bluuebunny/crossref_metadata_2025_split huggingface dataset:
UNDERSTANDING MEASUREMENT OF POSTURAL HYPOTENSION: A NATIONWIDE SURVEY OF PRIMARY CARE PRACTICE IN ENGLAND
Authors: McDonagh Sinead , Cross Rosina , Masoli Jane , Konya Judit , Abel Gary , Sheppard James , Jakubowski Bethany , Bhanu Cini , Fordham Jayne , Turner Katrina , Lamb Sallie , Payne Rupert , McManus Richard , Campbell John , Clark Christopher 
Published: June 2023

Objective:
Postural hypotension (PH), the drop in blood pressure (BP) on standing, is associated with falls, all-cause mortality and cognitive decline. PH diagnostic criteria require lying-to-standing BP measurements. PH is common, with prevalence estimated at 19% in older primary care patients, yet it is infrequently (<1%) recorded in routine English primary care data, suggesting PH testing and/or recording is under-utilised in this setting; reasons for such limited PH testing and/or recording have not yet been explored in detail.
The aim of this study was to understand current PH measurement and management strategies in primary care practices across England.

Design and method:
Clinical Research Networks circulated an online survey to primary care staff involved in measurement of BP from 10th August until 8th December 2022. Responses were summarised as percentages and/or median (inter-quartile ranges (IQR)) and chi2 tests. Modelling is underway to explore response variations according to professional and practice characteristics. Final analyses will be presented at the conference.

Results:
Replies from 703 practitioners in 242 practices were received; predominantly from doctors (51%), nurses (28%) and healthcare assistants (HCAs; 11%), plus pharmacists, paramedics and other roles; median age 45 (IQR 38 to 53) years, 72% female. Overall, doctors (97%) and nurses (92%) reported checking for PH more often than HCAs (82%) or pharmacists (80%; p < 0.001). They all usually check when symptoms are present (97%). Other reasons for checking - patients aged over 80 years (24%); hypertension reviews (17%); medication reviews (12%) or diabetes reviews (11%) – were all more commonly undertaken by allied health professionals than by doctors (p < 0.001). Standing BP measurements are regarded as feasible, usually (77%) following sitting; only 22% use lying-to-standing measurements. 64% observe a rest period (median 5 (2 to 5) minutes) before sitting or lying measurements and 1 (IQR 1 to 2) standing BP measurements are made, usually (66%) within the first minute of standing.

Conclusions:
Findings suggest that most PH assessments in primary care do not meet current guideline criteria. Results from this survey will inform future national guidelines to support PH detection.
WHICH SYSTOLIC BLOOD PRESSURE SHOWS CLOSEST ASSOCIATIONS WITH LEFT VENTRICULAR MASS? THE INTERNATIONAL 24 HOUR AORTIC BLOOD PRESSURE CONSORTIUM (I24ABC)
Authors: Danninger Kathrin , Weber Thomas , Wassertheurer Siegfried , Protogerou Athanase , Sherman James E. , Sala Enrique Rodilla , Muiesan Maria Lorenza , Giannattasio Cristina , Hametner Bernhard , Ortner Stefan , Li Yan , Pascual Jose Maria , McEniery Carmel , Stergiou George S. , Gomes Marco Antonio Mota , McDonnell Barry , Sierra Alejandro De La , Piskorz Daniel , Perl Sabine , Zhang Yi 
Published: June 2023

Objective:
Central systolic blood pressure (cSBP) may be closer associated with hypertensive organ damage, namely left ventricular mass (LVM) and hypertrophy (LVH), as compared to brachial SBP (bSBP), and 24hour ambulatory SBP may be closer associated with LVM and LVH, as compared to office SBP. We sought to address this by pooling data from 21 centers worldwide.

Design and method:
In all centers, bSBP and cSBP was measured with the same validated oscillometric upper arm device (Mobil-O-Graph, I.E.M., Germany), using a transfer function for central pressure, and systolic/diastolic pressure (cSBPC1) or mean/diastolic pressure (cSBPC2) calibration. LVM was determined by echocardiography, and indexed to body surface area (LVMi).

Results:
We studied 2367 participants (45.5% women), 31.3% treated with antihypertensives. Mean age of 50.8 years (range 10-104 years). Average brachial office BP was 137/89 mm Hg, average brachial 24hour BP was 126/80 mm Hg. Average LVMi was 89.9 g/m2, and 24.1% had LVH.
The correlation coefficients between LVMi and office bSBP, office cSBPC1, office cSBPC2, 24hour bSBP, 24hour cSBPC1, and 24hour cSBPC2 were 0.21, 0.20, 0.29, 0.31, 0.29, and 0.38, respectively. Based on z-statistics, the relationship between LVMi and office /24hour cSBPC2 was closer than with the other office/24hour SBPs (p = 0.0001 and 0.0002 for comparison with bSBPs, respectively). These findings were consistent in men and women, across all age groups, in lean, overweight and obese individuals, and in individuals with or without antihypertensives. In ROC analysis, the area under the curve (AUC) for detection of LVH was 0.626, 0.632, 0.668, 0.659, 0.653, and 0.687 for office bSBP, office cSBPC1, office cSBPC2, 24hour bSBP, 24hour cSBPC1, and 24hour cSBPC2, respectively – Figure). The AUC for office/24hour cSBPC2 was significantly larger, as compared to office/24hour bSBP (p < 0.0001 for both comparisons).

Conclusions:
In a large international research consortium, we observed that 24hour cSBP, measured with an oscillometric cuff, shows a significantly closer association with hypertensive cardiac organ damage than the related brachial SBPs. In addition, the method of waveform calibration is crucial.
THRESHOLDS FOR WHITE-COAT AND MASKED BLOOD PRESSURE EFFECTS: AN AMBULATORY BLOOD PRESSURE MONITORING STUDY
Authors: Pont Christian Dal , Feitosa Audes D. M. , Viana Gustavo M. , Starke Siegmar , Azevedo Guilherme S. A. , Mota Marco A. , Barroso Weimar S. , Miranda Roberto D. , Barbosa Eduardo C. D. , Brandão Andréa , Bezerra Rodrigo , Feitosa Camila L.D. M. , Gonçalves Thales A. T. , Nobre Fernando , Jr Decio Mion , Sposito Andrei , Nadruz Wilson 
Published: June 2023

Objective:
The values used to define white-coat and masked blood pressure (BP) effects are usually arbitrary. This study aimed at investigating the accuracy of various thresholds based on the differences (DBP) between office BP (OBP) and 24h-ambulatory BP monitoring (ABPM) to identify white-coat (WCH) and masked (MH) hypertension, which are phenotypes assumed to carry adverse prognosis.

Design and method:
This cross-sectional study included 11,350 [Derivation cohort; 45% men, mean age = 55.1 ± 14.1 years, OBP = 132.1 ± 17.6/83.9 ± 12.5 mmHg, ABPM = 121.6 ± 11.4/76.1 ± 9.6 mmHg, 25% using antihypertensive medications (AH)] and 7,220 [Validation cohort; 46% men, mean age = 58.6 ± 15.1 years, OBP = 136.8 ± 18.7/87.6 ± 13.0 mmHg, ABPM = 125.5 ± 12.6/77.7 ± 10.3 mmHg; 32% using AH] unique individuals who underwent OBP and ABPM measurements. We compared the sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and area under the curve (AUC) of 8 different ↗BP thresholds to detect WCH (↗systolicBP/↗diastolicBP = +28/+17, +20/+15, +20/+10, +16/+11, +15/+9, +14/+9 mmHg and ↗systolicBP = +13 and +10 mmHg) and eight different ↗BP thresholds to detect MH (↗systolicBP/↗diastolicBP = -14/-9, -5/-2, -3/-1, -1/-1, 0/0, +2/+2 mmHg and ↗systolicBP = -5 and -3 mmHg), built from formerly reported criteria in the literature. WCH was defined as OBP> = 140/90mmHg and ABPM < 130/80mmHg, and MH was defined as OBP < 140/90mmHg and ABPM> = 130/80mmHg.

Results:
The +20/+15 mmHg threshold showed the best AUC (0.804, 95%CI = 0.794 - 0.814) to detect WCH in the Derivation cohort, with sensitivity, specificity, PPV and NPV of 80.6%, 80.2%, 42.3%, and 95.8%, respectively. The +2/+2 mmHg threshold showed the highest AUC (0.741, 95%CI = 0.728 - 0.754) to detect MH, with sensitivity, specificity, PPV and NPV of 78.9%, 69.3%, 22.0% and 96.8%, respectively. Both threshold values also had the best accuracy to detect WCH (0.767, 95%CI = 0.754 - 0.780) and MH (0.767, 95%CI = 0.750 - 0.784) in the Validation cohort. In secondary analyses, these thresholds had the best accuracy to detect WCH and MH in individuals using or not AH, and to detect individuals with higher and lower office-than-home BP stages, respectively, in both cohorts.

Conclusions:
The +20/+15 and +2/+2 mmHg ↗BP thresholds had the best accuracy to detect hypertensive patients with WCH and MH, respectively, and may be indicators of marked white-coat and masked BP effects.
CAN RECORDING KOROTKOFF SOUNDS DURING BRACHIAL CUFF INFLATION PROVIDE MORE ACCURATE NON-INVASIVE ESTIMATES OF INTRA-ARTERIAL BLOOD PRESSURE?
Authors: Celler Branko , Yong Andy , Rubenis Imants , Butlin Mark , Argha Reza , Rehan Rajan , Avolio Alberto 
Published: June 2023

Objective:
We have previously demonstrated that recording onset and termination of Korotkoff sounds as markers of systolic (SBP) and diastolic (DBP) during brachial cuff deflation results in underestimation of true SBP. In this study we explore whether recording Korotkoff sounds during cuff inflation provides more accurate non-invasive estimates of intra-arterial blood pressure (IABP).

Design and method:
Experiments were carried out on 15 participants, (14 males, 64.3 ± 10.4 years; one female, 86 yo), undergoing coronary angiography. A conventional (oscillometric) BP cuff, with a microphone for Korotkoff sounds, was placed on the upper arm. The cuff was inflated at rate of approximately 2.5mm Hg/sec and deflated at the same rate. Inflation and deflation cycles were randomised and separated by 2 - 3 minutes. IABP was measured below the cuff with a fluid-filled catheter inserted via the radial artery and an external transducer. Korotkoff sounds were processed electronically, and custom algorithms identified the cuff pressure (CP) at which the first and last Korotkoff sounds were heard.

Results:
Systolic (SBP), and diastolic (DBP) pressure were 147.7.6 ± 12.7 and 70.7 ± 9.7mmHg. The CP at which the brachial artery closes during rapid (∼20mmHg/sec) cuff inflation (132.0 ± 17.1) was similar to that of slow (2.5mmHg/sec) inflation (132.0 ± 16.3 mmHg). However, peak Korotkoff sound energy was significantly reduced (P = 0.003) from 0.19 ± 0.1 to 0.15 ± 0.09 RMS volts and the Korotkoff sounds were often observed to disappear prematurely before brachial artery closure. Difference between intra-arterial SBP and CP at the last recorded Korotkoff sound (27.5 ± 9.3 mmHg) during cuff inflation was significantly higher (P = 0.0025) than during slow cuff deflation (18.9 ± 8.3 mmHg). In contrast, DBP recorded at first onset of the Korotkoff sounds (70.5 ± 11.1 mmHg) was consistently similar to intra-arterial DBP (70.7 ± 9.7 mmHg).

Conclusions:
SBP estimates derived from the last Korotkoff sound recorded as the cuff inflates generates greater errors than when Korotkoff sounds are first recorded as the cuff deflates. In contrast, the estimate of DBP derived from the first onset of the Korotkoff sound as the cuff inflates, appears to reflect accurately the true intra-arterial DBP.
THE INFLUENCE OF BASELINE DIASTOLIC BLOOD PRESSURE ON THE EFFECTS OF INTENSIVE BLOOD PRESSURE LOWERING: RESULTS FROM THE STEP RANDOMIZED TRIAL
Authors: Yang Ruixue , Cai Jun 
Published: June 2023

Objective:
The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial reported cardiovascular benefits of intensive systolic blood pressure (SBP) lowering. However, the influence of baseline diastolic blood pressure (DBP) on the effects of intensive SBP lowering on cardiovascular outcomes has not been fully elucidated.

Design and method:
In this post hoc analysis of the STEP trial, participants were randomly assigned to receive intensive (110 to <130 mmHg) or standard SBP treatment (130 to <150 mmHg) and categorized by baseline DBP into subgroups: <70, 70 - 79, and > = 80 mmHg. The primary outcome was a composite of stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. A competing risk proportional hazards regression model was used in the analysis. We compared results across subgroups stratified by baseline DBP levels by including a multiplicative interaction term between SBP treatment arms and subgroups (treatment arm* subgroup).

Results:
Of the 8,511 participants, 960, 2,474, and 5,077 had baseline DBP divided in intervals of <70, 70 - 79, and > = 80 mmHg, respectively. A reduction in the primary outcome was observed among those randomized to intensive SBP lowering in each DBP subgroup but was significant only in the subset of participants with baseline DBP > = 80 mmHg (<70 mmHg: adjusted hazard ratio, 0.81 [95% confidence interval, 0.43 - 1.51]; 70 - 79 mmHg: 0.80 [0.55 - 1.15]; > = 80 mmHg: 0.73 [0.54 - 0.97]). There were no significant interactions between SBP treatment and baseline DBP subgroups for the primary and secondary outcomes (all P for interaction >0.05). The sensitivity analyses showed consistent results with the main analysis.

Conclusions:
Baseline DBP levels did not modify the beneficial effects of intensive SBP lowering on cardiovascular outcomes.
REMNANT CHOLESTEROL AND INTENSIVE BLOOD PRESSURE CONTROL IN OLDER PATIENTS WITH HYPERTENSION: A POST HOC ANALYSIS OF THE STEP RANDOMIZED TRIAL
Authors: Yang Ruixue , Cai Jun 
Published: June 2023

Objective:
Emerging evidence shows the close relationship between remnant cholesterol (RC) and hypertension. However, it is unknown whether RC is associated with the effect of intensive systolic blood pressure (SBP) lowering on cardiovascular outcomes. We aimed to determine the influence of baseline RC on the effect of intensive SBP lowering in hypertensive patients.

Design and method:
We performed a post-hoc analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Participants were randomly allocated to intensive SBP treatment (110 to <130 mmHg) or standard SBP treatment (130 to <150 mmHg). RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol. The median RC concentration was used to categorize participants into low and high RC groups. The primary outcome was a composite of stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes.

Results:
Of the 8,511 participants in the STEP trial, 8,276 participants had available baseline RC concentrations (low RC group: n = 4,200; high RC group: n = 4,076). After a median follow-up of 3.33 years, a reduction in the primary outcome was observed in participants allocated to receive intensive SBP lowering in both groups; however, the reduction was only significant in the high RC group (high RC group: adjusted hazard ratio [aHR] 0.62; 95% confidence interval [CI] 0.45–0.84; low RC group: 0.91 [0.67–1.24]; P for interaction = 0.09). Intensive SBP treatment decreased all-cause mortality in the high RC group (aHR 0.48; 95% CI 0.28 – 0.81) but increased it in the low RC group (aHR 2.51; 95% CI 1.47 – 4.28; P for interaction <0.001). Among the adverse events, only hypotension was slightly increased in the high RC group (adjusted relative risk 1.48; 95% CI 1.02 – 2.16).

Conclusions:
Patients with high RC experienced greater cardiovascular benefits with intensive SBP lowering.
SEX DIFFERENCES IN INDIVIDUALS WITH OFFICE HIGH NORMAL BLOOD PRESSURE WHO DEVELOPED HYPERTENSION IN 3-YEAR FOLLOW-UP
Authors: Kalos Theodoros , Dimitriadis Kyriakos , Konstantinidis Dimitrios , Siafi Eirini , Kakouri Niki , Iliakis Panagiotis , Liatakis Ioannis , Leontsinis Ioannis , Tsioufis Panagiotis , Polyzos Dimitrios , Filippou Christina , Drogaris Sotirios , Fragoulis Christos , Thomopoulos Costas , Tsioufis Konstantinos 
Published: June 2023

Objective:
Recent data demonstrated that females develop target organ damage earlier than men. Normotensive individuals with office high normal blood pressure (BP) who remain at normotensive range for at least 3 years demonstrate hemodynamic differences according to their gender.

Design and method:
100 individuals with high normal BP were followed-up for 3 consecutive years. During enrolment they underwent ambulatory BP monitor (ABPM), electrocardiogram (ECG), echocardiogram, carotid-femoral pulse wave velocity (PWV), sympathetic drive was assessed by muscle sympathetic nerve activity (MSNA) to assess sympathetic drive, a negative for ischemia treadmill exercise stress test (TST) (Bruce protocol) and blood sampling. Follow-up was scheduled every 6 months for 3 consecutive years, where BP measurements were assessed in office and with ambulatory BP monitoring (ABPM). All participants offered lifestyle advise to lower their BP. Endpoint was development of hypertension (HTN). Then they divided into males and females (postmenopausal).

Results:
19 males and 21 females developed HTN. Men were younger than women (51vs58y, p = 0.03). Office and ABPM measurements did not differ significantly. Men exhibit higher waist to hip ratio (0.92vs0.86, p = 0.012), higher uric acid levels (5.6vs4.7mg/dL) and better kidney function according 2021 CKD-EPI GFR (97vs87,p = 0.03). Contrary HDL levels were lower (54vs66mg/dL, p = 0.048).
From those who remained normotensive (24 males and 36 females), men exhibit increased left ventricular mass index (90vs82, p = 0.045) compared to women. Interestingly to those who became hypertensive left ventricular mass index was similar (79vs81gr/m2, p = 0.53).
Women had greater sympathetic drive as recorded from MSNA levels (33vs36bursts/min,p = 0.012) and MSNA per 100bpm (47vs54burst,p = 0.041).
Arterial stiffness as recorded from c-fPWV (8.3vs8.2m/s) did not differ significantly among genders.
In TST (Bruce protocol) men exercised two extra minutes on average (9vs7min, p < 0.0001), achieving greater exercise duration and METs (11.2vs8.8, p = < 0.0001) accordingly. SBP at peak exercise was higher in men (208vs197mmHg, p = 0.03).

Conclusions:
Women who became hypertensive equalized their heart volume with men, demonstrate greater sympathetic activity and worsening of their kidney function. Additionally, their exercise capacity was significantly reduced in comparison with men. Overall, it seems there are structural alterations in heart and kidneys that demonstrates the need to prevent earlier the organ damage during high blood pressure stage in women.
DEFICIENCY OF COMPLEMENT C3A AND C5A RECEPTORS DOES NOT PREVENT ANGIOTENSIN II–INDUCED HYPERTENSION AND HYPERTENSIVE END ORGAN DAMAGE
Authors: Dreher Leonie , Bode Marlies , Herrnstadt Georg Rudolf , Ehnert Nicolas , Kirkerup Pia , Lindemeyer Maja T. , Meyer-Schwesinger Catharine , Ehmke Heimo , Köhl Jörg , Huber Tobias B. , Wiech Thorsten , Wenzel Ulrich O. 
Published: June 2023

Objective:
Complement activation may play an important role in pathophysiology of hypertension and associated end organ damage through its effect on tissue integrity and immune responses. The anaphylatoxins C3a and C5a are highly active effectors of the complement system operating through binding to their receptors C3a3R and C5aR1. Recently it was suggested that regulatory T cells (Tregs) are downregulated in hypertension and that combined deficiency of C3aR and C5aR1 in lymphocytes upregulates Tregs and heals hypertension (Circ Res 122: 970-983, 2018).

Design and method:
To further address the role of C3aR, C5aR1 and Tregs in human and murine hypertension we used data from the European Renal cDNA Bank, renal single cell sequencing and renal immunohistochemistry of hypertensive patients.

Results:
Expression of C3aR and C5aR1 was mainly found in myeloid cells and almost absent in lymphocytes and resident renal cells. An increased expression of C3aR, C5aR1 as well as forkhead box protein 3 (FoxP3), a known marker for Tregs, was found in the kidney in hypertension.
Next we determined whether C3aR deficiency or C3aR/C5aR1 double deficiency decreases blood pressure and hypertensive injury in angiotensin (Ang) II infused mice.
No difference was found for blood pressure, renal injury (glomerular filtration rate, albuminuria, glomerular and tubulointerstitial injury, inflammation) and cardiac injury (cardiac fibrosis, heart weight, gene expression) between C3aR knockout and wildtype mice as well as C3aR/C5aR1 double knockout respectively. Ang II as well as DOCA salt induced hypertension resulted in an increased number of Tregs in the kidney. Isolation of a very pure (>99%) Treg population from a RORC x FIR double fluorescence reporter mouse revealed low abundance of C3aR and absence of C5aR1 in murine Tregs.

Conclusions:
In summary, hypertensive nephropathy in patients and mice is characterized by an increased expression of anaphylatoxin receptors and Tregs. However, deficiency of C3aR alone or C3aR and C5aR1 combined does not influence blood pressure or hypertensive end organ damage. Targeting the anaphylatoxin receptors C3aR alone or in combination with C5aR1 is not useful to treat cardiovascular disease in hypertension.
CARDIOVASCULAR RISK IN TREATED HYPERTENSIVE PATIENTS WITH ISOLATED DIASTOLIC HYPERTENSION AND ISOLATED LOW DIASTOLIC BLOOD PRESSURE
Authors: Chang Wei -Lun , Chen Ying -Fan , Chuang Shao -Yuan , Lee Yu -Hsuan , Shiu Ming -Neng , Guo Chao -Yu , Huang Chi -Jung , Chiang Chern -En , Chen Chen -Huan , Staessen Jan A. , Asayama Kei , Ohkubo Takayoshi , Niiranen Teemu J. , Boggia Jose , Cheng Hao -Min 
Published: June 2023

Objective:
Antihypertensive therapy in the elderly often targets at systolic blood pressure (SBP) and excessive lowering of diastolic blood pressure (DBP) may occur. Evidence on the cardiovascular risk of isolated diastolic hypertension (IDH) is inconsistent. This study investigated whether IDH and isolated low diastolic blood pressure (ILDBP) were associated with major adverse cardiovascular events (MACE) in patients who were receiving antihypertensive therapy and had normalized SBP.

Design and method:
A total of 7582 hypertensive patients aged > = 50 years and with on-treatment SBP <130 mmHg from the Systolic Blood Pressure Intervention Trial (SPRINT) were analyzed. Average DBP of 60 mmHg during follow-up visits was determined as the lower boundary by a multivariate adaptive regression spline analysis for MACE. According to the on-treatment DBP, patients were divided into <60 mmHg (ILDBP, n = 1031), 60–79 mmHg (n = 5432), and > = 80 mmHg (IDH, n = 1119). Time-varying Cox proportional hazards model was used to estimate the MACE risk, comparing IDH or ILDBP with DBP 60–79 mmHg. External validation was carried out with a two-stage meta-analysis of individual participant data (IPD) for 3560 individuals from six cohorts.

Results:
The SPRINT participants had a median age of 68.2 years, and 64.9% of whom were men. During a median follow-up of 3.5 years, 512 patients had MACE. Incidence of MACE per 100 person-years was 3.9 case for ILDBP, 1.9 cases for DBP 60 – 79 mmHg, and 1.8 cases for IDH. Compared with DBP 60 – 79 mmHg, ILDBP was associated with a 1.32-fold increased MACE risk (95% CI: 1.05 – 1.66), but IDH was not (hazard ratio: 1.18, 95% CI: 0.87 – 1.59). Among the 50 – 64 years subgroup, IDH was associated with a 1.59-fold increased MACE risk (95% CI: 1.01 – 2.49), with effect modification by age (P for interaction 0.005). The IPD meta-analysis also suggested a significantly higher risk for MACE among patients with ILDBP (hazard ratio: 1.22, 95% CI: 1.03 – 1.46), compared to patients with DBP 60 – 79 mmHg.

Conclusions:
Among patients on antihypertensive medications with normalized SBP, excessively low DBP increased the MACE risk but IDH did not. More research is needed to develop appropriate treatment strategies for ILDBP.