bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P224: The Role Of Gata3 In Renin Cell Identity
Authors: Neyra Jesus , Medrano Silvia , Martini Alexandre G , Lopez Maria Luisa , Gomez Ariel R
Published: October 2023

Renin cells act as precursors cells of the kidney vasculature and show high plasticity in postnatal life in response to challenges to homeostasis. Our scRNA-seq studies revealed that the dual-zinc finger transcription factor Gata3, important for cell lineage commitment and differentiation inseveral tissues, is expressed in mouse renin cells. We found an enhancer associated with
Gata3
in renin cells leading us to hypothesize that
GATA3
is important for renin cell identity. We studied 60 and 120-day-old mice carrying a conditional deletion of Gata3 in renin cells: Gata3
fl/fl
;Ren1
dCre/+
(
Gata3-cKO
) and control Gata3
fl/fl
;Ren1
d+/+
. BUN and plasma renin levels were measured from blood samples collected by cardiac puncture. Ren1, Acta2, and Gata3 were visualized in kidney sections by immunostaining. Histological analysis was performed with H&E, PAS, or Masson’s Trichrome chemical reactions. The juxtaglomerular area (JGA) index was calculated as a ratio of renin-positive JGAs per the total number of glomeruli.
Gata3-cKO
mice have: 1) a marked reduction in Gata3 staining; 2) a marked reduction of Ren1 (1.78 ± 0.51 (n=5) vs. 12.96 ± 2.29 (n=6), p=.0006) and Akr1b7 (2.12 ± 0.35 (n=5) vs. 19.75 ± 5.43 (n=7), p<0.0001) mRNAs compared to controls under threat; 3) a significant decrease in circulating plasma renin compared to controls under basal conditions (15609 ± 14281 pg/ml (n=5) vs. 78778 ± 33925 pg/ml (n=7), p=.0039) and physiological threat (265981 ± 79431 vs. 62347 ± 75631 pg/ml (n=5), p=.0032); 4) a significantly reduced JGA index (28.47 ± 2.32 (n=5) vs. 44.42 ± 2.72 (n=5), p=.0001); 5) flattened JG cells with misplaced renin staining in the Bowman’s capsule; 6) renal abnormalities with evidence of glomerular sclerosis/fibrosis, hemorrhage with aneurysms, and evidence of inflammatory cell infiltration; 7) misplaced Acta2 staining in the intraglomerular mesangium, interstitium, and Bowman’s capsule.

Our results suggest a role of Gata3 in the identity of cells of the renin lineage.
Abstract P233: Single-cell Transcriptomic Characterization Of Aortic Lymphocyte Heterogeneity During Hypertension
Authors: Jelinic Maria , Figueiredo Galvao Hericka Bruna , Dona Malathi , Farrugia Gabriella E , Haslem Asha , Diep Henry , Sobey Christopher G , Lewsey Mathew G , Pinto Alexander , Drummond Grant , Vinh Antony
Published: October 2023

Vascular inflammation is a hallmark of hypertension. T and B lymphocytes accumulate in the aortic wall during hypertension; however, it is unclear which subtypes or functions contribute to disease progression. Thus, we aimed to characterize T and B cell subtypes, activation states and phenotypes in hypertension. Angiotensin II infusion (0.7 mg/kg/day;
s.c.
for 28 days, n = 15) was used to induce hypertension in 12-week-old male C57BL/6 mice. Age-matched normotensive controls received vehicle infusion (0.5% NaCl, 0.1% acetic acid;
s.c.
for 28 days, n = 11). Systolic blood pressure (SBP) was measured weekly by tail-cuff plethysmography. Aortic stiffness and fibrosis were assessed at endpoint via high resolution ultrasound and picrosirius red-staining, respectively. Whole aortas (n = 3 per treatment group) were isolated and digested into single-cell suspensions and enriched for live, nucleated, metabolically active cells. Single-cell RNA sequencing was performed using Chromium 10x and NovaSeq genomics platforms. Bioinformatic analyses identified cell types, acquired molecular and biological activities and inferred gene regulatory networks. At endpoint, angiotensin II-treated mice had elevated SBP (179 ± 4 vs. 124 ± 2 mmHg;
P
< 0.0001), with increased aortic pulse wave velocity (1.5 ± 0.2 vs 3.1 ± 0.3 m/s;
P
= 0.001) and collagen content (51 ± 2% vs. 60 ± 2% wall area;
P
= 0.02), compared to vehicle controls. Total aortic T cells and B cells increased by 16% (184 vs. 215 cells) and 74% (433 vs. 771 cells) in hypertension, respectively. These increases were attributed to the expansion of CD8+, regulatory T cells (Tregs), gamma-delta (GD) T cells, immature transitional B2 cells, naïve B2, memory B2, B1 B cells and plasma cells, with a reduction in regulatory B2 B cells (Bregs). Gene ontology analyses revealed both pro- and anti-inflammatory B and T cells were activated during hypertension. However, antigen receptor activity pathways were only enriched in GD T cells, B1 B cells and effector Bregs (running enrichment scores > 0.2). Overall, these findings identify GD T cells, B1 B cells and effector Bregs as key lymphocyte subtypes that drive vascular inflammation during experimental hypertension and aortic stiffening.
Abstract P300: Blood Pressure Increase Upon High Dietary Potassium Supplementation Is Not Associated With Renal Sodium Retention Or Plasma Volume Expansion
Authors: Ehmke Heimo , Vitzthum Helga , Steffen Philine , Marx Christian , Ewald Jan , Morhenn Karoline M , Seniuk Anika
Published: October 2023

Background:
High dietary K
+
supplementation increases arterial blood pressure in humans and in mice. The mechanisms underlying this unexpected response are still not fully understood. Recent studies in mice reported an activation of the epithelial sodium channel (ENaC) suggesting that renal Na
+
retention may prominently contribute to the blood pressure increase caused by a high KCl intake. Here, we tested whether a high K
+
intake causes renal Na
+
retention and plasma volume expansion.

Methods:
Na
+
-replete C57BL/6J mice were subjected to either a normal (0.93%, NK) or a high (5%, HK) KCl or KCitrate diet for up to 14 days. Blood pressure responses to diets and to the additional administration of the ENaC blocker amiloride were measured using radiotelemetry in unrestrained animals. Plasma aldosterone concentrations were quantified by ELISA. Renal Na
+
retention was assessed by determining urinary Na
+
excretion. To detect plasma volume expansion, we used a dilution method (Evans blue), determined blood hematocrit, and estimated end diastolic left ventricular volume by echocardiography after 10 days of diet.

Results:
Both high K
+
diets increased arterial blood pressure selectively in the dark phase by a nearly identical extent (ΔMAP dark: HKCl +12.7±2.3 mm Hg, p=0.0045, HKCit +12.1±3.0 mm Hg, p=0.0211; ΔMAP light: HKCl -0.2±1.5 mm Hg, p>0.9999, HKCit +2.4±2.2 mm Hg, p=0.9692, 1-way ANOVA, n=7). Even though plasma aldosterone levels were markedly elevated (HKCl 9.9-fold, p=0.0001, HKCit 4.6-fold, p=0.0116, 1-way ANOVA, n=11-12), neither a reduction of renal Na
+
excretion (urinary [Na
+
]/[creatinine] NK 1.0±0.14, HKCl 1.40±0.23, p=0.3873, HKCit 0.94±0.20, p<0.9999, 1-way ANOVA, n=7-13) nor an expansion of plasma volume (NK 898±23 μl, HKCl 918±57 μl, p>0.9999, HKCit 870±62 μl, p>0.9999, 1-way ANOVA, n=6-13) was detected upon the two high K
+
diets. Amiloride did not normalize arterial blood pressure in mice fed a HKCl or HKCit diet (ΔMAP dark: HKCl +1.2±2.3 mm Hg, p=0.6391 HKCit +2.8±2.0 mm Hg, p=0.2472, 2-tailed paired t-test, n=4).

Conclusions:
Our findings indicate that excessive K
+
intake causes elevated blood pressure independent of renal Na
+
retention and volume expansion in Na
+
-replete mice.
Abstract P304: Coronary Flow Reserve In Primary Aldosteronism
Authors: Rossitto Giacomo , Barchitta Agatella , Bagordo Domenico , Nervo Giona , Ruzza Luisa , Cabrelle Giulio , Bertoldi Giovanni , Berton Chiara , Caroccia Brasilina , Torresan Francesca , Iacobone Maurizio , Rossi Gian P
Published: October 2023

Introduction:
Primary aldosteronism (PA) is characterized by excess cardiovascular risk, underpinned by evidence of microvascular dysfunction. Whether this extends to the coronary vasculature and, as such, regresses after appropriate treatment remains to be determined.

Aim:
To investigate the presence of coronary microvascular dysfunction and its reversibility in PA patients.

Methods:
Fifteen PA patients with evidence of lateralized aldosterone overproduction at adrenal vein sampling underwent Doppler echocardiography for the assessment of Coronary flow reserve (CFR: diastolic peak flow on the anterior descending coronary artery during pharmacological [dipyridamole, n=14] or physical stress [n=1] -induced hyperaemia/basal flow) and the ratio between diastolic peak flow and left ventricle mass (FMR), at the time of diagnosis (after withdrawal of RAAS-interfering drugs and normalization of kalemia with K supplementation) and 4-6 months after specific treatment. In case CFR was ≤ 2.5 or the stress protocol suggested potential ischemia, regardless of CFR, a coronary CT angiography (coroCT) was performed to exclude underlying macrovascular coronary artery disease.

Results:
Out of 15 PA patients (5F; 52±10 yo; BP:149/91±17/11 mmHg; sK
+
=3.5±0.6 at diagnosis and 3.8±0.3 mmol/L on KCl supplements; DRC=3.0 [2.0-5.5] mIU/L; PAC=747 [417-1430] pmol/L), 14 were cured by unilateral adrenalectomy (127/81±13/11 mmHg; sK
+
=4.3±0.4 mmol/L; DRC=11.8 [6.7-19.2] mIU/L; PAC=200 [136-244] pmol/L, p<0.05 for all); one patient experienced incomplete biochemical cure and was managed with long-term mineralocorticoid receptor antagonism. At the time of diagnosis, n=7 (46%), n=3 (20%) and n=1 (7%) patients showed CFR ≤ 3.0, 2.5 and 2.0, respectively; none had evidence of macrovascular disease at coroCT. In parallel to a reduction in left ventricular mass (trend; p=0.084), both CFR and FRM significantly increased after treatment (CFR=3.1 [2.6-3.3] vs. 3.4 [3.1-4.6], p=0.013; FMR=0.71±0.33 vs. 0.91±0.32 cm x g/sec x m
2
, p=0.038).

Conclusions:
Treatment of PA improves coronary microvascular function, as assessed by established prognostic indices like CFR and FMR.
Abstract P307: What A Difference Hypertension Makes: The Adventitia Hands Off To PVAT For Extracellular Matrix Remodeling As Blood Pressure Rises In The High Fat Fed Dahl SS Rat.
Authors: Wilson Caitlin S , Thompson Janice , Terrian Leah , Lauver Adam A , Fink Gregory D , Sather Lisa , Bhattacharya Sudin , Watts Stephanie W
Published: October 2023

Tunica media extracellular matrix remodeling is well understood to occur in response to elevation of blood pressure, considered a protective response. Remodeling of other tunicas is not well known. We have a long-term hypothesis that perivascular adipose tissue (PVAT) is responsive to hypertension and likely remodels to assist the blood vessel in protection against higher pressures. Here, we used the tunica adventitia and PVAT of the thoracic aorta in measuring extracellular matrix genes from 5 pairs of Dahl SS male rats on 8 or 24 weeks of feeding from weaning on a control (10% fat) or high fat (HF; 60%) diet. These times were picked given relative increases mean arterial blood pressure (mm Hg) in the HF
vs
control (mmHg increase; 8 week: 14±5; 24 week = 35±8; p<0.05). The adventitia and PVAT were dissected apart, RNA isolated, cDNA synthesized and run on RT2 profiler array kits for ECM and Cell Adhesion genes. Differentially expressed genes (HF 2 fold > Con) were determined in Cytoscape, followed by identification of Hub Genes and construction of a Gene Regulatory network. At 8 weeks on HF diet, the adventitia had 29 upregulated genes (vs Con diet) while the PVAT had none. By contrast, at 24 weeks on diet, the HF adventitia had 3 upregulated genes while PVAT had 47. The top two genes elevated at 8 weeks in adventitia where thrombospondin 1 and collagen 8a1. Surprisingly, at 24 weeks, thrombospondin 1 was one of the three top genes upregulated in PVAT. The following transcription factors were identified as regulators of those genes upregulated in the 8 week adventitia:
Adarb1, Fos, Gm10323, Smad3 and Mapk1
. By contrast, the key transcription factors for DEGS in the 24 week PVAT were
Stat1, Bcl6B, Tsnax, Pax8, and Jun. Adarb1 (Adenosine deaminase RNA specific B1)
was also determined to be a key regulator in PVAT remodeling. These data support that the PVAT responds biologically once blood pressure is elevated.
Abstract P322: Absorption, Metabolism, And Elimination Of Nonsteroidal Mineralocorticoid Receptor Antagonist Ocedurenone In Humans
Authors: Yang Fred , Tan Judy , McCabe James , Liu Jinrong , Wang Ping , Zhang Jay
Published: October 2023

Objective:
Ocedurenone is a novel nonsteroidal mineralocorticoid receptor antagonist under development for the treatment of uncontrolled/resistant hypertension in patients with advanced chronic kidney disease. A phase 1, open-label study was conducted to determine absorption, metabolism, and excretion of
14
C labeled Ocedurenone following a single oral dose in healthy male subjects.

Methods:
A total of seven healthy subjects between 18 and 55 years of age with a body mass index between 18.0 and 32.0 kg/m
2
were selected and received a single oral dose ocedurenone (5 mg, 100 μCi of [
14
C]-ocedurenone). Blood, urine and feces samples were collected for determination of ocedurenone in plasma, total radioactivity in whole blood and plasma, and metabolite profiling and identification.

Results:
Fecal excretion was the predominant route and mean cumulative percent of total radioactivity eliminated via feces was 84.2% (4.23 of 5). Urine excretion was the minor route, only 6.91% (0.347 of 5) of total radioactivity was collected. Ocedurenone geometric mean Cmax, AUC0-tlast and AUC0-∞ were 92.7 ng/mL, 6510 h*ng/mL and 6560 h*ng/mL, respectively. The geometric mean Cmax of total radioactivity in plasma and whole blood was 123 and 71.5 ngEq/g, respectively. The geometric mean AUC0-tlast and AUC0-∞ of total radioactivity in plasma and whole blood were 9660 and 9910 h*ngEq/g and 5240 and 5570 h*ngEq/g, respectively. Mean whole blood/plasma ratio for total radioactivity was 0.562 for AUC0-∞, indicating little association of radioactivity with red blood cells. In addition to parent drug, 12 metabolites were detected in various matrices. Unchanged ocedurenone was major circulating entities, oxidation and dehydrogenation were the major metabolic pathways. One subject experienced 1 mild adverse event. No serious adverse event and all events resolved without intervention.

Conclusion:
Ocedurenone appears to be safe and well-tolerated after single oral 0.5 mg dose in humans. The primary route of elimination was fecal after steadily absorbed and extensively metabolized primarily through oxidation and dehydrogenation.
Abstract P324: Hypertension As A Predictor Of Sleep Disturbances Among Adults In The National Health Interview Survey (2013-2018)
Authors: Baptiste Diana L , Turkson-Ocran Ruth-Alma N , Ogungbe Oluwabunmi V , Koirala Binu , Botchway Marian , Metlock Faith , Liu Xiaoyue , Gbaba Serina , Dennison Cheryl R , Commodore-Mensah Yvonne
Published: October 2023

Background:
Suboptimal sleep is a risk factor for hypertension (HTN) and is one of the eight risk factors for cardiovascular disease (CVD). However, the association between sleep disturbances and HTN is unclear.

Objective:
To examine the relationship between sleep disturbances and HTN among adults in the U.S. We hypothesized that higher sleep disturbance scores are associated with HTN.

Methods:
We used a cross-sectional design to examine the 2013-2018 National Health Interview Survey. We computed a sleep disturbance score, composite of five components of suboptimal sleep; sleep duration, trouble falling asleep, staying asleep, sleep medication use, and restful. The sleep disturbance score ranges from 0-10 high scores reflect worse sleep disturbance and were categorized into quartiles. Survey-weighted multinomial logistic regression models were fitted, adjusting for covariates.

Results:
A total of 190,217 participants were included; 31% had HTN, mean age was 47.2 (±0.09 SE) years, and 49% were male. Mean sleep disturbance score was 2.7; mild sleep disturbance was observed in 21%, moderate in 33%, severe in 13%, and very severe in 33%. In the fully adjusted model, the odds of moderate (adjusted odds ratio (aOR): 1.30; 95% Confidence Intervals, 95%CI: [1.15,1.47]) and severe sleep disturbances (aOR: 1.42; [1.30,1.56]) were 30% and 42%, respectively, higher in persons with HTN compared to those without HTN (Table).

Conclusion:
Adults with self-reported HTN are more likely to have higher sleep disturbances, hence, HTN may play a larger role in sleep outcomes. When screening for HTN, it is also important to screen for sleep patterns that may have an adverse effect on health outcomes.
Abstract P336: Sodium, Potassium And Calories: Implications For Implementing A Recommended Diet In Adults With Hypertension. A Cross Sectional Analysis Of NHANES 1999-2020.
Authors: Cheema Asad , Buhnerkempe Michael , Prakash Vivek , Botchway Albert , Settelmyer Zachary , King Kristin , Roy Stephen , Adekola Oritsegbubemi , Flack John M
Published: October 2023

Background:
Evidence-based dietary recommendations for sodium and potassium have been made for adults with hypertension. Foods high in sodium are typically low in potassium and vice versa. This study aimed to investigate the relationship between these dietary components and their implication for simultaneously achieving recommended daily dietary intakes in individuals with hypertension.

Methods:
Data on hypertensive adults was pooled from ten National Health and Nutrition Examination Surveys (1999 - 2020) and weighted to provide national estimates. Dietary electrolyte intake was stratified as: 1) sodium ≤ 2300 mg/d [recommended] or ≤ 3000 mg/d [adequate], and 2) potassium > 4700 mg/d [recommended] or 3400 mg/d (men) and > 2600 mg/d (women) [adequate].

Results:
Few hypertensives met recommended intakes of sodium (25.7%) and potassium (6.4%) with virtually none meeting both levels (0.1%). Fewer individuals met potassium recommendations after the 2015 Dietary Guidelines for Americans were made (2015-2020 vs. earlier, p =0.006) with those meeting recommended sodium remaining similar (p = 0.97). Meeting adequate intakes of sodium (44.1%), potassium (33.1%), and both intakes simultaneously (6.6%) was more common. The correlations between sodium and potassium, calories and sodium, and calories and potassium were 0.63, 0.77, and 0.74, respectively. However, individuals who met adequate potassium levels (and not sodium) had the highest calorie intake (median [IQR] = 2912 [2368, 3666]), with those meeting adequate sodium levels only having the lowest (1402 [1083, 1757]), and those who met neither intake (2254 [1854, 2717]) and those meeting both adequate intakes in between (1866 [1568, 2256], p < 0.001). Meeting adequate sodium only results in the lowest potassium intake (1680 mg [1241, 2152]), while meeting adequate potassium only results in the highest sodium intake (4801 mg [3840, 6215]).

Conclusion:
Hypertensives almost never meet both recommended intakes of sodium and potassium with higher intakes of potassium associated with high sodium and calories. Altering contemporary diets to augment potassium while reducing sodium will require strategies that decouple the positive association of potassium with both sodium and calories.
Abstract P339: Association Between Self-monitored Blood Pressure, Heart Rate, And Anxiety Symptoms In A Digital Heart Health Self-management Program
Authors: Paz Yehuda E , Pargaonkar Vedant S , Roach Brian J , Jacob Michael S
Published: October 2023

Introduction:
Anxiety is a risk factor for hypertension and other cardiovascular (CV) diseases, and this relationship may be mediated by direct biological effects and/or indirectly via behaviors. We aimed to study the association between change in blood pressure (BP), heart rate (HR), and anxiety symptom severity among participants enrolled in a smartphone-based CV risk self-management program.

Methods:
We retrospectively studied participants with hypertension engaging with digital coaching focused on non-pharmacological lifestyle interventions, and who completed at least two generalized anxiety disorder (GAD-7) questionnaires between April 2020 and March 2023. Change in GAD-7 score was correlated with change in systolic BP, diastolic BP, and HR, controlling for age, gender, number of GAD-7 self-assessments, and initial GAD-7 score. Median BP and HR for the week of each GAD-7 self-assessment was used, and all change scores were converted to rate of change per day to control for variable time between scores.

Results:
A total of 5079 (age 58 ± 0.15y, 58% female) participants were included. Median days between GAD-7 scores was 148 (IQR 47-330). At baseline, mean GAD-7 was 7 (± 0.001), mean BP was 135/83 (± 0.28/0.18) mm Hg, and mean HR was 75 (± 0.22) bpm. Severe anxiety (GAD-7 > 14) was reported in 605 (12%) participants, and 34.3% were stage 2 hypertensive. By follow up, most of those with severe anxiety at baseline (430, 71%) showed reduced GAD-7 score (mean change = -4.5 ± 0.23). Both SBP (β = 0.03 ± 0.008, t = 3.6) and HR (β = 0.02 ± 0.009, t = 2.3) rate of change were associated with GAD-7 change such that the more participants reduced SBP or HR, the greater the reduction in anxiety symptoms. Initial GAD-7 scores were negatively associated with GAD change (β = -0.2 ± 0.016, t = -12.3). No other variable was statistically significant (all ps > 0.15).

Conclusion:
In a smartphone-based CV risk self-management program, reduction in systolic BP and HR is associated with improvement in anxiety symptoms, suggesting that digital coaching targeting CV risk factors has the potential to also improve mental health.
Abstract P340:
Codonopsis Lanceolata
Extract Prevents Metabolic And Cardiovascular Alterations In Short-term High-fat/high-fructose Diet-fed Adolescent Rats
Authors: Seol Geun Hee , Kim Yoo Jin , Shin You Kyoung , Kim Uihwan , Park Jubin , Kim Soyoung
Published: October 2023

Fast food consumption, which has increased among adolescents, has been associated with the risk of cardio-metabolic disorders. However, the effects of short-term high-fat/high-fructose diet (HFFD) on cardiovascular and metabolic parameters in adolescent rats has not yet been evaluated. Also, preventive effects of
codonopsis lanceolata
(CL) in these rats are unknown. Therefore, we investigated the effects of short-term HFFD consumption on cardiovascular and metabolic factors in adolescent rats, as well as the preventive effects of CL extract. Adolescent rats were fed a 60% high-fat diet plus 10% fructose water for 2 weeks. During this time, CL extract (200 or 400 mg/kg) was administered once daily. Short-term HFFD increased visceral white adipose tissue (WAT) weight, fasting blood sugar (FBS) concentration and water intake in adolescent rats. This diet also significantly increased systolic blood pressure (SBP), heart rate, and phenylephrine-induced vasocontraction. CL extract, however, effectively reduced visceral WAT weight, FBS, SBP and heart rate in short-term HFFD-fed adolescent rats. These findings indicate that exposure to HFFD for only 2 weeks induced cardiovascular and metabolic alterations in adolescent rats and that CL extract is effective in preventing these harmful effects of short-term HFFD in adolescent rats. This work was by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2021R1A2C2004118).
*
Corresponding author.

Keywords:
high-fat/high-fructose diet; adolescent;
codonopsis lanceolata
; prevention; visceral white adipose tissue; fasting blood sugar; systolic blood pressure
Abstract P341: Age Differences In The Impact Of Dietary Salt On Blood Pressure In Male Rats
Authors: Sun Fen , Zhang Jin-Yang , Jin Qi , Wang Qiu-Xiang , Zhao Lu-Ping , Jin Chao , Xu Jun-Tao , Yin Meng-Jia
Published: October 2023

Background:
The role of dietary salt intake in the modulation of blood pressure (BP) levels is crucial, yet difficult to regulate experimentally in humans due to ethical considerations. Previous research has primarily focused on the impact of exceptionally high salt diets on BP, which lacks clinical relevance due to the extreme nature of such diets. Therefore, this study investigates the influence of moderate-high salt diets on BP levels and BP variability, and whether there are age differences.

Methods:
Male Sprague-Dawley rats (young adult, 3 months; and aged 22-24 months old) were subjected to either a control diet containing 0.4% NaCl (sodium chloride) or moderate-high salt diets containing 1% NaCl for 12 weeks. BP levels and BP variability (BPV) were measured repeatedly at baseline, 2, 4, 8, and 12 weeks after the onset of the diet. Blood sodium (Na+) was measured at the endpoint.

Results:
Our preliminary results indicated that aged rats demonstrated an increase in blood sodium levels when subjected to the moderate-high salt diet, a change that was not observed in the young adult rats. Both the young adult and aged rats displayed an increase in systolic BP levels in response to the moderate-high salt diet. However, there were no significant alterations noted in systolic BPV across both age groups. Neither diastolic BP levels nor diastolic BPV showed any significant variation in response to the moderate-high salt diet in both the young adult and aged rat groups.

Conclusions:
This study suggested age differences in the effects of a moderate-high salt diet on BP levels but not BP variability in male rats.

Funding Sources:
This research was funded by the START-UP FUNDING OF HANGZHOU NORMAL UNIVERSITY, grant number 4255C50221204123 (Dr. Fen Sun).
Abstract P348: Utilizing A Whatsapp Community To Enhance Hypertension Control And Address Misconceptions Among Patients With High Blood Pressure
Authors: SIGAMANI ALBEN
Published: October 2023

A prospective intervention study was conducted, involving patients diagnosed with hypertension and exhibiting misconceptions regarding the condition. The study explored the impact of a WhatsApp community in promoting knowledge exchange, peer support, and adherence to hypertension management strategies. A total of 3000 patients were enrolled in the study, all of whom had been diagnosed with high blood pressure and displayed misconceptions surrounding hypertension. The WhatsApp community provided a platform for these patients to interact, share experiences, and receive guidance from healthcare professionals. The community facilitated the exchange of accurate information regarding hypertension, its causes, risk factors, and effective management strategies. Among the population, 30% were below 40 years of age and predominantly male (70%). About 18% were not on active treatment and a further 12% had switched themselves onto alternative medicines for fear of prescription medicines. Through active participation in the WhatsApp community, patients gained a deeper understanding of hypertension (formative assessment through quizzes), dispelled misconceptions (direct question and answer sessions), and received valuable support from peers facing similar challenges. This real-time communication fostered a sense of empowerment and accountability among the patients. These findings highlight the potential of utilizing technology-based platforms, such as WhatsApp communities, as effective tools for improving hypertension control and addressing misconceptions among patients. Implementing similar interventions in healthcare settings can lead to enhanced patient education, improved adherence, and ultimately better health outcomes for individuals with hypertension.
Abstract P350: Longitudinal And Summary Blood Pressure Measures And Clinical Decision-making Around Antihypertensive Therapeutic Intensification
Authors: Martin Ben , Sutherland Susan E , Rakotz Michael , Egan Brent M
Published: October 2023

Background:
The rate of treatment intensification (TI) emerges as the most important factor impacting BP control. BP has been consistently reported as the most potent clinical factor in deciding to intensify pharmacotherapy for hypertension. This study aims to quantify the relationship between measured BP and variance in therapeutic intensification (TI).

Methods:
Data for defining and modeling antihypertensive TI comes from ambulatory primary care clinics at five distinct health care organizations. Mixed-effects logistic regression was used to model longitudinal BP related information and antihypertensive TI at visits with uncontrolled BP (≥140/≥90 mmHg).

Results:
TI increased as a function of progressively higher SBP (Table 1) and DBP for both current and previous visit BP values. Yet, current and prior visit BP accounted for only 2.8% and 0.8%, respectively, of the variance in TI.

Conclusion:
Current and historical BP values impact TI. While BP is the most important factor influencing TI, its impact is limited. Highly efficient point-of-care access to previous BP might improve the rate of TI. Yet, there are potent factors limiting TI which require attention.
Abstract P355: Random-effects Modeling Of Implicit Differences Between Patients, Clinicians, And Institutions And Antihypertensive Therapeutic Intensification
Authors: Martin Ben , Sutherland Susan E , Rakotz Michael , Egan Brent M
Published: October 2023

Background:
Evidence points to treatment intensification (TI) as the most important factor impacting BP control. In our modeling of TI from EHR data, 13.2% of variance in TI could be explained by care-process and clinical factors. TI is usually framed as a clinician trait, but evidence has yet to show a significant contribution from clinician-related variables to TI in hypertension management. Random effects modeling can quantify the impact of implicit differences between patients, clinicians, and institutions on antihypertensive (AH) TI.

Methods:
Data for defining and modeling AH TI comes from ambulatory primary care clinics at five health care organizations. Multivariable mixed-effects logistic regression was used to model AH TI and several clinical and encounter related variables. Random intercepts were added to the model for each individual patient, clinician, site, and health care organization (HCO).

Results:
Comparing stepwise R
2
for a multivariable model of AH TI with random intercepts for patient, clinician, site, and HCO indicates implicit variation between clinicians adds virtually nothing to variation in TI (0.001%) vs. 0.5% for patient, 0.3% for site, and 0.2% for HCO-related differences.

Conclusion:
Among the variables examined, the primary source of variation in TI is explained by patient differences. The collective contribution to TI by site and HCO differences were comparable to patient, but clinician differences were essentially non-contributory. The data suggest the patient-clinician relationship (patient-centered care) and HCO impact TI. Greater understanding of these dynamics could potentially improve the low rate of TI for uncontrolled BP.
Abstract P362: Length Of Stay Discrepancies Between Rural And Urban Hospitals - A Cross Sectional Analysis Of Cardiovascular Disease Health Inequity
Authors: Schmidt Patrik , Allu Sai V , Parikh Harsh , Shrivastava Shitij , Khaja Misbahuddin
Published: October 2023

Introduction:
Rural communities have historically been shown to have greater obstacles to healthcare compared to their urban counterparts. These barriers manifest through multiple factors such as a reduced access to healthcare and public health services, lower availability of specialty care, and a larger number of uninsured. Compounded with a greater poverty rate, these disparities in minority populations have been shown to parallel their worse health outcomes and higher death rates. Our study aims to highlight cardiovascular disease health inequity between rural and urban populations through a cross-sectional analysis of the Length of Stay (LOS) with respect to cardiovascular disease admissions, specifically for unstable angina (UA), NSTEMI, and STEMI.

Methods:
This is a cross-sectional review for the LOS estimates in patients with cardiovascular disease in the state of New York, stratified by the type of community hospital. This review utilizes the 2020 National Inpatient Sample (NIS) for the state of New York. Cardiovascular disease was categorized using ICD-10 codes for STEMI (I21), NSTEMI (I21.4), and Unstable Angina (I20.0). Community hospital setting was categorized as either rural or urban, determined by the zip code of the primary inpatient hospital.

Results:
LOS was unique across both classification of cardiovascular disease (
p
<0.001) and community hospital setting (
p
<0.001). Overall, the LOS was less in urban-level community hospitals compared to their rural counterparts, 3.5 days vs 5.1 days (
p
<0.001), as shown in Figure 1. Stratified by the cardiovascular disease classifications, admissions in rural hospitals had an overall increased LOS, 0.8 days for UA (
p
<0.001), 1.4 days for NSTEMI (
p
<0.001), and 2.7 days for STEMI (
p
<0.001).

Conclusion:
The LOS of patients admitted for ACS was significantly higher across the board for rural hospitals. Furthermore, there was a stepwise increase in the comparative LOS between these two communities as the severity of their cardiovascular disease increased. Factors such as socioeconomic status, general access to healthcare and preventative services, insurance status, and availability of specialty care services are just some of the factors that contribute to rural health disparities.
Abstract P365: Left Ventricular Hypertrophy In Hypertension-correlation Of Electrocardiography Criteria, Echocardiography And Myocardial Strain Imaging
Authors: Jadhav Uday M , Khilari Vaidehi S
Published: October 2023

Background:
LVH on ECG has been defined by 37 different criteria with modest degree of differences in accuracy amongst them leading to a lack of consensus.

Objectives:
Study aims to correlate sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) of selected 17 standard ECG criteria in the diagnosis of LVH, correlation with echocardiography and myocardial global longitudinal strain (GLS).

Demographics:
Average age of the 104 hypertensive individuals included in the study was 61.86 years with 43.3% women. 73% of subjects had LVH on echocardiography with mean LVMI 115.97g/m2 and mean RWT 0.5.

Results:
Groningen criteria (24.70%) and Cornell voltage criteria (20.98%) had the best sensitivity for LVH detection. Groningen criteria was defined as QV2+R1+RV5+RV6+SV2+SV4+SV5+SV6 >= 49.5 mm in women and R1+RV5+SII+ SV2+SV6 x QRS duration >= 4500mm msec in men. Sensitivity for other criteria were lesser; Peguero Lo presti(PL) 13.58%, Sokolow Lyon index(SL) 11.11% and Cornell voltage product (CVP) 6.17%. Specificity and Positive predictive value (PPV) with Groningen criteria were 90% and 95.6% and with Cornell voltage criteria 100% and 100% respectively. Best sensitivity results were on combining all 17 ECG LVH criteria (39.5%). Addition of Groningen criteria improved the sensitivity of SL+CV+PL from 28.39% to 38.3%. Combination of the commonly used CV+SL+PL criteria yielded better sensitivity (28.39%) as compared to CV (20.98%) alone. Subjects with mild LVH on echo had an average GLS of -15.46+/-2.4% in 75%, subjects with moderate LVH had an average GLS of -14.23+/-2.8% in 71.4% and subjects with severe LVH had an average GLS of -12.6+/-4.9% in 80%.

Conclusion:
Irrespective of the voltage criteria used, singular or in combination, sensitivity to diagnose LVH proven on echocardiography is low. Novel Groningen criteria was more sensitive than the previously established standard ECG LVH criteria and had the highest association amongst all in patients with reduction in average GLS. Combination of four criteria SL+CV+PL+Groningen had the best sensitivity (38.3%) which improved only by 1.2% if all 17 criteria were combined.
Abstract P374: Greater Burden Of Chronic Kidney Disease Is Associated With Hypertension Prevalence And Management In South Africa
Authors: Peer Nasheeta , Kengne Andre-Pascal
Published: October 2023

Introduction:
Complications e.g., chronic kidney disease (CKD) are frequent with longstanding hypertension, particularly if poorly managed.

Hypothesis:
We assessed the hypothesis that prevalence and associations of CKD differed by hypertension prevalence, awareness, treatment and control in South Africa using five CKD estimates.

Methods:
In this randomly selected cross-sectional study, glomerular filtration rate (GFR) was estimated by CKD Epidemiology Collaboration (CKD-EPI) equations [CKD-EPI creatinine (CKD-EPIcr), CKD-EPI cystatin C, CKD-EPI creatinine-cystatin C], Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault formula (CGF). Blood pressures were measured, and history of hypertension management collected.

Results:
Among 1092 participants, mean age 43.5 years, 64% women, the prevalence of hypertension was 42% with similar rates in men (41%) and women (43%). In participants with hypertension (n=460), awareness, treatment and control were 61.5% (283/460), 47.2% (217/460) and 27.0% (124/460), with better rates in women compared with men (p<0.001). CKD prevalence (GFR<60 mL/min/1.73m
2
) was 2.0-5.9% overall using 5 formulae, and significantly higher in participants with (3.9-10.2%) compared to without hypertension (0.6-2.7%) (p<0.001). In participants with hypertension, CKD was higher in those aware (5.7-13.8%) vs unaware (1.1-4.5%) of their diagnosis (p≤0.015), on treatment (6.9-14.3%) vs none (1.2-6.6%) (p≤0.016), and those with controlled (BP<140/90 mmHg) vs uncontrolled hypertension (6.5-15.1% vs. 3-8%, p≤0.096). In models adjusted for age, sex and obesity, higher hypertension prevalence and awareness were significantly (p<0.05) associated with CKD by CKD-EPIcr and MDRD equations; hypertension treatment was significantly associated with CKD by CKD-EPIcr, MDRD and CGF formulae, while hypertension control was not associated with CKD.

Conclusions:
This study highlights the higher prevalence and greater likelihood of CKD in participants with hypertension and those who were diagnosed and receiving treatment, likely due to the longer duration of their hypertension compared with their counterparts. Higher CKD in the diagnosed and treated reinforces the need for optimal control, which was low in this cohort.
Abstract P383: The Renal Mechanisms Involved In The Response To Salt Intake Are Sex Related In Mice.
Authors: Moore Shaun C , Campisi Raisha , Asico Laureano D , Kumar Megha , Jose Pedro A , Armando Ines
Published: October 2023

Dopamine receptor D2 (Drd2) plays an important role in maintaining normal blood pressure (BP) by regulating renal Na
+
transport. Knockdown
of Drd2
in renal proximal tubule cells (RPTCs) may affect BP and Na
+
transport differently between male and female mice. We studied the effects of Drd2 in RPTCs of the mouse kidney by generating

Drd2
fl/fl
,

P

SGLT2
::Cre
+

mice (D2R
PT-/-
) that lack D2R only in RPTC and

Drd2
fl/fl
,

P

SGLT2
::Cre
-

(D2R
PT+/+
) mice that do not have the deletion. The study was performed in male and female mice on normal (0.8% NaCl, NS) and low (0.025-0.05% NaCl; LS) salt diets. On NS diet mean arterial pressures (MAPs, mm Hg), measured under pentobarbital anesthesia, were similar in male D2R
PT+/+
(86.38±2.20, n=13) and D2R
PT-/-
(91.58±1.63, n=19) and female D2R
PT+/+
(82.57±2.33, n=14) and D2R
PT-/-
(85.17±6.09, n=12) mice . By contrast, in D2R
PT-/-
mice, LS diet similarly increased MAP in male (108.11±7.04 (n=10) and female (103.00±9.98 (n=5) mice. The renal NHE3 protein expression (%) was higher in male than female mice (D2R
PT+/+
: 100±4 (male) vs 30±15 (female); n=8/group; P<0.0001; D2R
PT-/-
117±10 (male) vs 44±16 (female); n=8/group; P<0.02 ). However, NKCC expression (%) was higher in female than male D2R
PT+/+
(788±10 (female) vs 100±4 (male), n=8/group; P<0.01); there was no difference between D2R
PT-/-
male and female mice. The expressions of Na
+
-K
+
/ATPase, NCC, SGLT2, and ENaC were similar in males and females of the two genotypes. These findings suggest that on LS diet D2R knockdown in the RPTC increases BP in both male and female mice but the changes in NHE3 and NKCC expressions are different between male and female mice. These results suggests that the MAP response to salt intake is not affected by sex but the renal mechanisms involved are sex-related.
Abstract P385: Sex-specific Long Non-coding Gene Expression In Rat Nephron Segments
Authors: Geurts Aron M , Yang Chun , Novak Emily , Therani Bhavika , Liu Yong , Greene Andrew S , Rao Sridhar , Liang Mingyu , Liu Pengyuan , Cowley Allen W
Published: October 2023

Transcriptomic and proteomic approaches have identified electrolyte transporters, channels and claudins with sex-specific expression along the nephron which adapt to physiological stressors in a sex-specific manner to maintain proper fluid and electrolyte homeostasis. Yet, less is known how long non-coding gene expression in specific nephron segments differs between sexes. We performed polyA-independent RNA-seq on manually isolated proximal tubule (PT) and medullary thick ascending limb (mTAL) from 6-7-week-old male and female Dahl salt sensitive rats. Sex specific gene expression differences [log2(fold change) ≥ 0.5 or ≤ -0.5; p adj ≤ 0.05] are summarized in the table. More sex-specific differences of both protein coding and lncRNA genes were detected in PT compared to mTAL. lncRNAs were less likely to demonstrate sex-specific differences than protein coding genes (p=2.59e-12 for PT and p=5.68e-3 for mTAL). Rare lncRNAs were expressed in one sex or the other (sex-exclusive). An interesting example is ENSRNOG00000069167 and ENSRNOG00000063718 which are transcribed on opposite strands from an overlapping sequence in male or female mTAL, respectively. Multiple sex-exclusive lncRNAs were colocalized with protein coding genes significantly enriched in the same sex, suggesting they may be co-regulated within a specific chromatin domain. For example, ENSRNOG00000068738 was exclusively expressed in male PT and is colocalized in a ~560-kbp region with Pcnx1 and Sipa1l1, both of which were also enriched in male PT. Collectively, these results extend our understanding of sex-specific gene expression differences in these nephron segments to include long non-coding genes.
Abstract P386: Rat Remap Initiative At The Rat Genome Database (RGD): A Resource Of Integrated Transcriptomic And Epigenomic Data For Laboratory Rats
Authors: Geurts Aron M , Tutaj Monika , Demos Wendy , De Pons Jeffrey , Greene Andrew , Rao Sridhar , Cowley Allen W , Liang Mingyu , Liu Pengyuan , Kwitek Anne E
Published: October 2023

Complex traits including the genetic control of blood pressure have been associated with both coding and non-coding single nucleotide polymorphisms (SNPs) at more than a thousand loci across the human genome. Many of these haplotypes are found between and distant from genes, and their mechanisms leading to blood pressure variation are largely unknown. Attempts to compare and translate these non-coding mechanisms to animal model systems such as the laboratory rat are difficult, but even further complicated by the difficulty of accessing already existing large-scale genome-wide datasets including transcriptomic and epigenomic (e.g. chromatin accessibility, transcription factor binding, and DNA methylation) data that are currently distributed across a variety of public data repositories and supplementary datasets. These datasets are often annotated to previous and less complete reference genome assemblies, further hampering their broad use without time consuming reanalysis. Collectively, these challenges impede discovery and leveraging of these datasets across the broader research community toward understanding mechanisms controlling complex traits such as blood pressure. To address these challenges, the Rat ReMap Initiative seeks to establish a framework for a publicly accessible resource for rat genomic, transcriptomic and epigenomic data to housed within RGD, with analysis updated to the current reference genome assembly. Users will be able to explore and find these datasets, link to the original raw data, and access analyzed summary data files. Remapped datasets will be linked to existing genomic features, strain, and genetic variation annotations to link with disease, pathways, phenotypes, and models portals already annotated and maintained in the Rat Genome Database (RGD). Here we report our initial efforts to standardize metadata and remap a targeted set of publicly available rat transcriptome, chromatin accessibility and transcription factor binding datasets, some across multiple ages and both sexes, onto the newest rat reference assembly (mRatBN7.2), and to integrate them into an updated genome browser (JBrowse2) and into a comparative genome map browser (VCMap) at RGD.
Abstract P388: Thumbs Down: A Rare Familial Cause Of Hypertension Associated With Brachydactyly
Authors: Finley Katherine E , Panzarino Valerie
Published: October 2023

While hypertension (HTN) is extremely common in adults, genetic HTN syndromes with onset in childhood are much less common and present a unique challenge for healthcare providers. Many of these syndromes are rare and children are only screened annually for HTN, leading to delayed initiation of antihypertensives. We present a case of an otherwise healthy 7-year-old male who was noted to have persistently elevated blood pressures (BP) associated with headaches. Echocardiogram revealed normal cardiac function and anatomy without hypertrophy. Basic metabolic panel, urinalysis, and renal ultrasound revealed normal renal structure and function with no evidence of renal artery stenosis on Doppler. Additional negative workup included a thyroid function panel, serum renin, and 24-hour urine catecholamines. On ambulatory blood pressure monitoring, maximum BP was 157/107 with average BP of 139/81. His HTN did not respond to a low salt diet, so lisinopril was initiated. As the patient aged, his HTN persisted despite appropriate medical therapy and he developed short stature (height 3.7
th
percentile). He had short, thick fingers and toes on exam consistent with brachydactyly. On further questioning, there was a family history of pediatric onset HTN associated with suspected brachydactyly in his paternal grandfather, father, and paternal half-sister, however no family members had received a formal diagnosis. He was ultimately diagnosed with hypertension and brachydactyly syndrome (HTNB), a rare autosomal dominant disorder characterized by early onset severe HTN, short stature, brachydactyly, and increased risk of recurrent strokes under age 50. Incidence is unknown due to the rarity of reported cases, which makes screening and recognition more difficult. This case demonstrates the utility of recognizing phenotypic features of genetic hypertensive syndromes to aid in early diagnosis, resulting in reduced morbidity/mortality and counseling for family members. Blood pressure screening including ambulatory blood pressure monitoring should be considered in any patient with brachydactyly and/or short stature, even if phenotypic features are mild. Anti-hypertensive medication should be initiated early given the untreated clinical course of this disease.