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Potential Biomakers for Predicting AAA Expansion

Potential Biomakers for Predicting AAA Expansion. Jes S. Lindholt. Amsterdam 2010. Amsterdam 2010. Vascular Research Unit, Viborg Hospital, Denmark. Background: why biomarkers ?. 85-90% of screen-detected AAA is below 5½ cm in size

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Potential Biomakers for Predicting AAA Expansion

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  1. Potential Biomakers for Predicting AAA Expansion Jes S. Lindholt Amsterdam 2010 Amsterdam 2010 Vascular Research Unit, Viborg Hospital, Denmark

  2. Background: why biomarkers ? • 85-90% of screen-detected AAA is below 5½ cm in size • Earlier AAA surgery produces more safe surgery + better QoL • Only half benefit of surgery. - more nuanced indication of operation • Monitoring endovascular excluded AAA for endoleak • Monitoring pharmacological treatment to inhibit aneurysmal progression

  3. The aim • to find potential present serological biomarkers for expansion in the literature of all publications from 1985 to 2010 by conducting a systematic review Urbonavicius S, Urbonaviciene G, Honoré B, Henneberg EW, Vorum H, Lindholt JS. Eur J Vasc Endovasc Surg. 2008 Sep;36(3):273-80;

  4. PRISMA FLOW CHART 924 hits Excluded due to irrelevant title 740 potentially relevant titles Excluded due to irrelevant abstract – mainlyanimals, wall, case-controls and surrogate markers as size, and volume 290 potentially relevant abstracts Excluded due to irrelevant content – mainlycase-controls, surrogate markers as size, and volume 51 includedpapers

  5. End-points • Mean annual expansion rate - Average growth rate - Linear model of expansion • Statistics - Correlation analysis and - multivariate regression analysis - Above and below median of growth rate - Above and below interobserver variation of the measurements • Prediction of surgery - Survival analysis - ROC curve analysis

  6. Degradation products:Elastin peptides (EP) • N=79 • EP vs growth rate, 1st year: r = 0.40 (0.20-0.57) Lindholt et al. Eur J Vasc Endovasc Surg 1997;21:235-240

  7. Degradation products: elastin peptides (EP) • ROC curve analysis: optimal sensitivity and specificity of 67% and 60% - similar to last AAA size • Chichester Aneurysm Screening Programme 39 unoperated AAA > 6 cm: 12 ruptured later • S-EP was significantly higher in AAA rupturing later Lindholt et al. Eur J Vasc Endovasc Surg: 2001;21:546-550

  8. Degradation products: Elastin peptides (EP)- limitations • EP: an ELISA based upon polyclonal antibodies • ”Poor” correlation between generations of ELISAs: r=0.46 • Standardized ELISA needed for clinical application • Lindholt et al. Int J Angio: 2001;21:546-50

  9. Compensatory disordered collagen: Procollagen-N-III-propeptide (NPIIIP) • N=99 • NPIIIP vs growth rate: r=0.24 (0.02-0.44) • No potential for predicting surgery Lindholt et al. Eur J Vasc Endovasc Surg: 2001;21:235-240

  10. Inflammation: specific cytokines

  11. Inflammation acute phase reactants

  12. Matrix degradation: Involved proteases and their inhibitors

  13. Intraluminal thrombus

  14. Triggering factorsLipids

  15. Triggering factorsSmoking, Homocysteine and Ig-C.pneumoniae

  16. Conclusions • Several potential serological predictors • Few with clinical potential: - Elastin peptides – (standardized ELISA needed) - Plasmin or tPA – the common proteolytic activator - MMP9 ? - γ-Interferon? - Ig-CP by ELISA ? • Multivariate approach • Confirmation in larger cohortes • International collaboration needed • New methodologies in the hunt

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