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BACKGROUND AND AIMS Orthostatic blood pressure decrease or increase has been related to cardiovascular events in hypertensive patients. Large blood pressure changes after orthostatic stress are associated with autonomic and neurohormonal abnormalities; aortic atherosclerosis (ATS) may also play a role. METHODS We investigated the interaction of ATS on the prognostic value of postural blood pressure changes. In a cohort of 958 hypertensive patients with an aortography (mean ± standard deviation age 44 ± 11 years, 61% men, mean blood pressure 182/110 mmHg), blood pressure was measured after 10 min of rest in the supine position. Systolic blood pressure (SBP) was also measured in standing position, 1 min after the supine position. Blood pressure changes were calculated as supine SBP minus standing SBP and analyzed as absolute or arithmetic means. ATS was assessed using an aortography score. RESULTS After 15 years of follow-up, 280 all-cause and 167 cardiovascular deaths occurred. In a multivariable Cox regression analysis adjusted for major cardiovascular risk factors and stratified according to ATS status, SBP changes were statistically associated with all-cause and cardiovascular mortality only in the presence of ATS: tertile 3 versus 1, 2.99 (1.37-6.49) and 4.08 (1.55-10.72) respectively, tertile 3 versus 2, 2.89 (1.29-6.46) and 4.82 (1.79-12.98), respectively (p for interaction: 0.003 for all-cause and 0.003 for cardiovascular mortality) for absolute changes. The hazard associated with the magnitude of SBP changes was more important than that associated with its direction. CONCLUSIONS The prognostic significance of postural SBP changes is markedly influenced by ATS in hypertensive patients.