bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
DIFFERENTIAL EFFECTS OF RENAL DENERVATION ON SKIN AND MUSCLE SYMPATHETIC NERVE TRAFFIC IN RESISTANT AND UNCONTROLLED HYPERTENSION
Authors: Vanoli Jennifer , Dell’Oro Raffaella , Trevano Fosca Quarti , Cuspidi Cesare , Grassi Guido
Published: June 2023

Objective:

Renal denervation (RDN) exerts profound sympathoinhibitory effects. No information is available, however, on whether these effects have a regional or a more generalized behaviour.

Design and method:

In 14 patients with resistant hypertension (RHT, age 58.3 ± 2.2 yrs, mean ± SEM) we recorded via the microneurographic technique muscle and skin sympathetic nerve traffic (MSNA and SSNA, respectively) before, 1 month and 3 months following RDN. Measurements included clinic blood pressure (BP) and heart rate (HR), 24-hour BP and HR, together with routine laboratory and echocardiographic variables. Ten age-matched RHT patients who did not undergo RDN served as controls.

Results:

MSNA, but not SSNA, was markedky higher in RHT. RDN caused a significant reduction in MSNA 1 month following RDN, the reduction becoming greater for magnitude after 3 months (from 68.1 ± 2.5 to 64.8 ± 2.4 and 63.1 ± 2.6 bursts/100heartbeats, P < 0.05). This effect was not accompanied by any significant change in SSNA (from 13.1 ± 0.5 to 13.4 ± 0.6 and 13.3 ± 0.4 bursts/minute, P = NS). No quantitative and, in some cases, no qualitative relationship was found between the BP and the MSNA reduction induced by RDN. No significant change in the various sympathetic markers was detected in the control group who did not undergo RDN and followed for a 3 month observation.

Conclusions:

These data provide the first evidence that RDN 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.
CARDIORESPIRATORY FITNESS AND STROKE INCIDENCE IN HYPERTENSIVE PATIENTS
Authors: Kokkinos Peter , Pittaras Andreas , Doumas Michalis , Samuel Immanuel Babu , Howard Dominique , Faselis Angelique , Gorsuch Balinda , Myers Jonathan
Published: June 2023

Objective:

Stroke incidence is significantly higher in hypertensive patients compared to normotensive subjects. Cardiorespiratory fitness (CRF) is associated with a more favorable cardiovascular health. The CRF-stroke incidence association in hypertensive patients has not been fully explored. Thus, the objective of the current study was to evaluate the association between CRF assessed objectively by a standardized exercise test, and stroke incidence in hypertensive patients.

Design and method:

From 1999 to 2020, we identified 460,172 hypertensive patients (mean age: 63.1 ± 8.7 years) with a normal response to an exercise treadmill test (ETT) and no prior history of stroke. We established five CRF categories based on age-stratified quintiles of peak metabolic equivalents (MET) achieved: Least-Fit (4.5 ± 1.2 METs; n = 106,620); Low-Fit (6.9 ± 1.1; n = 120,327); Moderate-Fit (8.3 ± 1.2 METs; n = 89,748); Fit (10.3 ± 0.9 METs; n = 107,323); and High-Fit (13.1 ± 1.6 METs; n = 36,154). A multivariable Cox proportional hazards model was constructed to estimate hazard ratios (HR) and 95% confidence intervals [CI] for incidence of stroke across CRF categories. The model was adjusted for age, resting blood pressure, gender, race, coronary artery disease, smoking status, chronic kidney disease, atrial fibrillation, other cardiac risk factors, and medications. The Least-fit category was used as the reference group.

Results:

During follow-up (median = 10.6 years; 4,955,021 person-years), 11,868 individuals had a stroke (2.4 events per 1,000 person-years). The risk for stroke was 8% lower for each 1-MET increase in exercise capacity (HR = 0.92, CI: 0.91 - 0.93; p < 0.001). The risk across fitness categories, declined progressively with increased CRF and was by 15% for the Least-Fit individuals (HR = 0.85; CI: 0.81 - 0.89), approximately 30% to 40% for Moderate-fit and Fit individuals, and 45% lower (HR = 0.55; CI: 0.50 - 0.60; p < 0.001) for High-Fit individuals.

Conclusions:

Increased CRF was inversely related to stroke incidence in hypertensive patients. The association was independent and graded. These finding support the concept that health care professional should encourage patients to engage in habitual physical activity of moderate intensity and progressively aim to meet the physical activity guidelines proposed by authorities.
HIGH SODIUM INTAKE - EFFECTS ON AFFERENT RENAL NERVE ACTIVITY
Authors: Rodionova Kristina , Ditting Tilmann , Linz Peter , Hilgers Karl F. , Ott Christian , Schmieder Roland E. , Schiffer Mario , Amann Kerstin , Veelken Roland
Published: June 2023

Objective:

Previous work of ours suggests that the sensitivity of renal afferent neurons is decreased under pathological conditions. Here we tested the hypothesis that pathologically decreased sensitivity of renal afferent neurons due to high salt diet is normalized after renal denervation.

Design and method:

Six male Sprague Dawley (SD) rats were put on high salt diet (HS; 8% NaCl) for 10 days. In another group of 18 rats on high salt diet (HS) left kidneys were denervated (DNX) 7 days prior to examination. 17 rats on standard diet with and without DNX were used as controls. Dorsal root ganglion neurons with renal afferents were investigated in primary neuronal cell culture using current clamp mode to assess action potential generation during current injection. Neurons were characterized as tonic highly active (less than 5 action potentials, AP) and phasic less active neurons (more than 5 AP upon stimulation).

Results:

In renal neurons from rats on HS the relation of tonic to phasic neurons shifted towards less active phasic units (62% tonic neurons in control vs. 42% on HS, p < 0.05, z-test). Denervation (DNX) of the left kidney in rats on high salt diet (HS-DNX) led to a recovery of afferent renal DRG neurons remaining vital after denervation. They regained their electrophysiological property of mainly tonic firing (42% tonic neurons in HS vs. 71% HS-DNX, p < 0.05, z-test).

Conclusions:

In rats on high salt diet the proportion of highly active tonic neurons with renal afferents decreased at the expense of less active phasic neurons. This HS effect could be abolished by DNX. Hence the input of afferent renal pathways to the central nervous system was normalized form the first neuron onward to the brain.
PATIENT'S PERSPECTIVES ON TREATMENT ADHERENCE IN HYPERTENSION: RESULTS OF AN ESH SURVEY IN POLAND
Authors: Prejbisz Aleksander , Dobrowolski Piotr , Burnier Michel , Azizi Michel , Cornelissen Veronique , Cunha Vitoria , Gupta Pankaj , Persu Alexandre , Vaclavik Jan , Versmissen Jorie , Kreutz Reinhold , Januszewicz Andrzej
Published: June 2023

Objective:

The ESH Working group on Lifestyle, Cardiovascular Therapy and Adherence has developed a web-based questionnaire in different languages to investigate patients’ perspectives on hypertension and treatment adherence. The objective of this survey was to decipher patients’ perception of motivations for and barriers to treatment adherence in hypertension.

Design and method:

In Poland, a dedicated recruitment strategy has been developed to invite adult patients to complete the survey via targeted information on patient group websites and social media only. In other countries a direct communication from healthcare professional to patient was preferred. Data were collected from May to September 2022. Descriptive statistics were used for analyses.

Results:

We included 1359 participants (962 men (71%); 67% were hypertensive for >5 years, 88% were treated with antihypertensive medications for at least 3 months). The total median number of tablets taken every day was 4 of which 2 were antihypertensive medications. Antihypertensive medications were prescribed most frequently once (56%) or twice (36%) daily. On a 10-point Likert scale, participants reported a modest impact of hypertension on their quality of life (4), social and family life (2). The median level of stress was 5 out of 10 points. Ninety two of patients performed self-blood pressure measurements at home, most frequently every day (34%) and a few times a week (28%). Self-reported adherence to treatment was perfect in 43% of patients, very high in 30% and intermediate-low in 26% of patients. Main reasons for low adherence to medication included forgetfulness (41%), improvement in well-being (15%), side effects (14%) and running out of medications (11%). The most useful approaches to support adherence reported by participants were cheaper and single-pill combinations as well as leaflets providing better information on treatment. Information provided by physicians on hypertension and its treatment was considered sufficient only for 54% of patients.

Conclusions:

In a web-based ESH survey in Poland, over 1,300 participants reported a modest impact of hypertension on their quality of life and a moderate level of anxiety, usually non-intentional non-adherence to prescribed antihypertensive medications, and the necessity to improve the information provided to them.
URBAN-RURAL DISPARITIES IN THE PREVALENCE AND MANAGEMENT OF ATRIAL FIBRILLATION IN ELDERLY CHINESE
Authors: Zhang Wei , Chen Yi , Hu Lei-Xiao , Xia Jia-Hui , Ye Xiao-Fei , Wang Wen-Yuewang , Wang Xin-Yu , Li Yan , Wang Ji-Guang
Published: June 2023

Objective:

Atrial fibrillation is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese.

Design and method:

Consecutive participants aged above 65 years attending outpatient clinics were enrolled for atrial fibrillation screening using handheld single-lead electrocardiogram (ECG, BP7900, Omron Healthcare, Kyoto, Japan and Kardia Mobile®, Mountain View, California, USA) from April 2017 to December 2022 (NCT04111419). Each ECG rhythm strip was reviewed form the research team. Atrial fibrillation or uninterpretable single-lead ECGs were referred for 12-lead ECG. Blood pressure was measured 3 times consecutively with a 30-60 seconds interval using an automated oscillometric blood pressure monitor (HEM-9200T; Omron Healthcare, Kyoto, Japan).

Results:

The mean age of the 29,166 participants was 72.2±5.8 years, and 54.6% were women. The overall prevalence of atrial fibrillation was 4.6% (n = 1347). Atrial fibrillation was more prevalent in 7073 rural than 22093 urban participants (5.6% vs. 4.3%, P<0.0001). Multivariate logistic regression analysis identified that overweight/obesity (odds ratio [OR], 1.35; 95% confidence interval [CI] 1.17 to 1.54) in urban areas, whereas current smoking (OR, 1.62; 95% CI 1.20 to 2.17) and alcohol consumption (OR, 1.42; 95% CI 1.04 to 1.93) in rural areas were specific risk factors for prevalent atrial fibrillation. In patients with known atrial fibrillation in urban (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received atrial fibrillation treatment (P<0.0001), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.047). Similar proportions of atrial fibrillation patients in urban and rural areas had concomitant hypertension (78.1%). However, in patients with known atrial fibrillation and treated hypertension, systolic/diastolic blood pressure was significantly (P< = 0.01) higher in rural (n = 475, 140.0/83.9 mmHg) than urban areas (n = 222, 135.7/79.0 mmHg).

Conclusions:

In China, there are urban-rural disparities in atrial fibrillation in the elderly, with a higher prevalence and worse management in rural than urban areas.
THE INFLUENCE OF HYPERTENSION ON HEART FAILURE'S PHENOTYPES IN PATIENTS WITH HEART FAILURE AND ATRIAL FIBRILLATION, IN COMPARISON TO PATIENTS WITH HEART FAILURE AND SINUS RHYTHM
Authors: (Pogacean) Manuela-Claudia Lacatusu , German-Sallo Marta , Tatar Maria Cristina
Published: June 2023

Objective:

Atrial fibrillation is being characterised as both an etiological factor and a consequence for developing heart failure, while it does the same for the latter.

Our aim was to identify whether and in which way, the presence of hypertension influences the development of the three phenotypes of heart failure in patients with heart failure and atrial fibrillation, as well as in patients with heart failure alone.

Design and method:

We analysed 194 patients: 97 with heart failure and atrial fibrillation (group A) and 97 patients with heart failure in sinus rhythm (group B), randomly selected from 2019 to 2021. The phenotypes of heart failure were selected according to 2021 European Society of Cardiology Guidelines: patients with heart failure with reduced ejection fraction (1), with mildly reduced ejection fraction (2) and with preserved ejection fraction (3).

Results:

In patients belonging to A1 group (n = 44) the result was that hypertension has not played a significant role in developing this phenotype (p = 0.1347), in comparison to patients in B1 group (n = 30), where the association between hypertension and heart failure with reduced ejection fraction was statistically significant (p = 0.0263). What is more, patients in A2 group (n = 14), as well as those in B2 group (n = 24), were not associated with the presence of hypertension (p = 0.4686, respectively p = 0.5638). As well as the latter, hypertension did not influence the development of heart failure with preserved ejection fraction in both groups.

Conclusions:

Taking into consideration that hypertension illustrates a common aetiology for both pathologies mentioned above, we discovered that hypertension's presence influenced more the heart failure in sinus rhythm group, concluding that atrial fibrillation associated with heart failure did not pose an additive risk factor for hypertension developing. In addition, regarding the phenotypes, it was heart failure with a reduced ejection fraction that was influenced by hypertension. Further researches will improve the comprehensive relationship between hypertension, atrial fibrillation and heart failure, leading towards better management strategies.
ASSOCIATION OF G894T NOS3 GENE POLYMORPHISM WITH ATRIAL FIBRILLATION IN PATIENTS WITH ARTERIAL HYPERTENSION IN UZBEK POPULATION
Authors: Radjabova Guliruh , Abdullayeva Guzal , Pulatova Muazzam , Sherbadalova Nigora , Zakirova Dilorom , Ibragimova Iroda , Shukurova Dilyafruz , Mashkhurova Zarina , Abdullayev Alisher
Published: June 2023

Objective:

To estimate influence of G894T polymorphism of NOS3 gene on risk of developing AF with AH in Uzbekistan.

Design and method:

Study included 206 patients with AH I–III degree (JSC/JSC, 2018) of both sexes. Mean age of patients was 58.82 ± 11.91 years, the mean duration of hypertension was 10.9 ± 7.2 years. To verify AF, ECG Holter monitoring was performed using a Cardiospy monitor. Genotyping of G894T polymorphism of the NOS3 gene was performed using real-time PCR using gene-specific primers of allele-specific probes, followed by fluorescence detection of corresponding alleles. Results of all studies were considered statistically significant at p<0.05

Results:

Relationship between G894T polymorphism of NOS3 gene and risk of developing AF, patients were divided into two groups: cases, n = 91 - with AF and controls, n = 115 - without AF. Among cases, following distribution of genotypes and alleles of G894T polymorphism of the NOS3 gene was revealed: GG genotype - determined in 52.7%, GT genotype - in 45.1%, TT genotype - 2.2%, p = 0.000. Allelic distribution showed predominance of carriage of the G allele: G allele - 75.3%, T allele - 24.7%, p = 0.000. Among controls, allelic distribution was with significant prevalence of the G allele: G allele in 75.7%, T allele in 24.3%, respectively, Xi = 119.035, p = 0. 000. Ratio of GG:GT:TT - genotypes was as follows: 60.0%: 31.3%: 8.7%, Xi = 68.426, p = 0.000.

An analysis revealed protective effect of G allele G894T gene polymorphism on risk of developing AF with AH. Based on general model of inheritance, protective effect of GG genotype on risk of developing AF in hypertensive patients was found: general model of inheritance demonstrated significant accumulation of GG genotype among controls 60.0% (Xi2 = 6.72 P = 0.03; OR = 0.74, 95% CI 0.43-1.30), while GT genotype was less common in 31.3% and the TT genotype is even rarer in - 8.7%. Whereas in cases GG and GT genotypes were found in same ratio: 52.7%: 45.1%, respectively.

Conclusions:

Results obtained indicate significantly greater accumulation of GG genotype G894T gene polymorphism among AH without AF. Carriage of GG genotype G894T gene polymorphism is associated with low risk of developing AF with AH.
PREDICTION OF CORONARY ARTERY DISEASE USING URINARY PROTEOMICS
Authors: Wei Dongmei , Melgare Jesus D. , Aelst Lucas van , Vanassche Thomas , Verhamme Peter , Janssens Stefan , Peter Karlheinz , Zhang Zhen-Yu
Published: June 2023

Objective:

Coronary artery disease (CAD) is multifactorial, caused by complex pathophysiology, and contributes to a high burden of mortality worldwide. Urinary proteomic analyses may help to identify predictive biomarkers and provide insights into the pathogenesis of CAD.

Design and method:

Urinary proteome was analyzed in 965 participants using capillary electrophoresis coupled with mass spectrometry. A proteomic classifier was developed in a discovery cohort with 36 individuals with CAD and 36 matched controls using the support vector machine. The classifier was tested in a validation cohort with 115 individuals who progressed to CAD and 778 controls and compared with a previously developed CAD-associated classifier, ACSP75. The Framingham risk score was available in 737 participants. Bioinformatics analysis was performed based on the CAD-associated peptides.

Results:

The novel proteomic classifier was comprised of 160 urinary peptides, mainly related to collagen turnover, lipid metabolism, and inflammation. In the validation cohort, the classifier provided an AUC of 0.82 (95% CI: 0.78-0.87) for the CAD prediction in 8 years, superior to ACSP75 (AUC: 0.53, 95% CI: 0.47-0.60). On top of ACSP75, the addition of the novel classifier improved the AUC to 0.84 (95% CI: 0.80-0.89). In a multivariable Cox model, a 1-SD increment in the novel classifier was associated with CAD (HR: 1.54, 95% CI: 1.26-1.89, P<0.0001) higher risk of CAD. The new classifier further improved the risk reclassification of CAD on top of the Framingham risk score (net reclassification index: 0.61, 95% CI: 0.25-0.95, P = 0.001).

Conclusions:

A novel urinary proteomic classifier related to collagen metabolism, lipids, and inflammation showed potential for the risk prediction of CAD. Urinary proteome provides an alternative approach to personalized prevention.
ASSOCIATIONS OF SERUM BIOMARKERS WITH BLOOD PRESSURE IN EX-PRETERM CHILDREN AND ADOLESCENTS
Authors: Chainoglou Athanasia , Sarafidis Kosmas , Taparkou Anna , Farmaki Evangelia , Chrysaidou Katerina , Gidaris Dimos , Kollios Konstantinos , Kotsis Vasilios , Stabouli Stella
Published: June 2023

Objective:

Preterm birth is considered a risk factor for the development of hypertension throughout life course. The aims of the present study were to assess the levels of serum biomarkers in ex-preterm children and adolescents compared to healthy controls and to examine for associations with office, ambulatory BP parameters, and pulse wave velocity.

Design and method:

The study population included 52 preterm and 26 term born children and adolescents who underwent office, ambulatory BP monitoring, and assessment of pulse wave velocity. Serum biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), and matrix metalloproteinase-2, -9 (MMP-2, -9) were measured using double-antibody sandwich enzyme-linked Immunosorbent assay.

Results:

Thirty-five % of the study population presented office hypertension, 38.5% of the ex-preterm and 28% of the term children. Seventeen % of the ex-preterm group presented ABP hypertension. None of the controls had ABP hypertension. Half of the ex-preterm children had white-coat hypertension. Serum NGAL and MMP-2 and -9 levels did not differ between ex-preterm and term groups. NGAL and MMP-9 presented significant correlations with office systolic BP z score (r = 0.33, p<0.005, and r = 0.30, p<0.05, respectively) and day systolic BP z score (r = 0.29, p<0.01, and r = 0.23, p<0.05, respectively). The above associations were also observed in the ex-preterm, but not in the term group. There was no association between any biomarker and PWV. In univariate analysis NGAL presented significant correlations with office (B = 0.009, 95%CI 0.001-0.017, p<0.05) and day systolic BP z-score (B = 0.009, 95%CI 0.001-0.017, p< 0.05) in the ex-preterm group after adjustment for age, sex, birth weight and gestational age. The receiver operating characteristic (ROC) curve analysis showed that NGAL predicted hypertension in ex-preterm children with area under the curve (AUC) 0.713, 95% CI 0.57-0.85, p = 0.010.

Conclusions:

In ex-preterm children and adolescents NGAL and MMP-9 presented significant associations with systolic BP. The associations for NGAL persisted after adjustment for birth parameters, age and sex suggesting that NGAL should be further investigated as it could serve as early biomarker of hypertension evolution in ex-preterm children and adolescents.
BIOFLUID SPECIFICITY OF LONG NON-CODING RNA PROFILE IN HYPERTENSION: RELEVANCE OF EXOSOMAL FRACTION
Authors: Martinez-Arroyo Olga , Ortega Ana , Riffo-Campos Angela L. , Perez-Hernandez Javier , Flores-Chova Ana , Redon Josep , Cortés Raquel
Published: June 2023

Objective:

Non-coding RNA (ncRNA)-mediated targeting of various genes regulates the molecular mechanisms of the pathogenesis of hypertension (HTN). However, very few circulating long ncRNAs (lncRNAs) have been reported to be altered in essential HTN. The aim of this study was to identify simultaneously the lncRNA profiles in circulating plasma and packaged them into exosomes associated with UAE in HTN using deep sequencing technology. We also assessed the effect of the biofluid origin on lncRNA signature and regulated pathways.

Design and method:

In a cohort of hypertensive patients with (n = 22) or without urinary albumin excretion (UAE) (n = 26), we analyzed by next generation sequencing the lncRNA profile associated to UAE. Then, long Non-Coding RNA target predictions and molecular pathways analyses were performed through GO terms and KEGG pathways.

Results:

Plasma exosomes showed higher diversity and fold change of lncRNAs than plasma, and low transcript overlapping was found between the two biofluids. The majority of unique differentially expressed lncRNA in the exosome fraction were downregulated (71%) in albuminuric patients and 61% in plasma samples. In addition, in plasma samples only 40% of statistically significant transcripts had a log2 fod change higher or equal to 2 or lower or equal to -2, compared with 100% top lncRNAs in exosomal fraction. Enrichment analysis identified different biological pathways regulated in plasma or exosome fraction, which were implicated in fatty acid metabolism, extracellular matrix, and mechanisms of sorting ncRNAs into exosomes, while plasma pathways were implicated in genome reorganization, interference with RNA polymerase, and as scaffolds for assembling transcriptional regulators.

Conclusions:

Our study found a biofluid specific lncRNA profile associated with albuminuria, with higher diversity in exosomal fraction, which identifies several potential targets that may be utilized to study mechanisms of albuminuria and cardiovascular damage.
THE DIFFERENCE IN BLOOD PRESSURE BETWEEN THE TUNNEL BLOOD PRESSURE MONITORS IN THE WAITING AREA AND UPPER ARM BLOOD PRESSURE MONITORS IN THE CLINIC
Authors: Yang Shijie , Zhou Zhanyang , Miao Huanhuan , Zhang Yuqing
Published: June 2023

Objective:

Tunnel blood pressure as an out-of-clinic screening program is often more casual, and its consistency with office blood pressure dominated by upper arm blood pressure and whether it can replace office blood pressure remains unclear. The aim of this study was to analyze the differences between the two blood pressure measurements.

Design and method:

The study dates from the Majiapu community, which is a big community in Beijing. We analyzed blood pressure with different measurements containing tunnel (waiting area,9002P) and upper arm (clinic, OMRON 1120U) blood pressure measurements. We compare the two measurements by the mean average value and standard deviation (SD) of the two measurements. Besides, we compare the mean blood pressure in the subgroups which contain the age, sex, blood lipids, blood glucose, and different blood pressure levels.

Results:

In this study, a cohort of 35069 individuals aged 0 to 105 years, 19443 were randomly assigned to the tunnel blood pressure measurement group (TBPG) and 15626 to the upper arm blood pressure measurement group (UBPG). The qualified rate of the UBPG was 64.76% in 140/90 mm Hg and 54.66% in 130/80 mm Hg. In baseline, the mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 134.0±21.3 mm Hg and 76.3±12.0 in the TBPG, 134.9±22.3 mm Hg and 80.3±12.5 in the UBPG. In the age more than 60 years subgroup, the mean SBP in the TBPG with 139.0±21.1 mm Hg was similar to the other group, which was 138.5±22.4 mm Hg, the mean DBP was on the contrary, which was 74.8±11.4 and 79.6±11.9 mm Hg respectively. Similar results can be found in the age< 60 years, sex, blood lipids, and blood glucose subgroups. In the BP more than 140/90 mmHg subgroup, the SBP difference was only 0.1 mmHg, but the DBP was 5 mmHg, as same as the BP more than 130/80 mmHg subgroup. The DBP difference was much smaller in the low BP level.

Conclusions:

The clinic SBP for the tunnel (waiting area) and upper arm (clinic) blood pressure monitors were similar, but the DBP differ significantly between the two groups.
ASSESSING THE QUALITY OF PHOTOPLETHYSMOGRAPHY SIGNALS FOR ARTERIAL PULSE WAVE SENSING
Authors: Villeneuve Emma , Auclair Loïc , Prada-Mejia Robinson , Anglade Daniel , Sandre-Ballester Caroline , Gerbelot Rémi , Blandin Pierre , Perriollat Mathieu
Published: June 2023

Objective:

Cardiovascular health has an impact on the arterial blood pulse wave features, such as shape and speed. Photoplethysmography (PPG) allows measuring the light absorption variation in the skin due to the blood pulse wave. This study aims at collecting good quality PPG signals for pulse wave sensing. First, the signal quality must be accurately defined and quantified. Then, it must be assessed for several sensor locations during both rest and exercise.

Design and method:

Based on ECG peaks, the PPG signal is split into beats, which are then fitted to a 4-long piece-wise linear function. Beats are valid only if they follow a specific slope pattern (the second slope has the opposite sign to the other three), and if they have a dichrotic notch. The signal quality is then quantified by the percentage of valid beats.

The initial cohort of the clinical trial (NCT05393401, approved by Human Research Review Board (CPP SM I) and Health French Ministry) includes five healthy subjects (1F/4M, age [37-60] years). Their brachial and radial arteries are located by ultrasound. Each subject is monitored with a multi-sensing homemade platform with PPG sensors and ECG; the distance between the LED and the photodiode is 9mm. Measurements are realized with sensors directly above the artery on the elbow, the wrist and the carotid, first at rest and then during a physical exercise.

Results:

Based on these preliminary results, the quality of PPG signals is best at the wrist whether at rest (48%) or exercise (44%). The second best option is the forearm and the worst is the carotid. The quality during exercise is similar, with a decrease of 4% at the wrist.

Conclusions:

The signal quality of PPG sensors is strongly impacted by the position along the arteries. The pressure applied on sensors and the extended arm posture also improve the signal quality. Further work should be undertaken to study the feasibility of pulse wave analysis for ambulatory blood pressure monitoring.
HIGH BLOOD PRESSURE IN WOMEN ACCORDING TO CARDIOVASCULAR RISK FACTORS AND ANTIHYPERTENSIVE TREATMENT: THE IMPORTANCE OF DETECTION
Authors: Barragan Adriana Puente , Hiciano Cecilia Jimenez
Published: June 2023

Objective:

To evaluate the relationship between the presence of high blood pressure in a group of Mexican women, according to cardiovascular risk factors and antihypertensive treatment.

Design and method:

We analyzed the data of 341 women, > 18 years, with multiple risk factors, who attended cardiovascular imaging department. Cardiovascular risk factors and antihypertensive treatment were analyzed. Hypertension was classified according to the European Society of Cardiology (ESC) Guidelines (SBP >140 mmHg and DBP > 90 mmHg). Statistical analysis: SPSS v23; descriptive and comparative analysis with chi-square, confidence level 95%.

Results:

Mean age 58±15.6; Cardiovascular risk factors: hypertension 201 (58.9%), diabetes126 (37%), 136 (40%) dyslipidemia, tobacco use 97 (27.8%), chronic kidney disease 63 (18.5%); 248 (72.7%) were menopausal. A total of 198 (58.1%) patients with hypertension were on pharmacological treatment: 88 (44.5%) with monotherapy, 85 (42.9%) on dual therapy, and 25 (12.6%) with multiple therapies; (46.4%) were non-controlled. There were 143 (41.9%) patients, that were detected and classified as hypertensive according to European Society of Hypertension guidelines: Grade 1 88 (61.5%), Grade 2, 22 (15.38%), Grade 3, 6 (4.1%). A relationship between hypertensive women, kidney disease (47.6%, p = 0.001), and menopause was found (37.9%, p: 0.039).

Conclusions:

Hypertension is an important cardiovascular risk factor in women. Most are associated with others risk factors; more than fifty percent were on multiple therapy and uncontrolled. It is necessary to optimize antihypertensive treatment to improve hypertension control, especially in postmenopausal women and with kidney disease. Screening also must be improved to prevent future complications.