bluuebunny/crossref_metadata_2025 huggingface dataset:
GENERALISED MICROVASCULAR DYSFUNCTION IS NONLINEARLY ASSOCIATED WITH HIGHER EXERCISE BLOOD PRESSURE – THE MAASTRICHT STUDY
Authors: Zhou Tan Lai , Kroon Abraham , Houben Alfonsius , Jansen Jacobus , Berendschot Tos , Webers Caroll , Van der Kallen Carla , Schram Miranda , Stehouwer Coen
Published: June 2022

Objective:

Exercise blood pressure (BP), both high and low responses, is associated with the development of cardiovascular disease and all-cause mortality. However, it is unclear whether microvascular dysfunction is a determinant of exercise BP. Therefore, we investigated whether microvascular dysfunction was (nonlinearly) associated with exercise BP.

Design and method:

In the population-based Maastricht Study (n = 1,688; age 59 ± 8 years; 51% men), generalised microvascular dysfunction was constructed by a composite score of features of cerebral small vessel disease, retinal microvascular features, albuminuria, heat-induced skin hyperaemia and plasma biomarkers of microvascular dysfunction. Similarly, we constructed a composite score of exercise systolic BP and diastolic BP by combining BP at moderate workload, at peak exercise, change per minute and at 4 minutes after recovery. We used linear regression with adjustments for age, sex, lifestyle and cardiovascular risk factors, including resting BP. Nonlinearity was investigated by adding a quadratic term of generalised microvascular dysfunction

Results:

After adjustments, generalised microvascular dysfunction was nonlinearly associated with both the composite score of exercise SBP and DBP in an inverted U-shape fashion (p-nonlinear for exercise SBP < .001; for exercise DBP .001). When we divided microvascular dysfunction into quintiles, exercise SBP and DBP did not become higher after the middle quintile, and plateaued or were lower in the highest quintiles of microvascular dysfunction.

Conclusions:

Generalised microvascular dysfunction is nonlinearly associated with higher exercise SBP and DBP in an inverted U-shape fashion. These findings support the hypothesis that generalised microvascular dysfunction is a determinant of both high and low exercise BP responses.
EXPOSURES TO INTIMATE PARTNER VIOLENCE AND NON-PARTNER SEXUAL VIOLENCE ARE ASSOCIATED WITH HYPERTENSION IN SOUTH AFRICAN WOMEN
Authors: Nguyen Kim , Abrahams Naeemah , Jewkes Rachel , Mhlongo Shibe , Seedat Soraya , Meyers Bronwyn , Lombard Carl , Garcia-Moreno Claudia , Chirwa Esnat , Kengne Andre , Peer Nasheeta
Published: June 2022

Objective:

South African women suffer from a dual burden of gender-based violence and hypertension. Studies suggest abuse exposures may increase the risk of hypertension by contributing to psychological stress, but this association has not been clearly described. This study described the associations of intimate partner violence (IPV), non-partner sexual violence (NPSV) and sexual harassment (SH) exposures with hypertension, and potential mediators of those associations in South African women aged 18 to 40 years.

Design and method:

Baseline data from the Rape Impact Cohort Evaluation study, including history of sexual, physical, emotional and economic IPV, NPSV and SH were examined using validated questionnaires. Hypertension was based on measured blood pressure (equal or higher than 140/90 mmHg) or a previous diagnosis. Logistic regression models examining the associations between various types of IPV, NPSV and hypertension adjusted for traditional hypertension risk factors and other traumatic exposures including recent rape incident. Mediation effects of body mass index, HIV infection, current smoking, alcohol binge drinking, depressive symptom scores and post-traumatic stress symptom (PTSS) scores on the associations using multiple mediation models adjusted for age and recent rape exposure.

Results:

Among 1742 women, 218 (12.5%) had hypertension. Hypertension prevalence was higher in women with, compared to without, a history of all four types of IPV (15% vs. 9%), sexual (19% vs. 11%), physical (16% vs. 9%), emotional (17% vs. 9%) and economic IPV (19% vs. 11%); NPSV (18% vs. 11%) and SH (29% vs. 11%), (p-values were equal or above 0.001). More than one episode of NPSV (adjusted odds ratio (aOR): 1.63; 95%CI: 1.27–2.67), any SH (aOR: 2.56; 95%CI: 1.60–4.03), frequent physical (aOR: 1.44; 95%CI: 1.06–1.95) and emotional IPV (aOR: 1.45; 95%CI: 1.06–1.98), and greater severity score of emotional IPV (aOR: 1.05; 95%CI: 1.02–1.08) were associated with hypertension. Current depression, PTSS and/or alcohol binge drinking completely or partially mediated these associations.

Conclusions:

The modifiable associations of IPV, NPSV and SH with hypertension highlight that, while gender-based violence must be prevented, public health interventions should incorporate monitoring blood pressure of violence victims, determining a history of violence in hypertension patients, and providing counselling.
MRI IN THE ASSESSMENT OF CEREBRAL INJURY AND CEREBROPROTECTIVE EFFECTS OF RENAL DENERVATION IN RESISTANT ARTERIAL HYPERTENSION
Authors: Sukhareva Anna , Falkovskaya Alla , Baev Andrey E. , Mochula Olga V. , Maksimova Alexandra S. , Ryumshina Nadezhda I. , Shelkovnikova Tatyana A. , Zyubanova Irina V. , Tsoi Ekaterina I. , Manukyan Musheg A. , Mordovin Viktor F. , Ussov Vladimir Yu
Published: June 2022

Objective:

The purpose of this single-centre, prospective, comparative study was to evaluate the pattern and severity of the brain structural changes in patients with resistant hypertension (RH) based on MRI assessments and their changes one year after renal denervation (RDN).

Design and method:

The study comprised 58 patients with RH, aged 52.1 ± 9.1 years, who underwent RDN. Patients underwent office blood pressure measurements, 24-hour blood pressure monitoring, and brain MRI scanning. Using brain MRI, the cerebrospinal fluid (CSF) system measurements, the presence of periventricular leukoaraiosis and focal changes in the brain white matter were evaluated.

Results:

Initially, patients with RH had a high incidence of the structural brain alterations: 75% with fine focal brain lesions, 75% with impaired CSF dynamics, 23% with sulcal widening, and 90% with periventricular oedema. After RDN, a significant hypotensive effect was noted. According to brain MRI, the number of patients without impaired CSF dynamics did not change significantly: 25% initially, and 20% a year later (χ
2 = 0.63 p = 0.43, and χ2 = 0.72 p = 0.40). The number of patients with grade I impaired CSF dynamics after 6 months significantly increased after 12 months from 50% to 64% (χ2 = 4.00, p = 0.046) due to lowering the number of patients without impaired CSF dynamics and patients with grade II impaired CSF dynamics (χ2 = 1.56, p = 0.21). The number of patients with sulcal widening significantly decreased: from 23% to 8% one year following RDN (χ2 = 40.21 p = 0.000). The incidence of periventricular cerebral oedema did not significantly change one year after the procedure; however, the incidence of fine focal brain lesions significantly decreased (from 75 to 60%, p = 0.02).

Conclusions:

Thus, it has been revealed that patients with RH are characterised by a high incidence of structural brain alterations based on MRI assessments. A year after bilateral renal denervation, there are significant improvement in intracranial hypertension signs and decrease in the incidence of fine focal brain lesions, without a significant change in the CSF dynamics parameters (Table 1). Figure 1 shows a clinical example of a decrease in the number of fine focal brain lesions after the intervention.
RELATIONSHIP BETWEEN COGNITIVE IMPAIRMENT AND HYPERTENSION MEDIATED ORGAN DAMAGE: THE VOBARNO STUDY
Authors: Arnoldi Chiara , Capellini Sara , Zuccotti Luca , Paini Anna , Salvetti Massimo , Rozzini Luca , Aggiusti Carlo , Bertacchini Fabio , Stassaldi Deborah , Padovani Alessandro , Muiesan Maria Lorenza
Published: June 2022

Objective:

Background Several studies have suggested the presence of a relationship between hypertension in mid-life and the subsequent development of mild cognitive impairment (MCI) and dementia.

Aim: to analyze the relationship between baseline blood pressure (BP), cardiovascular risk factors and presence of Hypertension Mediated Organ Damage (HMOD) and cognitive performances oppler after a follow-up period of 12 years in 149 subjects participating into the Vobarno Study.

Design and method:

149 subjects (52% female, mean age 54.9 ± 8, 9 ± 3.25 school years, 59% hypertensives) underwent blood chemistry, arterial pressure measurement, echocardiography, carotid oppler ultrasound and measurement of central arterial pressure (PWA) and carotid-femoral pulse wave velocity (PWV). All subjects underwent a neuropsychological evaluation with standardized tests performed at a follow-up visit 12 years later.

Results:

57 subjects with MCI at follow-up had baseline higher arterial pressure values (SBP and PP clinical and 24 h p < 0.05), IMT (1.23 ± 0.34 vs 1.12 ± 0.25 p < 0.05), and PWV (11.45 ± 3.37 m/sec vs 10.49 ± 1.74 p < 0.05) than those observed in the 92 subjects without MCI. Subjects with MCI were divided in two groups according to presence of amnesia (18 and 21% of total, respectively). Baseline IMT was significantly higher in subjects who developed non-amnesic MCI when compared with patients without MCI (Meanmax 1.30 ± 0.36 mm vs 1.12 ± 0.25 mm p < 0.05; CBmax 1.30 ± 0.29 mm vs 1.16 ± 0.24 mm p < 0.05); no differences were found between amnesic and nonamnesic subjects.

Conclusions:

our results show that baseline presence of hypertension and HMOD may be associated with cognitive performance detected after a mean period of 10 years. Aortic stiffness (measured as PWV) appears to be a less sensitive predictor of cognitive decline than increased IMT.
CURRENT PRACTICES OF BP MEASUREMENT IN CHILDREN AND ADOLESCENTS ACROSS EUROPEAN COUNTRIES: A SURVEY BY THE HYPERCHILDNET COST ACTION WG ON DEVICES
Authors: Stampouli Styliani , Floriano Fabiana , López-Valcárcel Beatriz , Wuhl Elke , Lurbe Empar
Published: June 2022

Objective:

Objective: The main objective was to carry out a survey on current practices of BP measurement used among health care providers involved in the care of children and adolescents.

Design and method:

Design and methods: A 22 questions survey was released online from September 2, 2021 to September 27, 2021. The survey's link was sent to primary care physicians and pediatricians from the 22 European COST country members and it was also posted on the HyperChildNET website.

Results:

Results: The survey was assessed by 476 individuals and fully completed by 293. It was answered by general practioneers and pediatricians as well as pediatric nephrologists, pediatric cardiologists and pediatric endocrinologists, half of them working in primary care and the other half in hospital settings. Office BP measurement was used for clinical decision-making by 49% of the survey respondents while 29.7% used ABPM (Ambulatory BP Monitoring) and 16% home BP measurements. Only 11% routinely screen for high BP in normotensive children (Figure). Auscultatory and oscillometric devices were used in 57% and 41% of the settings, respectively. The main reason for selecting a BP device was availability in the institution in 60%, ease to use in 25.5% and validation in the relevant age group in 11.5%. Cuff size was selected according to individual child or adolescent mid arm circumference by 55% of the responders. A usual pitfall was combining cuffs from different devices and manufactures reported by 47.7% of the responders. Moreover, 42% performed only one BP measurement at each office BP visit. There was heterogeneity on the reference values used to evaluate the BP status with 27.4% using country specific BP reference tables and the rest different guidelines’ staging schemes. Eighty-three % used published reference values and 15.4% internet-based application for BP staging in children and adolescents.

Conclusions:

Conclusions: Variation in practices among health care providers show the emerging need of defining criteria to benchmark the different BP measurement devices, as well as to promote awareness for the evaluation of hypertensive children across Europe.
LIPID INDICES, ARTERIAL DAMAGE AND ALBUMINURIA IN PEDIATRIC PATIENTS WITH UNTREATED PRIMARY HYPERTENSION
Authors: Skrzypczyk Piotr , Pawlik Katarzyna , Bujanowicz Adam , Wroniewicz Tobiasz , Szyszka Michal , Ofiara Anna , Panczyk-Tomaszewska Malgorzata
Published: June 2022

Objective:

Adult data proved that dyslipidemia is associated with cardiovascular risk. Our study aimed to analyze the relation between lipid indices, arterial damage and urinary albumin excretion (UAE) in children with primary hypertension (PH).

Design and method:

In 87 pediatric patients (15.10 ± 2.68 years, 60 boys, 27 girls) with untreated PH, we nalysed total, high-density, and low-density lipoprotein cholesterol (T-C, LDL-C, HDL-C), triglycerides (TG), and lipid indices: TG/HDL-C, Non-HDL-C, T-C/HDL-C, LDL-C/HDL-C, atherogenic index of plasma (AIP), atherogenic index (AI), lipoprotein combine index (LCI), and CHOLIndex (LDL-C - HDL-C). Additionally, we assessed 24 h ABPM, central and peripheral office BP, and arterial damage: aortic PWV, AIx75HR, cIMT, carotid arterial stiffness estimated by ultrasonic wall tracking (E-tracking - ET) and UAE [mg/24 h]. Lipid reference values were taken from the American Academy of Paediatrics 2011 Guidelines.

Results:

In the study group, borderline/high T-C was found in 22 (25.3%), LDL-C in 10 (11.5%), TG in 45 (51.7%), and borderline/low HDL-C in 28 (32.2%) patients; overall, 60 (69.0%) patients had dyslipidemia. Children with borderline/high LDL-C had significantly higher aPWV (5.83 ± 1.78 vs. 5.26 ± 0.78 [m/s], p = 0.047) and UAE (16 [8–122] vs. 8 [5–22] [mg/24], p = 0.034) compared to patients with normal LDL-C. In 87 studied children, UAE correlated with T-C and LDL-C (R = 0.269, p = 0.017; R = 0.245, p = 0.030) and AIx75HR with T-C (R = 0.228, p = 0.035). Also, ET augmentation index (ET AIx) correlated with HDL-C, T-C/HDL-C and AI (R = -0.245, p = 0.023; R = 0.233, p = 0.031; R = 0.233, p = 0.031), and maximal diameter of common carotid artery (D_max) with HDL-C, TG/HDL-C, T-C/HDL-C, LDL-C/HDL-C, AIP, and AI (R = -0.332, p = 0.002; R = 0.220, p = 0.042; R = 0.255, p = 0.018; R = 0.223, p = 0.039; R = 0.220, p = 0.042; R = 0.255; p = 0.018). Logistic regression revealed that the rise in CHOLIndex increased risk of elevated (>30 mg/24 h) UAE (OR: 1.035 95CI: 1.008–1.070).

Conclusions:

1. Lipid disturbances are common in pediatric patients with PH

2. Elevated lipid indices are associated with common carotid artery diameter and stiffness in hypertensive children and adolescents.

3. Pediatric patients with PH and abnormal LDL cholesterol are at risk of increased aortic stiffness.

4. CHOLIndex may serve as a marker of risk of hypertensive nephropathy in pediatric patients with PH.
CIRCADIAN BLOOD PRESSURE PROFILE IN PEDIATRIC PATIENTS WITH PRIMARY HYPERTENSION
Authors: Skrzypczyk Piotr , Ofiara Anna , Szyszka Michal , Wabik Anna , Pietrzak Radoslaw , Werner Bozena , Panczyk-Tomaszewska Malgorzata
Published: June 2022

Objective:

Disturbed circadian blood pressure (BP) profile is a risk factor for cardiovascular complications in adults. The study aimed to evaluate factors affecting circadian BP profile and its association with hypertension-mediated organ damage (HMOD) in pediatric patients with primary hypertension (PH).

Design and method:

The study included 112 children (79 boys, 33 girls, 14.7 ± 2.7 years) with untreated PH. Circadian BP profile was assessed by 24-hour ABPM. Disturbed circadian BP profile (non-dipping) was defined as a nocturnal drop in systolic or diastolic BP (SBP, DBP) < 10%. A nocturnal drop in SBP or DBP > 20% was defined as extreme dipping. Patients were evaluated for central BP, HMOD (left ventricular mass index - LVMI, aortic pulse wave velocity, augmentation index (AIx75HR), intima-media thickness, albuminuria), and clinical and biochemical parameters, including sodium-potassium balance.

Results:

In the study group, the mean nocturnal drop in SBP was 10.9 ± 5.9 [%] and in DBP - 16.2 ± 8.5 [%]. Non-dipping was found in 50 (44.6%) children and extreme-dipping in 29 (25.9%) patients. The nocturnal drop in SBP correlated negatively with Z-scores of body weight (r = -0.191, p = 0.043) and BMI (r = -0.242, p = 0.010) and with LVMI [g/m2.7] (r = -0.395, p = 0.006). The nocturnal drop in SBP and DBP correlated positively with urinary potassium excretion [mmol/kg/24 h] (r = 0.656, p = 0.001 and r = 0.540, p = 0.011, respectively). Patients with disturbed circadian blood pressure profile were characterized by higher LVMI (44.5 ± 12.5 vs. 36.8 ± 8.8 [g/m2.7]) and albuminuria (median: 10.8, IQR: 5.3–53.3 vs. median: 8.1, IQR: 5.5–16.4 [mg/24 h], p = 0.043) and lower urinary potassium excretion (0.6 ± 0.2 vs. 1.1 ± 0.3 [mmol/kg/24 h]). Extreme-dipping patients had a higher AIx75HR than the other patients (median: + 3.3, IQR: -6.3- + 17.7 vs. -4.6, IQR: -17.3- + 4.0 [%], p = 0.048).

Conclusions:

1. Disturbed circadian BP profile is common in children with PH and should not be considered a marker of secondary hypertension.

2. Disturbed circadian BP profile may be associated with higher body weight and lower dietary potassium intake.

3. Pediatric patients with PH and disturbed BP profile are at risk for HMOD: left ventricular hypertrophy and microalbuminuria.

4. Extreme-dipping may be associated with increased arterial stiffness in children with PH.
SERUM MYOSTATIN IS ASSOCIATED WITH PULSE WAVE VELOCITY RATIO IN HEALTHY ADOLESCENTS. THE MACISTE STUDY
Authors: Pucci Giacomo , D’Abbondanza Marco , Curcio Rosa , Alcidi Riccardo , Campanella Tommaso , Chiatti Lorenzo , Veca Vito , Sanesi Leandro , Anastasio Fabio , Nunziangeli Luisa , Ministrini Stefano , Vaudo Gaetano
Published: June 2022

Objective:

Serum myostatin (sMSTN) is a proteic compound that regulates muscle growth and production of extracellular matrix. sMSTN also exerts profibrotic and antihypertrophic effects on smooth muscle cells and fibroblasts.

Aortic-brachial pulse wave velocity ratio (PWVr) is a pressure-independent measure of arterial stiffness gradient between the aorta and peripheral muscular arteries, known to reflect early arterial ageing and to be associated with cardiovascular (CV) risk. We explored the association between sMSTN and arterial stiffness gradient, measured through the PWVr, in a cohort of healthy adolescents.

Design and method:

128 healthy subjects (mean age 17 ± 2 years, 59% men) were randomly recruited among participants of the Metabolic And Cardiovascular Investigation at School, TErni (MACISTE) study, a cross-sectional survey conducted at the “Renato Donatelli” High School in Terni, Italy. sMSTN was measured through enzyme-linked immunosorbent assay. PWV was measured by applanation tonometry (SphygmoCor) along the carotid-femoral (cf-PWV, aortic) and the carotid-radial (cr-PWV, brachial) pathways and expressed as the ratio between cf-PWV and cr-PWV. Blood pressure (BP) was recorded at the same time of PWV measurement and expressed as systolic/diastolic BP percentiles (z-score) based on age, sex and height.

Results:

Mean BP was 126 ± 12/68 ± 8 mmHg (z-score 1.2 ± 0.9/0.3 ± 0.7). Mean Cf-PWV was 5.1 ± 0.9 m/s, cr-PWV was 6.9 ± 0.9 m/s. PWVr was 0.75 ± 0.12. PWVr increased linearly at increasing quartiles of sMSTN (0.71 ± 0.09, 0.74 ± 0.13, 0.75 ± 0.14, 0.78 ± 0.12, p for trend = 0.03, Figure 1). Subjects with PWVr above average had higher BMI (21.7 ± 2.6 Kg/m2 vs 20.8 ± 2.3 Kg/m2, p = 0.04) and SBP (1.39 ± 0.97 vs 0.97 ± 0.91, p = 0.01), whereas they did not differ in terms of age, sex, heart rate, measures of adiposity, and other CV risk factors. In a multivariate linear model, PWVr was independently predicted by SBP and sMSTN, both if expressed as continuous variable (beta = 0.21, p = 0.018) or in quartiles (beta = 0.26, p = 0.011).

Conclusions:

In a cohort of healthy Italian adolescents, sMSTN was positively and independently associated to increased PWVr, a measure of arterial stiffness gradient. Our preliminary results raise the hypothesis that sMSTN might differentially interfere with structural and functional components of the arterial wall, and ultimately might contribute to the accelerated arterial ageing in adolescents.
VASCULAR AGING IN THE YOUNG: CAROTID STIFFNESS POPULATION CENTILES AND ASSOCIATION WITH BLOOD PRESSURE IN THE KIGGS COHORT
Authors: Büschges Julia , Rosario Angelika Schaffrath , Sarganas Giselle , Königstein Karsten , Schmidt-Trucksäss Arno , Neuhauser Hannelore
Published: June 2022

Objective:

Functional characteristics of the vascular system underly changes associated with aging, such as increasing arterial stiffness. Research suggests that these age-associated changes may be accelerated in the presence of cardiovascular risk factors. So far, normative data on arterial stiffness in unselected adolescents and young adults have been scarce. Recently, measurements of carotid stiffness (cS) parameters have been included in a national health examination survey.

Design and method:

The population-based KiGGS cohort 11-year-follow-up included high-resolution B-mode sonography with semi-automated edge-detection and automatic electrocardiogram-gated real-time quality control. In 4,305 participants aged 14–28 years, distensibility coefficient (DC), stiffness index ß, Young's (YEM) and Peterson's elastic modulus (Ep) were assessed. Centiles were modelled by sex, age and height simultaneously, using generalized additive models for location, scale and shape. Log- binomial regression models were used to investigate associations of blood pressure with cS > = 90th centile (P90) as outcomes. Hypertensive blood pressure was defined according to German guidelines (> = P95 systolic or diastolic for age, height and sex according to KiGGS centiles until age 17 and > = 140/90 mmHg from age 18).

Results:

Multivariable models show that hypertensive blood pressure in childhood is associated with an increased risk of elevated cS (> = P90 for age, height and sex) eleven years later for all parameters of cS, with the exception of stiffness index

ß (no association). Effect estimates for DC, YEM and Ep range from 1.77 [CI 1.28–2.44] for DC to 1.41 [CI 0.99–2.01] for YEM. Cross-sectional associations of blood pressure with cS parameters show even stronger associations (relative risks between 1.3 and 3.3).

Conclusions:

Using state-of-the-art sonography and centiles computed with novel statistical methods, this study confirms that, at the population level, hypertensive blood pressure in childhood is linked to increased carotid stiffness in young adulthood. The results emphasize that healthy lifestyles and healthy living environments in childhood and adolescence represent an early investment in cardiovascular health.
SYSTOLIC AND DIASTOLIC LEFT VENTRICULAR DYSFUNCTION IN CHILDREN WITH PRIMARY HYPERTENSION: A SYSTEMATIC REVIEW
Authors: Azukaitis Karolis , Rus Rina , Sagsak Elif , Jankauskiene Augustina , Sinha Manish , Litwin Mieczyslaw , Wg Hyperchildnet
Published: June 2022

Objective:

Evaluation of left ventricular (LV) function provides important insights about target-organ damage in children with primary hypertension (PH). We aimed to summarize evidence about LV systolic and diastolic function in pediatric PH by performing a systematic review.

Design and method:

718 papers (published between 2000–2021) retrieved by a liberal search strategy in PubMed database using keywords relevant to pediatric hypertension and LV underwent abstract and title screening and 37 underwent full-text review. 22 articles providing comparison of LV function parameters between children with PH and normotensive controls were selected.

Results:

Analysis included a total of 1430 children (age range: 5–21 years) with PH (6.7% white-coat). Reported prevalence of LV hypertrophy was 7.7–48% (n = 15 studies). Majority of studies used ultrasound and 1 used magnetic resonance imaging for LV function evaluation.

None of 15 studies reporting systolic parameters such as fractional shortening or ejection fraction (EF) reported differences from controls except for 2 studies with lower EF within normal range. 5 studies used strain analysis for LV systolic function assessment with lowered strain in 60%. Strain parameters correlated with LV mass (n = 2), obesity indices (n = 2), blood pressure (BP) (n = 2) and other (age, sex, race and antihypertensive therapy; all n = 1). 5 studies evaluated Tei index with increased values in 60%. 1 study assessed first-phase EF (EF1) which was lower in children with PH and higher LV mass.

Most studies evaluated diastolic function by E/A (n = 19) and E/e‘ (n = 16) that were impaired compared to controls in 47% and 94%, respectively. Measures of diastolic function correlated with LV mass (n = 3), obesity indices (n = 3), BP (n = 2), insulin resistance (n = 2), age (n = 2) and other (neutrophile-lymphocyte ratio, puberty, heart rate and EF1; all n = 1).

Conclusions:

Children with PH exhibit signs of impaired LV function with predominance of diastolic dysfunction. Conventional ultrasound measures appear to lack sensitivity, thus tissue Doppler imaging and strain analysis may be preferred measures to quantify subclinical LV dysfunction in children with PH.
NON-INVASIVE BIOCHEMICAL SCORES OF NAFLD AND CAROTID MORPHOFUNCTIONAL ALTERATIONS IN NEVER TREATED ESSENTIAL HYPERTENSIVE PATIENTS
Authors: Candusso Giulia , Catena Cristiana , Soardo Giorgio , Baiano Valeria , Scandolin Laura , Bulfone Luca , Vacca Antonio , Donnini Debora , Da Porto Andrea , Brosolo Gabriele , Colussi Gianluca , Cavarape Alessandro , Vivarelli Cinzia , Bertin Nicole , Sechi Leonardo
Published: June 2022

Objective:

The non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular events. At the same time a subclinical carotid change is associated with mortality and morbidity in hypertension. However it's unclear if there is a relationship between NAFLD and subclinical carotid damage in essential hypertension (EH). We searched for relationships between biochemical non-invasive NAFLD scores and subclinical carotid damage in a group of naïve EH patients.

Design and method:

In 299 naïve EH subjects (age 50 ± 13 years, 132 males) we evaluated clinical characteristics, biochemical scores of liver steatosis, as liver Fat Score (LFS), and fibrosis, as NAFLD Fibrosis Score (NFS), APRI, Fibrometer, and FIB-4, presence of echographic steatosis, metabolic syndrome, diabetes, levels of glucose, insulin, HOMA, lipids, glomerular filtration rate (GFR), reactive C protein (RCP), liver tests, platelet count, smoking habit and physical activity. By ultrasound carotid examination we measured the intima-media thickness (IMT), presence of carotid plaques, and in 115 subjects we calculated the carotid stiffness indexes, as the distension coefficient, the beta-stiffness, and the Young elastic module.

Results:

The IMT significantly increased across quartiles of LFS (P = 0.036), NFS (P = 0.001) and FIB-4 (P = 0.003). IMT was independently associated with FIB-4 (B = 0.380, P = 0.003) and NFS (B = 0.221, P = 0.013) scores. A IMT > 0.9 mm was independently associated with FIB-4 (P = 0.042). Patients with plaques had higher APRI (P = 0.005), Fibrometer (0.023), NFS (P < 0.001) and FIB-4 (P = 0.005) scores, and prevalence of plaques increased progressively across quartiles of LFS (P = 0.046), NFS (P < 0.001) and FIB-4 (P = 0.005). There was an independent association between carotid distension coefficient and Fibrometer (B = -0.360, P = 0.029), and between beta-stiffness and Fibrometer (B = 0.340, P = 0.036).

Conclusions:

In naïve EH patients the carotid IMT and carotid stiffness are independently associated with non-invasive NAFLD indexes. This association could induce to a more careful evaluation of a non-alcoholic liver damage in EH patients with subclinical carotid alterations. Moreover, studies are needed to clarify if profibrotic mechanisms are the base of both damages.
GLOMERULAR HYPERFILTRATION MAY CONTRIBUTE TO RENAL TROPISM AND KIDNEY INJURY IN COVID-19 BY UPREGULATING ACE2 IN HUMAN PODOCYTES
Authors: Bolbrinker Juliane , Mangelsen Eva , Kourpa Aikaterini , Debora Kaiser , Daniela Panakova , Reinhold Kreutz
Published: June 2022

Objective:

Apart from the respiratory system, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can potentially infect multiple other organs including podocytes in the kidney. The latter play a crucial role in glomerular filtration. Podocytes can be damaged by increased fluid flow shear stress (FFSS) of the ultrafiltrate in Bowman's space in the setting of glomerular hyperfiltration that occurs in disease states such as hypertension, diabetes or in several forms of chronic kidney disease. These conditions are associated with an increased risk of a more severe course of coronavirus disease 2019 (COVID-19) and mortality.

Design and method:

To assess the susceptibility of human podocytes (hPC) for SARS-CoV-2 infection in the context of hyperfiltration in vitro, we used a recently established model system (Streamer® Shear Stress Device)) to mimic hyperfiltration by exposing hPC to increased FFSS of 1 dyne/cm2 for 2 h. In this setting we nalysed the effects of FFSS on mRNA expression of angiotensin I-converting enzyme 2 (ACE2) as the pivotal entry receptor for SARS-CoV-2 infection in hPC. Moreover, other potential critical host cell factors including transmembrane serine protease 2 (TMPRSS2), furin (FURIN), and neuropilin 1 (NRP1) were also assessed in parallel with changes of the F-actin fiber structure, i.e. an important cytoskeletal marker in hPC.

Results:

Under control conditions, hPC displayed long, parallel F-actin fibers crossing the entire cell body. After FFSS, an enrichment of cells that express F-actin in a cortically condensed pattern near the cell membrane was observed. FFSS induced a significant upregulation of ACE2 expression (about twofold) and of all other nalysed SARS-CoV-2 entry factors in hPC (p < 0.05, respectively compared to control conditions, Figure 1 with data plotted as log2fold change [FC]).

Conclusions:

Our data support a potential link between glomerular hyperfiltration, podocyte damage and renal tropism of SARS-CoV-2 that may contribute to kidney damage including albuminuria development in COVID-19 patients.
IMMUNE DYSREGULATION INDUCED BY SPIKE PROTEIN 1 OF SARS-COV-2 INCREASES ENDOTHELIAL CELL DYSFUNCTION VIA TYPE I AND TYPE III INTERFERON ACTIVATION PATHWAYS
Authors: Rios Francisco J. , Montezano Augusto C. , Camargo Livia L. , Lopes Rheure A. , Garcia-Redondo Ana B. , Aranday-Cortes Eliju , Briones Ana M. , Mclauchlan John , Touyz Rhian M.
Published: June 2022

Objective:

COVID19-associated immunopathology is associated with increased production of interferon (IFN)-alpha (IFNα) and lambda3 (IFNL3). Effects of IFNs are mediated by interferon-stimulated genes (ISGs) and influence expression of angiotensin-converting enzyme 2 (ACE2), the receptor for S-protein (S1P) of SARS-CoV-2. Increasing evidence indicates vascular inflammation in cardiovascular sequelae of COVID19. We hypothesized that S1P-induced immune/inflammatory responses in endothelial cells (EC) are mediated via IFNα and IFNL3.

Design and method:

Human ECs were stimulated with S1P (1 μg/mL), IFNα (100ng/mL) or IFNL3 (100IU/mL). Because ACE2, metalloproteinase domain-17 (ADAM17) and type-II transmembrane serine protease (TMPRSS2) are important for SARS-CoV-2 infection, cells were treated with inhibitors of ADAM17 (marimastat, 3.8 nM), ACE2 (MLN4760, 440pM), and TMPRSS2 (camostat, 50 μM). Gene and protein expression was investigated by real-time PCR immunoblotting, respectively. Vascular function was assessed in mesenteric arteries from wild-type (WT) normotensive and hypertensive mice and in ISG15-deficient (ISG15KO) mice.

Results:

EC stimulated with S1P increased expression of IFNα (3-fold), IFNL3 (4-fold) and ISG (2-fold)(p < 0.05). EC exhibited higher responses to IFNα (ISG15: 16-fold) than to IFNL3 (ISG15: 1.7-fold)(p < 0.05). S1P increased gene expression of IL-6 (1.3-fold), TNFα (6.2-fold) and IL-1β (3.3-fold), effects that were maximized by IFNs. Only marimastat inhibited S1P effects. IL-6 was increased by IFNα (1,230pg/mL) and IFNL3 (1,124pg/mL) vs control (591pg/mL). This was associated with increased phosphorylation of Stat1 (134%), Stat2 (102%), ERK1/2 (42%). Nitric oxide production and eNOS phosphorylation (Ser1177) were reduced by IFNα and (40%) and IFNL3 (40%). Reduced endothelium relaxation maximal response (%Emax) was observed in vessels from WT-mice stimulated with IFNα (67%) and IFNL3 (71%) vs control (82%)(p < 0.05) but not in vessels from ISG15KO mice. Increased contraction was observed only in vessels from hypertensive mice treated with IFNα (9.1 ± 0.5mN vs control: 7.3 ± 0.3mN, p < 0.05).

Conclusions:

In ECs, S1P, IFNα and IFNL3 increased ISG15 and IL-6, processes that involve ADAM17. Inflammation induced by S1P was amplified by IFNs. IFNs induce vascular dysfunction through ISG15-dependent mechanisms, with augmented effects in hypertension. Our findings demonstrate that S1P induces immune/inflammatory responses that may be important in endotheliitis associated with COVID-19. This is especially important in the presence of cardiovascular risk factors, including hypertension.
THE IMPACT OF HYPERTENSION AND ANTIHIPERTENSIVE TREATMENTS ON PATIENTS WITH SARS-COV-2: A RETROSPECTIVE-COHORT STUDY
Authors: Luque Paula , Castilla-Guerra Luis , Sanchez Nieves , Delgado Maria , Alegre Maria , Carmona Eduardo , Rico Miguel Angel
Published: June 2022

Objective:

Hypertension is one of the most important factors for cardiovascular disease. It has been repeatedly proposed as a prognostic factor of severe COVID-19 and has been included in clinical risk scores to predict the occurrence of critical illness in ospitalised with COVID-19. Also, it has been postulated the relation between antihypertensive drugs and the severity of COVID-19. The aims of our study were to analyze whether hypertension and antihypertensive treatment represent an independent risk factor for death or intensive care unit admission in patients with SARS-COV2.

Design and method:

Observational, retrospective, single-center cohort study of all patients admitted to Hospital Virgen Macarena diagnosed with COVID-19 between the months of March and December 2020. A bivariate analysis was performed using Pearson's chi-square

Results:

608 patients required admission for COVID-19. A total of 83.7% were hypertensive, specifically 75.9% were under antihypertensive treatment (35.7% with only 1 drug, 29.9% were taking two drugs, 9% with three drugs, and 1.3% with 4 drugs). 26.2% were treated with an ACEI, 24.8% with ARA-II, 16.8% with calcium-antagonists, 30.9% with diuretics, 21.2% with beta-blockers, 0, 5% with alpha-blockers). Hypertension did not show a statistically significant relationship with mortality (p = 0.34), increase in mortality and ICU admissions. Neither treatment with ACEI (p = 0.4), ARB-II (p = 0.45), calcium antagonists (p = 0.53), diuretics (p = 0.68), alpha blockers (p = 0.07) demonstrated relation with those items. Surprisingly, beta-blockers increased the mortality in patients with SARS-COV2 (p = 0.048). Probably this results can be explained as these drugs were indicated for rate control in patients with atrial fibrillation (p = 0.006). The number of antihypertensive drugs used also did not show a statistically significant relationship with an increase in mortality (p = 0.978).

Conclusions:

Hypertension is a highly prevalent pathology in patients ospitalised with COVID-19 infection. However, high blood pressure was not associated with a higher risk for mortality in patients with SARS-COV-2, neither the type or the number of antihypertensive drug used. Only beta-blockers alter outcomes in hypertensive patients with COVID-19, as they were associated with more deaths.
CHANGES IN RETINAL VESSEL DIAMETER ARE ASSOCIATED WITH CEREBRAL MICROBLEEDS IN NEUROLOGICALLY ASYMPTOMATIC INDIVIDUALS WITH TYPE 1 DIABETES
Authors: Tarkkonen Aleksi , Fickweiler Ward , Sun Jennifer , Thorn Lena , Eriksson Marika , Groop Per-Henrik , Forsblom Carol , Putaala Jukka , Martola Juha , Gordin Daniel
Published: June 2022

Objective:

We observed recently that a third of asymptomatic individuals with type 1 diabetes (T1D) showed signs of cerebral small-vessel disease in brain magnetic resonance imaging (MRI). Here, we aimed to explore the relationship between an easily applicable quantitative measure of retinal vessel diameters (RVD) and cerebrovascular changes in these individuals.

Design and method:

We included 188 individuals with type 1 diabetes and 30 healthy sex and age matched (49% males, median age 40 years) controls. Any neurological signs or symptoms were exclusion criteria. All subjects underwent a clinical and biochemical work-up, as well as brain MRI. Both retinas were phenotyped by measuring the width of all vessels located 0.5 to 1.0 disc diameters from the disc margin by a computer-assisted method (IVAN software). Summarized estimates for central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) represented average retinal vessel diameters. The arteriole-to-venule ratio (AVR) was calculated as an additional estimate of early retinal vascular pathology. Associations between blood pressure (BP), cerebral microbleeds (CMBs), white-matter hyperintensities (Fazekas classification), and CRAE, CRVE, and AVR were assessed with non-parametric tests and linear regression models.

Results:

No difference in CRAE, CRVE, or AVR were found between individuals with type 1 diabetes and controls. An expected correlation between BP and CRAE (p = 0.01) was observed. Median AVR was lower among individuals with T1D and cerebral microbleeds (p = 0.02) compared to those without. A correlation between AVR and the number of CMBs (p = 0.035) was also found. Further, median CRAE was lower among those with > 10 CMBs (p = 0.039) compared to those without. We observed no correlations between RVD and white-matter hyperintensities.

Conclusions:

Individuals with CMBs had lower CRAE and AVR suggesting that early vascular changes in the retinal are indicative of cerebrovascular pathology in middle aged individuals with T1D.
LEVERAGING TECHNOLOGY TO SUPPORT PEOPLE LIVING WITH HYPERTENSION AND DIABETES DURING THE COVID-19 PANDEMIC
Authors: Uagboe Aima Adebo , Ogboye Ayoposi , Munee Maria Moosa , Rahman Km Jawadur , Akpakli Jonas Kofi , Mobisson Nneka
Published: June 2022

Objective:

The aim of this study is to analyse the impact of a digital self-care intervention during the Covid-19 pandemic on the control of hypertension and diabetes in low-income populations comorbid with these conditions.

Design and method:

This was a retrospective study of 665 people in Nigeria (213 male, 431 female. Mean age - 58 years) with comorbid diabetes and hypertension enrolled on mDoc's digital self-care CompleteHealth™ platform from March 2020 till November 2021. Through the virtual platform, they were able to track their blood pressure and fasting blood glucose levels as well as co-create action plans with goals suited to achieve the best health outcomes with a virtual health coach. They were given personalised guidance and health education to help control their conditions. The change in blood pressure and fasting blood glucose level was calculated as the difference between the baseline value of the metric (the first value entered on CompleteHealth™) and the average of subsequent values entered on the platform.

Results:

600 people (90.2%) had at least 1 interaction with a virtual health coach for a total of 10,030 interactions with the coach-led multidisciplinary team. Of the 665 people included in the study, 407 (61,2%) entered a subsequent blood pressure value, with systolic and diastolic blood pressure declining by an average of 6.25 mmHg and 4.27 mmHg respectively. 68.3% of these people had controlled blood pressure at the end-line, up from 41.8% at the baseline. 50.6% of these people saw an improvement in both systolic and diastolic blood pressure of 19.52 mmHg and 12.63 mmHg respectively. Of the 266 people (40%) who entered multiple blood glucose levels, 31.95% had controlled blood glucose levels with an average decline of 15.5 mmol/L. 58.65% saw an improvement in their blood pressure value of 44.44 mmol/L.

Conclusions:

Our findings suggest that digital self-care can play a key role in supporting low-income populations living with diabetes and hypertension during the COVID-19 pandemic where restrictions exist on in-person service provision.
DEVELOPMENT OF AN ADRENOCORTICAL CELL MODEL OF CALCIUM SIGNALING MODULATION TO DECIPHER THE MOLECULAR MECHANISMS RESPONSIBLE FOR PRIMARY ALDOSTERONISM
Authors: Fedlaoui Bakhta , Cosentino Teresa , Sayed Zeina Al , Giscos-Douriez Isabelle , Fernandes-Rosa Fabio L. , Hulot Jean-Sebastien , Magnus Chris , Sternson Scott M. , Zennaro Maria-Christina , Boulkroun Sheerazed
Published: June 2022

Objective:

Primary aldosteronism (PA) is the most frequent form of secondary hypertension. The identification of germline or somatic mutations in different genes coding for ion channels (KCNJ5, CACNA1D, CACNA1H and CLCN2) and ATPases (ATP1A1 and ATP2B3) defines PA as a channelopathy. These mutations promote activation of calcium signaling, the main trigger for aldosterone biosynthesis.

The objective of our work was to elucidate, using chemogenetic tools, the molecular mechanisms underlying the development of PA by modulating sodium entry into the cells, mimicking some of known mutations identified in PA.

Design and method:

We have developed an adrenocortical H295R_S2 cell line stably expressing a chimeric ion channel receptor formed by the extracellular ligand-binding domain of the α7 nicotinic acetylcholine receptor fused to the ion pore domain of the serotonin receptor 5HT3α and named α7–5HT3. Mutations have been introduced in the ligand binding domain to allow only synthetic drugs to activate this channel receptor. Activation of α7–5HT3 by a specific drug, PSEM-817 leads to sodium entry into the cells. This cell line was characterized in terms of intracellular calcium concentrations, cell proliferation, aldosterone production, steroidogenic expression and electrophysiological properties.

Results:

Treatment of α7–5HT3 expressing cells with increasing concentration of PSEM-817 (from 10–9 to 10–5 M) induced a significant increase in intracellular calcium concentrations, similarly to potassium (12 mM) or angiotensin II (10–8 M). This stimulation of calcium signaling did not affect cell proliferation, but was responsible for an increase in CYP11B2 expression and aldosterone production after 24 h of treatment. However, while increased intracellular calcium concentrations were observed starting from 10–8 M of PSEM-817, CYP11B2 expression and aldosterone production were only affected starting from 10–7 M, suggesting a dose dependent effect. Finally, whereas cells were hyperpolarized in absence of stimulation (around -60 mV), PSEM-817 induced a strong depolarization, cells rising to a membrane potential around -10 mV.

Conclusions:

This cell line, in which we can modulate the intracellular calcium concentration “on demand”, is a useful tool for a better understanding of the alterations of intracellular ion balance and calcium signaling in the pathophysiology of PA.
PRELIMINARY REPORT: BLOOD PRESSURE TRAJECTORIES OVER TIME IN A MULTI-ETHNIC POPULATION
Authors: Vriend Esther Martha Ca , Bouwmeester Thomas Adriaan , Galenkamp Henrike , Collard Didier , van den Born Bert-Jan Hendrik
Published: June 2022

Objective:

Objective: Hypertension remains the leading cause of cardiovascular diseases worldwide. Major interethnic differences in the prevalence of hypertension exist. Exploring blood pressure (BP) levels in a large prospective multi-ethnic population provides insight in interethnic differences in blood pressure trajectories across the life course.

Design and method:

Design and method: We examined BP course over time in participants from the HEalthy Life in an Urban Setting (HELIUS) study. Participants aged 18–70 years from Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin with BP data at baseline and follow-up were included. BP levels were corrected for the use of antihypertensive medication. BP change over time was expressed as delta systolic blood pressure (delta SBP) and delta diastolic blood pressure (delta DBP). Multivariate regression analyses were performed to assess the association between ethnicity and BP levels at follow-up, with correction for sex, age, follow-up time, change of BMI and blood pressure levels at baseline.

Results:

Results: In total 8.053 participants (mean age 46.2 (12.4) years, 43.8% female) were included. Median follow-up time was 6.2 (5.3–7.1) years. Overall there was a slight increase in SBP over time (129.41 mmHg at baseline vs. 129.87 at follow-up), while diastolic blood pressure levels tended to decrease (delta DBP = -0.59 mmHg) (Figure 1). The highest SBP increase was found in the Ghanaian population (+1.84 mmHg), while the largest decrease was observed in in the Dutch population (-0.28 mmHg). The lowest DBP decrease was found in the Ghanaian population (-0.02 mmHg) and the highest decrease in the South-Asian Surinamese population (-1.31 mmHg). Multivariable regression analysis showed a strong association between ethnicity and SBP at follow-up, especially for the Ghanaian population (β = 5.51 (95%CI 4.42 – 6.61), p = 2.2e-16) compared to the Dutch reference population. For DBP these interethnic differences were also present, but less pronounced.

Conclusions:

Conclusions: Major interethnic differences in the course of blood pressure over time were found, with substantially higher SBP levels in the Ghanaian population compared to the reference Dutch population.
HIGHER SYSTOLIC BLOOD PRESSURE IN FEMALE PATIENTS WITH MITOCHONDRIAL DISEASE
Authors: Deinum Jaap , Viering Daan , Van Borselen Marjolein D , Bindels René , De Baaij Jeroen , Janssen Mirian Ch
Published: June 2022

Objective:

Previous research suggests that hypertension is more prevalent among patients with mitochondrial diseases. Blood pressure (BP) is linearly related to increased cardiovascular risk, and this relationship is strongest for systolic blood pressure; nevertheless, studies on systolic and diastolic blood pressure in mitochondrial diseases have not yet been performed.

Design and method:

In a retrospective case-control study design, BP in mitochondrial disease patients was compared to BP in a population cohort. Secondly, using multiple linear regression, we examined blood pressure differences in various genetic mitochondrial diseases. Lastly, we explored additional predictors of BP in a subgroup with the m.3243A>G variant.

Results:

286 genetically confirmed mitochondrial disease patients were included. Of these patients 180 carried the m.3243A>G mitochondrial DNA variant. Systolic BP (SBP) was 9 mmHg higher in female mitochondrial disease patients than in the general female population (95% CI: 4.4 - 13.3 mmHg, p < 0.001), while male patients had similar BP compared to controls. BP was not significantly different in patients with (1) m.8344A>G and m.8363G>A, (2) a mtDNA deletion or (3) a nuclear mutation compared to m.3243A>G patients. Higher SBP was a predictor of left ventricular hypertrophy in the m.3243A>G subgroup (p = 0.04).

Conclusions:

Novel aspects of the role of mitochondrial dysfunction in blood pressure regulation are exposed in this study. Compared to the general population, female mitochondrial disease patients have a higher SBP. Left ventricular hypertrophy is more prevalent in patients with higher SBP. Clinicians should be aware of this to prevent hypertensive complications in mitochondrial disease patients.