Liora Ben-Arie

Predictors of All-Cause Mortality in Clinical Ambulatory Monitoring: Unique Aspects of Blood Pressure During Sleep

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 55±16 (58% treated) referred for ambulatory monitoring (1991–2005). Sleep, including daytime sleep, was recorded by diary. Linkage with the national population register identified 303 deaths during 27 750 person-years of follow-up. Hazard ratios (HRs) for mortality in Cox proportional hazards models that included age, sex, hypertension, and diabetes treatment were 1.32 (95% CI: 0.99 to 1.76) for awake hypertension (≥135/85 mm Hg), and 1.67 (95% CI: 1.25 to 2.23) for sleep hypertension (≥120/70 mm Hg). By quintile analysis, the upper fifths of systolic and diastolic dipping during sleep were associated with adjusted HRs of 0.58 (95% CI: 0.41 to 0.82) and 0.68 (95% CI: 0.48 to 0.96), respectively. In a model controlling for awake systolic blood pressure, hazards associated with reduced systolic dipping increased from dippers (>10%; HR: 1.0), through nondippers (0% to 9.9%; HR: 1.30; 95% CI: 1.00 to 1.69) to risers (<0%; HR: 1.96; 95% CI: 1.43 to 2.96). Thus, in practice, ambulatory blood pressure predicts mortality significantly better than clinic blood pressure. The availability of blood pressure measures during sleep and, in particular, the pattern of dipping add clinically predictive information and provide further justification for the use of ambulatory monitoring in patient management.

Dipping Status May Be Determined by Nocturnal Urination

Nondipping, ie, failure to reduce blood pressure by ≥10% during the night, is considered an important prognostic variable of 24-hour ambulatory blood pressure monitoring. However, some people wake up at night to urinate. Usually, 24-hour ambulatory blood pressure monitoring–derived blood pressure includes these rises in the nighttime blood pressure mean. We identified 97 subjects undergoing 24-hour ambulatory blood pressure monitoring who reported waking up at night to urinate. We assessed the 24-hour ambulatory blood pressure monitoring first using total daytime and total nighttime means and then using actual daytime awake and nighttime asleep (as reported by the patient) means. Nocturnal decline in blood pressure was 14.4±8.5/11.8±6.1 mm Hg with the first method and 17.1±8.3/13.8±5.9 mm Hg with the second one (P <0.00001). Although the absolute difference between the nocturnal blood pressure declines calculated by the 2 methods was small, the effect on nocturnal dip was profound. Average systolic blood pressure dipping was 10.1% by the total day–total night method and 12.0% by the actual day awake–night asleep method (P ≤0.00001), and that of diastolic blood pressure was 14.2% and 16.7%, respectively (P ≤0.00001). The prevalence of systolic blood pressure nondipping decreased from 42.2% by the first method to 31.9% by the second method (P ≤0.0056), and that of diastolic blood pressure nondipping decreased from 22.6% to 11.3% (P ≤0.00001). Inclusion of awake blood pressure measurements during the night obscured the normal dipping pattern in people who woke up to urinate. Thus, taking into account people’s actual behavior increases the accuracy of the results.

How should patients treated with α-blockers be followed? Insights from an ambulatory blood pressure monitoring database

Objective Adrenergic alpha-antagonists have been suggested to confer lesser protection, compared to diuretics, when used as first agents for hypertension. While differences in clinic blood pressure may be partly responsible, this inferiority is unexpected in light of the metabolic advantages of α-blockade. The aim of this study was to evaluate the relationship between use of α-blockers and blood pressure dipping. Methods A database of a 24-h ambulatory monitoring service was cross-sectionally evaluated for associations between antihypertensives and dipping. There were 681 treated subjects during a 3-year period (age 63 ± 14, 57% female). Results Overall, 78 of 681 treated hypertensive subjects used α-blockers (11%). Nine per cent of dippers and 16% of nondippers were treated with α-blockade, odds ratio 2.0. Whereas clinic, 24-h, and awake blood pressures were similar in α-blocker users and nonusers, sleep blood pressure was significantly higher in the former group. Furthermore, significantly fewer subjects given α-blockers had a controlled sleep blood pressure. Among α-blocker nonusers sleep blood pressure was the best controlled category, whereas in α-blocker users manual blood pressure had the highest rate of control. Generally, accounting for covariates of α-blockade (age, gender, diabetes, total number of medications) did not influence the above-mentioned trends. Finally, a limited negative dose–response relationship between α-blockade and dipping magnitude was also noticed. Conclusions We found a significant negative association between adrenergic α-blockade and the magnitude of sleep-related blood pressure decline. Awaiting results from interventional studies, this may suggest a need to perform ambulatory monitoring in patients given alpha-blocking agents (or at least supine and standing measurements), and may partially clarify the inferiority of doxazosin in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

Lack of association between body-mass index and white-coat hypertension among referred patients.

ObjectiveThe association between body-mass index and ambulatory blood pressure variables is not straightforward. Specifically, there are contradicting data regarding the correlation between obesity and white-coat hypertension. The aim of this report was to study the relationship between body-mass index and the white-coat effect, defined by ambulatory monitoring. MethodsA retrospective analysis of a prospectively collected ambulatory blood pressure monitoring laboratory database was performed. We analyzed 3928 unselected ambulatory monitoring sessions of nontreated (n=1654) and treated (n=2274) patients, for statistical associations between body-mass index and blood pressure variables. Body-mass index was categorized according to National Institutes of Health classification or quartiles. ResultsOffice and ambulatory blood pressure variables correlated with body-mass index in untreated patients. Unadjusted, the systolic white-coat effect did not differ by body-mass index category, whereas the diastolic effect was higher in obese patients. Adjustment for age, sex and office blood pressure revealed inverse associations of body-mass index category with the systolic white-coat effect, in both untreated and treated patients. When determined categorically, neither overweight/obese untreated or treated patients had increased prevalence of white-coat hypertension. Multivariate linear regression models confirmed the negative correlation between body-mass index and the systolic white-coat effect in untreated (&bgr;=−0.24, P<0.0001) and treated (&bgr;=−0.14, P<0.05) patients. ConclusionIn patients referred for ambulatory blood pressure monitoring there was no association between body-mass index and white-coat hypertension.