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Objectives: Greater vulnerability of Black vs. White individuals to cardiovascular disease (CVD) and chronic kidney disease (CKD) is well charted in the United States, but studies involving sub-Saharan blacks are scarce., Methods: Baseline data (2021-2024) were collected in 168 sub-Saharan Blacks and 93 European Whites in an ongoing clinical trial (NCT04299529), using standardized patient selection criteria. Data included clinical and biochemical risk factors, ECG and echocardiographic traits, Framingham CVD risk, CKD grades (KDIGO 2024), self-assessed symptoms (WHO questionnaire), and urinary proteomic profiles predictive of left ventricular dysfunction (LVD) and CKD, HF1, and CKD273, respectively. Racial comparisons rested on unadjusted and multivariable-adjusted analyses., Results: Despite being younger (60.4 vs. 68.3 years), blacks had a worse risk profile, as evidenced by higher diabetes prevalence, higher BMI, faster heart rate, unfavourable serum cholesterol fractions, lower estimated glomerular filtration rate, microalbuminuria, and sedentary lifestyle. This resulted in blacks having higher 10-year CVD risk, higher heart age (index of vascular ageing with chronological age as reference), and a worse CKD grades. In both races, CKD273 increased with CKD grade, but CKD273 and HF1 were not different by race. These observations were robust in subgroup and adjusted analyses., Conclusion: This study did not differentiate host (genetic, molecular, and pathogenic) from environmental drivers of disease. Nonetheless, the findings call for a multipronged and comprehensive implementation of innovative health policies in sub-Saharan countries. Education, research, empowerment of stakeholders, and international learned societies connecting experts from a wide array of disciplines should vigorously sustain this effort., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Blood pressure (BP) is a key contributor to the lifetime risk of preclinical organ damage and cardiovascular disease. Traditional clinic-based BP readings are typically measured infrequently and under standardized/resting conditions and therefore do not capture BP values during normal everyday activity. Therefore, current hypertension guidelines emphasize the importance of incorporating out-of-office BP measurement into strategies for hypertension diagnosis and management. However, conventional home and ambulatory BP monitoring devices use the upper-arm cuff oscillometric method and only provide intermittent BP readings under static conditions or in a limited number of situations. New innovations include technologies for BP estimation based on processing of sensor signals supported by artificial intelligence tools, technologies for remote monitoring, reporting and storage of BP data, and technologies for BP data interpretation and patient interaction designed to improve hypertension management ("digital therapeutics"). The number and volume of data relating to new devices/technologies is increasing rapidly and will continue to grow. This International Society of Hypertension position paper describes the new devices/technologies, presents evidence relating to new BP measurement techniques and related indices, highlights standard for the validation of new devices/technologies, discusses the reliability and utility of novel BP monitoring devices, the association of these metrics with clinical outcomes, and the use of digital therapeutics. It also highlights the challenges and evidence gaps that need to be overcome before these new technologies can be considered as a user-friendly and accurate source of novel BP data to inform clinical hypertension management strategies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: We undertook time-stratified analyses of the National Health and Nutrition Examination Survey in the US to assess time trends (1999-2020) in the associations of blood lead (BL) with blood pressure, mortality, the BL-associated population attributable fraction (PAF)., Methods: Vital status of participants, 20-79 years old at enrolment, was ascertained via the National Death Index. Regressions, mediation analyses and PAF were multivariable adjusted and standardized to 2020 US Census data., Results: In time-stratified analyses, BL decreased from 1.76 μg/dl in 1999-2004 to 0.93 μg/dl in 2017-2020, while the proportion of individuals with BL < 1 μg/dl increased from 19.2% to 63.0%. Total mortality was unrelated to BL (hazard ratio (HR) for a fourfold BL increment: 1.05 [95% confidence interval, CI: 0.93-1.17]). The HR for cardiovascular death was 1.44 (1.01-2.07) in the 1999-2000 cycle, but lost significance thereafter. BL was directly related to cardiovascular mortality, whereas the indirect BL pathway via BP was not significant. Low socioeconomic status (SES) was directly related to BL and cardiovascular mortality, but the indirect SES pathway via BL lost significance in 2007-2010. From 1999-2004 to 2017-2020, cardiovascular PAF decreased ( P  < 0.001) from 7.80% (0.17-14.4%) to 2.50% (0.05-4.68%) and number of lead-attributable cardiovascular deaths from 53 878 (1167-99 253) to 7539 (160-14 108)., Conclusion: Due to implementation of strict environmental policies, lead exposure is no longer associated with total mortality, and the mildly increased cardiovascular mortality is not associated with blood lead via blood pressure in the United States., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Blood pressure (BP) variability (BPV) can be assessed using office (OBP), home (HBP), or ambulatory BP (ABP) measurements. This analysis investigated the association and agreement between OBP, HBP, and ABP measurements for BPV assessment at baseline and 10 weeks after initiating antihypertensive drug therapy., Methods: Untreated hypertensive patients with elevated BPV were randomized to receive an angiotensin-converting enzyme inhibitor (ramipril) or a calcium channel blocker (nifedipine GITS) in a 10-week, open-label, blinded-end point study. BPV was assessed using standard deviation (SD) and coefficient of variation (CV) (reading-to-reading analyses)., Results: Data from 146 participants from three research centers (Athens/Greece; Milan/Italy; Shanghai/China) were analyzed [mean age 53 ± 10 (SD) years, male individuals 60%, baseline systolic OBP, HBP, and 24 h ABP 144 ± 9, 138 ± 10, and 143 ± 10 mmHg, respectively]. Post-treatment minus pre-treatment systolic CV difference was: OBP: 0.3%, P  = 0.28; HBP: -0.2%, P  = 0.20; 24 h ABP: 1.1%, P  < 0.001. Home and ambulatory (not office) BPV indices presented weak-to-moderate correlation, both before and during treatment (range of coefficients 0.04-0.33). The correlation coefficient between systolic HBP and awake ABP CV was 0.21 and 0.28 before and during treatment, respectively ( P  < 0.05/< 0.001, respectively). Home and ambulatory (not office) BPV indices presented slight-to-fair agreement (range 64-73%) in detecting participants with high systolic BPV (top quartile of respective distributions) both before and during treatment (kappa range 0.04-0.27)., Conclusion: These data showed a weak-to-moderate association between out-of-office (but not office) BPV indices both before and during BP-lowering treatment, with reasonable agreement in detecting individuals with high BPV. Out-of-office BP measurements provide more similar and consistent BPV information than office measurements., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In China, the prevalence of hypertension is high and the use of combination antihypertensive therapy is low, which contributes to inadequate blood pressure (BP) control. The availability of simplified treatments combining complementary BP-lowering agents may help more patients achieve their goals., Methods: This Phase III, multicenter, randomized, double-blind, noninferiority study included Chinese adults with mild-to-moderate hypertension. Following a 1-month run-in on perindopril/indapamide bi-therapy, patients with uncontrolled systolic/diastolic BP (≥140/90 mmHg) were randomized to perindopril 5 mg/indapamide 1.25 mg/amlodipine 5 mg (Per/Ind/Aml) single-pill combination (SPC) or perindopril 4 mg/indapamide 1.25 mg plus amlodipine 5 mg (Per/Ind + Aml) for 6 months. Uptitration was permitted from month 2 onwards. The primary efficacy objective was the noninferiority of Per/Ind/Aml in lowering office systolic BP at 2 months. The secondary objectives included the effectiveness of SPC on diastolic BP, uptitration efficacy, and office BP control (systolic/diastolic <140/90 mmHg). A subgroup of patients participated in 24-h ambulatory BP monitoring (ABPM)., Results: A total of 532 patients were randomized: Per/Ind/Aml ( n  = 262) and Per/Ind + Aml ( n  = 269). Overall, the mean (±SD) age was 55.7 ± 8.8 years, 60.7% were male, and the mean office systolic/diastolic BP at baseline on Per/Ind was 150.4/97.2 mmHg. Systolic BP decreased in both groups at 2 months from baseline: -14.99 ± 14.46 mmHg Per/Ind/Aml versus -14.49 ± 12.87 mmHg Per/Ind +Aml. A predefined noninferiority margin of 4 mmHg was observed ( P  < 0.001). The effectiveness of the Per/Ind/Aml SPC was also demonstrated for all secondary endpoints. ABPM demonstrated sustained BP control over 24 h. Both treatments were well tolerated., Conclusions: Per/Ind/Aml is an effective substitute for Per/Ind + Aml, providing at least equivalent BP control over 24 h in a single pill, with comparable safety., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: We investigated seasonal variation in ambulatory blood pressure control in hypertensive patients on clinic blood pressure-guided antihypertensive treatment., Methods: The study participants were hypertensive patients enrolled in an 8-week therapeutic study. Antihypertensive treatment was initiated with long-acting dihydropyridine calcium channel blockers amlodipine 5 mg/day or the gastrointestinal therapeutic system (GITS) formulation of nifedipine 30 mg/day, with the possible up-titration to amlodipine 10 mg/day or nifedipine-GITS 60 mg/day at 4 weeks of follow-up., Results: The proportion of up-titration to higher dosages of antihypertensive drugs at 4 weeks of follow-up was higher in patients who commenced treatment in autumn/winter ( n  = 302) than those who commenced treatment in spring/summer ( n  = 199, 24.5 vs. 12.0%, P  < 0.001). The control rate of clinic blood pressure, however, was lower in autumn/winter than in spring/summer at 4 (56.7 vs. 70.7%, P  = 0.003) and 8 weeks of follow-up (52.5 vs. 74.9%, P  < 0.001). At 8 weeks, patients who commenced treatment in autumn/winter, compared with those who commenced treatment in spring/summer, had a significantly ( P ≤0.03) smaller daytime (mean between-season difference -3.2/-2.8 mmHg) but greater nighttime SBP/DBP reduction (3.6/1.6 mmHg). Accordingly, at 8 weeks, the prevalence of nondippers was significantly ( P  < 0.001) higher in spring/summer than in autumn/winter for both SBP (54.8 vs. 30.0%) and DBP (53.4 vs. 28.8%)., Conclusion: Clinic blood pressure-guided antihypertensive treatment requires a higher dosage of medication in cold than warm seasons, which may have led to over- and under-treatment of nighttime blood pressure, respectively., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: There is intense effort to develop cuffless blood pressure (BP) measuring devices, and several are already on the market claiming that they provide accurate measurements. These devices are heterogeneous in measurement principle, intended use, functions, and calibration, and have special accuracy issues requiring different validation than classic cuff BP monitors. To date, there are no generally accepted protocols for their validation to ensure adequate accuracy for clinical use., Objective: This statement by the European Society of Hypertension (ESH) Working Group on BP Monitoring and Cardiovascular Variability recommends procedures for validating intermittent cuffless BP devices (providing measurements every >30 sec and usually 30-60 min, or upon user initiation), which are most common., Validation Procedures: Six validation tests are defined for evaluating different aspects of intermittent cuffless devices: static test (absolute BP accuracy); device position test (hydrostatic pressure effect robustness); treatment test (BP decrease accuracy); awake/asleep test (BP change accuracy); exercise test (BP increase accuracy); and recalibration test (cuff calibration stability over time). Not all these tests are required for a given device. The necessary tests depend on whether the device requires individual user calibration, measures automatically or manually, and takes measurements in more than one position., Conclusion: The validation of cuffless BP devices is complex and needs to be tailored according to their functions and calibration. These ESH recommendations present specific, clinically meaningful, and pragmatic validation procedures for different types of intermittent cuffless devices to ensure that only accurate devices will be used in the evaluation and management of hypertension., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

Background: Homocysteine (Hcy) is an independent risk factor for cardiovascular diseases, and elevated plasma Hcy levels could aggravate vascular injury in hypertension. Hyperhomocysteinemia can change the methylation status of global DNA and specific genes. In the present study, we aim to examine the comprehensive influence of Hcy levels on DNA methylation status in patients with hypertension., Methods: Epigenome-wide methylation profiles of the peripheral leukocyte DNA of 218 patients with hypertension were analyzed using the Illumina Infinium Methylation EPIC BeadChip. Differentially methylated positions (DMPs) associated with serum Hcy levels were identified by mixed linear regression with the adjustment of potential confounders. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to determine the potential functions of the identified DMPs. The association between the methylation level of DMPs and carotid-femoral pulse wave velocity (Cf-PWV) was also analyzed., Results: Five DMPs at cg13169662, cg03179312, cg21976560, cg25262698, and cg09433843 showed significant association with serum Hcy levels (false discovery rate-corrected P  < 0.05). An additional six CpG sites met the threshold for suggestive significance ( P  < 1 × 10 -6 ), among which three DMPs (cg25781123, cg26463106, and cg06679221) were annotated to THUMPD3 . Furthermore, the methylation levels of cg13169662 and cg25262698 (RPRD1A) were significantly associated with Cf-PWV., Conclusion: Our results suggest that Hcy could induce DNA methylation alteration in patients with hypertension. Further functional research is warranted to elucidate the concrete role of DMPs in hypertension., (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.)

Objective: Automated cuff blood pressure (BP) devices are widely used for ambulatory, home, and office BP measurement. However, an automated device, which is accurate in the general adult population may be inaccurate in some special populations. A 2018 Collaborative Statement by the US Association for the Advancement of Medical Instrumentation, the European Society of Hypertension, and the International Organization for Standardization (ISO) considered three special populations requiring separate validation (age <3 years, pregnancy, and atrial fibrillation). An ISO Task Group was appointed to identify evidence for additional special populations., Method: Evidence on potential special populations was identified from the STRIDE BP database, which performs systematic PubMed searches for published validation studies of automated cuff BP monitors. Devices that passed in a general population, but failed in potential special populations were identified., Results: Of 338 publications (549 validations, 348 devices) in the STRIDE BP database, 29 publications (38 validations, 25 devices) involved 4 potential special populations: (i) age 12-18 years: 3 of 7 devices failed but passed in a general population; (ii) age more than 65 years: 1 of 11 devices failed but passed in a general population; (iii) diabetes type-2: 4 devices (all passed); (iv) chronic kidney disease: 2 of 7 devices failed but passed in a general population., Conclusion: Some evidence suggest that the automated cuff BP devices may have different accuracy in adolescents and in patients with chronic kidney disease than in the general population. More research is needed to confirm these findings and investigate other potential special populations., (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: The aim of this study was to investigate the clinical characteristics of renal artery fibromuscular dysplasia (FMD) in patients in China and identify the cure rate of hypertension after angioplasty., Methods: Consecutive hypertensive patients with renal artery stenosis caused by FMD who underwent catheter-based angiography, and were followed at two Chinese referral centres, were retrospectively analysed. All patients underwent a detailed investigation, including demographic characteristics, clinical characteristics, biochemical sampling, Doppler ultrasonography of carotid arteries, magnetic resonance angiography (MRA) of the intracranial artery, and CTA or MRA of the abdominal artery and catheter-based renal angiography. Patients were routinely followed up at 1 month, 6 months and every year after the procedure., Results: Among 245 study participants, with a mean diagnosed age of 26.9 ± 9.9 years, 137 (55.9%) were women, and 38 (15.5%) were children. All patients were diagnosed with hypertension at a mean age of 23.4 ± 8.4 years. There were 73.5% focal and 15.2% multivessel cases. Aneurysms, arterial dissections and total occlusions were found in 21.6, 4.1 and 12.2% of patients, respectively. Patients with multifocal FMD were older (26.0 vs. 23.7 years, P  = 0.021) and more often female (70.8 vs. 50.6%, P  = 0.004). Among children with renal FMD, 55.2% were men, and 86.8% were focal. After a median follow-up of 7.0 years, multifocal FMD had a higher cure rate of hypertension than focal FMD after revascularization (71.7 vs. 55.8%, P  = 0.032)., Conclusion: In a cohort of mostly young Chinese patients, the prevalence of hypertension associated with renal FMD is similar in both sexes. Focal FMDs were more frequent than the multifocal ones and, after angioplasty, were associated with a worse blood pressure outcome., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The role of pulse pressure (PP) 'widening' at older and younger age as a cardiovascular risk factor is still controversial. Mean PP, as determined from repeated blood pressure (BP) readings, can be expressed as a sum of two components: 'elastic PP' (elPP) and 'stiffening PP' (stPP) associated, respectively, with stiffness at the diastole and its relative change during the systole. We investigated the association of 24-h ambulatory PP, elPP, and stPP ('PP variables') with mortality and composite cardiovascular events in different age classes., Method: Longitudinal population-based cohort study of adults with baseline observations that included 24-h ambulatory BP. Age classes were age 40 or less, 40-50, 50-60, 60-70, and over 70 years. Co-primary endpoints were total mortality and composite cardiovascular events. The relative risk expressed by hazard ratio per 1SD increase for each of the PP variables was calculated from multivariable-adjusted Cox regression models., Results: The 11 848 participants from 13 cohorts (age 53 ± 16 years, 50% men) were followed for up for 13.7 ± 6.7 years. A total of 2946 participants died (18.1 per 1000 person-years) and 2093 experienced a fatal or nonfatal cardiovascular event (12.9 per 1000 person-years). Mean PP, elPP, and stPP were, respectively, 49.7, 43.5, and 6.2 mmHg, and elPP and stPP were uncorrelated ( r  = -0.07). At age 50-60 years, all PP variables displayed association with risk for almost all outcomes. From age over 60 years to age over 70 years, hazard ratios of of PP and elPP were similar and decreased gradually but differently for pulse rate lower than or higher than 70 bpm, whereas stPP lacked predictive power in most cases. For age 40 years or less, elPP showed protective power for coronary events, whereas stPP and PP predicted stroke events. Adjusted and unadjusted hazard ratio variations were similar over the entire age range., Conclusion: This study provides a new basis for associating PP components with outcome and arterial properties in different age groups and at different pulse rates for both old and young age. The similarity between adjusted and unadjusted hazard ratios supports the clinical usefulness of PP components but further studies are needed to assess the prognostic significance of the PP components, especially at the young age., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Even though it has been more than a decade since renal denervation (RDN) was first used to treat hypertension and an intense effort on researching this therapy has been made, it is still not clear how RDN fits into the antihypertensive arsenal. There is no question that RDN lowers blood pressure (BP), it does so to an extent at best corresponding to one antihypertensive drug. The procedure has an excellent safety record. However, it remains clinically impossible to predict whose BP responds to RDN and whose does not. Long-term efficacy data on BP reduction are still unconvincing despite the recent results in the SPYRAL HTN-ON MED trial; experimental studies indicate that reinnervation is occurring after RDN. Although BP is an acceptable surrogate endpoint, there is complete lack of outcome data with RDN. Clear indications for RDN are lacking although patients with resistant hypertension, those with documented increase in activity of the sympathetic system and perhaps those who desire to take fewest medication may be considered., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Antihypertensive drug therapy is one of the most efficient medical interventions for preventing disability and death globally. Most of the evidence supporting its benefits has been derived from outcome trials with morning dosing of medications. Accumulating evidence suggests an adverse prognosis associated with night-time hypertension, nondipping blood pressure (BP) profile and morning BP surge, with increased incidence of cardiovascular events during the first few morning hours. These observations provide justification for complete 24-h BP control as being the primary goal of antihypertensive treatment. Bedtime administration of antihypertensive drugs has also been proposed as a potentially more effective treatment strategy than morning administration. This Position Paper by the International Society of Hypertension reviewed the published evidence on the clinical relevance of the diurnal variation in BP and the timing of antihypertensive drug treatment, aiming to provide consensus recommendations for clinical practice. Eight published outcome hypertension studies involved bedtime dosing of antihypertensive drugs, and all had major methodological and/or other flaws and a high risk of bias in testing the impact of bedtime compared to morning treatment. Three ongoing, well designed, prospective, randomized controlled outcome trials are expected to provide high-quality data on the efficacy and safety of evening or bedtime versus morning drug dosing. Until that information is available, preferred use of bedtime drug dosing of antihypertensive drugs should not be routinely recommended in clinical practice. Complete 24-h control of BP should be targeted using readily available, long-acting antihypertensive medications as monotherapy or combinations administered in a single morning dose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Many cuffless blood pressure (BP) measuring devices are currently on the market claiming that they provide accurate BP measurements. These technologies have considerable potential to improve the awareness, treatment, and management of hypertension. However, recent guidelines by the European Society of Hypertension do not recommend cuffless devices for the diagnosis and management of hypertension., Objective: This statement by the European Society of Hypertension Working Group on BP Monitoring and Cardiovascular Variability presents the types of cuffless BP technologies, issues in their validation, and recommendations for clinical practice., Statements: Cuffless BP monitors constitute a wide and heterogeneous group of novel technologies and devices with different intended uses. Cuffless BP devices have specific accuracy issues, which render the established validation protocols for cuff BP devices inadequate for their validation. In 2014, the Institute of Electrical and Electronics Engineers published a standard for the validation of cuffless BP devices, and the International Organization for Standardization is currently developing another standard. The validation of cuffless devices should address issues related to the need of individual cuff calibration, the stability of measurements post calibration, the ability to track BP changes, and the implementation of machine learning technology. Clinical field investigations may also be considered and issues regarding the clinical implementation of cuffless BP readings should be investigated., Conclusion: Cuffless BP devices have considerable potential for changing the diagnosis and management of hypertension. However, fundamental questions regarding their accuracy, performance, and implementation need to be carefully addressed before they can be recommended for clinical use., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Guidelines differed on the required number of blood pressure (BP) readings for accurate BP assessment. We, therefore, compared the mean of the first two BP readings with the overall mean of three readings in the diagnosis of hypertension., Methods: BP was measured three times consecutively with a 1 min interval using a validated automated electronic BP monitor in volunteers aged at least 18 years. The mean of the first and second BP readings was compared with the mean of the three blood pressure readings for the diagnostic accuracy of hypertension., Results: Of the 77 520 study participants, 65.2 and 25.2% had a SBP or DBP difference at least 5 mmHg and at least 10 mmHg between the first and second BP readings, respectively. Regardless whether the BP difference between the first two BP readings was at least 5 mmHg or at least 10 mmHg for systolic and diastolic alone or both, significant (P < 0.0001) SBP/DBP differences between the mean of the first two BP readings and the overall mean of three readings were observed with an absolute value up to 1.28/1.11 mmHg. However, the mean of the first two BP readings exhibited good reliability and sufficient agreement in the diagnosis of hypertension with a kappa statistic at least 0.88, except that the difference between the first and second BP readings was at least 10 mmHg for both systolic and diastolic (κ=0.79). The diagnostic accuracy was similar across age quartile, sex, and BP category., Conclusion: Two BP readings may be sufficient, unless the BP difference between the two readings was at least 10 mmHg for both systolic and diastolic., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Blood pressure variability is a common physiological phenomenon; however, the association between within-visit and visit-to-visit variability in blood pressure and all-cause mortality remains uncertain., Methods: We conducted a retrospective analysis of blood pressure variability among 11 721 adults who underwent blood pressure measurement on three occasions within a period of 6 months. Within-visit and visit-to-visit variability was quantified using the standard deviation and maximum--minimum difference between measures. The predictive effect of this variability on all-cause mortality was evaluated using Kaplan--Meier survival curves and Cox regression analysis., Results: The incidence of all-cause mortality was significantly higher for participants in the top quintile of within-visit and visit-to-visit blood pressure variability and for those with sustained high within-visit variability. Within-visit variability was not retained as a risk factor after adjustment in Cox regression models. The hazard ratio for mortality increased from 48 to 55% for the top quintile of visit-to-visit blood pressure variability and from 56 to 61% for sustained high within-visit variability. The risk of mortality remained statistically higher even if visit-to-visit blood pressure variability was added to the model, including consistency of within-visit blood pressure variability and vice versa., Conclusion: Visit-to-visit and sustained high within-visit blood pressure variability were significant positive prognostic factors for all-cause mortality. Our findings underlined the clinical significance of achieving stable blood pressure in an effective plan of hypertension management., (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: Limited data exist on the optimum level of SBP in thrombolyzed patients with acute ischemic stroke (AIS). We aimed to determine the effects of intensive blood pressure (BP) lowering, specifically in patients with severe AIS who participated in the international, Enhanced Control of Hypertension and Thrombolysis Stroke Study., Methods: Prespecificed subgroup analyzes of the BP arm of Enhanced Control of Hypertension and Thrombolysis Stroke Study, a multicenter, partial-factorial, open, blinded outcome assessed trial, in which 2227 thrombolysis-eligible and treated AIS patients with elevated SBP (>150 mmHg) were randomized to intensive (target 130-140 mmHg) or guideline-recommended (<180 mmHg) BP management. Severe stroke was defined by computed tomography or magnetic resonance angiogram confirmation of large-vessel occlusion, receipt of endovascular therapy, final diagnosis of large artery atheromatous disease, or high (>10) baseline neurological scores on the National Institutes of Health Stroke Scale. The primary efficacy outcome was death or any disability (modified Rankin scale scores 2-6). The key safety outcome was intracranial hemorrhage (ICH). Treatment effects estimated in logistic regression models are reported as odds ratios (ORs) with 95% confidence intervals (CIs)., Results: There were 1311 patients [mean age 67 years; 37% female; median baseline National Institutes of Health Stroke Scale of 11 (range 6.0-15.0)] with severe AIS. Overall, there was no significant difference in the primary outcome of death or disability. However, intensive BP lowering significantly increased mortality (OR 1.52, 95% CI 1.09-2.13; P = 0.014) compared with guideline BP lowering, despite significantly lowering clinician-reported ICH (OR 0.63, 95% CI 0.43-0.92; P = 0.016)., Conclusion: Intensive BP lowering is associated with increased mortality in patients with severe AIS despite lowering the risk of ICH. Further randomized trials are required to provide reliable evidence over the optimum SBP target in the most serious type of AIS., Trial Registration: ClinicalTrials.gov Identifier: NCT01422616., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We investigated right ventricular function using speckle tracking echocardiography (STE) in patients with primary aldosteronism., Methods: Our study included 51 primary aldosteronism patients and 50 age and sex-matched primary hypertensive patients. We performed two-dimensional echocardiography to measure cardiac structure and function. We performed STE offline analysis on right ventricular four-chamber (RV4CLS) and free wall longitudinal strains (RVFWLS)., Results: Primary aldosteronism patients, compared with primary hypertensive patients, had a significantly (P ≤ 0.045) greater left ventricular mass index (112.0 ± 22.6 vs. 95.8 ± 18.5 g/m) and left atrial volume index (26.9 ± 6.0 vs. 24.7 ± 5.6 ml/m) and higher prevalence of left ventricular concentric hypertrophy (35.3 vs. 12.0%), although they had similarly normal left ventricular ejection fraction (55-77%). Primary aldosteronism patients also had a significantly (P ≤ 0.047) larger right atrium and ventricle, lower tricuspid annular plane systolic excursion, and higher E/E't (the peak early filling velocity of trans-tricuspid flow to the peak early filling velocity of lateral tricuspid annulus ratio), estimated pulmonary arterial systolic pressure and right ventricular index of myocardial performance. On the right ventricular strain analysis, primary aldosteronism patients had a significantly (P < 0.001) lower RV4CLS (-18.1 ± 2.5 vs. -23.3 ± 3.4%) and RVFWLS (-21.7 ± 3.7 vs. -27.9 ± 4.5%) than primary hypertensive patients. Overall, RV4CLS and RVFWLS were significantly (r = -0.58 to -0.41, P < 0.001) correlated with plasma aldosterone concentration and 24-h urinary aldosterone excretion. After adjustment for confounding factors, the associations for RV4CLS and RVFWLS with 24-h urinary aldosterone excretion remained significant (P < 0.001), with a standardized coefficient of -0.48 and -0.55, respectively., Conclusion: In addition to left ventricular abnormalities, primary aldosteronism patients also show impaired right ventricular function, probably because of hyperaldosteronism.

Objectives: Cardiovascular dysautonomia can be present at early, late and even prodromal stages of Parkinson's disease. This study aimed to describe the characteristics of 24-h ambulatory blood pressure (BP) monitoring and investigate the frequency of cardiovascular dysautonomia in Parkinson's disease without an abnormal BP history., Methods: Parkinson's disease patients without history of abnormal BP were consecutively enrolled from three Chinese centres, on whom office BP measurement, neurological evaluations and 24-h ambulatory BP monitoring were performed., Results: Totally, 101 Parkinson's disease patients (42.6% women) with an average age of 66.6 ± 8.2 years were included in our cohort, and data analysis revealed that 26 (25.74%) patients suffered from orthostatic hypotension, among whom 18 (69.23%) were symptomatic. Patients with orthostatic hypotension compared with those without had significantly higher nocturnal SBP level, and more severe nonmotor symptoms, autonomic dysfunction and cognitive impairment. Further, 54 out of 101 (53.47%) individuals had a reverse dipping pattern in SBP and/or DBP. Reverse dippers had more cases of orthostatic hypotension (P < 0.001), and more severe nonmotor symptoms. SBP dipping ratio of less than -2.98% generated 76.9% of sensitivity, 69.3% of specificity, 46.5% of positive predictive value (PPV), 89.7% of negative predictive value (NPV) and 77.4% of accuracy, while diastolic dipping ratio of less than -1.80% generated 76.9% of sensitivity, 70.7% specificity, 47.6% of PPV, 89.8% of NPV and 77.8% of accuracy for suspecting orthostatic hypotension., Conclusion: Orthostatic hypotension can occur in one-fourth Parkinson's disease patients without abnormal BP history, and reverse dipping was present in more than half of patients with Parkinson's disease. Reverse dipping pattern was helpful to suspect orthostatic hypotension.

: Blood pressure (BP) exhibits seasonal variation with lower levels at higher environmental temperatures and higher at lower temperatures. This is a global phenomenon affecting both sexes, all age groups, normotensive individuals, and hypertensive patients. In treated hypertensive patients it may result in excessive BP decline in summer, or rise in winter, possibly deserving treatment modification. This Consensus Statement by the European Society of Hypertension Working Group on BP Monitoring and Cardiovascular Variability provides a review of the evidence on the seasonal BP variation regarding its epidemiology, pathophysiology, relevance, magnitude, and the findings using different measurement methods. Consensus recommendations are provided for health professionals on how to evaluate the seasonal BP changes in treated hypertensive patients and when treatment modification might be justified. (i) In treated hypertensive patients symptoms appearing with temperature rise and suggesting overtreatment must be investigated for possible excessive BP drop due to seasonal variation. On the other hand, a BP rise during cold weather, might be due to seasonal variation. (ii) The seasonal BP changes should be confirmed by repeated office measurements; preferably with home or ambulatory BP monitoring. Other reasons for BP change must be excluded. (iii) Similar issues might appear in people traveling from cold to hot places, or the reverse. (iv) BP levels below the recommended treatment goal should be considered for possible down-titration, particularly if there are symptoms suggesting overtreatment. SBP less than 110 mmHg requires consideration for treatment down-titration, even in asymptomatic patients. Further research is needed on the optimal management of the seasonal BP changes.

Background: Smokers may smoke cigarettes during ambulatory or home blood pressure (BP) monitoring but not clinic measurement. We investigated the prevalence of masked hypertension in relation to cigarette smoking in Chinese outpatients enrolled in a multicenter registry., Methods: Our study included 1646 men [494 (30.0%) current smokers]. We defined masked hypertension as a normal clinic SBP/DBP (<140/90 mmHg) and elevated daytime (≥135/85 mmHg) or night-time (≥120/70 mmHg) ambulatory or morning or evening home SBP/DBP (≥135/85 mmHg)., Results: In all men, multiple logistic regression showed that current cigarette smoking was significantly associated with daytime [prevalence 18.7%, odds ratio (OR) 1.69, 95% confidence interval 1.27-2.25, P = 0.0003] but not night-time (prevalence 27.1%, P = 0.32) ambulatory masked hypertension and associated with evening (prevalence 14.6%, OR 1.81, confidence interval 1.33-2.47, P = 0.0002) but not morning (prevalence 17.6%, P = 0.29) home masked hypertension. The associations were more pronounced for heavy smoking (≥20 cigarettes/day) relative to never smoking for both masked daytime ambulatory (OR 1.97, P = 0.001) and evening home hypertension (OR 2.40, P < 0.0001) or in patients over 55 years of age (P for interaction in relation to daytime ambulatory masked hypertension = 0.005). In men with clinic normotension (n = 742), the associations were also significant (P < 0.01), particularly in those with a normal to high-normal clinic BP (n = 619, P < 0.04)., Conclusion: Cigarette smoking was associated with increased odds of masked daytime ambulatory and evening home hypertension, especially in heavy smoking or older men.

Background: The method of evaluating office blood pressure (OBP) varies greatly among different guidelines., Objectives: We performed a cohort study to compare the association of various directly transferred attended automated OBP (AOBP) estimations with all-cause and cardiovascular mortalities., Methods: Overall, 475 181 sets of OBPs from 35 622 participants aged 35 years or older were extracted from the electronic health record of the Xinzhuang town hospital in the Minhang District, Shanghai, China. Each set of OBPs contained three consecutive AOBPs that were transferred directly to the electronic health record. The mean of three OBPs, mean of the last two OBPs, and alternative average OBP were calculated., Results: The difference between the first and average OBPs changed along with the calendar month, and it was highest in December (5.3/2.1 mmHg) and lowest in July (3.8/2.0 mmHg). The subjects older than 80 years of age displayed the largest discrepancy in the blood pressure control rate according to the first OBP or average OBP (12.1%). During the 3.9-year follow-up, 1055 deaths occurred. The alternative average SBP was associated with both all-cause [hazard ratio: 1.07, 95% confidence interval (CI): 1.04-1.11] and cardiovascular (hazard ratio: 1.17, 95% CI: 1.11-1.23) mortalities. The uncontrolled alternative average OBP remained significantly associated with an increasing risk of all-cause (hazard ratio: 1.24, 95% CI: 1.09-1.40) and cardiovascular (hazard ratio: 1.53, 95% CI: 1.25-1.86) mortality, but not the average of the last two or mean of three readings., Conclusion: We observed an obvious discrepancy in the OBP level and OBP control rate according to different AOBP estimations. The alternative average OBP seemed to be more powerful in predicting both all-cause and cardiovascular mortalities than the average of the last two or mean of three readings.

: The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organisation for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP.

Objective: We evaluated the characteristics of patients with treatment-resistant hypertension (TRH) and the prevalence of TRH in a large multicountry sample of specialist tertiary centres., Methods: The Survey of PatIents with treatment ResIstant hyperTension (SPIRIT) study was a retrospective review of medical records of patients seen at tertiary centres located in Western Europe, Eastern Europe, North America, South America, Australia and Asia. Data on demographics, medical history and medication use were extracted from medical records. Prevalence and incidence of TRH were based upon estimated catchment populations., Results: On thousand, five hundred and fifty-five patients from 76 centres were included, mostly from centres that specialize in hypertension (55%), cardiology (11%) or nephrology (19%). Mean age was 64, 60% were men, 62% were Caucasian, 36% had chronic kidney disease, 41% had diabetes, 12% were smokers and 31% had a previous cardiovascular event. Daytime and night-time ambulatory blood pressure (BP) was the most frequently used measurement for diagnosis (82%). Ninety-five percent of patients were prescribed diuretics, 93% an inhibitor of the renin-angiotensin system, 86% a calcium channel blocker, 74% a beta-blocker and 36% an aldosterone antagonist. The overall estimated mean incidence of TRH was 5.8 per 100 000 per year (ranging between 2.3 and 14.0 across regions) and the corresponding estimated mean prevalence of TRH was 23.9 per 100 000 (ranging between 7.6 and 90.5 across regions)., Conclusion: Observed variation likely reflects real differences in patient characteristics and physician management practices across regions and specialities but may also reflect differences in patient selection and errors in estimation of catchment population across participating centres.

Background: We investigated the left atrial myocardial deformation in patients with primary aldosteronism using the speckle-tracking echocardiographic (STE) strain imaging technique., Methods: Our study included 107 primary aldosteronism patients [52 aldosterone-producing adenoma (APA) and 55 idiopathic hyperaldosteronism (IHA)] and 50 primary hypertensive patients. We performed conventional echocardiography to measure left atrial volume and ejection fraction, and STE to estimate left atrial myocardial deformation including peak velocity, strain and strain rate and calculate the ratio of E/e' to left atrial strain during left ventricular systole as the left atrial stiffness index., Results: Patients with APA, compared with those with IHA and primary hypertension had a significantly (P < 0.001) lower serum potassium concentration and higher 24-h urinary aldosterone excretion and plasma aldosterone-to-renin ratio. Patients with APA had a significantly (P < 0.01) larger maximal, precontraction, and minimal left atrial volumes and lower total, active and passive left atrial emptying fractions than those with IHA and primary hypertension. Among the three groups, patients with APA showed lowest left atrial velocity, strain, and strain rate during ventricular systole, early diastole and late diastole (P < 0.05) and highest left atrial stiffness index (P < 0.001). In unadjusted analysis, the left atrial strain, strain rate and stiffness index were significantly (P < 0.05) associated with plasma aldosterone concentration and urinary aldosterone excretion. After adjustment for various confounding factors, these associations remained statistically significant for urinary aldosterone excretion (P < 0.05) but not plasma aldosterone concentration (P ≥ 0.05)., Conclusion: Patients with primary aldosteronism, especially APA, had impaired left atrial deformation mechanics and increased left atrial stiffness, providing a promising insight into early detection of subclinical left atrial dysfunction by strain echocardiography.

Background: In a comparative meta-analysis, we investigated the prognostic value of masked hypertension and masked uncontrolled hypertension defined by ambulatory or home blood pressure (BP) monitoring., Methods: We searched English literature published till 2 September 2018 to identify prospective observational studies. Masked hypertension was defined as a normal clinic BP (<140/90 mmHg) in the presence of an elevated 24 h, daytime or night-time ambulatory or home BP. Clinical outcomes included all-cause and cardiovascular mortality, and fatal and nonfatal cardiovascular, stroke, cardiac, coronary and renal disease events., Results: In total, 21 studies (n = 130 318) were included. Overall, compared with normotensive participants, masked hypertensive patients had a 5.7/2.9 mmHg higher clinic BP and 18.7/9.8 mmHg higher out-of-office BP. The pooled risk ratio for masked hypertension versus normotension was 1.67 (95% confidence interval, 1.32-2.13) and 2.19 (1.72-2.78) for all-cause (eight studies) and cardiovascular mortality (three studies), respectively, and 1.71 (1.53-1.91), 1.95 (1.36-2.80), 1.76 (1.33-2.33), 1.62 (0.27-9.60), 3.85 (2.03-7.31) for fatal and nonfatal cardiovascular (15 studies), stroke (two studies), cardiac (two studies), coronary (two studies) and renal disease events (two studies), respectively. Risk ratios for all-cause mortality (1.78 versus 1.40, P = 0.16) and fatal and nonfatal cardiovascular events (1.81 versus 1.61, P = 0.29) were similar between studies on ambulatory and home BP monitoring in the overall analyses. The analyses in subgroups according to treatment status (untreated, treated or mixed) and sampling approach (population or referred patients) were confirmatory., Conclusion: Masked hypertension and masked uncontrolled hypertension were associated with unfavorable clinical outcomes, regardless of the out-of-office BP monitoring techniques.

: In the past 30 years, several organizations have developed protocols for clinical validation of blood pressure measuring devices. An international initiative was recently launched by the US Association for the Advancement of Medical Instrumentation (AAMI), the European Society of Hypertension Working Group on Blood Pressure Monitoring (ESH) and the International Organization for Standardization (ISO), aiming to reach consensus on a universal AAMI/ESH/ISO validation standard. The purpose of this statement by the ESH Working Group on Blood Pressure Monitoring is to provide practical guidance for investigators performing validation studies according to the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018), to ensure that its stipulations are meticulously implemented and data are fully reported. Thus, this statement provides: a list of key recommendations for validation studies of intermittent non-invasive automated blood pressure measuring devices according to the AAMI/ESH/ISO Universal Standard; practical stepwise guidance for researchers performing these validation studies; a checklist for authors and reviewers of such studies; an example of a complete validation study report.

This article is a comprehensive document on the diagnosis and management of fibromuscular dysplasia (FMD) which was commissioned by the Working Group 'Hypertension and the Kidney' of the European Society of Hypertension (ESH) and the Society for Vascular Medicine (SVM). This document updates previous consensus documents/scientific statements on FMD published in 2014 with full harmonization of the position of European and US experts. In addition to practical consensus-based clinical recommendations, including a consensus protocol for catheter-based angiography and percutaneous angioplasty for renal FMD, the document also includes the first analysis of the European/International FMD Registry and provides updated data from the US Registry for FMD. Finally, it provides insights on ongoing research programs and proposes future research directions for understanding this multifaceted arterial disease.

Objectives: To investigate the relationship between common carotid artery diameter (CCA-D) and target organ damage (TOD) in essential hypertension., Methods and Results: A total of 200 essential hypertensive patients were enrolled (mean age 62.5 ± 9.5, men 59.0%) and were classified into two groups by the height-adjusted mean median of CCA-D: patients with CCA-D/height less than 3.905 mm/m (n = 100, 50%) and patients with CCA-D/height more than 3.905 mm/m (n = 100, 50%). Patients with CCA-D/height more than 3.905 mm/m have higher left ventricular mass index (LVMI) (P < 0.001) and higher prevalence of left ventricular hypertrophy (LVH) (P < 0.001), higher mean common carotid intima-media thickness (P = 0.008) and higher prevalence of carotid artery sclerosis (P = 0.03), higher pulse wave velocity (PWV) (P < 0.001) and higher prevalence of increased arterial stiffness (P = 0.01), higher urinary albumin/creatinine ratio (P = 0.001) and higher prevalence of microalbuminuria (P = 0.02) and greater number of TODs (P < 0.001) compared with the patients with CCA-D/height less than 3.905 mm/m. CCA-D was significantly correlated with LVMI, PWV and logarithmically transformed urinary albumin/creatinine ratio (r = 0.299, P < 0.001; r = 0.212, P = 0.007; r = 0.224, P = 0.005, respectively) after adjusting for cardiovascular risk factors. Multivariable stepwise linear regression analysis showed that number of TODs as well as individual TOD, including LVMI, PWV and logarithmically transformed urinary albumin/creatinine ratio, were independently correlated to height-adjusted mean CCA-D (all P < 0.05)., Conclusion: Height-adjusted mean CCA-D was an independent risk factor for individual TOD, including LVMI, PWV and urinary albumin/creatinine ratio, as well as overall number of TODs in essential hypertension.

Introduction: The European Society of Hypertension (ESH) International Protocol (ESH-IP) for the validation of blood pressure (BP) measuring devices was published in 2002, with the main objective of simplifying the validation procedures, so that more BP monitors would be subjected to independent validation. This article provides an overview of the international impact of the ESH-IP and of the lessons learned from its use, to be able to justify further developments in validation protocols., Methods: A review of published (PubMed) validation studies from 2002 to 2017 was performed., Results: One hundred and seventy-seven validation studies using the ESH-IP, 59 using the British Hypertension Society protocol, 46 using the Association for the Advancement of Medical Instrumentation (AAMI) standard and 23 using the International Organization for Standardization (ISO) standard were identified. Lists of validated office-clinic, home and ambulatory BP monitors are provided. Of the ESH-IP studies, 93% tested oscillometric devices, 80% upper arm, 71% home, 25% office and 7% ambulatory monitors (some had more than one function)., Conclusion: The original goal of the ESH-IP has been fulfilled in that in the last decade the number of published validation studies has more than doubled. It is now recognized that the provision of accurate devices would be best served by having a universal protocol. An international initiative has been put in place by AAMI, ESH and ISO experts aiming to reach consensus for a universal validation protocol to be accepted worldwide, which will allow a more thorough evaluation of the accuracy and performance of future BP monitors.

: In the last 30 years, several organizations, such as the US Association for the Advancement of Medical Instrumentation (AAMI), the British Hypertension Society, the European Society of Hypertension (ESH) Working Group on Blood Pressure (BP) Monitoring and the International Organization for Standardization (ISO) have developed protocols for clinical validation of BP measuring devices. However, it is recognized that science, as well as patients, consumers and manufacturers would be best served if all BP measuring devices were assessed for accuracy according to an agreed single validation protocol that had global acceptance. Therefore, an international initiative was taken by AAMI, ESH and ISO experts who agreed to develop a universal standard for device validation. This statement presents the key aspects of a validation procedure, which were agreed by the AAMI, ESH and ISO representatives as the basis for a single universal validation protocol. As soon as the AAMI/ESH/ISO standard is fully developed, this will be regarded as the single universal standard and will replace all other previous standards/protocols.

Background: Increased morning blood pressure (BP) has been associated with fatal and nonfatal cardiovascular events, especially in Asians., Method: To detect the control status of home BP, we performed a home BP monitoring study, including elderly patients with hypertension who had controlled documented office BP in Chinese primary care clinics. In 707 participants from Xinzhuang County Hospital in Shanghai, the home BP was measured by a memory-equipped device three times daily for seven consecutive days., Results: The prevalence of uncontrolled hypertension was 51.3% in the morning and 42% in the evening. Uncontrolled morning hypertension was associated with age [odds ratio (OR): 1.074; 95% confidence interval (CI): 1.041-1.108], office SBP (OR: 1.027; 95% CI: 1.015-1.039), office DBP (OR: 1.042; 95% CI: 1.021-1.064), and the number of antihypertensive drugs taken (OR: 1.387; 95% CI: 1.059-1.817), whereas it was inversely associated with the use of long-acting antihypertensive drugs (OR: 0.588; 95% CI: 0.355-0.973). Compared with office BP, the home morning BP showed a more significant association with age and short-acting antihypertensive drugs., Conclusion: The prevalence of uncontrolled home BP is high in elderly Chinese hypertensive patients, especially in the morning, and home BP monitoring might be a feasible method for detecting it. The use of long-acting antihypertensive drugs might help to improve morning hypertension.

Background: Cerebral syndromes in older humans, secondary stroke in younger persons following trauma, and sickle cell anaemia in children, are linked by unexplained microvascular damage and high cerebral pressure or flow pulsations. The aim of this study was to characterize age-related pressure and flow waveforms patterns entering the brain, to explain these in terms of disturbed physiological function, and to consider clinical implications., Method: Blood flow velocity waves were measured in four cerebral vascular territories by transcranial Doppler of 1020 apparently normal patients (497 men, 21-78 years). Central pressure waveforms were generated from radial artery applanation tonometry with SphygmoCor. Relationships were described in time and frequency domains., Results and Conclusion: Flow waveforms entering the brain showed similar pattern to central aortic pressure waveforms, and similar changes with age. Augmentation index of flow and of pressure had high correlation at different ages, and in men and women (r = 0.58, P < 0.01). Calculated cerebral vascular impedance was similar in both sexes, and at different ages, with low modulus and phase, indicating a dilated, passive cerebral vascular bed. This vascular bed is subject to pressure and flow fluctuations generated directly by the heart and boosted by strong wave reflections from the lower body., Conclusion: Cerebral microvascular damage in older patients is attributable to high pulsatile pressure tearing the delicate media, causing haemorrhage, and high pulsatile flow dislodging endothelial cells, causing thrombosis and microinfarcts. High pulsations in older patients are caused by early wave reflection from the lower body. Reduction of or delay in wave reflection is a logical strategy for aortic stiffening in older humans.

Objective: Whether or not calcium-regulating hormones stiffen arteries independent of blood pressure (BP) is uncertain. We investigated the independent associations of carotid-femoral pulse wave velocity (PWV) with 25-hydroxy-vitamin D [25(OH)D], parathyroid hormone (PTH) and 24-h ambulatory BP in untreated Chinese patients., Methods: Consecutive untreated patients referred for ambulatory BP monitoring were recruited. PWV was measured with a high-fidelity micromanometer and the SphygmoCor software (AtCor Medical, West Ryde, New South Wales, Australia). Serum 25(OH)D and PTH were determined by electrochemiluminescence immunoassay. Analysis of variance, single and multiple regressions were applied for analyses., Results: In 1052 untreated patients (50.7% women; mean age, 51 years), PWV averaged 7.8 m/s, 24-h SBP/DBP 126.5/81.7 mmHg, serum 25(OH)D and PTH 36.0 nmol/l and 61.6 pg/ml, respectively. In multivariable-adjusted analyses, BP (P < 0.001) and PTH (P = 0.012) increased from less than 25th to at least 75th percentile of the PWV distribution. In continuous analyses, PWV independently increased by 0.40/0.23 m/s per 1-SD increment in SBP/DBP (P < 0.001) and by 0.14 m/s for a doubling of serum PTH (P = 0.029). Associations of PWV with BP were tighter than with PTH (P < 0.001). In pathway analysis, the effect of PTH on PWV did not run via serum or urinary calcium (P = 0.65), but PTH had both a direct (P = 0.026) and a BP-mediated indirect effect (P = 0.043) on PWV. In none of our analyses were PWV associated with serum 25(OH)D., Conclusion: Arterial stiffness, as assessed by PWV, independently increased both with BP and with PTH, but BP remains the main driver of arterial stiffening.

: The aim of the current article is to review the current evidence on the role of morning blood pressure (BP) in the management of hypertension. Morning BP surge had been and will continue to be a hot topic of hypertension research. However, more evidence is needed to prove its clinical usefulness in the management of hypertension. Masked morning hypertension, as the other forms of masked hypertension, requires more research. The concept of morning BP monitoring could be clinically relevant in the therapeutic management of hypertension and in the prevention of cardiovascular complications by defining and treating morning hypertension. Antihypertensive medication is usually taken in the morning. The presence of uncontrolled morning BP during trough effect hours could be a hallmark of inadequate antihypertensive regimen, such as, for instance, the use of short-acting or intermediate-acting drugs, under dosing of drugs, or no or low use of combination therapy. To improve the management of hypertension in general and morning hypertension in particular, long-acting antihypertensive drugs should be used in appropriate often full dosages and in proper combinations. The clinical usefulness of antihypertensive drugs of specific mechanisms against morning BP or split or timed dosing of long-acting drugs in controlling morning BP remains under investigation. In conclusion, there is some evidence that morning BP is critical in the incidence of cardiovascular complications. However, proving its clinical usefulness in the management of hypertension requires further research.

Objective: The objective of this study is to evaluate the efficacy and safety of sacubitril/valsartan (LCZ696, an angiotensin receptor and neprilysin inhibitor) add-on to amlodipine compared with amlodipine monotherapy in Asian patients with systolic hypertension uncontrolled with amlodipine., Methods: Patients with mean clinic SBP at least 145 mmHg and less than 180 mmHg after a 4-week treatment with amlodipine 5 mg/day were randomized to receive LCZ696/amlodipine (200/5 mg/day) or amlodipine 5 mg/day for 8 weeks. The primary assessment was the superiority of LCZ696/amlodipine versus amlodipine in lowering 24-h ambulatory SBP from baseline to week 8. Secondary assessments included 24-h ambulatory DBP and pulse pressure (PP), daytime and night-time BP, clinic BP and PP, BP control/responder rate (<140/90 mmHg or a reduction ≥20/10 mmHg from baseline), and safety., Results: Of the 371 patients screened, 266 (71.7%) patients (mean age 55.4 years; 24-h SBP/DBP 139.0/86.1 mmHg at baseline) who did not respond to 4-week treatment with amlodipine 5 mg/day were randomized. At week 8, LCZ696/amlodipine provided greater reductions in 24-h SBP compared with amlodipine monotherapy from baseline (-13.9 versus -0.8 mmHg, P < 0.001). All the secondary efficacy assessments were significantly (P < 0.001) in favour of LCZ696/amlodipine, for instance, 24-h PP (-5.8 versus -0.6 mmHg). Overall, the incidence of adverse events was 20.0% with LCZ696/amlodipine and 21.3% with amlodipine., Conclusion: LCZ696/amlodipine showed significantly greater 24-h ambulatory BP and PP reductions compared with amlodipine monotherapy. Both treatments were generally well tolerated. Therefore, LCZ696/amlodipine combination could be an effective treatment for patients with systolic hypertension uncontrolled with amlodipine.

Objective: We assessed the prognostic value of ECG left ventricular hypertrophy (LVH) using Sokolow-Lyon (SL-LVH), Cornell voltage (CV-LVH) or Cornell product (CP-LVH) criteria in 3043 hypertensive people aged 80 years and over enrolled in the Hypertension in the Very Elderly Trial., Methods: Multivariate Cox proportional hazard models were used to estimate hazard ratios with 95% confidence intervals (CIs) for all-cause mortality, cardiovascular diseases, stroke and heart failure in participants with and without LVH at baseline. The mean follow-up was 2.1 years., Results: LVH identified by CV-LVH or CP-LVH criteria was associated with a 1.6-1.9-fold risk of cardiovascular disease and stroke. The presence of CP-LVH was associated with an increased risk of heart failure (hazard ratio 2.38, 95% CI 1.16-4.86). In sex-specific analyses, CV-LVH (hazard ratio 1.94, 95% CI 1.06-3.55) and CP-LVH (hazard ratio 2.36, 95% CI 1.25-4.45) were associated with an increased risk of stroke in women and of heart failure in men, CV-LVH (hazard ratio 6.47, 95% CI 1.41-29.79) and CP-LVH (10.63, 95% CI 3.58-31.57), respectively. There was no significant increase in the risk of any outcomes associated with Sokolow-Lyon-LVH. LVH identified by these three methods was not a significant predictor of all-cause mortality., Conclusion: Use of Cornell voltage and Cornell product criteria for LVH predicted the risk of cardiovascular disease and stroke. Only Cornell product was associated with an increased risk of heart failure. This was particularly the case in men. The identification of ECG LVH proved to be important in very elderly hypertensive people.

Objective: We investigated hypertension and diabetes mellitus in two management settings, namely cardiology and endocrinology, and their associations with albuminuria while accounting for the management of these two diseases., Methods: Our multicentre registry included patients (≥20 years) seen for hypertension in cardiology or for diabetes mellitus in endocrinology. We administered a questionnaire and measured blood pressure, glycosylated haemoglobin A1c and albuminuria., Results: Presence of both hypertension and diabetes was observed in 32.9% of hypertensive patients in cardiology (n = 1291) and 58.9% of diabetic patients in endocrinology (n = 1168). When both diseases were present, the use of combination antihypertensive therapy [odds ratio (OR) 0.31, P < 0.0001] and inhibitors of the renin-angiotensin system (OR 0.66, P = 0.0009) was less frequent in endocrinology than cardiology, and the use of combination antidiabetic therapy (OR 0.16, P < 0.0001) was less frequent in cardiology than endocrinology. The control of hypertension and diabetes, however, was not different between the two management settings (P ≥ 0.21), regardless of the therapeutic target (SBP/DBP < 140/90 or 130/80 mmHg and glycosylated haemoglobin A1c <7.0 or 6.5%). The prevalence of albuminuria was higher (P ≤ 0.02) in the presence of both diseases (23.3%) than those with either hypertension (12.6%) or diabetes alone (15.9%)., Conclusion: Hypertension and diabetes mellitus were often jointly present, especially in the setting of endocrinology. The management was insufficient on the use of combination antihypertensive therapy and inhibitors of the renin-angiotensin system in endocrinology and for combination antidiabetic therapy in cardiology, indicating a need for more intensive management and better control of both clinical conditions.

Background: We investigated accuracy of home blood pressure (BP) monitoring in the diagnosis of white-coat and masked hypertension in comparison with ambulatory BP monitoring., Methods: Our study participants were enrolled in the China Ambulatory and Home BP Registry, and underwent clinic, home, and 24-h ambulatory BP measurements. We defined white-coat hypertension as an elevated clinic SBP/DBP (≥140/90 mmHg) and a normal 24-h ambulatory (<130/80 mmHg) or home SBP/DBP (<135/85 mmHg), and masked hypertension as a normal clinic SBP/DBP (<140/90 mmHg) and an elevated 24-h ambulatory (≥130/80 mmHg) or home SBP/DBP (≥135/85 mmHg)., Results: In untreated patients (n = 573), the prevalence of white-coat hypertension (13.1 vs. 19.9%), masked hypertension (17.8 vs. 13.1%), and sustained hypertension (46.4 vs. 39.6%) significantly (P ≤ 0.02) differed between 24-h ambulatory and home BP monitoring. In treated patients (n = 1201), only the prevalence of masked hypertension differed significantly (18.7 vs. 14.5%; P = 0.005). Regardless of the treatment status, home compared with 24-h ambulatory BP had low sensitivity (range 47-74%), but high specificity (86-94%), and accordingly low positive (41-87%), but high negative predictive values (80-94%), and had moderate diagnostic agreement (82-85%) and Kappa statistic (0.41-0.66). In untreated and treated patients, age advancing was associated with a higher prevalence of white-coat hypertension and a lower prevalence of masked hypertension defined by 24-h ambulatory (P ≤ 0.03) but not home BP (P ≥ 0.10)., Conclusion: Home BP monitoring has high specificity, but low sensitivity in the diagnosis of white-coat and masked hypertension, and may therefore behave as a complementary to, but not a replacement of, ambulatory BP monitoring.

Objectives: We found impaired brachial flow-mediated dilation (FMD) was associated with the number of target organ damage (TOD) in 2007. The present study investigated whether FMD predicted TOD progression in essential hypertension., Methods and Results: Endothelium-dependent FMD was measured in 280 adults in 2007. At the third year of examination, 199 patients (mean age 62.5 ± 9.5, men 59.3%) were approached for participation in our study. Patients were divided into two groups: normal FMD group (FMD ≥10) and impaired FMD group (FMD <10). In patients with 0-1 TOD at baseline, impaired FMD group (n = 65) led to thicker intima-media thickness (P = 0.02), increased carotid-to-femoral pulse wave velocity (P = 0.03), increased urinary albumin/creatinine ratio (P = 0.04) and increased TOD number (P = 0.02), as compared with the normal FMD group (n = 59) at the end of the follow-up, even after adjusting for age and sex, whereas the relationship did not exist in 2-4 TOD group at baseline. TOD number increase was associated with the prevalence of diabetes mellitus (β = 0.180, P = 0.035), blood pressure control (β = -0.277, P = 0.001), low-density lipoprotein cholesterol (β = 0.234, P = 0.006) and baseline FMD (β = -0.168, P = 0.043) in stepwise multivariate regression analysis. FMD remained a significant predictor of TOD number increase in multiple logistic regression analysis after adjustment for several known risk factors (relative risk 0.92, 95% confidence interval 0.85-0.99, P = 0.042, for each 1% increase in FMD)., Conclusion: FMD is a predictor of future TOD progression in low-risk essential hypertensive patients, but has little predictive value in the late stage of TOD.