Value of Excess Pressure Integral for Predicting 15-Year All-Cause and Cardiovascular Mortalities in End-Stage Renal Disease Patients Jui-Tzu Huang Medical undergraduate student; Hao-Min Cheng, MD, PhD; Wen-Chung Yu, MD; Yao-Ping Lin, MD, PhD; Shih-Hsien Sung, MD, PhD; Jiun-Jr Wang, PhD; Chung-Li Wu, MS; Chen-Huan Chen, MD Background-—The excess pressure integral (XSPI), derived from analysis of the arterial pressure curve, may be a significant predictor of cardiovascular events in high-risk patients. We comprehensively investigated the prognostic value of XSPI for predicting long-term mortality in end-stage renal disease patients undergoing regular hemodialysis. Methods and Results- —A total of 267 uremic patients (50.2% female; mean age 54.2Æ14.9 years) receiving regular hemodialysis for more than 6 months were enrolled. Cardiovascular parameters were obtained by echocardiography and applanation tonometry. Calibrated carotid arterial pressure waveforms were analyzed according to the wave-transmission and reservoir-wave theories. Multivariable Cox proportional hazard models were constructed to account for age, sex, diabetes mellitus, albumin, body mass index, and hemodialysis treatment adequacy. Incremental utility of the parameters to risk stratification was assessed by net reclassification improvement. During a median follow-up of 15.3 years, 124 deaths (46.4%) incurred. Baseline XSPI was significantly predictive of all-cause (hazard ratio per 1 SD 1.4, 95% confidence interval 1.15-1.70, P=0.0006) and cardiovascular mortalities (1.47, 1.18-1.84, P=0.0006) after accounting for the covariates. The addition of XSPI to the base prognostic model significantly improved prediction of both all-cause mortality (net reclassification improvement=0.1549, P=0.0012) and cardiovascular mortality (net reclassification improvement=0.1535, P=0.0033). XSPI was superior to carotid-pulse wave velocity, forward and backward wave amplitudes, and left ventricular ejection fraction in consideration of overall independent and incremental prognostics values. Conclusions-—In end-stage renal disease patients undergoing regular hemodialysis, XSPI was significantly predictive of long-term mortality and demonstrated an incremental value to conventional prognostic factors. ( J Am Heart Assoc. 2017;6:e006701. DOI: 10.1161/JAHA.117.006701.) Key Words: cardiovascular mortality • hemodynamics • prognosis • reservoir-pressure analysis • uremia T he prevalence of end-stage renal disease (ESRD) patients is rising globally. 1 Although the facilities and techniques for dialysis have improved substantially, the mortality remains high. 2,3 The disproportionally elevated cardiovascular morbid- ity and mortality in ESRD patients undergoing dialysis cannot be fully explained by the traditional cardiovascular risk factors such as aging, hypertension, diabetes mellitus, dyslipidemia, obesity, and smoking. 4 Consequently, increasing attention presently is paid to the emerging prognostic factors to improve the risk stratification and identify the targeted therapies for ESRD patients. 5 Among the first of these efforts, arterial factors, including arterial stiffness 6,7 and arterial wave reflec- tion, 8 have been identified as useful prognostic factors for cardiovascular outcomes in hemodialysis patients. Therefore, high blood pressure (BP) and hemodynamic overload are widely accepted as the main contributing factors to the left From the Faculty of Medicine (J.-T.H., H.-M.C., W.-C.Y., Y.-P.L., S.-H.S., C.-H.C.) and Institute of Public Health and Community Medicine Research Center (H.-M.C., C.- H.C.), National Yang-Ming University, Taipei, Taiwan; Department of Medical Education, Center for Evidence-based Medicine (H.-M.C., C.-L.W., C.-H.C.) and Department of Internal Medicine (W.-C.Y., Y.-P.L., S.-H.S.), Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan (J.-J.W.). Accompanying Tables S1 and S2 are available at http://jaha.ahajournals.org/content/6/12/e006701/DC1/embed/inline-supplementary-material-1.pdf Correspondence to: Hao-Min Cheng, MD, PhD, No. 201, Sec. 2, Shih-Pai Road, Beitou District, Taipei, Taiwan 112, China. E-mail: hmcheng@vghtpe.gov.tw or Chen- Huan Chen, MD, Department of Medical Education, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan. E-mail: chench@vghtpe.gov.tw Received May 17, 2017; accepted October 13, 2017. ª 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. DOI: 10.1161/JAHA.117.006701 Journal of the American Heart Association 1 ORIGINAL RESEARCH by guest on November 30, 2017 http://jaha.ahajournals.org/ Downloaded from