. pDES was higher in patients with AAA compared with control subjects (mean±SD: 0.46±0.22 versus 0.33±0.16 ng/mL; P<0.001) and had the strongest correlation with AAA diameter ( r=0.39; P<0.0001) of any serum biomarker. After adjustment for baseline AAA diameter, pDES was associated with an AAA event (hazard ratio, 2.03 per SD increase [95% CI, 1.02–4.02]; P=0.044). In addition to AAA diameter, pDES provided incremental improvement in risk stratification (continuous net reclassification improvement, 34.4% [95% CI, −10.8% to 57.5%; P=0.09]; integrated discrimination improvement, 0.04 [95% CI, 0.00–0.15; P=0.050]).

          Conclusions

          pDES concentrations predict disease severity and clinical outcomes in patients with AAA.

          Clinical Trial Registration

          http:// www.isrctn.com. Unique identifier: ISRCTN76413758.

          Related collections

          Most cited references37

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          Aortic dissection precedes formation of aneurysms and atherosclerosis in angiotensin II-infused, apolipoprotein E-deficient mice.

          We sought to define the temporal characteristics of angiotensin II (AngII)-induced abdominal aortic aneurysms (AAAs) and to provide mechanistic insight into the development of this vascular pathology in apolipoprotein E-deficient (apoE-/-) mice. Male apoE-/- mice were infused with AngII for 1 to 56 days. Suprarenal arteries were sequentially sectioned, and cellular features were defined by histologic and immunocytochemical techniques. The initial identified event was medial accumulation of macrophages in regions of elastin degradation. Subsequent medial dissection was associated with luminal dilation and thrombus formation. Thrombi were usually constrained by adventitial tissue, although approximately 10% of mice died due to rupture. Thrombi led to profound inflammation that was characterized by infiltration of macrophages and T and B lymphocytes. Remodeling of the tissues was associated with regeneration of elastin fibers and reendothelialization of the dilated luminal surface. Aneurysmal tissue underwent profound neovascularization. Atherosclerotic lesions were only detected after development of the aneurysms. The initial event in AngII-induced AAA is a focal dissection in the suprarenal region. The progression of AAA precedes the development of overt atherosclerotic lesions.
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            Screening for abdominal aortic aneurysm: a best-evidence systematic review for the U.S. Preventive Services Task Force.

            While the prognosis for abdominal aortic aneurysm (AAA) rupture is poor, ultrasound imaging is an accurate and reliable test for detecting AAAs before rupture. To examine the benefits and harms of population-based AAA screening. MEDLINE (1994 to July 2004) supplemented by the Cochrane Library, a reference list of retrieved articles, and expert suggestions. Randomized trials of AAA population screening, population studies of AAA risk factors, and data on adverse screening and treatment events from randomized trials and cohort studies. All studies were reviewed, abstracted, and rated for quality by using predefined criteria. The authors identified 4 population-based randomized, controlled trials of AAA screening in men 65 years of age and older. On the basis of meta-analysis, an invitation to attend screening was associated with a significant reduction in AAA-related mortality (odds ratio, 0.57 [95% CI, 0.45 to 0.74]). A meta-analysis of 3 trials revealed no significant difference in all-cause mortality (odds ratio, 0.98 [CI, 0.95 to 1.02]). No significant reduction in AAA-related mortality was found in 1 study of AAA screening in women. Screening does not appear to be associated with significant physical or psychological harms. Major treatment harms include an operative mortality rate of 2% to 6% and significant risk for major complications. The population screening studies focused on men and provided no information on racial or ethnic groups. No information was available on uninvited control group characteristics, so the importance of risk factors such as tobacco use or family history could not be assessed. Since all trials were conducted in countries other than the United States, generalizability to the U.S. population is uncertain. For men age 65 to 75 years, an invitation to attend AAA screening reduces AAA-related mortality.
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              Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture, and Need for Surgical Repair

              (2017)
              Supplemental Digital Content is available in the text.
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                Author and article information

                Contributors
                j.t.j.huang@dundee.ac.uk
                a.choy@dundee.ac.uk
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                09 October 2019
                15 October 2019
                : 8
                : 20 ( doiID: 10.1002/jah3.v8.20 )
                : e013743
                Affiliations
                [ 1 ] Division of Molecular and Clinical Medicine University of Dundee Dundee United Kingdom
                [ 2 ] Division of Systems Medicine University of Dundee Dundee United Kingdom
                [ 3 ] British Heart Foundation/University of Edinburgh Centre for Cardiovascular Science Edinburgh United Kingdom
                [ 4 ] Department of Cardiovascular Sciences and National Institute for Health Research Leicester Biomedical Research Centre University of Leicester Glenfield Hospital Leicester United Kingdom
                [ 5 ] Department of Cardiovascular Science National Heart Center Singapore
                Author notes
                [*] [* ]* Correspondence to: Jeffrey T. J. Huang, PhD, and Anna‐Maria Choy, MD, Division of Molecular and Clinical Medicine, University of Dundee, Dundee DD1 9SY, United Kingdom. E‐mails: j.t.j.huang@ 123456dundee.ac.uk and a.choy@ 123456dundee.ac.uk
                Article
                JAH34494
                10.1161/JAHA.119.013743
                6818029
                31595818
                29de234d-1fff-4694-a308-5886fa0f5b95
                © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 26 June 2019
                : 06 September 2019
                Page count
                Figures: 5, Tables: 4, Pages: 9, Words: 6362
                Funding
                Funded by: Tenovus Scotland Major Research Grant
                Award ID: T17/22
                Funded by: Chief Scientist Office Catalytic Grant
                Award ID: CGA/17/07
                Funded by: National Health Service Education for Scotland/Chief Scientist Office Postdoctoral Clinical Lectureship
                Award ID: PCL 17/07
                Funded by: National Institute of Healthcare Research Efficacy and Mechanism Evaluation Program
                Funded by: British Heart Foundation
                Award ID: CH/09/002
                Award ID: RE/13/3/30183
                Award ID: RM/13/2/30158
                Award ID: CS/14/2/30841
                Funded by: Wellcome Trust Senior Investigator Award
                Award ID: WT103782AIA
                Funded by: Academic Department of Military Surgery and Trauma
                Funded by: Circulation Foundation
                Funded by: National Institute for Health Research
                Funded by: Academy of Medical Sciences
                Award ID: SGCL13
                Categories
                Original Research
                Original Research
                Vascular Medicine
                Custom metadata
                2.0
                jah34494
                15 October 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.7.0 mode:remove_FC converted:15.10.2019

                Cardiovascular Medicine
                abdominal aortic aneurysm,aortic rupture,desmosine,elastin,aneurysm,vascular disease,diagnostic testing,biomarkers

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