bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P314: A Community Outreach Program Focused on Hypertension Awareness Reaches 600+ People in Rural Georgia and Works to Build the Next Generation of Biomedical Scientists
Authors: Dent Elena , Ilatovskaya Daria , Pinkerton Brittany , Crider Emily , Ryan Michael , Sullivan Jennifer
Published: October 2024

The U.S. national average for the prevalence of hypertension in women aged 35-44 is 10.8%. In southeastern states including Georgia, Mississippi, and South Carolina, the prevalence of hypertension in women of this same age group is 13.5%, 17.8%, and 15.5%, respectively. The increase is mostly observed in Black women from non-metro areas. Thus, a need exists to improve awareness of cardiovascular risk in these communities and to support scientific research to improve the understanding of how sex contributes to differences in cardiovascular risk factors like hypertension.

Rural Obese At Risk (ROAR) establishes a Specialized Center of Research Excellence on Sex Differences (SCORE) homed at Augusta University, spanning three Southeast universities. The overall goal is to establish ROAR as a national resource and recognized leader in cardiovascular disease in females, and to change perceptions and awareness surrounding cardiovascular risk in women across the Southeast, particularly in high-risk groups.

One objective of ROAR Augusta is to establish a community outreach pipeline of trained scientists to increase awareness of sex as a biological variable (SABV), promote optimal cardiovascular healthcare for men and women, and empower the community to self-monitor and identify barriers to improving access to healthcare through the Community Engagement Core (CEC). The CEC aims to develop meaningful relationships among the research, medical, and lay communities promoting the increase of awareness of the importance of blood pressure control in women through community outreach, a Qualitative Needs Assessment, design and dissemination of unique illustrative educational materials related to cardiovascular disease in women, and the launch of a
Blood Pressure Checks for Women
campaign. In six months (December 2023 – May 2024), ROAR participated in 10 community events providing blood pressure checks and educational materials and reaching more than 600 people in 6 counties; awarded one pre-doctoral career enhancement mini-sabbatical; awarded three early career SABV pilot grants; hosted a SABV symposium reaching 120 biomedical scientists; and hosted a SABV seminar and workshop reaching 142 biomedical scientists. In conclusion, the ROAR CEC is well on its way to positively impacting hypertension perceptions and awareness in women across the Southeast.
Abstract P319: Organizational Determinants to Hypertension Management: A Qualitative Examination at Two Academic Learning Health Systems
Authors: Kramer Justin , Gupta Aditi , Ellis Shellie , Reed Jessica , Pokharel Yashashwi , McWilliams Andrew , Taylor Yhenneko
Published: October 2024

Background:
Hypertension management is a national priority. However, hypertension control rates are suboptimal and vary across clinics, even among those in the same health system and geographic region.

Objective:
To identify organizational barriers and facilitators that impact hypertension management at the provider- and clinic-level.

Design:
Semi-structured interviews were conducted with primary care providers (N=25) and patients with uncontrolled hypertension (N=22). Participants were recruited from thirteen family and internal medicine clinics across two academic learning health systems.

Participants:
Twenty-five providers and twenty-two patients were recruited from clinics across North Carolina and Kansas.

Approach:
Interviews were analyzed using both inductive and deductive coding methodologies. A health equity framework scaffolded interview guide design and codebook development, with thematic analysis employed to categorize emergent themes across the four framework domains.

Key Results:
Participants discussed organizational and clinic-level barriers and facilitators that impact hypertension management, with health systems’ resource centralization being frequently mentioned. Some participants lauded centralized interventions for improving patient access and increasing touchpoints, while others lamented reductions in their clinic’s staffing to accommodate centralized workflows. Insufficient in-clinic staffing and blood pressure (BP) measurement equipment, limited exam rooms, short appointment duration, and hurried clinic environments were all mentioned as challenges to hypertension management, particularly as they hindered adherence to BP recheck policies. Appointment availability was mentioned as a barrier, however providers referenced clinics’ use of virtual and/or nurse-specific visits as a mechanism to increase patient access. Multiple providers noted that tasks central to hypertension management, like BP telemonitoring and MyChart correspondence, go unaccounted for on their schedules and can lead to unpaid work, which they linked with increased stress and burnout.

Conclusions:
Primary care clinics experience multiple interrelated organizational barriers to effective hypertension management. Future studies should examine the impact of different clinic staffing models, including multidisciplinary care teams, telemedicine, and remote BP monitoring, on BP outcomes in diverse primary care settings.
Abstract P323: Pre-Hypertension And Its Determinants In Apparently Healthy Medical Undergraduates Of An Indian Tertiary Care Setting
Authors: Boyapati Sri Pranvi , KUTIKUPPALA L V SIMHACHALAM , Ganduboina Rohit , Tummala Nayanika
Published: October 2024

Introduction:
Medical undergraduates, who are just entering adulthood, due to stress and lifestyle changes, are prone and susceptive to hypertension. Numerous studies have reported a high rate of incidence of prehypertension in medical students compared to other people. Prehypertension can lead to clinical hypertension that may progress to cardiovascular disease (CVD).

Materials and Methods:
A cross-sectional study was done on 88 medical undergraduates in seemingly good health. Students of age 18-23 years and of either gender in a government medical college of India is taken into the study. This pilot study was commenced only after receiving approval from the Institutional Ethics Committee and gaining informed consent from the participants of the study.

Results:
Out of 88 subjects of the study, 55 were male, and 38 subjects were female, with 57% and 43%, respectively. Male gender was considered a risk factor for prehypertension. Data collected on BMI and given scores appropriately and the mean of BMI scores is obtained as 0.36 with a standard deviation of 0.61 (0.36 ± 0.61).

Conclusion:
By modifying the significant risk factors by health educating the individuals, the progression of prehypertension to CVD and other further complications can be prevented.
Abstract P327: Comparing the Blood Pressure Response to Antihypertensive Treatment Intensification and Dose Increase to No Action for Uncontrolled Hypertension
Authors: Barrett Robert , Riesser Benjamin , Sutherland Susan , Rakotz Michael , Egan Brent
Published: October 2024

Background:
The addition of a new antihypertension medication class (CA) or dose increase (DI) in patients with hypertension (HTN) is relatively infrequent when HTN is uncontrolled (blood pressure [BP, mmHg] ≥ 140/90) during outpatient visits. We compared systolic (S)BP changes following CA, DI, or no medication changes for uncontrolled BP.

Methods:
A patient cohort from 6 diverse healthcare organizations, engaged in a quality improvement program, was identified with previously diagnosed HTN. Uncontrolled outpatient SBP measurements observed at participating program sites were compared to follow-up measurements within 7 to 120 days for evaluating SBP change. ANCOVA and linear regression analyses were used to control clinical and demographic covariates and assess differences in SBP change following treatment decision.

Results:
A prospective cohort of 124,068 patients with HTN spanning 280,937 events was identified, mean age 63.3 ± 13.9. Class addition reduced SBP 2.0 mmHg (95% CI, 1.81 – 2.24), whereas dose increase did not lower SBP [-0.07 (95% CI, -0.31, 0.16)].

Conclusion:
In this study, CA lowered BP modestly, whereas DI appeared ineffective. Since patients were not randomized, our results may under-estimate the effects of CA and DI on BP, i.e., clinicians may have expected a greater decline of SBP than simply regression to the mean for patients with uncontrolled hypertension in the absence of DI or TI. Our data are consistent with reports that CA has a greater effect to lower BP than DI. Our findings also highlight some challenges of interpreting real world data compared to randomized clinical trials.
Abstract P341: Orthostatic Hypertension Does Not Alter the Effect of Intensive Blood Pressure Treatment on Cardiovascular Disease and All-Cause Mortality: An Individual-Level Meta-analysis
Authors: Juraschek Stephen , Hu Jiun-Ruey , Cluett Jennifer , Mita Carol , Lipsitz Lewis , Appel Lawrence , Beckett Nigel , Davis Barry , Holman Rury , Miller Edgar , Mukamal Kenneth , Peters Ruth , Staessen Jan , Taylor Addison , Wright Jackson , Cushman William
Published: October 2024

Background:
Orthostatic hypertension (OHTN) is common among adults with hypertension (HTN) and associated with cardiovascular disease (CVD). It is unclear whether HTN treatment reduces CVD outcomes similarly in adults with OHTN as adults without OHTN.

Methods:
We performed an individual-level meta-analysis, updating a previous systematic review of MEDLINE, EMBASE, and CENTRAL databases through November 13, 2023, which included randomized trials of blood pressure (BP) pharmacologic treatment (more intensive BP goal or active agent) on CVD or death. CVD events were adjudicated and included fatal and nonfatal coronary heart disease, stroke, and congestive heart failure. OHTN was defined as a rise in systolic BP ≥20 mmHg and/or diastolic BP ≥10 mmHg after changing positions from sitting to standing. Effects were examined overall and by trial type (BP goal or active agent), using Cox proportional hazard models adjusted for age and sex.

Results:
Of the 9 trials included, there were 29,235 participants followed for median of 4 years (mean age 69.5±10.9 years; 48.3% female; 21.0% with OHTN at baseline). Baseline OHTN was not associated with a higher risk of CVD or death (HR 1.03; 95% CI: 0.95, 1.13). More intensive BP treatment or active therapy lowered risk of CVD or death among those with OHTN at baseline (HR 0.80; 95% CI: 0.69, 0.93) and without OHTN at baseline (HR 0.81; 95% CI: 0.75, 0.87) with no difference between strata (
P
-interaction 0.95) (
Figure
).

Conclusion:
While baseline OHTN was common among adults with HTN, it was not associated with CVD or death and did not alter the protective effect of more intensive treatment. More intensive treatment is an effective approach to prevent CVD events among adults with OHTN.
Abstract P345: Long-Term Blood Pressure Variability and Physical Performance Measures in Community-Dwelling Older Adults
Authors: Ernst Michael , Webb Katherine , Sheets Kerry , Woods Robyn , Fravel Michelle , Beilin Lawrence , Espinoza Sara , Orchard Suzanne , owen alice , Wolfe Rory , Murray Anne , Ryan Joanne , Shah Raj , Polkinghorne Kevan , Reid Christopher
Published: October 2024

High degrees of long-term, visit-to-visit blood pressure variability (BPV) independently predict increased risks of cardiovascular disease, cognitive decline, and frailty in older adults. Measures of physical performance such as gait speed and grip strength can predict loss of independence and mortality in older adults, but are not routinely measured in practice. Shared pathways of underlying physiologic deterioration may exist between high BPV and progressive loss of gait speed and grip strength. We examined the association between long term, visit-to-visit BPV and change in gait speed and grip strength in participants of the ASPirin in Reducing Events in the Elderly (ASPREE) study, a randomized primary prevention trial of low-dose aspirin conducted in 19,114 community-dwelling adults in Australia and the U.S. who were without independence-limiting physical disability at enrollment, and its extended long-term observational follow-up (ASPREE-XT). Long-term BPV was estimated in each participant using the standard deviation (SD) of the means of three within-visit systolic BPs obtained using a validated automated oscillometric BP monitor from the baseline and first two annual ASPREE visits. During ASPREE and continued into ASPREE-XT, participants underwent annual/biennial measures of grip strength using a Jamar hand grip dynamometer, and completed a timed 3 meter walk at normal pace. Linear mixed models were used to examine changes in gait speed and grip strength trajectories over a median of 5.2 years of follow-up after the second annual ASPREE visit (end of BPV estimation window). After covariate adjustment, the highest SD tertile of BPV, compared to the lowest SD tertile, was associated with greater declines in gait speed over time, and reduced grip strength cross-sectionally (see accompanying Table). Our findings suggest that long-term BPV is an important predictor of progressive loss of physical performance, particularly gait speed, in older adults. Since BP is routinely measured in practice, characterization of the visit-to-visit BPV may help identify older adults at risk of future declines in physical function and loss of independence.
Abstract P349: Prediabetes Increases the Risk of Frailty in Pre-frail Hypertensive Older Adults: Beneficial Effects of Metformin Treatment
Authors: Mone Pasquale , Visco Valeria , Pansini Antonella , Ciccarelli Michele , Iaccarino Guido , Santulli Gaetano
Published: October 2024

Background:
Prediabetes has garnered increasing attention due to its association with cardiovascular conditions, especially hypertension, which increases the risk of prefrailty and frailty among older individuals.

Methods:
We screened older adults with prefrailty and hypertension from March 2021 to January 2023. We assessed the correlation linking cognitive dysfunction (Montreal Cognitive Assessment score), insulin resistance (triglyceride-to-glucose index), and physical impairment (5-meter gait speed). Then, we measured the risk of developing frailty after a 1-year follow-up period, adjusting the outcome using multivariable Cox regression analysis. We also investigated the impact of administering 500 mg of metformin once daily to a subset of frail subjects for an additional 6 months.

Results:
We assessed the relationship between the triglyceride-to-glucose index and the Montreal Cognitive Assessment score, observing a significant correlation (r: 0.880; P<0.0001). Similarly, we analyzed the association between the triglyceride-to-glucose index and 5-meter gait speed, uncovering a significant link between insulin resistance and physical impairment (r: 0.809; P<0.0001). Prediabetes was found to significantly (P<0.0001) elevate the risk of frailty development compared with individuals without prediabetes by the end of the 1-year follow-up, a finding confirmed via multivariable analysis with Cox regression. Furthermore, among the subgroup of subjects who developed frailty, those who received metformin exhibited a significant decrease in frailty levels (P<0.0001).

Conclusions:
Insulin resistance and prediabetes play substantial roles in the development of cognitive and physical impairments, highlighting their importance in managing hypertension, even before the onset of frank diabetes. Metformin, a well-established drug for the treatment of diabetes, has shown favorable effects in mitigating frailty.
Abstract P351: Obesity in Early Life Leads to Endothelial and Erectile Dysfunction in Young Adult Rats.
Authors: dos Passos Rinaldo , Vieira dos Santos Cintia , Moura Kawane , Townsend Paul , Wilson Emily , Tomazini Goncalves Tiago , DosAnjos Moraes Raiana , Wenceslau Camilla , McCarthy Cam , Silva Carneiro Fernando , Ceravolo Graziela , Webb R Clinton , Priviero Fernanda
Published: October 2024

Background:
Erectile dysfunction (ED) is largely associated with obesity, however, the consequences of early life obesity for ED in young adulthood are unknown. We hypothesize that obesity induced by preweaning overfeeding impairs vascular and erectile function and affects blood pressure in young adult male rats (5-month-old).

Methods:
At postnatal day (PND) 1, Wistar rats were divided into a normal litter (NL, 5 female + 5 male pups/dam) or small litter (SL, 2 male + 1 female pup/dam) during lactation. After weaning, SL pups had increased body weight. Next, rats from both groups returned to normal size colonies (4-5 rats per cage) and were fed standard chow. At PND160, we evaluated body weight and fat pad deposition, mean arterial pressure (MAP) by tail-cuff, and pudendal artery (PA) and corpus cavernosum (CC) reactivity. Concentration-response curves to phenylephrine (PE) or acetylcholine (ACh) were performed in both preparations. In the CC, contraction and relaxation to electrical field stimulation (EFS) were obtained. Concentration-response curves were analyzed using non-linear regression analysis. RNA sequencing (RNAseq) analyses were performed in both PA and CC. Data were analyzed by Student’s t-test and presented as mean ± S.E.M. Statistical significance was set at p<0.05.

Results:
At PND160 no differences in body weight were observed in SL (594±14g) compared to NL (559±13g), however, there was an increase in fat deposition in SL (retroperitoneal fat: NL 7.47±0.69g vs SL 11.25±1.23g; perigonadal fat: NL 10.05±0.55g vs SL 13.24±1.16g). MAP was higher in SL (120.5±1.20 mmHg vs 114.9±0.58 NL). In the PA, ACh-induced relaxation was reduced in SL (Emax: 28±6%) vs NL (Emax: 68±5.5%), with no changes in the contraction to PE. In the CC, EFS-induced relaxation was significantly decreased in SL rats compared to NL rats (16 Hz: NL 3.06 ± 0.28% vs SL 2.39 ± 0.53%). RNAseq revealed that, in PA from SL rats, 289 and 224 genes were down and upregulated, respectively, while in the CC from SL rats, 115 genes were downregulated, and 110 genes were upregulated. Among them,
hcn2
gene (which encodes HCN2, the hyperpolarization-activated cyclic nucleotide-gated potassium and sodium channel 2) was strongly downregulated in both PA and CC, and this may affect mechanotransduction.

Conclusion:
Our data shows that early-life obesity causes long-lasting vascular and cavernous damage that might be associated with endothelial and erectile dysfunction in young adulthood.
Abstract P357: Renal Male and Female Cortical Mitochondria Display Bioenergetic Differences in Response to Varying Substrates
Authors: Schibalski Ryan , Cherezova Alena , Jones Adam , Stadler Krisztian , Ilatovskaya Daria
Published: October 2024

Introduction:
In general, renal disease susceptibility is higher in males than in age-matched females until menopause. The damage to renal proximal tubules (PT) is key to the onset of kidney disease development due to their high capacity for reabsorption and intense mitochondrial metabolism. Our previous data identified higher oxygen consumption in the renal cortex of healthy male Sprague Dawley rats and lower H
2
O
2
production compared to females. We hypothesize that sex differences in renal mitochondrial substrate reliance trigger differential bioenergetic responses in PTs, which contributes to kidney disease development later in life.

Methods:
11-week-old male and female Sprague Dawley rats were acquired from Charles River Labs. The kidneys were flushed, and the renal cortex was used for
ex vivo
experiments. Mitochondria were isolated with differential centrifugation, and rovided with different substrate combinations: 10mM pyruvate and 2mM malate (PM), 5mM of glutamate, malate, and succinate (GMS), or 5mM succinate only (S). Spectrofluorimetry was employed to measure membrane potential (TMRM) and H
2
O
2
production (Amplex Red), XF24e Seahorse was used for oxygen consumption rate (OCR). OriginPro was used for statistical analysis (one-way ANOVA with post hoc test) and data displayed as mean ± SEM.

Results:
Seahorse revealed that male renal cortical mitochondria exhibit higher basal and maximum OCR compared to females when provided with the GMS or PM substrate combinations (39.4 ± 1.18 vs 26.5± 0.88, respectively for basal GMS, and 52.0 ± 2.33 vs 32.6 ± 1.24 maximum respiration GMS, p<0.001). However, similar OCR was observed when mitochondria were provided succinate only (31.2 ± 1.67 vs 28.7 ± 1.30, respectively for basal and 50.5 ± 2.49 vs 51.1 ± 1.76 maximum respiration, p>0.05). Mitochondrial membrane potential was higher in females compared to males when succinate only was provided (p<0.001), whereas similar mitochondrial membrane potential was observed between males and females when GMS or PM were used. Regardless of the substrate combination used, H
2
O
2
production was higher in female renal mitochondria compared to males (p<0.001).

Conclusions:
We report that male and female renal cortical mitochondria display unique bioenergetic properties in response to varying substrates. These basal bioenergetic differences may contribute to the difference in susceptibility to kidney diseases later in life.
Abstract P359: Greater NLRP3 in Males Results in a More Pro-Inflammatory T cell Profile, but Comparable Increases in Blood Pressure to Females with DOCA-Salt
Authors: Liss Cameron , Belanger Kasey , Badrak Jeanine , Sullivan Kelly , Hanson Peyton , Sullivan Jennifer
Published: October 2024

T cells contribute to the development of hypertension, but what mediates T cell activation in hypertension is still being investigated. The NLRP3 inflammasome is a key mediator of the inflammatory response, and NLRP3 contributes to deoxycorticosterone acetate (DOCA)-salt hypertension in male mice. Little is known regarding the role of NLRP3 in hypertensive females, but we previously published that greater increases in blood pressure (BP) in male DOCA-salt rats vs females is associated with a more pro-inflammatory T cell profile. The goal of the current study was to test the hypothesis that greater NLRP3 activation in males contributes to greater increases in BP and a more pro-inflammatory T cell profile than in females.

Methods:
Initial studies measured NLRP3 and IL1-β mRNA expression in kidneys of uninephrectomized (UNX) male and female Sprague Dawley rats randomized to vehicle or DOCA treatment (n=5/group). Additional UNX male and female rats were randomized to DOCA plus vehicle or an NLRP3 inhibitor, MCC950 (10 mg/kg), for 3 weeks. BP was measured via telemetry (n=5/group). Kidneys were harvested for flow cytometric analysis of T cells. Data were compared via 2-way ANOVA.

Results:
DOCA increased renal NLRP3 and IL1-β mRNA in males and females (NLRP3: P
treatment
<0.0001, P
sex
=0.0014; IL1-β: P
treatment
<0.0001, P
sex
=0.05), and increases were greater in males (P
interaction
=0.04, P
interaction
=0.02, respectively). DOCA treatment increased BP in males (105±4 to 190±1 mmHg) and females (97±3 to 167±5 mmHg), and treatment with MCC950 attenuated DOCA-induced increases in BP in both sexes (males: 107±3 to 174±2 mmHg; females: 98±3 to 159±7 mmHg; P
treatment
=0.004). Terminal BP values were compared and while BP was higher in males, the impact of MCC950 was comparable between the sexes (P
sex
=0.0001; P
interaction
=0.4). However, MCC950 attenuated DOCA-induced increases in renal CD4
+
T cells and Th17 cells to a greater degree in males than in females (CD4+: P
treatment
<0.001, P
sex
=0.03, P
interaction
=0.04; Th17 cells: P
treatment
<0.001, P
sex
=0.001, P
interaction
=0.04).

Conclusions:
NLRP3 contributes to the development of DOCA-salt induced increases in BP and inflammation in both males and females. However, males have greater NLRP3-mediated increases in renal T cells than females. The impact of this mechanism on renal function and the potential for targeted hypertensive therapies needs to be further examined.
Abstract P360: MicroRNAs: Potential Biomarkers and Therapeutic Targets for Hypertensive Nephropathy
Authors: Al Kayed Hadeel , Altintas Mehmet , Oktay Ahmet
Published: October 2024

Introduction:
Hypertensive nephropathy (HN) is the second most common cause of end-stage renal disease after diabetic nephropathy. miRNAs are small epigenetic modulators whose levels change in many diseases. This review summarizes the diagnostic and therapeutic potential of miRNAs in HN.

Methodology:
We conducted a thorough literature review on PubMed, including both retrospective and prospective studies on animal and human subjects. Additional references were sourced through cross-referencing the bibliographies of the initial articles.

Results:
Our literature review revealed that intra-renal levels of miR-200a, miR-141, miR-200b, miR-205, miR-429, and miR-192 were elevated in patients with HN. Conversely, intra-renal miR-204-5p levels were decreased, and further reductions in animal models using anti-miR-204-5p or miR-204 gene knockout exacerbated renal injury.

Exposure of renal tissue to exogenous albumin increased intra-renal miR-184 levels, prompting further investigation into whether albumin excretion from kidney injury alters miRNA expression or if miRNA dysregulation initiates kidney injury and subsequent albumin excretion.

Urinary miR-146a, miR-184, and miR-34a levels were lower in patients with albuminuria than those without, whereas urinary miR-200a levels were higher. Interestingly, urinary miR-21 levels increased before the onset of albuminuria in hypertensive mice.

A positive correlation was also observed between miR-208b and miR-133a levels in blood cells and urinary albumin excretion (UAE). Notably, plasma levels of miR-let-7g-5p and miR-191-5p correlated positively with eGFR but not with UAE. Since miRNA levels varied based on the sampling source, a pivotal study identified a consistent miRNA profile in HN patients, showing that miR-208a and miR-301a were upregulated in urine yet downregulated in plasma.

The therapeutic potential of miRNAs was highlighted by an animal study showing that the knockdown of miR-103a-3p can nullify albuminuria in hypertensive mice.

Conclusion:
The role of miRNAs in HN is increasingly evident. Studies have linked varying miRNA expression profiles in patients with HN, and specific miRNAs were detectable earlier than albuminuria. Furthermore, certain miRNAs correlate with eGFR independently of UAE. Targeting specific miRNAs, using miRNA mimics and anti-miRNAs, could underpin preventive and therapeutic strategies. These findings advocate for further research into miRNAs as potential biomarkers and therapeutic targets for HN.
Abstract P361: Characterization of a Constitutive Adiponectin-Cre Rat Reveals Expression in Adipocyte, Endothelial and Neuronal Lineages
Authors: Demireva Elena , Mallett Christiane , Watts Stephanie , Jackson William , Flood Emma , McClusky Bridie , Lauver Adam , Christian Barbara , Xie Huirong
Published: October 2024

Introduction:
The Dahl salt-sensitive (DahlSS) rat is a valuable model for studying hypertension and blood pressure regulation. To create new genetic tools for probing gene function specifically within adipose tissues in this model, we engineered a constitutive Adipoq-Cre rat on a DahlSS genomic background using CRISPR-Cas9 genome editing.

Methods:
A P2A-Cre cassette was inserted in-frame with the endogenous Adiponectin gene (ENSRNOG00065003537) to enable bicistronic expression from the major transcript (Adipoq-201; ENSRNOT00060022350.1). CRISPR targeting was achieved by microinjecting rat zygotes with a ribonucleoprotein (RNP) complex consisting of Cas9 protein and single guide RNA with a target near the stop codon, and a homology-directed repair plasmid template carrying the Cre recombinase cassette. To evaluate the pattern of Cre expression, Adipoq-Cre DahlSS rats were crossed with a Rosa-CAG-LSL-tdTomato LE reporter line (RRRC#: 009389). The progeny were analyzed for tdTomato reporter expression by cryo-fluorescence tomography (CFT) at postnatal day 10 (P10) and 10 weeks of age, using a Xerra
TM
EMIT imaging platform (50um sections). A Zeiss LSM 880 system was used to image fresh Vectashield-mounted tissues with a Plan-Apochromat 20x objective and a 561nm laser.

Results:
Strong CFT signal was detected in all examined adipose depots including subcutaneous, gonadal, and retroperitoneal white adipose tissue, interscapular brown adipose tissue, and perivascular adipose tissue (PVAT). Expression was also detected in the CNS. Confocal imaging of mesenteric PVAT and thoracic aorta PVAT revealed expression in adipocytes, endothelial cells, and peripheral nerves.

Conclusion:
The newly developed constitutive DahlSS Adipoq-Cre recombinase knockin drives expression in white and brown adipose depots but the presence of expression in non-adipocyte cells suggests either developmental or adult adiponectin expression in endothelial and neuronal lineages, limiting its ability to drive strictly adipose-specific gene expression.
Abstract P369: Hospital Outcomes of Hypertensive Emergency in Black and White Patients.
Authors: Amoah Joseph , Asafu-Adjaye Frempong , Somoza-Cano Francisco , Amoah Nana Nyarko , Fatuyi Michael , Dekowski Sammir
Published: October 2024

Objectives:
A rapid and severe increase in blood pressure resulting in new or progressive end-organ damage is defined as a hypertensive emergency. Our study sought to estimate the clinical outcomes of black and white patients admitted for hypertensive emergency.

Methods:
Using the National Inpatient Sample Database of 2020 (NIS), retrospective data of black and white patients who were admitted for hypertensive emergency were identified using ICD-10 codes. Outcomes were in-hospital mortality, cerebrovascular accident (CVA), acute kidney injury (AKI), myocardial infarction (MI), pulmonary edema, acute hypoxic respiratory failure, length of hospital stay, and total hospital charges.

Results:
A total of 59690 patients were admitted for hypertensive emergency. 80.6% of patients were either black or white. Black patients were younger (54 years, 95% CI 54 – 55 VS 65 years, 95% CI 65 – 65) when compared to white patients. There were no statistically significant differences in inpatient mortality (p=0.2345), myocardial infarction (p=0.8618), and pulmonary edema (p=0.8835). Black patients had increased acute kidney injury (p<0.0001), acute hypoxic respiratory failure (p=0.0014), length of hospital stays (4 days, 95% CI 4 – 5 VS 3 days, 95% CI 3 – 4), and total hospital charges ($47,132.68, 95% CI $44,808.58 - $49,456.79 VS $43,882.58, 95% CI $42,394.76 - $45,370.39). White patients had increased cerebrovascular accident (p<0.0001) when compared to black patients.

Conclusion:
Per this study, there was no difference in in-hospital mortality between black and white patients admitted for hypertensive emergency. Black patients had increased AKI, acute hypoxic respiratory failure, length of hospital stays, and charges.
Abstract P383: Increased renal afferent nerve activity and peak response to pro-inflammatory cytokine interleukin 6 in isolated dorsal root ganglion neurons from hypertensive rats
Authors: Hayoz Sebastien , Adams Mason , Clinch Deanna , Foster Thaiane , Flynn Madeleine , Fusco Giuliana , Hoyt Abigail , Kim Dae-Kyung , Kwasny Kaitlyn , Rautenberg Josiah , Robertson Gavin , Robertson Tevin , Sahota Rohit , Nilsson Arielle , Zozobrado Lizetta , Banek Christopher
Published: October 2024

Renal afferent nerves are reported to mediate the progression of hypertension in preclinical models, putatively via an aberrant increase in activation. The underlying source of this nerve activation is unknown but we hypothesized renal inflammatory cytokines are a primary driver. We previously reported interleukin 6 (IL-6) is increased in the kidneys of hypertensive rats, and intrarenal administration of IL-6 can activate renal afferent nerves. Though these data are promising, the direct effects of IL-6 on afferent renal nerves remain unclear. We hypothesized that isolated renal afferent neurons from hypertensive rats will have increased activity and responsiveness to inflammatory cytokine IL-6 compared to normotensive controls. To test our hypothesis, we tested the direct effects of interleukin-6 (IL-6) on renal afferent nerve action potentials (AP) generated in freshly isolated dorsal root ganglion (DRG) neurons. To model salt-sensitive hypertension, uninephrectomized rats (n=6) were administered deoxycorticosterone acetate (DOCA; 100mg, sc) and 0.9% saline for drinking water for 21 days. Control rats (n=6) were uninephrectomized. To label renal afferent nerves, neuronal tracer DiI was introduced by intrarenal injection 6 days prior to DRG collection. DRGs from T10-L1 were isolated, enzymatically digested and dissociated, and cultured overnight for whole-cell patch-clamp the following day. DiI-positive neurons from both control and DOCA rats generated AP during the delivery of 100, 200, and 300 pA current steps. Data were analyzed by two-way, repeat-measures ANOVA (α=.05). At baseline, DOCA neurons had a higher (p<0.05) mean AP frequency compared to controls (no difference in AP mean peak amplitude or AP duration). In both groups, increasing concentrations of IL-6 (0. 4, 4, and 40 ng/ml) elicited a dose-dependent increase in AP peak amplitude compared to baseline. No difference was detected in IL-6 responses between DOCA and controls. Overall, these data supported our original hypothesis that pro-inflammatory cytokine IL-6 would increase renal afferent nerve activity, and that said activity is increased in hypertensive DOCA-salt rats. IL-6 accumulation triggered by end organ damage due to hypertension might lead to increased afferent renal nerve activity, which exacerbates the hypertensive phenotype through a sympatho-excitatory response. Additional measurements of isolated DRG responses to pro-inflammatory mediators are underway for direct comparison.
Abstract P387: Survival trajectories of the patients with malignant hypertension in the Rice Diet Program
Authors: Luft Friedrich , Neelon Francis , Klemmer Philip , McDowel William , Bohannon Anastacia , Sanoff Scott , Lin Pao-Hwa
Published: October 2024

Malignant hypertension (MH), severe arterial hypertension accompanied by retinal hemorrhage (Class III), papilledema (Class IV), or both was untreatable in 1942. Walter Kempner treated MH patients with a very low sodium (~200 mg/day), protein (~5% of calories), and fat (~5% of calories) diet with success in some patients. The scope and efficacy of this “Rice” Diet (RD) was not clear. We analyzed data from 563 non-diabetic MH patients treated from 1942-1988. The cohort, mostly male (69.4%) with a median age 51 years and median BMI 24.01 provided several interesting findings. First, the number of MH patients increased until the early 1950s, but then declined sharply by 1955, before effective pharmacotherapy was available. This sudden MH “disappearance” seems real, but is unexplained by therapy or other known events. Second, 341 MH patients showed that median survival more that doubled with RD treatment compared to untreated MH patients described by Keith-Wagner-Barker (KWB) in 1939. Third, the RD-diet survival benefit began after ~90-100 days into treatment. During the first ~90-100 RD days, survival closely tracks that of untreated MH patients described by KWB; thereafter, survival curves diverged substantially (e.g., calculated half-time survival for Class IV increased from 163.5 to 815.5 days,
Figure
). Fourth, serial retinal photographs of 359 MH patients, showed that of 343 with initial hemorrhage, 36 of 177 patients surviving at 1 year (20%) still had hemorrhage; of 146 with initial papilledema, only 1 of 76 patients surviving at 1 year (1%) still had papilledema. Fifth, survival curves of MH patients with only hemorrhage or only papilledema were similar; however, survival was markedly shorter in those with both hemorrhage and papilledema, implying that the deleterious effects of vascular and neuropathic changes are independent of one another and additive. Remaining questions concern: why did MH “suddenly” disappear; how does RD impact vaculopathy; what factors impact survival trajectories.
Abstract P397: Effects of Dietary Sodium Reduction on Systemic Inflammation: Findings from DASH-Sodium Study
Authors: Zhu Haidong , Huang Ying , Dong Yanbin
Published: October 2024

Background:
High sodium intake is a significant risk factor for hypertension and cardiovascular disease. Animal studies have demonstrated that high salt diet promotes tissue inflammation and increases systemic inflammation, such that it is plausible that sodium induced inflammation might be another pathway to hypertension. However, whether the link between dietary sodium intake and systematic inflammation in humans remains unclear due to limited human studies, different designs and inconsistent findings. Therefore, we tested the hypothesis that dietary sodium reduction reduces systemic inflammation in humans by leveraging the randomized controlled trial design of the DASH-Sodium study.

Methods:
DASH-Sodium study was a multicenter, randomized trial comparing the effects on blood pressure (BP) of three levels of sodium intake (3450 mg/d, 2300mg/d, and 1150 mg/d) in two diets (DASH vs American) among US adults. Five systematic inflammatory markers including hs-CRP, IFN-γ, IL-6, IL-10, and TNF-α were measured at each study visit in stored plasma samples from 224 participants. Two-level mixed-effects linear regression models were used to assess the effect of sodium reduction on inflammatory markers with adjustment of covariates.

Results:
A total of 224 participants (aged 49.4±9.5 yrs, 61% female, 62% black, and 2% other races) from the DASH-Sodium study were included in the analyses. Overall, compared to high sodium group, low sodium group had slightly elevated hs-CRP (
p
=0.013), and intermediate sodium group had decreased TNF-α (
p
=0.011). Both significances, however, disappeared after adjusting for multiple testing (
p
adjust
>0.01).

Conclusion:
Modest dietary sodium reduction as recommended did not induce significant changes in systematic inflammation in humans.
Abstract P400: Adherence to First Line Antihypertensive Medication Prescription Recommendations by Race
Authors: Nguyen Andrew , Le Jonathan , Huang Tzu Yu , Botting Patrick , Cheng Susan , Ebinger Joseph
Published: October 2024

Introduction:
The burden of hypertension is not felt uniformly across the population, with non-Hispanic Black (NHB) adults experiencing the highest rates of hypertension-attributable mortality. The 2017 AHA guidelines recommend calcium channel blockers (CCBs) and thiazide-like diuretics as initial medications for NHB patients, with ACE/ARBs a first line recommendation for other populations. It remains unclear to what degree providers adhere to these race-specific recommendations.

Methods:
We examined electronic health record data of all hypertensive adults (first blood pressure >140/90 mmHg) starting antihypertensive therapy between 1/2013-12/2022. We excluded patients with a diagnosis of CAD/MI, diabetes, stroke, heart failure, or CKD. We specifically identified the order in which each antihypertensive medication class was prescribed.

Results:
We identified a total of n=26,862 patients, of whom n=4015 (14.95%) were NHB. CCBs were the most prescribed first line antihypertensive agent for NHBs, followed by ACE/ARBs, then diuretics. By comparison, for all other patients, ACE/ARBs were the most prescribed first agent, followed by CCBs, then beta-blockers (Figure 1A-B). Over the study period, initial use of CCBs increased and diuretic use decreased for both groups (Figure 1C-D).

Conclusions:
Following guidelines, the most frequently prescribed first line antihypertensive agents were CCBs and ACE/ARBs for NHB and non-NHB populations, respectively, with decreasing diuretic use. The identified patterns increased over the study period, indicating an overuse of ACE/ARB and underuse of diuretics among NHB patients.
Abstract P401: Documentation of Elevated Blood Pressure Measurements in the Emergency Department: Exploratory Analysis of Factors Associated with Discussion and Comparison to Other Settings
Authors: Chapman Cole , Faine Brett , Carter Barry , Talan David , Polgreen Philip , Polgreen Linnea
Published: October 2024

Introduction:
Asymptomatic hypertension is common among emergency department (ED) patients. However, follow-up occurs infrequently. Because recognition of elevated readings is a prerequisite for referrals, we investigated the factors associated with the documentation of discussion of elevated BP in provider notes.

Methods:
We used electronic medical record data to identify patients who had an outpatient ED, primary care, or urgent care visit with elevated BP (>=140/90 mm Hg) and no prior hypertension diagnosis, 2017-2021. We calculated the percentage of visits in which provider clinical and/or discharge notes mentioned hypertension or elevated BP, beyond the reporting of vitals. We modeled the probability that the notes mentioned elevated BP or hypertension. Covariates included the busyness of the care setting at the time of the visit, patient demographics, visit vitals, and diagnoses.

Results:
We identified 13,777 distinct patients with 18,036 ED visits, 3,563 urgent care visits, and 27,895 primary care visits with elevated BP levels. BP was discussed in the notes for 27% of ED visits compared to 51.4% of primary care and 51.1% of urgent care visits. The probability of mentioning BP did not rise with the degree of BP elevation for ED visits, but it did for primary care and urgent care visits (See Figure). Elevated BP was more likely to be discussed in the notes of ED visits when the visit was related to a cardiac complaint, when elevated BP was mentioned in previous notes, and when the ED was less busy than normal.

Conclusions:
Elevated BP levels are frequently not discussed in ED clinical notes. Discussions of BP measurements in notes may be an easy-to-measure marker for clinical recognition of elevated BP measurements.
Abstract P403: Implementation of Knowledge Exchange Sessions to Catalyze Advancement of Sustainable Community-Clinical Relationships that Prioritize Hypertension Control.
Authors: Aguirre Diana , King Linda , Shine Kyna
Published: October 2024

Introduction/Background:
The American Heart Association’s National Hypertension Control Initiative (NHCI) collaborated with public health champions by participating in Learning Collaboratives (LC) in five regions across the United States to address hypertension through LC groups that facilitated the exchange of best practices and lessons learned. LCs convene stakeholders for expert-led sessions to promote collaboration in the health care ecosystem.

Research Questions/Hypothesis:
LCs can be an effective way for national initiatives to convene in expert-led sessions on best practices in hypertension control, including the advancement of Community-Clinical Linkages (CCL) by fostering collaboration among diverse health care stakeholders.

Methods/Approach:
NHCI planned to convene stakeholders in 5 regions to learn how they operationalized the Centers for Disease Control and Prevention CCL approach. Areas were chosen based on criteria such as highly engaged NHCI Community Health Centers, NHCI funded community-based organizations with strong administrative capacity, a robust community health worker network, and active Primary Care Associations. Local assessments conducted during the planning phase led NHCI to pivot and collaborate with existing LCs instead of initiating new ones. During these LCs, NHCI conducted listening sessions to enhance collaboration and community-health center integration through knowledge exchange discussions and co-learning experiences.

Results/Data:
NHCI staff worked with local field staff to understand community needs. They leveraged trusted relationships with public health champions to identify LCs for conducting listening sessions. The local field staffs’ strong relationships with public health advocates presented NHCI with opportunities to plan meetings to obtain the buy-in for the listening sessions. NHCI conducted 6 listening sessions in 5 regions. Engagement in local LCs provided insight on operationalizing CCLs to address hypertension. Stakeholders exchanged best practices, lessons learned, strategies, and social determinants of health to advance CCLs for hypertension control.

Conclusion(s):
Leveraging trusted relationships and participating in existing LCs is key to conducting successful listening sessions around best practices in hypertension control, including the advancement of Community-Clinical Linkages.
Abstract P408: Association of Social Risk Factors with Cardiovascular-Kidney-Metabolic Syndrome at Baseline in Youth with Hypertension Disorders: A SUPERHERO Analysis
Authors: Onugha Elizabeth , Vincent Carol , Harry Giya , Murphy Maggie , South Andrew
Published: October 2024

Poor cardiovascular-kidney-metabolic (CKM) health is associated with an increased risk for cardiovascular disease events and cardiovascular mortality in adults. There is a disproportionate burden of CKM syndrome among adults with social risk factors, and the presence of social risk factors can contribute to health and healthcare disparities in patients with CKM syndrome. Nothing is known about the association of social risk factors with CKM syndrome in youth with hypertension disorders.

We conducted a cross-sectional analysis of baseline data from the Study of the Epidemiology of Pediatric Hypertension (SUPERHERO), a retrospective Registry of electronic health record data obtained using standardized and validated biomedical informatics scripts. Inclusion criteria were youth <19 years old who received care from subspecialists for hypertension disorders from 1/1/2026–12/31/2023 defined by ICD-10 codes. Exclusion criteria were kidney failure on dialysis, kidney transplantation, or pregnancy by ICD-10 codes. The outcome was CKM syndrome defined by ICD-10 codes and included no risk, stage 1 and stage 2 CKM syndrome; for this analysis we excluded those who were unclassified (
n
=630, 7%). Exposure was presence of at least one social risk factor defined by ICD-10 codes and included food access, transportation, housing, income, education, employment, family, and crime. We used directed acyclic graph-informed bivariate generalized linear models; no biasing paths were present so no additional covariates were included.

Of 8,726 participants, the mean age was 12.8 years (
SD
4.5) and 62% were male. CKM syndrome stage 1 prevalence was 20% and CKM stage 2 was 65%. Seventy-four (0.8%) youth had at least one social risk factor. Presence of social risk factors was not associated with CKM syndrome (OR 0.9, 95% CL 0.6 to 1.5).

Among youth referred for hypertension disorders, we found that those with social risk factors were not more likely to have CKM syndrome. Given the low prevalence of social risk factors by ICD-10 codes only in this early SUPERHERO phase, there is a critical need for a transdisciplinary approach to more comprehensively screen for and identify social risk factors. Further investigation into this important topic may inform risk stratification based on presence of social risk factors and targeted interventions to improve CKM health. Future SUPERHERO analysis will investigate the impact of interventions addressing social risk factors on CKM health outcomes.