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One of the most recognized methods for assessing AS is through arterial pulse wave velocity (aPWV), which provides valuable clinical insights into vascular health. However, its measurement typically requires specialized equipment, making it inaccessible in primary healthcare centers and low-resource settings. In this study, we developed and validated different machine learning models to estimate aPWV using common clinical markers routinely collected in standard medical examinations. Thus, we trained five regression models: Linear Regression, Polynomial Regression (PR), Gradient Boosting Regression, Support Vector Regression, and Neural Networks (NNs) on the EVasCu dataset, a cohort of apparently healthy individuals. A 10-fold cross-validation demonstrated that PR and NN achieved the highest predictive performance, effectively capturing nonlinear relationships in the data. External validation on two independent datasets, VascuNET (a healthy population) and ExIC-FEp (a cohort of cardiopathic patients), confirmed the robustness of PR and NN (R2&gt;0.90) across different vascular conditions. These results indicate that by using easily accessible clinical variables and AI-driven insights, it is possible to develop a cost-effective tool for aPWV estimation, enabling early cardiovascular risk stratification in underserved and rural areas where specialized AS measurement devices are unavailable.<\/jats:p>","DOI":"10.3390\/app15094788","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T10:42:09Z","timestamp":1745577729000},"page":"4788","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Development of a Non-Invasive Clinical Machine Learning System for Arterial Pulse Wave Velocity Estimation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2343-3186","authenticated-orcid":false,"given":"Arturo","family":"Martinez-Rodrigo","sequence":"first","affiliation":[{"name":"COMETA Research Group, Informatics Systems Department, University of Castilla-La Mancha, 16071 Cuenca, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7588-8927","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Pedrosa","sequence":"additional","affiliation":[{"name":"Institute for Systems and Computer Engineering, Technology and Science (INESC TEC), R. 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