bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.