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Here, we introduce a fluid mechanics model designed to simulate the haemodynamic impact of PAD on AAA-associated risk factors. Our focus lies on quantifying the uncertainty inherent in controlling the flow rates within PAD-affected vessels and predicting AAA risk factors derived from wall shear stress. We perform a sensitivity analysis on nine critical model parameters through simulations of three-dimensional blood flow within a comprehensive arterial geometry. Our results show effective control of the flow rates using two-element Windkessel models, although specific outlets need attention. Quantities of interest like endothelial cell activation potential (ECAP) and relative residence time are instructive for identifying high-risk regions, with ECAP showing greater reliability and adaptability. Our analysis reveals that the uncertainty in the quantities of interest is 187% of that of the input parameters. Notably, parameters governing the amplitude and frequency of the inlet velocity exert the strongest influence on the risk factors\u2019 variability and warrant precise determination. This study forms the foundation for patient-specific simulations involving PAD and AAAs which should ultimately improve patient outcomes and reduce associated mortality rates.<\/jats:p>","DOI":"10.1098\/rsif.2023.0656","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T19:05:17Z","timestamp":1712689517000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Uncertainty quantification of the impact of peripheral arterial disease on abdominal aortic aneurysms in blood flow simulations"],"prefix":"10.1098","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0863-7068","authenticated-orcid":true,"given":"Sharp C. Y.","family":"Lo","sequence":"first","affiliation":[{"name":"London, UK 1","department":["Centre for Computational Science, University College London"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9606-0408","authenticated-orcid":true,"given":"Jon W. S.","family":"McCullough","sequence":"additional","affiliation":[{"name":"London, UK 1","department":["Centre for Computational Science, University College London"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Xue","sequence":"additional","affiliation":[{"name":"London, UK 1","department":["Centre for Computational Science, University College London"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8787-7256","authenticated-orcid":true,"given":"Peter V.","family":"Coveney","sequence":"additional","affiliation":[{"name":"London, UK 1","department":["Centre for Computational Science, University College London"]},{"name":"London, UK 2","department":["Advanced Research Computing Centre, University College London"]},{"name":"Amsterdam, The Netherlands 3","department":["Informatics Institute, Faculty of Science, University of Amsterdam"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2024,4,10]]},"reference":[{"key":"2026010520262180100_RSIF20230656C1","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1007\/s10237-014-0557-9","article-title":"Mechano-biology in the thoracic aortic aneurysm: a review and case study","volume":"13","author":"Martufi","year":"2014","journal-title":"Biomech. 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