Pediatric Ambulatory Blood Pressure Monitoring Research Articles

O105 ISOLATED NOCTURNAL HYPERTENSION AND TARGET ORGAN INJURY IN YOUTH

Background and Objective: New American Heart Association (AHA) recommendations in 2022 for pediatric ambulatory blood pressure monitoring (ABPM) established static blood pressure (BP) cutoffs to define hypertension with an optimal sensitivity-specificity balance to best capture target organ injury (TOI). This increased the prevalence of ABPM hypertension, specifically isolated nocturnal hypertension. We utilized ABPM data from the SHIP-AHOY cohort to describe the epidemiology of INH in youth and to evaluate associations between INH and TOI. Methods: We defined INH as wake BP <130/80 mmHg and sleep BP >110/65 mmHg. INH was also evaluated by the 2014 AHA definition: wake BP <95th percentile with sleep BP >95th percentile. Primary outcome was left ventricular hypertrophy (LVH), defined as left ventricular mass index >38.6 g/m2.7. Cardiovascular risk factor (CVRF) scores described the number of risk factors for cardiovascular disease (dyslipidemia, obesity, hypertension by clinic systolic BP, insulin resistance) fro each participant. Logistic regression models assessed the association of INH with LVH, adjusted for age, sex, CVRF score, and ABPM tolerability. Results: Of 397 participants, 77 had INH, mostly (62%) due to elevated systolic BPs only. Median age and height were higher in INH than normotension (16.1 v 15.1 years, P=0.022) (height z-score 1.13 v 0.23, P=0.039). Other characteristics did not differ significantly between groups (Table 1). Estimated glomerular filtration rate was lower in INH. Among those with INH, 27% (N=19/71) had LVH, a greater proportion than found with 2014 definitions (21%, N=7/33). Children with INH had 2.61-fold adjusted odds of LVH compared to normotension (95%CI [1.20,5.69], P=0.016). Conclusions: Over 20% of the SHIP-AHOY cohort had INH, accounting for >1/3 of hypertension overall. INH was associated with older age and taller height, mostly due to systolic BP. Compared to 2014 guidelines, the 2022 definition of INH captured a higher prevalence of LVH. INH was independently associated with increased odds of LVH. Future studies should follow children with INH longitudinally for potential development of daytime hypertension. Table 1: Demographic, Anthropomorphic, and Clinical Characteristics of Isolated Nocturnal Hypertension vs Normotension

Clinician response after receipt of abnormal pediatric ambulatory blood pressure monitoring - characteristics associated with inertia and action.

Ambulatory Blood Pressure Monitoring (ABPM) is recommended for diagnosis and management of hypertension. We aimed to identify characteristics associated with physician action after receipt of abnormal findings. This was a retrospective cross-sectional analysis of patients 5-22years old who underwent 24-h ABPM between 2003-2022, met criteria for masked or ambulatory hypertension, and had a pediatric nephrology clinic visit within 2weeks of ABPM. "Action" was defined as medication change/initiation, lifestyle or adherence counseling, evaluation ordered, or interpretation with no change. Characteristics of children with/without 1 or more actions were compared using Student t-tests and Chi-square. Regression analyses explored the independent association of patient characteristics with physician action. 115 patients with masked (n = 53) and ambulatory (n = 62) hypertension were included: mean age 13.0years, 48% female, 38% Black race, 21% with chronic kidney disease, and 25% overweight/obesity. 97 (84%) encounters had a documented physician action. Medication change (52%), evaluation ordered (40%), and prescribed lifestyle change (35%) were the most common actions. Adherence counseling for medication and lifestyle recommendations were documented in 3% of encounters. 24-h, wake SBP load, and sleep DBP load were significantly higher among those with physician action. Patients with > 1 action had greater adiposity, SBP, and dipping. Neither age, obesity, nor kidney disease were independently associated with physician action. While most abnormal ABPMs were acted upon, 16% did not have a documented action. Greater BP load was one of the few characteristics associated with physician action. Of potential actions, adherence counseling was underutilized.

Reclassification of Adolescent Ambulatory Prehypertension and Unclassified Blood Pressures by 2022 American Heart Association Pediatric Ambulatory Blood Pressure Monitoring Guidelines

To describe the epidemiology of reclassification of prehypertensive and unclassified adolescents by 2022 American Heart Association pediatric ambulatory blood pressure monitoring (ABPM) guidelines, and to evaluate the association of the new diagnostic categories with left ventricular hypertrophy (LVH). A single-center, retrospective review of ABPM reports from adolescents 13-21years old, from 2015 through 2022, was performed. Adolescents with prehypertension or unclassified by 2014 guidelines were reclassified by 2022 definitions. Logistic regression models evaluated the association of reclassification phenotypes with LVH. A majority of prehypertensive adolescents reclassified to hypertension (70%, n=49/70). More than one-half (57%, n=28/49) of the hypertension was isolated nocturnal hypertension, and 80% was systolic hypertension. Reclassification to hypertension was more common in males. The majority (55.6%) of unclassified adolescents were reclassified to normotension. No demographic or clinical variables were associated with reclassification categories. LVH was not associated with hypertension in the reclassified prehypertensive or unclassified groups. The 2022 ABPM guidelines clearly define blood pressure phenotypes. However, reclassification to hypertension was not associated with an increased odds of LVH. Because most prehypertensive adolescents reclassified as hypertensive by nighttime BPs alone, this study highlights the lowered threshold for nocturnal hypertension. Prospective studies in larger, well-defined cohorts are needed to describe better the predictive value of 2022 BP phenotypes for target organ damage.

Association of Isolated Nocturnal Hypertension (INH) and Target Organ Damage in Light of the 2022 American Heart Association (AHA) Pediatric Ambulatory Blood Pressure Monitoring (ABPM) Guidelines

Association of Isolated Nocturnal Hypertension (INH) and Target Organ Damage in Light of the 2022 American Heart Association (AHA) Pediatric Ambulatory Blood Pressure Monitoring (ABPM) Guidelines

Impact of the 2022 American Heart Association pediatric ambulatory blood pressure monitoring statement on the diagnosis of hypertension.

The diagnosis of hypertension and hypertension-induced target organ injury by the 2022 American Heart Association (AHA) ambulatory blood pressure threshold as compared with 2014 AHA and 2016 European Society of Hypertension (ESH) thresholds has not been evaluated. In a cross-sectional study (n = 291, aged 5-18years, at a tertiary care outpatient clinic), we compared 2022 AHA with 2014 AHA and ESH thresholds (revised with 2018 adult ESH thresholds where applicable) to diagnose ambulatory hypertension (AH), and detect ambulatory arterial stiffness index (AASI) and left ventricular target organ injury (LVTOI). The 2022 AHA threshold diagnosed significantly more AH (53%) than the 2014 AHA (42%, p < 0.01) and ESH (36%, p < 0.001) thresholds. The 2022 AHA threshold demonstrated only a moderate agreement with the 2014 AHA (kappa (k) = 0.77) and ESH (k = 0.66) thresholds to diagnose AH. Adjusted logistic regression analysis found that only the 2022 AHA threshold predicted elevated AASI significantly (odds ratio 2.40, 95% CI 1.09, 5.25, p = 0.02; AUC 0.61, p < 0.01). In those with elevated AASI, more participants had AH by the 2022 AHA threshold (72%) than the 2014 AHA (46%, p = 0.02) and ESH (48%, p = 0.03) thresholds. AH defined by the 2022 AHA threshold continued to maintain higher odds, larger AUC, and higher sensitivity to identify LVTOI than the 2014 AHA and ESH thresholds; however, the difference did not reach a statistically significant level. AH defined by the 2022 AHA threshold diagnoses more children with hypertension and identifies more children with hypertension-induced target organ injury than the 2014 AHA and ESH thresholds. A higher resolution version of the Graphical abstract is available as Supplementary information.

Ambulatory Blood Pressure Monitoring in Pediatrics, an Update on Interpretation and Classification of Hypertension Phenotypes.

This review highlights the major changes reflected in the 2022 American Heart Association (AHA) Scientific Statement on Ambulatory Blood Pressure Monitoring (ABPM) in Children and Adolescents with a specific focus on the newly defined phenotypes of hypertension and their epidemiology and associated outcomes. The 2022 AHA guidelines' most notable changes include the following: (1) alignment of blood pressure (BP) thresholds with the 2017 American Academy of Pediatrics (AAP) clinical practice guidelines, 2017 American College of Cardiology (ACC)/AHA hypertension guidelines, and 2016 European Society of Hypertension (ESH) pediatric recommendations; (2) expansion of the use of ABPM to diagnose and phenotype pediatric hypertension in all pediatric patients; (3) removal of BP loads from diagnostic criteria; and (4) simplified classification of new hypertension phenotypes to prognosticate risks and guide clinical management. Recent studies suggest that utilizing the 2022 AHA pediatric ABPM guidelines will increase the prevalence of pediatric ambulatory hypertension, especially for wake ambulatory hypertension in older, taller males and for nocturnal hypertension in both males and females ≥ 8years of age. The new definitions simplify the ambulatory hypertension criteria to include only the elements most predictive of future health outcomes, increase the sensitivity of BP thresholds in alignment with recent data and other guidelines, and thus make hypertension diagnoses more clinically meaningful. This guideline will also aid in the transition of adolescents and young adults to adult medical care. Further studies will be necessary to study ambulatory BP norms in a more diverse pediatric population and evaluate the impact of these guidelines on prevalence and future outcomes.

Updates to Pediatric Ambulatory Blood Pressure Monitoring in Clinical Practice: a Review and Strategies for Expanding Access

Updates to Pediatric Ambulatory Blood Pressure Monitoring in Clinical Practice: a Review and Strategies for Expanding Access

Ambulatory Blood Pressure Monitoring in Children and Adolescents: 2022 Update: A Scientific Statement From the American Heart Association.

Use of ambulatory blood pressure monitoring in children and adolescents has markedly increased since publication of the last American Heart Association scientific statement on pediatric ambulatory blood pressure monitoring in 2014. In addition, there has also been significant expansion of the evidence base for use of ambulatory blood pressure monitoring in the pediatric population, including new data linking ambulatory blood pressure levels with the development of blood pressure-related target organ damage. Last, additional data have recently been published that enable simplification of the classification of pediatric ambulatory monitoring studies. This scientific statement presents a succinct review of this new evidence, guidance on optimal application of ambulatory blood pressure monitoring in the clinical setting, and an updated classification scheme for the interpretation of ambulatory blood pressure monitoring in children and adolescents. We also highlight areas of uncertainty where additional research is needed.

Pediatric Ambulatory Blood Pressure Classification: The Case for a Change.

In 1997, Soergel et al1 published the first set of normative values for ambulatory blood pressure monitoring (ABPM) in children. Since then, the clinical utility of ABPM has increased dramatically, and now, ABPM is accepted as the standard method to confirm the diagnosis of hypertension in children. Despite significant progress in the field of pediatric ABPM, many important questions remain unanswered. One of the most controversial issues is how to define ambulatory hypertension in children. The purpose of this review is to discuss the limitations of the current pediatric ABPM classification scheme and to provide the justification and rationale for a new classification.

630 Longer Sleep Duration Reduces the Odds of Hypertension in Children Referred to Nephrology for Elevated Blood Pressure

Abstract Introduction Lifestyle modification is often prescribed as first line-therapy for hypertension in childhood. We aimed to determine if there was an association between sleep duration and hypertension in children referred for evaluation to Nephrology for elevated blood pressure (BP). We hypothesized that, longer sleep duration would be associated with a reduced likelihood of a hypertension diagnosis. Methods Medical record data were retrospectively extracted from patients referred to the Children’s Hospital of Philadelphia’s pediatric nephrology clinic for the evaluation of elevated BP, without a prior hypertension diagnosis. Ambulatory blood pressure monitoring (ABPM) data collected between December 2015 to December 2018 were extracted. Hypertension was defined by ABPM according to American Heart Association recommendations for pediatric ABPM and we evaluated BP indexed to sex and height. Sleep duration was calculated as the difference between self-reported time of sleep onset and offset. Regression models were adjusted for age, sex, race, body mass index, and weeknight status. Results Our sample included 249 patients, with a mean age of 14.5 (SD: 3.1) years. Of these, 29% were obese and 42% met criteria for hypertension. Mean sleep duration was 9.3 (SD: 1.6) hours per night and duration was shorter with increasing age in years (β=-0.11, 95% CI: -0.18, -0.05) and on week vs. weekend nights (β=-0.62, 95% CI: -1.05, -0.24). Each additional hour of sleep was associated with lower daytime systolic BP Index Z-score (β=-0.12, 95% CI: -0.20, -0.05), lower daytime diastolic BP Index Z-score (β=-0.11, 95% CI: -0.19, -0.03) and 19% reduced odds of daytime hypertension (OR=0.81, 95% CI: 0.67, 0.98). Each additional hour of earlier timing of sleep onset was associated with lower daytime systolic BP Index Z-score (β=-0.10, 95% CI: -0.19, -0.01), lower daytime diastolic BP Index Z-score (β=-0.16, 95% CI -0.25, -0.06) and 16% reduced odds of daytime hypertension (OR=0.84, 95% CI: 0.68, 1.05). Conclusion In children referred for the evaluation of elevated BP, longer sleep duration and earlier sleep onset were associated with a reduced likelihood of being diagnosed with hypertension. Targeting improvements in sleep should be further investigated as part of first line therapy to treat pediatric hypertension. Support (if any) NIH/NHLBI K01HL123612

Comparison of Pediatric and Adult Ambulatory Blood Pressure Monitoring Criteria for the Diagnosis of Hypertension and Detection of Left Ventricular Hypertrophy in Adolescents

To compare pediatric ambulatory blood pressure monitoring (ABPM) criteria with adult ABPM criteria for the diagnosis of hypertension and detection of left ventricular hypertrophy (LVH) in adolescents. ABPM and echocardiography reports from adolescents age 13-21years from 2015 to 2019 were analyzed. The concordance of hypertension based on pediatric criteria (American Heart Association 2014) was compared with adult criteria from American College of Cardiology/American Heart Association 2017 (overall BP≥125/75mm Hg, wake BP≥130/80mm Hg, sleep BP≥110/65mm Hg) using the Cohen kappa statistic. Logistic regression, adjusted for body mass index z score, and receiver operating characteristic curves (ROCs) compared pediatric criteria vs adult criteria in predicting LVH (left ventricular mass index >95th percentile reference values and left ventricular mass index >51g/m2.7). Of 306 adolescents, 140 (45.8%) had hypertension based on pediatric criteria vs 228 (74.5%) based on adult criteria; the agreement was poor (59.3%, n=137, kappa=0.41). A higher prevalence of LVH was captured by adult criteria only (n=91) compared with pediatric criteria only (n=3). Logistic regression found no significant differences between pediatric and adult criteria in the detection of LVH >95th percentile (OR 1.24, CI 0.66, 2.31, P=.51) or >51g/m2.7 (OR 1.06, CI 0.47, 2.40, P=.89). ROCs for pediatric criteria were not significant for detecting LVH >95th percentile (0.50, P=.91) or >51g/m2.7 (0.55, P=.45), whereas the ROC for adult criteria was significant for detecting LVH >95th percentile (0.59, P=.045) but not >51g/m2.7 (0.63, P=.07). Although all individuals with LVH >51g/m2.7 were hypertensive by adult criteria, 8 of these individuals were missed by pediatric criteria. Adult criteria captured a higher prevalence of LVH and appeared to predict better LVH than pediatric criteria. A consideration to align ABPM criteria for diagnosing hypertension in adolescents with adult guidelines is warranted.

Ambulatory Blood Pressure Monitoring in Children and Adolescents: a Review of Recent Literature and New Guidelines.

This is a review of ambulatory blood pressure monitoring (ABPM) use in pediatrics, focusing on research published in the last 3 to 4years. Recent data has shown that ABPM is more strongly associated with end-organ damage than casual BP, and that obesity and secondary causes of hypertension are strongly associated with nocturnal hypertension. There is evidence that ABPM is useful in management of a larger variety of diagnoses than previously thought. New guidelines from the American Academy of Pediatrics recognize the importance of ABPM in the management of pediatric hypertension. ABPM has an important and growing role in the diagnosis and management of hypertension in children and adolescents. Future efforts should include developing more generalizable normative data and investigating associations between pediatric ABPM results and adult outcomes.

Diagnosis and management of white‐coat hypertension in children and adolescents: A Midwest Pediatric Nephrology Consortium study

Although the definition of white-coat hypertension (WCH) in children and adolescents is clearly defined, little is known about how this condition is actually approached clinically. To better understand the contemporary approach to the diagnosis and management of WCH in pediatric patients, the authors surveyed the membership of the Midwest Pediatric Nephrology Consortium. Seventy-four faculty pediatric nephrologists responded to the survey. The survey results demonstrated uniformity in diagnosing WCH, including ambulatory blood pressure monitoring use in 93% of the respondents and a 75% adherence rate according to the 2014 American Heart Association scientific statement on pediatric ambulatory blood pressure monitoring. A total of 85% of respondents would not embark on further diagnostic evaluation once the WCH diagnosis was established, and none would initiate antihypertensive medications. There was a wide variety of practice habits in follow-up of WCH including frequency of office and out-of-office follow-up blood pressure measurements, the setting and timing of physician follow-up, and the role of repeat ambulatory blood pressure monitoring. The results of this survey highlight the need for prospective studies aimed at establishing the optimal approach to pediatric patients with WCH.

The Use of Ambulatory Blood Pressure Monitoring As Standard of Care in Pediatrics.

Hypertension (HTN) is a significant global health problem, responsible for 7.5 million deaths each year worldwide. The prevalence of HTN is increasing in the pediatric population likely attributed to the increase in childhood obesity. Recent work has also shown that blood pressure (BP) tends to track from childhood to adulthood including BP-related target organ damage. In the last 25–30 years, pediatric use of ambulatory blood pressure monitoring (ABPM) has been expanding mainly in the setting of initial elevated BP measurement evaluation, HTN therapy efficacy follow-up, and renal disease. However, there are many clinical areas where ABPM could potentially be used but is currently underutilized. This review summarizes the current knowledge and the uses of pediatric ABPM and explores clinical areas where it can be very useful both to detect HTN and its longitudinal follow-up. And thus, ABPM could serve as a critical tool to potentially prevent early cardiovascular mortality and morbidity in wide variety of populations. With solid data to support ABPM’s superiority over clinic BP measurements and these clinical areas for its expansion, ABPM should now be part of standard of care in BP evaluation and management in pediatrics.

Update: ambulatory blood pressure monitoring in children and adolescents: a scientific statement from the American Heart Association.

Ambulatory blood pressure monitoring (ABPM) has established roles in the evaluation and management of hypertension in adults but has only been applied to children and adolescents more recently.1 In 2008, the American Heart Association (AHA) issued the first set of consensus recommendations for performance and interpretation of ABPM in pediatrics. Since then, ABPM has found increasing use in children and adolescents, as recently summarized.2 The present document updates the 2008 AHA statement on the use of ABPM in the pediatric population3 with additional data published since the release of that report and also presents a revised interpretation schema. Because no outcome studies are yet available relating ABPM levels in children to outcomes such as myocardial infarction or stroke, these guidelines are largely driven by expert opinion, although they are also informed by available pediatric data on ABPM and surrogate markers of cardiovascular disease. ### Epidemiology of Hypertension High blood pressure (BP) is the leading risk factor–related cause of death throughout the world, accounting for 12.8% of all deaths, including 51% of stroke deaths and 45% of coronary heart disease deaths.4 In the United States, 33.0% of adults >20 years of age have hypertension.5 As our population continues to age, this will only increase, because 90% of people with normal BP at age 55 years will go on to develop hypertension in their lifetimes.6 The prevalence of hypertension in youths is also on the rise. US National Health and Nutrition Examination Survey (NHANES) data from 1963 to 2002 showed a 2.3% increase in prehypertension and a 1% increase in hypertension from 1988 to 1999, with higher rates in non-Hispanic blacks and Mexican Americans.7 In fact, the entire distribution of childhood BP has shifted upward in the United States by 1.4 mm Hg for systolic BP (SBP) and 3.3 …

Pediatric ambulatory blood pressure monitoring: diagnosis of hypertension

Pediatric hypertension (HTN) is a growing concern and should be diagnosed and treated aggressively to reduce the global disease burden. Ambulatory blood pressure monitoring (ABPM) is a useful clinical tool providing a more accurate description of the patient's blood pressure (BP) than office BP measurements, and can be considered the "gold standard" in the evaluation of the pediatric patient with a concern for HTN. The American Heart Association have suggested criteria for diagnosing ambulatory HTN, and research continues into further clarification of how to best utilize the large volume of data obtained from an ABPM report. ABPM has some limitations; however, the advantages far outweigh these. Routine use of ABPM is recommended among clinicians to better evaluate and assess the severity of a child's HTN, and for proper management in order to prevent target organ damage and the resulting sequelae, thereby reducing the burden of cardiovascular risk in hypertensive children and adolescents.

Pediatric Ambulatory Blood Pressure Monitoring: Indications and Interpretations

The prevalence of hypertension in children and adolescents is increasing, especially in obese and ethnic children. The adverse long-term effects of hypertension beginning in youth are known; therefore, it is important to identify young patients who need intervention. Unfortunately, measuring blood pressure (BP) is difficult due to the variety of techniques available and innate biologic variation in BP levels. Ambulatory BP monitoring may overcome some of the challenges clinicians face when attempting to categorize a young patient's BP levels. In this article, the authors review the use of ambulatory BP monitoring in pediatrics, discuss interpretation of ambulatory BP monitoring, and discuss gaps in knowledge in usage of this technique in the management of pediatric hypertension.

Ambulatory blood pressure monitoring in children: imperfect yet essential

There has been increasing emphasis on hypertension and early cardiovascular disease in the pediatric age group over the past decade as a result of various factors, including the obesity epidemic and publication of new clinical guidelines. A key component of identifying children and adolescents with definite or potential hypertension is proper blood pressure (BP) measurement. While ambulatory blood pressure monitoring (ABPM) offers the potential for improved detection of youths at increased cardiovascular risk, it has not been widely adopted. This commentary highlights the crucial role of ABPM in the context of current trends, while at the same time identifying the current barriers to more widespread application of this technique. Chief among these is the lack of a robust, universally applicable database of pediatric ABPM normative values. Even in the absence of ideal normative data, ABPM can and should be widely applied, and a potential algorithm for such an approach is presented.

The Clinical Application of Ambulatory Blood Pressure Monitoring in Pediatrics

Management of hypertension (HTN) largely relies on proper and accurate measurement of blood pressure (BP). Even following the criteria for HTN diagnosis defined in the Fourth report on high BP in children and adolescents, inaccurate diagnosis and misdiagnosis can occur with white coat effect and masked HTN. The use of Ambulatory Blood Pressure Monitoring (ABPM) has been increasing in pediatrics in the last 20 years. The main use of ABPM is to differentiate between sustained HTN and white coat HTN in patients who have elevated casual BP measurements and to detect masked HTN in high risk patients. ABPM is most useful in patients with casual BP within 20% of the 95th percentile for age, gender, and height. This report will highlight the use of ABPM in the evaluation of elevated BP and management of HTN in pediatrics. The discussion includes a review of various non-invasive BP measuring techniques, a description of ABPM and ABPM-unique data and diagnoses, updated ABPM clinical data more specific to pediatrics, its use in HTN clinical trials, and future outlook and direction of ABPM in pediatrics.

The choice of threshold limits for pediatric ambulatory blood pressure monitoring influences clinical decisions

Hypertension in children may be defined by blood pressure elevated above the 95th percentile according to sex and age. Population data for ambulatory blood pressure provide different age-related and sex-related threshold limits to office-derived data. We sought to determine whether, when using ambulatory blood pressure monitoring in a clinical setting, changing 95th percentile threshold limit sets from office-derived to ambulatory blood pressure-derived would lead to different diagnostic decisions. Three nephrologists who were blinded as to patient identity and limit setting method reported on 42 ambulatory blood pressure records from a mixed group of patients aged 5-18 years by using both office-derived threshold limits for the 95th centile of blood pressure and ambulatory blood pressure-derived limits. Decisions regarding the presence or absence of hypertension were compared for each patient according to the limit set. Thirty-five (83%) patients were considered to be hypertensive when office-derived threshold limits were used and 20% (P=0.005) fewer records were reported as showing hypertension when ambulatory blood pressure-derived threshold limits were used. When ambulatory blood pressure limits were applied, there were fewer records with an awake systolic blood pressure load >50% (P=0.004) and the average awake systolic blood pressure load was significantly lower (P<0.001). Ambulatory blood pressure normative data tend to provide higher blood pressure limits for age and sex. Consequently, when ambulatory blood pressure data are used to set threshold limits, clinical decisions based on ambulatory blood pressure may be different than when office limits are used. These findings demonstrate the importance of using the most appropriate limit sets to analyze ambulatory blood pressure and when interpreting ambulatory blood pressure-based research.