bluuebunny/crossref_metadata_2025 huggingface dataset:
S-22-6: RENAL EXPRESSION OF MICRORNAS AND THEIR ASSOCIATION WITH BLOOD PRESSURE REGULATION - INSIGHTS FROM SMALL RNA-SEQUENCING OF 493 HUMAN KIDNEYS
Authors: Scannali David , Xu Xiaoguang , Eales James M , Drzal Maciej , Rainey Timothy , Bogdanski Pawel , Wystrychowski Wojciech , Zywiec Joanna , Szczechowska Ewa Zukowska , Guzik Tomasz J , Morris Andrew P , Charchar Fadi J , Tomaszewski Maciej
Published: January 2023

The kidney is a critical regulator of blood pressure (BP) and a contributor to cardiovascular health. Recently, microRNAs (miRNAs) have emerged as potential mediators of genetic predisposition to cardiovascular and kidney disorders, yet their overall role in blood pressure control has not been fully characterised. We sought to identify and catalogue all renal miRNAs, investigate which of them are genetically regulated and assess whether their expression-modifying single nucleotide polymorphisms (SNPs) overlap with genetic variants associated with BP in previous genome-wide association studies (GWAS).

We first characterised the entire renal miRNA transcriptome through de novo small RNA-sequencing of 493 human kidney samples. We then integrated these expression profiles with genotype information to perform expression quantitative trait loci (eQTL) analysis - the largest of its kind - and identify genetically regulated miRNAs and their regulatory SNPs. We then examined the extent to which miRNA-regulating variants overlapped with the curated list of BP-associated GWAS SNPs.

We identified 1,459 mature miRNAs expressed in the human kidney, and the top 50 most highly expressed miRNAs accounted for 24.2% of the measured expression. We also discovered that 78% of miRNA genes expressed in the kidney were intragenic to other genes and 58% mapped to an intron of those genes. After correction for multiple testing, our eQTL analysis had identified 140 genetically regulated miRNAs in the kidney. They were controlled by 19,901 unique SNPs (eSNPs) with a total of 21,805 miRNA-eSNP pairs. Functional annotation of miRNA eSNPs demonstrated 2.54-fold enrichment for kidney enhancer regions and 1.69-fold enrichment for kidney promoters when compared to randomly selected SNPs. Through overlap with GWAS SNPs for systolic, diastolic and pulse pressures, we identified 8 kidney BP miRNA eSNPs responsible for the regulation of 9 mature miRNAs.

Collectively, we generated a catalogue of miRNAs expressed in the human kidney, annotated novel kidney relevant miRNAs and their regulatory variants and discovered 9 renal microRNAs that may act as mediators of genetic predisposition to high BP.
S-25-4: HIGHER URINARY ANGIOTENSIN CONVERTING ENZYME ACTIVITY IS OBSERVED IN BRAZILIAN CHILDREN AND ADOLESCENTS WITH DYSLIPIDEMIA
Authors: Cruz Nayara Azinheira Nobrega , Oliveira Lilian Caroline Goncalves de , Mill Jose Geraldo , Casarini Dulce Elena
Published: January 2023

Angiotensin converting enzyme (ACE) is upregulated in patients with hyperlipidemia and atherosclerosis and contributes to oxidation and accumulation of low-density lipoproteins in blood vessels. Blockage of dyslipidemia and ACE have a synergic effect preventing or ameliorating cardiovascular disease.

Objective:

Investigate whether ACE activity is modulated in childhood dyslipidemia and can be associated with high cardiovascular risk profile.

Design and methods:

a cross-sectional study with 360 individuals (190 boys and 170 girls) aged from 6 to 19 year (mean 11.6) was performed. Anthropometric measurements, blood pressure assessment and fasting lipid concentrations were evaluated. Participants were divided according to the levels of each lipoprotein (Total cholesterol (TC), triglycerides (TG), LDL-C, HDL-C, and non-HDL) into three groups: normolipidemic, borderline and dyslipidemic. Reference values were according to American Academy of Pediatrics and Brazilian Pediatric Society. ACE activity in urine was measured with the fluorogenic substrates Z-Phe-His-Leu-OH (Z-FHL) and hippuryl-His-Leu-OH (h-HL). ACE activity ratio to infer N-domain activity was calculated (Z-FHL/h-HL).

Results:

Dyslipidemic levels of HDL-C, TG and LDL-C were observed in 23%, 9% and 3% of the participants, respectively. These clinical alterations were more frequent in obese children (Chi-square, p < 0.001). ACE activity measured with Z-FHL was higher in the groups with borderline and dyslipidemic values of HDL-C than in normolipidemic group (0.077 vs 0.070 vs 0.037 nmol/min/mg of creatinine, p = 0.01). The ratio of ACE activity was augmented in HDL-C borderline group when compared to HDL-C normolipidemic group (5.06 vs 2.39, p < 0.01) and in LDL-C dyslipidemic group than in LDL-C borderline and LDL-C normolipidemic groups (8.66 vs 1.84 vs 2.88, p = 0.02). Additionally, volunteers with normal levels of TG presented lower diastolic blood pressure (DBP) mmHg (p = 0.02), percentile of DBP (p < 0.01), and percentile of systolic blood pressure (SBP) (p < 0.01) than volunteers with borderline and dyslipidemic levels of TG. Also, increased DBP mmHg was observed in borderline and dyslipidemic HDL-C groups when compared to normolipidic HDL-C group.

Conclusion:

ACE presented a cross-link with dyslipidemia in childhood and adolescence, as hypertriglyceridemia, HDL-C deficiency and high LDL-C were related to higher ACE activity (mainly N-domain able to inactivate angiotensin 1–7, a vasodilator peptide). ACE upregulation, dyslipidemia and obesity are known to activate molecular mechanism contributing to high cardiovascular risk profile, in agreement, impairment in lipoprotein levels was associated with higher blood pressure. This is relevant evidence that ACE modulation can contribute to higher risk of hypertension and other cardiometabolic alterations still in childhood and adolescence.
S-25-6: INTERCONCEPTION CARE FOR THE WOMEN WHO SUFFERED FROM HYPERTENSIVE DISORDERS OF PREGNANCY
Authors: Mito Asako
Published: January 2023

Interconception Care is Care provided to mothers between pregnancies to improve health outcomes for patients (and their infants). It is important to view postpartum care and preconception care as a continuum, and emphasizes the evaluation of a patients health through a life course perspective that acknowledges the influence of pregnancy on health trajectory. Women with adverse pregnancy outcomes (APO) such as hypertensive disordes of pregnancy, gestational diabetes, preterm delivery, small for gestational age, large for gestational age, placental abruption, and miscarriages, stillbirths, are at high risk for future development of chronic diseases or Atherosclerotic CVD. Some guidelines recommend that health care providers inform women affected by APO of the risks of future disease and instruct them to maintain a healthy lifestyle postpartum. Referral to an appropriate health provider is recommended, too. However, a clear follow-up system for these women has not yet been established. One reason for this is the lack of evidence for risk stratification and corresponding management during the interconception period, taking into account the next pregnancy. There might also be a lack of awareness among health care providers (especially primary care physicians or internists) about these women. Comprehensive care is needed for postpartum women including prevention and management of chronic disease, pregnancy history, family planning, preconception counseling, postpartum weight management, and postpartum mental health care. This presentation will present the risk of future development of chronic disease in women affected by hypertensive disorders of pregnancy from our cohort study, and will discuss the management of women during the interconception period.
S-26-2: ULTRASOUND RENAL DENERVATION ACROSS THE HYPERTENSION SPECTRUM
Authors: Azizi Michel
Published: January 2023

In addition to lifestyle changes and pharmacotherapy, endovascular catheter-based renal denervation (RDN) has emerged as a BP-lowering treatment, but early trials reported inconsistent results. Subsequently, sham-controlled trials with more optimized study designs, improved catheter designs, procedural performance, and endpoint ascertainment were successfully conducted in patients with hypertension. Among these trials, the RADIANCE-HTN trial compared endovascular ultrasound renal denervation (uRDN) with a sham procedure in two separate cohorts. Within the first (SOLO) cohort of subjects with mild-to-moderate hypertension who were weaned off medications, a 6.3 mmHg greater reduction in daytime ambulatory SBP was demonstrated with uRDN vs. a sham procedure at two months. The BP- lowering effect of uRDN was maintained at six- and twelve months with less medications needed to achieve similar BP in the uRDN group compared with the sham group. In addition, the TRIO cohort of RADIANCE-HTN randomized 136 patients with hypertension resistant to three or more antihypertensive medications. Eligible patients were switched to a daily, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic, and if BP remained uncontrolled, were then randomized to uRDN or a sham procedure. At 2 months, the uRDN had a 4.5 mmHg greater decrease in daytime ambulatory SBP compared with sham. The BP-lowering effect of uRDN was sustained at 6 months with less prescribed medications, notably aldosterone antagonists, vs. sham. Adverse events were infrequent and similar between groups in the two cohorts. The maintenance of a BP-lowering effect of uRDN at 6 months mirror the results of the RADIANCE-HTN SOLO trial at 6 months and therefore, demonstrates persistent BP lowering efficacy of uRDN across a broad spectrum of patients with mild hypertension to severe and resistant hypertesion.
S-27-5: DELETION OF AT1A RECEPTORS IN THE PROXIMAL TUBULES AUGMENTS NATRIURETIC RESPONSE TO ATRIAL NATRIURETIC PEPTIDE VIA NPR/CGMP/NO SIGNALING
Authors: Li Xiao C , Wang Chih Hong , Hassan Rumana , Leite Ana Paula Oliveira , Sato Akemi , Dugas Courtney , Sato Ryosuke , Zhuo Jia L
Published: January 2023

Objective:

The proximal tubules of the kidney play a critical role in maintaining normal body salt and fluid balance and blood pressure homeostasis in part by interactions between two key vasoactive hormone receptors. In the proximal tubules, angiotensin II (Ang II) binds and activate AT1a receptors to stimulate proximal tubule Na+ reabsorption, whereas atrial natriuretic peptide (ANP) binds and activates NPRA receptors to inhibit Ang II-induced proximal tubule Na+ reabsorption. These two vasoactive systems play important counteracting roles in the proximal tubules to control proximal tubule Na+ reabsorption in the kidney and maintain blood pressure homeostasis. However, it is not known whether the hypotensive and natriuretic responses to ANP may be augmented by deletion of AT1 (AT1a) receptors selectively in the proximal tubules of the kidney.

Design and Methods:

The present study used a novel mouse model with proximal tubule-specific knockout of AT1a receptors in the kidney, PT-Agtr1a
-/-, to test the hypothesis that deletion of AT1a receptors selectively in the proximal tubules indeed augments the hypotensive and natriuretic responses to ANP. Four groups (n = 9–12 per group) of adult male wild-type and PT-Agtr1a
-/- mice were infused without (served as time controls) or with ANP via osmotic minipump (10 ng/min, i.p.) continuously for 2 weeks.

Results:

Basal blood pressure was about 16 ± 3 mmHg lower (P < 0.01), fractional proximal tubule Na+ reabsorption was significantly lower (P < 0.05), whereas 24 h urinary Na+ excretion was significantly higher in PT-Agtr1a
-/- mice (P < 0.01), compared with age-matched wild-type mice. ANP infusion significantly decreased blood pressure and increased the natriuretic response in PT-Agtr1a
-/- mice further by inhibiting proximal tubule Na+ reabsorption, compared with wild-type controls (P < 0.01). The augmented hypotensive and natriuretic responses to ANP infusion in PT-Agtr1a
-/- mice was associated with increased plasma and kidney cGMP levels (P < 0.01), kidney cortical NPRA and NPRC mRNA expression (P < 0.05), total endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS proteins (P < 0.01), and urinary nitric oxide (NO) excretion (P < 0.01), respectively.

Conclusions:

Taken together, the results of the present study provide further new insights into the important physiological roles for intratubular Ang II/AT1a and ANP/NPRA in the proximal tubules to regulate proximal tubule Na+ reabsorption and help maintain blood pressure homeostasis. Supported by 2R01DK067299-10A1, 2R01DK102429-03A1, and 1 R01DK123144-01.
S-27-7: ROLE OF THE UBIQUITIN LIGASE KLHL3 IN BLOOD PRESSURE AND ELECTROLYTE HOMEOSTASIS
Authors: Shibata Shigeru
Published: January 2023

Genetic studies on familial hypertensive and hypotensive disorders followed by the biochemical analysis have provided fundamental insights into the regulation of NaCl transport mechanisms in the renal nephron. One such example is the analysis of pseudohypoaldosteronism type II (also known as Gordon syndrome), which led to the identification of previously unrecognized constituents engaged in electrolyte and blood pressure homeostasis. Kelch-like 3 (KLHL3) is a component of cullin-RING (really interesting new gene) ubiquitin ligase whose mutations have been shown to cause pseudohypoaldosteronism type II through several mechanisms, including impaired ability to bind target substrates and altered protein stability. Studies to date have also provided insights into the physiological mechanisms that regulate KLHL3 function, which involves phosphorylation at the substrate-binding domain that is counter-regulated by protein kinase C and phosphatase calcineurin. Moreover, accumulating data indicate that these mechanisms are likely involved in the acquired forms of hypertension, particularly those associated with lifestyle related disorders such as obesity. Recent advance on the function of KLHL3 in the kidney, as well as its pathogenic roles in electrolyte disorders, will be reviewed and discussed.
S-28-1: CARDIOVASCULAR OUTCOMES IN ADULTS WITH HYPERTENSION WITH EVENING VERSUS MORNING DOSING OF USUAL ANTIHYPERTENSIVES IN THE UK. THE TIME STUDY
Authors: MacDonald Thomas MacLennal , Mackenzie Isla Shelah , Rogers Amy , Poulter Neil R , Williams Bryan , Brown Morris J , Webb David J , Ford Ian , Rorie David , Grieve Kerr , Pigazzani Fillippo , Rothwell Peter M , Young Robin , McConnachie Alex , Lang Chim C
Published: January 2023

Background:

Studies have suggested that evening dosing with antihypertensive therapy might have better outcomes than morning dosing. The Treatment in Morning versus Evening study aimed to investigate whether evening dosing of usual antihypertensive medication improves major cardiovascular outcomes compared with morning dosing in patients with hypertension.

Methods:

The TIME study is a prospective, pragmatic, decentralised, parallel group study in the UK, that recruited adults with hypertension and taking at least one antihypertensive medication. Eligible participants were randomly assigned 1 to 1, without restriction, stratification, or minimisation, to take all of their usual antihypertensive medications in either the morning, 0600 to 1000 h, or in the evening, 2000 to 0000 h.. Participants were followed up for the composite primary endpoint of vascular death or hospitalisation for non fatal myocardial infarction or non fatal stroke. Endpoints were identified by participant report or record linkage to National Health Service datasets and adjudicated by a committee masked to treatment allocation. The primary endpoint was assessed as the time to first occurrence of an event in the intention to treat population i.e. all participants randomly assigned to a treatment group.

Findings:

Between Dec 17, 2011, and June 5, 2018, 24610 individuals were screened and 21104 were randomly assigned 10503 to evening and 10601 to morning dosing groups. Mean age at study entry was 65·1 years, SD 9·3, 12136 or 57·5 percent participants were men; 8968, 90·5 percent were White, and 2725 or 13·0 percent had a previous cardiovascular disease. By the end of study follow up on March 31, 2021, median follow up was 5·2 years, IQR 4·9, 5·7, 529 of 10503 participants assigned to evening treatment and 318 of 10601 assigned to morning treatment had withdrawn from all follow up. A primary endpoint event occurred in 362 participants assigned to evening treatment that is 0·69 events per 100 patient years and 390 assigned to morning treatment that is 0·72 events per 100 patient years, unadjusted hazard ratio 0·95, 95percent CI 0·83 to 1·10, p 0·53. No safety concerns were identified. An analysis of outcome by adherence to dosing time will be presented at the meeting.

Interpretation Evening dosing of usual antihypertensive medication was not different from morning dosing in terms of major cardiovascular outcomes. Patients can be advised that they can take their regular antihypertensive medications at a convenient time that minimises any undesirable effects.

Funding British Heart Foundation and the British and Irish Hypertension Society.
S-30-5: DIETARY PATTERNS AND CARDIOVASCULAR AND KIDNEY PHENOTYPES IN AN URUGUAYAN POPULATION COHORT
Authors: Moliterno Paula , Donangelo Carmen Marino , Borgarello Luciana , Pécora Matías , Olascoaga Alicia , Noboa Oscar , Boggia José
Published: January 2023

The impact of habitual diet on chronic diseases has not been extensively characterized in South America, were cardiovascular risk factors are highly prevalent. Although aging plays an important and unavoidable role in the development of chronic diseases, sustained exposure to unhealthy diets fastens physiological and morphological changes leading to early vascular aging and premature advancement of disease. We aimed to identify major dietary patterns (DP) in an adult cohort in Uruguay (Genotype Phenotype and Environment of Hypertension Study, GEFA HT UY) and to assess associations with metabolic, anthropometric characteristics, and cardiovascular and kidney phenotypes. In a cross-sectional study (n = 294), dietary information was collected through an interview using an adapted food frequency questionnaire and DP were derived by the principal component analysis. Blood and urine parameters, anthropometrics, blood pressure, pulse wave velocity, and glomerular filtration rate were measured. Multivariable adjusted linear models and adjusted binary logistic regression were used. Three DP were identified (Meat, Prudent, Cereal and Mate) explaining 22.6% of total variance in food intake. The traditional Meat DP, characterized by red and barbecued meat, processed meat, bread, and soft drinks, was associated with worse blood lipid profile. Prudent DP, characterized by vegetables, fish, and nuts, and lower loads for bread and crackers, was associated with reduced risk of vitamin D deficiency. Cereal and Mate DP, was characterized by higher loads of cereals, bread, and crackers, and mate infusion, with higher odds of excessive body weight. No direct associations of dietary patterns with hypertension, arterial stiffness, chronic kidney disease, and nephrolithiasis were found in the studied population, nor by age categories or sex.
S-33-3: EVALUATING THE PREVALENCE, AWARENESS, AND CONTROL OF HYPERTENSION: A COMMUNITY, BASED CROSS SECTIONAL STUDY
Authors: Elamin Maha Ismail , Hassan Dina Ahmed , Elamin Marwa Ismail , Beheri Hind Mamoun , Alall Asma Abd , Fahal Naema Ahmed , Medani Safa Ahmed , Musa Azza Basheir , Ali Ibtisam Ahmed
Published: January 2023

Objective:

The main objectives of our screening survey is to detect the prevalence, control, awareness and risk factors of hypertension

Design and method:

This cross-sectional screening survey was conducted among 23168 adults, during the May Measurement Month 2018 campaign in six states. Volunteers ≧ 18 years were recruited through opportunistic sampling. Each participant had three blood pressure measurements and completed a questionnaire on demographic and medical history. Hypertensive patients were defined as those having systolic BP ≧ 130mmHg or diastolic BP ≧ 80 mmHg, or taking antihypertensive medication, control of hypertension was defined a systolic BP ≦140 mmHg and a diastolic BP ≦ 90 mmHg.

Results:

The overall prevalence of hypertension was 25.9% among the study participants (14.8% for males and 11.1% for females). The majority of identified hypertensive participants (74.1%) had no previous history of known hypertension. Overall 63.0% were on treatment and 35.6 % had controlled blood pressure. In the multivariable regression model, factors associated with increased awareness of having hypertension included female sex (OR 1.37 95% CI 1.12: 1.69), older age > 60 years (OR 1.81 95%, CI 1.36: 2.40), frequently measured their BP (OR 21.3 95% CI 15.3: 29.7), and presence of comorbidities (P < 0.001), Compared to individuals with a normal BMI, overweight participants were more likely to have hypertension (OR 1.63, 95% CI 1.48: 1.79) and more likely to have the disease uncontrolled (OR1.47, 95% 1.33: 1.63). Diabetic patients also had less BP control, while a history of myocardial infarction or stroke did not influence the rates of BP control among hypertensive subjects.

Conclusion:

Our study suggests that the prevalence of hypertension is increasing. Our data also demonstrated a striking lack of awareness of the disease and alarming levels of poor disease control particularly among young adults, overweight subjects and diabetics.
S-35-7: OBSTRUCTIVE SLEEP APNEA AND RISK OF CKD: FINDINGS FROM THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY
Authors: Matsushita Kunihiro
Published: January 2023

Several cross-sectional studies have shown the association between obstructive sleep apnea (OSA) and chronic kidney disease. Recently, we investigated the prospective association of OSA with incident CKD using data from the Atherosclerosis Risk in Communities (ARIC) Study (J Am Soc Nephrol. 2020;8:1859–1869). In this study, we observed a modest association of OSA with incident CKD, but this association was attenuated once accounting for adiposity or other potential confounders. In this presentation, I will present key results from that ARIC study and other relevant studies and discuss the etiological association between OSA and CKD.
S-38-6: DYSFUNCTION OF ATP2B1, ONE OF HYPERTENSION ASSOCIATED GENES, IN CD4+ T CELLS INDUCE COLITIS THROUGH THE CD4+ T-CELL DYSREGULATION
Authors: Javkhlant Amarsanaa , Toyama Kensuke , Mogi Masaki
Published: January 2023

Introduction:

ATP2B1 is known as one of the key genes associated with hypertension developments, which were derived from SNPs analysis. ATP2B1 gene encodes the calcium pumps, which excreting calcium ions from cells and maintaining intracellular calcium homeostasis. Lack of ATP2B1 in CD4-positive (CD4+) T-cells increase an intracellular calcium levels, and which results in the activation of immune responses such as differentiation, cytokine production and proliferation. Immune system of gastrointestinal tract plays an important role in preventing viral and bacterial infection from the foreign environment. Especially, CD4+T-cells play critical roles in the fine tune of an intestinal inflammatory response. We hypothesized that ATP2B1 dysfunction in CD4+T-cell may contribute to the gastrointestinal inflammation. We aimed to clarify the role of ATP2B1 in the CD4+T-cell to the gastrointestinal tract.

Methods:

CD4+T-cell specific knockout of ATP2B1 mice (CD4+T-ATP2B1-KO) were created using the Cre-loxP system (deletion site; exon-10). Lymphocytes were separated from the peripheral blood, spleen, and thymus, and thereafter CD4+T-cells were isolated by the FACS method. Gel electrophoresis-based DNA-sequencing was performed. To quantify mRNA levels, realtime-PCR was performed.

Results:

ATP2B1 gene in CD4+T-cell of thymus, spleen and blood were amplified by PCR, and DNA-sequencing revealed that the exon-10 of ATP2B1 gene was definitely deleted in the CD4+T-ATP2B1-KO mice. Percentages of CD4+T-cell in the thymus were same between KO and control mice, while those in both spleen and blood of the KO mice decreased significantly compared to control mice. Incidentally, blood pressure in KO mice was lower than that in control. Expression levels of both T-bet and GATA3 in the blood of KO mice were significantly increased more than those of control mice, which possibly indicating that Th1 and Th2 are activating. Interestingly, this KO mice show diarrhea and colon wall thickening while control mice did not. There were mucosal changes such as a reduction of intestinal crypts, thickening of intestinal epithelium, and cell clumps in intestinal epithelium (appearing to be inflammatory cells) in the KO mice colon. Surprisingly, colon length of KO mice was significantly shorter than that of controls even before the diarrhea occurred, and TNF-alpha and gp91 expression was increased more in the colon of KO mice than in controls.

Conclusion:

Lack of ATP2B1 in CD4+T-cells lead to the reduction of CD4+T-cells and shift to Th1 and Th2 activation, which may contribute to colitis via the activation of TNF-alpha and/or oxidative stress.
S-44-5: RELATIONS OF AGE, VISCERAL FAT AREA, HOMA-R, AND LIFESTYLE HABITS WITH HYPERTENSION IN THE COMPREHENSIVE HEALTH CHECKUP PROGRAM
Authors: Hirose Hiroshi , Shimizu Ryoko , Mori Masaaki
Published: January 2023

Objective:

Relations of visceral fat with hypertension (HT) have been reported in both Caucasians and in Asians. However, few studies have examined each systolic and diastolic blood pressure (BP) in detail. We investigated the relations of BP status with various metabolic parameters, including visceral fat area (VFA), subcutaneous fat area (SFA), insulin resistance index HOMA-R and lifestyle habits in participants in our health checkup program.

Design and method:

Cross-sectional study. A total of 3,480 male and 2,467 female subjects, aged 16–93 years (median: 59 years), who participated in the comprehensive health checkup program at our University Hospital, were enrolled in this study. Informed consent was obtained from each subject, and subjects who met the predetermined exclusion criteria or were on treatment for diabetes mellitus (DM) were excluded from the analyses. We divided participants into 4 groups according to BP status criteria: normotensive (NT), high normal (HN), HT, and HT with medication (HT+Tx). We used low-energy computed tomography to measure VFA, SFA, and waist circumference at the umbilical level.

Results:

Participants aged 50–70 years in the HN, HT, and HT+Tx groups had significantly higher mean VFAs compared with subjects in the NT group (P < 0.0001 for both gender). Exercise habit was not related with HT status in either gender. In univariate and multivariate analyses, systolic BP was correlated with age, VFA, and HOMA-R, and diastolic BP was correlated with VFA, family history (FH) of HT, and alcohol intake (> 20 g/day). Furthermore, multiple logistic regression analyses (including HT+Tx group) with HT as a dependent variable revealed that age, FH of HT, VFA, HOMA-R, and alcohol intake were relevant (Table, P < 0.0001).

Conclusions:

These results from our comprehensive health checkup program suggest that age, FH of HT, VFA, HOMA-R, and alcohol intake are independently related to HT status.
S-46-4: NONDIPPER PULSE RATE PATTERN WAS ASSOCIATED WITH BLOOD PRESSURE VARIABILITY AND INCREASE OF BNP: J-HOP STUDY
Authors: Kabutoya Tomoyuki , Hoshide Satoshi , Kario Kazuomi
Published: January 2023

Background:

The association between nondipper pulse rate (PR) pattern was reported. However, the association between nondipper PR pattern, blood pressure variability and hypertensive target organ damage remains unclear.

Methods:

Ambulatory BP monitoring (ABPM) was conducted in 1,003 hypertensive patients enrolled in the Japan Morning Surge Home Blood Pressure (J HOP) Study. Ambulatory BP monitoring was performed on a weekday with an automatic system that recorded the wearers BP and PR every 30 minutes for 24 hours. Nondipper PR status was defined as (awake PR minus sleep PR)/awake PR < 0.1, and we evaluated standard deviation (SD) of systolic BP in daytime and nighttime as BP variability. We also measured the brain natriuretic peptide level (BNP), and conducted echocardiography to estimate the left ventricular mass index (LVMI).

Results:

The SD of systolic BP in nighttime, BNP and LVMI in patients with nondipper PR (N = 247) were higher than that in patients with dipper PR (N = 756, SD of systolic BP: 13.3 ± 4.6 vs. 12.7 ± 4.1 mmHg, p = 0.041; median BNP: 25.2 vs. 17.6 pg/dL, p < 0.001, LVMI: 101.4 ± 29.1 vs. 97.3 ± 42.2 g/m2, p = 0.021). Systolic BP in nighttime in patient with nondipper PR was similar to that in patient with dipper PR (119.5 ± 15.2 vs. 119.9 ± 15.1 mmHg, p = 0.63). The SD of systolic BP in nighttime was associated with BNP and LVMI (BNP: r = 0.08, p = 0.006; LVMI r = 0.10, p = 0.001). Nondipper PR was independently associated with BNP (β = 0.10, p < 0.001), but not with LVMI (β = 0.03, p = 0.37) after adjustment for systolic BP and SD of systolic BP in nighttime.

Conclusions:

Nondipper PR pattern was associated with blood pressure variability and hypertensive target organ damage in patients with cardiovascular risk factor.
S-50-5: SALT SENSITIVITY AS MARKER FOR HYPERTENSION MANAGEMENT
Authors: Lanzani Chiara Livia , Citterio Lorena , Simonini Marco , Laura Zagato , Paolo Manunta
Published: January 2023

Arterial hypertension is one of the most critical risk factors for cardiovascular (CV) disease, stroke, and chronic kidney disease (CKD). According to the current guidelines on hypertension management, the identification of one or more CV risk factors requires an earlier and more intensive treatment paradigm. Salt sensitivity (SSy), defined as susceptibility to changes in blood pressure related to dietary salt intake, is a well-known independent risk factor for CV disease in both the general and hypertensive population, even though it is not included in current guidelines.

Is has been reported that SSy affects 30_50% of hypertensive and 25% of normotensive subjects. Salt sensitivity is more common in the elderly, women, African Americans, and patients with CKD and insulin resistance.

The diagnosis of SSy is complex and not entirely standardized. The two main methods for SSy assessment are the dietary protocol versus the acute salt load. The dietary protocols typically evaluate the blood pressure variation between short periods of low and high sodium diet and often differ in both the duration and the amount of salt intake. Acute test (which consists of an i.v. infusion of 2 L of physiological solution over 2 hours) evaluates mean blood pressure (MBP) variation between the end and the start of the infusion. Three different blood pressure responses are possible: no substantial variation [salt resistant (SR) subjects], an increase in blood pressure [salt sensitive (SS) subjects], or a paradoxical decrease in blood pressure [reverse salt sensitive (RSS) subjects]. Although RSS subjects have been recognized as a third distinct group since the early 1990 s, many studies included them in the group of SR subjects. Recently, the concept of reverse salt sensitivity has been re-evaluated in relation to CV risk.

Previous studies have shown an increased risk of developing cardiovascular events, hypertensive heart disease and microalbuminuria among SS patients.

In our recent paper, the SS and RSS condition appear to be equivalent risk factors for CV events in hypertensives.

Finally, a J curve relationship between dietary salt and cardiovascular damage has been proposed.

Different pathophysiological mechanisms can be involved in SSy: renal autoregulation (Pressure natriuresis curve), Renin angiotensin aldosterone system, sympathetic nervous system activity, Insulin resistance, peripheral vascular resistances, sodium storage skin, genetic predisposition.

Classification according to salt sensitivity can help in personalization of salt intake indication, intensity of therapy and timing of follow up.
S-51-3: EMPAGLIFLOZIN AMELIORATES CARDIAC HYPERTROPHY AND RENAL INJURY WITH SYMPATHOINHIBITION IN A RAT MODEL OF HYPERTENSIVE HEART FAILURE
Authors: Matsumoto Sho , Shinohara Keisuke , Ikeda Shota , Kashihara Soichiro , Nakashima Ryosuke , Yoshida Daisuke , Ono Yoshiyasu , Tsutsui Hiroyuki
Published: January 2023

Objective:

SGLT2 inhibitors have been reported to have cardio- and reno-protective effects; however, its mechanisms are not fully understood. Sympathetic activation is critically involved in cardiac and renal damage during the development of hypertensive heart failure. In this study, we examined whether empagliflozin inhibits cardiac and renal damage with sympathoinhibition in the phase of cardiac hypertrophy using a rat model of hypertensive heart failure.

Design and method:

Male Dahl salt-sensitive rats were fed 0.3% low-salt (LS, n = 6) or 8% high-salt diet from 6 weeks of age and the high-salt-fed rats were assigned to the vehicle (HS-VEH, n = 6) or empagliflozin (HS-EMPA, n = 6) treatment groups at 8 weeks. Systolic blood pressure was measured by tail-cuff method at 6, 8, and 12 weeks. At 12 weeks, organ weight, plasma creatinine, and plasma norepinephrine were measured. Renal fibrosis was evaluated by Sirius red staining. The expression of c-Fos, a marker of neuronal activity, in the hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM), in which the presympathetic neurons are located, was evaluated by immunostaining.

Results:

Systolic blood pressure was elevated in HS-VEH and HS-EMPA compared to LS, whereas there was no significant difference between HS-VEH and HS-EMPA (at 12 weeks, LS 127.1 ± 5.3 mmHg, HS-VEH 224.5 ± 20.1 mmHg, HS-EMPA 223.8 ± 24.4 mmHg; p < 0.05 vs LS). Left ventricular weight was increased in HS-VEH compared to LS (1.13 ± 0.02 vs 0.90 ± 0.02 g, p < 0.05), and the increase was attenuated in HS-EMPA (1.06 ± 0.04 g, p < 0.05 vs HS-VEH). Kidney weight was similarly increased both in HS-VEH and HS-EMPA compared to LS; however, empagliflozin significantly attenuated the high salt-induced increases in renal fibrosis and plasma creatinine (LS 0.20 ± 0.02 mg/dL, HS-VEH 0.34 ± 0.06 mg/dL, HS-EMPA 0.20 ± 0.04 mg/dL; p < 0.05 for HS-VEH vs LS and HS-EMPA vs HS-VEH). Plasma norepinephrine was increased in HS-VEH compared to LS (1304 ± 627 vs 268 ± 54.5 pg/mL, p < 0.05) and was suppressed in HS-EMPA (648 ± 419 pg/mL, p = 0.05 vs VEH), which was consistent with the finding that the increase in c-Fos positive neurons within the PVN and RVLM in HS-VEH was significantly attenuated in HS-EMPA.

Conclusions:

In Dahl salt-sensitive hypertensive heart failure model, empagliflozin inhibits sympathetic activation and ameliorates cardiac hypertrophy and renal injury without lowering blood pressure in the pre-heart failure phase.
S-53-1: SOCIOECONOMIC FACTORS AND PREVENTION OF CARDIOVASCULAR DISEASES IN ASIA
Authors: Gupta Rajeev
Published: January 2023

Focus on social determinants of health is important for primordial and primary prevention of cardiovascular diseases (CVD). There are multiple social determinants and are macrolevel factors: social and human development, location related factors, and policies that influence rural and urban planning, environmental pollution, healthcare infrastructure, health financing, quality of health systems, taxation on harmful products (tobacco, alcohol, trans fats), and subsidizing healthy foods. Individual level factors are: multiple social factors, education, income, employment, stress, early life events, addictions including tobacco, and availability, affordability and adherence to medicines and healthy lifestyles. Studies have shown that countries with better development have lower CVD incidence and mortality, also in Asia. Healthy lifestyles (healthy diet, physical activity, tobacco control) and awareness, treatment and control of major risk factors (hypertension, diabetes, dyslipidemias) are more in better developed Asian countries due to better health systems and universal health coverage policies. At individual level higher socioeconomic status and better educational level are associated with lower prevalence of CVD risk factors and better treatment and control of hypertension, dyslipidemias and diabetes.

Interventions to address social determinants are limited and include focus on political, economic and social interventions. UN Sustainable Development Goals related to poverty eradication, zero hunger, good health and wellbeing, quality education, gender equality, decent work, economic growth, reduced inequalities, sustainable communities, responsible consumption or production, and climate action address social determinants of health. Creation of health infrastructure in rural and deprived locations, macrolevel financing, manpower deployment and workforce training are important evidence-based interventions.

Interventions to improve quality of general education and health literacy and education of medical professionals and non-physician health workers have shown to ameliorate CVD related disparities. Public health interventions include life-course approach for prevention and control of risk factors, better and safe facilities for promotion of physical activity, tobacco, smoking and alcohol control policies, taxation on trans fats, sugars, sugar-sweetened beverages and salt, universal health care focussed on early CVD diagnosis and management, availability of medicines and focus on technological innovations to promote adherence to medicines and healthy lifestyles. At the individual level better CVD risk-factor control can be achieved by focus on individual social determinant and improved professional-patient communication via professional medical education, health worker related focus, patient health literacy, and greater patient involvement.
S-55-5: CT GUIDED AND TRANSVENOUS RADIOFREQUENCY ABLATION FOR PRIMARY ALDOSTERONISM
Authors: Takase Kei
Published: January 2023

We are developing minimally invasive treatments for primary aldosteronism. In this presentation, we will introduce our research and clinical studies on percutaneous and transvenous radiofrequency ablation (RFA).

Based on the preclinical studies, a protocol for ablating human adrenal glands and intraoperative blood pressure control methods were developed. First-in-human procedure was performed. Flexible RFA catheter was inserted into the upper lateral tributary of the left adrenal vein. The position of the RFA catheter was confirmed by CT. Ablations were performed while applying energy of 7000 J twice to each location, pulling back the catheter several millimeters in sequence. The aldosterone-producing adenoma was completely ablated to normalize the serum aldosterone level.

CT-guided RFA was able to treat PA with a high success rate. However, approximately 50% of the left aldosterone producing adenomas were difficult to puncture due to anatomical reason, while most of the right adrenal adenoma could be treated by CT-guided RFA. The transvenous RFA catheter is much easier to insert into the left adrenal vein than into the right, suggesting that the two RFA methods have complementary roles. Furthermore, it may be possible to perform AVS diagnosis and RFA treatment in a single procedure.
S-56-2: HOME BLOOD PRESSURE MEASUREMENT FOR HYPERTENSION MANAGEMENT IN THE REAL WORLD: THE IMPORTANCE OF REPORTING HOME BLOOD PRESSURE TO DOCTORS
Authors: Rhee Moo Yong , Kim Je Sang , Won Ki Bum , Kim Ji Hyun , Do Ungjeong , Kim Hae Young , Nah Deuk Young
Published: January 2023

Introduction:

Most studies that sought the effect of home blood pressure (HBP) measurements were conducted in controlled conditions or by measuring office BP. We investigated the effects of HBP measurements on the management of hypertension in the real world, through measurement of ambulatory BP.

Methods:

Patients taking antihypertensive drugs (>1 year) and > = 20 years of age were recruited. A survey asking the duration and frequency of HBP measurements if the participants reported their HBP results to their clinicians was conducted. The patients were divided into (1) HBPM(-) group: HBP was not measured (n = 467), (2) HBPM(+)UR group: HBP was measured but not reported (n = 81), and (3) RHBPM(+)R group: HBP was measured and reported (n = 125).

Results:

The HBPM(+)R group had lower office systolic blood pressure (SBP, 125.8 ± 9.9 vs 128.5 ± 11.4 mmHg, p = 0.035), 24-hour SBP (121.0 ± 9.8 vs 124.1 ± 11.2 mmHg, p = 0.009), and daytime SBP (122.7 ± 10.9 vs 125.9 ± 12.2 mmHg, p = 0.017) than the HBPM(-) group, and lower nighttime SBP (114.8 ± 11.8 vs 119.9 ± 10.8, p = 0.005) and diastolic blood pressure (DBP, 72.6 ± 9.0 vs 76.6 ± 8.4 mmHg, p = 0.008) than the HBPM(+)UR group. In the multivariate analysis, the difference in 24-hour and daytime SBP and nighttime DBP remained significant. There was a significant difference between groups in regard to the control of office DBP [70.6% for HBPM(+)R, 60.4% for HBPM(-), and 55.0% for HBPM(+)UR groups; p = 0.047]; 24-hour SBP (68.3%, 57.0% and 53.1%, respectively; p = 0.046), nighttime SBP (36.7%, 31.2% and 18.5%, respectively; p = 0.021) and nighttime DBP (20.8%, 19.8% and 7.4%, respectively; p = 0.023). Nighttime SBP and DBP control rate of the HBPM(+)R group were higher than those of HBPM(+)UR group (p = 0.007 and 0.010). Among the patients measuring home BP, the adjusted odds ratio for 24-hour and nighttime BP control in the HBPM(+)R group were 2.176 (95%CI, 1.010–4.687) and 36.651 (95%CI, 1.110–12.005), respectively, compared to the HBPM(+)UR group.

Conclusion:

This study shows that patients with hypertension should not only take HBP measurements but also report these to the treating clinician for appropriate management of hypertension.
APSH-OP-1: THERAPEUTIC TARGET AND CLINICAL IMPACT OF DAY-TO-DAY BLOOD PRESSURE VARIABILITY IN HYPERTENSIVE PATIENTS WITH COVID-19
Authors: Jagannatha Gusti Ngurah Prana , Yasmin AA Ayu Dwi Adelia , Pradnyana I Wayan Agus Surya , Kamardi Stanly , Pangkahila Elionardo Enrique
Published: January 2023

Objectives:

Blood pressure variability (BPV) plays an important role in hypertensive patients, and frequently associated with organ damage. Although hypertension is the most common comorbidity in COVID-19, the impact of BPV and therapeutic target of BPV to outcome in COVID-19 patients with hypertension remain unclear. The aim of this study is to investigate the relationship between BPV and severity of COVID-19, in-hospital mortality, hypertensive status, and efficacy of antihypertensives in suppress hypertensive covid-19 patient's BPV.

Design and method:

This was a cohort retrospective study that enrolled 351 patients hospitalized with COVID-19. Subjects were classified according to the presence of hypertension, the severity of COVID-19, and BPV status. Mean Arterial Pressure (MAP) was measured at 6 a.m. and 6 p.m. during hospitalization, and BPV was calculated as the coefficient of variation of MAP (MAPCV). MAPCV values above the median were defined as high BPV. We compared the hypertensive status, COVID-19 severity, in-hospital mortality and antihypertensive agents between the BPV groups.

Results:

The mean age was 53.85 ± 18.84 years-old. Subjects with high BPV were significantly associated with hypertension status (PR = 1.38; 95%CI = 1.13–1.70; p = 0.003) or severe COVID-19 (PR = 1.39; 95%CI = 1.09–1.76; p = 0.005). In laboratory findings, high BPV group had higher CRP (55.15 ± 50.80 vs 97.79 ± 77.17), higher creatinine cerum (1.80 ± 3.15 vs 0.91 ± 0.14) and high BPV status also significantly increased risk of mortality (HR = 2.30; 95%CI = 1.73–3,86; p = <0.001). Patients with combination of severe COVID-19 status, hypertension (+) and high BPV status had the highest risk of in-hospital mortality (HR = 3.51; 95%CI = 2.32–4,97; p < 0.001) compared to other combination status of groups. In COVID-19 patients with hypertension, combination teraphy with CCB as well as CCB monoteraphy significantly decreased BPV (PR = 0.50; 95%CI = 0.27–0.93; p = 0.004) and mortality (HR = 0.17; 95%CI = 0.05–0.56; p = 0.004).

Conclusions:

High BPV was associated with hypertensive status and severe COVID-19, and these factors together increased in-hospital mortality. CCB are antihypertensive agents that were potentially effective in suppressing BPV and mortality in COVID-19 patients.
APSH-OP-3: VITAMIN D DEFICIENCY EXACERBATES MONOCROTALINE-INDUCED PULMONARY ARTERIAL HYPERTENSION IN RATS: POSSIBLE INVOLVEMENT OF TGF- β/α-SMA SIGNALING PATHWAY
Authors: Shah Sadia , Yadav Harlokesh Narayan
Published: January 2023

Objective:

Vitamin D deficiency is highly prevalent and associated with poor prognosis in patients with pulmonary arterial hypertension (PAH). Therefore, this study compared the disease severity in normal and vitamin D deficient rats in terms of hemodynamic, echocardiographic, biochemical, histopathological, and immunohistochemical parameters. We also examined whether vitamin D supplementation would benefit the symptoms in normal and deficient rats. The molecular basis of vitamin D action, which may be exerted via the TGF- β/α-SMA signaling pathways, was studied by molecular techniques in vivo and in vitro.

Design and method:

Wistar rats were fed with a standard or a vitamin D deficient (VDD) diet to induce vitamin D deficiency. PAH was induced by a single s.c. dose of monocrotaline (MCT) 50 mg/kg. Normal rats were divided into vitamin D 100 IU/d pre-treated and 100 IU/d or 200 IU/d treated groups whereas VDD rats were treated with 100 IU/d (Fig. 1 a). siRNA was used to silence the vitamin D receptor in human umbilical vein endothelial cells (HUVECs). Calcitriol (50 nm) was added to HUVECs before and after the exposure of TGF- β (10ng/ml) (Fig 1 b). The expression and level of TGF- β and α-SMA were done using immunohistochemistry, western blot and PCR techniques in vivo and in vitro.

Results:

The same dose of MCT significantly increased the disease-associated parameters in the vitamin D deficient group compared to the rats with normal serum vitamin D levels. Effect of vitamin D 100 IU/d in VDD rats was comparable to 100 IU/d pre-treated and 200 IU/d treated normal rats measured in terms of hemodynamic, echocardiographic, histopathological, oxidative stress parameters and expression and level of TGF- β and α-SMA, which were significantly attenuated by administration of L-NAME (20 mg/kg), a selective inhibitor of eNOS. Exposure of TGF-β markedly increases the expression of α-SMA in vitamin D silenced HUVECs and also in normal HUVECs, which were averted by treatment or pre-treatment of calcitriol (50 nM).

Conclusion:

The disease severity increases in the rats with low serum vitamin D levels, which is ameliorated with vitamin D treatment. Moreover, vitamin D is more effective in treating PAH in vitamin D deficient rats than in normal rats, even at a low dose. This effect of vitamin D in the PAH disease model is mediated by the TGF- β/α-SMA signaling pathway.