bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P117: Improving Hypertension Control In A Veterans Affairs Resident Primary Care Clinic, A Mixed-Methods Study
Authors: Vendiola Jean Alyxa F , O'Halloran Meghan , Hughes Ashley M
Published: October 2023

Introduction:
Hypertension (HTN) is a critical modifiable risk factor for cardiovascular disease (CVD). In 2017, ACC/AHA guidelines recommended a blood pressure (BP) target of ≤ 130/80 mmHg for patients with high CVD risk. Prior research in the primary care clinic showed poor adherence with up-to-date guidance for BP control. The current study targets resident physician prescribing barriers to improve HTN control.

Method:
The study was conducted in a large Midwest VA Patient Aligned Care Team (PACT) staffed by 49 Internal Medicine resident physicians and 10 supervising physicians. Physician prescribing barriers were identified via semi-structured interviews. Interventions included physician education on BP goals and treatment, guided self-audit exercise, and revised implementation of EMR HTN order menu. Therapeutic inertia (TI) data was collected weekly from October 2022 to May 2023.

Results:
Major themes of prescribing barriers identified by physician interviews were patient non-adherence, lack of guideline-integrated practices, and lack of knowledge of single-pill combination agents (Table 1). Therapeutic inertia was examined for patients with high CVD risk and uncontrolled BP at a PACT visit. Baseline TI from June to October 2022 was 88.2% (128 of 145 patients had no change in antihypertensive therapy). Post-intervention TI was 88.4% (107 of 121 patients had no change in antihypertensive therapy).

Conclusion:
This study highlights the ongoing need to engage resident physicians with interactive tools to increase awareness of updated HTN guidelines. Identifying barriers to resident prescribing behaviors can be used to target interventions.
Abstract P129: Cardiovascular Safety Of Severe And Sustained Hypoxia Exposure In Physically Fit Patients Following Myocardial Infarction
Authors: Hoenemann Jan N , Gerlach Darius , Hoffmann Fabian , Weis Henning , Zaha Vlad G , Sadek Hesham A , Reuter Hannes , Baldus Stephan , Splettstoesser Frank , Frede Stilla , Levine Benjamin D , Jordan Jens , Limper Ulrich , Tank Jens
Published: October 2023

In mice, hypoxia exposure corresponding to 8000 m altitude over several weeks induced myocardial proliferation and improved left ventricular ejection fraction following myocardial infarction. To enable translation of these findings from mice to patients with myocardial infarction, we determined whether exposure to severe sustained hypoxia is limited by right ventricular failure secondary to hypoxia-induced pulmonary hypertension. We enrolled three men who suffered myocardial infarctions 49-126 months prior to the study (left ventricular ejection fraction 47±7 %) but were otherwise healthy and one male, healthy control person. We induced hypoxia by adding nitrogen to ambient air until alveolar oxygen partial pressure decreased to 35 mmHg. Normobaric hypoxia was then maintained for 14 consecutive days (FiO2=0.095) corresponding to 6062- 6224 m altitude. We added 1% oxygen over night to ameliorate sleep and prevent acute mountain sickness. We conducted echocardiography at baseline, during hypoxia in hypoxic conditions and 3 days after reconditioning. Measurements included right ventricular to atrial pressure gradient as surrogate for pulmonary artery systolic pressure (PAPsys), tricuspid annulus systolic excursion (TAPSE) and right ventricular (RV) free wall strain. Hypoxia induced pulmonary hypertension, that rapidly abated in recovery (baseline: 35±3 mmHg, hypoxia: 47±9, recovery: 28±1, p=0.0292). TAPSE was not reduced by hypoxic exposure (baseline: 28±3 mmHg, hypoxia: 26±1 recovery: 29±2, p=0.0693) and right ventricular free wall strain was maintained (baseline: -22.4±3.9 mmHg, hypoxia: -24±5.4 recovery: -22.7±1.5, p=0.8493). The healthy control person showed similar responses. No signs or symptoms of right heart failure occurred throughout the study. In highly selected patients with myocardial infarction, substantial normobaric hypoxia induced pulmonary hypertension, however, right ventricular function was well preserved. These observations pave the way for translational studies on hypoxia-induced cardiovascular regeneration and may have implications for patients traveling to high altitude.
Abstract P149: Prevalence, Trend And Clinical Outcomes Of Hypertensive Urgency And Emergency Before And During The Covid-19 Pandemic: A Comparative Nationwide Analysis (2019 Vs. 2020)
Authors: Hashem Anas , Khalouf Amani , Salah Mohamed Mohamed , Ismayl Mahmoud , Rai Devesh , Osama Muhammad , Feitell Scott , Balla Sudarshan
Published: October 2023

Background:
Data on the prevalence trend and clinical outcomes of hypertensive urgency and emergency during the COVID-19 pandemic remains limited. Hence, we aim to compare the prevalence of hypertensive urgency and emergency between the years 2019 and 2020 and compare the clinical outcomes between both years.

Methods:
We used the National Inpatient Sample (2019-2020) to obtain all patients with hypertensive urgency (ICD-10: I160) and emergency (ICD-10: I161). We excluded all patients who tested positive for COVID-19 infection. We measured the trends annually in 4 quarters. Multivariate logistic regression was used to measure the adjusted outcomes.

Results:
We found a total of 188,801 patients with hypertensive urgency (2019: 95,731 - 2020: 93,070) and 112,257 patients with hypertensive emergency (2019: 55,456 - 2020: 56,801). The trend in hypertensive urgency showed a significant drop in the second and fourth quarters of the year 2020 (p<0.01),

Figure 1

. On multivariate logistic regression, the in-hospital mortality odds among hypertensive emergencies were higher in the year 2020 (aOR 1.08, 95%CI [1.01-1.15]) with no difference in hypertensive urgency. Other complications included hemorrhagic shock, ischemic stroke and acute kidney injury (AKI) were worse among hypertensive emergencies in the year 2020,

Figure 1

. There were no differences in the length of stay in both years, regardless of the severity of hypertension.

Conclusion:
Hypertension urgency was less in the second and fourth quarters in the year 2020. The overall in-hospital complications were worse for hypertensive emergencies in the year 2020 including mortality, hemorrhagic and ischemic stroke and AKI.
Abstract P150: Dynamic Alu Cpg Methylation Change In Elevated Diastolic Blood Pressure
Authors: Jiraboonsri Suvinai , Meevassana Jiraroch
Published: October 2023

Hypertension is recognized as age-related disease. However, its interaction with aging at the epigenetic level is still not fully understood. Hypomethylation of Alu elements, the most abundant class of interspersed repetitive sequence in the genome, is associated with global hypomethylation, an important epigenetic event of aging. Dermal fibroblasts have been observed to be affected by hypertension. In vitro study has shown that hypertension accelerated expression of age-related phenotypes. Therefore, in our study, we aimed to examine the relationship between blood pressure, age and Alu methylation status using dermal fibroblasts as a model. Biopsies of dermal fibroblasts were performed on 39 patients with various ages and blood pressure statuses. The patients were grouped into three categories based on their systolic blood pressure (SBP) and diastolic blood pressure (DBP): Normal (SBP = 130 mmHg; DBP = 85 mmHg), High Normal (SBP = 130-139 mmHg; DBP = 85-89 mmHg) and Hypertensive (SBP ≥ 140 mmHg; DBP ≥ 90 mmHg). Combined Bisulfite Restriction Analysis was performed to determine the Alu methylation level and pattern. The data was analyzed using Two Way ANOVA factoring in age groups. The Alu methylation level in the normal, high normal and hypertensive groups according to SBP is 30.3 ± 2.15%, 30.2 ± 2.15%, and 30.1 ± 2.06% and 29.6 ± 1.85%, 31.1 ± 1.78%, and 30.2 ± 2.48% according to DBP (data displaying in mean ± SD). The percentages of
u
C
u
C methylation pattern were 42.8 ± 5.57%, 42.7 ± 3.84%, 41.9 ± 4.84%, 44.2 ± 5.19%, 40.4 ± 2.95%, and 42.3 ± 4.79% for normal, high normal and hypertensive group, by SBP and DBP respectively. There were statistically significant differences between groups of DBP status with methylation level lowest in the high normal group.
u
C
u
C methylation pattern was the highest in high normal DBP group (p-value < 0.05). There was also a statistically significant interaction between age and DBP level to Alu methylation. However, there was no statistically significant difference between SBP groups. We conclude that there is a dynamic Alu methylation change in the elevation of DBP with overarching trend of Alu hypomethylation. This phenomenon suggests that Alu methylation may have a role in how hypertension accelerate cellular aging in different tissues.
Abstract P157: IMPACT OF CONCURRENT ATRIAL FIBRILLATION ON HYPERTENSIVE EMERGENCIES:
Authors: Muhyieddeen Amer , Chang Joseph , Ranasinghe Sachini , SALEH KHALED , ABDULLAH KHALED , Rasheed Oune , Nomigolzar Soroush
Published: October 2023

Introduction:
In patients suffering from hypertension, the presence of concurrent atrial fibrillation tends to escalate the risk of severe conditions and worsen outcomes. This study, aimed to delve into the impact that a simultaneous diagnosis of atrial fibrillation can have on patients admitted for hypertensive emergencies during the initial year of the COVID-19 pandemic.

Methods:
We examined data from the 2020 National Inpatient Sample to identify patients primarily admitted due to a hypertensive emergency. We used ICD-10 codes to distinguish between those with and without concurrent atrial fibrillation. We employed logistic and linear regression analyses and accounted for potential confounders. We deemed the results as statistically significant when the 2-tailed p-value was less than 0.05.

Results:
During 2020, there were a total of 1,221,535 admissions for hypertensive emergencies. Notably, 470,440 (38.5%), involved patients concurrently diagnosed with atrial fibrillation. After adjusting for variables such as age, race, gender, the size and geographic location of the hospital, insurance coverage, income level, and existing comorbidities, patients hospitalized for hypertensive emergencies, who were also diagnosed with atrial fibrillation, demonstrated an elevated risk of in-hospital mortality (aOR 1.25, 95% CI 1.18-1.32). This patient group was also more likely to require the initiation of mechanical ventilation (aOR 1.06, 95% CI 1.03-1.09), vasopressor therapy (aOR 1.71, 95% CI 1.52-1.92), and mechanical circulatory support (aOR 1.71, 95% CI 1.32-2.21). Intriguingly, despite the increased risks in these areas, these patients displayed a reduced rate of hemodialysis initiation (aOR 0.82, 95% CI 0.79-0.86).

Conclusion:
Atrial fibrillation seemingly has a critical influence on the in-hospital outcomes of patients admitted for hypertensive emergencies, generally leading to more unfavorable results. Given the anticipated increased prevalence of atrial fibrillation in an aging population, understanding its pathophysiology and potential contribution to the complexity of diseases in patients with severe hypertension represents a crucial area for further investigation.
Abstract P159: Adipocyte Progenitor Subtypes In Perivascular Adipose Tissues: Effect Of Site And Spatial Location
Authors: Rendon Cristian J , Sempere Lorenzo F , Watts Stephanie W , Contreras G A
Published: October 2023

Hypertension-induced remodeling leads to excessive extracellular matrix (ECM) deposition in the different vascular tunicas including the outermost layer, perivascular adipose tissue (PVAT). Hypertension also reduces PVAT adipocyte populations. The number of adipocytes are maintained by continuous adipogenesis of progenitor cells (AP) expressing PDGFRα, but not all AP are created equal. In brown adipose tissue (AT), distinct AP subpopulations have defined spatial distributions and distinct adipogenic and fibrogenic potential. For example,

Bmper
+

AP are restricted to brown AT parenchyma and express Col IV and V; these preferentially differentiate into adipocytes. Fibro-adipogenic AP such as

Pi16
+

abound in the fascia and express Fn1 and Col XII, while

Gdf10
+

close to blood vessels express Col I and Fbln1. However, how AP subtypes distribute in and contribute to PVAT remodeling is currently unknown. We hypothesize that AP subtypes from PVAT have different spatial distributions. We collected PVAT from the thoracic (atPVAT) and abdominal (abPVAT) aorta and mesenteric (mesPVAT) sites from 30-week-old male lineage tracing mice (
PDGFRa
-CreERT2/R26-LSL-tdTomato; n = 5). We traced Pdgfrα
+
AP by inducing tdTomato expression (tamoxifen, 150 mg/kg, IP, 5d). Arterial sections with PVAT were stained (6-plex IHC) with DAPI and antibodies against BMPER, PI16, GDF10, and PPARG to define AP subpopulations in the fascia, parenchyma, and adventitia using ImageScope Cellular IF Algorithm (reported as % cells/total AP±SD). In all PVAT depots, we found the presence of all AP subtypes. BMPER and PPARG had a nuclear expression, while PI16 and GDF10 were in the cytoplasm and membrane. APs co-expressing PPARG were highly abundant in the parenchyma of atPVAT (82% 8 of 10±15.3) vs. mesPVAT (37% 4 of 11±22.1). BMPER and PI16 had no differences in their PVAT distribution. In atPVAT, GDF10 had higher expression in the adventitia (72% 8 of 11±24) vs. parenchyma (36% 4 of 11±23.2) and fascia (16% 3 of 18±15.2). Our results show the diversity of AP populations in different PVAT depots, which can contribute differently to hypertension-induced PVAT remodeling. Future experiments will evaluate how hypertensive conditions affect the fate of AP subtypes in PVAT.
Abstract P161: Addressing Hypertension And Aging In Growing Tribal Afro-pakistani And Indigenous Migrant Populations In San Joaquin
Authors: Siddiqui Maha
Published: October 2023

Introduction:
San Joaquin Valley (SJV) Pakistani indigenous elderly migrants (SJIEM) and tribal Afro-Pakistani elderly populations (TAPEP) face health problems due to poor nutritional habits, financial and emotional stress from loss of social status, loss of physical capabilities, orthopedic disorders (OD), loneliness, reduced income which can increase risk for hypertension (HTN) and cardiovascular disease (CVD). Pakistan is ranked as the 12th highest source country for immigration into USA. SJV has a growing rate of at risk for HTN in SJIEM and TAPEP who live with their full time working adult children.

Objectives:
Trainees conducted HTN screenings at mosques located in the most medically served region, SJV to reduce CVD risk and spread awareness on HTN, stress management, nutrition, OD, exercise, and their implications in SJIEM and TAPEP.

Methods:
I trained medically ambitious low-income minority high school students to conduct blood pressure screenings with cultural humility and serve as health coaches for SJIM and TAPEP at SJV mosques. HTN screenings, stress management guidance, nutrition and heart health talks were conducted at SJV mosques with Imam (religious leader) for adult children and elderly.

Findings:

-Approximately (≈) 83% (91 of 110) of SJIEM & TAPEP felt financial & emotional stress during COVID and last year

-≈68% (74 of 110) of SJIEM & TAPEP are hypertensive

-≈68% (74 of 110) of SJIEM & TAPEP are at risk for CVD

-≈2% (2 of 110) of SJIEM & TAPEP reported daily physical exercise

-≈12% (13 of 110) of SJIEM & TAPEP were encouraged to physically exercise

-≈90% (99 of 110) of SJIEM & TAPEP suffer from at least one form of OD

-≈95% (105 of 110) of SJIEM & TAPEP eat over 4 servings of red meat per week

-≈94% (103 of 110) of SJIEM & TAPEP prefer to rest than physically exercise

-≈89% (97 of 110) of SJIEM & TAPEP felt dissatisfied by SJV medical treatment

Direct Outcomes:

-Development of self advocacy for health in SJIEM and TAPEP

-Improved patient provider trustAdult children felt more confident in caring for elderly parents with nutrition and physical therapy

-Youth learned the value of multiculturalism and service to disadvantaged communities

-Program students are determined to pursue medicine and address health disparities in indigenous communities
Abstract P164: Montelukast, A Leucine Rich Repeat Containing 8A Inhibitor, Decreases Contractility Of Vaginal Smooth Muscle In Diabetic Mice: A Possible Treatment For Female Sexual Dysfunction In Diabetes
Authors: Wilczynski Stephanie , Priviero Fernanda , Rodrigues dos Passos Rinaldo , Choi Hyehun , Lamb Fred S , Webb R Clinton C
Published: October 2023

Vaginal smooth muscle (VaSM) is critical to sexual function, desire, and arousal. Individuals with hypertension or diabetes have smooth muscle dysfunction which is associated with elevated superoxide anion production and increased inflammation in smooth muscle. Further, endothelial dysfunction is common in the small arteries, like the pudendal arteries, that supply the sex organs in females. This loss of function could contribute to female sexual dysfunction (FSD). This study aims to bridge the gap to treat hypertensive or diabetic individuals’ sexual dysfunction and discover non-hormonal treatments to increase blood flow to the VaSM and clitoral tissue. In this study, we hypothesize that the inhibition of leucine rich repeat containing 8A (LRRC8A) volume regulated anion channels (VRACs) will decrease the contraction to endothelin-1 (ET-1) in vaginal smooth muscle of lean and diabetic (db/db) mice. LRRC8A channels have been proposed to modulate entry of extracellular superoxide (O
•-
) associated with NADPH oxidase activity. The activity of NADPH oxidase is increased in diabetes and hypertension. Female young lean and db/db (12 wks) mice underwent distal vaginal dissection. The VaSM was then mounted on a strip myograph for measurement of isometric force development. Contraction to ET-1 was performed in the absence and presence of the LRRC8A inhibitor, montelukast (1uM) (MONT) after a 30-minute incubation. The weight/length of VaSM (mg/mm) was used to normalize the maximum contraction (mN). Measures of weight/length in db/db mice VaSM tissue were less than in lean mice (p=0.0112). In lean mice, force development to ET-1 was significantly less after incubation with MONT (logEC50 control 8.428 +/- 0.06886 vs. drug 7.859 +/- 0.06083, p= 0.0007 ). In db/db mice, force development to ET-1 was significantly less after incubation with MONT (logEC50 control 8.779 +/- 0.1007 vs. drug 7.278 +/- 0.05490 , p= 0.0004). Treatment with an inhibitor of LRRC8A offers a novel approach to treat FSD and should be further researched to observe its overall impact. LRRC8A may play an important physiological role in the maintenance of the contractile response by managing the flux of O
•-
in the VaSM, making it an important potential target in conditions like hypertension and diabetes.
Abstract P166: Prebiotic Dietary Fiber Supplementation Attenuates Gut Microbiota Dysbiosis And Age-dependent Hypertension-driven Cognitive Impairment
Authors: Nist Kayla , Capriglione Angela , Wainford Richard D
Published: October 2023

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

Methods:
In 3 and 16 month (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, cognitive function (novel object recognition), hippocampal blood brain barrier (BBB) integrity (by FITC extravasation), gut microbiota taxonomy (by WGS) and short chain fatty acid (SCFA) levels (by GC-MS) were assessed.

Results:
Aged 16M rats exhibit gut microbiota dysbiosis, HTN, hippocampal BBB leakage and impaired cognition. FMT to 3M rats evoked gut microbiota dysbiosis (3M vs 3M + FMT: Cecal Bray-Curtis β diversity PCoA Species Bacteria, P=<0.05) and HTN. 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 microbiota dysbiosis (16M vs 16M + HPF: Fecal Bray-Curtis β Diversity PCoA Species Bacteria, P<0.05, PCoA MetaCyc, P<0.05; 16M pre vs post HPF: Fecal Bray-Curtis β Diversity PCoA Species Bacteria, P<0.05), increased SCFA levels, reduced BP and hippocampal BBB permeability and improved cognition.

Conclusions:
Gut microbiota 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 P169: Differences In Cardiovascular Autonomic Dysfunction Between Postural Tachycardia Syndrome And Long COVID-19 Postural Tachycardia Syndrome: A Prospective Cohort Study
Authors: Abbasi Khuzeman , Castro Robert A , Aden Luul A , Golchha Meenakshi , Rigo Stefano , Diedrich Andre' , Okamoto Luis E , Biaggioni Italo O , Shibao Cyndya A
Published: October 2023

Post-acute sequelae of COVID-19 infection or Long COVID-19 is a debilitating condition affecting 140 million US adults. Some Long COVID-19 patients develop cardiovascular autonomic dysfunction, particularly Postural Tachycardia Syndrome or POTS. It is unknown, however, if there are differences in cardiovascular autonomic reflexes, autonomic symptoms, or quality of life between these populations. We prospectively enrolled 42 patients (20 Long COVID-19 POTS and 22 POTS patients), 93% (39 of 42) females referred to the Vanderbilt Autonomic Dysfunction Clinic. These patients underwent standardized autonomic function testing, including head-up tilt (HUT), Valsalva maneuver (VM) and Sinus arrhythmia (SA). Autonomic symptoms were measured with COMPASS-31 survey, and quality of life assessment with EQ-5D.

Results:
Both groups were matched by age (37 ± 11.3 vs. 33 ± 9.3, p=0.393) and BMI (29 ± 7.5 vs. 30 ± 7.6, p=0.951). Supine SBP (p=0.145), DBP (p=0.258) and HR (p=0.130) were similar between groups. The increase in HR during 10-min HUT were similar between groups (Figure A), and upright HR absolute values were slightly but significantly lower in Long COVID-19 POTS than in POTS patients (100 ± 16.7 vs. 109 ± 27.5, p=0.04). Sympathetic vasoconstriction and cardiovagal function were similar between groups with no differences during VM and SA, respectively. Long COVID-19 POTS had a greater COMPASS-31 total score (80 ± 12.9 vs. 48 ± 8.8 in POTS, p=0.001), affecting all 6 domains (Figure B). EQ-5D was similar between groups (p =0.692).

Conclusion:
Autonomic symptoms were disproportionately higher in Long-COVID-19 POTS than in POTS, despite similar cardiovascular autonomic reflexes.
Abstract P172: Dietary Sodium-to-Fiber Ratio Is Independently Associated With Body Composition And Blood Pressure In Healthy Adults
Authors: Hutchison Zach J , Linder Braxton A , Tharpe McKenna A , Barnett Alex M , Culver Meral N , Sanchez Sofia O , Jeong Soolim , Stute Nina L , Watso Joseph C , Grosicki Gregory J , Robinson Austin T
Published: October 2023

Background:
High dietary sodium (Na
+
) is associated with poorer body composition, increased blood pressure (BP), and decreased vascular function, whereas high dietary fiber typically has opposing associations. However, it is unknown whether dietary Na
+
indexed to fiber (
i.e.,
Na
+
/Fiber) is an independent predictor of body composition and cardiovascular health. Therefore, we examined relations between Na
+
/Fiber, body composition, BP, and vascular function.

Methods:
We assessed body composition using body mass index (BMI) and waist:hip ratio, brachial BP via oscillometry, arterial stiffness via carotid-femoral pulse wave velocity (cf-PWV), and endothelial function via brachial artery flow-mediated dilation (FMD). Participants (n=50; 22 Male/28 Female, 35±16 years, BMI: 27±4 kg/m
2
, BP 116±11/70±7 mmHg, mean±SD) completed 3-day food and fluid logs to derive daily Na
+
and fiber intake. We used unadjusted and covariate-adjusted Pearson’s correlations to assess relations between Na
+
/Fiber and physiological outcomes. We used ANCOVA to compare physiological outcomes between tertiles of Na
+
/Fiber ratio. Covariates included age, sex, race, and dietary potassium.

Results:
In unadjusted models, Na
+
/Fiber was correlated with BMI (r = 0.444,
p
= 0.001), waist:hip ratio (r = 0.320,
p
= 0.023), brachial systolic (r = 0.316,
p
= 0.026), and diastolic BP (r = 0.321,
p
= 0.023), but not cf-PWV (r = 0.126,
p
= 0.383) or FMD (r = 0.120,
p
= 0.408). With covariate adjustment, Na
+
/Fiber remained correlated with BMI (r = 0.417,
p
= 0.004), waist:hip ratio (r = 0.438,
p
= 0.002), and systolic BP (r = 0.297,
p
= 0.045). Using ANCOVA, there was an effect of Na
+
/Fiber on BMI and waist:hip ratio (
ps
< 0.021). There was also an effect of Na
+
/Fiber on systolic BP (overall
p
= 0.014; high: 123±3 mmHg, middle: 114±3 mmHg, low: 113±3 mmHg), with significant post hoc differences between the high and middle tertiles (
p
= 0.029) and the high and low tertiles (
p
= 0.038). Importantly, dietary Na
+
/Fiber more strongly associated with BMI, waist:hip ratio, and BP than Na
+
and fiber alone.

Conclusion:
Our preliminary data indicate that Na
+
/Fiber ratio is an independent predictor of poorer body composition and increased blood pressure in healthy adults.
Abstract P177: Antigen-presenting Cell Vitamin D3 Modulates Salt-sensitive Hypertension In Humans
Authors: Albritton Claude F , Saleem Mohammad , Pitzer Ashley , Ertuglu Lale , Kirabo Annet
Published: October 2023

Salt-sensitivity of blood pressure (SSBP) is a condition in which high sodium intake causes shifts in blood pressure that are associated with cardiovascular disease and mortality. Recent studies from our lab indicate that increased sodium concentrations activate antigen-presenting cells (APCs), leading to SSBP. Vitamin D3 has been shown to attenuate inflammation, but its mechanisms and contribution to SSBP remain unknown. We hypothesized that vitamin D anti-inflammatory signaling in immune cells attenuates SSBP. To test this hypothesis, we performed bulk-RNA sequencing on monocytes after high-salt exposure and noticed an increase in vitamin D receptor (VDR) expression (NS: 1781.18 ± 222.33; HS: 2922.18 ± 371.65). Additionally, we performed single-cell CITE-Seq analysis on peripheral blood mononuclear cells isolated from hypertensive individuals after a rigorous inpatient salt-loading and salt-depletion protocol over a three-day period. On the second day when salt treatment was introduced, we observed an increase in VDR expression within APCs. Conversely, we observed a drop in VDR expression on the third day when salt was depleted from the APCs in salt-sensitive but not salt-resistant individuals. These results suggest that VDRs play an important role in modulating SSBP.
Abstract P182: Neutrophil Extracellular Traps Are Formed In Response To Hypertensive Stretch And Contribute To Vascular Dysfunction In Hypertension
Authors: Krishnan Jaya , De La Visitacion Nestor , Ao Mingfang , Hennen Elizabeth M , Patrick David M
Published: October 2023

Background:
Neutrophils play a crucial role in the innate immune response, in part by the release of neutrophil extracellular traps (NETs), which consist of decondensed chromatin and proteins including citrullinated histone 3 (H3-Cit). The process of NETosis involves the disassociation of DNA from the nucleosome catalyzed by the enzyme peptidyl arginine deiminase 4 (PAD4). TRPV4 is a mechanosensitive calcium channel expressed in neutrophils. Studies of human subjects and rodent models have described the accumulation of NETs in renal and vascular tissue in hypertension (HTN), however the causative role of NETs has not been described. We hypothesized that NETs form in response to hypertensive stretch and contribute to endothelial cell (EC) dysfunction and HTN.

Methods:
Mice deficient for
Padi4
lack the PAD4 enzyme and cannot efficiently form NETs.

Padi4
-/-

and
C57Bl/6J
mice were treated with 490 ng/kg/min angiotensin (Ang) II for 4 weeks. Blood pressure was measured by radiotelemetry. Vascular reactivity studies were performed on mesenteric arteries. Vascular infiltration was measured by flow cytometry. Murine neutrophils and aortic ECs were co-cultured and subjected to uniaxial stretch under normotensive (5%) and hypertensive (10%) conditions. Neutrophils were treated with a TRPV4 agonist (GSK1016790A) and NETs were quantified by immunofluorescence.

Results:

Padi4
-/-

mice exhibit attenuated HTN and improved vascular reactivity following Ang II treatment (systolic BP 159.4 ± 1.4 mmHg in
C57Bl/6J
mice vs 147.9 ± 2.6 mmHg in

Padi4
-/-

mice, n= 7-8, p= 0.007). Flow cytometry revealed a marked reduction in aortic infiltration of immune cells in

Padi4
-/-

mice compared to
C57Bl/6J
mice. Co-culture of murine neutrophils with ECs improves neutrophil survival and augments NETosis. Hypertensive stretch of co-cultured neutrophils and ECs augmented NETosis compared to normotensive stretch. Immunoblot revealed increased H3-Cit in neutrophils exposed to hypertensive stretch. Neutrophils treated with GSK1016790A exhibit augmented NETosis.

Conclusions:
These findings suggest a vital role of stretch-induced NETosis as a mediator of EC dysfunction and HTN. Mechanistically, both agonism of neutrophil TRPV4 and hypertensive stretch of ECs augment NETosis.
Abstract P192: Provider And Health System Level Variability In Initial Antihypertensive Intensity: A Mixed Modeling Approach In Newly Treated Patients With Hypertension
Authors: Keshwani Shailina , Smith Kayla , Winterstein Almut , Gurka Matthew , Walsh Marta , Libby Anne , Hogan William , Pepine Carl , Cooper-Dehoff Rhonda M , Smith Steven M
Published: October 2023

Background:
Initial antiHTN regimen intensity varies across patients, presumably due to factors like age, comorbidities, or baseline BP. However, the extent to which initial regimen intensity is influenced by patient factors, versus provider characteristics or preferences, and health system contexts, is unknown.

Methods:
We conducted a cross-sectional study of adults with newly-treated HTN in the OneFL+ Consortium with Medicaid or Medicare claims linked to EHR data from their treatment initiation visit. We used linear mixed modeling with prescriber nested within health system as random effects to estimate variability in total therapeutic intensity score (TTIS) – a patient’s total daily dose (TDD) divided by the recommended max TDD for a drug, summed across the initial regimen. We modeled patient- (demographics, BP, BMI, comorbidities) and provider-level (sex, specialty) factors as fixed effects and calculated intraclass correlation coefficients (ICC), to estimate relative variance in TTIS attributable to provider preference (ICC
P
) and health system (ICC
H
).

Results:
A total of 3970 patients (mean ± SD age, 59 ± 18.4 y; 58% women; 38% Black) were included. In the full model, 11.4% of the observed TTIS variation was attributed to provider (p<0.0001) and 3.9% to health system context (p=0.17), leaving 84.7% of TTIS variation within patients. The most influential factors in TTIS variation were Black race, male sex, and comorbidity profile (T2DM, CKD) (Table).

Conclusion:
Provider preference accounted for a significant but modest amount of variation in initial antiHTN regimen intensity. Most of the variance in TTIS was explained by patient factors.
Abstract P195: Association Of Unmet Social Needs With Antihypertensive Medication Prescription And Dietitian Referral: Interim Analysis Of The Study Of The Epidemiology Of Pediatric Hypertension Registry (SUPERHERO)
Authors: Onugha Elizabeth A , Campbell Jessica F , Londeree Jackson , Misurac Jason , Riar Sandeep , Sethna Christine , Siddiqui Sahar , Weaver Donald J , Yamaguchi Ikuyo , Vincent Carol , South Andrew
Published: October 2023

HTN is a significant public health concern with increasing prevalence in youth. Optimizing BP control with both lifestyle counseling and antihypertensive medications improves health outcomes. However, adequate BP control remains difficult in majority of patients, in part due to a lack of understanding of how social determinants of health affect dietitian referral and initiation of antihypertensive therapy.

We performed a cross-sectional analysis of baseline EHR data from the SUPERHERO Registry in youth who received initial care from sub-specialists for HTN disorders defined by ICD-10 codes from 1/1/2015-12/31/2022. We excluded those with pregnancy, kidney transplantation, and dialysis. We examined the association of individual-level social drivers (transportation, finances, food access housing) with the likelihood of antihypertensive medication prescription and dietitian referral at initial visit in youth with HTN disorders using unadjusted generalized linear models.

Of our large cohort of 11,580, only 47 youth had at least one unmet social need (0.4%). Participants with at least one unmet social need were 1.81 times more likely to be prescribed antihypertensive medication (95% CL 0.94- 3.48; p= 0.08) and 6.73 times more likely to be referred to a dietitian (95% CL 3.7-12.25).

We found that children with at least one unmet social need were more likely to be referred to a dietitian at the initial visit than those without an unmet social need. The small number of participants with unmet social needs might reflect poor screening or documentation practices. It is imperative that screening for unmet social needs is incorporated into clinical practice in youth with HTN disorders.
Abstract P196: Association Of Chronic Kidney Disease With Blood Pressure Severity And Target Organ Injury At Baseline In Youth Referred For Hypertension Disorders
Authors: Vincent Carol , Campbell Jessica F , Londeree Jackson , Misurac Jason , Murphy Maggie , Onugha Elizabeth , Riar Sandeep , Sethna Christine , Siddiqui Sahar , Weaver Donald J , Yamaguchi Ikuyo , South Andrew
Published: October 2023

Youth with chronic kidney disease (CKD) are at risk for hypertension (HTN) and associated target organ injury (TOI). This population may need an alternate screening schedule for TOI. Our objective was to determine the association of CKD with TOI and blood pressure (BP) severity at baseline in youth referred for HTN disorders, hypothesizing that we would see lower BP severity and less cardiac TOI in youth with CKD. This is an interim analysis using baseline data from the SUPERHERO Registry, a multisite retrospective study of youth referred for HTN disorders. Inclusion criteria were age <19 years and HTN disorder identified by ICD-10 codes from 1/1/2015-12/31/2022 at initial visit to a subspecialty clinic. Exclusion criteria were kidney failure on dialysis, kidney transplantation, or pregnancy by ICD-10 codes. Our exposure was presence of CKD by ICD-10 code. Our outcomes were presence of TOI (kidney and/or heart) by ICD-10 codes and BP severity from in-clinic BP measurement. We unadjusted generalized linear models. Of 11,580 participants, 488 (4%) had a diagnosis of CKD (Table). Youth with CKD had significantly higher risk of kidney-specific TOI (RR 2.81; 95% CL 2.23 to 3.52) and significantly lower BP by BP classification (OR 0.68; 95% CL 0.57 to 0.81) and lower systolic BP in adolescents (β -5.7 mmHg; 95% CL -7.4 to -4.0). Our findings could reflect differential management of patients with established subspecialty care who develop HTN and have early TOI screening or are already on anti-hypertensive medication for proteinuria. Future steps include analyzing rates of TOI screening and laboratory and echocardiogram results for precision.
Abstract P199: Plasma Metabolomic Profiles Related To Blood Pressure (BP) In Early And Mid-adolescence: Findings From The Project Viva Cohort
Authors: Zhang Mingyu , Perng Wei , Rifas-Shiman Sheryl L , Oken Emily , Hivert Marie-France
Published: October 2023

Background:
The identification of metabolites related to BP may afford opportunities to reveal novel biomarkers, elucidate pathogenesis, and provide potential intervention targets for prevention of hypertension.

Methods:
We conducted 2 cross-sectional analyses using data from the Early Teen (
n
= 560, median age: 12.9y; IQR: 12.5-13.3y) and Mid-Teen (
n
= 503, median age: 17.4y; IQR: 17.2-17.8y) visits of Project Viva. At each visit, we assayed plasma metabolites via untargeted metabolomics profiling (1135 at Early Teen; 1278 at Mid-Teen) and measured systolic BP (SBP) and diastolic BP (DBP). Using weighted-correlation network analysis, we identified metabolite modules and examined associations with BP using Spearman's partial correlations, adjusting for age, sex, and height. We used false discovery rate (FDR) to account for testing across multiple modules.

Results:
At the Early Teen visit, we identified a module of 59 metabolites (
Figure
; Network 7) comprised primarily of steroids (e.g., 24 androgenic steroids, 19 corticosteroids) that was correlated with higher SBP and DBP (ρ
adjusted
= 0.13-0.16; FDR ≤ 0.03). Associations were similar between males vs. females. Within this network, androgenic steroids (e.g., androstenediol (3beta,17beta) disulfate and monosulfate) seemed to drive the overall associations. At the Mid-Teen visit, the module primarily consisting of androgenic steroids was also correlated with higher SBP in the unadjusted models (ρ
crude
= 0.23; FDR < 0.01), but the association was attenuated in the adjusted model.

Conclusions:
A distinct module of metabolites, largely driven by androgenic steroids, was associated with higher BP in adolescents.
Abstract P204: Acute Kidney Injury Prior To Pregnancy Induces Renal And Endothelial Dysfunction Which Predisposes Pregnant Rats To Adverse Pregnancy Outcomes
Authors: Moronge Desmond , Ayulo Victor , Godley Hannah , Mellott Elisabeth , Gillis Ellen E , Ogbi Safia , Sullivan Jennifer C , Faulkner Jessica L
Published: October 2023

Clinical data report an increase in adverse pregnancy outcomes in women with a history of AKI despite clinical recovery prior to pregnancy. We developed a rat model of pregnancy post-AKI in which female Sprague-Dawley (SD) rats recover normal creatinine clearance 30 days post-AKI, however, exhibit endothelial dysfunction, elevated plasma creatinine and fetal growth restriction (FGR) during pregnancy compared to sham. We hypothesized that AKI-induced endothelial dysfunction predisposes pregnant rats to adverse pregnancy events including renal dysfunction and FGR, and further, that sildenafil will ablate endothelial dysfunction and prevent AKI-induced FGR. Female SD rats were randomized to 45-minute warm bilateral renal ischemia reperfusion or sham (N=6-8/grp) and 15 days post-surgery were put on vehicle or sildenafil chow (50 mg/kg/day) and mated 30 days post sham/AKI surgery. Gestational day 1 (GD1) was determined via vaginal smear. Plasma and 24-hour urine collection, vascular and renal injury were analyzed in pre-pregnancy (30 days post-AKI/Sham) or late pregnancy (GD20). Although previous cohorts show creatinine clearance normalizes 30 days post-AKI, urine kidney injury marker-1 (KIM-1) was greater in AKI rats compared to sham after 30 days (580±169 pg/24hrs vs 257±17, P=0.09) which remained elevated at GD20 of pregnancy (283±28 vs 216±12, P=0.06). Mason Trichrome revealed increases in glomerular (0.93±0.08 vs 0.04±0.04 score, *P<0.05) and tubular fibrosis (1.7±0.19 vs 0.0±0.0, *P<0.05) in post-AKI pregnant rats at GD20 compared to sham. Endothelial-dependent relaxation to acetylcholine (ACh) in 3
rd
order mesenteric arteries, measured by wire myography, was impaired in both 30-day post-AKI rats (concentration-response, 1nM-10μM, 2-w ANOVA, RM, *P<0.05) and in post-AKI GD20 groups (*P<0.05) compared to respective shams. Sildenafil treatment restored endothelial function at GD20 (P>0.05) and restored pup weights in post-AKI pregnant GD20 rats (1.18g±0.23 g vs 2.11±0.19, *P<0.05). Collectively, these data indicate that AKI induces endothelial dysfunction in female rats predisposing them to adverse renal adaptations and FGR in pregnancy, which is potentially prevented by improvement of endothelial function with sildenafil.
Abstract P206: Novel Dual-function Redox Modulator Therapy For Preeclampsia
Authors: Pintye Diana , Sziva Reka E , Mastyugin Maxim , Lo Agnes , Salahuddin Saira , Zsengeller Zsuzsanna K
Published: October 2023

Introduction:
Preeclampsia is a hypertensive disorder of pregnancy which is associated with substantial morbidity for the mother and fetus. Reduced nitric oxide bioavailability and oxidative stress are key in the maternal and fetal pathophysiology of preeclampsia.

Method:
In this study, we assessed the potential therapeutic effect and mechanisms of action of a novel dual-function nitric oxide donor/redox modulator, AKT-1005, in an animal model of Ad.sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis. Ad.sFlt1-overexpressing CD1 mice were treated via minipump with AKT-1005 (20 mg/kg) or vehicle (n=15 per group).

Results:
Treatment with AKT-1005 for 7 days significantly reduced sFlt1-induced hypertension and endotheliosis of the kidney glomeruli. Kidney function was also assessed by cystatin C ELISA, which showed significant reduction in AKT-1005 treated mice compared to controls. AKT-1005 treatment increased NO bioavailabilty as assessed by Griess method. The increase of free plasma sEndoglin (anti-angiogenic factor) following Ad.sFlt-1 was ameliorated after treatment with AKT-1005. Similarly, sEndoglin expression in placental tissue was reduced in the AKT-1005 treated group, which correlated with improved placental histology, reduced oxidative stress and increased endothelial expression of CD31. Moreover, wire myography studies in female mesenteric vessels have shown vasodilating capacity of AKT-1005.

Conclusion:
Our findings suggest that AKT-1005 significantly extenuates the sFlt-1-induced preeclampsia phenotypes by inhibiting oxidative stress, anti-angiogenic response, and increasing NO bioavailability. Further studies are needed to assess safety and efficacy of this type of dual-function redox-modulator therapy in animal models. Additional research is warranted to investigate the role of AKT-1005 as a novel therapeutic agent for vascular disorders such as preeclampsia.
Abstract P216: Multiomics Approach To Unravel The Molecular Mechanisms Responsible For Kidney Concentric Arterial And Arteriolar Hypertrophy
Authors: almeida Lucas
Published: October 2023

Introduction:
Experimental or spontaneous mutations of any of the renin-angiotensin system (RAS) genes or treatment with RAS inhibitors in mammals -including humans- lead to kidney concentric arterial and arteriolar hypertrophy (CAAH), a silent, progressive, and severe thickening of the intrarenal arterial tree. Therefore, it is crucial to comprehend the identity and fate changes of the vascular smooth muscle cells (VSMCs) as they switch their phenotype to renin-producing cells (RPC) during the progression of the arteriolar disease.

Objective:
Using new mouse models and single-cell ‘omic’ approaches available in our lab to assess the chromatin landscape of the RPCs and VSMCs, we aim to identify the genomic hotspots that determine the initiation, evolution, and ultimate fate of the diseased cells.

Methods:
We generated two murine models. In the first model (

Ren1
c-/-
;Ren1
cCre
;R26R
mTmG

) the renin gene is deleted while the cells (renin null cells) are labeled green (GFP+) from embryonic life. In the second model (

SMMHC
CreERt2
; R26R
tdTomato
; Ren1
cYFP

) VSMCs are labeled red (tdTomato+) upon tamoxifen injection whereas cells currently expressing renin are labeled yellow (YFP+). Kidney cells expressing the different fluorophores were isolated by Fluorescence Activated Cell Sorting and processed for Single Cell Multiome ATAC (Assay for Transposase-Accessible Chromatin) + Gene Expression, using 10X Genomics Chromium technology.

Results:
The wall thickness of the afferent arterioles in Ren1
C
KO mice was significantly increased when compared to control (4.54 ± 0.17 μm vs 11.57 ± 0.91 μm,
P
<0.0001). The hypertrophic arterioles were covered along their lengths with cells positive for renin, suggesting that renin cells were involved in the hypertrophy. As the mice got older, SMCs accumulate inwardly and concentrically, obstructing the vessels lumens, leading to focal fibrosis.

Conclusion:
Our studies showed that deletion of the renin gene led to CAAH. Experiments involving transcriptomics and epigenomics are ongoing to understand the evolution of the CAAH and identify and transcriptional profile changes that occur at the single-cell level.
Abstract P222: Effect Of Western Diet On Pathophysiology And Cardiac Gene Expression Profile In Human AT1 Receptor Over-Expressing Hypertensive Transgenic Mice
Authors: Ketkar Harshada
Published: October 2023

Human angiotensin II type 1 receptor (hAT1R) gene overexpression may lead to pathophysiological outcomes due to an overdrive of the renin angiotensin system. Our transgenic (TG) mice containing Hap-I (hypertensive genotype) of human AT1R gene are more prone to develop metabolic syndrome (MetS) as compared to TG mice with Hap-II (normotensive genotype). The increased risk of MetS, especially in hypertension, is compounded by the effects of aging and Western diet (WD), which may lead to cardiac complications. However, the underlying mechanisms are not well examined. In this regard, we studied the pathophysiological changes and alterations in transcription profile in the heart of aged Hap-I and Hap-II TG mice following exposure to WD. Aged mice (20-24 months) were maintained on a regular diet or high fat diet with 2% NaCl (WD) for 16 weeks. Following administration of WD, blood pressure increased significantly in Hap-I animals (~15 mmHg), in comparison to Hap-II (~7 mmHg). With respect to Hap-II, aged Hap-I mice show larger heart weight-to-body weight ratio and higher levels of fibrosis on treatment with WD. The TF Activation Profiling (Signosis) after WD treatment shows an increased activation of transcription factors including USF1, CEBP, STAT1, HNF1 in the nuclear extracts from heart of Hap-I TG mice as compared to the Hap-II animals. Competition assay (Promoter-binding TF profiling plate arrays, Signosis) shows stronger binding to the promoter for these TFs binding to the promoter of hAT1R, leading to overexpression of hAT1R in HAP-I TG animals. Transcriptomic analysis from RNA sequencing revealed that WD significantly altered the expression of >500 genes from cardiac tissue of WD treated Hap-I aged mice (compared to control diet treated age-matched mice). Bioinformatics analysis, using Qiagen IPA software, identified major alterations in main canonical pathways involved in cardiac function, inflammation, and oxidative damage. Overall, these results indicate that Western diet promotes hypertension, hypertrophy, and fibrosis in the heart of aged mice. Results from these studies will assist in the identification of novel molecules and mechanisms involved in hypertension and associated cardiac pathophysiology.