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Objectives: In hemodialysis patients, central hemodynamics, stiffness, and wave reflections assessed through ambulatory blood pressure monitoring (ABPM) showed superior prognostic value for cardiovascular (CV) events than peripheral blood pressures (BPs). No such evidence is available for lower-risk hypertensive patients., Methods: In 591 hypertensive patients (mean age 58 ± 14 years, 49% males), ambulatory brachial and central BP, pulse wave velocity (PWV), and augmentation index (AIx) were obtained with a validated upper arm cuff-based pulse wave analysis technology. Information on treatment for hypertension (73% of patients), dyslipidemia (27%), diabetes (8%), CV disease history (25%), was collected. Patients were censored for CV events or all-cause death over 4.2 years., Results: One hundred and four events (24 fatal) were recorded. Advanced age [hazard ratio and 95% confidence interval: 1.03 (1.01, 1.05), P  = 0.0001], female sex [1.57 (1.05, 2.33), P  = 0.027], CV disease [2.22 (1.50, 3.29), P  = 0.0001], increased 24-h central pulse pressure (PP) [1.56 (1.05, 2.31), P  = 0.027], PWV [1.59 (1.07, 2.36), P  = 0.022], or AIx [1.59 (1.08, 2.36), P  = 0.020] were significantly associated with a worse prognosis (univariate Cox regression analysis). The prognostic power of peripheral and central BPs was lower. However, PWV [1.02 (0.64, 1.63), P  = 0.924], AIx [1.06 (0.66, 1.69), P  = 0.823], and central PP [1.18 (0.76, 1.82), P  = 0.471], were not significant predictors in multivariate analyses., Conclusions: In hypertensive patients, ambulatory central PP, PWV, and AIx are associated with an increased risk of CV morbidity and all-cause mortality. However, this association is not independent of other patient characteristics., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To develop scientific consensus recommendations for the optimal design and functions of different types of blood pressure (BP) measuring devices used in clinical practice for the detection, management, and long-term follow-up of hypertension., Methods: A scientific consensus meeting was performed by the European Society of Hypertension (ESH) Working Group on BP Monitoring and Cardiovascular Variability and STRIDE BP (Science and Technology for Regional Innovation and Development in Europe) during the 2022 Scientific Meeting of the ESH in Athens, Greece. Manufacturers were also invited to provide their feedback on BP device design and development. Thirty-one international experts in clinical hypertension and BP monitoring contributed to the development of consensus recommendations on the optimal design of BP devices., Statement: International consensus was reached on the requirements for the design and features of five types of BP monitors, including office (or clinic) BP monitors, ambulatory BP monitors, home BP monitors, home BP telemonitors, and kiosk BP monitors for public spaces. For each device type "essential" requirements (must have), and "optional" ones (may have) are presented, as well as additional comments on the optimal device design and features., Conclusions: These consensus recommendations aim at providing manufacturers of BP devices with the requirements that are considered mandatory, or optional, by clinical experts involved in the detection and management of hypertension. They are also directed to administrative healthcare personnel involved in the provision and purchase of BP devices so that they can recommend the most appropriate ones., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Hypertension management is directed by cuff blood pressure (BP), but this may be inaccurate, potentially influencing cardiovascular disease (CVD) events and health costs. This study aimed to determine the impact on CVD events and related costs of the differences between cuff and invasive SBP., Methods: Microsimulations based on Markov modelling over one year were used to determine the differences in the number of CVD events (myocardial infarction or coronary death, stroke, atrial fibrillation or heart failure) predicted by Framingham risk and total CVD health costs based on cuff SBP compared with invasive (aortic) SBP. Modelling was based on international consortium data from 1678 participants undergoing cardiac catheterization and 30 separate studies. Cuff underestimation and overestimation were defined as cuff SBP less than invasive SBP and cuff SBP greater than invasive SBP, respectively., Results: The proportion of people with cuff SBP underestimation versus overestimation progressively increased as SBP increased. This reached a maximum ratio of 16 : 1 in people with hypertension grades II and III. Both the number of CVD events missed (predominantly stroke, coronary death and myocardial infarction) and associated health costs increased stepwise across levels of SBP control, as cuff SBP underestimation increased. The maximum number of CVD events potentially missed (11.8/1000 patients) and highest costs ($241 300 USD/1000 patients) were seen in people with hypertension grades II and III and with at least 15 mmHg of cuff SBP underestimation., Conclusion: Cuff SBP underestimation can result in potentially preventable CVD events being missed and major increases in health costs. These issues could be remedied with improved cuff SBP accuracy., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Blood pressure is not a static parameter, but rather undergoes continuous fluctuations over time, as a result of the interaction between environmental and behavioural factors on one side and intrinsic cardiovascular regulatory mechanisms on the other side. Increased blood pressure variability (BPV) may indicate an impaired cardiovascular regulation and may represent a cardiovascular risk factor itself, having been associated with increased all-cause and cardiovascular mortality, stroke, coronary artery disease, heart failure, end-stage renal disease, and dementia incidence. Nonetheless, BPV was considered only a research issue in previous hypertension management guidelines, because the available evidence on its clinical relevance presents several gaps and is based on heterogeneous studies with limited standardization of methods for BPV assessment. The aim of this position paper, with contributions from members of the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability and from a number of international experts, is to summarize the available evidence in the field of BPV assessment methodology and clinical applications and to provide practical indications on how to measure and interpret BPV in research and clinical settings based on currently available data. Pending issues and clinical and methodological recommendations supported by available evidence are also reported. The information provided by this paper should contribute to a better standardization of future studies on BPV, but should also provide clinicians with some indications on how BPV can be managed based on currently available data., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Ambulatory blood pressure monitoring (ABPM) provides extensive information on several BP parameters other than the average BP during daily life. Through this analysis of the TEMPLAR study, we sought to understand better the features of age-related changes in ABP patterns and phenotypes., Methods: ABPMs were obtained in 53 350 individuals visiting 866 Italian community pharmacies (age 3-101 years, 54.3% female individuals). ABPM patterns were assessed across 10-year age categories., Results: SBP steadily increased with age. DBP increased from the youth to the middle adulthood and then declined. Daytime BP was higher than night-time BP, but the difference narrowed with aging, reducing the prevalence of dippers. An enhanced SBP morning surge and increased prevalence of abnormal morning rise were observed with aging. SBP and DBP variabilities increased with age with a typical U or J shape, more evident in the case of DBP. The proportion of participants with ambulatory hypertension increased with age. However, an elevated daytime BP was more common in younger individuals and elevated night-time hypertension in older individuals. The prevalence of white-coat hypertension remained stable or slightly declined through the age groups, whereas that of masked hypertension steadily increased., Conclusion: Our results confirm that ABP patterns interplay and change in a complex way with age. Such changes, particularly the age-related increase in BP variability and prevalence of nocturnal hypertension, nondipping, enhanced morning rise, and masked hypertension, may increase the risk of cardiovascular events and must be carefully considered by the physician when managing BP in the elderly., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The coronavirus disease 2019 pandemic caused an unprecedented shift from in person care to delivering healthcare remotely. To limit infectious spread, patients and providers rapidly adopted distant evaluation with online or telephone-based diagnosis and management of hypertension. It is likely that virtual care of chronic diseases including hypertension will continue in some form into the future. The purpose of the International Society of Hypertension's (ISH) position paper is to provide practical guidance on the virtual management of hypertension to improve its diagnosis and blood pressure control based on the currently available evidence and international experts' opinion for nonpregnant adults. Virtual care represents the provision of healthcare services at a distance with communication conducted between healthcare providers, healthcare users and their circle of care. This statement provides consensus guidance on: selecting blood pressure monitoring devices, accurate home blood pressure assessments, delivering patient education virtually, health behavior modification, medication adjustment and long-term virtual monitoring. We further provide recommendations on modalities for the virtual assessment and management of hypertension across the spectrum of resource availability and patient ability., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Low-quality ambulatory blood pressure monitoring (ABPM) due to recurring artifacts may limit its clinical value. We evaluated the features and impact on BP control and patient management of ABPMs performed in Italian community pharmacies, according to their quality., Methods: Twenty-four-hour ABPMs were obtained by a clinically validated, automated upper arm device and uploaded on a certified web-based telemedicine platform (www.tholomeus.net). The system automatically evaluated the quality of the recording according to current guidelines. In case of poor ABPM quality, the pharmacist was prompted to repeat the test. All the ABPMs were labeled as valid or invalid. Demographic and clinical characteristics of the patients and BP control were compared between the two groups., Results: A total of 45 232 ABPMs were obtained in as many patients through 812 pharmacies (87.7% recordings were valid). Factors significantly associated with a better ABPM quality were younger age, use of antihypertensive medications, presence of at least one cardiovascular risk factor, concomitant disease or treatment, a test performed in the coldest months, and residence in the cooler northern regions of the country. The 24-h and daytime ambulatory BP level and the prevalence of ambulatory hypertension and white-coat hypertension were higher, and the prevalence of masked hypertension lower in patients with valid recordings. High odds of obtaining a valid recording were observed in patients repeating the ABPM., Conclusion: Ambulatory BP telemonitoring is feasible in community pharmacies as long as potential predictors of unsuccessful outcomes are taken into account and adequately managed., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The present paper provides an update of previous recommendations on Home Blood Pressure Monitoring from the European Society of Hypertension (ESH) Working Group on Blood Pressure Monitoring and Cardiovascular Variability sequentially published in years 2000, 2008 and 2010. This update has taken into account new evidence in this field, including a recent statement by the American Heart association, as well as technological developments, which have occurred over the past 20 years. The present document has been developed by the same ESH Working Group with inputs from an international team of experts, and has been endorsed by the ESH., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: India Heart Study (IHS) is aimed at investigating the agreement between office blood pressure measurement (OBPM) and self (S)BPM in a hypertension-naive population., Methods: A total of 18 918 individuals (aged 42.6 ± 11.7 years, 62.7% men), visiting 1237 primary care physicians across India, underwent OBPM. They performed SBPM for a period of 1 week using a validated oscillometric BP monitor that was preprogrammed to adhere to a guideline-based SBPM-schedule and blinded to the results. Thereafter, individuals underwent a second OBPM. Available laboratory results were obtained. Thresholds for elevated OBPM and SBPM were 140/90 and 135/85 mmHg, respectively., Results: On the basis of first-visit OBPM and SBPM, there were 5787 (30.6%) individuals with normotension; 5208 (27.5%) with hypertension; 4485 (23.7%) with white-coat hypertension (WCH) and 3438 (18.2%) with masked hypertension. Thus, a diagnosis contradiction between SBPM and first-visit OBPM was seen in 9870 (41.9%) individuals. On the basis of second-visit OBPM, the normotension, hypertension, WCH and masked hypertension prevalence values were 7875 (41.6%); 4857 (25.7%); 2397 (12.7%) and 3789 (20.0%). There was poor agreement (kappa value 0.37) between OBPM of visit 1 and 2 with a diagnosis difference in 6027 (31.8%) individuals. The majority of masked hypertension and WCH individuals had BP values close to thresholds., Conclusion: There was a poor agreement between OBPM of visit1 and visit 2. Likewise, the agreement between OBPM at both visits and SBPM was poor. SBPM being considered to have a better correlation with patient prognosis should be the preferred method for diagnosing hypertension.

Objective: In this analysis of the telehealth-based Vascular health ASsessment Of The hypertENSive patients Registry, we checked how 24-h central and peripheral hemodynamics compare with hypertension-mediated organ damage (HMOD)., Methods: In 646 hypertensive patients (mean age 52 ± 16 years, 54% males, 65% treated) we obtained ambulatory brachial and central SBP and pulse pressure (PP), SBP, and PP variability, pulse wave velocity and augmentation index with a validated cuff-based technology. HMOD was defined by an increased left ventricular mass index (cardiac damage, evaluated in 482 patients), an increased intima-media thickness (vascular damage, n = 368), or a decreased estimated glomerular filtration rate or increased urine albumin excretion (renal damage, n = 388)., Results: Ambulatory SBP and PPs were significantly associated with cardiac damage: the largest odds ratio was observed for 24-h central SBP [1.032 (1.012, 1.051), P = 0.001] and PP [1.042 (1.015, 1.069), P = 0.002], the weakest for brachial estimates. The association was less strong for vascular damage with a trend to the superiority of 24-h central [1.036 (0.997, 1.076), P = 0.070] over brachial PP [1.031 (1.000, 1.062), P = 0.052]. No statistically significant association was observed for renal damage. SBP and PP variabilities, pulse wave velocity and augmentation index were not associated with any form of HMOD. In the multivariate analysis, age was associated with any type of HMOD, whereas central SBP and PP were predictive of an increased risk of cardiac damage., Conclusion: In hypertensive patients a variable association exists between peripheral and central hemodynamics and various types of HMOD, with the most predictive power being observed for central SBP and PP for cardiac damage.

Objective: To evaluate the impact of olmesartan alone or combined with one to three antihypertensive drugs on 24-h blood pressure variability (BPV) and on distribution of BP reduction in a pooled individual data analysis of 10 double-blind, randomized, ambulatory BP monitoring (ABPM) studies., Methods: ABPMs were performed before and after 6-12 weeks of treatment with placebo (n = 119), active control monotherapy [n = 1195, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), dihydropyridine calcium channel blockers (DCCBs)] olmesartan monotherapy (n = 1410), active control dual combination [n = 79, DCCB + thiazide diuretic (TD)], olmesartan dual combination (n = 637, DCCB or TD), and triple combination therapy (n = 102, DCCB+TD). 24-h BPV was calculated as unweighted or weighted SD of the mean BP, and average real variability. BP control was assessed by smoothness index and treatment-on-variability index., Results: The greatest effect on 24-h systolic BPV/diastolic BPV was observed under olmesartan triple [-2.6/-1.9; -1.9/-1.3; -1.4/-1.3 mmHg] and active control dual combination [-1.8/-1.4; -1.9/-1.5; -1.2/-1.1 mmHg]. Smoothness indexes and treatment-on-variability indexes were significantly (P = 0.0001) higher under olmesartan dual (1.53/1.22, 1.67/1.29, 2.05/1.59), olmesartan triple (2.47/1.85, 2.80/2.06, 3.64/2.67), or active control dual combination (1.70/1.26, 1.85/1.33, 2.29/1.65) than under monotherapies (control: 0.86/0.73, 0.80/0.65, 1.01/0.82; olmesartan: 1.02/0.86, 0.95/0.78, 1.23/1.00). They were also greater in patients receiving high-dose olmesartan monotherapy or high-dose olmesartan dual combination than in the corresponding low-dose group., Conclusion: Olmesartan plus a DCCB and/or a TD produces a larger, more sustained, and smoother BP reduction than placebo and monotherapies, a desirable feature for a more effective prevention of the cardiovascular consequences of uncontrolled hypertension.

Objective: The Ambulatory blood pressure Registry TEleMonitoring of hypertension and cardiovascular rISk project was designed to set up an international registry including clinic blood pressure (CBP) and ambulatory blood pressure (ABP) measurements in patients attending hypertension clinics in all five continents, aiming to assess different daily life hypertension types., Methods: Cross-sectional ABP, CBP and demographic data, medical history and cardiovascular risk profile were provided from existing databases by hypertension clinics. Hypertension types were evaluated considering CBP (≥140/90 mmHg) and 24-h ABP (≥130/80 mmHg)., Results: Overall, 14 143 patients from 27 countries across all five continents were analyzed (Europe 73%, Africa 3%, America 9%, Asia 14% and Australia 2%). Mean age was 57 ± 14 years, men 51%, treated for hypertension 46%, cardiovascular disease 14%, people with diabetes 14%, dyslipidemia 33% and smokers 19%. The prevalence of hypertension was higher by CBP than by ABP monitoring (72 vs. 60%, P < 0.0001). Sustained hypertension (elevated CBP and ABP) was detected in 49% of patients. White-coat hypertension (WCH, elevated CBP with normal ABP) was more common than masked hypertension (elevated ABP with normal CBP) (23 vs. 10%; P < 0.0001). Sustained hypertension was more common in Europe and America and in elderly, men, obese patients with cardiovascular comorbidities. WCH was less common in Australia, America and Africa, and more common in elderly, obese women. Masked hypertension was more common in Asia and in men with diabetes. Smoking was a determinant for sustained hypertension and masked hypertension., Conclusion: Our analysis showed an unbalanced distribution of WCH and masked hypertension patterns among different continents, suggesting an interplay of genetic and environmental factors, and likely also different healthcare administrative and practice patterns.

Objective: Whether all antihypertensive drugs are equally effective in patients with metabolic syndrome is still unclear. The goal of the Zofenopril in Advanced MEtabolic Syndrome (ZAMES) study was to investigate whether treatment with the fixed-dose combination of sulphydril-containing angiotensin-converting enzyme inhibitor zofenopril plus hydrochlorothiazide is at least as effective as that with the angiotensin receptor blocker irbesartan plus hydrochlorothiazide in patients with metabolic syndrome and essential hypertension, uncontrolled by a previous monotherapy., Methods: We enrolled 721 patients in a multicenter, international (Italy and Romania), randomized, double-blind, parallel group, phase III study. Following a 1-week screening withdrawal period, 482 patients (mean age 59 ± 10 years, 53% men) bearing a SBP at least 140 mmHg and/or DBP at least 90 mmHg plus metabolic syndrome (ATP-III criteria) were randomly allocated to a fixed-dose combination of zofenopril 30 mg plus hydrochlorothiazide 12.5 mg or irbesartan 150 mg plus hydrochlorothiazide 12.5 mg once daily for a cumulative period of 24 weeks. After 8 and 16 weeks, zofenopril and irbesartan doses were doubled in nonnormalized study participants. The study endpoint was the office DBP reduction at study end. In 20% of patients, an ambulatory blood pressure monitoring was performed., Results: The prevalence of diabetes at baseline was significantly (P < 0.05) greater in the zofenopril plus hydrochlorothiazide group (82%) than in the irbesartan plus hydrochlorothiazide (73%) group. Baseline-adjusted DBP reductions were superimposable (P = 0.370) with zofenopril plus hydrochlorothiazide [n = 231; 9.8 (95% confidence interval: 11.1, 8.4) mmHg] and irbesartan plus hydrochlorothiazide [n = 235; 10.4 (11.8, 9.0) mmHg]. The same was for SBP [17.0 (19.2, 14.8) mmHg zofenopril plus hydrochlorothiazide vs. 18.8 (21.0, 16.6) mmHg irbesartan plus hydrochlorothiazide, P = 0.113]. Rate of normalized and responder patients (SBP/DBP < 140/90 mmHg or SBP reduction more than 20 mmHg or DBP reduction more than 10 mmHg) did not differ at study end (65.8% and 77.5% zofenopril plus hydrochlorothiazide vs. 67.7% and 81.5% irbesartan plus hydrochlorothiazide; P = 0.695, P = 0.301). These results were confirmed in the 69 study participants undergoing ambulatory blood pressure monitoring (35 zofenopril plus hydrochlorothiazide; 34 irbesartan plus hydrochlorothiazide), with a comparable 24-h average BP reduction [BP difference between-treatment: SBP: 0.1 (-5.7, 5.9) mmHg, P = 0.975; DBP: -0.9 (-3.8, 2.0) mmHg, P = 0.541]. Both drugs attained similar BP reductions also in the last 6 h of the dosing interval [between-treatment difference SBP: 0.1 (-7.4, 7.5) mmHg P = 0.990; DBP: -0.9 (-4.4, 2.6) mmHg, P = 0.602]. Metabolic and renal indexes were not altered. Few patients were withdrawn for moderate adverse events (5% zofenopril plus hydrochlorothiazide; 5% irbesartan plus hydrochlorothiazide)., Conclusion: This is the first study supporting the comparable antihypertensive and metabolic response to fixed-dose combinations of sulphydril-containing angiotensin-converting enzyme inhibitors (zofenopril) or angiotensin receptor blockers (Irbesartan) with a diuretic in patients with advanced metabolic syndrome and nonresponders to monotherapy. The results of this study can further improve the clinical management of high cardiovascular risk patients with hypertension and metabolic syndrome, because these two drug combinations increase the number of available combinations, which may significantly improve patients' adherence in this special clinical condition that is frequently found in everyday practice.

Office blood pressure measurement has been the basis for hypertension evaluation for almost a century. However, the evaluation of blood pressure out of the office using ambulatory or self-home monitoring is now strongly recommended for the accurate diagnosis in many, if not all, cases with suspected hypertension. Moreover, there is evidence that the variability of blood pressure might offer prognostic information that is independent of the average blood pressure level. Recently, advancement in technology has provided noninvasive evaluation of central (aortic) blood pressure, which might have attributes that are additive to the conventional brachial blood pressure measurement. This position statement, developed by international experts, deals with key research and practical issues in regard to peripheral blood pressure measurement (office, home, and ambulatory), blood pressure variability, and central blood pressure measurement. The objective is to present current achievements, identify gaps in knowledge and issues concerning clinical application, and present relevant research questions and directions to investigators and manufacturers for future research and development (primary goal).

Objective: To compare zofenopril + hydrochlorothiazide (Z + H) vs. irbesartan + hydrochlorothiazide (I + H) efficacy on daytime SBP in elderly (>65 years) patients with isolated systolic hypertension (ISH), untreated or uncontrolled by a previous monotherapy., Methods: After a 1-week run-in, 230 ISH patients (office SBP ≥ 140  mmHg and DBP < 90  mmHg + daytime SBP ≥ 135  mmHg and daytime DBP < 85  mmHg) were randomized double-blind to 18-week treatment with Z + H (30 + 12.5  mg) or I + H (150 + 12.5  mg) once daily, in an international, multicenter study. Z and I doses could be doubled after 6 and 12 weeks, and nitrendipine 20  mg added at 12 weeks in nonnormalized patients., Results: In the full analysis set (n = 216) baseline-adjusted average (95% confidence interval) daytime SBP reductions after 6 weeks (primary study end point) were similar (P = 0.888) with Z + H [7.7 (10.7, 4.6)  mmHg, n = 107] and I + H [7.9 (10.7, 5.0)  mmHg, n = 109]. Daytime SBP reductions were sustained during the study, and larger (P = 0.028) with low-dose Z + H at study end [16.2 (20.0, 12.5)  mmHg vs. 11.2 (14.4, 7.9)  mmHg I + H]. Daytime SBP normalization (<135 mmHg) rate was similar under Z + H and I + H at 6 and 12 weeks, but more common under Z + H at 18 weeks (68.2 vs. 56.0%, P = 0.031). Both drugs equally reduced SBP in the last 6 h of the dosing interval and homogeneously reduced SBP throughout the 24 h. The proportion of patients reporting drug-related adverse events was low (Z + H: 4.4% vs. I + H: 6.0%; P = 0.574)., Conclusion: Elderly patients with ISH respond well to both low and high-dose Z or I combined with H.

Objective: To compare a combination of a dihydropyridine calcium-channel blocker with an angiotensin converting enzyme inhibitor vs. monotherapy with one or the other drug and placebo for their effects on home blood pressure (HBP)., Methods: After a 2-week placebo wash-out, patients with an elevated office blood pressure (BP) (diastolic 100-109 and systolic <180 mmHg) and HBP (diastolic ≥85 mmHg) were randomized double-blind to a 10-week treatment with placebo, lercanidipine, 10 or 20 mg daily, enalapril, 10 or 20 mg daily, or the four possible combinations. In addition to office BP, HBP was self-measured via a validated semiautomatic device twice in the morning and twice in the evening during the 7 days before randomization and at the end of treatment. Baseline and treatment HBP values were separately averaged for each day, morning, evening or the whole monitoring period, excluding the first day. Day-by-day HBP variability was defined as the SD or the variation coefficient of the daily BP averages., Results: Eight hundred and fifty-four patients with valid HBP recordings at baseline and at the end of treatment were analyzed (intention-to-treat population). From the baseline value (147.0±11.6 mmHg) systolic/diastolic HBP showed a small reduction (average baseline-adjusted change: -1.8/-1.6 mmHg) with placebo, a more marked significant fall with monotherapies (-8.8/-5.9 mmHg, P < 0.001/<0.001 vs. placebo) and even more with combination treatment (11.6/-7.6 mmHg, P < 0.001/ < 0.001 vs. placebo and P < 0.01/ < 0.05 vs. monotherapy). A similar pattern was observed for each of the days of the BP self-monitoring period as well as for either morning or evening values, although the difference between mono and combination treatment appeared to be consistently significant for the morning values only. Day-by-day systolic BP-SD was unaffected by placebo and slightly reduced by drug treatments, with no, however, significant changes in SBP-variation coefficient. Baseline and end of treatment HBP values showed a limited correlation with office BP values, this being particularly the case for treatment-induced changes (correlation coefficients: 0.37 for systolic and 0.45 for diastolic BP)., Conclusion: This large HBP database shows that the lercanidipine-enalapril combination lowers HBP more effectively than the corresponding monotherapies and placebo, and that this greater effect is consistent between days., Trial Registration: ClinicalTrials.gov identifier: NCT01093807.

Given the increasing use of ambulatory blood pressure monitoring (ABPM) in both clinical practice and hypertension research, a group of scientists, participating in the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability, in year 2013 published a comprehensive position paper dealing with all aspects of the technique, based on the available scientific evidence for ABPM. The present work represents an updated schematic summary of the most important aspects related to the use of ABPM in daily practice, and is aimed at providing recommendations for proper use of this technique in a clinical setting by both specialists and practicing physicians. The present article details the requirements and the methodological issues to be addressed for using ABPM in clinical practice, The clinical indications for ABPM suggested by the available studies, among which white-coat phenomena, masked hypertension, and nocturnal hypertension, are outlined in detail, and the place of home measurement of blood pressure in relation to ABPM is discussed. The role of ABPM in pharmacological, epidemiological, and clinical research is also briefly mentioned. Finally, the implementation of ABPM in practice is considered in relation to the situation of different countries with regard to the reimbursement and the availability of ABPM in primary care practices, hospital clinics, and pharmacies.

Ambulatory blood pressure monitoring (ABPM) is being used increasingly in both clinical practice and hypertension research. Although there are many guidelines that emphasize the indications for ABPM, there is no comprehensive guideline dealing with all aspects of the technique. It was agreed at a consensus meeting on ABPM in Milan in 2011 that the 34 attendees should prepare a comprehensive position paper on the scientific evidence for ABPM.This position paper considers the historical background, the advantages and limitations of ABPM, the threshold levels for practice, and the cost-effectiveness of the technique. It examines the need for selecting an appropriate device, the accuracy of devices, the additional information and indices that ABPM devices may provide, and the software requirements.At a practical level, the paper details the requirements for using ABPM in clinical practice, editing considerations, the number of measurements required, and the circumstances, such as obesity and arrhythmias, when particular care needs to be taken when using ABPM.The clinical indications for ABPM, among which white-coat phenomena, masked hypertension, and nocturnal hypertension appear to be prominent, are outlined in detail along with special considerations that apply in certain clinical circumstances, such as childhood, the elderly and pregnancy, and in cardiovascular illness, examples being stroke and chronic renal disease, and the place of home measurement of blood pressure in relation to ABPM is appraised.The role of ABPM in research circumstances, such as pharmacological trials and in the prediction of outcome in epidemiological studies is examined and finally the implementation of ABPM in practice is considered in relation to the issue of reimbursement in different countries, the provision of the technique by primary care practices, hospital clinics and pharmacies, and the growing role of registries of ABPM in many countries.

Background: Antecedent hypertension represents a risk factor for adverse outcomes in survivors of acute myocardial infarction (AMI). Prognosis of such patients might be greatly improved by drugs enhancing blood pressure control. In the present retrospective analysis of the randomized, double-blind, parallel-group, SMILE-4 study we compared the efficacy of zofenopril 60 mg and acetylsalicylic acid (ASA) 100 mg versus ramipril 10 mg and ASA in patients with AMI complicated by left ventricular dysfunction, classified according to a history of hypertension., Methods: The primary study end-point was 1-year combined occurrence of death or hospitalization for cardiovascular causes. Hypertension was defined according to medical history and current blood pressure values at entry and could be determined in 682 of 716 patients of the intention-to-treat analysis., Results: One hundred and fifty-seven patients (23%) were normotensives and 525 (77%) hypertensives. In the normotensive population the primary end-point occurred in 19 of 76 zofenopril-treated patients (25%) and in 23 of 81 ramipril-treated patients (28%) [odds ratio (95% confidence interval): 0.84 (0.41-1.71), P = 0.631]. In the hypertensive population, major cardiovascular outcomes were reported in 84 of 273 zofenopril-treated patients (31%) and in 99 of 252 ramipril-treated patients (39%), with a 31% significantly (P = 0.041) lower risk with zofenopril [0.69 (0.48-0.99)]. The superiority of zofenopril versus ramipril was particularly evident in patients with isolated systolic hypertension [n = 131, 0.48 (0.23-0.99), P = 0.045]., Conclusion: This retrospective analysis of the SMILE-4 study confirmed the good efficacy of zofenopril and ASA in the prevention of long-term cardiovascular outcomes also in the subgroup of patients with hypertension.

Objective: To systematically review data from randomized controlled studies on the effectiveness of home blood pressure telemonitoring (HBPT) versus usual care with respect to improvement of BP control, healthcare resources utilization and costs, patient's quality of life and adverse events., Methods: Electronic databases were searched for publications in English. The benefit and relative risk (RR) were estimated applying a random-effect model., Results: Twenty-three randomized controlled trials with a high level of heterogeneity were selected (7037 patients). Compared to usual care, HBPT improved office SBP by 4.71 mmHg [95% confidence interval (CI): 6.18, 3.24; P < 0.001] and DBP by 2.45 mmHg (3.33, 1.57; P < 0.001). A larger proportion of patients achieved office BP normalization (<140/90 mmHg nondiabetic patients and <130/80 mmHg diabetic patients) in the intervention group [RR: 1.16 (1.04, 1.29); P < 0.001]. HBPT led to a significantly larger prescription of antihypertensive medications [+0.40 (+0.17,+0.62), P < 0.001], but to therapeutic adherence and rate of office consultations similar to usual care. Healthcare costs were significantly (P < 0.001) larger in the HBPT group [+662.92 (+540.81, +785.04) euros per patient], but were similar to those of the usual care when only medical costs were considered [-12.4 (-930.52, +906.23) euros; P = 0.767]. Use of HBPT helped improving the physical component of quality of life [SF-12 or SF-36 questionnaire: +2.78 (+1.15, +4.41) P < 0.001]. No difference was observed in the risk of adverse events [RR: 1.22 (0.86, 1.71); P = 0.111]., Conclusion: HBPT may represent a useful tool to improve hypertension control and associated healthcare outcomes, although it is still more costly compared with usual care.

Objective: To assess the antihypertensive efficacy of olmesartan medoxomil and ramipril on 24-h ambulatory blood pressure (ABP) in elderly hypertensive patients by pooled data analysis of two studies with identical designs (one Italian, one European)., Methods: After a 2-week placebo wash-out 1453 elderly hypertensive patients (65-89 years; sitting office DBP 90-109 mmHg and/or sitting office SBP 140-179 mmHg) were randomized to a 12-week double-blind treatment with olmesartan medoxomil 10 mg or ramipril 2.5 mg once-daily, up-titrated (20 and 40 mg olmesartan medoxomil; 5 and 10 mg ramipril) after 2 and 6 weeks in patients without normalized office BP. 24-h ABP was recorded at randomization and after 12 weeks., Results: In 715 patients with valid baseline and end-of-treatment recordings baseline-adjusted 24-h SBP and DBP reductions were greater with olmesartan medoxomil (n = 356) than with ramipril (n = 359) [between-treatment differences and 95% confidence interval (CI), SBP: 2.2 (3.8, 0.6), P = 0.006; DBP: 1.3 (2.2, 0.3), P = 0.009]. Olmesartan medoxomil showed larger BP reductions in the last 6 h from the dosing interval and higher smoothness indices than ramipril. Olmesartan medoxomil reduced the SBP morning rise [-2.8 (-4.9, -0.8) mmHg], whereas ramipril did not [+1.5 (-0.6, +3.6) mmHg; P = 0.004 between-treatments]. Five hundred and eighty-two patients with sustained hypertension (office and 24-h ambulatory hypertension) showed the largest antihypertensive effect, with between-treatment differences still in favor of olmesartan medoxomil [SBP: 2.1 (3.9, 0.4), P = 0.019; DBP: 1.2 (2.3, 0.1), P = 0.032]., Conclusions: Olmesartan medoxomil provides a more effective and sustained 24-h BP control than ramipril in elderly hypertensive patients, particularly in the hours farthest from last intake.

Objective: To compare the efficacy and safety of the angiotensin II antagonist olmesartan medoxomil (O) and the ACE inhibitor ramipril (R) in elderly patients with essential arterial hypertension., Methods: After a 2-week placebo wash-out 1102 treated or untreated elderly hypertensive patients aged 65-89 years (office sitting diastolic blood pressure, DBP, 90-109 mmHg and/or office sitting systolic blood pressure, SBP, 140-179 mmHg) were randomized double-blind to 12-week treatment with O 10 mg or R 2.5 mg once-daily. After the first 2 and 6 weeks doses could be doubled in non-normalized [blood pressure (BP) < 140/90 mmHg for nondiabetic and < 130/80 mmHg for diabetic) individuals, up to 40 mg for O and 10 mg for R. Office BPs were assessed at randomization, after 2, 6 and 12 weeks of treatment, whereas 24-h ambulatory BP was recorded at randomization and after 12 weeks., Results: In the intention-to-treat population (542 patients O and 539 R) after 12 weeks of treatment baseline-adjusted office SBP and DBP reductions were greater (P < 0.01) with O [17.8 (95% confidence interval: 16.8/18.9) and 9.2 (8.6/9.8) mmHg] than with R [15.7 (14.7/16.8) and 7.7 (7.1/8.3) mmHg]. BP normalization rate was also greater under O (52.6 vs. 46.0% R, P < 0.05). In the subgroup of patients with valid ambulatory BP recording (318 O and 312 R) the reduction in 24-h average BP was larger (P < 0.05) with O [SBP: 11.0 (12.2/9.9) and DBP: 6.5 (7.2/5.8) mmHg] than with R [9.0 (10.2/7.9) and 5.4 (6.1/4.7) mmHg]. The larger blood pressure reduction obtained with O was particularly evident in the last 6 h from the dosing interval; a better homogeneity of the 24-h BP control with O was confirmed by higher smoothness indices. The proportion of patients with drug-related adverse events was comparable in the two groups (3.6 O vs. 3.6% R), as well as the number of patients discontinuing study drug because of a side effect (14 O vs. 19 R)., Conclusion: In elderly patients with essential arterial hypertension O provides an effective, prolonged and well tolerated BP control, representing a useful option among first-line drug treatments of hypertension in this age group.

Background: Conventional calculation of mean 24-h ambulatory blood pressure (BP), SBP and DBP based on the average of all BP readings disregards the fact that a larger number of measurements is usually scheduled during the daytime than at night, an imbalance possibly leading to an overestimation of 24-h average BP. The aim of our study was to quantify this possible bias and to explore its determinants., Methods: Four hundred and fifty untreated individuals were subdivided into three groups (150 individuals each) with three different ambulatory blood pressure measurement schedules for day/night: group I, four (day)/two (night) readings/h; group II, four (day)/three (night) readings/h; and group III, with BP readings every 30 min throughout 24 h. Hourly and 24-h averages were computed. The conventional 24-h averages of all SBP and DBP values were compared with the averages of hourly SBP and DBP mean values (time-weighted quantification). The difference between 24-h conventional and 24-h time-weighted BP was computed in each group and related to the degree of nocturnal BP dip and to the ratio between the number of readings of day and night., Result: In the three groups, 24-h conventional and 24-h time-weighted BP values were highly correlated (r > 0.99), 24-h conventional SBP and DBP being significantly higher (P < 0.01) than the corresponding 24-h time-weighted values in groups I and II but not in group III (Bland-Altman analysis). The bias magnitude was related to the day/night ratio in number of readings and to nocturnal BP dip in groups I and II (P < 0.01) but not in group III., Conclusion: The higher number of readings/h during daytime leads to an overestimation of conventional 24-h average BP, particularly in individuals with preserved nocturnal BP dipping. This can be avoided either by scheduling the same number of readings/h throughout 24 h or by performing a time-weighted quantification of 24-h BP. The clinical implications of these different approaches deserve further investigation.

Background: Self blood pressure monitoring at home may improve blood pressure control and patients' compliance with treatment, but its implementation in daily practice faces difficulties. Teletransmission facilities may offer a more efficient approach to long-term home blood pressure monitoring., Methods: Twelve general practitioners screened 391 consecutive uncontrolled mild-moderate hypertensive patients (80% treated), 329 of whom (58 +/- 11 years, 54% men) were randomized to either usual care on the basis of office blood pressure (group A, n = 113) or to integrated care on the basis of teletransmitted home blood pressure (group B, n = 216). Twenty-four-hour ambulatory blood pressure monitoring was performed at baseline and after 6 months, during which treatment was optimized according to either office (group A) or home (group B) blood pressure values. We compared differences between groups in the rate of daytime ambulatory blood pressure normalization (<130/80 mmHg), need of treatment changes during follow-up, quality of life scores, and healthcare costs., Results: Baseline office blood pressures were 149 +/- 12/89 +/- 9 and 148 +/- 13/89 +/- 7 mmHg in groups A (n = 111) and B (n = 187) respectively, the corresponding daytime values being 140 +/- 11/84 +/- 8 and 139 +/- 11/84 +/- 8 mmHg. The percentage of daytime blood pressure normalization was higher in group B (62%) than in group A (50%) (P < 0.05). There were less frequent treatment changes in group B than in group A (9 vs. 14%, P < 0.05). Quality of life tended to be higher and costs lower in group B., Conclusion: Patients' management based on home blood pressure teletransmission led to a better control of ambulatory blood pressure than with usual care, with a more regular treatment regimen.

Objectives: Information on the features of long-term modifications of clinic and 24-h ambulatory blood pressure (ABP) by treatment is limited. The present study aimed to address this issue., Methods: Ambulatory BP monitoring and clinic BP (CBP) measurements were performed at baseline and at yearly intervals over a 4-year follow-up period in 1523 hypertensives (56.1 +/- 7.6 years) randomized to treatment with lacidipine or atenolol in the European Lacidipine Study on Atherosclerosis (ELSA)., Results: CBP was always greater than ABP, while reductions in all BP values (greater for CBP than for ABP) were on average maintained throughout 4 years, CBP changes showing limited relationship with ABP changes (r = 0.14-0.27). BP reductions by treatment during daytime and night-time were correlated (r = 0.63-0.73). BP normalization was achieved in a greater percentage of patients for CBP (41.7%) than for ABP (25.3%), with systolic BP control being always less common than diastolic BP control. BP normalization was more frequent at single yearly visits than throughout the 4 years. Twenty-four-hour BP variability was reduced by treatment over 4 years in absolute but not in normalized units., Conclusions: The present study provides the best evidence available on long-term effect of antihypertensive treatment on both ABP and CBP. On average, ABP was sustainedly reduced by treatment throughout the follow-up period, but 24-h BP was more difficult to control than CBP. In several patients, ABP control was unstable between visits, the percentage of patients under control over 4 years being much less than that of those controlled at each year. Treatment induced a reduction in absolute but not in normalized BP variability estimates. This has clinical implications because of the prognostic importance of ABP mean values and variability.

Objectives: The International Nifedipine GITS Study Intervention as a Goal in Hypertension Treatment (INSIGHT) showed, by means of office blood pressure measurements, that long-term treatment with nifedipine GITS is as effective as diuretics in preventing cardiovascular and cerebrovascular complications. However, since office blood pressure measurements reflect to a limited extent blood pressure outside the office, a side-arm INSIGHT study in which patients underwent both office measurement and 24 h ambulatory blood pressure monitoring was also performed., Design and Methods: The study had a randomized, double-blind, parallel group design. After 4 weeks of placebo, mild-to-moderate essential hypertensive patients were randomized to nifedipine GITS 30 mg or amiloride 2.5 + hydrochlorothiazide 5 mg for 3.1 years. Dose titration was performed by dose doubling and addition of atenolol 25-50 mg or enalapril 5-10 mg, or other drugs when needed. Analysis was carried out by intention-to-treat and included computation of 24 h, day and night ambulatory blood pressure and heart rate values. Additional analyses included computation of the trough-to-peak ratio and the smoothness index (the ratio between the average of the 24-hourly blood pressure reductions after treatment and its standard deviation)., Results: A total of 151 patients were recruited and 149 were valid for analysis: 78 patients had 24 h ambulatory recordings both at baseline and during treatment and 134 during treatment. Office, 24 h and day and night blood pressures were all significantly and similarly reduced by both treatments. Office and ambulatory heart rate was left unchanged by diuretics, while it was slightly reduced by nifedipine. Median trough-to-peak ratios were always > 0.5 and superimposable between the two treatment groups. Similarly, smoothness indices of systolic and diastolic blood pressures were comparably high for nifedipine and diuretics, thus demonstrating a similar well-balanced antihypertensive response to both drugs. No significant differences were observed between the two treatment groups in the number of cardiovascular events (17 in the nifedipine-based and 26 in the diuretics-based treatment group)., Conclusions: In the INSIGHT study, the long-term antihypertensive effect on 24 h blood pressure and the cardiovascular protection of nifedipine was similar to that of diuretics.

Background: Baseline data from the European Lacidipine Study on Atherosclerosis (ELSA) have shown that carotid intima-media thickness (IMT) is not related to diastolic blood pressure (BP), but that it is related to clinic systolic (S) or pulse pressure (PP) and more so to their 24 h average values. The aim of the present study was to determine whether IMT independently relates to additional information obtained through ambulatory BP, in particular to SBP or PP variability., Methods and Results: In 1663 hypertensive patients, after a wash-out period from antihypertensive treatment (mean age 56.2 +/- 7.65 years), IMT was assessed from 12 different carotid sites. Ambulatory BP measurements were performed every 15 min (day) and every 20 min (night). IMT values were positively related to 24 h, day and night average SBP and PP. There was some relationship of IMT with day-night or clinic-day SBP and PP differences. The most important finding, however, was that IMT values were related with 24 h SBP or PP standard deviation (P < 0.001), a measure of overall SBP or PP variability. The relationship was seen also by multiple regression analysis, the standard deviation for SBP or PP only following age and 24 h average SBP or PP in accounting for IMT values., Conclusions: This is the first demonstration from a large database that not only average 24 h PP and SBP values, but also 24 h BP fluctuations, are associated with, and possibly determinants of, the alterations of large artery structure in hypertension.

Background and Aims: The Hypertension Optimal Treatment (HOT) study showed that when antihypertensive treatment reduces diastolic blood pressure well below 90 mmHg, there can be a further reduction of cardiovascular events, particularly myocardial infarction, with no evidence of a J-shaped curve at lower pressures. Office measurement, however, gives no information about blood pressure outside the office. This paper describes a HOT substudy in which patients underwent both office measurement and 24 h ambulatory blood pressure monitoring., Methods: The mean age of the substudy population was 62 +/- 7 years. Substudy patients were treated for a median period of 2 years. All received the dihydropyridine calcium antagonist felodipine, while some also received an ACE-inhibitor, a beta-blocker or a diuretic. Average 24 h, day and night ambulatory blood pressure values were computed at baseline (n = 277) and during treatment (n = 347): 112 patients had been randomized to a target office diastolic blood pressure

Objective: To evaluate the antihypertensive effect of lercanidipine once a day at three different doses (2.5, 5 and 10 mg) by clinic and ambulatory blood pressure., Methods: After 3 weeks of a placebo run-in, 243 mild to moderate essential hypertensives (mean+/-SD age 51+/-8 years) were randomly allocated to lercanidipine at 2.5, 5 or 10 mg or a placebo for 4 weeks, in a double-blind parallel-group design. At the end of each period, supine clinic blood pressure (standard sphygmomanometry) and 24 h ambulatory blood pressure (Spacelabs 90207) were measured. The duration and homogeneity of the antihypertensive effect of the active drug compared with placebo over 24 h was evaluated by calculating the smoothness index, the ratio of the mean of the 24 hourly blood pressure changes to the corresponding SD. The higher the smoothness index, the greater and the smoother is the antihypertensive effect of a drug over the 24 h., Results: In 211 patients with valid clinic blood pressure data at the end of treatment, larger systolic/diastolic blood pressure reductions were found in the 5 mg (10+/-12/8+/-6 mmHg; P< 0.05 versus placebo, diastolic blood pressure only) and the 10 mg (12+/-11/9+/-7 mmHg; P < 0.05 versus placebo, both pressures) lercanidipine groups than in the placebo (5+/-11/4+/-8 mmHg) and 2.5 mg lercanidipine (7+/-12/6 +/-7 mmHg) groups. In 105 patients with complete 24 h ambulatory blood pressure recordings, there were significantly (P< 0.05 versus placebo) larger reductions in the 10 mg (9+/-7/7+/-5 mmHg) than the 2.5 mg (1+/-10/1+/-6 mmHg) and placebo (2+/-6/1+/-4 mmHg) groups. The reduction in 24 h blood pressure with 5 mg lercanidipine (6+/-7/4+/-5 mmHg) was significantly greater compared with placebo for diastolic pressure only, and when hourly average blood pressure changes were considered, this reduction did not extend to the final hours of the dosing interval. No significant changes in the clinic or 24 h heart rate were induced by placebo or lercanidipine. The smoothness index was significantly (P< 0.05) lower for 2.5 mg lercanidipine and placebo (0.2+/-0.5 and 0.3+/-0.7 for systolic and 0.1+/-0.4 and 0.2+/-0.7 for diastolic blood pressure) than for the 5 and 10 mg doses (0.7+/-1 and 1+/-0.7 for systolic and 0.7+/-1 and 1+/-0.9 for diastolic blood pressure)., Conclusions: At a dose of 10 mg, lercanidipine had a significant and durable antihypertensive effect over 24 h, but at 5 mg, the effect was less consistent and did not last 24 h. There was no clinically relevant reduction in clinic or ambulatory blood pressure with 2.5 mg lercanidipine, and the effect was superimposable on that of placebo.

Objective: To introduce a new method, the smoothness index, for assessing the homogeneity of 24 h blood pressure reduction by antihypertensive treatment and to compare it with the trough : peak ratio; and to assess the ability of both indices to predict a reduction in the left ventricular mass index induced by treatment., Patients and Methods: In 174 patients with essential hypertension and left ventricular hypertrophy, enrolled in the Study on Ambulatory Monitoring of Pressure and Lisinopril Evaluation (SAMPLE), aged 20-65 years, we measured clinic blood pressure, 24 h ambulatory blood pressure and the left ventricular mass index (echocardiography) before and after treatment with lisinopril at 20 mg with the addition of 12.5 or 25 mg hydrochlorothiazide as needed to reach a sufficient blood pressure reduction. The following parameters were computed for systolic and diastolic ambulatory blood pressure: (1) hourly and 24 h blood pressure averages (+/- SD) at baseline and after 3 and 12 months of treatment; (2) hourly blood pressure changes from baseline after 3 and 12 months of treatment, and their average (+/- SD) over 24 h; (3) the trough : peak ratio after 3 and 12 months of treatment; and (4) the smoothness index after 3 and 12 months of treatment Similar calculations were also performed at the end of a final study month during which active treatment was withdrawn and placebo was substituted (n = 164)., Results: The smoothness index for systolic and diastolic ambulatory blood pressure computed after 3 months of treatment was more closely related to its corresponding values after 12 months of treatment than the trough : peak ratio values computed after the same time periods were (r = 0.68 versus 0.38 for systolic and 0.68 versus 0.42 for diastolic blood pressure, respectively). The smoothness index showed an inverse correlation with the 24 h standard deviation of systolic and diastolic blood pressure (r = -0.25 and -0.16, P < 0.01 and < 0.05, respectively, for 12 months of treatment), while the trough : peak ratio did not (r = -0.01 to -0.12, NS). A treatment-induced reduction in the left ventricular mass index was related to the smoothness index for systolic and diastolic blood pressure (r = -0.35 and -0.32, P< 0.001 with 12 months of treatment), but not to the corresponding trough : peak ratios., Conclusions: The smoothness index identifies the occurrence of a balanced 24 h blood pressure reduction with treatment and correlates with the favourable effects of treatment on left ventricular hypertrophy better than the commonly used trough : peak ratio.

Objective: To assess whether modifications in the nighttime blood pressure fall caused by antihypertensive treatment predict the regression of end-organ damage of hypertension., Methods: The analysis was performed in patients with essential hypertension and echocardiographically detected left ventricular hypertrophy involved in the SAMPLE study. For each patient, ambulatory blood pressure monitoring and echocardiographic determination of left ventricular mass index were performed at the end of a 4-week wash-out pretreatment period, after 3 and 12 months of treatment with lisinopril or with lisinopril plus hydrochlorothiazide and after a final 4-week placebo period. For each ambulatory blood pressure monitoring the 24 h average, daytime average (0600-2400 h), night-time average (2400-0600 h) and day-night difference was computed. The percentages of dipper and non-dipper patients (i.e. the patients with night blood pressure falls greater and less than 10% of the daytime average, respectively) were also computed., Results: The reproducibility of the day-night difference was low, both for comparison of the pretreatment and final placebo periods (n = 170) and for comparison of the third and the 12th month of treatment (n = 180). The reproducibility of the dipper-non-dipper dichotomy was also low, 35-40% of patients becoming non-dippers if they were dippers and vice versa, both with and without treatment The changes in left ventricular mass index after 12 months of treatment were significantly (P<0.01) related to the changes in 24 h, daytime and night-time blood pressure (r always > 0.33), but this was not the case for the treatment-induced modification of the day-night difference (r= -0.03 and -0.008 for systolic and diastolic blood pressures, respectively)., Conclusions: Our results show that day-night blood pressure changes and the classification of patients into dippers and non-dippers are poorly reproducible over time. It also provides the first prospective evidence that treatment-induced changes in day-night blood pressure difference are not related to treatment-induced regression of left ventricular mass index, thus having a limited clinical significance.

Background: The difference between clinic and ambulatory average daytime blood pressures is frequently taken as a surrogate measure of the 'white-coat effect' (i.e. the pressor reaction triggered in the patient by the physician's visit)., Objective: To assess the reproducibility of this difference and its relationship with clinic and average ambulatory daytime blood pressure levels., Design and Methods: These issues were addressed with two large groups of subjects in whom both clinic and ambulatory blood pressures were measured, namely 783 outpatients with systolic and diastolic essential hypertension [Group 1, aged 50.8+/-9.4 years (mean +/- SD)], participating in standardized Italian trials of antihypertensive drugs, and 506 elderly patients (group 2, age 71+/-7 years) with isolated systolic hypertension, participating in the European Syst-Eur trial., Results: The clinic-daytime blood pressure difference for the essential systolic and diastolic hypertensive patients (group 1) was 13.6+/-14.3 mmHg for systolic and 9.1+/-8.6 mmHg for diastolic blood pressure (P always < 0.01). This difference for the elderly patients with isolated systolic hypertension (group 2) was 21.2+/-16.0 mmHg for systolic and only 1.3+/-10.2 mmHg for diastolic blood pressure (P < 0.01 and P < 0.05, respectively). In both studies little or no systematic clinic-daytime difference could be observed for heart rate. The reproducibility of the clinic-daytime blood pressure difference, tested for 108 essential systolic and diastolic hypertensive patients from group 1 and 128 isolated systolic hypertensives from group 2, was invariably lower than that both of daytime and of clinic blood pressure values. Finally, the clinic-daytime blood pressure difference was progressively higher for increasing levels of clinic blood pressure and progressively lower for higher levels of ambulatory daytime blood pressure., Conclusions: Thus, the clinic-daytime blood pressure difference has a limited reproducibility; depends not only on clinic but also on daytime average blood pressure, which means that its size is a function of the blood pressure criteria employed for selection of the patients in a trial; and is never associated with a systematic clinic-daytime difference in heart rate, which further questions its use as a reliable surrogate measure of the true pressor response induced in the patient by the doctor's visit.

Objective: To investigate whether a clinic-ambulatory blood pressure difference persists with time under active drug treatment or placebo and to determine whether and how it interferes with the evaluation of the efficacy of antihypertensive treatment., Design and Methods: In 382 mild or moderate essential hypertensive patients (mean age +/- SD 51.5 +/- 9.2 years) clinic and ambulatory (SpaceLabs 90207 device) blood pressures were measured twice, under baseline conditions and after 4-8 weeks of antihypertensive treatment by calcium antagonists or angiotensin converting enzyme inhibitors (n = 266) or of placebo administration (n = 116). In each patient the difference between clinic and daytime average blood pressure was taken as a surrogate measure of the magnitude of the 'white-coat effect', separately for systolic and diastolic blood pressures. The changes in this difference induced by treatment and by placebo and the relationship between the blood pressure changes induced by drug treatment and by placebo and the magnitude of the difference before and during treatment or placebo, respectively, were computed., Results: Before drug treatment, the difference was 16.6 +/- 13.6 and 10.1 +/- 7.9 mmHg for systolic and diastolic blood pressures, respectively. During treatment the corresponding values were 11.9 +/- 14.2 and 6.8 +/- 9.2 mmHg; both of the reductions were statistically significant. Both for systolic and for diastolic blood pressure, the reduction in clinic blood pressure caused by treatment was directly related to the clinic-ambulatory difference before treatment, but inversely related to the magnitude of that difference persisting during treatment. The clinic-ambulatory blood pressure difference observed before placebo was attenuated during placebo, the magnitude of the attenuation being similar to that found under drug treatment. No significant difference between clinic and daytime average heart rate was ever observed before and during active treatment or placebo., Conclusions: A considerable clinic-ambulatory blood pressure difference persists during several weeks of antihypertensive treatment, but its magnitude is significantly attenuated. This leads to an overestimation of the effectiveness of antihypertensive treatment when this is assessed by clinic blood pressure measurements only. This overestimation is greater in subjects with an initially greater difference because in these subjects the subsequent attenuation is greater. Because similar phenomena are observed with placebo, the attenuation in the difference during drug treatment is likely to reflect merely habituation to clinic blood pressure measurements with time.

Objective: To investigate whether nocturnal blood pressure fall is blunted in renovascular hypertension and can therefore be used as a diagnostic criterion for this condition., Methods: In 14 renovascular hypertensive patients (age 43.8+/-2.1 years, mean+/-SEM, clinic blood pressure 173.6+/-3.7 mmHg systolic and 109.0+/-2.0 mmHg diastolic) and in 14 age- and blood pressure-matched essential hypertensive controls 24 h ambulatory blood pressure was measured after washout from drug treatment, during angiotensin converting enzyme inhibitor treatment and, in renovascular hypertension, also after percutaneous transluminal renal angioplasty., Results: The 24 h average systolic and diastolic blood pressures were 146.4+/-5.7 and 97.5+/-3.6 mmHg in renovascular and 144.3+/-1.2 and 98.0+/-2.2 mmHg in essential hypertensive patients. The angiotensin converting enzyme inhibitor treatment reduced 24 h average systolic and diastolic blood pressures by 8.5% and 9.7% in the renovascular and by 8.3% and 10.8% in the essential hypertensive group. Greater systolic and diastolic blood pressure reductions (-18.2% and -18.1%) were observed in renovascular hypertensive patients after percutaneous transluminal renal angioplasty. Blood pressure fell by about 10% during the night and the fall was similar in renovascular and in essential hypertensive patients. In the former group, nocturnal hypotension was similar after washout, during angiotensin converting enzyme inhibitor treatment and after percutaneous transluminal renal angioplasty. Similar results were obtained for nocturnal bradycardia., Conclusions: Nocturnal blood pressure fall is equally manifest in renovascular and essential hypertension. The removal of the renal artery stenosis and blood pressure normalization do not enhance this phenomenon. Nocturnal hypotension seems therefore to be unaffected by renovascular hypertension.

Objective: To address several methodological questions related to calculation of trough:peak ratio from 24 h ambulatory blood pressure (BP) recordings., Methods: Data from patients with mild essential hypertension who were included in parallel group (n = 280) or cross-over studies (n = 39) were pooled. 24 h ambulatory BP recordings were available after 2- to 4-week washout from treatment and at the end of a 4- to 8-week period of treatment with calcium antagonists (n = 143), angiotensin converting enzyme inhibitors (n = 103) or placebo (73 patients from parallel group studies and 39 from a cross-over study). Each recording started between 0900 and 1000 h, immediately after the drug or placebo intake during the treatment phase. BP was measured at 15 min intervals during the day and at 15-20 min intervals during the night. Peak changes were calculated from systolic BP and diastolic BP 2-8 h after drug intake, and trough changes from readings taken during the last 4 h of the 24 h., Results: Peak changes induced by drug treatment were progressively reduced when data were averaged over 1, 2, 4 and 6 h. BP reproducibility showed a concomitant increase and the best compromise between correct estimate of peak changes and reproducibility was the average of the adjacent 2 h with the maximal BP fall. Peak and trough (average of last 2 h) changes showed a normal distribution, whereas trough:peak ratios showed non-normal distributions, large scatters and many individual values with no pharmacodynamic significance (namely, much above unity and below zero). Selecting responders to treatment reduced the dispersion and made the trough:peak ratio distribution normal. There was no correlation between trough:peak ratios and changes in BP variability (standard deviation of 24 h mean) induced by treatment. Placebo administration caused no trough but a modest peak fall. Peak changes during placebo also showed a wide scatter and a non-normal distribution, which makes correction with respect to average peak placebo data inappropriate in parallel-group studies. However, placebo correction may be performed for each subject in cross-over studies, leading to a reduction in peak changes and an increase in trough:peak ratio values., Conclusions: When the trough:peak ratio is assessed from ambulatory BP, peak and trough changes should preferably be computed over a 2 h time window. To remove values with no pharmacodynamic significance, the analysis should preferably be conducted only in responders to treatment at peak. Although placebo is accompanied by some peak effect, placebo correction might be appropriate only for individual subjects in cross-over studies.

Objectives: Hypertension is known to decrease arterial elasticity and systemic compliance. However, the arterial tree is not a homogeneous system, and whether a distal medium-sized artery such as the radial artery behaves like proximal arteries has not been determined. The aims of the present study were, first, to characterize non-invasively the mechanical properties of the radial artery through the determination of the pressure-diameter curve, the distensibility-pressure curve and the compliance-pressure curve, and, secondly, to compare untreated hypertensive patients with normotensive subjects., Methods: A new high-precision echo-tracking device was developed which allows the diameter of peripheral arteries to be measured continuously. By relating the changes in internal diameter (cross-sectional changes) to those in blood pressure, the cross-sectional arterial compliance could be determined., Participants: Seventy-eight untreated mild or moderate essential hypertensive patients aged 24-78 years were compared with 44 normotensive subjects aged 22-81 years. In order to increase the database and provide independent assessments of the variables examined, the cross-sectional study was performed independently using a standardized procedure in three different research centres., Results: The major finding was that diameter, distensibility and compliance of the radial artery of hypertensive patients were not significantly different from those of normotensive controls when the two populations were studied at their mean arterial pressure. Furthermore, when the two populations were compared for the same level of blood pressure, using distensibility--and compliance--pressure curves, it was clear that isobaric distensibility and compliance of hypertensives were not significantly lower than those of normotensives, being either unchanged or higher., Conclusions: These findings are in contrast with the well-known decrease in compliance of proximal large arteries due to hypertension. Whether such a difference between proximal large arteries and distal medium-sized arteries may be related to the structural vascular changes observed with long-standing hypertension is still difficult to analyse in humans, and requires further investigation.

Objective: To assess the reproducibility of average hourly blood pressure values obtained by 24-h non-invasive ambulatory monitoring., Patients: Fifteen outpatients with essential hypertension. In all subjects antihypertensive treatment was withdrawn for 4 weeks before and during the 4 weeks of the study., Methods: The 24-h blood pressure was monitored by a SpaceLabs 5300 device (four readings per hour during the day and three readings per hour during the night) twice, at a 4-week interval. Systolic (SBP) and diastolic blood pressure (DBP) were averaged for each hour and for the whole 24-h period, and hourly and 24-h reproducibility was quantified by the standard deviation of the mean difference (SDD) between the values obtained in the two recordings., Results: The SDD of hourly SBP and DBP was much greater than that of the 24-h values and ranged widely between the hours of recording. The SDD of hourly SBP and DBP were also variably greater than the SDD of the 24-h value in another 14 untreated essential hypertensives in whom 24-h ambulatory blood pressure was monitored intra-arterially twice at a 4-week interval to calculate hourly average blood pressure on thousands rather than on three or four values per hour., Conclusion: Reproducibility is less for hourly than for 24-h average blood pressure. This feature (which probably depends on behavioural differences between two recordings) suggests that ambulatory blood pressure measurement partly loses its advantages for reproducibility and reduction in trial size if the results are analysed over hourly periods.

Objective: To test the hypothesis that heavy smoking is associated with a persistent increase in blood pressure., Design: In 10 normotensive smokers asked to smoke one cigarette every 15 min for 1 h, blood pressure and heart rate were continuously monitored during the smoking period and during the preceding non-smoking hour. In six other normotensive smokers asked to smoke two cigarettes per hour throughout the whole day, blood pressure and heart rate were monitored non-invasively in ambulatory conditions for 8 h (0900-1700 h). Blood pressure monitoring was repeated during a non-smoking day., Methods: Beat-to-beat blood pressure and heart rate were monitored at rest by means of the Finapres device. Blood pressure signal was sampled at 165 Hz by a computer to calculate hourly data. Ambulatory blood pressure and heart rate were measured once every 10 min., Results: In resting conditions, the first cigarette caused an immediate and marked increase in blood pressure and heart rate, and the peak blood pressure and heart rate achieved were similar for the remaining three cigarettes. In each instance, the hemodynamic effects were so prolonged that throughout the smoking hour, blood pressure and heart rate were persistently higher than during the non-smoking hour. The standard deviations of systolic and diastolic blood pressure and heart rate were also higher during the smoking hour, indicating an increase in blood pressure and heart rate variability. In the six ambulant smokers, daytime blood pressure and heart rate were also persistently higher during smoking than during non-smoking., Conclusions: Heavy smoking is associated with a persistent rise in blood pressure and also with an increase in blood pressure variability. These effects (which may escape clinic blood pressure measurements performed during non-smoking) may account for some of the smoking-related cardiovascular risk.

Objective: In essential hypertension, captopril attenuates forearm vasoconstriction reflexly induced by deactivation of cardiopulmonary and arterial baroreceptors, thus exerting a sympathomoderating effect. We investigated whether this is a common effect of angiotensin converting enzyme (ACE) inhibitors., Methods and Design: Cardiopulmonary and arterial baroreceptors were deactivated by progressively reducing central venous pressure (CVP) through progressively greater lower body negative pressures in eight untreated mild essential hypertensives on a moderately low-sodium diet (50 mmol/l per day). This deactivation was performed after oral administration of the non-sulphidrylic ACE inhibitor benazepril (10 mg) and placebo according to a double-blind randomized crossover experimental design., Results: After placebo, the reduction in CVP increased forearm vascular resistance (FVR; mean arterial pressure: plethysmographic forearm blood flow ratio). After benazepril, baseline blood pressure (beat-to-beat finger pressure) and FVR were significantly reduced whilst plasma angiotensin II was suppressed and PRA increased (both measured by radioimmunoassay). The FVR increases induced by progressive CVP reduction were less than after placebo administration, and the overall difference was statistically significant. Benazepril did not affect the reflex FVR reduction observed by increasing CVP through leg raising, nor the reflex changes in plasma norepinephrine measured by high-performance liquid chromatography accompanying the changes in FVR., Conclusions: Benazepril attenuates sympathetic vasoconstriction as does captopril. This effect (which is mainly operative during an increased sympathetic drive and exerted through a reduction of adrenoceptor responsiveness) is thus likely to be a class- rather than a compound-related feature.

Twenty-four-hour mean ambulatory blood pressure has been shown to be devoid of a placebo effect. However, whether this is the case for different periods within the 24 h has not been established. In 27 essential hypertensive outpatients, blood pressure was measured in the doctor's office and by 24-h ambulatory blood pressure monitoring after a 3-week wash-out period from antihypertensive treatment (Control) and following 4 weeks of placebo administration. Office systolic and diastolic blood pressures were reduced by placebo (-9.6 +/- 2.6 and -3.1 +/- 1.7 mmHg, P less than 0.01, respectively), whereas 24-h mean blood pressure values did not show any significant change. This was not the case for all 24-h subperiods, however, because during the initial 8h, systolic and diastolic blood pressures were slightly (-4.1 +/- 9.2 and -2.5 +/- 6.4 mmHg) but significantly (P less than 0.05) lower during placebo than during control. Similar findings were obtained in 14 additional essential hypertensive patients in whom neither placebo nor any other treatment was employed between the two office and 24-h blood pressure measurements. Thus, placebo treatment is associated with a blood pressure reduction in the initial portion of the ambulatory blood pressure profile, probably because of an attenuation of an initial transient alerting response to the procedure. Although so small as to leave the 24-h blood pressure mean unaffected, this may lead to some overestimation of the antihypertensive effect of treatment during an appreciable portion of the circadian blood pressure tracing.