Abstract-The prognostic value of sleep blood pressure reported by recent studies is variable. Our aim was to examine the relationship of sleep blood pressure, measured by 24-hour ambulatory blood pressure monitoring, with all-cause mortality. We studied a cohort of 3957 patients aged 55Ϯ16 (58% treated) referred for ambulatory monitoring (1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005) Key Words: ambulatory blood pressure monitoring Ⅲ dipping Ⅲ mortality Ⅲ cohort Ⅲ sleep blood pressure D ata generated by 24-hour ambulatory blood pressure monitoring (ABPM) have been used to predict cardiovascular morbidity, as well as cardiovascular and all-cause mortality. [1][2][3][4][5][6][7][8][9] There is mounting evidence that this predictive ability is in part unrelated to clinic blood pressure (BP) measurements. Conceivably, ABPM reflects physiological states that are not captured by resting clinic measurements. 9 Moreover, ABPM reduces the influence of the measurement itself on BP values, namely the white-coat effect. In addition, ambulatory monitoring may unmask abnormal BP values that were not detected in the office. Thus, it is expected that ABPM would predict mortality above and beyond clinic measurements. There is still debate, however, whether in reality this is indeed the case and whether the use of this burdensome technique in clinical care is justified and contributes to patient management. 5 Another issue under debate concerns which component of the 24-hour ambulatory monitoring incorporates the most valuable prognostic information. Measurements taken during the waking state reflect, in part, physical activity, which may differ within and between patients. Thus, we hypothesized that, compared with awake BP, sleep measurements would relate to prognosis in a more profound way. Indeed, some 1,3,5,7,10,11 but not all 2 of the outcome studies have suggested this previously.In this study, we investigated all-cause mortality among patients who underwent ambulatory monitoring in a single center since 1991. We highlight sleep BP data identified by recorded sleeping periods, including afternoon naps. 12 We show that sleep BP, as well as nocturnal BP reduction (dipping, a somewhat controversial and infrequently studied topic 7,9,10,13 ) have independent predictive power. Methods Study PopulationData were extracted from our entire ABPM service database, from 1991 through 2005. All of the patients were included, except those Ͻ16 years old, pregnant women, and subjects with poor-quality ABPM (Ͻ50 valid measurements). Patients were referred for standard clinical indications at the discretion of the referring physician (mainly primary care practitioners, who have been shown to use ABPM for appropriate indications 14 ). We were not involved in the clinical care of these patients. Baseline data collected included demographic characteristics (age: 55 years [range: 16 to 93 years], sex (53% female), ethnicity (94% Jewish and 6% non-Jewish, predominantly Moslem Arabs), height (1.67 m; range...

Background: Although it has been somewhat overlooked, resting heart rate is an established predictor of cardiovascular and noncardiovascular outcome. We assessed the determinants and mortality associations of heart rate measured during ambulatory blood pressure monitoring (ABPM) to evaluate its informativeness during activity and sleep. Methods: We studied a cohort of 3957 patients aged 55 ± 16 (mean ± SD) years (58% treated for hypertension) who were referred for ABPM during 1991 to 2005. Heart rate nondipping was defined as follows: (awake value−sleep value)/awake valueϽ0.1. Linear and logistic regression models assessed covariate associations with ambulatory heart rate indices. All-cause mortality was analyzed by Cox proportional hazards modeling. Results: Female sex, body mass index (calculated as weight in kilograms divided by height in meters squared), and treated diabetes were positively related to awake and sleep heart rate, whereas age and treated hypertension were inversely associated. All these variables were associated with lower sleep-related heart rate dipping magnitude. Multivariate-adjusted odds ratios (95% confidence intervals) for heart rate nondipping were 1.02 (1.02-1.03) per year of age; 1.05 (1.03-1.06) for body mass index; 1.39 (1.20-1.60) for women; 1.30 (1.12-1.51) for nappers; 2.19 (1.87-2.57) for treated hypertensive patients; and 1.38 (1.09-1.76) for treated diabetic patients. Mortality analysis according to deciles of the different heart rate variables showed a robust linear relationship only for heart rate dip and a hazard ratio of 2.67 (1.31-5.47) for the lowest vs the highest decile. Conclusions: In clinical practice, ambulatory heart rate adds prognostic information beyond that of other ABPM predictors. Heart rate measures during sleep, and in particular the absence of dipping of heart rate to sleep levels, were independently associated with all-cause mortality.

In a group of consecutive subjects referred for ambulatory BP monitoring, masked hypertension was found to be as common as isolated clinic hypertension. Masking was correlated with male sex, young age, and higher awake heart rate, thus suggesting a causal relationship with greater daytime physical activity. The linear association of the masking and the white-coat effects to clinic BP suggests that regression toward the mean may partially explain these phenomena.

A prospective analysis of consecutive ambulatory blood pressure monitorings over a 5 month period identified 50 subjects (35%) who took an afternoon nap during the monitoring. The average duration of daytime sleep, as reported by the patients, was 1.8 +/- 0.6 h compared with the reported 7 +/- 2 h for nighttime sleep. Ambulatory blood pressure values during daytime awake periods were significantly higher compared with daytime sleep and nighttime sleep. The blood pressure decline during daytime sleep and nighttime sleep was similar. The pattern of blood pressure changes during daytime sleep was comparable in normotensive (n = 16), untreated (n = 10), and treated hypertensives (n = 24), irrespective of age, gender, and the level of blood pressure. The marked decline in blood pressure during daytime sleep suggests that sleep itself, rather than an endogenous circadian rhythm, is responsible for the blood pressure dip observed during both daytime sleep and nighttime sleep. Ignoring actual sleeping time in people who sleep during the day may greatly distort the day-night ambulatory blood pressure difference, when the latter is calculated on the basis of arbitrarily defined "day" and "night" periods.

We explored the predictive ability of the blood pressure variability ratio (BPVR), defined as the ratio of 24-h ambulatory systolic blood pressure variability to diastolic variability, and evaluated its predictable relation with blood pressure and the Ambulatory Arterial Stiffness Index (AASI). A total of 3433 consecutive patients were followed up to 16 years for all-cause mortality. Blood pressure variability was expressed by the standard deviation. BPVR, which is the systolic-on-diastolic slope estimated by a known type of symmetric regression ('reduced major axis'), was compared with other expressions of this slope and with AASI using other regression procedures. Time-dependent Cox proportional hazard models, adjusted for demographics, 24-h mean blood pressure, 24-h pulse pressure and dipping were used to assess the association of BPVR and slope-related parameters with all-cause mortality. We found that Pearson's correlation between BPVR and the symmetric slope was 0.957, and between 1-1/BPVR (an AASI-equivalent expression) and the symmetric version of AASI was 0.973. BPVR was entirely independent of mean arterial pressure (r¼0.013). Systolic and diastolic ambulatory blood pressure variability was not significantly associated with mortality. Over 16 years, BPVR predicted all-cause mortality [hazard ratio¼1.21 (95% CI 1.05-1.40) per 1 s.d. increase]. In time-dependent models, increased BPVR was strongly associated with an 18-month mortality, weakly related to 7 years mortality, showing no effect thereafter. Thus, the ratio between 24-h systolic and diastolic blood pressure variability, readily available from ambulatory monitoring reports, is an easy-to-calculate systolic-on-diastolic slope. It is a blood pressureindependent measure believed to express an arterial property, with prognostic power similar to that of AASI.