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However, interpretation is complicated by coexisting autonomic dysregulation and vascular mechanical alterations in hypertension. This study used a numerical model to disentangle these contributions, which cannot be isolated in\u00a0vivo. A closed\u2010loop mathematical model was developed to simulate cardiovascular variability during head\u2010up tilt (HUT), incorporating four heart chambers, systemic and pulmonary circulations, and short\u2010term autonomic regulation mechanisms via arterial and cardiopulmonary reflexes. Beat\u2010to\u2010beat heart rate and blood pressure fluctuations were simulated by introducing central autonomic noise into sympathetic efferent pathways and incorporating respiratory\u2010induced intrathoracic pressure variations. Three hypertension\u2010related alterations\u2014elevated peripheral resistance, reduced arterial compliance, and enhanced left ventricular contractility\u2014were simulated individually. Elevated vascular resistance suppressed both HRV and BPV via baroreflex saturation. Reduced arterial compliance increased BPV due to impaired pressure buffering but reduced HRV through diminished reflex feedback. Enhanced ventricular contractility amplified both HRV and BPV via stronger baroreflex\u2010driven oscillations and greater pulsatile pressure transmission. Generally, HRV was influenced by autonomic efferent fluctuations, respiratory vagal modulation, and baroreflex\u2010mediated feedback to pressure changes from respiration and orthostatic stress. BPV was more directly governed by mechanical fluctuations in stroke volume. HRV and BPV patterns emerge from interactions between mechanical and reflex mechanisms that modulate the transmission of underlying variability into measurable signals. This modeling framework offers mechanistic insights into beat\u2010to\u2010beat cardiovascular variability in hypertension and may support more accurate clinical interpretation.<\/jats:p>","DOI":"10.1002\/cnm.70148","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T07:11:34Z","timestamp":1770880294000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanistic Interpretation of Beat\u2010to\u2010Beat Cardiovascular Variability in Hypertension Using a Closed\u2010Loop Cardiovascular Model"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6874-4431","authenticated-orcid":false,"given":"Jia Hui","family":"Ooi","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Engineering Universiti Malaya  Kuala Lumpur Malaysia"},{"name":"Graduate School of Biomedical Engineering UNSW Sydney  Sydney New South Wales 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