bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P375: Cardiovascular Correlates of Hypertension in People With and Without HIV
Authors: Masenga Sepiso , Pilic Leta , Kirabo Annet
Published: October 2024

Introduction:
Hypertension is associated with cardiometabolic and cardiovascular disease (CVD) risk especially in people with HIV (PWH) and the elderly. Lack of adherence to antihypertensive drugs heightens the CVD risk. Salt-sensitivity of blood pressure (SSBP), characterized by increases in blood pressure in response to increases in dietary salt intake is a risk factor for hypertension and HIV may likely increase this risk.

Aim:
The goal of this study was to determine the differences in cardiometabolic and cardiovascular risk correlates of hypertension between PWH and HIV-negative.

Methods:
We conducted a cross-sectional study at a large referral hospital in Zambia. We randomly sampled 132 adult PWH and HIV-negative individuals with known SSBP from an ongoing large cohort study. We conducted cardiovascular and metabolic phenotyping. Data was collected using research electronic data capture and analyzed using StatCrunch. We adjusted the multivariable analysis for age, sex, and BMI. All participants signed written consents. The study was approved by the Zambia National Health Research Authority.

Results:
The median age (interquartile range) for PWH and HIV negative group were 52 (46-63) vs 46 (29-59) years, respectively (p<0.001). Females were preponderant in each group (32/50 PWH vs 50/82 HIV-negative). Hypertension was present in 28% (n=14/50) of PWH and 22% (18/82) among the HIV-negative. The factors associated with hypertension in the HIV-negative group after adjusting for age, sex, and BMI included development of
heart palpitations
following a salty meal ( AOR 4.53, 95% CI 1.10-2.18, p=0.047),
preference for low salt
(AOR 0.55, 95% CI 0.31-0.98, p=0.044),
peripheral artery disease
(AOR 5.90, 95% CI 0.39-8.95, p=0.003),
left ventricular internal dimension at end -diastole
(AOR 4.35, 95%CI 1.02-18.48, p=0.046),
Framingham risk score (2008) (
AOR 1.20, 95% CI 1.04-1.39, p=0.012), and
atherosclerotic cardiovascular disease risk
score (AOR 2.13, 95% CI 1.25-3.63, p=0.005). However, in PWH only waist circumference (AOR 1.16, 95%CI 1.03-1.32, p=0.015),
SSBP
(AOR 9.69 95%CI 1.84-51.00, p= 0.007), and
Interventricular septum thickness at end -diastole
(AOR 12, 95%CI 0.14-11.07, p=0.034) remained significantly associated with hypertension.

Conclusions:
Hypertension is associated with CVD in both PWH and HIV negative. However, the CVD phenotype and risk are different and require further investigation.
Abstract P378: Impaired Diurnal Control of Blood Pressure and Sodium Excretion in Aged Hypertensive Male Sprague Dawley Rats
Authors: Nist Kayla , McKenna James , Wainford Richard
Published: October 2024

Hypothesis:
The diurnal rhythmicity of blood pressure (BP) and sodium excretion is important to blood pressure regulation and is strongly influenced by the circadian clock genes. We hypothesized that the diurnal control of BP and natriuresis is impaired in aged male Sprague Dawley (SD) rats and may be associated with altered kidney expression of circadian clock gene proteins.

Methods:
Radiotelemetry (to record mean arterial BP (MAP)) and metabolic balance (to assess sodium excretion) was conducted in 3-month-old (3M) and 16-month-old (16M) male SD rats. On a separate day, 3M and 16M rats received an acute 900 μEq NaCl load by oral gavage at ZT0 and sodium excretion was assessed. Total renal cortex expression of Per1 and Bmal1 was assessed by immunoblotting (N=4-6/group ± SD).

Results:
16M rats exhibit significantly increased MAP and 24-h sodium retention vs. 3M rats [MAP (mmHg) 3M 102±4 vs. 16M 127±5, P<0.05; 24h Na retention (mEq/24h) 3M 0.3±0.1 vs. 16M 0.8±0.2, P<0.05). 16M rats exhibit an attenuation of the circadian MAP pattern compared to 3M rats. Aged rats have a significant decrease in the blood pressure rise during the dark (active) vs. 3M rats (Dark phase increase in MAP (mmHg) 3M +13.6±2.1 vs. 16M +4.8±1.9, P<0.05). 3M rats exhibit a classical diurnal pattern of 24-h sodium excretion with increased natriuresis during the dark (active) phase – a response that is attenuated in 16M rats that exhibit a significant reduction in the increase in natriuresis in the dark phase (Light phase UNaV (μEq/12h) 3M 380±48 vs. 16M 410±36, Dark phase natriuresis 3M 620±31 vs 16M 502±27, P<0.05). 16M rats had an impaired natriuretic response to an acute oral NaCl load in the first 12h post-gavage (UNaV 12h (μEq/12h) 3M 681±42 vs. 16M 243±39, P<0.05). In 16M old rats there was no change in renal Per1 and decreased renal Bmal1 protein (Bmal1 fold change 16M vs. 3M, 0.65±0.7, P<0.05).

Conclusions:
We observed impaired circadian control of blood pressure and renal sodium excretion in aged male SD rats. These changes in renal sodium handling may reflect endogenous decreases in renal Bmal1 levels with age and contribute to the observed hypertensive phenotype in aged rats.
Abstract P379: High Fiber Diet Attenuates Age-dependent Hypertension, Gut Dysbiosis, and Cognitive Impairment in Male Sprague Dawley Rats
Authors: Nist Kayla , Capriglione Angela , Wainford Richard
Published: October 2024

Hypothesis:
Gut dysbiosis contributes to age-dependent hypertension (HTN) driven cognitive impairment (CI), that is attenuated by prebiotic dietary fiber supplementation.

Methods:
In 3 and 16 month old (M) male Sprague Dawley rats, 3M rats receiving a fecal microbiota transplant (FMT) from 16M rats, and 16M rats fed a 6 week high prebiotic fiber (HPF) diet (n=4-6), BP, cognition (novel object recognition), paraventricular nucleus (PVN) and hippocampal blood brain barrier (BBB) integrity (FITC extravasation) and neuroinflammation (IBA1 and GFAP), gut microbiota taxonomy (by WGS) and short chain fatty acid (SCFA) levels (by GC-MS) were assessed.

Results:
16M rats exhibit gut dysbiosis, HTN, hippocampal BBB disruption and neuroinflammation, and CI. FMT to 3M rats evoked HTN and gut dysbiosis (3M vs 3M + FMT: Cecal Bray-Curtis b diversity PCoA Species Bacteria, P=<0.05). Linear Discriminant Analysis shows enrichment of cecal a)
Lactobacillales
(associated with lower BP) in 3M rats (LDA Log
10
4.69, P=0.022), b)
Alistipes putrendenis
in 16M rats (LDA Log
10
3.98, P=0.005), c) the
Bacteroides
genera (increased in HTN) in 3M + FMT rats (LDA Log
10
4.34, P=0.015). HPF attenuated gut dysbiosis (16M vs 16M + HPF: Fecal Bray-Curtis b Diversity PCoA Species Bacteria, P<0.05, PCoA MetaCyc, P<0.05; 16M pre vs post HPF: Fecal Bray-Curtis b Diversity PCoA Species Bacteria, P<0.05), increased SCFA levels, reduced BP, and improved PVN and hippocampal BBB disruption, hippocampal neuroinflammation and CI.

Conclusions:
Gut dysbiosis contributes to age-dependent HTN-driven CI. HPF supplementation, a readily implementable lifestyle intervention, attenuates HTN-driven CI via mechanisms independent of current antihypertensive medications.
Abstract P385: Effects Of a High Salt Diet On Glutamatergic Signaling In The Nucleus Of The Solitary Tract And Baroreflex Sensitivity
Authors: Viggiano Jesse , Coutinho Dominic , Martinez Diana
Published: October 2024

Hypertension remains a global health concern. Studies have shown a correlation with the loss of normal 24-hour blood pressure patterns and hypertension with a high salt diet. However, the mechanisms behind this are not fully known. The nucleus of the solitary tract (nTS), a key medullary nucleus involved in cardiorespiratory regulation, is known to modulate sympathetic outflow and blood pressure alterations.When blood pressure increases, baroreceptors in peripheral vessels detect these changes and send signals to the nTS through the neurotransmitter glutamate. Increased nTS glutamatergic signaling decreases blood pressure via efferent signals to the heart and blood vessels. The nTS integrates these signals and initiates responses through the baroreflex to counteract changes in blood pressure. Thus, baroreflex sensitivity (BRS), or a measure of how the baroreflex adjusts, serves as an indicator of the regulation of this feedback loop. An increased BRS indicates a more robust ability of the body to respond to blood pressure changes. Conversely, a reduced BRS is associated with hypertension, and autonomic dysfunction. Studies have shown that those with diet-induced hypertension also have a decreased BRS, however, the mechanism is not clear. We hypothesize that dysregulation of the 24-hour circadian glutamatergic signaling within the nTS may cause BRS decrease and hypertension. Salt-sensitive rats were subjected to either a normal salt diet (NSD, 0.4 % NaCl) or high salt diet (HSD, 4% NaCl) for 7 weeks. To determine nTS changes related to HSD, we measured blood pressure using 24/7 telemetry, and activation of glutamatergic neurons via immunohistochemistry (IHC). Antibodies against glutamate (CAMKII) and neuronal activation (cFos) were used to detect neuronal activation 6 hours apart, at the end of the NSD or HSD. Our preliminary findings reveal near significant decreases in glutamate signaling during the active period (at 9pm), suggesting a potential shift in the excitatory signaling in the nTS. Additionally, HSD over 7 weeks caused a significant increase in blood pressure and a decrease in BRS during the active period. Our preliminary data shows a connection between 24-hour regulation of glutamate within the nTS, diet-induced hypertension, and loss of BRS. This dysregulation in the blood pressure regulation underscores the importance of understanding the molecular mechanisms linking diet and development of disease.
Abstract P386: Predictors of Home Blood Pressure Response to Ultrasound Renal Denervation
Authors: Sharp Andrew , Azizi Michel , Kirtane Ajay , Bloch Michael , Baker Lemont , McClure Candace K , Fisher Naomi
Published: October 2024

Background:
Out-of-office blood pressure measurements are recommended for hypertension (HTN) management. The RADIANCE clinical trial program showed that ultrasound renal denervation (uRDN) significantly reduces daytime ambulatory systolic blood pressure (SBP) in patients with mild-to-moderate HTN (RADIANCE-HTN SOLO, RADIANCE II) and resistant HTN (RADIANCE-HTN TRIO). Previous analyses have assessed predictors of daytime ambulatory SBP response at 2-months. This analysis assessed predictors of home SBP (HSBP) at 2-months.

Method:
This analysis included 250 patients who were randomized to and received uRDN and were treated per-protocol. Separate linear regression models were used to assess predictors of the change in HSBP at 2-months. Multivariable regression analysis was conducted including variables with p-value<0.20. Backward selection with a stay criterion of 0.20 was used to select the predictors for the final multivariable analysis. Study was pre-defined as a covariate in the final model.

Results:
Patients were 69% male and 76% white; average age was 53.9 years and baseline office BP 155.5/101.5 mmHg. The only significant predictor (p< 0.05) resulting from the separate linear regression models adjusting for cohort was baseline HSBP. Other predictors included in the multivariable analyses (p<0.20) were sex, black race, screening medications(Y/N), orthostatic HTN, and right renal artery diameter. In the multivariable analyses, baseline HSBP was the only significant predictor of change in HSBP at 2-months (p=0.009, See Table).

Conclusions:
In this analysis of response to treatment with uRDN using home BPs, baseline HSBP was the only consistent significant predictor of response. Baseline BP value as a predictor of RDN response is consistent with prior analyses.
Abstract P388: Electrical Stimulation of the Porcine Carotid Sinus Nerve Reliably Decreases Blood Pressure and Heart Rate
Authors: ONeill Steven , Ukwela Jeremiah , Randolph Margaux , Marcu Vlad , Majerus Steve , Baskin Jonathan
Published: October 2024

Introduction:
Neuromodulation of the baroafferent pathway via direct carotid sinus nerve (CSN) stimulation is recognized as a potential therapeutic modality for treating uncontrolled hypertension. Although proof of concept has been demonstrated acutely in humans, there are many questions that remain in both acute and chronic applications. A translational non-companion large animal model is vital for safe development of this modality. Here we present data on the effects of CSN and baroafferent stimulation in farm pigs.

Hypothesis:
We hypothesized that an effective CSN-bioelectode interface in the pig would demonstrate significant and reproducible reductions in blood pressure in tandem with pulse rate (PR).

Methods:
Acute CSN stimulation was investigated in 9 anesthetized Yorkshire pigs. Following general anesthesia, CSNs were exposed and an application-specific electrode was placed. A fixed current paradigm was employed at constant 100Hz and 100µs pulse width. Following contact mapping to identify the baroafferent neurointerface, electrical current was escalated to establish dose-response curves. The primary outcome was systolic blood pressure (SBP) and secondary outcomes were diastolic pressure (DBP) and PR. Data were analyzed in Matlab to extract the baseline BP and PR, during and following stimulation. Statistical calculations used a one-sample Wilcoxon signed rank test. Explanted electrodes with surrounding tissue were evaluated using micro-computed tomography (μCT) and histologically.

Results:
Six of 9 animals were responders (n=7, 2 sides were stimulated in one animal), CSN stimulation caused average (mean±SD, p<0.001) decreases in SBP (6.8±7.2mmHg) and DBP (3.9±3.7mmHg), which tracked closely with decreases in PR (6.2±5.7bpm). Average maximum decreases were: SBP, 9.3±9.9mmHg; DBP, 7.7±6.4mmHg; and PR, 9.7±8.3bpm. Upon stimulation withdrawal, there was near-immediate recovery of both BP and HR. μCT and histological analysis of tissue samples demonstrated inter-animal anatomic heterogeneity.

Conclusions:
CSN stimulation causes reproducible reduction in BP synchronous with PR drops followed by near immediate recovery of both with stimulation withdrawal. Variations in animal response may be due to anatomical variation in CSN anatomy that can be overcome with further anatomical study. Pigs provide a robust large-animal model for investigating CSN stimulation, offering a platform to better understand baroafferent stimulation as treatment for uncontrolled hypertension.
Abstract P394: Pre-Existing Hypertension Intensifies Blood Brain Barrier Leakage But Not Astrogliosis Or Microgliosis After Traumatic Brain Injury In Mice
Authors: Nthenge-Ngumbau Dominic , Downing Hannah , DeGraff Zach , CHEN LEI , Daugherty Alan , Saatman Kathryn
Published: October 2024

The extent of brain damage accompanying traumatic brain injury (TBI) depends on the type and severity of insult and is modulated by age, sex, and comorbidities. Nearly half of all US adults suffer from hypertension. Not surprisingly, hypertension is the most common premorbid condition in people aged 50 or above hospitalized with a TBI. Hypertension has been linked to cerebrovascular damage, neuroinflammation and cognitive decline. Neurogenic hypertension is elevated blood pressure initiated by the local renin angiotensin system within the brain; often times involved in resistant hypertension (high blood pressure poorly responsive to common antihypertensives). Despite an overlap in several aspects of brain pathology induced by hypertension and triggered by TBI, little is understood about the impact of premorbid hypertension on outcomes following TBI. We hypothesize that hypertension induces mild blood-brain barrier leakiness and neuroinflammation, priming the brain for greater cerebrovascular damage after TBI. To test this hypothesis, mice were rendered hypertensive via subcutaneous infusion of 1000 ng/kg/min angiotensin-II (Ang-II) two weeks prior to and one week following induction of a moderate severity controlled cortical impact or sham injury. Vascular damage and astrocyte and microglia activation were examined using histology and immunohistochemistry. Quantification was performed using HALO image analysis software. Compared to injured normotensive mice, injured hypertensive mice exhibited significantly more IgG extravasation in the cortex denoting a potentiation of blood-brain barrier damage. Despite robust injury-induced astrogliosis and microgliosis, neither GFAP nor Iba1 immunostaining was further increased by hypertension. Microbleeds were observed more in the cortex and corpus callosum but much less in the hippocampi or thalami after injury and were equivalent in hypertensive and normotensive injured mice. This study contributes to laying the groundwork of identifying and characterizing hypertension as a significant premorbid risk factor for poor outcome after TBI and provides a logical basis for incorporation of pre-existing hypertension in preclinical models of TBI, increasing their clinical relevance and predictive validity.
Abstract P402: The Impact of Preeclampsia Education in Rural Communities
Authors: Hurd-Jackson Ashley , Santillan Mark , Boeldt Kara , Faro Elissa , Santillan Donna
Published: October 2024

Preeclampsia (PE) and other hypertensive disorders of pregnancy are the leading cause of maternal and perinatal morbidity and mortality. There are 4,000 PE cases/year in IA. Rural counties are at a significantly higher risk of pregnancy-related mortality. A lack of PE education regarding signs and symptoms may contribute to this risk. PE complications and mortality may be preventable with early implementation of patient education on preeclampsia during pregnancy. Our objective was to determine if implementing a magnet as an intervention increases patients' knowledge of the signs and symptoms of PE.

A magnet that includes common signs and symptoms of PE was designed to serve as an educational visual aid for patients. Pregnant patients ≥18 years old from two hospitals in Northwest IA were recruited. A pre-survey was given at a prenatal appointment prior to receiving the magnet. The post-magnet survey was administered during admission for delivery. The control group did not receive the magnet. Pre- and post-surveys asked about preeclampsia and current understanding, if they received a magnet, if it was referenced, number of healthcare visits, questions during visits about PE, and if they were diagnosed with PE.

Between 8/23-5/24, 62 pre- and 83 post-magnet surveys were collected. Statistical analyses were performed using a 95% confidence interval with p<0.05 considered significant. Ages ranged from 18-42 years old, with majority Caucasian patients (69% in pre-survey and 58% in post-survey). Levels of highest education obtained ranged from 4
th
grade to doctoral degree, with the majority completing high school as the highest level of education (29%).The magnet group rated their level of understanding of PE as good to excellent which was higher than both pre-intervention and control groups. Both control and magnet groups identified more symptoms and complications of PE on the post-survey compared to the pre-survey. Both control and magnet groups were noted to have increased discussions about preeclampsia with their physician. Lastly, both groups had increased knowledge on what to do if they developed symptoms on the post-survey compared to pre-survey responses. Of the magnet group, 71% thought receiving a magnet was helpful to increase awareness of PE.

Implementation of a magnet increased patient literacy regarding the signs, symptoms, and complications of PE, discussions with physicians, and knowledge of what to do if patients develop symptoms of PE.
Abstract P407: Sex and age differences in cardiovascular health in youth referred for hypertension disorders at baseline: A SUPERHERO Registry analysis
Authors: Murphy Maggie , Kiessling Stefan , Vincent Carol , Onugha Elizabeth , Riar Sandeep , Walsh Michael , South Andrew
Published: October 2024

Background:
The prevalence of hypertension (HTN) and other cardiovascular (CV) disease risk factors (e.g., target organ injury (TOI), obesity, dyslipidemia, hyperglycemia) are increasing steadily in youth. In adults, sex and age differences are established, but remain unknown in children (1–12 years) and adolescents (≥13 years).

Objective:
Determine sex and age differences in blood pressure (BP) severity, TOI, and CV health in youth referred for HTN disorders.

Design/Methods:
Cross-sectional analysis of baseline data from the Study of the Epidemiology of Pediatric Hypertension (SUPERHERO), a multisite retrospective Registry of youth referred to subspecialty care for HTN disorders using EHR data. Inclusion criteria were an initial subspecialty clinic visit for HTN disorders identified by ICD-10 codes from 1/1/2016–12/31/2023 and age <19 years. Exclusion criteria were kidney failure on dialysis, kidney transplantation, or pregnancy by ICD-10 codes. The exposures were sex and age at the index visit. Outcomes were BP severity at the index visit based on age, sex, and height-based U.S. guidelines, obesity by BMI or weight-for-length percentiles, and dyslipidemia, hyperglycemia, and TOI (heart and kidney-specific) by ICD-10 codes. We estimated the associations with unadjusted generalized linear models; our directed acyclic graphs did not identify any open, biasing paths necessitating adjustment for confounding factors .

Results:
Of the 9,356 participants, mean age ±
SD
was 12.8 ±4.5 years, 36% (n=3,372) were female, 56% (n=5,261) were adolescents, 23% (n=2,162) had stage 2 HTN, 5% (n=451) had TOI (2% heart, 3% kidney), 60% (n=5,655) had obesity, 9% (n=834) had dyslipidemia, and 10% (n=944) had hyperglycemia. Despite less BP severity, females had a higher risk of kidney TOI (RR 1.49, CI: 1.19 to 1.86), hyperglycemia (RR 1.48, CI: 1.3 to 1.68), and number of CV health risk factors (RR 1.1, CI:1.01 to 1.19). Compared to children, adolescents were more likely to have worse BP severity (RR 1.7, CI: 1.6 to 1.8) and HTN (RR 1.1, CI:1.1 to 1.2), and less risk for dyslipidemia (RR: 0.8, 0.7 to 0.9)

Conclusions:
In a large multisite cohort of youth referred for HTN disorders, females had a 49% higher risk of TOI and 48% greater risk for hyperglycemia despite lower BP severity. Adolescents had more severe BP and HTN compared to children. Next steps in this study include investigating age and sex differences in ambulatory BP and laboratory and echocardiogram data.
Abstract P415: The Current Cardiac Disease in Pregnancy -II Risk Score as a Predictor of Pregnancy Morbidity is Not Affected by Maternal Obesity
Authors: Morris Rachael , Voges-Haupt C. Flannery , Fowler Aurielle , Hogg James , Campbell Emily , Ohaegbulam Gail , Coats Laura , Alexander Nickens Myrna
Published: October 2024

Cardiovascular disease (CVD) is the most common cause of death in adults over 40 years of age. CVD remains a common cause of death in pregnancy and within the first-year post-partum, and Black women have higher cardiovascular risk during pregnancy than White women. There are several established mortality and morbidity prediction models for maternal cardiac complications including the Cardiac Disease in Pregnancy (CARPREG) risk score. CARPREG-II is the newest risk score which uses ten criteria to predict maternal cardiac complications. However, the only study to validate the CARPREG-II risk score had a large sample size with only 15% of patients with obesity (body mass index (BMI) >30 kg/m2). Obesity and increased obesity class are known risks factors for pregnancy related morbidity and mortality. Thus, the validity of CARPREG-II risk score as a predictor of cardiovascular risks and pregnancy outcomes in women with cardiac disease and obesity remains unknown. Therefore, the goals of our study were to assess the validity of the CARPREG-II score in Black and White women as a predictor of risk for cardiovascular morbidity and mortality in obese pregnant women and determine if obesity influences CARPREG-II score and pregnancy morbidity and mortality. For this study, we completed an IRB-approved retrospective chart review of 232 pregnant adult Black and White women who received care at the University of Mississippi Medical Center (UMMC) from January 2013 - 2020. We completed a CARPREG-II risk score and compared morbidity in patients with normal BMI (18-24.9 kg/m2), overweight (25-29.9 kg/m2), obesity class I (30-34.9 kg/m2), obesity class II (35-39.9 kg/m2), and obesity class III (>40 kg/m2). By race, the majority of White women were categorized as overweight; whereas the majority of Black women were categorized as obesity class II or III (p=0.0016). Although frequency of BMI category differed by race, CARPREG-II score did not differ as BMI increased in Black or White women, and obesity class did not influence CARPREG-II risk score. Our data indicate that Black women were more likely to have increased obesity, but obesity class did not influence CARPREG-II score. The lack of association between obesity class and CARPREG-II risk score indicate that the current CARPREG-II assessment is not an appropriate risk assessment tool for pregnant obese women and additional studies/tools are warranted to determine cardiovascular risks in pregnant obese women.
Abstract P416: RAAS Profiling in Human Pre-eclampsia Reveals Distinct Aldosterone Phenotypes
Authors: Shoemaker Robin , Patel Neil , Mirsky Elizabeth , Davis Dolph , Poglitsch Marko , Huang Hong , Bauer John , O'Brien John
Published: October 2024

Background:
Mechanisms underlying the development of pre-eclampsia in humans are not well-understood. Activation of the RAAS with markedly increased secretion of aldosterone is a key feature of normotensive pregnancy, and thought to be impaired in pre-eclampsia. The purpose of our study was to perform RAAS profiling in pre-eclampsia, where we hypothesized reduced concentrations of aldosterone in serum of patients with pre-eclampsia compared to pregnant patients without pre-eclampsia.

Methods:
This is a case-control study of 50 patients with pre-eclampsia and 50 gestational age-matched controls. Clinical characteristics (blood pressure, biochemical laboratory values) and blood samples were collected upon enrollment, and maternal and fetal outcomes were collected at delivery. Blood samples were analyzed for angiotensin I, angiotensin II, and aldosterone by LC-MS/MS using RAAS-Triple A. All patients have been recruited, and preliminary data are available for the cases.

Results:
The mean gestational age of pre-eclampsia cases was 27.9 + 6.2 weeks. RAAS profiling revealed two distinct subpopulations, where 35 patients had concentrations of aldosterone in serum that were characteristically low for pre-eclampsia: below 204 pmol/L, with median and interquartile range (IQR) of 120.0 and 35.0 – 132.2 pmol/L, and an aldosterone to angiotensin II ratio (AA2-R) of 1.05 (compared to previously published results where the median and IQR of aldosterone in pregnant women at 28 weeks was 724.8 and 376.6 – 1197 pmol/L, and median AA2-R of 4.15). In contrast, 15 patients had aldosterone concentrations more characteristic of normal pregnancy, with a median and IQR of 589.8 and 402.2– 769.6 pmol/L, and median AA2-R of 4.8). For comparison, a recent population study of non-pregnant adults determined median and IQR of aldosterone concentrations of 93 and 57.9 – 153.9 pmol/L using RAAS Triple-A.

Conclusions:
These data suggest two distinct phenotypes of pre-eclampsia based on RAAS profiling. Consistent with previous literature, our data indicate that pre-eclampsia is predominately characterized by reduced secretion of aldosterone, where concentrations are comparable to non-pregnant individuals. In contrast, we report that approximately one-third of patients with pre-eclampsia have elevated concentrations of aldosterone expected for pregnancy, suggesting multiple mechanisms for pre-eclampsia in humans defined by the presence or absence of elevated aldosterone secretion.
Abstract P425: Role of 24h UNaK ratio in patients with hypertension and resistant hypertension by gender and race
Authors: Rathi Hinal , Bag Soumyadeep , Sehar Alina , Patel Aesha , Roth Kaehler , Qamar Aleeza , Fanning John , Dudenbostel Tanja
Published: October 2024

RHTN is defined as blood pressure above goal despite using ≥3 antihypertensive medications. Patients with RHTN are at an increased risk for CVD compared to those with more easily controlled hypertension (HTN). High sodium intake and higher 24h urinary (U) sodium (Na) potassium(K) ratio is associated with higher CVD risk. The role of this ratio in RHTN has not been investigated.

Methods:
We conducted a cross-sectional analysis of a large cohort of 2397 black and white patients with RHTN who were referred to the RHTN Clinic at the University of Alabama at Birmingham and who underwent a 24h urine collection. Patients with HTN served as a control group.

Results:
Patients with RHTN had significantly higher 24h UNaK ratio than patients with HTN (3.2±1.6 vs 3.6 ±2.0, p <0.001 ) and had an earlier onset of HTN (38.8±13.7 years (yrs) vs 47.6±16.2 yrs, p=0.001) and longer duration 17.6±11.2 vs 12.0±10.7 yrs, p=0.001), higher BMI (32.6±7.2 vs 29.98±6.5 kg/m2), and 24-hourUNa (181±88 vs 164±77 mmol, p=0.01). Within the RHTN group (n=1340) females had a significant

higher

24h UNaK ratio than males (3.5±1.9 vs 3.2±1.7, p =0.006) and blacks had a significant higher 24h UNaK ratio than whites (3.0±1.6 vs 3.9±2.0, p<0.001).

Conclusion:
Higher 24h UNaK ratio as index of higher sodium and lower potassium intakes were found in patients with RHTN as well as resistant hypertensive females and blacks and may explain certain higher CV risks in these populations.
Abstract P426: Reduced
Nfatc1
Expression Results in Enhanced Pressure Natriuresis and Resistance to Salt-Sensitive Hypertension
Authors: Wang Yves , Nguyen Nhu , Le Luan , Franceschini Nora , Le Thu
Published: October 2024

Background:
Nuclear factor of activated T cells-cytoplasmic 1 (NFATc1) has recently been shown to have a non-canonical role in chronic kidney disease in humans by a trans-ethnic meta-analysis of genome-wide associate studies (GWAS). Follow-up studies in a salt-sensitive mouse model showed that
Nfatc1
mRNA expression was suppressed in the kidneys when animals were fed a high-salt diet. Here, we further explore the link between NFATc1 and salt-sensitive (SS) hypertension.

Methods:
Adult male wild-type (WT) and heterozygous
Nfatc1
knockout (Het) mice (2-5 months of age) on the SS 129S6 background were started on standard chow (0.8% NaCl, NSD) and then switched to a high-salt diet (6% NaCl, HSD). Systolic blood pressure (SBP) was measured by either tail cuff manometry with at least 2 weeks of training or implantable radiotelemetry transmitters with at least 2 weeks of post-surgical recovery. Immediately before and for 2-3 days after the change in diet, 24 h urine was collected using metabolic cages, and urinary sodium was measured by flame photometry. Sigmoid pressure-natriuresis curves were generated and the Hill slope was compared between genotypes.

Results:
WT mice showed a significant increase in SBP between NSD and after 3 weeks on HSD (127.8±9.9 vs 143.4±8.9, p = 0.0089, n = 9). In contrast, Het mice had no change in SBP (125.8±8.7 mmHg vs. 125.7±10.6 mmHg, p = 1.0, n = 9). During the initial switch to the HSD, SBP was not significantly different between WT and Het mice (133.2±2.9 vs. 134.4±3.0, p = 0.45, n = 7/group). However, WT mice had a shallower pressure-natriuresis curve (Hill slope of 0.58 vs. 0.93, 7 mice/group, 25/26 data points).

Conclusion:
Our data illustrates that decreasing
Nfatc1
expression in a mouse model is protective against SS hypertension. While acute increases in SBP in response to HSD remained in Het mice, sodium excretion was increased and SBP remained unchanged after 3 weeks, indicating that NFATc1 has the potential to be a therapeutic target against SS hypertension.
Abstract P431: Crosstalk Between Dopamine Receptors and AT1R in Hypertension Induced Cardiac Remodeling
Authors: Vishwakarma Nandini , Theobald Drew , Sriramula Srinivas , Katwa Laxmansa
Published: October 2024

Dopamine receptors are implicated in the regulation of cardiovascular function, yet their specific roles in the modulation of hypertension and cardiac remodeling are not fully understood. The angiotensin II type 1 receptor (AT1R) plays a critical role in the pathophysiology of hypertension by mediating vasoconstriction, sodium retention, and sympathetic nervous system activation. Previous studies from our lab have demonstrated that in Ang II-induced hypertension, there are alterations in D1R and D3R expression in the left ventricle (LV) compared to wild-type (WT) mice. Evidence indicates that AT1R and D1R form heterodimers and inhibition of AT1R has been shown to enhance D1R signaling in proximal tubules, suggesting a significant interaction between these receptor systems. However, the role of intracardiac dopamine receptors on AT1R expression during hypertension remains understudied. Therefore, this study aims to elucidate the crosstalk between intracardiac dopamine receptors and AT1R in the context of hypertension and cardiac remodeling by using in vitro and in vivo pharmacological and molecular methods combined with novel genetic models. Using global D3R deficient (D3KO) and WT mice, we observed that D3KO leads to alterations in AT1R gene expression in LV compared to WT hearts (p<0.001) and in isolated LV cardiac fibroblasts (p<0.0001). D3KO and WT mouse cardiac fibroblasts (mCFb) and human cardiac fibroblasts (hCFb) were stimulated with Ang II (300nM) ± D1R antagonist (SCH, 10µM) or D3R antagonist (SB, 10µM). D1R antagonism significantly increased AT1R (Agtr1 gene) levels in both WT and D3KO mCFb (p<0.01), whereas D3R antagonism reduced AT1R gene expression following Ang II stimulation (p<0.01). Furthermore, these data were confirmed in hCFb. To determine crosstalk between dopamine receptors and AT1R, we used proximity ligation assay (PLA) to examine the close proximity (<40nm) of receptor-receptor expression and interaction. Our results indicate that in mCFb and hCFb, there is an increase in D1R-AT1R interactions following Ang II both with and without D1R antagonism (p<0.05), however, AT1R-D3R interactions were reduced (p<0.05). These data suggest that dopamine receptor activity significantly influences AT1R gene expression, highlighting a potential modulatory role for dopamine receptors in the regulation of AT1R during hypertension.
Abstract P432: Screening for Primary Aldosteronism: Effect of Test and Cutoff Level on Positivity Rate
Authors: marcelli marco , Funder John , Bi Caixia , McPhaul Michael
Published: October 2024

Background:
The 2016 guidelines of the Endocrine Society proposed a screening test for primary aldosteronism (PA) based on an aldosterone renin ratio (ARR) ≥30. However, a plasma renin activity (PRA) suppressed to <1 ng/mL/h may indicate PA status better than the ARR.

Methods:
We conducted a retrospective analysis to compare the effectiveness of various screening tests for PA in a cohort of 94,829 consecutive patients who underwent ARR testing at Quest Diagnostics. The tests that were compared include ARR ≥20, ARR ≥30, PRA <1 ng/mL/h, and PRA <0.5 ng/mL/h. This comparison was made because the ARR tests may not be highly sensitive, while the PRA tests may not be highly specific. We also analyzed differences in test volume and positivity rate by region, race, ethnicity, and the time of day when the test was performed.

Results:
We observed that PRA <1 ng/mL/h identified 2.2 times as many PA cases as ARR ≥20 and 3.3 times as many cases as ARR ≥30. Likewise, PRA <0.5 ng/mL/h identified 1.3 times as many cases as ARR ≥20 and 1.9 times as many cases as ARR ≥30 (Table). We also found that PA positivity rates using ARR ≥20, ARR ≥30, PRA <1 ng/mL/h, and PRA <0.5 ng/mL/h were higher for tests performed before noon than after noon. Additionally, positivity rates were similar across US regions, although the Midwest had lower positivity for ARR tests than PRA tests, and the West had lower positivity for PRA tests than ARR tests. The PRA-based test continued to be positive more frequently than the two ARR-based tests regardless of race; however, non-Hispanic Black patients had a higher positivity rate than Hispanic, non-Hispanic White, and Asian patients, irrespective of the test used.

Conclusions:
Our data show that compared to PRA <1 ng/mL/h and <0.5 ng/mL/h, the ARR screening tool set at ≥20 or ≥30 potentially misses many patients with PA. If future prospective studies confirm this finding, one of the two suppressed PRA-based tests could become the preferred screening tool for PA.
Abstract P435: PROTEIN KINASE MODULATION IN THE INVESTIGATION OF ANGIOTENSIN-CONVERTING ENZYME AS A SIGNALING PATHWAY.
Authors: Yokota Rodrigo , Leite Ana Paula de Oliveira , Oliveira Lilian Caroline , Febba Gomes Andreia Cristina , Casarini Dulce Elena
Published: October 2024

The Renin-Angiotensin System (RAS) is a hormonal cascade intricately involved in regulating hydro electrolyte homeostasis and blood pressure control. The Angiotensin II peptide (ANGII) is the main and most potent biologically active product within this system, which is produced by the action of Angiotensin Converting Enzyme (ACE) on Angiotensin I. Dysregulation of the RAS is an important factor in the pathogenesis and progression of cardiovascular diseases and diabetes. Furthermore, ACE inhibitors (iECA) havebeen associated with the activation of signaling pathways, thus implicating ACE as a signal transducer molecule. This study aims to elucidate the significance of signaling pathways triggered by ACE and proteins that are differentially regulated when CHO-ECA cells are stimulated with ACE inhibitors. At approximately 80% confluency, the cells were deprived of serum and then stimulated with captopril (1μM) or enalapril (1μM) or vehicle for 2 and 5 minutes (n=10 in each group), to discerning the influence of sulfhydryl and carboxyl radicals. CHO-ECA cells were cultured for Kinase Array assay analysis using the Phospho-kinase Array Kit. This assay demonstrated that some pathways were positively modulated after captopril treatment after 2 minutes (AMPKa1, HSP27, Akt 1/2/3 T308) and after 5 (STATa/b, HSP60, b-Catenin). Some kinases were negatively modulated by captopril treatment (p53, PLC-γ1, Pyk2, eNOS). Conversely, treatment with enalapril modulated proteins differently at both treatment times. Some phospho-protein kinases were positively modulated in 2 minutes, such as PLC γ1, PYK2, and Yes, and others were positively modulated in 5 minutes (EGFR, GSK-3α/β, Lyn, PDGF Rβ, STAT 5a/b, WNK1 and STAT3 S2). The kinases AKT 1/2/3 T308, AKT 1/2/3 S743, CREB, Chk-2, c-Jun, JNK1/2/3, Lck, p38α, STAT3 Y705, β-Catenin were positively modulated in 2 and 5 minutes. The kinases eNOS, ERK1/2, GSK-3β, HSP27, p53 S15, p53 S46, MSK1/2, p70 S6 T389, p70 S6 T421/S424, PRAS40, Src, RSK1/2, RSK1/2/3, STAT1 and HSP60 were negatively modulated at 2 and 5 minutes. In conclusion, our findings augmented the current understanding of kinases modulated by captopril or enalapril, after ACE binding, highlighting the multifaceted role of ACE. Therefore, it can suggest that ACE may be a candidate to act not only as an enzyme but also as a signaling receptor and transducer protein.
Abstract P450: A dual probe ultrasound vector Doppler method for a robust and reliable estimation of blood flow volume and pulse wave velocity on the carotid artery
Authors: Mattesini Paolo , Ramalli Alessandro , Travagliati Marco , Confalonieri Federica , Baldasarre Leonardo
Published: October 2024

Background:
The arterial pulse wave velocity (PWV) is a strong marker of cardiovascular risk and hypertension. The development of devices enabling a robust and reliable assessment of PWV could play an important role in the early diagnosis and monitoring of those diseases. In this work, we propose an ultrasound technique to estimate blood flow volume (BFV) and PWV by simultaneously using two probes.

Methods:
Two linear arrays, held by a handle, image two cross-sections of the artery, on two planes intersecting at 40° at the vessel center (A). B-mode and color flow Doppler (CFD) images are reconstructed at high frame rate (HFR): the cross-section HFR CFDs, providing vector-Doppler imaging, avoid any assumptions on flow velocity direction and profile, thus enabling reliable BFV estimates; the HFR B-mode allows tracking the arterial wall, thus enabling robust and time-resolved estimates of the lumen area (B). PWV is estimated as the ratio between the change in flow and cross-sectional area during the early systole (C).

The method was preliminary verified by repeating 12 times the BFV and PWV estimation on the carotid artery of 8 healthy volunteers.

Results:
PWV and BFV measures were in the physiological range of 4.0-6.6 m/s (D) and 4.2-10.8 cm
3
/s, respectively. Measures were repeatable as proved by narrow interquartile ranges and low average standard deviations (1.4 m/s and 1.1 cm
3
/s, for PWV and BFV), which confirm the method's robustness.

Conclusions:
The proposed technique is suitable for BFV and PWV estimations. Since it is robust to probe repositioning and does not rely on any assumption of flow direction and profile, it could be implemented on wearable cardio-vascular wellness monitoring devices.
Abstract P452: Cell Populations and Transcriptomes Differ Across Blood Pressure and Sex in Perivascular Adipose Tissue: A Single-Nuclei RNA Sequencing Study
Authors: Terrian Leah , Thompson Janice , Panda Vishal , Watts Stephanie , Bhattacharya Sudin , Nault Rance
Published: October 2024

The perivascular adipose tissue (PVAT), fat that surrounds many blood vessels, is capable of modulating vascular tone through multiple modalities. Despite increasing research interest, PVAT remains less understood compared to other vascular layers. We hypothesized that the transcriptome and cell population of thoracic aorta PVAT (taPVAT) differ between hypertensive and normotensive rats. To test this hypothesis, we performed single-nucleus RNA-sequencing (snRNA-seq) on twenty-five taPVAT samples from male and female Dahl SS rats, fed either control (Con) chow or a high-fat diet (HFD) for 8 or 24 weeks. Mean arterial pressure (MAP) measurements showed elevated values in female rats fed a HFD for 24 weeks with a trend towards increasing blood pressure in male rats (Fig. 1a). Our analysis included at least three taPVAT samples per treatment group, resulting in 71,813 high-quality sequenced nuclei, representing eight major cell types (Fig. 1b) and twenty-eight cell sub-types. Within each cell type, the differences in population and gene expression across diet, diet duration, and sex were examined. The most substantial population proportion differences were observed across diet duration, with fewer differences noted across diet and sex (Fig. 1c). The total number of differentially expressed genes (DEGs) (adjusted p-value ≤ 0.05, |log
2
(fold change)| ≥ 1) across diet, diet duration, and sex were 191, 424, and 119, respectively. Interestingly, in the taPVAT from HFD fed rats, the gene
Csmd1
(CUB and Sushi multiple domains 1) was consistently upregulated across nearly all cell types. Whereas
Scd
(stearoyl-CoA desaturase), which is involved in fatty acid biosynthesis, was frequently the most downregulated gene. Pathway enrichment analysis revealed that the DEGs related to the HFD were associated with a decrease in lipid and fatty acid biosynthetic processes. DEGs related to rats fed a HFD for twenty-four weeks versus eight weeks were linked to an enrichment in inflammatory response and extracellular matrix organization pathways, and in HFD fed male rats compared to females, there was enrichment for leukocyte aggregation and peptidyl-cysteine modification pathways. In conclusion, our findings help paint a more detailed picture of the molecular and cellular changes in taPVAT associated with hypertension.
A new small-sized Calotes Cuvier (Squamata: Agamidae: Draconinae) from the Subansiri river basin, Arunachal Pradesh, India
Authors: PATEL HARSHIL , THACKERAY TEJAS , SHETH CHINTAN , KHANDEKAR AKSHAY , AGARWAL ISHAN
Published: October 2024

We describe a new species of small-sized Calotes from mid-elevation (~1270 m asl.), swidden or shifting cultivation areas in the Subansiri river basin, Upper Subansiri District, Arunachal Pradesh, India. Mitochondrial sequence data (ND2) recovers Calotes sinyik sp. nov. as the closely related sister taxon to an unnamed species from Medog, Tibet; the two falling in a broader clade including C. paulus + C. zolaiking and species of the C. emma and C. mystaceus groups. The new species is 7.8% divergent in ND2 sequence data from the unnamed lineage from Medog and deeply divergent (≥ 21.6–28.1%) from other congeners. The new species can easily be distinguished from regional congeners by its small adult body size (maximum snout to vent length of 65 mm) and heterogenous dorsal scales, and from its closest relatives C. paulus and C. zolaiking by having 54 or 55 midbody scale rows and 42 or 43 vertebral scales. It is likely that many more allied species remain to be discovered from Northeast India, which remains poorly surveyed across taxonomic groups.
Locally Defined Seasonal Rainfall Characteristics within the Horn of Africa Drylands from Rain Gauge Observations
Authors: Cocking Katherine , Singer Michael Bliss , MacLeod David , Cuthbert Mark O. , Rosolem Rafael , Muthusi Flavian , Paron Paolo , Kimutai Joyce , Omondi Phillip , Hassan Ahmed Mohamed , Teshome Asaminew , Michaelides Katerina
Published: October 2024

Seasonal rainfall is critical to lives and livelihoods within the Horn of Africa drylands (HAD), but it is highly variable in space and time. The main HAD rainfall seasons are typically defined as March–May (MAM) and October–December (OND). However, these 3-month periods are only generalized definitions of seasonality across the HAD, and local experience of rainfall may depart from these substantially. Here, we use daily rain gauge data with a duration of at least 10 years from 69 stations across the drylands of Kenya, Somalia, and Ethiopia to locally delineate key rainfall seasons. By calculating local seasonal rainfall timings, totals, and extremes, we obtain more accurate estimates of the spatial variability in rainfall delivery across the HAD, as well as climatological patterns. Results show high spatial variability in season onset, cessation, and length across the region, indicating that a homogenous classification of rainfall seasons across the HAD (e.g., MAM and OND) is inadequate for representing local rainfall characteristics. Our results show that the “long rains” season is not significantly longer than the “short rains” season over the period of study. This could be related to the previously documented decline of the “long rains” seasonal totals over recent decades. Several rainfall metrics also vary spatially between seasons, and the rainfall on the most extreme days can accumulate to double the local mean seasonal total. The locally defined rainfall seasons better capture the bulk of the rainfall during the season, giving improved characterization of rainfall metrics, consistent with the aim of a better understanding of rainfall impacts on local communities.