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Background: Association of Ambulatory Blood Pressure Monitoring (ABPM) with mortality depends on cardiac function in hemodialysis patients. Evidence for the predictive power of central Systolic Pressure (cSBP) is inconclusive. Thus, this study aimed to investigate the additional information of ambulatory cSBP in risk prediction in a cohort of hemodialysis patients. Methods: Within the ISAR-study cohort, 344 hemodialysis patients underwent 24 h ABPM on the dialysis day. All-cause and cardiovascular mortality served as endpoints. Risk prediction was performed using Cox regression in patients with or without atrial fibrillation (AF) or heart failure (HF) for peripheral (pSBP) and central systolic pressure calibrated with peripheral systolic and diastolic pressure (cSBP1) or peripheral mean and diastolic pressure (cSBP2). Results: During a mean follow-up of 37.6 (17.5 SD) months, 115 patients died, of whom 47 due to cardiovascular reasons. In patients with AF or HF, a negative association to mortality could be observed, independent of pressure location and calibration (see Table). In patients without AF or HF, these associations were to the opposite directions and cSBP2 was superior to pSBP and cSBP1 for all-cause (pSBP: HR = 1.01, p = 0.30; cSBP1: HR = 1.00, p = 0.77; cSBP2: HR = 1.01, p = 0.06) and cardiovascular (pSBP: HR =1.03, p = 0.02; cSBP1: HR = 1.02, p = 0.06; cSBP2: HR = 1.03, p = 0.003) mortality. This circumstance was confirmed in multivariable analysis combining pSBP and differences between pSBP and cSBP (see Table). Conclusions: This study provides evidence for the additional information of central systolic blood pressure and its dependency on calibration in risk prediction in hemodialysis patients. Further studies are needed to confirm these findings.