bluuebunny/crossref_metadata_2025 huggingface dataset:
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within the same class and titrations; CHANGE, for hypertensive patients for whom a therapeutic class had been added, withdrawn, and/or changed.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-18-6: SALT AND AGE-RELATED HYPERTENSION
Authors: Kawarazaki Wakako , Marumo Takeshi , Fujita Toshiro
Published: January 2023

Hypertension is the greatest risk factor for cardiovascular disease and stroke, and its incidence increases with age. Clinical studies have shown that salt intake is involved in the development of age-related hypertension and that salt sensitivity of blood pressure (BP) increases with age, but the mechanism was unknown. On the other hand, it was reported that circulating Klotho level, an anti-aging factor protein, decreased with age, and there was an inverse relationship between circulating Klotho and mean BP changes after saline infusion. We hypothesized that the decrease in circulating Klotho levels might be involved in the increase in salt sensitivity of BP with aging. We found that circulating Klotho significantly decreased in aged mice and Klotho heterozygous knockout (KO) mice than in young wild-type mice. They showed salt-sensitive hypertension unlike young wild-type mice, suggesting that a decrease in circulating Klotho was involved in the pathogenesis of salt-sensitive hypertension in aged mice. In both aged mice and Klotho heterozygous KO mice, it was revealed that vascular Wnt5a-RhoA pathway was activated and vasoconstriction was enhanced during high salt intake, resulting in hypertension. We also demonstrated that Klotho supplementation and Wnt and Rho kinase inhibitors significantly suppressed the BP elevation during high salt intake in these mice. Furthermore, we found that Wnt5a was essential for the activation of RhoA by Angiotensin II, an important agent in the formation of hypertension. Since increased vascular resistance of the renal arteries and decreased renal blood flow are involved in the pathogenesis of salt-sensitive hypertension. We analyzed the effects of Angiotensin II and RhoA stimulators to the renal arteries of high-salt fed aged mice and Klotho heterozygous KO mice. Marked vasoconstriction of the renal arteries and decrease in renal blood flow with BP elevation were observed, while responses were less in young mice. Augmented responses observed in aged mice and Klotho heterozygous KO mice were normalized by Klotho supplementation. These findings suggest that in aged mice with low circulating Klotho, salt intake causes activation of the vascular Wnt5a-RhoA pathway, resulting in increased contraction of the renal arteries as well as peripheral blood vessels, which reduces renal blood flow and eventually caused hypertension. We suggest that reducing salt consumption is highly important and lifestyle habits preserving adequate levels of Klotho are useful in the prevention of age-related hypertension. Wnt and Rho inhibitors may be new treatment options. Therapeutic development focusing on the unique background of aging may be applied to other age-related diseases.
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.
S-25-5: ASSESSING THE LEVEL OF PRACTICE AMONG PRIMARY CARE PHYSICIANS REGARDING HYPERTENSIVE DISEASE OF PREGNANCY(HDP): A CROSS-SECTIONAL NATIONAL SURVEY IN MALAYSIA
Authors: Sivaratnam Dhashani , Ching Siew Moi , Krishnan Girija Mohana , Hio Ahmad Najmi , Sultan Nursyafiqah Mohd , Neezar Mohd Nabil Mohd , Lim Hui Zhi , Zafirah Ain Aliah
Published: January 2023

Objectives:

Hypertensive disorders in pregnancy are one of the leading causes of maternal and neonatal morbidity and mortality worldwide. In Malaysia, The percentage of maternal death due to HDP rose from 15.2% (1997) to 18.1% (2007), resulting from the inaccessibility of healthcare services, lack of knowledge of complications by patients, and inadequately trained staff handle the difficulties. This study aimed to determine and evaluate the level of good practice for HDP among primary care physicians and the factors that influenced good knowledge regarding the management of HDP.

Design and method:

This cross sectional study recruited PCP practising in government or private clinics from Malaysia. It employed universal sampling through social networking, which was carried out using a validated self administered questionnaire through an online google form. The questionnaire consisted of 4 sections; social demography of the respondents, knowledge, attitude and practices involving HDP patients. Multivariate logistic regression was used to determine factors associated with poor practice on HPD.

Results:

A total of 176 participants were recruited for this study with a response rate of 46%, with a median age of 35 years (SD 7.28 years, 29 to 73.years). Most of the respondents were female (70.5% and practised in urban areas (55.7%) or the suburbs (31.8%). Most were in a group practice (75.6%), and only half the respondents had attended courses on HDP (53.5%). The following factors were found to correlate with good clinical practice: (1) age (p = 0.01), (2) practice location(p = 0.101) (3) average number of HDP patients seen in a week(p = 0.08) (4) availability of CPG in the clinic(p = 0.125) (5) duration since highest qualification (p = 0.04), (6) duration in primary care practice (p = 0.03) (7) Total of HDP attitude score(p = 0.04). In multiple logistic regression, duration since highest qualification(p = 0.02, OR 0.96, 95 %CI 0.886 to 1.040) and the average number of HDP patients seen per week(p = 0.025, OR 1.957, 95 %CI 1.038 to 1.731) were found to be predictors for good clinical practice.

Conclusion:

There is a low level of good practice among senior physicians and those who do not manage many HDP patients per week. Greater priority towards delivering more continuous medical education on HDP is required; to augment the clinical knowledge and skills, especially among senior physicians. Our study also revealed that physicians who worked with more HDP patients ensured their practice was up to date by the greater availability of the CPG in their clinic.
S-26-5: RENAL DENERVATION IN ASIA: GUIDELINES AND PERSPECTIVES IN CLINICAL PRACTICE
Authors: Kario Kazuomi
Published: January 2023

Hypertension Research will launch the special issue “A recent advance in renal denervation to clinical practice” in 2023 (Figure). Since the first proof-of-concept study in 2009, it has been passed for 13 years, the renal denervation is going to be introduced into clinical practice. The new clinical trials using the sham-control group have been performed. The meta-analysis and systematic review demonstrated that renal denervation is effective to reduce 24-hr blood pressure (BP), regardless of denervation techniques (Hypertens Res 2022;45:210–220). In 2022, the 2 major sham-controlled pivotal trials using the 2 different denervation techniques will be released. These study subjects had uncontrolled hypertension even medicated with one or more drugs. One is the SPYRAL On-Med Pivotal trial using the radiofrequency denervation technique and another is RADIANCE II trial using ultrasound technique, in which the trial, the Otsuka Holdings Co. Ltd (ReCor Medical Inc.). Inc released information on positive results in the market news.

In addition, a recently longer follow-up result of SPYRAL On-Med feasibility study demonstrated a long-term BP lowering effect for 24 hours persisted for at least 3 years (Lancet 2022;399:1401–1410). Especially, even after initiating the medication titration, in those with drug-resistant hypertension, who were medicated up to 3 or more drugs, a significant difference in the nighttime and morning BPs between the renal denervation group and sham-controlled groups was overt (ISH2022, Rapid online publication in Hypertens Res). This indicates that renal denervation exhibit an “always on” BP lowering effect throughout 24 hours, which covers nighttime and morning periods, the “pits’ fall” time of medication.

Recently guidelines/guidance and consensus statement include RDN in the option of antihypertensive treatment strategy. Positioning of renal denervation in the total management of hypertension in combination with non-pharmacological intervention and medication should be discussed. In addition, the patient preference studies demonstrated a consistently significant number of hypertensive patients preferred renal denervation. Cost-effectiveness should be soon addressed before clinical use.

Once 2 pivotal trials demonstrated clearly clinically meaningful positive results, renal denervation will be accepted to introduce into clinical practice. During the clinical practice after regulatory approval, the residual challenges of renal denervation such as how to detect the responders and how to assess the successful endpoints of the procedures should be addressed in real-world studies.

The Asia Renal Denervation Consortium consensus conference of Asian physicians actively performing renal denervation has been recently convened to share up-to-date information and regional perspectives, with the goal of consensus on RDN in Asia (Hypertension 2020;75:590–602).
S-27-6: ADAPTIVE IMMUNITY REGULATES RENAL SALT-RETENTION AND BLOOD PRESSURE
Authors: Mu Shengyu
Published: January 2023

Hypertension is a major public health problem, which contributes to a plethora of other cardiovascular diseases. A long-time postulate is that a defect in the kidney plays a key role in the development of hypertension. Years of intense research have confirmed that distal nephron plays important role in excessive salt retention, which contributes to the pathogenesis of hypertension. Yet the precise identity of this kidney defect and the downstream signaling mechanisms that impair sodium handling remain unclear. In the past decade, T cells, in particular CD8+ T cells (CD8Ts), have garnered attention as an important contributor to hypertension. T cells infiltrate into the kidneys of hypertensive animals, possibly driven by elevated perfusion pressure. Subsequently elevation of blood pressure and salt content stimulate T cell-activation and cytokine production. We recently reported a new mechanism by which renal infiltrated CD8Ts contribute to salt retention and hypertension: CD8Ts upregulate the sodium-chloride cotransporter (NCC) in the renal distal tubules, resulting in excessive salt retention via direct interactions between CD8Ts and renal distal convoluted tubule cells (DCTs) (Image in enclosed figure). This finding raises the exciting prospect that kidney-accumulation of CD8Ts and their interactions with DCTs represent one kidney defect in the pathogenesis of salt-sensitive hypertension. Although blocking NCC using thiazide temporarily lowered blood pressure in hypertensive animals, it failed to diminish T cell-homing to the kidneys, and hypertension returned after withdrawal of thiazide. Thus, in order to design effective therapeutics for salt-sensitive hypertension which interrupt the initial stimuli that trigger renal sodium retention, it is critical for us to define mechanisms of T cell-homing to the kidney and identify the key molecules mediating the CD8T-DCT interaction. Here, we further identified critical molecular players and demonstrated their roles in augmenting the CD8T-DCT interaction leading to salt-sensitive hypertension. We found that activated CD8Ts exhibit enhanced interaction with DCTs via IFNγ-induced upregulation of MHC-I and PDL1 in DCTs, thereby stimulating higher expression of NCC in DCTs to cause excessive salt retention and progressive elevation of blood pressure. Eliminating IFNγ or renal tubule-specific knockdown of PDL1 prevented T cell homing into the kidney, thereby attenuating hypertension in two different mouse models. These findings provide a new mechanism for T cell involvement in the pathogenesis of hypertension and reveal novel therapeutic targets.
S-28-2: EFFECT OF ESAXERENONE ON NOCTURNAL BLOOD PRESSURE COMBINED WITH RENIN-ANGIOTENSIN SYSTEM INHIBITOR OR CALCIUM CHANNEL BLOCKER IN UNCONTROLLED HYPERTENSION
Authors: Kario Kazuomi , Ito Sadayoshi , Itoh Hiroshi , Rakugi Hiromi , Okuda Yasuyuki , Yamakawa Satoru
Published: January 2023

Objective:

To evaluate the nighttime blood pressure(BP)-lowering effects of esaxerenone with different concomitant antihypertensive treatments, we conducted a post hoc analysis of a multicenter, open-label, long-term phase 3 study (NCT02722265) of esaxerenone, a highly selective mineralocorticoid receptor blocker, alone or in combination with a calcium channel blocker (CCB) or a renin-angiotensin system (RAS) inhibitor in patients with essential hypertension.

Design and method:

Patients had previously untreated essential hypertension, or had received only one RAS inhibitor or CCB as a baseline antihypertensive agent at the start of the study. All patients had a sitting systolic BP of 140 to < 180 mmHg and a sitting diastolic BP of 90 to < 110 mmHg, a 24-h ambulatory BP of ≧130/80 mmHg. In this post hoc analysis, patients were classified into 3 treatment groups; esaxerenone monotherapy, combination with a CCB and combination with RAS inhibitor and targeted on the patient without any additional antihypertensive treatment at Week 28. For these 3 groups, mean changes in 24-hour, early morning, daytime, and nighttime systolic BP in 24-h ambulatory BP, mean changes in N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, and changes in dipping pattern (extreme dippers, dippers, non-dippers, risers) were evaluated at 28 Week to include as many patients as possible available for analysis.

Results:

Of the total 368 patients in the study, 248 patients were included in this analysis and there were 153 in esaxerenone monotherapy, 48 in combination with a CCB and 48 in combination with a RAS inhibitor. Nighttime systolic BP statistically significantly decreased in all groups at Week 28 compared to baseline, with combination with a RAS inhibitor group showing the greatest change (-20.6 mmHg). Those changes were numerically greater than the daytime systolic blood pressure in all groups. The decrease in NT-proBNP from baseline to Week 28 was statistically significant in all group (p < 0.001, respectively) and the decrease in combination with RAS inhibitor was numerically greater than that of monotherapy.

A statistically significant shift in dipping pattern and changes from riser/non-dipper to dipper/extreme dipper pattern were found at Week 28 in Monotherapy (p < 0.05) and the same trend of shifting was shown in combination with RAS inhibitor (p = 0.1615). The prevalence of riser/non-dipper pattern was decreased from 58.2% to 47.7% in monotherapy and from 54.2% to 39.6% in combination with RAS inhibitor.

Conclusions:

Esaxerenone would provide a useful treatment option for nocturnal hypertension, especially in combination with RAS inhibitor, in uncontrolled hypertension.
S-28-4: ASSOCIATION BETWEEN INCOME AND PROGRESSION OF CHRONIC KIDNEY DISEASE IN JAPAN: A NATIONWIDE COHORT STUDY
Authors: Ishimura Nana , Inoue Kosuke , Kondo Naoki
Published: January 2023

Introduction:

Chronic kidney disease (CKD) is one of the major public health issues, causing 1.4 million death in 2019 worldwide. While previous studies have shown the relationship between socioeconomic status and CKD, little is known about whether its relationship exists even in a country where insurance is comprehensively covered. Thus, we conducted a nationwide study to examine the association between individual income levels and the progression of CKD in Japan, a country with universal health coverage.

Methods:

We used the national database from the Japan Health Insurance Association (kyokai-kempo) between April 2015 and March 2021. We included 6,318,952 adults who undertook health check-ups in 2015 and had estimated Glomerular Filtration Rate (eGFR) measured at least twice during the study period. A multivariable linear regression model was used to investigate the association between income deciles and the average change in eGFR per year. A multivariable Cox proportional hazard regression model was used to estimate the hazard ratio [HR] for kidney replacement therapy (dialysis or kidney transplantation) according to deciles of individual income. We conducted the subgroup analysis by gender and prefectures.

Results:

The mean age was 48.8 years and 33.5 % were women. After adjusting for potential confounders, the lowest income group (bottom 10th percentile) showed a 0.08 [95%CI, 0.06–0.09] ml/min/1.73 m2/year larger decrease in eGFR than the highest income group (top 10th percentile). In our time-to-event analysis, we found an increased risk of kidney replacement therapy among the lowest income groups (HR [95%CI], 2.22 [1.99–2.48]) than among the highest income group. We found a similar pattern across gender and prefectures.

Conclusion:

Individual income levels were associated with the progression of CKD, particularly for the initiation of kidney replacement therapy in Japan. Our findings highlight the importance of considering socioeconomic status in CKD prevention and management even when insurance is covered.
S-28-7: GENE VARIANTS THAT NEUTRALIZE MORTALITY RISK FROM HYPERTENSION AND THEREBY INCREASE LIFESPAN
Authors: Morris Brian J. , Chen Randi , Donlon Timothy A. , Maskai Kamal H. , Willcox D. Craig , Davy Philip M.C. , Allsopp Richard C. , Willcox Bradley J.
Published: January 2023

Objective:

To determine whether longevity genes extend lifespan by protecting against hypertension and/or other cardiometabolic diseases.

Design:

Prospective population based longitudinal study.

Methods:

We followed a cohort of 3,584 Japanese American men living on Oahu, Hawaii, who were recruited from 1965 to 1968 for the Kuakini Honolulu Heart Program, until Dec 2019 when 99% were deceased. Genotype frequencies of longevity associated SNPs in the genes FOXO3, PIK3R1, GHR, MAP3K5, CTGF, EGFR, FLT1, SIRT5 and SIRT7 were compared between subjects with and without ageing related diseases.

Results:

For FOXO3, PIK3R1, GHR, FLT1, MAP3K5 and EGFR, but not the other 3 longevity genes, longevity genotype increased lifespan by protecting against elevated risk of death posed by having hypertension, coronary artery disease or diabetes (cardiometabolic diseases, CMD), as follows: For FOXO3, covariate adjusted hazard ratios (HRs) for each of 9 longevity associated SNPs were 0.82 to 0.95 (P = 0.00008 to 0.020); covariate adjusted haplotype analysis HR = 0.81 (P = 0.0003); survival curve difference (covariate adjusted Cox proportional HR) was P = 0.0002. Strikingly, those men with a CMD who had the FOXO3 longevity genotype had similar survival as men without CMD. For the other genes, hazard ratios for reduction in the elevated risk of mortality from various CMDs conferred by the longevity associated SNP were: for PIK3R1, from hypertension or coronary artery disease, 1.17, for GHR, from hypertension, 1.20, for FLT1, from hypertension, 1.78, for MAP3K5, from CMD, 1.23, EGFR, from CMD, 1.10. None protected against risk of death from cancer.

Conclusions:

6 of 9 longevity genes exert their longevity effect by protecting against hypertension and/or other CMDs, possibly by amelioration of disease related cellular stress.
S-31-5: SOCIO-ECONOMIC IMPACT AND BURDEN OF HYPERTENSION IN THE PHILIPPINES PROJECTED IN 2050
Authors: Asis Leilani Basa Mercado Asis , Ona Deborah Ignacia David , Bonzon Dolores , Vilela Gilbert , Diaz Alejandro , Balmores Benjamin , Co Marlon , Mina Arnold Benjamin , Cabral Esperanza , Aquino Abdias , Abelardo Nelson , Gomez Lynn , Valdez Les Paul , Castillo Rafael
Published: January 2023

Objective:

Hypertension has remained the number one cause of cardiovascular death in the Philippines for over three (3) decades. Despite this finding, the burden accounted for by hypertension is investigated to a lesser extent in the country. We performed this study to determine the socio-economic impact and burden of hypertension if Filipinos are affected with uncontrolled high blood pressure and the results projected in the next 30 years.

Design and method:

Primary data thru interviews and Labor Force Survey were gathered (N = 806). Secondary data were obtained from the following agencies; Philippine Statistics Authority (PSA), Family Income and Expenditure Survey (FIES), National Demographic and Health Survey (NDHS), National Nutrition Survey, Institute for Health Metrics and Evaluation (IHME), United Nations World Population Prospects, and World Health Organization (WHO). Consequently, cost of illness (COI) was calculated using the direct costs, morbidity costs, and mortality costs.

Results:

Sixty-eight percent (68%) of the respondents were in the active workforce. The majority do not have comorbidities (87%), but those who have hypertensive heart disease, stroke, and kidney problems were the top comorbid conditions. The source of funds for expenses is primarily out-of-pocket (41%). Nearly all patients were not hospitalized (92%) in the past year. The few hospitalized (8%) were mainly due to hypertensive emergency. The impact (% of respondents) of uncontrolled hypertension on productivity at work showed the following; four (4) days missing work (72%) and ten (10) days lost of productivity (63%). The impact (% of respondents) of uncontrolled hypertension on productivity at home showed the following: six (6) days of household suspended (66%), eleven (11) days reduced household work (78%), and five (5) days affected social activity (60%). Hypertension sufferers 40 years and older will get the most significant share of productivity loss due to uncontrolled hypertension. The productivity loss of premature mortality accounts for a 17% of total economic burden in 2020 and this is expected to increase to 20% by 2050. In 2020, about 70% of the total economic burden is accounted for direct & indirect care. In the next 30 years (2020 - 2050), the economic cost of hypertension its present value is expected to increase from Php52.6 billion ($1 billion) in 2020 to Php97.3 billion ($1.8 billion) by 2050.

Conclusion:

The socio-economic impact of uncontrolled hypertension in the Philippines was enormous. The economic cost of hypertension will almost double in the next 30 years. Both productivity loss and premature mortality will have significant impact on the Philippine economy by 2050.
S-34-2: TRENDS IN HYPERTENSION IN SINGAPORE AND EVIDENCE-BASED SOLUTIONS
Authors: Jafar Tazeen H
Published: January 2023

Trends data on Singapore from the Institute of Health Metrics and Evaluation show that the attributable risk of cardiovascular disease (CVD) from high blood pressure (BP) declined from 1990 to 2010, then plateaued till about 2015, and has increased over the last five years. Moreover, several data sources, including the multi-institutional Sing Health Diabetes Registry, indicate a worsening in BP control from 2013 to 2019. Singapore acute myocardial infarction (AMI) registry shows a rise in the incidence of AMI during this time. These alarming trends collectively call for immediate action to improve BP control.

The SingHypertension cluster randomized controlled trial evaluated a multicomponent intervention versus usual care in eight polyclinics in Singapore: 4 clinics were randomized to intervention and 4 to usual care. 916 adults with uncontrolled hypertension were enrolled. The intervention comprised of physicians trained in risk-based treatment, subsidized single-pill combination (SPC) medications, nurse-delivered motivational conversation, and telephone follow-ups. At 24 months, the intervention led to improved BP control, lowered cardiovascular risk and albuminuria, and better quality of life in patients in intervention clinics compared to those in than care.

Wide-scale implementation of a multicomponent intervention such the SingHypertension is likely to reduce hypertension-related morbidity and mortality in Singapore and possibly many other countries.
S-35-2: THE IMPACT OF RENAL DENERVATION PROCEDURE ON THE USE OF ANTIHYPERTENSIVE DRUGS. A REAL-LIFE INVESTIGATION FROM ITALY
Authors: Rea Federico , Morabito Gabriella , Savare Laura , Corrao Giovanni , Mancia Giuseppe
Published: January 2023

Objective:

Randomized controlled trials have shown that renal denervation lowers office and ambulatory blood pressure. However, the clinical environment of controlled trials is different from that characterizing medical practice, making real-life data appropriate to provide information on a number of issues, e.g. whether renal denervation is followed by a change in the intensity and type of antihypertensive drug use. The aim of the present study was to evaluate whether patients undergoing renal denervation procedure in a real-life setting have a reduction in antihypertensive drug prescription over the subsequent years.

Design and method:

Using the healthcare utilization database of the Lombardy Region (Italy), the 136 patients who, during the period 2011–2016, were prescribed four or more antihypertensive drugs and underwent renal denervation were included in the study cohort. The number and type of antihypertensive drugs were assessed over the year before and during the three-year period after renal denervation. Hospitalizations for cardiovascular diseases were also assessed during the three years before and during the three years after renal denervation.

Results:

The median age of the patients was 67 years and 68% of them were men. Based on a multisource comorbidity score, about 40% of patients showed a poor or very poor clinical status. Before renal denervation, about 80% of the patients were prescribed four or five antihypertensive drugs. The number of drugs decreased after the denervation: after three years, patients prescribed 4/5 drugs were 57% and patients prescribed six drugs decreased from 18% to 2%.

Reduced prescription extended to all antihypertensive drugs throughout the post-denervation period. Compared to the year before the denervation, after three years prescription of diuretics was reduced by 15%, calcium channel blockers by 21%, angiotensin-converting enzyme inhibitors by 32%, angiotensin receptor blockers by 22%, beta-blockers by 20%, alfa-blockers by 30%, and mineralocorticoid receptor antagonists by 30%.

Hospitalizations for cardiovascular diseases did not show appreciable differences between the two periods (before and after the renal denervation).

Conclusions:

In the real-life setting, patients who underwent renal denervation had a clearcut reduction in antihypertensive drug prescription over the following years.
S-36-5: TEAM-BASED CARE TO DIAGNOSE, TREAT AND CONTROL HYPERTENSION: FINDINGS FROM RESOLVE TO SAVE LIVES (RTSL)
Authors: Appel Lawrence J
Published: January 2023

In order to achieve population-wide control of hypertension, team-based care is essential, especially in low- and middle-income countries (LMIC) where there are insufficient numbers of physicians to diagnose hypertension and prescribe medications. RTSL is a global initiative to dramatically improve hypertension control from 14% to 50% worldwide. One key aspect of our approach to team-based care is generating evidence useful in transforming health care delivery. Types of evidence can broadly be classified as follows: (1) literature synthesis to understand evidence on the types and effects of team-based care for hypertension, and (2) empirical studies of health system changes designed to scale up and improve hypertension care. The empirical studies are typically community-based and involve community health workers (CHWs) who are given greater responsibility beyond basic administrative and clinical tasks. Below are a sample of RTSL studies.

Our first study involved understanding the global gap between physician capacity and patient need. We documented that most low- and lower middle income countries did not have the physician capacity to provide 3 annual visit for patients with hypertension (figure). Our principal conclusion is that health system and policy changes are needed, including task-sharing. In a second study, we conducted a meta-analysis and documented that team-based care significantly lowers blood pressure in LMIC, with the extent of blood pressure reduction related to the clinical training of team members. In a third study, we conducted surveys to understand current level of task sharing and barriers to task sharing; few countries allowed non-physicians to conduct advanced clinical tasks, e.g. diagnosing hypertension, initiating treatment, and titrating medications. In a fourth study, MUTU conducted in Nepal, we tested a health system change in which CHWs, under the supervision of a physician, initiated and titrated treatment with amlodipine (MUTU results will be presented at ISH on Oct 16). Currently, we are designing a study in which CHWs, supervised remotely via telemedicine, initiate and titrate medication in persons with untreated hypertension in rural Bangladesh. Other studies involve developing and evaluating training materials for non-physician health care workers and modelling the effects of task shifting on the number of persons treated for hypertension in India, along with associated costs.

While these studies are being conducted, many RTSL countries have already implemented health system initiatives that involve team-based care for hypertension. These initiatives studies and RTSL studies hold great promise as a means to improve hypertension control rates in LMIC.
S-37-5: HOW TO CHECK WHETHER A BLOOD PRESSURE DEVICE HAS BEEN PROPERLY VALIDATED FOR ACCURACY
Authors: Sharman James E
Published: January 2023

Accurate measurement of blood pressure (BP) is a fundamental requirement for correct hypertension diagnosis and management. For BP measurement, hypertension guidelines recommend using an automated BP measuring device that has passed accuracy testing in accordance with an internationally-accepted validation protocol. These devices should be used for clinic, home and ambulatory BP monitoring.

Automated BP measuring devices confirmed to have been appropriately validated have less measurement variability and are more likely to be accurate compared with non-validated automated BP devices. Unfortunately, regulatory loopholes enable marketing and sale of automated BP measuring devices that have not passed appropriate validation testing. These devices are predominantly available in the online global marketplace, in which there are more than 3,500 different BP device models and where approximately 75% to 80% do not have evidence of being appropriately validated. These non-validated devices are also significantly cheaper and over-represented in terms of sales volume (based on top 100 sales lists internationally). Health practitioners and the public are generally unaware of these issues, and thus widespread education and resources are needed to address.

In collaboration with international organisations, the Lancet Commission on Hypertension Group and the World Hypertension League has created resources on how to check that a BP device has been properly tested for accuracy. These resources direct users to registries of validated BP device listings in different world regions with the goal of increasing the clinical use of BP devices that have been appropriately validated for accuracy.
S-38-3: LONG NONCODING RNA P21 ALLEVIATES ENDOTHELIAL PROGENITOR CELLS DAMAGE AND PROMOTES ENDOTHELIAL REPAIR IN HYPERTENSION THROUGH ENHANCING AUTOPHAGY
Authors: Li Chao , Li Yunlun
Published: January 2023

Objective:

Vascular damage of hypertension has been the focus of hypertension treatment, and endothelial progenitor cells (EPCs) play an important role in the repair of vascular endothelial damage. Functional damage and decreased number of EPCs are observed in the peripheral circulation of hypertensive patients, but its mechanism is not yet elucidated.

Methods:

Peripheral circulating endothelial progenitor cells of hypertensive patients were labeled and detected by flow cytometry. At the same time, the endothelial progenitor cells of hypertensive patients were cultured in vitro to detect their cell function and aging. The rat bone marrow-derived endothelial progenitor cells were isolated and cultured in vitro. After the intervention of AngII, the cell function, autophagy, and cell senescence were detected. PCR and WB were used to measure the expression and phosphorylation of SESN2, AMPK and TSC2.

Results:

Our results showed that the number of EPCs in hypertensive patients is significantly lower than that of normal population, and the cell function decreases with a higher proportion of EPCs at later stages. A decrease in autophagy is responsible for the senescence and damage of EPCs induced by AngII. Moreover, lncRNA-p21 plays a critical regulator role in the senescence and dysfunction of EPCs. Furthermore, lncRNA-p21 activates SESN2/AMPK/TSC2 pathway by promoting the transcriptional activity of p53 and lncRNA-p21 overexpression enhanced autophagy via AMPK/TSC2/mTOR pathway to protect against AngII-induced EPC damage. EPCs with lncRNA-p21 knockdown showed poor adhesion ability and vascular repair function. These results suggest that lncRNA-p21 enhances autophagy to alleviate endothelial progenitor cells damage and promote endothelial repair in hypertension through SESN2/AMPK/TSC2 pathway.

Conclusion:

The data provide evidence that a reversal of decreased autophagy serves as the protective mechanism of EPC injury in hypertensive patients, and lncRNA-p21 is a new therapeutic target for vascular endothelial repair in hypertension.