ORIGINAL ARTICLE A modified ambulatory arterial stiffness index is independently associated with all-cause mortality IZ Ben-Dov 1 , B Gavish 2 , JD Kark 3 , J Mekler 4 and M Bursztyn 4 1 Nephrology and Hypertension Services, Hadassah—Hebrew University Medical Center, Jerusalem, Israel; 2 InterCure Ltd, Lod, Israel; 3 Epidemiology Unit, Hadassah—Hebrew University Medical Center, Jerusalem, Israel and 4 Internal Medicine Department Mount-Scopus Campus, Hadassah—Hebrew University Medical Center, Jerusalem, Israel Dependence of the ambulatory arterial stiffness index (AASI) on data scattering interferes with its potential clinical relevance. We assessed the correlates and all-cause mortality associations of a modified AASI (s-AASI). AASI was derived from the 24-h diastolic vs systolic blood pressure linear regression line, whereas s- AASI was derived by symmetric regression (bisecting the line of diastolic vs systolic and systolic vs diastolic). Of 2918 patients 55% were women; age was 56 ± 16 years and body mass index was 27.3 ± 4.5 kg/m 2 . Average 24-h ambulatory blood pressure was 138±16/78±10 mm Hg. Applying the modified method for calculating AASI yielded a different measure: the negative correlation between AASI and blood pressure dipping (r ¼0.304, Po0.0001) was abolished (r ¼þ 0.223, Po0.0001), s-AASI was more dependent on age (r ¼ 0.266 vs r ¼ 0.089 for AASI), and prediction of all-cause mortality was enhanced; hazard ratio (95% confidence intervals) 1.17 (1.00–1.36) per 1 s.d. increase in s-AASI in the fully adjusted model as compared with 1.15 (0.97–1.36) for AASI. Journal of Human Hypertension (2008) 22, 761–766; doi:10.1038/jhh.2008.50; published online 29 May 2008 Keywords: ambulatory arterial stiffness index; ambulatory blood pressure monitoring; cohort; dipping; prognosis Introduction The linear relationship between systolic and dia- stolic blood pressure (BP) has been shown to reflect arterial properties. 1,2 A measure of this linear relationship, derived from ambulatory BP monitor- ing (ABPM), the Ambulatory Arterial Stiffness Index (AASI), 3 was recently shown to be associated with the metabolic syndrome, 4 with early signs of renal damage 5 and with other target organ damage 6 in patients with hypertension. In addition, AASI predicted prognosis, including cardiovascular and stroke mortality, 7,8 as well as stroke (but not cardiovascular events). 9 However, AASI is dependent on the ambulatory monitoring technique 10 as well as on the magnitude of sleep-related BP dipping. 2,11 Its definition im- plicitly involves the correlation coefficient between systolic BP and diastolic BP data, that is, its value depends on the data scattering. 2 These issues, as well as conceptual concerns regarding the physio- logical interpretation of AASI, 12–14 cast doubt on its genuineness and prognostic validity, 1,8,15 generating a lively debate. 10,12,13,16–21 In this study, we aimed to compare the associa- tions and prognostic implications of AASI with those of a modified AASI, 2 s-AASI. We hypothe- sized that the modification would yield a parameter with different clinical correlates and, more impor- tantly, with enhanced prognostic capabilities. We show that s-AASI, but not AASI predicts all-cause mortality independently of pulse pressure in a large cohort of patients referred for ambulatory monitoring of BP. Methods Study population Data were extracted from our entire ABPM service database from 1991 to 2005, which included 2918 eligible patients for whom AASIs could be deter- mined from existing raw monitoring data files (other, mainly earlier monitored patients had their raw data stored in files that were not assessable at this stage). Excluded were patients less than 16 years old, pregnant women and subjects with poor quality ABPM recordings (less than 50 valid measurements). Subjects with repeat monitoring(s) Received 15 March 2008; revised 19 April 2008; accepted 22 April 2008; published online 29 May 2008 Correspondence: Dr IZ Ben-Dov, Nephrology and Hypertension Services, Hadassah—Hebrew University Medical Center, Ein-Kerem, PO Box 12000, Jerusalem 91120, Israel. E-mail: iddobe@ekmd.huji.ac.il Journal of Human Hypertension (2008) 22, 761–766 & 2008 Macmillan Publishers Limited All rights reserved 0950-9240/08 $32.00 www.nature.com/jhh