Angeliki Ntineri

Out-of-office blood pressure and target organ damage in children and adolescents: a systematic review and meta-analysis.

Objective: In children, out-of-office blood pressure (BP) assessment (especially ambulatory monitoring) is regarded as indispensable for accurate hypertension diagnosis. This article reviewed the evidence on the association between out-of-office BP measurements and preclinical organ damage indices in children. Methods: A systematic review and meta-analysis of 93 relevant articles (1974–2012) was performed. Results: Analysis of 10 studies (n = 480, pooled age 14.4 years, with hypertension 33%, renal disease 27%, type 1 diabetes 10%) revealed a significant association between systolic ambulatory BP and left ventricular mass index (LVMI), with pooled correlation coefficient r = 0.40 [95% confidence interval (CI) 0.30–0.50]. Eleven studies reported data on LVMI differences between normotensive (n = 428) and hypertensive children (n = 432), with higher values in the latter group by 6.53 g/m2.7 (95% CI 4.73–8.33). A moderate association was found between systolic ambulatory BP and carotid intima–media thickness (three studies, n = 231, age 13.3 years, pooled r = 0.32, 95% CI 0.21–0.44), as well as between diastolic ambulatory BP and urine albumin excretion (five studies, n = 355, age 13.1 years, type 1 diabetes 42%, reflux nephropathy 28%, pooled r = 0.32, 95% CI 0.05–0.58). Two studies reported on the association between home BP and LVMI, with one of them showing comparable coefficients as for ambulatory monitoring. Conclusion: The available evidence suggests a moderate but significant association between ambulatory BP and preclinical organ damage, mainly based on studies in nephropathy and/or diabetes. More data are needed in essential hypertension without nephropathy or diabetes, as well as with home measurements.

Home Blood Pressure Monitoring: Primary Role in Hypertension Management

In the last two decades, considerable evidence on home blood pressure monitoring has accumulated and current guidelines recommend its wide application in clinical practice. First, several outcome studies have shown that the ability of home blood pressure measurements in predicting preclinical target organ damage and cardiovascular events is superior to that of the conventional office blood pressure measurements and similar to that of 24-hour ambulatory monitoring. Second, cross-sectional studies showed considerable agreement of home blood pressure measurements with ambulatory monitoring in detecting the white-coat and masked hypertension phenomena, in both untreated and treated subjects. Third, studies have shown larger blood pressure decline by using home blood pressure monitoring instead of office measurements for treatment adjustment. Fourth, in treated hypertensives, home blood pressure monitoring has been shown to improve long-term adherence to antihypertensive drug treatment and thus, has improved hypertension control rates. These data suggest that home blood pressure should no longer be regarded as only a screening tool that requires confirmation by ambulatory monitoring. Provided that an unbiased assessment is obtained according to current recommendations, home blood pressure monitoring should have primary role in diagnosis, treatment adjustment, and long-term follow-up of most cases with hypertension.

Association of night-time home blood pressure with night-time ambulatory blood pressure and target-organ damage: a systematic review and meta-analysis.

Objective: Night-time ambulatory blood pressure (nABP) is the most important aspect of the blood pressure profile in terms of prognosis. Novel low-cost home monitors allow automated night-time blood pressure monitoring (nHBP). This study reviewed the evidence on the association of nHBP with nABP and preclinical organ damage. Methods: Systematic review and meta-analysis. Results: Analysis of six studies (n = 1404) showed pooled difference between nHBP and nABP (SBP/DBP) at 1.4, 95% confidence interval (CI) 0.3, 2.6/−0.2, 95% CI −0.9, 0.6 mmHg, whereas the pooled correlation coefficient between nHBP and nABP (SBP/DBP) was r = 0.70, 95% CI 0.59, 0.81/r = 0.72, 95% CI 0.67, 0.77, respectively. Two studies (n = 212) investigated the agreement between nHBP and nABP in detecting nondippers with weighted agreement 77.3% (pooled kappa 0.27, 95% CI 0.08, 0.45). Three studies (n = 954) reported on the association of left ventricular mass index with systolic nHBP and nABP (pooled correlation coefficient r = 0.36, 95% CI 0.23, 0.50 and r = 0.32, 95% CI 0.10, 0.54, respectively, P = NS for comparison). Two studies (n = 950) reported on the association of urinary albumin excretion with systolic nHBP and nABP (pooled r = 0.39, 95% CI 0.21, 0.58 and r = 0.30, 95% CI 0.06, 0.55, respectively, P < 0.01 for comparison). Two studies (n = 350) reported on the association of common carotid intima–media thickness with systolic nHBP and nABP (pooled r = 0.31, 95% CI 0.16, 0.46 and r = 0.35, 95% CI 0.17, 0.53, respectively, P = NS for comparison). Conclusion: The available evidence suggests that nHBP and nABP present similar values and comparable relationship with target-organ damage. Studies on the prognostic value of nHBP are needed.

Is white-coat hypertension a harbinger of increased risk?

White-coat hypertension is defined by elevated office and normal out-of-office blood pressure (home or ambulatory) in untreated subjects. This condition is common in clinical practice and requires appropriate work-up for detection and management. Many studies have examined the relationship between white-coat hypertension and cardiovascular risk but with marked heterogeneity in the definitions and methodology applied. Thus, the results have been inconsistent leading to confusion in scientific research and clinical practice. Some but not all the relevant studies suggested that white-coat hypertension is associated with subclinical target-organ damage, yet the cross-sectional design of these studies and the fact that these indices are only surrogate end points do not allow firm conclusions to be drawn. In recent years, longitudinal studies have examined the prognostic significance of white-coat hypertension in terms of cardiovascular morbidity and mortality. Most of them indicate that white-coat hypertensive compared with normotensive subjects present a moderate—in most cases not significant—increase in risk. Meta-analyses of raw data from large databases, such as the International Database on Ambulatory blood pressure and Cardiovascular Outcomes (IDACO) and the International Database on HOme blood pressure in relation to Cardiovascular Outcomes (IDHOCO) allowed separate powered analyses in untreated subjects and provided a clearer picture regarding the modest risk associated with white-coat hypertension, especially in the long term. White-coat hypertension is regarded as an intermediate phenotype between normotension and hypertension associated with increased risk of developing sustained hypertension, and therefore requires regular follow-up using nonpharmacological measures.

The optimal schedule for self-home blood pressure monitoring.

I n 2008, the European Society of Hypertension (ESH) [1] and the American Heart Association [2] published guidelines for self-monitoring of blood pressure by patients at home (HBPM), providing almost identical recommendations with only minor differences. Both guidelines recommended HBPM for long-term monitoring of treated hypertension and also for the initial diagnostic phase of subjects with elevated blood pressure (BP) [1,2]. Moreover, a common recommendation was given for the optimal HBPM schedule, which should be based on a 7-day monitoring with duplicate morning and evening measurements, and the average should be calculated after discarding readings of the first day [1,2]. The amount of research work, discussions and debate on the optimal HBPM schedule is a typical example of ‘knowing more and more for less and less’, as Tom Pickering stated in the foreword of his book on ‘Ambulatory Monitoring and Blood Pressure Variability’ [3]. Several studies investigated the performance of HBPM in the diagnosis of hypertension phenotypes (sustained, white-coat, masked hypertension) in untreated and treated subjects, by taking ambulatory BP monitoring (ABPM) as reference method and implementing different HBPM schedules (Table 1) [4–18]. Given that hypertension remains the leading risk factor for death and disability globally [19] and HBPM is recommended for almost all subjects with elevated BP [1,2], the optimal HBPM schedule indeed is highly relevant for cardiovascular disease prevention. In this issue of the journal, Nunan et al. [18] present the results of a carefully conducted study in 203 untreated subjects investigating the optimal HBPM schedule by taking ABPM as reference. The main conclusion of the authors is that 5-day HBPM provides the optimal schedule, and there is no additional benefit by performing more measurements or by excluding the first day. Strengths of this study are: (i) it

Changing Relationship Among Office, Ambulatory, and Home Blood Pressure With Increasing Age: A Neglected Issue

See related article, pp 1073–1079 In this issue, Conen et al1 reported data showing changing relationship between office blood pressure (OBP) and awake ambulatory BP (aABP) with increasing age. This observation is not new,2–5 but it is largely neglected and ignored and has major clinical implications. BP is known to increase with aging, leading to increasing hypertension prevalence. This applies to BP measurements in and out of the office (Figure).1–3 The problems start here because, as Conen et al confirmed, the range of BP rise with age is much higher (about double) for OBP than aABP.1–3 As a result, a practical problem emerges because the relationship between OBP and aABP is not the same across all the age groups. Figure. Relationship between age and blood pressure assessed by different methods. Dotted horizontal line indicates hypertension threshold based on awake ambulatory blood pressure. Constructed from data reported by Conen et al,1 Ishikawa et al,2 and Stergiou et al.3 There is convincing evidence that in children and adolescents the relationship among OBP, aABP, and home BP (HBP) is not the same as in the adults. A comparison of normalcy tables currently recommended for defining hypertension in children and adolescents showed that the corresponding percentiles are consistently lower for HBP than for aABP.5 Moreover, there is a trend for OBP to be lower than HBP and aABP in younger children, yet this difference is progressively eliminated with increasing age. The findings in regard to aABP …

Assessment of drug effects on blood pressure variability: which method and which index?

B lood pressure (BP) is known to be a continuous variable with dynamic characteristics of variability in response to daily physical and mental stimuli. The idea that the variation of BP puts additional burden on the heart and vasculature beyond that of average BP has been regarded for decades as a reasonable concept by researchers, practitioners and even patients. However, in contrast to the straightforward approach required for the evaluation of average BP, the quantification of the BP variability (BPV) turned out to be a tricky task. Interestingly, several different lines of evidence suggest that the BPV has independent prognostic value beyond that of average BP. However, to date the plethora of methodological approaches applied in different studies and the lack of evidence on critical relevant research issues did not allow BPV to be used in practice as a tool for improving the management of hypertensive patients. For the quantification of BPV, several measurement methods and sampling of BP readings have been used, and several mathematical approaches have been applied (Tables 1–2) [1–10].

Relationship between office and home blood pressure with increasing age: The International Database of HOme blood pressure in relation to Cardiovascular Outcome (IDHOCO)

Home blood pressure (HBP) measurements are known to be lower than conventional office blood pressure (OBP) measurements. However, this difference might not be consistent across the entire age range and has not been adequately investigated. We assessed the relationship between OBP and HBP with increasing age using the International Database of HOme blood pressure in relation to Cardiovascular Outcome (IDHOCO). OBP, HBP and their difference were assessed across different decades of age. A total of 5689 untreated subjects aged 18–97 years, who had at least two OBP and HBP measurements, were included. Systolic OBP and HBP increased across older age categories (from 112 to 142 mm Hg and from 109 to 136 mm Hg, respectively), with OBP being higher than HBP by ∼7 mm Hg in subjects aged >30 years and lesser in younger subjects (P=0.001). Both diastolic OBP and HBP increased until the age of ∼50 years (from 71 to 79 mm Hg and from 66 to 76 mm Hg, respectively), with OBP being consistently higher than HBP and a trend toward a decreased OBP–HBP difference with aging (P<0.001). Determinants of a larger OBP–HBP difference were younger age, sustained hypertension, nonsmoking and negative cardiovascular disease history. These data suggest that in the general adult population, HBP is consistently lower than OBP across all the decades, but their difference might vary between age groups. Further research is needed to confirm these findings in younger and older subjects and in hypertensive individuals.

3B.02: 24-HOUR AMBULATORY CENTRAL BLOOD PRESSURE VARIABILITY AND TARGET-ORGAN DAMAGE IN ADOLESCENTS AND YOUNG ADULTS.

Objective: Some studies suggested that ambulatory blood pressure (ABP) variability may provide useful information beyond that of average ABP levels. This study investigated the relationship between central ABP variability and target-organ damage in young individuals in whom the central-peripheral blood pressure discrepancy might be considerable. Design and method: Apparently healthy adolescents and young adults referred for elevated blood pressure and healthy volunteers (age 12–26 years) were subjected to: (i) 24-hour monitoring of central ABP using a noninvasive brachial cuff-based oscillometric device (Mobil-O-Graph 24 h PWA); (ii) 24-hour pulse wave velocity (PWV) monitoring (Mobil-O-Graph 24 h PWA); (iii) echocardiographic determination of left ventricular mass index (LVMI); (iv) measurement (ultrasonography) of the common carotid intima-media thickness (IMT). The standard deviation (SD) of ABP (24-hour weighted/awake/asleep), as well as the respective coefficients of variation (CV) were used for assessing variability. Results: The study included 68 individuals (mean age 18.7 ± 4.7 years, 52 males, body mass index [BMI] 24.5 ± 4.7 kg/m2, 24 volunteers, 15 with hypertension [24-hour peripheral ABP >=95th percentile for adolescents or >=130/80 mmHg for adults]). LVMI was correlated with 24-hour/awake/asleep central systolic ABP (r=0.50/0.49/0.40, all p < 0.01), as well as with 24-hour weighted/awake/asleep SD of central systolic ABP (r = 0.40/0.37/0.30, all p < 0.05), whereas no association was observed for the respective CV. IMT was correlated with 24-hour/awake/asleep central pulse pressure (PP) (r = 0.37/0.33/0.27, all p < 0.05), 24-hour weighted/awake/asleep SD of central PP (r = 0.43/0.40/0.36, all p < 0.01) and the respective CV (r = 0.28/0.26/0.25, all p < 0.05). Regarding 24-hour PWV, there was a significant association with 24-hour/awake/asleep central systolic ABP (r = 0.94/0.88/0.84, all p < 0.001) and 24-hour weighted/awake/asleep SD of central PP (r = 0.48/0.51/0.25, all p < 0.05), but not with the respective CV. In multivariate regression analyses (independent variables: age, gender, BMI, central ABP and SD/CV of ABP values), LVMI and 24-hour PWV were determined by BMI, age, and 24-hour central systolic ABP, and IMT by male gender and 24-hour weighted SD of central PP. Conclusions: In young individuals, 24-hour central ABP variability appears to be associated only with early carotid damage when accounting for ABP levels, whereas LVMI and PWV are mainly determined by average ABP levels.

Atrial Fibrillation Detection During 24-Hour Ambulatory Blood Pressure MonitoringNovelty and Significance: Comparison With 24-Hour Electrocardiography

This study assessed the diagnostic accuracy of a novel 24-hour ambulatory blood pressure (ABP) monitor (Microlife WatchBP O3 Afib) with implemented algorithm for automated atrial fibrillation (AF) detection during each ABP measurement. One hundred subjects (mean age 70.6±8.2 [SD] years; men 53%; hypertensives 85%; 17 with permanent AF; 4 paroxysmal AF; and 79 non-AF) had simultaneous 24-hour ABP monitoring and 24-hour Holter monitoring. Among a total of 6410 valid ABP readings, 1091 (17%) were taken in ECG AF rhythm. In reading-to-reading ABP analysis, the sensitivity, specificity, and accuracy of ABP monitoring in detecting AF were 93%, 87%, and 88%, respectively. In non-AF subjects, 12.8% of the 24-hour ABP readings indicated false-positive AF, of whom 27% were taken during supraventricular premature beats. There was a strong association between the proportion of false-positive AF readings and that of supraventricular premature beats (r=0.67; P<0.001). Receiver operating characteristic curve revealed that in paroxysmal AF and non-AF subjects, AF-positive readings at 26% during 24-hour ABP monitoring had 100%/85% sensitivity/specificity (area under the curve 0.91; P<0.01) for detecting paroxysmal AF. These findings suggest that in elderly hypertensives, a novel 24-hour ABP monitor with AF detector has high sensitivity and moderate specificity for AF screening during routine ABP monitoring. Thus, in elderly hypertensives, a 24-hour ABP recording with at least 26% of the readings suggesting AF indicates a high probability for AF diagnosis and should be regarded as an indication for performing 24-hour Holter monitoring.