Impact of home and clinical blood pressure variability on arteriosclerosis and metabolic indicators: a prospective multicenter registry study

Out-of-office blood pressure measurement in children and adolescents

he conventional measurement of blood pressure(BP) in the office or clinic has been the cornerstonefor hypertension management for decades. How-ever, because of the white-coat and the masked hyper-tension phenomena, out-of-office BP monitoring withambulatory or home measurements is often required [1].ExtensiveresearchonambulatoryBPmonitoringhasestab-lished its role as the most accurate tool for hypertensiondiagnosis [1–3].Onthecontrary,despitetheincreasinguseof home BP monitoring by hypertensive patients in thedaily management of their high BP condition, research inthisfield,inparticularwhenconsideringoutcometrials,hasbeen delayed as compared to ambulatory BP monitoring[4,5].

Hypertension is a well recognized global public health issue and a major cause of cardiovascular events and death throughout the world [1–3]. It is responsible for about 13% of all deaths and 3.7% of total disability-adjusted life-years [1–3]. Globally, the overall prevalence of hypertension in adults was around 40% in 2008, and the number of adults with hypertension in 2025 has been projected to increase by about 60% to a total of 1.56 billion [1–5]. Hypertension is a chronic disease that requires periodic and correct measurements of blood pressure (BP) through three different but complementary alternatives: office BP, home BP, and 24-h ambulatory BP. Measurement of BP in the office is the cornerstone on which the knowledge of hypertension is based. Antihypertensive treatment targeted on office BP reduces the risk of cardiovascular disease, and the degree of benefit is associated with the magnitude of BP reduction [6–13]. However, office-based BP readings are limited in the amount of information they can provide as they represent a single snapshot in time [14–16]. Conversely, ambulatory BP monitoring (ABPM) provides a direct record of BP throughout the whole day in patients engaged in their usual activities. Frequent readings recorded at predefined intervals during wakefulness and sleep enable clinicians to obtain a more precise estimation of a patient's BP, to asses BP levels in the outpatient setting, and to study BP variability and circadian BP profile [15]. Furthermore, the evidence that ABPM provides information over and beyond conventional BP measurement has been growing steadily over the past 25 years, and the rationale for its use in clinical practice is soundly based [14,16–19]. Of note, clinical studies focused on the prognostic value of on-treatment ambulatory BP showed that ambulatory BP predicts cardiovascular events even after adjustment for classic risk factors including office measurements of BP [20–22]. In the office versus ambulatory blood pressure study, Clement et al.[21] assessed the association between ambulatory BP in treated patients and subsequent cardiovascular events with a median follow-up of 5 years. After adjustment for several confounders, including BP measured at the physician's office, higher mean values for 24-h ambulatory SBP and DBP were independent risk factors for new cardiovascular events. The adjusted relative risk (RR) of cardiovascular events associated with a 1-SD increment in BP was 1.34 [95% confidence interval (CI): 1.11–1.62] for 24-h ambulatory SBP, 1.30 (95% CI: 1.08–1.58) for ambulatory SBP during the daytime, and 1.27 (95% CI: 1.07–1.57) for ambulatory SBP during the night-time. For ambulatory DBP, the corresponding RRs of cardiovascular events associated with a 1-SD increment were 1.21 (95% CI: 1.01–1.46), 1.24 (95% CI: 1.03–1.49), and 1.18 (95% CI: 0.98–1.40). Similarly, in a prospective analysis of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale study [20], only 27% of treated hypertensive patients achieved office BP control (defined as BP < 140/90 mmHg), and 37% of patients achieved ambulatory BP control (defined as daytime BP < 135/85 mmHg). Ambulatory BP control significantly predicted a lesser risk for subsequent cardiovascular disease, whereas office BP control did not [20]. To date, ABPM appears to be an indispensable diagnostic tool in patients with established or suspected hypertension to refine cardiovascular risk stratification and guide therapeutic strategies. However, the use of ABPM for hypertension management may be more expensive than that of office or home BP. This aspect has been addressed by a recent comparative study estimating the resources consumed and subsequent costs for hypertension management, using home BP monitoring alone versus combined clinic measurements and ABPM (C/ABPM). Briefly, untreated hypertensive patients were randomized to use home BP or C/ABPM for antihypertensive treatment initiation and titration. The total cost of the first year of hypertension management was lower in home BP monitoring than C/ABPM arm (€1336.0 versus €1473.5 per patient, respectively), and there was no difference in achieved BP control and drug expenditure. The cost for subsequent years was €348.9 and €440.2 per patient, respectively, for home BP monitoring and C/ABPM arm and €2731.4 versus €3234.3 per patient, respectively (P < 0.001) for a 5-year projection. In view of the cost and limited availability of ABPM, increasing attention is being given to home monitoring with inexpensive semiautomated devices. In particular, this technique has attracted considerable attention in recent years because of the potential for better classification of hypertensive status and hypertension management compared with office BP [23,24]. A relationship between home BP values and the risk of cardiovascular disease has been documented in several observational studies [23,24]. These studies also have shown that the relationship with cardiovascular risk is steeper for home than for clinic BP [23,24]. On the contrary, there is no evidence from intervention studies that home BP is superior to office BP in guiding the treatment of hypertension. Hence, it remains uncertain whether tailoring treatment on the basis of home BP provides a better cardiovascular protection than traditional treatment based on office BP. To further investigate the hypothesis that on-treatment home BP monitoring provides information of prognostic significance, Shimada et al.[25] performed an additional analysis of the Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure (HONEST) study. The report published in the current issue of the Journal [25] includes data from more than 20 000 hypertensive patients followed for about 2 years. Specifically, Shimada et al.[25] investigated the prognostic significance of office SBP and morning home SBP measured at several time points. Three types of BP measurements were evaluated: baseline BP, BP during follow-up (defined as the mean of all available BP measurements), and the achieved BP (defined as the BP measurement at the last time point during the follow-up period or the preceding day of the first cardiovascular event). Briefly, Shimada et al.[25] demonstrated that SBP during follow-up (as compared with SBP at baseline) and morning home SBP (as compared with clinic SBP) had a better prognostic significance in predicting cardiovascular events. When morning home and clinic SBP during follow-up were included in the same survival model, only morning home SBP during follow-up was identified as a significant predictive factor (hazard ratio per 1 mmHg increase: 1.033, 95% CI: 1.020–10.46, P < 0.0001) [25]. Despite the interesting results on the relation between home BP and outcomes in treated hypertensive patients, some methodological aspects of the analysis by Shimada et al.[25] need to be addressed for a proper interpretation of results. First, the percentage of patients who measured home BP according to current guidelines [26] ranged from 82.1% at baseline to 93.9% after 24 months, and the proportion of missing data on clinic BP measured at predefined time points is not reported. As pointed out by Agarwal [27] in a previous commentary on the HONEST study, if the missing data on clinic BP or home BP are not at random, they might selectively affect the association of home or clinic BP with outcomes. Second, when BP is taken at home to establish the diagnosis of hypertension or to assess BP control, the optimal schedule of BP measurements is still undefined. Increasing evidence suggests that at least 12–14 measurements should be obtained, with both morning and evening measurements taken over a period of 1 week. Yet in the HONEST study [25], home BP was only measured in two different days for each measurement point. Another aspect of the analysis by Shimada et al.[25] needs to be mentioned. To investigate the prognostic significance of clinic and home SBP, Shimada et al. developed several risk prediction models to estimate standardized hazard ratios (1 mmHg increase) and the 2-year absolute risk of cardiovascular events for each level of BP variable. To evaluate the model's discrimination ability and the clinical usefulness of added predictors, they also computed the concordance index and the net reclassification improvement (NRI), respectively. They computed NRI values when morning home SBP was added into the model including office SBP, and when clinic SBP was added into the model including morning home SBP. Interpretation of the results led the authors to conclude that follow-up morning home SBP had better reclassification ability [25]. The choice of a risk-category-based NRI seems reasonable in this context because it can demonstrate how many patients would be reallocated into different clinical risk categories by the addition of a specific BP variable. Unfortunately, Shimada et al.[25] did not report the components of the overall NRI to show the net percentages of patients with or without events correctly reclassified [28–30], and they reported overall NRI values well below 0.2, which should be considered weak and scarcely informative on a clinical standpoint. In conclusion, the use of on-treatment home BP, as recorded in the HONEST study [25], is difficult to translate into clinical decisions applied to drug treatment. However, the stage is set for a large, multinational, and intervention study formally testing the superiority of home versus office BP as a target for clinical decisions. According to current evidence, home BP monitoring provides complementary information to office and 24-h ambulatory BP [15]. It should be considered as a complementary, rather than a competitive, method to evaluate out-of-office BP [31,32]. ABPM remains mandatory to obtain information on components of the ambulatory BP profile which proved prognostic significance, including nocturnal BP dipping, ambulatory pulse pressure, night-time BP, and BP variability [16,33–38]. ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.

In 2008, the European Society of Hypertension (ESH) [1] and the American Heart Association/American Society of Hypertension [2] published guidelines for home blood pressure (HBP) monitoring and both recommended this method to be widely applied in clinical practice in both the initial diagnostic phase in patients with elevated blood pressure (BP) and also in the long-term follow-up of treated hypertension. These recommendations are based on the evidence about the prognostic value of HBP, its diagnostic ability, its cost-effectiveness, and its good acceptance by hypertensive patients [1,2]. Several studies have assessed the diagnostic value of HBP monitoring by taking ambulatory blood pressure (ABP) monitoring as reference method [1–4]. These studies, however, were quite heterogeneous with regard to their methodology and/or their objectives. First, 11 studies included untreated patients (n = 1866), whereas seven studies included treated hypertensive patients (n = 1059) [3,4]. Moreover, these previous studies included individuals on triple therapy, diabetic patients, patients with renal failure, on hemodialysis, or children and adolescents [3,4]. Second, the diagnostic endpoint was either white-coat hypertension, masked hypertension, sustained hypertension, white-coat effect, masked uncontrolled hypertension, resistant hypertension, or a mixture of these. Third, some studies have taken daytime ABP as reference whereas others focused on 24-h ABP as their reference, and different HBP schedules have been used [3,4]. The results of all these studies, although largely varying according to the diagnostic endpoint, tend to agree in indicating a higher specificity and higher negative predictive value with lower sensitivity and lower positive predictive value for the HBP monitoring method as compared with ABP monitoring. In this issue of the Journal of Hypertension, Kang et al.[5] provide further evidence in this regard, by reporting on the results of a cross-sectional study including data from 1774 patients in China, aimed at comparing the diagnostic accuracy of HBP with that of 24-h ABP monitoring. The results of this study are largely in line with the findings of the above-mentioned previous articles. Moreover, in these previous studies [3,4], there was moderate-to-substantial diagnostic agreement between the two methods (κ statistic 0.40–0.70) [6], a finding that is confirmed by the data by Kang et al.[5] who reported κ-statistic values 0.40–0.66 in untreated and 0.41–0.58 in treated patients when comparing the diagnostic agreement between HBP and ABP monitoring. Although rather confirmatory of previous papers, the study by Kang et al.[5] has several points of strength. First, analyses were performed on a large sample of individuals. Second, both treated and untreated individuals were included. Third, assessments of white-coat, masked and sustained hypertension were included in a single analysis. Fourth, 24 h rather than daytime ABP values were chosen to be taken as reference BP level, which means that night-time ABP was not ignored, in line with recent ESH ABP monitoring guidelines [7,8]. Indeed, the prevalence of masked hypertension was always significantly larger when this condition was assessed by 24-h ABP monitoring, regardless of the antihypertensive treatment status. Fifth, HBP monitoring was implemented according to the recommended schedule by ESH guidelines [1], with 7-day monitoring and duplicate morning and evening measurements. Sixth, assessment of HBP was based on readings exported by the device memory, which thus prevented misreporting; and seventh, implementation and conduction of this study was done in China where there are scarce data comparing HBP with ABP. Overall, the findings by Kang et al.[5] strengthen the importance of current recommendations indicating that presence of masked hypertension should be evaluated by taking into account a whole 24-h monitoring period and not only limiting the assessment to the awake period [7,8]. Somehow surprisingly, however, authors did not find an association between masked hypertension and advanced age, diabetes mellitus, and, more in general, major cardiovascular risk factors, a finding which is in contrast with other population studies [9–11]. Probably, this is related to the fact that cardiovascular risk level was only low to moderate in this study, and the mean age of the population was younger than in the previous articles. An additional explanation of such finding might be that Chinese hypertensive patients may behave differently from Caucasian individuals, and thus cross comparison of data collected in different ethnic groups worldwide could be useful to identify possible differences. The findings on the diagnostic agreement between HBP and ABP monitoring data in the study by Kang et al.[5] are supported by the results of a similar European study, which found a good agreement between HBP and ABP [12]. In fact, in this article, Nasothimiou et al.[12] also separately analyzed untreated and treated patients and focused on the assessment of white-coat, masked, and sustained hypertension, by investigating in a large dataset the diagnostic ability of HBP versus ABP [12]. Comparison of the two studies in Table 1 shows a striking similarity in the results with a high degree of diagnostic agreement between the two methods, ranging from 80 to 90% across all the hypertension phenotypes in both untreated and treated individuals.TABLE 1: Diagnostic agreement between home and ambulatory blood pressure monitoring in two studies that assessed all hypertension phenotypes separately in untreated and treated patientsThe occurrence of some degree of diagnostic disagreement between HBP and ABP is not an unexpected finding, and should be interpreted by taking into account a few important factors. First, the reproducibility of both HBP and ABP, although being clearly superior to that of office BP, is still imperfect, which means that some level of diagnostic disagreement would be expected even when the same BP monitoring method (HBP or ABP) is applied twice [13]. Thus, on such a background, the level of agreement between the two methods observed in the study by Kang et al.[5] as well as in the previous studies [3,4] might be regarded as excellent. Second, any diagnostic disagreement between HBP and ABP does not necessarily mean that ABP is the correct method and HBP is wrong. In fact, a level of disagreement should be expected because, although the two methods have important similarities (given that they both provide multiple measurements in the usual environment of each individual), they also have important differences. ABP is usually monitored only once, although over 24 h and in fully ambulatory conditions, at work, at home, and during sleep, whereas HBP is monitored over several days, weeks, or months, but always in the same environment and posture (seated after a few minutes of rest, at home). Third, because of the above-mentioned methodological differences, HBP and ABP monitoring appear to have a complementary rather than a competitive role in the evaluation of hypertension and provide similar but also different information about the BP profile and behavior. These data are supported by a study in 2051 patients assessed with HBP and ABP monitoring in Italy, which compared white-coat hypertensive patients who had normal HBP and ABP values with those who showed normal values only with one of these out-office BP monitoring methods, and showed that the latter group had higher risk of cardiovascular event and death [14]. An additional and important difference between data obtained in the study by Kang et al.[5] and data obtained in the previous studies is that in both untreated and treated patients of the study by Kang et al.[5], average diastolic HBP was at similar levels with average 24-h diastolic ABP, whereas systolic HBP was by 4–5 mmHg higher than 24-h systolic ABP. The study by Kang et al.[5] represents one of the first large studies assessing the respective diagnostic values of HBP versus ABP in the detection of white-coat and masked hypertension, in either untreated or treated hypertensive patients. This observational study, based on data collected in a large sample of Chinese hypertensive patients referring to hypertension clinics, yields several relevant new pieces of information on the features of white-coat and masked hypertension as assessed by these BP measuring methods. The low sensitivity and high specificity of home BP suggest that this technique may be useful to exclude a diagnosis of masked or white-coat hypertension but not to confirm its presence. This means that, in terms of hypertension management, ABP monitoring stands as the ideal tool to assess BP control, whereas HBP appears to be a complementary technique [1]. As a matter of fact, although ABP allows repeated measurements to be obtained both during awake activities and night sleep, this is not usually the case for HBP. On the contrary, at variance from 24-h ABP monitoring, self-BP measurements at home are collected over successive days, weeks, or months, which makes HBP monitoring a useful approach to BP assessment during long-term follow-up. With HBP monitoring, however, measurements are usually taken only during waking hours, without any possibility to have information also on night-time BP levels. Thus, on the background of the growing awareness on the importance of night-time BP, in the future, the power of HBP for detecting masked or white-coat hypertension should be tested by considering the inclusion of sleep readings. This possibility is currently provided by new devices for HBP monitoring that allow a number of night-time automated HBP measurements to be obtained. Use of these novel diagnostic tools may thus allow to more precisely check the predictive value of HBP vis-à-vis that of ABP, under more similar settings. In conclusion, the study by Kang et al.[5], together with the previous studies assessing the diagnostic ability of HBP monitoring, support the position of the ESH [1] that recommended the wide application of the method as a reliable alternative to ABP monitoring for the detection of the white-coat and masked hypertension phenomena and the confirmation of sustained hypertension both in the initial evaluation of untreated hypertension and also in the long-term follow-up, when assessing the occurrence of an effective BP control. ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.

Out-of-Office Blood Pressure Monitoring: A Comparison of Ambulatory Blood Pressure Monitoring and Home (Self) Monitoring Of Blood Pressure.

Can We Study Hypertension in Patients on Dialysis? Yes We Can

Home blood pressure (BP) variability (BPV) and BP phenotypes such as white-coat hypertension (WCH), white-coat uncontrolled hypertension (WUCH), masked hypertension (MH) and masked uncontrolled hypertension (MUCH) are predictors of adverse cardiovascular events. This study compared home BPV across BP phenotypes built from abnormal office BP (OBP) and home BP monitoring (HBPM) thresholds defined by three distinct societies [European Society of Hypertension (ESH): OBP ≥ 140/90 mmHg and HBPM ≥ 135/85 mmHg; American College of Cardiology/American Heart Association (ACC/AHA): OBP and HBPM ≥ 130/80 mmHg and Brazilian Society of Cardiology (BSC): OBP ≥ 140/90 mmHg and HBPM ≥ 130/80 mmHg]. This cross-sectional study evaluated 51 194 treated (37% men, age = 61 ± 15 years) and 56 100 untreated (41% men, age = 54 ± 16 years) individuals from 1045 Brazilian centers who underwent OBP and HBPM measurements. Systolic and diastolic home BPV were estimated as the: standard deviation, coefficient of variation, and the variability independent of the mean of HBPM. Results of adjusted analysis showed that home BPV parameters were significantly greater in individuals with WCH/WUCH according to the BSC criteria, in those with MH/MUCH defined by the ACC/AHA criteria, and tended to be greater in individuals with either MH/MUCH or WCH/WUCH defined by the ESH criteria.Furthermore, restricted cubic spline analysis showed a U-shaped association between BPV and the difference between OBP and HBPM in treated and untreated individuals. Home BPV was greater in WCH/WUCH and/or MH/MUCH depending on the criteria used to define abnormal OBP and HBPM thresholds. These findings underscore the need to standardize abnormal BP criteria in clinical practice.

Cardiovascular Risk Associated With White-Coat Hypertension: Con Side of the Argument.

Inconsistencies between the office and out-of-office blood pressure (BP) values (described as white-coat hypertension or masked hypertension) may be attributable in part to differences in the BP monitoring devices used. We studied consistency in the classification of BP control (well-controlled BP vs. uncontrolled BP) among office, home, and ambulatory BPs by using a validated "all-in-one" BP monitoring device. In the nationwide, general practitioner-based multicenter HI-JAMP study, 2,322 hypertensive patients treated with antihypertensive drugs underwent office BP measurements and 24-hour ambulatory BP monitoring (ABPM), consecutively followed by 5-day home BP monitoring (HBPM), for a total of seven BP measurement days. Using the thresholds of the JSH2019 and ESC2018 guidelines, the patients with consistent classification of well-controlled status in the office (<140 mmHg) and home systolic BP (SBP) (<135 mmHg) (n = 970) also tended to have well-controlled 24-hour SBP (<130 mmHg) (n = 808, 83.3%). The patients with the consistent classification of uncontrolled status in office and home SBP (n = 579) also tended to have uncontrolled 24-hour SBP (n = 444, 80.9%). Among the patients with inconsistent classifications of office and home BP control (n = 803), 46.1% had inconsistent ABPM-vs.-HBPM out-of-office BP control status. When the 2017 ACC/AHA thresholds were applied as an alternative, the results were essentially the same. The combined assessment of the office and home BP is useful in clinical practice. Especially for patients whose office BP classification and home BP classification conflict, the complementary clinical use of both HBPM and ABPM might be recommended.

To the Editor: We read with interest the paper by Sega et al regarding the prognostic value of ambulatory, home, and office blood pressure in the PAMELA population.1 However, we find that the main conclusions of the report may be driven by the lack of adjustment for confounders. The relationships between level of blood pressure and risk were not adjusted for age, which may have a major influence on risk over a long time span. There is indeed a relation between age and blood pressure,2 and therefore, these results may be biased. The comparisons of the various blood pressures were also not adjusted for potential confounders, with the argument that “no adjustment for age, sex, and other cardiovascular risk factors was made because comparisons between the predictive value of various blood pressure values involved the same sample.” However, it has been shown in a general Belgian population that the within-subject differences between office and ambulatory blood pressure measurements increased with older age and greater body mass index.3 In addition, in the Danish MONICA population, the within-subject differences between office and ambulatory blood pressure measurements increased with older age, diagnosis of hypertension, male gender, and presence of diabetes.4 So, to assess the true prognostic value of office blood pressure versus that of ambulatory blood pressure, it is mandatory to explore whether adjustments for other relevant cardiovascular risk factors would change the results. Recently, it was shown in the Danish MONICA population that ambulatory blood pressure was a much better predictor of all-cause mortality and cardiovascular mortality than office blood pressure, taking other relevant risk factors into account.5 Accordingly, to make the results from previous studies comparable to the PAMELA study, we would like to know the results of adjusted analyses. Until that time, the conclusion that …

Managing White‐Coat Effect

Objective: Inconsistencies between office and out-of-office blood pressure (BP) values (described as white-coat hypertension or masked hypertension) may be attributable in part to differences in the BP monitoring devices used. We studied the inconsistency of the classification of BP control (well-controlled BP vs. uncontrolled BP) among office, home, and ambulatory BPs by using a validated all-in-one BP monitoring device. Design and method: In the nationwide, general practitioner-based multicenter HI-JAMP study, 2,322 hypertensive patients treated with antihypertensive drugs underwent office BP measurements and 24-h ambulatory BP monitoring (ABPM), consecutively followed by 5-day home BP monitoring (HBPM), using the same all-in-one device over a total of seven BP measurement days. Results: Using the thresholds of the JSH2019 and ESC2018 guidelines, the subjects with consistently well-controlled office (&lt;140mmHg) and home systolic BP (SBP) (&lt;135mmHg) (n = 970) also tended to have well-controlled 24-h SBP (&lt;130mmHg) (n = 808, 83.3%). The subjects with consistently uncontrolled office and home SBP (n = 579) also tended to have uncontrolled 24-h SBP (n = 444, 80.9%). Among the subjects with inconsistent classifications of office and home BP control (n = 803), 46.1% had inconsistent ABPM-vs.-HBPM out-of-office BP control status. When the 2017 ACC/AHA thresholds or JSH2019 target BP thresholds were applied as an alternative, the results were essentially the same. Conclusions: The combined assessment of office and home BP is useful in clinical practice. Especially for patients whose office BP classification and home BP classification conflict, the complementary clinical use of both HBPM and ABPM might be recommended.

A series of articles1–4⇓⇓⇓ published recently in The Lancet and Lancet Neurology raise an interesting issue that has implications for both the clinical management of hypertension and future research in hypertension, particularly in the development and use of different classes of blood pressure (BP)–lowering drugs. These studies, which were led by Peter Rothwell at the John Radcliffe Hospital in Oxford, United Kingdom, suggest that, whereas there is undoubted and well-proven benefit in the current practice of reducing mean BP to prevent cardiovascular events, there may be additional benefit in also reducing BP variability (BPV), especially to prevent stroke. The studies suggest, moreover, that different classes of drugs are superior to others in reducing BPV (calcium channel blockers being best and the β-blocker atenolol being worst). However, these articles, by virtue of their sheer volume (≈50 pages of printed text and many pages of supplementary web appendix data), could overwhelm all but the most stoic readers, and misinterpretation of the data could lead to confusion and have an adverse effect on clinical practice. It is important, therefore, to assess the scientific reality and determine how attention to BPV might benefit patients with hypertension. In the first analysis, systolic BPV between visits and maximum BP reached in 4 cohorts of patients with previous transient ischemic attacks were strong predictors for subsequent stroke.1 In treated hypertensive patients in the Anglo-Scandinavian Cardiac Outcome Trial-Blood Pressure Lowering Arm systolic BPV between visits was also a strong predictor of stroke and coronary events independent of mean clinic or ambulatory BP measurement (ABPM). BPV on ABPM was a weaker predictor overall but was related to visit-to-visit variability. Traditional measures of variability, such as SD and coefficient of variation (CV), were used in these analyses, but one of the problems encountered in the …

Introduction For practical reasons, blood pressure values measured by physicians or nurses in a medical environment remain the clinical basis of the diagnosis and management of arterial hypertension around the world as recommended by all guidelines [1–4]. Nevertheless, measurements of blood pressure outside the office have gained an increasing popularity over the last decades not only to ascertain the diagnosis of hypertension but also to follow the impact of therapeutic interventions. Out-of-office blood pressure measurements can be obtained either by 24-h ambulatory blood pressure monitoring or by home blood pressure monitoring. As reviewed recently [5], both sets of out-of-office blood pressure offer undeniable advantages when compared to office blood pressure. First, both ambulatory blood pressure and home blood pressure monitoring provide more reliable and reproducible information on blood pressure. Second, blood pressure values obtained by ambulatory blood pressure and home blood pressure monitoring appear to be more closely related to target organ damage than office blood pressure and hence have a greater prognostic relevance than office blood pressure. Third, certain diagnosis such as white coat hypertension and masked hypertension can only be diagnosed using out-of-office blood pressure measurements. Fourth, when used in the clinical follow-up of treated hypertensive patients to evaluate the impact of drug treatment, ambulatory blood pressure monitoring as well as home blood pressure monitoring has the advantage of not being affected by a placebo effect. Finally, evidence has been provided that treatment-induced reduction in 24-h blood pressure may predict better than office blood pressure the regression of end organ damage (particularly the cardiac one) induced by antihypertensive drug. Many of these information have been achieved during the past two decades by a number of studies carried out in different populations around the world, including the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study [6–10]. When should out-office blood pressure be measured? Despite their advantages, ambulatory blood pressure monitoring as well as home blood pressure monitoring is not regarded as a routine procedure that should be applied to all hypertensive patients essentially for economical reasons. However, this issue is debated because the clinical information gathered with these measurements may potentially result in financial savings when applied adequately. The European and American guidelines for the management of hypertension have defined some indications for the use of ambulatory blood pressure monitoring in hypertension [1,2]. These include patients with resistant hypertension, patients with a high variability of office blood pressure, low-risk patients with a high blood pressure, patients with suspected episodes of hypotension, patients with a large discrepancy between office and home blood pressures, and finally patients with special clinical conditions such as pregnancy or sleep apnea syndrome. Outside these indications, the use of ambulatory blood pressure monitoring could be discussed both in terms of feasibility and economics. Theoretically, a measurement of out-of-office blood pressure could be recommended to all new patients with as suspected hypertension to confirm the diagnosis of hypertension and to refine the patient's cardiovascular risk profile. Therefore, ambulatory blood pressure monitoring could be recommended to all high cardiovascular risk patients before starting any treatment and later under therapy to ascertain the adequacy of the control of blood pressure. Ambulatory blood pressure values in diabetic patients In this issue of the Journal of Hypertension, Leitao et al.[11] report the results of a cross-sectional study performed to estimate the daytime ambulatory blood pressure monitoring values corresponding to the target office blood pressure of 130/80 mmHg for diabetic (as defined by the American Diabetes Association) and to assess which diabetic patients may actually benefit from ambulatory blood pressure monitoring. They included 554 patients in this analysis. Regression analyses were performed to analyze the ambulatory blood pressure monitoring values corresponding to office blood pressure and receiver operating characteristics (ROC) curves were used to assess the sensitivity and specificity of office blood pressure in diagnosing daytime ambulatory blood pressure monitoring hypertension. According to their regression equations, the daytime ambulatory blood pressure monitoring corresponding to the target office blood pressure of 130/80 mmHg was 129/79 mmHg and the daytime ambulatory blood pressure monitoring value corresponding to 140/90 mmHg at the office was 134/82 mmHg. As expected, discrepancies between ambulatory blood pressure monitoring and office blood pressure were due essentially to masked hypertension (about 10% of cases) and white coat hypertension (between 19% for systolic blood pressure and 26% for diastolic blood pressure). Interestingly, when office blood pressure was lower than 120 mmHg systolic and 70 mmHg diastolic, the sensitivity to rule out hypertension using ambulatory blood pressure monitoring was 90%. Similarly, when office blood pressure was more than 145 mmHg systolic and more than 90 mmHg diastolic the sensitivity to confirm hypertension using ambulatory blood pressure monitoring was 90%. Within these two sets of limits, 38% of patients would be misclassified if only office blood pressure values would be considered for the diagnosis. Thus, using the cut-off values of less than 120/70 mmHg and more than 140/90 mmHg at the office, 56% of the population sample would need an ambulatory blood pressure monitoring to confirm the diagnosis of hypertension. According to these results, only diabetics with an office blood pressure between 120 and 140 mmHg systolic and/or a diastolic blood pressure between 70 and 90 mmHg would really benefit from an out-office assessment of blood pressure. This would limit the use of ambulatory blood pressure monitoring to only 50% of the diabetic patients. Studies implications and limitations The results of this provide interesting practical information on the use of ambulatory blood pressure monitoring in diabetic patients. However, they also have some limitations. The first one is the fact that the entire analysis is based on daytime ambulatory blood pressure only. Although the authors have measured 24-h blood pressure, they have not considered the nighttime blood pressure. This is unfortunate because there is increasing evidence that nighttime is a better predictor of cardiovascular risk than daytime blood pressure. Moreover, diabetic patients are often characterized by an absence of the physiological fall in blood pressure reflecting a nondipping pattern at night. Diabetes may even be the cause of a reverse dipping, that is an increase in blood pressure at night. Both the nondipping and the reverse dipping pattern of blood pressure have been associated with an increased risk of developing target organ damages such as left ventricular hypertrophy, microalbuminuria, renal dysfunction, and cerebral vascular lesions [5,12]. Thus, when assessing the cardiovascular risk profile linked to hypertension in diabetic patients, nighttime blood pressure should be included. Indeed, it is not uncommon in diabetes that daytime normotensive patients exhibit a nocturnal hypertension. This type of patients would be misdiagnosed using the algorithm proposed by the authors. Recently, the results of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial have shown that in diabetic patients the reduction of cardiovascular morbidity and mortality obtained by lowering office blood pressure below 120 mmHg systolic is not greater than that seen reducing blood pressure below 130 mmHg [13]. On the contrary, a systolic blood pressure below 120 mmHg may result in an increased risk of developing cardiac complications, as suggested by the recent post hoc analysis of diabetic patients with coronary heart diseases having participated in the INternational VErapamil SR-Trandolapril (INVEST) Study [14]. If a low blood pressure increases the risk of cardiac complications in diabetics, one might have to reconsider the necessity to perform an ambulatory blood pressure monitoring in diabetic patients with a blood pressure <120/70 mmHg in contrast to the proposals of Leitao et al. Indeed, in treated diabetic patients with a low office blood pressure, ambulatory blood pressure monitoring could be of importance to diagnosis episodes of asymptomatic hypotension episodes which might increase their cardiac risk. Thus, in the analysis of daytime and nighttime blood pressure values, it would be of interest to assess whether the percentage of ambulatory blood pressure values below a certain level is indeed associated with an increased risk of some cardiovascular complications. In this respect, it is important to mention that the analysis presented by Leitao et al. does not provide any information on the presence in this particular patients population of cardiac organ damage. The study also does not provide any data such on the occurrence of cardiovascular events and deaths, as it was not a prospective cohort study. Both these two sets of information should be thus provided by future clinical trials.

This study investigated the associations between various indicators of home blood pressure (BP) variability and albuminuria as well as the reproducibility of these indicators in perimenopausal women, who are likely to exhibit increased BP variability. As a measure of organ damage, urinary albumin/creatinine ratio (UACR) was examined at baseline in 151 women aged 40-59 years. Home BP was measured in duplicate in both morning and evening for 12 weeks using a home BP monitor. The following home BP variability indicators were calculated biweekly: mean, maximum, minimum, difference between maximum and minimum, average real variability (ARV), SD, and coefficient of variation. In simple correlation, the ARV of systolic BP (SBP) (morning + evening and morning), maximum SBP (evening), and maximum diastolic BP (all time points) were most strongly correlated with UACR. In multivariate linear regression, the maximum, minimum, and ARV of SBP (morning) and both mean and maximum SBP (evening) were significantly associated with Box-Cox transformed UACR after adjustment for age, body mass index, and lifestyle. In particular, maximum SBP had the lowest P value among those BP indicators. Furthermore, maximum morning SBP tended to distinguish high-normal albuminuria (UACR ≥ 10 mg/g Cr) more clearly than mean morning SBP. The mean, maximum, and minimum values of home BP demonstrated the greatest reproducibility among all indicators. Maximum home BP is associated with UACR and exhibits high reproducibility in perimenopausal women. These findings raise the hypothesis that maximum home SBP may be suitable to detect kidney damage.