bluuebunny/crossref_metadata_2025_split huggingface dataset:
S-10-3: CAN ACHIEVED AVERAGE SYSTOLIC BLOOD PRESSURE BELOW 130 MMHG CAUSE HARM IN ELDERLY HYPERTENSIVE PATIENTS WITH LEFT VENTRICULAR HYPERTROPHY?
Authors: Heimark Sondre , Julius Stevo , Mancia Giuseppe , Soraas Camilla , Mehlum Maria , Wachtell Kristian , Liestol Knut , Kjeldsen Sverre Erik , Weber Michael 
Published: January 2023

Objectives:
We previously reported increased mortality in hypertensive patients > 55 yrs. (average 67 yrs., n = 9,193) with left ventricular hypertrophy (LVH) who achieved in-treatment systolic blood pressure (SBP) < 130 mmHg during an average of 5 yrs. of treatment. Possibly hypertrophic myocardium with degenerated microcirculation becomes ischemic causing fatal complications. The present study aimed to investigate similar elderly patients with LVH in a parallel outcome trial and test the hypothesis that achieved average SBP < 130 mmHg may cause harm in the elderly.

Design and Methods:
Of 15,245 participating hypertensive patients we identified a population without cardiovascular events during the first 18 months (n = 13,808) after enrollment with discontinuation of previous antihypertensive medications and subsequent up-titration of randomized study drugs and stabilization of SBP. Of these 2,458 patients had electrocardiographic LVH with or without strain. Patients who achieved average SBP > = 140 mmHg during the coming 30 months of follow-up (main population n = 5,505, LVH n = 1,200) served as reference groups. Cox-analyses adjusted for age, gender, and a number of baseline variables were used to compare the primary cardiac composite endpoint including fatal events, stroke and congestive heart failure for patients who achieved average SBP 130–139 mmHg (main population n = 5,833, LVH n = 939) and patients who achieved average SBP < 130 mmHg (main population n = 2,465, LVH n = 319).

Results:
The TABLE shows hazard ratios and 95% confidence intervals for groups with achieved average SBP 130–139 mmHg and < 130 mmHg for the primary cardiac endpoint, stroke and heart failure in the main population and in LVH patients. For the main population achieved average SBP < 130 mmHg prevented primary cardiac events and stroke but not heart failure. For the LVH patients achieved average SBP < 140 mmHg prevented the primary event but < 130 mmHg did not. However, the risks for stroke and heart failure were not significantly reduced with SBP < 140 mmHg in the LVH patients and the risk of heart failure was non-significantly increased < 130 mmHg.

Conclusions:
Achieved average SBP < 130 mmHg prevents the primary cardiac endpoint and stroke but not heart failure in elderly hypertensive patients. The risk of primary cardiac events was not significantly reduced < 130 mmHg in the LVH patients, and the risks for stroke and heart failure were not significantly reduced < 140 mmHg. On the contrary, < 130 mmHg the risk for heart failure was increased though not significantly. Target SBP thus remains highly uncertain in elderly LVH patients and needs further investigation.
S-12-2: ENHANCING MAS1:ETBR INTERACTION AS A POTENTIAL VASOPROTECTIVE STRATEGY IN STROKE-PRONE SHR
Authors: Kuriakose Jithin , Montezano Augusto , Lopes Rheure Alves , Sin Yuan Yan , McAbney John , Scott Kayley , Beattie Wendy , Graham Delyth , Baillie George Scott , Touyz Rhian 
Published: January 2023

We previously demonstrated that Ang-(1–7) has anti-inflammatory effects in endothelial cells by inducing interaction between Mas1 and ETBR. Using HTS of > 20,000 druggable compounds, we identified several compounds that enhance Mas1:ETBR interaction as a novel strategy to promote vasoprotection.
The objective of this study was to evaluate effects of 2 candidate compounds, termed enhancers 3 and 4 (Enh3 and Enh4), on functional responses in vascular smooth muscle cells (VSMCs) and their therapeutic potential in hypertensive (SHRSP) rats. VSMCs from normotensive (WKY) and SHRSP rats were exposed to Enh3 and Enh4(10–5 M; 5–30 mins). Expression of pro-contractile and mitogenic molecules was assessed by immunoblotting. Ca2+ influx was evaluated using fluorescence microscopy. ROCK2 activity was assessed using a colorimetric immunoassay which detected MYPT1 phosphorylation at Thr696. Male SHRSP rats (18–21weeks) were treated subcutaneously with Enh4 (10 mg/kg/day) for 7 days. Changes in blood pressure and vascular function were assessed via radiotelemetry and wire myography respectively. In WKY VSMCs, Enh3 reduced basal ERK1/2 phosphorylation (26.8 ± 5.9% vs veh,), an effect absent in SHRSP VSMCs, while Enh4 had no effect. Only in SHRSP VSMCs, Enh3, but not Enh4, reduced basal AKT phosphorylation (63.5 ± 8.9% vs veh). Enh4, but not Enh3, reduced basal MLC20 phosphorylation (54.9 ± 7.5% vs veh) in WKY but not in SHRSP VSMCs. ET-1-induced Ca2+ influx in WKY and SHRSP VSMCs was unaffected by Enh3 and Enh4. Assessment of Ca2+ -independent contractile mechanisms in VSMCs showed that ROCK2 activity is increased in SHRSP compared to WKY VSMCs (WKY: 0.27 ± 0.05; SHRSP:4.78 ± 0.34) and Enh4, but not Enh3, reduced ROCK2 activity in SHRSP VSMCs (61.5 ± 0.43% vs veh). Enh4 treatment in SHRSP rats reduced daytime systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) (SBP:4.26 ± 1.98; DBP:1.48 ± 0.92; MAP:2.07 ± 0.99 vs veh) compared to baseline. Furthermore, Enh4 treatment reduced U46619 induced contraction in SHRSP rat vessels (Emax(Mn): Veh- 13.16 ± 1.81; Enh4- 9.48 ± 1.31). Taken together, enhancing Mas1:ETBR interaction attenuates mitogenic and contractile signaling pathways in WKY and SHRSP VSMCs, and does not increase Ca2+ signaling, important in VSMC contraction. Enhancing Mas1:ETBR interaction reduces blood pressure and improves vascular function in SHRSP rats. Hence, Mas1:ETBR enhancers may be of potential therapeutic use as a new vasoprotective strategy to improve vascular function and to reduce blood pressure in hypertension.
S-12-3: BENEFICIAL EFFECTS OF EMPAGLIFLOZIN ON METABOLIC PARAMETERS AND DIASTOLIC FUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS FED A HIGH-FAT DIET
Authors: Vaneckova Ivana , Hojna Silvie , Zicha Josef , Malinska Hana , Huttl Martina , Papousek Frantisek 
Published: January 2023

Objective:
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial pathological syndrome characterized by lipid accumulation in hepatocytes. This can lead to non-alcoholic steatohepatitis (NASH) which can progress to liver fibrosis, cirrhosis and liver cancer. Unfortunately, the pathogenesis of NAFLD is still unknown. However, current studies suggest that gliflozins, primarily antidiabetics, could have beneficial effects on liver metabolism. The aim of this study was therefore to examine whether empagliflozin (10 mg.kg-1.day-1 in drinking fluid) will have beneficial effects.

Design and methods:
NAFLD was induced by eight weeks of high-fat diet feeding (60% protein) in adult (6-month-old) spontaneously hypertensive rats (SHR). Control SHR were fed a standard diet. Then, the animals were either untreated or treated with empagliflozin for eight weeks. The evaluation of renal function (metabolic cages) and oral glucose tolerance (OGT) test were performed before the start of the treatment and at the end of the study. Cardiac function evaluated by echocardiography as well as metabolic parameters in serum and in liver were determined at the end of the experiment.

Results:
High-fat diet feeding increased body weight and visceral adiposity. Moreover, it worsened insulin resistance (evaluated as OGT test). In addition, it induced increase in triglycerides and cholesterol levels. Although it had no effect on renal function, it substantially deteriorated not only systolic but also diastolic function of the heart in SHR rats. Empagliflozin had no effect on body weight or visceral fat deposition but improved insulin sensitivity (OGT test) and several metabolic parameters (plasma insulin, non-esterified fatty acids, uric acid and HDL-cholesterol). Moreover, it had beneficial effects on systolic (fractional shortening) and especially diastolic (PWTd, RWT, and E/A ratio) function.

Conclusions:
Our results demonstrated that the treatment with empagliflozin had beneficial hepatoprotective and cardioprotective actions in hypertensive rats with experimentally induced non-alcoholic liver fatty disease.
S-16-3: ANTIHYPERTENSIVE TREATMENT PRESCRIBING BEHAVIOURS IN FRENCH GENERAL PRACTICE IN 2021
Authors: Mourad Jean Jacques 
Published: January 2023

Hypertension (HT) is the leading reason for visits to general practitioners (GPs). Due to insufficient adherence and marked therapeutic inertia, there is room for improving blood pressure control in France. The objective of this study is to describe the antihypertensive treatment prescribing behaviours in French general practice.

Method:
Data from the IQVIA Longitudinal Patient Database (LPD) France were used. LPD France is a permanent observatory to which a nationally representative panel of physicians, including GPs (n = 1200), contribute anonymised electronic medical records (EMR). The analysis included all antihypertensive treatment prescriptions from July 2020 to June 2021, which were then extrapolated to the entire population. The following definitions were used to categorise the prescribing behaviours: INITIATION, for hypertensive patients already registered with the GP and who had been prescribed an antihypertensive treatment for the first time in 24 months; RENEWAL, for hypertensive patients whose therapeutic class had not changed, apart from dosage modifications, changes of molecule within the same class and titrations; CHANGE, for hypertensive patients for whom a therapeutic class had been added, withdrawn, and/or changed.

Results:
In 2021, a total of 11 557 545 hypertensive patients had received an antihypertensive treatment prescription following consultation with a GP. These were distributed as follows (see figure).

Conclusion:
These findings provide informative data on the prescribing behaviours of GPs, primarily marked by a renewal rate that does not appear to reflect the reality of blood pressure control in France. Prescription modifications are in the minority, and essentially consist of class rotations. This observation requires urgent reflection when it comes to the training of prescribers and the value placed on blood pressure control under the French public health objectives pay-for-performance scheme (ROSP).∗IQVIA EMR LPD Médecins Généralistes “. EMR = Electronic Medical Records, LPD = Longitudinal Patient Data
S-18-4: ACE2 IS INVOLVED IN SARS-COV-2 INDUCED ENDOTHELIAL CELL INFLAMMATION INDEPENDENT OF VIRAL REPLICATION
Authors: Montezano Augusto , Camargo Livia L , Mary Sheon , Neves Karla B , Rios Francisco J , Lopes Rheure A , Beattie Wendy , Herbert Imogen , Herder Vanessa , Szemiel Agnieszka M , McFarlane Steven , Palmarini Massimo , Bhella David , Touyz Rhian M 
Published: January 2023

Objective:
COVID-19 association with cardiovascular disease is thought to be due to endothelial cell inflammation. ACE2 interactions with SARS-CoV-2 spike protein S1 subunit is important to viral infection. Here we questioned whether SARS-CoV-2 induces vascular inflammation via ACE2 and whether this is related to viral infection.

Design and Methods:
Human microvascular endothelial cells (EC) were exposed to recombinant S1p (rS1p) 0.66 ug/mL for 10 min, 5 h and 24 h. Gene expression was assessed by RT-PCR and levels of IL6 and MCP1, as well as ACE2 activity, were assessed by ELISA. Expression of ICAM1 and PAI1 was assessed by immunoblotting. ACE2 activity was blocked by MLN4760 (ACE2 inhibitor) and siRNA. Viral infection was assessed by exposing Vero E6 (kidney epithelial cells; pos ctl) and EC to 105 pfu of SARS-CoV-2 where virus titre was measured by plaque assay.

Results:
rS1p increased IL6 mRNA (14.2 ± 2.1 vs. C:0.61 ± 0.03 2^-ddCT) and levels (1221.2 ± 18.3 vs. C:22.77 ± 3.2 pg/mL); MCP1 mRNA (5.55 ± 0.62 vs. C:0.65 ± 0.04 2^-ddCT) and levels (1110 ± 13.33 vs. C:876.9 ± 33.4 pg/mL); ICAM1 (17.7 ± 3.1 vs. C:3.9 ± 0.4 AU) and PAI1 (5.6 ± 0.7 vs. C: 2.9 ± 0.2), p < 0.05. MLN4760, but not rS1p, decreased ACE2 activity (367.4 ± 18 vs. C: 1011 ± 268 RFU, p < 0.05) and blocked rS1p effects on ICAM1 and PAI1. ACE2 siRNA blocked rS1p-induced IL6 release, ICAM1, and PAI1 responses as well as rS1p-induced NFkB activation. EC were not susceptible to SARS-CoV-2 infection, while the virus replicated well in Vero E6.

Conclusion:
rS1p induces an inflammatory response through ACE2 in endothelial cells; an effect that was independent of viral infection.
S-19-3: ANGIOTENSIN II REDUCES THE EXPRESSION OF CX43 AND INHIBITS THE C-SRC /MAPK/ERK PATHWAY VIA CX43 IN CARDIOMYOCYTES
Authors: Fan Xin , Chen Xinrong , Sun Runmin , Kou Chengkun , Wang Wenting , Wang Qiongying , Yu Jing 
Published: January 2023

Background:
Hypertension is associated with abnormal renin angiotensin system (RAS). Angiotensin II (AngII), an important substance in RAS, is closely related to cardiomyocyte injury. Connexin43 (Cx43), a key structural protein in cardiomyocyte membrane, takes part in signal transduction and substance transport. Cx43 may cause extracellular interstitial fibrosis.It is known that Cx43 increases collagen I in heart tissue by regulating nuclear factor kappa B and Mechanistic metalloproteinase.However, the relationship between Ang II and Cx43 has been controversial,and how Ang II affects Cx43-related pathway is unclear. Otherwise, the activation and inhibition of the c-SRC /MAPK/ERK pathway may is related to Cx43, but the fact which is the forward is not sure.

Objective:
The purpose of this study is to explore whether Ang II affects the expression of Cx43 and inhibits c-Src /MAPK/ERK pathway via Cx43.

Methods:
First,we given rat cardiomyocytes (H9C2 cells) different concentrations of Ang II (10–5 M,10–6 M and 10–7 M,for 48 h), and establish Ang II groups. There is a contral group, which was given normal culture without Ang II. Second,we given H9C2 cells the Gap26,which is the inhibition of Cx43.Proteins of Cx43 and c-SRC /MAPK/ERK pathway from all groups were detected by Western Blot, and mRNA of these proteins were detected by PCR. SPSS was used for statistical analysis to compare the difference between all the groups.

Result:
First, compared with the control group, protein of Cx43, c-SRC, ERK2 and ERK1 were significantly decreased in Ang II group, and when the concentration of Ang II was 10–5 M, these proteins were the least. mRNA of Cx43, ERK2 and ERK1 also were cut down after giving Ang II (only 10–5 M).Second, the Gap26-intervention group had the lower expression protein and mRNA of Cx43, c-SRC, ERK2 and ERK1.

Conclusion:
We proved that Angiotensin II can reduce the expression of Cx43 and inhibit c-SRC /MAPK/ERK pathway via Cx43 in cardiomyocytes.Based on the role of Cx43 and c-Src /MAPK/ERK pathway, hypertesion may injury the cardiomyocytes via RAS and these pathways.
S-22-4: GENOME WIDE ASSOCIATION STUDY OF FIBROMUSCULAR DYSPLASIA REVEALS MECHANISTIC LINKS WITH BLOOD PRESSURE REGULATION AND OTHER VASCULAR DISEASES
Authors: Georges Adrien , Yang Min Lee , Berrandou Takiy Eddine , Liu Lu , Sayed Ines Sadoug , Dikilitas Ozan , Vikkula Mikka , Januszewicz Andrzej , Kullo Iftikhar J , Azizi Michel , Jeunemaitre Xavier , Persu Alexandre , Kovacic Jason C , Ganesh Santhi K , Naji Nabila Bouatia 
Published: January 2023

Introduction:
Fibromuscular dysplasia (FMD) is a non-atherosclerotic arteriopathy of unknown etiology, afflicting mostly middle-aged women. It is characterized by stenotic lesions of the vascular wall in middle-size arteries, sometimes associated with dissection, aneurysm or tortuosity. Renovascular hypertension is a major presentation of FMD and 50–85% of FMD patients are hypertensive.

Methods & Results:
We report results from the first genome-wide association meta-analysis of six studies including 1556 FMD cases and 7100 controls. We identified four robustly associated loci (PHACTR1, LRP1, ATP2B1, and LIMA1). Using colocalization and transcriptome-wide association analysis with arterial expression datasets, we found PHACTR1, LRP1 and ATP2B1 as target genes at FMD loci and identified one additional locus (SLC24A3). We analysed chromatin accessibility in artery-derived primary cells and found that FMD associated variants were located in arterial specific regulatory elements active in smooth muscle cells. Target genes were broadly involved in mechanisms related to actin cytoskeleton and intracellular calcium homeostasis, central to vascular contraction.
All FMD loci were also associated to at least one blood pressure trait. Colocalization analysis supported the same genetic variants to cause association to FMD and systolic blood pressure at PHACTR1, ATP2B1 and LIMA1 loci, and for FMD and pulse pressure at PHACTR1, LRP1 and ATP2B1 loci. Using genome-wide genetic correlation, we found a significant association between FMD and blood pressure. Mendelian Randomization analysis supported genetically determined systolic blood pressure to significantly increase the risk of FMD. However, we confirmed using adjusted and stratified analyses that hypertension status alone was not driving the association with FMD at top loci. We also report an important genetic overlap of FMD with migraine, intracranial aneurysm, coronary artery disease and myocardial infarction.

Conclusion:
Our study confirms FMD as a polygenic disease following a complex genetic mode of inheritance. We find that FMD shares an important part of its genetic basis with blood pressure regulation, involving in particular several genes related to intracellular calcium homeostasis and vascular smooth muscle contraction. These results are consistent with previous studies showing systemic alterations in vascular contraction in FMD patients, even outside of affected arterial beds. While the mechanisms through which FMD may cause renovascular hypertension are well known, further studies will be required to determine how alterations in vascular contraction may lead to the arterial remodeling observed in FMD.
S-23-1: OCCUPATIONAL AND ENVIRONMENTAL INFLUENCES ON HYPERTENSION
Authors: Bursztyn Michael 
Published: January 2023

In this brief review I shall try to discuss several topics related to hypertension which maybe associated with occupational and environmental effects. Effects of dietary sodium will not be discussed as these are extensively discussed elsewhere. Occupational stress is difficult to define but there seems to be a relationship between high demands and relatively low control, and blood pressure in both men and women despite different professional distribution.
Noise, a relatively less recognized stressor that may be associated with hypertension Both industrial noise and urban noise. Recently due to the Covid19 lockdown and reduction of aircraft noise in relevant areas a reduction of blood-pressure was noted. Seasonal variation with rise of blood pressure during cold and perhaps shorter daytime light seasons, and subsequent reduction in the summer with its higher temperatures and longer light hours is one environmental factor. Air pollution, especially that associated with high level small particulate matter equal to, or smaller than 0.25 μm, was associated with hypertension in several studies, with quite and ethnic and geographic variability. High altitude exposure (higher than 2500 m), involves hypoxemia (in addition to radiation, cold temperatures, and dehydration because of dryness of inhaled air), resulting in renin angiotensin system activation and sympathetically induced vascular contraction, and elevation of pulse rate and blood-pressure at rest and an exaggerated increase during exercise. Immigration seems to be associated with hypertension through different mechanisms in different populations. Mechanisms of these effects are not well understood though some must be mediated through sympathetic activation, others through the renin angiotensin system though, hypoxemia, altered redox state and inflammation all might participate along with other mechanisms
S-23-3: EFFECT OF A WORKPLACE-BASED PRIMARY PREVENTION INTERVENTION FOR CARDIOVASCULAR DISEASE ON INCIDENCE OF HYPERTENSION - A CLUSTER RANDOMIZED CONTROLLED TRIAL
Authors: Hu Zhen 
Published: January 2023

Objective:
A workplace-based primary prevention intervention for cardiovascular disease could be an effective approach to encourage employees to adopt a healthy lifestyle and control the occurrence of hypertension. Our objective is to assess the effect of a workplace-based, multicomponent primary intervention strategy for cardiovascular disease on controlling the incidence of hypertension.

Methods:
A cluster randomized clinical trial was conducted from January 2013 to December 2014 in 60 workplaces across 20 urban regions in China. Workplaces were randomized to either the intervention group (n = 40) or control group (n = 20). All employee participants in each workplace were asked to complete standard questionnaire surveys and physical examinations. Employees in the intervention group were given a two-year workplace wellness intervention program, while those in the control group only maintained the existing health management measures in the workplace and did not receive additional intervention. The incidence of hypertension in baseline non-hypertensive patients in the intervention and control groups, as well as changes in blood pressure levels and lifestyle factors were assessed at the end of the trial.

Results:
Overall, 21,667 participants (16,488 in the intervention group and 5,179 in the control group) were included (mean [SD] age, 39.2 [9.0] years; 13,207 men [61.0%]). After 24 months of the intervention, the incidence of hypertension in baseline non-hypertensive patients was 7.2% in the intervention group and 8.2% in the control group (RR = 0.88, 95% CI,0.79 to 0.98, P = 0.012). The intervention effect was significant on systolic BP level (beta = -0.42, 95% CI, -0.80 to -0.05; P = 0.027) and on diastolic BP level (beta = -0.37, 95% CI, -0.67 to -0.07; P = 0.014). Moreover, greater improvement was reported in healthy lifestyle, such as the rates of smoking (-1.6%; 95% CI, -2.5% to -0.6%; P < 0.001), drinking (-3.1%; 95% CI, -4.0% to -2.2%; P < 0.001), regular exercise (10.9%; 95% CI, 9.8% to 11.9%; P < 0.001), perceived stress (-5.7%; 95% CI, -6.6% to -4.7%; P = 0.025), fatty food intake (-9.0%; 95% CI, -10.1% to -7.9%; P < 0.001) and excessive use of salt (-5.5%; 95% CI, -6.3% to -4.6%; P < 0.001).

Conclusion:
This trial found that workplace-based primary prevention interventions for cardiovascular disease appeared to be effective in reducing the prevalence of hypertension, leading to measurable benefits such as lower blood pressure and adoption of healthy lifestyle habits. The intervention can therefore be considered for large-scale use or inclusion in workplaces health promotion programs in China and other countries.