The HYPEDIA study aimed at evaluating the implementation of the 2018 European guidelines for treating hypertension in primary care. A nationwide prospective non-interventional cross-sectional study was performed in consecutive untreated or treated hypertensives recruited mainly in primary care in Greece. Participants' characteristics, office blood pressure (BP) (triplicate automated measurements, Microlife BPA3 PC) and treatment changes were recorded on a cloud platform. A total of 3,122 patients (mean age 64 ± 12.5 [SD] years, 52% males) were assessed by 181 doctors and 3 hospital centers. In 772 untreated hypertensives (25%), drug treatment was initiated in the majority, with monotherapy in 53.4%, two-drug combination in 36.3%, and three drugs in 10.3%. Angiotensin receptor blocker (ARB) monotherapy was initiated in 30%, ARB/calcium channel blocker (CCB) 20%, ARB/thiazide 8%, angiotensin converting enzyme inhibitor (ACEi)-based 19%. Of the combinations used, 97% were in single-pill. Among 977 treated hypertensives aged <65 years, 79% had BP ≥ 130/80 mmHg (systolic and/or diastolic), whereas among 1,373 aged ≥65 years, 66% had BP ≥ 140/80 mmHg. ARBs were used in 69% of treated hypertensives, CCBs 47%, ACEis 19%, diuretics 39%, beta-blockers 19%. Treatment modification was decided in 53% of treated hypertensives aged <65 years with BP ≥ 130/80 mmHg and in 62% of those ≥65 years with BP ≥ 140/80 mmHg. Renin-angiotensin system blocker-based therapy constitutes the basis of antihypertensive drug treatment in most patients in primary care, with wide use of single-pill combinations. In almost half of treated uncontrolled hypertensives, treatment was not intensified, suggesting suboptimal implementation of the guidelines and possible physician inertia.

Clinically validated, automated arm-cuff blood pressure measuring devices (BPMDs) are recommended for BP measurement. However, most BPMDs available for purchase by consumers globally are not properly validated. This is a problem because non-validated BPMDs are less accurate and precise than validated ones, and therefore if used clinically could lead to misdiagnosis and mismanagement of BP. In response to this problem, several validated device lists have been developed, which can be used by clinicians and consumers to identify devices that have passed clinical validation testing. The purpose of this review is to describe the resources that are available for finding validated BPMDs in different world regions, to identify the differences between validated device lists, and describe current gaps and challenges. How to use validated BPMDs properly is also summarised.

Automated 'oscillometric' blood pressure (BP) measuring devices (BPMDs) were developed in the 1970s to replace manual auscultatory BP measurement by mercury sphygmomanometer. Automated BPMDs that have passed accuracy testing versus a reference auscultatory sphygmomanometer using a scientifically accepted validation protocol are recommended for clinical use globally. Currently, there are many thousands of unique automated BPMDs manufactured by hundreds of companies, with each device using proprietary algorithms to estimate BP and using a method of operation that is largely unchanged since inception. Validated automated BPMDs provide similar BP values to those recorded using manual auscultation albeit with potential sources of error mostly associated with using empirical algorithms to derive BP from waveform pulsations. Much of the work to derive contemporary BP thresholds and treatment targets used to manage cardiovascular disease risk was obtained using automated BPMDs. While there is room for future refinement to improve accuracy for better individual risk stratification, validated BPMDs remain the recommended standard for office and out-of-office BP measurement to be used in hypertension diagnosis and management worldwide.

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.

Current hypertension guidelines recommend using the average values of several blood pressure (BP) readings obtained both in and out of the office for the diagnosis and management of hypertension. In-office BP measurement using an upper-arm cuff constitutes the evidence-based reference method for current BP classification and treatment targets. However, out-of-office BP evaluation using 24 h ambulatory or home BP monitoring is recommended by all major medical associations for obtaining further insights into the BP profile of an individual and how it relates to their daily activities. Importantly, the highly variable nature of office and out-of-office BP readings has been widely acknowledged, including the association of BP variability with cardiovascular outcomes. However, to date, the implications of BP variability on cardiovascular outcomes have largely been ignored, with limited application in clinical practice. Novel cuffless wearable technologies might provide a detailed assessment of the 24 h BP profile and behaviour over weeks or months. These devices offer many advantages for researchers and patients compared with traditional BP monitors, but their accuracy and utility remain uncertain. In this Review, we outline and compare conventional and novel methods and techniques for assessing average BP levels and BP variability, and reflect on the utility and potential of these methods for improving the treatment and management of patients with hypertension.

Cuffless blood pressure (BP) measurement has become a popular field due to clinical need and technological opportunity. However, no method has been broadly accepted hitherto. The objective of this review is to accelerate progress in the development and application of cuffless BP measurement methods. We begin by describing the principles of conventional BP measurement, outstanding hypertension/hypotension problems that could be addressed with cuffless methods, and recent technological advances, including smartphone proliferation and wearable sensing, that are driving the field. We then present all major cuffless methods under investigation, including their current evidence. Our presentation includes calibrated methods (i.e., pulse transit time, pulse wave analysis, and facial video processing) and uncalibrated methods (i.e., cuffless oscillometry, ultrasound, and volume control). The calibrated methods can offer convenience advantages, whereas the uncalibrated methods do not require periodic cuff device usage or demographic inputs. We conclude by summarizing the field and highlighting potentially useful future research directions.

RXRs are nuclear receptors acting as transcription regulators that control key cellular processes in all tissues. All type II nuclear receptors require RXRs for transcriptional activity by forming heterodimeric complexes. Recent whole-exome sequencing studies have identified the RXRα S427F hotspot mutation in 5% of the bladder cancer patients, which is always located at the interface of RXRα with its obligatory dimerization partners. Here, we show that mutation of S427 deregulates transcriptional activity of RXRα dimers, albeit with diverse allosteric mechanisms of action depending on its dimeric partner. S427F acts by allosteric mechanisms, which range from inducing the collapse of the binding pocket to allosteric stabilization of active co-activator competent RXRα states. Unexpectedly, RXR S427F heterodimerization leads to either loss- or gain-of-function complexes, in both cases likely compromising its tumor suppressor activity. This is the first report of a cancer-associated single amino acid substitution that affects the function of the mutant protein variably depending on its dimerization partner.

The present study compared the blood pressure variability (BPV) among office (OBP), home (HBP), and ambulatory blood pressure (ABP) measurements and assessed their determinants, as well as their agreement in identifying individuals with high BPV. Individuals attending a hypertension clinic had OBP measurements (2-3 visits) and underwent HBP monitoring (3-7 days, duplicate morning and evening measurements) and ABP monitoring (24 h, 20-min intervals). BPV was quantified using the standard deviation (SD), coefficient of variation (CV), and variability independent of the mean (VIM) using all BP readings obtained by each method. A total of 626 participants were analyzed (age 52.8 ± 12.0 years, 57.7% males, 33.1% treated). Systolic BPV was usually higher than diastolic BPV, and out-of-office BPV was higher than office BPV, with ambulatory BPV giving the highest values. BPV was higher in women than men, yet it was not different between untreated and treated individuals. Associations among BPV indices assessed using different measurement methods were weak (r 0.1-0.3) but were stronger between out-of-office BPV indices. The agreement between methods in detecting individuals with high BPV was low (30-40%) but was higher between out-of-office BPV indices. Older age was an independent determinant of increased OBP variability. Older age, female sex, smoking, and overweight/obesity were determinants of increased out-of-office BPV. These data suggest that BPV differs with different BP measurement methods, reflecting different pathophysiological phenomena, whereas the selection of the BPV index is less important. Office and out-of-office BP measurements appear to be complementary methods in assessing BPV.

Several novel cuffless wearable devices and smartphone applications claiming that they can measure blood pressure (BP) are appearing on the market. These technologies are very attractive and promising, with increasing interest among health care professionals for their potential use. Moreover, they are becoming popular among patients with hypertension and healthy people. However, at the present time, there are serious issues about BP measurement accuracy of cuffless devices and the 2021 European Society of Hypertension Guidelines on BP measurement do not recommend them for clinical use. Cuffless devices have special validation issues, which have been recently recognized. It is important to note that the 2018 Universal Standard for the validation of automated BP measurement devices developed by the American Association for the Advancement of Medical Instrumentation, the European Society of Hypertension, and the International Organization for Standardization is inappropriate for the validation of cuffless devices. Unfortunately, there is an increasing number of publications presenting data on the accuracy of novel cuffless BP measurement devices, with inadequate methodology and potentially misleading conclusions. The objective of this review is to facilitate understanding of the capabilities and limitations of emerging cuffless BP measurement devices. First, the potential and the types of these devices are described. Then, the unique challenges in evaluating the BP measurement accuracy of cuffless devices are explained. Studies from the literature and computer simulations are employed to illustrate these challenges. Finally, proposals are given on how to evaluate cuffless devices including presenting and interpreting relevant study results.

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.