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Candidate plasma biomarkers for predicting ascending aortic aneurysm in bicuspid aortic valve disease.

cam.issuedOnline2018-06-22
dc.contributor.authorHarrison, Oliver J
dc.contributor.authorCagampang, Felino
dc.contributor.authorOhri, Sunil K
dc.contributor.authorTorrens, Christopher
dc.contributor.authorSalhiyyah, Kareem
dc.contributor.authorModi, Amit
dc.contributor.authorMoorjani, Narain
dc.contributor.authorWhetton, Anthony D
dc.contributor.authorTownsend, Paul A
dc.contributor.orcidHarrison, Oliver J [0000-0001-6396-6708]
dc.date.accessioned2018-06-22T06:04:25Z
dc.date.available2018-06-22T06:04:25Z
dc.date.issued2018-06-22
dc.date.updated2018-06-22T06:04:21Z
dc.description.abstractBACKGROUND: Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality affecting 1-2% of the population and is associated with a significantly increased risk of ascending aortic aneurysm. However, predicting which patients will develop aneurysms remains a challenge. This pilot study aimed to identify candidate plasma biomarkers for monitoring ascending aortic diameter and predicting risk of future aneurysm in BAV patients. METHODS: Plasma samples were collected pre-operatively from BAV patients undergoing aortic valve surgery. Maximum ascending aortic diameter was measured on pre-operative transoesophageal echocardiography. Maximum diameter ≥ 45 mm was classified as aneurysmal. Sequential Window Acquisition of all THeoretical Mass Spectra (SWATH-MS), an advanced mass spectrometry technique, was used to identify and quantify all proteins within the samples. Protein abundance and aortic diameter were correlated using logistic regression. Levene's test was used to identify proteins demonstrating low abundance variability in the aneurysmal patients (consistent expression in disease), and high variability in the non-aneurysmal patients (differential expression between 'at risk' and not 'at risk' patients). RESULTS: Fifteen plasma samples were collected (seven non-aneurysmal and 8 aneurysmal BAV patients). The mean age of the patients was 55.5 years and the majority were female (10/15, 67%). Four proteins (haemoglobin subunits alpha, beta and delta and mannan-binding lectin serine protease) correlated significantly with maximal ascending aortic diameter (p < 0.05, r = 0.5-0.6). Five plasma proteins demonstrated significantly lower variability in the aneurysmal group and may indicate increased risk of aneurysm in non-aneurysmal patients (DNA-dependent protein kinase catalytic subunit, lumican, tetranectin, gelsolin and cartilage acidic protein 1). A further 7 proteins were identified only in the aneurysmal group (matrin-3, glucose-6-phosphate isomerase, coactosin-like protein, peptidyl-prolyl cis-trans isomerase A, golgin subfamily B member 1, myeloperoxidase and 2'-deoxynucleoside 5'-phosphate N-hydrolase 1). CONCLUSIONS: This study is the first to identify candidate plasma biomarkers for predicting aortic diameter and risk of future aneurysm in BAV patients. It provides valuable pilot data and proof of principle that could be used to design a large-scale prospective investigation. Ultimately, a more affordable 'off-the-shelf' follow-on blood assay could then be developed in place of SWATH-MS, for use in the healthcare setting.
dc.identifier.citationJournal of Cardiothoracic Surgery. 2018 Jun 22;13(1):76
dc.identifier.doi10.17863/CAM.24669
dc.identifier.eissn1749-8090
dc.identifier.issn1749-8090
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/277374
dc.language.isoeng
dc.language.rfc3066en
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1186/s13019-018-0762-1
dc.rights.holderThe Author(s).
dc.subjectAscending aortic aneurysm
dc.subjectBicuspid aortic valve
dc.subjectPlasma biomarker
dc.subjectRisk prediction
dc.subjectAdult
dc.subjectAged
dc.subjectAorta
dc.subjectAortic Aneurysm
dc.subjectAortic Valve
dc.subjectBicuspid Aortic Valve Disease
dc.subjectBiomarkers
dc.subjectEchocardiography, Transesophageal
dc.subjectFemale
dc.subjectHeart Valve Diseases
dc.subjectHumans
dc.subjectLogistic Models
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectPilot Projects
dc.subjectProspective Studies
dc.subjectRisk Factors
dc.titleCandidate plasma biomarkers for predicting ascending aortic aneurysm in bicuspid aortic valve disease.
dc.typeJournal Article
dcterms.dateAccepted2018-06-15
prism.publicationNameJ Cardiothorac Surg
rioxxterms.versionofrecord10.1186/s13019-018-0762-1

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