bluuebunny/crossref_metadata_2025_split huggingface dataset:
LEVERAGING TELE-EDUCATION AS AN EFFECTIVE PLATFORM TO PROVIDE EASY ACCESS TO HEALTHCARE WORKERS ON HYPERTENSION MANAGEMENT IN SUB-SAHARAN AFRICA
Authors: Muktar Maryam , Dabiri Olabisi , Okeke Chika , Ogboye Ayoposi , Odukwe Adaora , Mobisson Nneka 
Published: June 2023

Objective:
This study aims at showing the efficacy of using tele-education in making knowledge easily accessible to healthcare workers by using the University of New Mexico's Project ECHO® model. This model provides healthcare workers access to evidence-based knowledge to combat the challenges associated with sub-optimal training and depleting resources across Sub-Saharan Africa's healthcare system. This effort has led to significant improvement in the quality of healthcare service delivery.

Design and method:
Aggregate data were obtained from 4 Tele-education sessions conducted between August 2022- November 2022 to improve the capacity of Healthcare workers. Each session included a didactic presentation by a subject matter expert and a case study presentation by a healthcare worker. The case presentation involved citing real-life hypertension-related cases at the health facility to enable peer-to-peer learning exchange, as encouraged by the ECHO® model for Healthcare workers. The impacts of the sessions were measured using the pre and post-session tests to evaluate the knowledge gained by participants.

Results:
The population of this study was the 1,389 Healthcare workers from different cadres (such as doctors, nurses, midwives, lab scientists, Community Health Extension Workers (CHEWs), and mid-level managers) who joined the tele-education sessions. There was an average knowledge gain of 11.1%. Over 1.7 million indirect beneficiaries (patients) were reached through services provided by these trained Healthcare workers.

Conclusions:
The knowledge gained demonstrated the effectiveness of tele-education in improving the capacity of Healthcare workers to provide quality services in managing patients living with or at risk of hypertension. Tele-education cuts across most of the barriers encountered in spreading knowledge to healthcare workers and promotes health literacy and improved service delivery.
EFFECTS OF CAROTID BARORECEPTOR STIMULATION ON REGIONAL SYMPATHETIC ACTIVITY IN CHRONIC HEART FAILURE
Authors: Vanoli Jennifer , Dell’Oro Raffaella , Gronda Edoardo , Quarti-Trevano Fosca , Seravalle Gino , Grassi Guido 
Published: June 2023

Objective:
Carotid baroreceptor stimulation (BAT) exerts in heart failure (CHF) sympatho-inhibitory effects. No information is available, however, on whether these effects have a regional or a more generalized behaviour.

Design and method:
In 9 CHF patients (age 58.3 ± 252 yrs, mean ± SD) we recorded via the microneurographic technique muscle and skin sympathetic nerve traffic (MSNA and SSNA, respectively) before, 6 and 12 months following BAT. Measurements included left ventricular ejection fraction (LVEF), brain natriuretic peptide BNP (elisa), 6-minute walking test (6WT), New York Heart Association (NYHA) class, Minnesota score, together with routine laboratory variables. 10 age-matched CHF patients not underwent BAT served as controls.

Results:
BAT caused significant increase in LVEF (from 33.4 ± 5.1 to 37.1 ± 5.4%, P < 0.05) and in 6 WT, and a significant reduction in the Minnesota score and in NYHA class (from 3.3 ± 0.4 to 2.4 ± 0.4 a.u), unaltering BNP. MSNA, but not SSNA, was markedky activated in CHF. BAT caused a significant reduction in MSNA 6 and 12 months follow-up (from 70.7 ± 2.7 to 47.0 ± 4.3 and 44.1 ± 3.5 bursts/100heartbeats, means ± SD, P < 0.05). This effect was not accompanied by any significant change in SSNA (from 11.3 ± 2.1 to 11.5 ± 1.7 and 11.6 ± 2.1 bursts/minute, P = NS). A significant correlation was found between baseline MSNA values and the MSNA changes after BAT, which were also related to the LVEF modifications. No significant change in the various variables was detected in the control group followed for a 12 month observation.

Conclusions:
These data provide the first evidence that BAT exerts heterogeneous effects on sympathetic cardiovascular drive, inducing a marked reduction in MSNA but not in SSNA, which appears to be within the normal range in this condition. These effects may depend on the different reflex modulation regulating neuroadrenergic drive in these cardiovascular districts.
CHANGES IN ECHOCARDIOGRAPHIC INDICES FOLLOWING KIDNEY TRANSPLANTATION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Betsikos Achilleas , Theodorakopoulou Marieta , Korogiannou Maria , Marinaki Smaragdi , Papagianni Aikaterini , Boletis John , Tsioufis Konstantinos , Sarafidis Pantelis 
Published: June 2023

Objective:
Cardiovascular disease is the leading cause of death in ESKD and uremic cardiomyopathy contributes significantly to the increased cardiovascular risk in these patients. Kidney transplantation is associated with improved survival compared to dialysis. This systematic review and meta-analysis (CRD42022371202) aims to assess the changes in echocardiographic indices in patients before and following kidney transplantation

Design and method:
We included studies in adult subjects with echocardiographic assessments before (baseline) and following kidney transplantation (>1 month follow-up). The primary outcome measure was left-ventricular mass index (LVMI). Literature search involved PubMed, Web-of-Science and Scopus databases, manual search of article references and grey literature.

Results:
From 6463 records initially retrieved, 35 studies with a total of 2692 participants were included in the final quantitative meta-analysis. From 30 studies (2211 patients) reporting the primary outcome, LVMI was significantly decreased after kidney transplantation compared to pre-transplantation values [WMD -21.16 g/m2, 95%CI(-27.21, -15.12), I2 = 88%, P < 0.001]. In subgroup analysis, higher differences were evident among 6 studies (N = 163) evaluating LVMI < 6 months after kidney transplantation [WMD -41.54 g/m2, 95%CI (-51.31, -31.78), I2 = 13%, P < 0.001] and lower differences among 24 studies (N = 2048) evaluating LVMI >6 months after kidney transplantation [WMD -16.64 g/m2, 95%CI(-22.79, -10.49), I2 = 88%, P < 0.001]. In sensitivity analyses, patients receiving kidney from living kidney donors (WMD; -76.90 g/m2, 95%CI (-122.13, -31.67), I2 = 88%, P < 0.001) and those on hemodialysis before KTx [WMD;-33.76 g/m2, 95%CI (-51.51, -16.00), I2 = 92% P < 0.001] presented higher LVMI reductions following transplantation.

Conclusions:
Kidney transplantation is associated with significant reductions in LVMI compared to the pre-transplantation levels. This could be another factor contributing to the lower cardiovascular risk observed in KTRs compared to dialysis patients
THE (PRO)RENIN RECEPTOR IS INVOLVED IN KIDNEY ORGANOID DEVELOPMENT
Authors: Lin Hui , Li Shengbing , Mullick Adam , Bosch Thierry van den , Hoogduijn Martin , Danser A.H. Jan 
Published: June 2023

Objective:
The (pro)renin receptor [(P)RR], a receptor for prorenin and renin, is widely distributed in the body, including the kidneys. Studies in (P)RR knockout mouse models indicate that (P)RR ablation can be detrimental to renal development and function. However, the lack of human models hinders investigation into the role of (P)RR in human kidney development. The advent of human induced pluripotent stem cell (iPSC) – derived kidney organoids provides a tool to study the role of (P)RR in human kidney development.

Design and method:
To investigate the effects of (P)RR knockdown on kidney organoid development, human iPSC – derived kidney organoids were generated according to a previously described protocol. We silenced the (P)RR by introducing (P)RR antisense oligonucleotides (ASOs) by electroporation at the stage of iPSCs and nephron progenitor cells induction, respectively. The development of kidney organoids was monitored morphologically and through protein expression analysis of nephron markers by immunohistochemistry staining which was quantified by Image J.

Results:
After silencing the (P)RR at the initial stage of differentiation, the size of iPSCs-derived organoids was substantially smaller, but the size of tubular structures was bigger. We observed a decrease by 50% in both WT1 (glomerular cell marker) and PDGFR↑ (stromal cell marker) expressions in (P)RR-knockdown organoids, a 4-fold and 2-fold increase in expressions of fibrogenic cell markers ↑-SMA and COL1A1 respectively, and no change in Villin1 (proximal tubular cell marker) and Cadherin-1 (distal tubular cell marker) expression. Additionally, (P)RR knockdown at the stage of nephron progenitor cells induction decreased the expressions of Villin1 and Cadherin-1 in organoids by 50% and 60% separately, while it induced a 4-, 3-, 2- and 2-fold increase in the expressions of CD31 (endothelial cell marker), PDGFR↑, ↑-SMA and COL1A1 respectively.

Conclusions:
This study shows that (P)RR silencing at the initial stage of differentiation or at the stage of nephron progenitor cells induction impaired normal development of kidney organoids. Its absence caused a shift into the direction of fibrogenic cells. This study provides new insights into the understanding the role of (P)RR in human kidney development.
BEAT-TO-BEAT VARIABILITY OF INVASIVE PULSE WAVE VELOCITY: TECHNICAL AND CLINICAL ASPECTS
Authors: Giudici Alessandro , Grillo Andrea , Scalise Filippo , Reesink Koen D. , Delhaas Tammo , Salvi Paolo , Parati Gianfranco , Spronck Bart 
Published: June 2023

Objective:
Invasive foot-to-foot pulse wave velocity (PWV) is the reference standard for validating new non-invasive PWV-measuring devices. Because of acute haemodynamic variability and data processing issues, PWV shows beat-to-beat variability, which may have important clinical and technical implications. Though current device validation guidelines suggest averaging over at least n = 3 heartbeats to cope with variability, quantitative data on PWV's beat-to-beat variability is lacking. We aimed to quantify this variability and its impact on the confidence of the PWV estimate.

Design and method:
Pressure waveforms were acquired in n = 82 individuals in the ascending aorta and iliac bifurcation using a dual-tip intra-aortic catheter. For each individual, two datasets were recorded: 1) simultaneous ascending and iliac pressure acquisitions (with ECG), and 2) an additional ascending aorta pressure acquisition (with ECG). Pressure wave foot detection was performed using the intersecting interpolant method. By combining the iliac pressure recording from the first acquisition with the ascending aorta pressure recording from the second acquisition, we evaluated how a sequential acquisition protocol (e.g., catheter pull-back) affects the variability. Furthermore, we estimated how averaging over n consecutive heartbeats affects the standard deviation (SD) of such n-beats-averaged estimate of PWV.

Results:
PWV was 10.93 ± 4.24 and 11.12 ± 4.42 m/s (mean ± between-subject SD) for simultaneous (PWVsim) and sequential acquisitions (PWVseq; p = 0.002), respectively. The average within-subject SD ( = variability) was 0.48 ± 0.28 m/s for PWVsim and 1.47 ± 1.20 m/s for PWVseq (p < 0.001). This increase in variability was mainly due to the beat-to-beat variability of the ECG R-wave-to-pressure foot time interval, which was ∼2 times higher than that of the simultaneous foot-to-foot transit time (Figure A). Averaging over n = 3 reduced the variability of PWVsim to 0.37 ± 0.25 m/s, while n = 10.24 (median) is required to reach a comparable variability for PWVseq (Figure B).

Conclusions:
Variability of an invasive foot-to-foot PWV estimate increases considerably when using sequential rather than simultaneous acquisitions. This increase is caused by the high beat-to-beat variability of the duration of the pre-ejection period. To reduce the effective variability of a sequential acquisition to the same level as that of a simultaneous acquisition, averaging over an approximately threefold higher number of heartbeats is required.
ARTERIAL STIFFNESS IN NORMOTENSIVE PATIENTS WITH HYPOPARATHYROIDISM COMPARED TO CONTROLS
Authors: Cosenso-Martin Luciana Neves , Vilela-Martin Jose F , Yugar-Toledo Juan C 
Published: June 2023

Objective:
Hypoparathyroidism is a rare disease characterized by the inability of parathyroid hormone (PTH) to maintain calcium homeostasis. Multiple etiologies, congenital or acquired can cause this morbidity. However, the most common cause is hormone deficiency secondary to cervical surgical explorations. Patients with post-surgical hypoparathyroidism have an increased risk of mortality, with various clinical and molecular evidence of the effects on the cardiovascular system. This study aimed to assess arterial stiffness by measuring the carotid-femoral pulse wave velocity (PWV) in a population of patients with hypoparathyroidism.

Design and method:
This is a cross-sectional study with 30 patients with post-surgical hypoparathyroidism and 25 normal volunteers from the Endocrinology Outpatient Clinic of the Medical School. Arterial stiffness was evaluated by the analysis of PWV using SphygmoCor system. Statistical analysis was made with software IBM-SPSS Statistics 27 (IBM Corporation, NY, USA).

Results:
The average PWV in patients with hypoparathyroidism was not different compared to controls (8.70 vs 7.50; p = 0.084). However, when comparing only normotensive patients in both groups (21 hypoparathyroidism and 16 controls), levels of PWV in patients with hypoparathyroidism was higher and statistically significant (7.64 vs 6.50; p = 0.039). Age, hypertension, LDL cholesterol levels, ionized calcium, total calcium, and the Calcium x Phosphorus product were independent predictor variables for PWV.

Conclusions:
Post-surgical hypoparathyroidism increases arterial stiffness in normotensive individuals, evaluated by PWV and total calcium level, as well the Calcium x Phosphorus product are involved in this condition. Therefore, vascular stiffness may be one of the pathophysiologic mechanisms of the cardiovascular disease in patients with hypoparathyroidism. Further studies are necessary to elucidate this condition.
PLASMA METABOLOMIC PROFILING PREDICTS AORTIC STIFFNESS AND RISK OF INCIDENT CARDIOVASCULAR DISEASE AND MORTALITY AFTER 16 YEARS OF FOLLOW-UP IN THE GENERAL POPULATION
Authors: Johansson Madeleine , Engstrom Gunnar , Orho-Melander Marju , Melander Olle , Nilsson Peter M. , Ottosson Filip 
Published: June 2023

Objective:
The mechanisms and metabolomic profile underlying early vascular ageing have not been explored in the general population. We aimed to investigate the plasma metabolomic profile in aortic stiffness (vascular ageing) and associated risk of incident cardiovascular disease and mortality in the general population.

Design and method:
We analysed 108 metabolites in plasma of 5172 individuals from two prospective population-based cohorts with over 16 years of follow-up. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Metabolite-predicted PWV was calculated in the older population based on the LASSO regression model by randomly assigning a training set (80%) and validation set (20%) in the younger cohort. Correlations between metabolite-predicted PWV and traditional cardiovascular risk factors were assessed by Spearman. Cox regression was used to calculate risk of incident cardiovascular disease and mortality, and all-cause mortality. All models were adjusted for age, sex and traditional cardiovascular risk factors.

Results:
Study characteristics are displayed in Table 1. Aortic stiffness was positively associated with following metabolites: long-chain acyl carnitines (C16:0, C16:1 and C13:0), dimethylguanidino valeric acid (DMGV), glutamate and cysteine, while serine was negatively associated with aortic stiffness (Figure 1A). The plasma metabolome predicted aortic stiffness in the validation cohort with good accuracy (R2 0.25, Figure 1B). Metabolite-predicted aortic stiffness was significantly correlated with age (r = 0.68), SBP (r = 0.49), BMI (r = 0.43), and sex (r = 0.20) in both cohorts cross-sectionally. During an average follow-up of 16 years, aortic stiffness predicted by baseline metabolites was associated with increased risk of incident coronary artery disease, incident stroke, cardiovascular mortality, and all-cause mortality in the older population (Figure 1C).

Conclusions:
For the first time, we show that aortic stiffness (vascular ageing) is predicted by altered metabolism of glutamate, acylcarnitine, cysteine, serine, and DMGV in the general population. These metabolic disturbances precede aortic stiffness by several years and are also associated with increased cardiovascular risk factor burden, and future risk of coronary artery disease, stroke, cardiovascular mortality, and all-cause mortality. Our results highlight the relevance of investigating the molecular pathways related to aortic stiffness. Further metabolomics studies are warranted to verify these findings in independent populations.
CENTRAL AND PERIPHERAL HAEMODYNAMIC RESPONSE TO COFFEE CONSUMPTION IN THE COHORT OF THE BRISIGHELLA HEART STUDY
Authors: Fogacci Federica , Cicero Arrigo , D’Addato Sergio , Grandi Elisa , Rizzoli Elisabetta , Borghi Claudio 
Published: June 2023

Objective:
Even though coffee consumption has been clearly related to a number of benefits on the cardiovascular system, its effect on blood pressure (BP) has not been fully elucidated.

Design and method:
In this sub-analysis of the Brisighella Heart Study (BHS), we assessed the central and peripheral BP response to coffee drinking in a sub-cohort of 720 men (47.9%) and 783 women (52.1%), for whom a full set of clinical, laboratory and haemodynamic parameters was available.

Results:
According to our observations, moderate coffee drinking was associated to either higher levels of systolic BP (SBP) compared to heavy coffee consumption and lower SBP than non-coffee drinking (p-value for trend <0.05). In particular, people who drank 2 cups of coffee per day and people who drank >3 cups per day had respectively 5.2 ± 1.6 mmHg (p = 0.010) and 9.7 ± 3.2 mmHg (p = 0.007) lower SBP than non-coffee drinkers. Similar trends were also observed for peripheral pulse pressure (PP), aortic BP and aortic PP. In the age-adjusted multiple linear regression model, negative predictors of SBP, PP, aortic BP and aortic PP were the estimated glomerular filtration rate (eGFR), female sex and coffee consumption. Positive predictors included body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C).

Conclusions:
Our findings show that regular coffee drinking lowers SBP, PP, aortic BP and aortic PP, without having any effect on arterial stiffness.
PREDICTING PREECLAMPSIA DURING PREGNANCY: THE VALUE OF BLOOD PRESSURE MEASUREMENT TRENDS TO IDENTIFY WOMEN AT HIGHEST RISK
Authors: Harris Katie , Xu Lily , Kat Annelien De , Shang Jie , Woodward Mark , Hirst Jane , Henry Amanda 
Published: June 2023

Objective:
Hypertensive disorders of pregnancy, including preeclampsia are serious complications increasing the risk of morbidity and mortality for both mother and baby.
We hypothesise that blood pressure (BP) trends during pregnancy are a useful, accessible and practical predictor of preeclampsia onset. In this study we aimed to determine: (i) the association between mean arterial pressure (MAP), Systolic BP (SBP) and Diastolic BP (DBP) at time of pregnancy booking with subsequent preeclampsia development, and (ii) whether repeated measures of BP thought pregnancy can improve prediction of preeclampsia.

Design and method:
Data were from 11,008 women with a singleton pregnancy who received antenatal care and gave birth across three metropolitan Sydney hospitals 2017-2020. BP measurements were represented as MAP, SBP and DBP.
Three sets of logistic regression models were used to yield odds ratios (ORs) with 95% confidence intervals (CIs) for the association of preeclampsia with: (1) booking BP, (2) summary BP measurements (mean, maximum, standard deviation (SD)) and (3) growth curve parameters (mean BP, slope and standard error of slope) derived from mixed effects models, representing each women's BP trajectory. Akaike's information criterion was used to determine the ‘best fitting’ model.

Results:
Booking BP was taken between 5 and 15 weeks of pregnancy (median 14 weeks). There were 80,624 BP measurements taken throughout pregnancy, the number and timing varied between women: median (min, max): 8(3,17) measurements. There were 191 cases of preeclampsia.
Booking MAP before 16 weeks’ gestation (OR (95%CI) (per SD higher) (1.78 (1.53, 2.06) yielded a better model fit than SBP (1.67 (1.44, 1.94) or DBP (1.66 1.43, 1.96)) for preeclampsia. Of the summary measures, maximum MAP yielded the best fitting model (OR (95%CI) (per SD higher): 4.37 (3.76, 5.11). Growth curve parameters were significant predictors of preeclampsia, and substantially improved model fit in comparison to booking BP alone.

Conclusions:
Booking visit MAP was more strongly associated with preeclampsia than SBP or DBP. Using repeated BP measures, in the form of summary MAP measures and BP trajectories, improved the prediction of preeclampsia.
PARACETAMOL AND BLOOD PRESSURE CONTROL IN 45211 PATIENTS TREATED FOR HYPERTENSION: A CROSS-SECTIONAL STUDY FROM THE SWEDISH PRIMARY CARE CARDIOVASCULAR DATABASE
Authors: Gottlieb Hanna , Sundström Anders , Boström Kristina Bengtsson , Hasselström Jan , Hjerpe Per , Ljungman Charlotta , Manhem Karin , Mourtzinis Georgios , Qvarnsström Miriam , Wettermark Björn , Kahan Thomas 
Published: June 2023

Objective:
Paracetamol (acetaminophen) is widely recommended for analgetic and antipyretic indications due to its perceived high safety. However, studies have shown contradicting results regarding the effect of paracetamol on blood pressure (BP). We aimed to study how regular paracetamol use could affect BP control in patients on antihypertensive mediation.

Design and method:
Data for 42 511 patients attending primary care and a documented diagnosis of hypertension before 2007 (to rule out new onset of hypertension) and with 1 or more BP measurements recorded 2007–2008 were collected from the Swedish primary care cardiovascular database (SPCCD). There were 8 367 paracetamol users, defined as 1 or more dispensed prescriptions 6 months prior to the last BP recorded, and 34 144 non-users of paracetamol. Target BP was set to <140/90 mm Hg. Dose-response relationships were examined by the number of defined daily doses (DDD) dispensed. Multivariate linear regression analyses accounted for potential confounders.

Results:
Paracetamol users were older, had higher creatinine levels, more often diabetes, cardiovascular diseases and musculoskeletal diseases, and lower educational level than non-users (all P < 0.001), but attained target systolic and diastolic BP to similar degrees (58 and 93% vs 58 and 92%, respectively). There were no relations between number of DDD and systolic and diastolic BP in paracetamol users, also when DDD deciles were evaluated to account for the low proportion of patients with high DDD dispensed (all R2 <0.001). Sensitivity analyses including dispensed prescriptions of paracetamol 3 months before and 6 months after the first BP measurement provided similar results. Paracetamol had no impact on attaining target BP in subgroup analyses on patients with diabetes, musculoskeletal diseases, with concomitant use of NSAID, or in relation to number of antihypertensive medications (suggesting severity of hypertensive disease).

Conclusions:
Concomitant use of paracetamol does not impair the ability to reach target BP in hypertensive patients. No dose-response relationship was observed between dispensed prescriptions of paracetamol and BP.